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CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS| August 15, 2003
Allogeneic compared with autologous stem cell transplantation in the treatment of patients younger than 46 years with acute myeloid leukemia (AML) in first complete remission (CR1): an intention-to-treat analysis of the EORTC/GIMEMAAML-10 trial
Stefan Suciu,
Stefan Suciu
From the European Organization for Research and Treatment of Cancer (EORTC) Data Center, Brussels, Belgium; Department of Cellular Biotechnology and Hematology, University La Sapienza, Roma, Italy; Department of Hematology, St Radboud University Hospital, Nijmegen, The Netherlands; Department of Hematology, Hotel-Dieu, Paris, France; Department of Medicine, Hospital S. Giovanni Battista, Torino, Italy; Department of Hematology, University Hospital Rebro, Zagreb, Croatia; Department of Hematology, University Federico II Medical School, Napoli, Italy; Department of Hematology, Hospital Edouard Herriot, Lyon, France; Department of Hematology, Hospital Ferrarotto, Catania, Italy; Department of Hematology, Hospital Necker, Paris, France; Department of Hematology, University degli Study di Bari, Bari, Italy; Department of Hematology, Hospital Cervello, Palermo, Italy; Department of Hematology, Catholic University, Rome Italy; Department of Hematology, Institut Gustave Roussy, Villejuif, France; Department of Hematology, Civil Hospital, Pescara, Italy; Department of Hematology, Klinikum Grosshadern Ludwig-Maximilians, Muenchen, Germany; Department of Hematology, University Tor Vergata, Roma, Italy; Gruppo Italiano Malattie Ematologiche dell' Adulto (GIMEMA) Data Center, Department of Cellular Biotechnology and Hematology, University La Sapienza, Roma, Italy; Center for Human Genetics, University of Leuven, Leuven, Belgium; Department of Hematology, and Leiden University Medical Center, Leiden, the Netherlands.
Franco Mandelli,
Franco Mandelli
Theo de Witte,
Theo de Witte
Robert Zittoun,
Robert Zittoun
Eugenio Gallo,
Eugenio Gallo
Boris Labar,
Boris Labar
Gennaro De Rosa,
Gennaro De Rosa
Amine Belhabri,
Amine Belhabri
Rosario Giustolisi,
Rosario Giustolisi
Richard Delarue,
Richard Delarue
Vincenzo Liso,
Vincenzo Liso
Salvatore Mirto,
Salvatore Mirto
Giuseppe Leone,
Jean-Henri Bourhis,
Jean-Henri Bourhis
Giuseppe Fioritoni,
Giuseppe Fioritoni
Ulrich Jehn,
Ulrich Jehn
Sergio Amadori,
Sergio Amadori
Paola Fazi,
Paola Fazi
Anne Hagemeijer,
Anne Hagemeijer
Roel Willemze,
Roel Willemze
the EORTC and GIMEMA Leukemia Groups
Stefan Suciu, Franco Mandelli, Theo de Witte, Robert Zittoun, Eugenio Gallo, Boris Labar, Gennaro De Rosa, Amine Belhabri, Rosario Giustolisi, Richard Delarue, Vincenzo Liso, Salvatore Mirto, Giuseppe Leone, Jean-Henri Bourhis, Giuseppe Fioritoni, Ulrich Jehn, Sergio Amadori, Paola Fazi, Anne Hagemeijer, Roel Willemze, the EORTC and GIMEMA Leukemia Groups; Allogeneic compared with autologous stem cell transplantation in the treatment of patients younger than 46 years with acute myeloid leukemia (AML) in first complete remission (CR1): an intention-to-treat analysis of the EORTC/GIMEMAAML-10 trial. Blood 2003; 102 (4): 1232–1240. doi: https://doi.org/10.1182/blood-2002-12-3714
In the European Organization for Research and Treatment of Cancer Leukemia Group and Gruppo Italiano Malattie Ematologiche dell' Adulto (EORTC-LG/GIMEMA) acute myeloid leukemia (AML)–10 trial, patients in first complete remission (CR1) received a single intensive consolidation (IC) course. Subsequently, those patients younger than 46 years with an HLA-identical sibling donor were assigned to undergo allogeneic (allo) stem cell transplantation (SCT), and patients without such a donor were planned for autologous (auto) SCT. Between November 1993 and December 1999, of 1198 patients aged younger than 46 years, 822 achieved CR. The study group constituted 734 patients who received IC: 293 had a sibling donor and 441 did not. Allo-SCT and auto-SCT were performed in 68.9% and 55.8%, respectively. Cytogenetic determination was successfully performed in 446 patients. Risk groups were good (t(8;21), inv16), intermediate (NN or –Y only), and bad/very bad (all others). Median follow-up was 4 years; 289 patients relapsed, 66 died in CR1, and 293 died. Intention-to-treat analysis revealed that the 4-year disease-free survival (DFS) rate of patients with a donor versus those without a donor was 52.2% versus 42.2%, P = .044; hazard ratio = 0.80, 95% confidence interval (0.64, 0.995), the relapse incidence was 30.4% versus 52.5%, death in CR1 was 17.4% versus 5.3%, and the survival rate was 58.3% versus 50.8% (P = .18). The DFS rates in patients with and without a sibling donor were similar in patients with good/intermediate risk but were 43.4% and 18.4%, respectively, in patients with bad/very bad risk cytogenetics. In younger patients (15-35 years), the difference was more pronounced. The strategy to perform early allo-SCT led to better overall results than auto-SCT, especially for younger patients or those with bad/very bad risk cytogenetics.
Clinical Trials and Observations, Neoplasia, Transplantation
allopurinol, complete remission, cytogenetics, donors, european organization for research and treatment of cancer, leukemia, myelocytic, acute, intention to treat analysis, autologous stem cell transplant, hematopoietic stem cell transplantation
Current standard treatment strategy for patients with acute myelogenous leukemia (AML) younger than 60 years consists of 1 or 2 induction courses with cytosine arabinoside and an anthracycline followed in the case of complete remission (CR) by one or more intensive consolidation (IC) chemotherapy courses. There is no consensus about the subsequent treatment modality. Some prefer only chemotherapy,1 ie, continuation of consolidation courses and/or maintenance chemotherapy; others proceed with some form of allogeneic or autologous stem cell transplantation (allo- or auto-SCT). Several large randomized studies comparing IC courses with stem cell transplantation, in which patients with an HLA-identical donor were scheduled to receive an allograft, report contradictory results.2-11 However, the sizes of these studies were small, the follow-up was insufficient, or the intensity of chemotherapy preceding SCT was not optimal or different. In some studies comparing chemotherapy versus auto-SCT versus allo-SCT, the design was not appropriate to assess the difference between auto-SCT and allo-SCT in terms of disease-free survival (DFS).2,3,6,10 In other studies the analyses were performed according to treatment actually given, the data on cytogenetics were scarce, or the proportion of patients who received the intended randomized treatment modality or the intended allo-SCT was too low.12 The comparison of the effects of allo- and auto-SCT has also been performed on the basis of registration data of the International and European Blood and Bone Marrow Transplantation Registries.13-15 Because these registries contain only data of patients in whom a transplantation has been performed, this type of analysis is biased because of selection of patients with good performance, variability of the interval between the moment of remission and the transplantation, and exclusion of early relapses.16
In the previous AML-8A trial of the European Organization for Research and Treatment of Cancer (EORTC) Leukemia Group and the Italian Gruppo Italiano Malattie Ematologiche dell' Adulto (GIMEMA) group, it has been shown that auto-SCT leads to a significantly longer DFS than a second IC course, but significant differences between auto-SCT and allo-SCT could not be detected.6
The EORTC and GIMEMA researchers subsequently conducted a randomized study (AML-10 trial) for patients with AML younger than 61 years. All patients were randomly assigned at the time of diagnosis for 1 of 3 anthracyclines added to cytosine arabinoside and etoposide as remission induction treatment. After achievement of CR an IC course was given. This course was to be followed by an allo-SCT in the patients with a HLA-identical family donor or by auto-SCT in those who lacked such a donor. In the latter group of patients a second randomization was performed to investigate the long-term results of transplantation with peripheral blood stem cells compared with bone marrow–derived stem cells.17
The AML-10 trial offers the possibility in patients up to the age of 45 years to assess the value of early allo-SCT versus auto-SCT on the basis of intention to treat18 by comparing the outcome of the group of patients with an HLA-identical sibling donor (donor group) with the outcome of patients without such a donor (no donor group).
Our analysis indicates that the strategy to perform an early allo-SCT was indeed justified in this group of patients younger than 45 years, as it led to a longer DFS than the strategy to perform an early auto-SCT. Subgroup analysis shows that patients with cytogenetical bad/very bad risk characteristics have a better outcome when a sibling donor is available. Because of a high treatment-related mortality (TRM) observed in patients with a donor and with good cytogenetic features, one may question the wisdom of performing an allo-SCT in CR1 in this group of patients. Furthermore, because of a relatively high TRM in patients aged 36 to 45 years, the prognosis of these patients with or without a sibling donor is almost identical, whereas in younger patients the differences were prominent.
The EORTC-LG/GIMEMAAML-10 protocol was approved by the EORTC Protocol Review Committee and by the Ethical Committee of each participating center. The study was conducted from November 1993 to December 1999 in 80 European centers. All patients, up to the age of 60 years, with previously untreated AML, except acute promyelocytic leukemia, with more than 30% blast cells in the bone marrow, were eligible. Patients with a blast crisis of chronic myeloid leukemia (CML), AML supervening after other myeloproliferative diseases, or AML following a myelodysplastic syndrome of more than 6 months' duration and patients with severe heart, lung, liver, renal, hepatic, or neurologic diseases were excluded from registration. Before randomization, all patients had to give their informed consent, which was in accordance with the Helsinki protocol.
Random assignment for daunorubicin, mitoxantrone, or idarubicin was performed at the time of registration. Remission induction treatment consisted of cytosine arabinoside 25 mg/m2 intravenous bolus followed immediately by 100 mg/m2 given as a continuous infusion daily for 10 days; etoposide 100 mg/m2 in 0.9% saline daily by intravenous infusion (1 hour) on days 1 to 5; and one of the following: daunorubicin 50 mg/m2 on days 1, 3, and 5 as a 5-minute infusion or mitoxantrone 12 mg/m2 as a 30-minute infusion on days 1, 3, and 5 or idarubicin 10 mg/m2 as a 5-minute infusion on days 1, 3, and 5. In case of partial remission a second remission induction course was given. In case of CR a single course of consolidation therapy was administered, which consisted of intermediate-dose cytosine arabinoside (500 mg/m2 every 12 hours in a 2-hour infusion on days 1-6) and the anthracycline, randomly assigned at registration, given on days 4 to 6. Patients with a sibling donor were assigned to undergo an allogeneic SCT. All patients without such a donor had to receive an autologous blood or bone marrow stem cell transplant without any purging. The recommended conditioning regimens were as follows: cyclophosphamide (60 mg/kg on 2 consecutive days) and total body irradiation, preferably fractionated (6 fractions of 2 Gy over 3 days; dose rate < 0.06 Gy/min), or busulphan 4 mg/kg per day on days –8, –7, –6, and –5 combined with cyclophosphamide 60 mg/kg on days –4 and –3. Graft-versus-host prophylaxis was performed according to the local policy. T-cell depletion of the allogeneic graft was performed in 49 cases by monoclonal antibodies (n = 24), elutriation (n = 17), and other techniques (n = 8).
Between November 1993 and December 1999, a total of 2157 patients were randomly assigned in the AML-10 study. Among 1198 patients aged between 15 and 46 years, 62 patients were considered as inevaluable for the treatment response, mainly because of the lack of clinical documentation. Of the remaining 1136 patients, 822 (72.4%) entered complete remission after 1 or 2 courses of induction therapy. Among them, 50 patients were off-protocol treatment because of toxicity (n = 27) or other reason (n = 8), or they were poorly documented thereafter (n = 15). Of 772 patients who received consolidation, 38 have not been HLA typed because of refusal (n = 9), early death/toxicity (n = 20), logistic reasons (n = 5), and other or unknown reasons (n = 4). Among the 734 patients, 55 had no sibling. Of the remaining 679 patients, 293 had an HLA-identical sibling donor (donor group) and 386 had no family donor. By adding to this latter group those 55 patients with no siblings, a group of 441 patients has been formed, which was designated as the no donor group. The median follow-up was 4 years; 289 patients relapsed, 66 died in CR1, and overall 293 patients died. With a total of 355 events, the a posteriori statistical power in detecting a difference in the 4-year DFS rates between 42.4% and 52.2% was approximately 0.70.
Criteria of evaluation
The Cancer and Leukemia Group B (CALGB) criteria for response to treatment and relapse were used.19 CR was defined as a morphologic normal marrow with less than 5% blasts. Normal findings for peripheral blood and differential counts (ie, platelets ≥ 100 × 109/L, polymorphonuclear leukocyte [PMN] ≥ 1.5 × 109/L, hemoglobin ≥ 12 g/dL) were required at the evaluation of the induction course or at the evaluation of consolidation. Among patients who reached CR, relapse was defined as the presence of more than 10% blasts in the bone marrow or blasts in extramedullary sites.
As cytogenetic classification the International System for Cytogenetic Nomenclature (ISCN) has been applied.20 A central review (by A.H.) of cytogenetics has been performed. Twenty analyzed metaphases were required to include a patient in the cytogenetic normal karyotype (NN group). Complex abnormalities were defined as a clone with at least 4 unrelated abnormalities. The patients with unknown, not done, or unsuccessful cytogenetics were grouped together as unknown. Regarding morphology, the French-American-British (FAB) cytologic classification has been used, and a central review has been done in 44% of cases.21,22
The disease-free survival (DFS) was calculated from the date of CR until the date of first relapse or of death in first CR. The time to relapse and time to death in CR were calculated as the DFS; patients who died in CR and those who relapsed were respectively censored at that moment for these 2 analyses. By definition all patients who died in CR were considered as death from treatment-related mortality (TRM). The duration of survival was calculated from the date of CR until the date of death; patients still alive were censored at their last follow-up.
Actuarial curves were calculated according to the Kaplan-Meier technique.23 The standard errors (SE) of the estimates were computed using the Greenwood formula.23 The estimates of the incidence of relapse and of death in CR, and their corresponding standard errors, were obtained using the cumulative incidence method, in which the risks of death in CR and of relapse were considered as competing risks.24 The differences between actuarial curves were tested for statistical significance using the 2-tailed log-rank test,23 whereas for the cumulative incidences the Gray test was used.24 The Cox proportional hazards model was used to obtain the estimate and the 95% confidence interval (CI) of the hazard ratio (HR) of the instantaneous event rate in one group versus the one in another group, as specified by a given variable, and the Wald test was used to determine the prognostic significance.23 The Cox model was also used to determine the independent prognostic factors among those that appeared important in univariate analyses (P < .1), or an a priori interaction with the donor availability group was suspected (eg, age). The prognostic interaction between 2 variables was tested by including the product of these 2 variables into the model. All analyses were based on the intent-to-treat principle.
The cutoff date was April 8, 2002. SAS 8.1 statistical software (SAS Institute, Cary, NC) was used.
Relationship between initial patient characteristics and donor availability
The characteristics of patients with a sibling donor (donor group) and without a sibling donor (no donor group) are shown in Table 1. The distribution regarding age, white blood cell (WBC) count at diagnosis, FAB subtype, and the CR rate after the first induction course was similar in both groups. In each group approximately one third of patients had received 1 of the 3 anthracyclines, and the sex ratio (M/F) was 1.04 in both groups. Results of cytogenetic examination were unknown in 288 patients: 170 (38.5%) in the no donor group versus 118 (40.3%) in the donor group. In the remaining 446 patients, the following risk groups were considered: good (t(8;21) or inv16) in 123 patients, intermediate (NN or –Y only) in 165 patients, bad (all other abnormalities, without good and very bad cytogenetic features) in 78 patients, and very bad risk (–5, 5q–, –7, 7q–, complex abnormalities, abnormal (abn) 3q, t(9;22), t(6;9), or abn 11q23 and absence of good cytogenetic features) in 80 patients. These subgroups were quite well distributed between the 2 study groups (Table 1); the percentage of patients with very bad risk was slightly higher in the donor group (24.0%) than in the no donor group (14.0%).
Patient characteristics according to donor availability
No donor, N = 441
Donor, N = 293
Age, y, median (range) 33 (15-45) 35 (15-45)
Between 15 y and 25 y, n (%) 114 (25.9) 67 (22.9)
Between 36 y and 45 y, n (%) 185 (42.0) 138 (47.1)
Median WBC count, × 109/L (range) 19.2 (0.4-336) 16.4 (0.6-420)
FAB type
Unknown, n (%) 5 (1.1) 2 (0.7)
M0, n (%) 14 (3.2) 9 (3.1)
M1, n (%) 71 (16.1) 46 (15.7)
M2, n (%) 157 (35.6) 106 (36.2)
M3, n (%)* 2 (0.5) 0 (0.0)
M4E, n (%) 25 (5.6) 22 (7.5)
M6-M7, n (%) 9 (2.1) 11 (3.7)
Courses needed to reach CR
1, n (%) 410 (93.0) 267 (91.1)
2, n (%) 31 (7.0) 26 (8.9)
Unknown, n (%) 170 (38.5) 118 (40.3)
Successful, n (%) 271 (61.5) 175 (59.7)
Good risk, n [%]† 73 [26.9] 50 [28.6]
Intermediate risk, n [%]‡ 104 [38.4] 61 [34.9]
Bad, n [%]§ 56 [20.7] 22 [12.6]
Very bad, n [%]∥
38 [14.0]
Percentages between brackets were calculated for those with a successful examination.
M3 according to the cytology review, but M5 and M2 according to the local cytologist.
Presence of t(8;21) or inv(16).
NN or -Y only.
Presence of other abnormalities without good or very bad cytogenetic features.
Presence of -5, 5q-, -7, 7q-, complex abnormalities, abn 3q, t(9;22), t(6;9), or abn 11q23, and absence of good cytogenetic features.
Relationship between donor availability and stem cell transplantation
Allo-SCT in first CR was performed in 202 (68.9%) of 293 patients with a sibling donor, and auto-SCT was performed in 246 (55.8%) of 441 patients without such a donor. The conditioning regimen consisting of either busulphan + cyclophosphamide or cyclophosphamide + total body irradiation (TBI) was administered in 56% and 44%, respectively, of patients receiving allografts and in 75% and 25%, respectively, in patients receiving autotransplants. Eleven (2.5%) patients in the no donor group received transplants in first CR with stem cells of a matched unrelated or phenotypically identical related donor. Seven (2.5%) patients with a sibling donor received an autologous SC transplant. The percentages of actually performed SCTs in the cytogenetic subgroups are shown in Table 2.
Performed stem cell transplantation according to the donor availability group in each cytogenetic subgroup and each age group
Autologous (%)
Allogeneic (%)
Unknown 92 (54.1) 1 (0.6) 2 (1.7) 73 (61.9)
Successful 154 (56.8) 10 (3.7) 5 (2.9) 129 (73.7)
Good risk 46 (63.0) 1 (1.4) 4 (8.0) 36 (72.0)
Intermediate risk 65 (62.5) 2 (1.9) 1 (1.6) 46 (75.4)
Bad risk 29 (51.8) 2 (3.6) 0 (0.0) 17 (77.3)
Very bad risk 14 (36.8) 5 (13.2) 0 (0.0) 30 (71.4)
Age, y
Between 15 and 25 62 (54.4) 4 (3.5) 0 (0.0) 45 (67.2)
11 (2.5)
The exact number of patients in each cytogenetic or age group is given in Table 1.
Although the percentages of actually performed SCTs in the donor group were only slightly different among the cytogenetic subgroups, in the no donor group a lower percentage (45.7%) of patients with bad/very bad cytogenetics received an autologous SC transplant, and 7.4% of this subgroup received transplants with stem cells of a matched unrelated donor. The low autologous transplantation rate was due mainly to a high early relapse rate before SCT could be performed in the bad/very bad risk group; of 44 patients (Table 3) who have not received transplants, 37 relapsed early. The reasons for no transplantation according to the donor availability, in each cytogenetic subgroup, are indicated in Table 3.
Number of patients for each reason for not performing stem cell transplantation (SCT) according to the donor availability group in each cytogenetic subgroup
Donor, N = 84
Toxicity
Refusal of protocol violation
Other/not documented
Refusal of protocol or violation
Unknown 77 12 20 23 22 43 14 7 5 17
Good risk 26 1 8 14 3 10 1 2 4 3
Intermediate risk 37 9 12 13 3 14 7 1 3 3
Bad risk 25 12 4 6 3 5 1 1 1 2
Very bad risk
The study group was divided into groupings of patients aged 16 to 25, 26 to 35, and 36 to 45 years. Table 2 shows that the percentages of patients who had an auto- or allo-SCT performed in those with and without a donor were quite similar in each age grouping.
Effect of donor availability on outcome
The 4-year DFS rate of the donor group was superior to that of the no donor group: 52.2% versus 42.2%, P = .044; hazard ratio = 0.80; 95% confidence interval, 0.64-0.995. In the first 9 months the curves were superimposable (hazard ratio = 0.99; 95% CI, 0.73-1.33; P = .92), but thereafter, a divergence occurred between them (hazard ratio = 0.64; 95% CI, 0.46-0.88; P = .006). The relapse incidence was 30.4% versus 52.5% (P < .0001), and the incidence of death in CR was 17.4% versus 5.3% (P < .0001), respectively. The survival from CR rate was 58.3% versus 50.8% (P = .18); hazard ratio = 0.84; and 95% confidence interval, 0.67-1.08 (Figures 1, 2, and 3).
DFS from CR according to donor availability. The estimates of the 4-year DFS rates (± SE) for the donor group (dotted line) and the no donor group (solid line) are given. The 4-year cumulative incidence of relapse and of death in CR are given in italics at the right of the graph. N indicates number of patients; O, observed number of events (relapse or death in first CR). P is determined by the log-rank test.
Cumulative incidence of relapse and cumulative incidence of death in complete remission according to donor availability. N indicates number of patients; R, observed number of relapses; D, observed number of deaths in first CR. P is determined by the Gray test.
Duration of survival from complete remission according to donor availability. N indicates number of patients; O, observed number of deaths. P is determined by the log-rank test.
Effect of cytogenetics and donor availability on outcome
The most important prognostic factor for the DFS (P < .0001) was initial cytogenetics: patients with good risk cytogenetics had a better outcome than those with intermediate risk cytogenetics, whereas those with bad or very bad risk cytogenetic characteristics had a far worse outcome. The outcome of patients with unknown cytogenetic examination was similar to that of those with known cytogenetic features (HR = 1.17).
Because of the slight imbalance of the distribution of patients with bad/very bad risk cytogenetics between the donor and no donor group, the Cox model shows that the difference in DFS adjusted for the initial cytogenetic features slightly increased: the estimated hazard ratio was 0.78 (P = .024) when the 2 risk groups, bad and very bad, were pooled together (Table 4, model 1) and was 0.75 (P = .012) when these 2 groups were separated. When we included in the Cox model not only variable cytogenetics (prognostic score based on binary variables corresponding to good, intermediate, bad/very bad, and unknown groups) and the donor availability but also their interaction, this interaction was marginally significant (P = .07). Therefore, the difference between the outcomes of the 2 groups might have been influenced by the cytogenetic risk group.
Results of the Cox Proportional Hazards Model regarding the disease-free survival when only cytogenetics and donor availability were considered (model 1) and when cytogenetics and the interaction between each age group and donor availability were considered (model 2)
Hazard ratio*
P†
Good risk 0.58 0.40, 0.84 .004
Bad/very bad 1.63 1.22, 2.17 .0009
Unknown 0.95 0.72, 1.25 .70
Donor vs no donor 0.78 0.63, 0.97 .025
Donor vs no donor
If aged between 15 and 25 y 0.64 0.43, 0.97 .04
If aged between 36 and 45 y
0.70, 1.22
A value > 1 indicates that the outcome is worse in the given category compared with the baseline.
P was determined by the Wald test.
In the 446 patients with a successful cytogenetic examination the estimated hazard ratio for the DFS comparison of the donor versus no donor groups was 0.89 (P = .40), and the 95% confidence interval was 0.68 to 1.17. The relapse incidence was 32.7% versus 51.9%; the death in CR incidence was 18.5% versus 5.5%. The results in terms of DFS in each cytogenetic subgroup and according to the availability of a sibling donor, along with the 4-year estimate rates of DFS and of the cumulative incidences of relapse and of death in CR, are shown in Figure 4A-C.
DFS from CR according to donor availability in 4 cytogenetic groups. The cytogenetic groups were good risk (A), intermediate risk (B), bad/very bad risk (C), and unknown (D). The estimates of the 4-year DFS rates (± SE) for the donor group (dotted line) and the no donor group (solid line) are given. The 4-year cumulative incidences of relapse and of death in CR are given in italics. N indicates number of patients; O, observed number of events (relapse or death in first CR). P was determined by the log-rank test.
The 4-year survival rates in the donor versus no donor group, in the cytogenetic prognostic groups (good, intermediate, and bad/very bad) were 68.1% (± 6.8%) versus 73.9% (± 5.5%), 53.4% (± 6.8%) versus 54.3% (± 5.3%), and 50.2% (± 6.7%) versus 29.4% (± 5.3%), respectively. The estimates of the hazard ratios for the comparison donor versus no donor in each of the 3 cytogenetic groups are given in Table 5. In the cytogenetic good and intermediate risk group, patients with a sibling donor did not have a better outcome (DFS and survival) than those without a sibling donor: the estimated hazard ratios were more than 1 and the lower 95% confidence interval was 0.66 or more. The reductions in the relapse incidences of the donor group were largely counterbalanced by an increase in the risk of death in CR. In the cytogenetic bad and very bad risk groups, patients with a sibling donor do have a considerably better outcome than those without such a donor: the estimated hazard ratio for the DFS and survival was 0.58 and 0.62, respectively. The increase in the TRM was largely compensated by the reduction in the relapse incidence. Therefore, for the comparison of donor versus no donor in terms of DFS, the decrease observed in the hazard ratios 1.21, 1.16, and 0.58 in the good, intermediate, and bad/very bad cytogenetic risk groups, respectively, appeared to be significant (P = .024), as indicated by the Cox model, in which the cytogenetic risk group (considered as an ordered variable), donor availability, and their interaction have been included. For survival, the interaction between these 2 variables was significant as well (P = .035).
Comparison of donor versus no donor in 3 cytogenetic groups and the 3 age groups according to different endpoints
Disease-free survival
Time to relapse
Time to death in CR
Cytogenetic groups
Good 1.21 (0.66, 2.25) 0.83 (0.38, 1.78) 3.03 (0.91, 10.06) 1.41 (0.70, 2.82)
Intermediate 1.16 (0.75, 1.81) 0.84 (0.50, 1.41) 4.06 (1.41, 11.68) 1.14 (0.70, 1.86)
Bad/very bad 0.58 (0.39, 0.87) 0.42 (0.26, 0.68) 2.70 (0.93, 7.80) 0.62 (0.40, 0.96)
15-25 y 0.65 (0.41, 1.04) 0.53 (0.32, 0.89) 2.28 (0.64, 8.10) 0.63 (0.37, 1.07)
36-45 y
Numbers are shown as estimated hazard ratio (95% CI).
Patients with an unknown cytogenetic analysis (N = 288) showed the same trends as the whole study group: a 4-year DFS rate of 57.8% versus 41.2% (Figure 4D), an estimated hazard ratio (95% CI) of 0.66 (0.45, 0.96), and a survival rate of 62.1% (± 5.2%) vs. 50.6% (± 4.7%).
Additional multivariate analyses
The multivariate Cox model showed that in addition to cytogenetic subgroup (good, intermediate, bad/very bad, unknown), the following factors were important independent prognostic factors: initial WBC count (continuous variable) (P = .0003) and FAB subtype (other subgroup versus M2 or M4E, P = .027). Adjusting for these factors, the donor group remained to show a better outcome than the no donor group (HR = 0.77, P = .019). The interaction term between the variable donor availability and a prognostic score based on cytogenetic subgroup, WBC count, and FAB subgroup was marginally significant (P = .09), suggesting that the worse the prognosis the higher the difference between donor and no donor groups. In patients with known cytogenetics, FAB subgroup and WBC count were of low prognostic importance once cytogenetics was included in the model. In patients with unknown cytogenetics, donor availability (hazard ratio = 0.61, P = .01), FAB subgroup (P = .03), and WBC count (P < .0001) were the most important independent prognostic factors for DFS.
Comparative cytogenetic grouping
The differences in terms of DFS for the comparison of donor versus no donor according to the classifications used by the EORTC/GIMEMA, SWOG/ECOG (Southwest Oncology Group/Eastern Cooperative Oncology Group), and MRC (Medical Research Council) are given in Table 6. According to all 3 classifications the outcome of the donor group was not superior to the no donor group in patients with good risk abnormalities and in patients with intermediate risk abnormalities as defined by NN or –Y alone or those comprising some additional features, such as +8, +6, del(12p).28 In patients classified as others by each of the 3 groupings, the donor group had a better outcome than the no donor group. In the intermediate group by the MRC, containing NN, –Y, and others, a slight DFS advantage in favor of the donor group was observed. Although the definition of the very bad, adverse, and unfavorable group by the 3 leukemia research groups was slightly different, the estimated hazard ratios pointed in the same direction, as they were 0.65, 0.59, and 0.64, respectively, for the EORTC/GIMEMA (n = 80), SWOG/ECOG (n = 105), and MRC (n = 30) grouping.
DFS analysis for the comparison of donor versus no donor according to the cytogenetic groups and 3 possible grouping systems
No donor, n
Donor, n
Estimated HR
EORTC/GIMEMA
Favorable* 73 50 1.21 0.66, 2.25
NN, -Y only 104 61 1.16 0.75, 1.81
Others (bad)* 56 22 0.33 0.15, 0.75
Very bad* 38 42 0.65 0.39, 1.10
SWOG/ECOG
Favorable† 67 46 1.27 0.67, 2.42
Intermediate‡ 116 67 1.02 0.67, 1.55
Others 36 9 0.27 0.07, 1.16
Unfavorable§ 52 53 0.64 0.40, 1.02
Others 81 47 0.55 0.64, 0.88
Intermediate∥ 0.83 0.60, 1.14
Adverse¶
Favorable cytogenetics is the presence of t(8;21) or inv(16); bad is the presence of other abnormalities without good or very bad cytogenetic features; very bad is the presence of -5, 5q-, -7, 7q-, complex abnormalities, abn 3q, t(9;22), t(6;9), or abn 11q23, and absence of good cytogenetic features.
Favorable cytogenetics in this grouping system is the presence of inv(16) with/without secondary aberrations; t(8;21) without del(9q) and complex karyotype.
Intermediate cytogenetics is the presence of NN, +8, +6, -Y, del(12p) without presence of unfavorable features.
Unfavorable cytogenetics is the presence of -7, 7q-, -5, 5q-, abn (3q), 9q, 11q, 20q, 21q, 17p, t(6;9), t(9;22), or complex, defined as a clone with at least 3 unrelated abnormalities.
Intermediate is the combination of the NN, -Y only group with the other group.
Adverse cytogenetics in this grouping system is the presence of -7, -5, 5q-, abn (3q), or complex, defined as a clone with at least 5 unrelated abnormalities.
Effect of age and donor availability on outcome
Overall, the results with respect to DFS and survival were not different between the age groups (15-25, 26-35, and 36-45 years). Figure 5A-C shows the comparison of the donor and no donor groups in terms of DFS and indicates the 4-year cumulative incidence of relapse and of death in CR according to the 3 age groups.
DFS from CR according to donor availability in the 3 age groups. The age groups were 15 to 25 years (A), 26 to 35 years (B), and 36 to 45 years (C). The estimates of the 4-year DFS rates (± SE) for the donor group (dotted line) and the no donor group (solid line) are given. The 4-year cumulative incidences of relapse and of death in CR are given in italics. N indicates number of patients; O, observed number of events (relapse or death in first CR). P was determined by the log-rank test.
As shown in Table 5, in patients aged 35 years or younger, the DFS for the patients with a sibling donor was longer than for those without a donor, because of a lower incidence of relapse (HR was approximately 0.50) and a lower increase in the TRM incidence (HR was approximately 2.5). In older patients (aged 36-45 years) the lower incidence of relapse (29.6% versus 48.3%, HR = 0.65) for the donor group was counterbalanced by a far higher incidence of death in CR (21.1% versus 5.5%, HR = 3.91). The 4-year survival rates in the donor versus no donor group, in the 3 age categories (15-25, 26-35, and 36-45 years) were 64.0% (± 6.7%) versus 50.8% (± 5.2%), 61.9% (± 5.7%) versus 49.6% (± 4.8%), and 53.4% (± 4.6%) versus 51.6% (± 4.3%), respectively.
In Table 4, model 2, the donor versus no donor comparison has been adjusted for the cytogenetics and assessed in each age group; the estimated hazard ratios were 0.64, 0.68, and 0.92 in the 3 age groups, respectively. An interaction between age (considered as an ordered categorical variable) and donor availability was detected, indicating that the older the patients the smaller the difference in terms of DFS (P = .036) and survival (P = .012) between the no donor and donor groups.
In this study we show for the first time that using analysis by intention to treat for the patients in the EORTC-LG/GIMEMA AML-10 trial in CR1 aged younger than 46 years assigned to allo-SCT has a significantly better outcome than for those who were planned to undergo an auto-SCT. This finding seems specifically true for patients with bad or very bad risk cytogenetics. This conclusion is justified because this AML-10 trial is the first large study in which prospectively only the 2 transplantation modalities are offered at an early time point of entering CR.
Already in our previous EORTC-GIMEMA AML-8A trial, the DFS rate of the no donor group was inferior to that of the donor group; but here the no donor group was composed of patients who were randomly assigned to receive autologous bone marrow transplant (auto-BMT) or a second chemotherapy consolidation. Furthermore, the 6-year survival rate in the AML-8A trial was 8% higher for the donor group as compared with the no donor group, but, because of a limited number of deaths, the difference was not significant (P = .24).11 Similarly, Burnett et al25 reported in the recent MRC AML-10 study in which patients after 4 chemotherapy cycles continued with allo- or auto-SCT or no further treatment25 that the patients with a donor had a higher 7-year DFS rate than the patients without a donor (50% versus 42%; P = .01). However, the composition of their study group was different, as it included children, patients with acute promyelocytic leukemia, and patients aged older than 45 years, and only 24% of the patients without a donor received an auto-SC transplant.
In our current study all patients aged younger than 46 years who achieved a CR and were consolidated by one course of intensive chemotherapy were eligible for either allo- or auto-SCT, depending on the biologic availability of a sibling donor. The 2 groups, donor and no donor, were comparable with respect to sex, age, initial WBC count, FAB classification, cytogenetic distribution, and number of courses to reach CR. Only 55.8% of the patients actually received an auto-SC transplant and 68.9% received an allo-SC transplant. Although this figure might be viewed as a limitation, we are convinced, like others,18,26 that comparison on the basis of intention to treat is the only way to reliably evaluate a treatment strategy. Failure to undergo the assigned transplantation was usually because of early relapse, poor clinical condition, refusal of the patient, or failure to harvest sufficient number of stem cells. In other prospective studies the frequency to perform a transplantation is somehow comparable with ours,2,5,6,25,26 although this finding may depend on the trial design, number and intensity of chemotherapy courses before the planned SCT, and patient selection.
In the cytogenetic subgroups of our study the frequency of transplantation differed. Only 50% of patients without a sibling donor and bad/very bad risk cytogenetics did undergo a transplantation, compared with 73% of the same subgroup of patients in the donor group. This frequency was mainly because of early relapses and failure to harvest sufficient stem cells in the no donor group. In contrast, 72% of patients with good risk cytogenetics with a donor received allo-SC transplants, whereas 63% of those without a donor received auto-SC transplants. These percentages are higher than in the MRC AML-10 study (52% and 22%, respectively).25 The reasons may be the long interval between the achievement of CR and the possible transplantation date in the MRC study because of the prolonged administration of the chemotherapy courses and the high TRM rate reported among patients registered before 1994.25
The significant difference in 4-year DFS rate of 10% (95% CI, 1.9%-18.1%) in favor of the donor group was due to the lower relapse incidence (22%) despite a higher TRM (12%). In patients who received the planned treatment, the TRM incidence after allo-SCT (20%) or after auto-SCT (5%) is comparable to the data reported by different registries for patients with AML in first CR.13-15 The 4-year DFS percentages for patients who actually received the planned allo- or auto-SC transplant were approximately 10% higher than in the donor and no donor groups. Adjustment for cytogenetics led to an HR = 0.73 (P = .033). This finding indicates how biased the results are when based on the treatment given instead of the treatment planned.
Successful cytogenetic data were available in 60.8% of the patients. The unknown group comes mainly from centers at which, at that time, cytogenetics was not routinely performed but includes also patients in whom cytogenetics had failed because of insufficient material or failure of marrow cells to form enough metaphases. The unknown group achieved similar results as the whole study group with respect to DFS, relapse incidence, and TRM. These findings add to the assumption that the not cytogenetically tested patients represent a random selection of patients.
Overall DFS for the good, intermediate, bad, and very bad risk cytogenetic subgroups followed the same pattern as reported in other large studies, despite the fact that the definition of the cytogenetic subgroups is not exactly the same.27,28
In the patients with good risk the strategy to perform an allo-SCT led to a slightly lower DFS rate than the strategy to perform an auto-SCT. The lower relapse incidence in the donor group could not balance the higher TRM observed after allo-SCT. Both kinds of transplantations led to quite satisfactory DFS rates (61%-65% at 4 years). In the MRC study the 7-year DFS rate in the patients with good risk with a donor was lower (53%) than in the patients without a donor (66%) because of a high TRM rate (24%).25 A similar trend has been observed in the SWOG/ECOG study (5-year survival, 63% versus 71%).28 These data suggest that in this subgroup of patients with AML, allo-SCT may be restricted to second-line therapy.29 Also in the patients with intermediate risk (NN, –Y only), we could not detect a difference in DFS. Again, the better antileukemic activity of the treatment in patients of the donor group could not balance the higher TRM. The MRC AML-10 study identified an advantage in favor of patients with intermediate risk with a donor. This advantage might be due to their definition of intermediate risk.25,27 Their group of patients with an NN or –Y only karyotype was supplemented with those with bad risk cytogenetics, according to our definition, in which we have detected the largest difference between the 2 groups. In the SWOG/ECOG study, the results of allo-SCT group were not superior to auto-SCT in the intermediate risk group, which comprised the patients with NN and –Y and those with +8, +6, or del(12p) only.28
The situation is totally different for patients with AML with bad or very bad risk cytogenetics. Here, the strategy to perform an allo-SCT led to DFS and survival rates that were only slightly inferior to those obtained in the other cytogenetic subgroups. However, dramatically inferior results were seen in the no donor group, because of an extremely high relapse rate. Only approximately 20% of the patients with bad and very bad risk remained in first CR, and approximately 30% are alive at 4 years from CR. It is clear that auto-SCT in these patients is a highly insufficient treatment approach. This finding contrasts with results of patients in the donor group: the 4-year DFS rate was approximately 65% and 35% in patients with bad and very bad risk, respectively. This observation is in line with the SWOG/ECOG study in which patients in the allogenic bone marrow transplantation (allo-BMT) group (n = 18) had better results than those in auto-BMT (n = 20) or chemotherapy (n = 20) groups.28 In the MRC study, in patients with adverse cytogenetics, both groups, those with a donor (n = 21) or without a donor (n = 67), had very poor results: the 7-year DFS rate was 14% versus 24%, respectively. This finding may be the consequence of their application of late transplantation. Early application of an allo-SCT by stem cells from a related or unrelated donor might be indicated in this subgroup of patients with AML.
In the younger patient groups the difference between the 2 transplantation approaches was most prominent, because of a low TRM and relapse rate among those who had a sibling donor. In contrast, in patients aged 36 to 45 years, the TRM incidence in the donor group was as high as 21%, which led to similar DFS rates in the donor and no donor groups; adjustment by cytogenetics confirms these findings. Similar observations have been reported by the MRC.25
The superiority of early allo-SCT over early auto-SCT using identical conditioning regimens is likely because of a graft-versus-leukemia effect. However, the advantage of the increased antileukemic effect of allo-SCT is diminished by increased iatrogenic mortality of the transplantation procedure. However, several new developments have been introduced in the transplantation procedure, such as nonmyeloablative conditioning,30 and SCT followed by adapted doses of donor lymphocyte transfusions.31 These approaches may reduce the morbidity and mortality from conditioning and graft-versus-host disease, while maintaining the graft-versus-leukemia effect. Trials with these modified techniques in the good and intermediate risk groups of patients with AML are warranted.
The list of the members of the EORTC or GIMEMA groups who participated in this study: Drs de Witte and Muus (Nijmegen), Dr Zittoun (Paris), Dr Labar (Zagreb), Dr Belhabri (Lyon), Drs Delarue and Varet (Paris), Dr. Sinnige (Den Bosch), Dr Bourhis (Paris), Dr Jehn (Muenchen), Dr Hagemeijer (Leuven), Dr Willemze (Lieden), Dr Vreugdenhil (Veldhoven), Drs Bron and Stryckmans† (Brussels), Dr Selleslag (Brugge), Dr De Bock (Antwerpen), Dr Berneman (Antwerpen), Dr Vermeulen (Verviers), Dr Feremans (Brussels), Dr Andrien (Liège), Dr Fillet (Liège), Dr Thyss (Nice), Dr Dreyfus (Paris), Dr. Roozendaal (Amsterdam), Drs Mandelli and Petti (Rome), Dr Gallo (Torino), Dr De Rosa (Napoli), Dr Giustolisi (Catania), Dr Liso (Bari), Dr Mirto (Palermo), Dr Leone (Roma), Dr Fioritoni (Pescara), Dr Amadori (Roma), Drs Fazi and Vignetti (Roma), Dr Rossi Ferrini (Firenze), Dr Volpe (Avellino), Dr Leoni (Ancona), Dr Broccia (Cagliari), Dr Peta (Catanzaro), Dr Mariani (Palermo), Dr Nobile (Reggio Calabria), Dr Damasio (Genova), Dr Rizzoli (Parma), Dr Mettivier (Napoli), Dr Ferrara (Napoli), Dr De Blasio (Latina), Dr Martelli (Perugia), Dr Ricciuti (Potenza), Dr Majolino (Roma), Dr Gabbas (Nuoro), Dr Lucarelli (Pesaro), Dr Bordignon (Milano), Dr Bodini (Cremona), Dr Gallamini (Cuneo), Dr Monaco (Foggia), Dr Mozzana (Gallarate), Dr Saglio (Orbassano), Dr Mazza (Taranto), and Dr Carotenuto† (San Giovanni Rotondo). † indicates deceased.
Prepublished online as Blood First Edition Paper, April 24, 2003; DOI 10.1182/blood-2002-12-3714.
Supported in part by grants from the Kay Kendall Foundation, the Leukemia Cooperative Group of the EORTC, and the National Cancer Institute (grants 5U10-CA11488-23 through 5U10-CA11488-32).
A list of the members of the EORTC and GIMEMA Leukemia Groups appears in the "Appendix."
We thank Saint Jude Children's Research Hospital for providing an SAS macro, allowing the computation of the cumulative incidences of relapse and of death in CR. We thank the data managers of the EORTC (Mr Solbu, Ms Dardenne, Ms Rodts) as well. We thank the cytogeneticists of the different institutions, in particular A. Bernheim (Villejuif), M. Mancini (Rome), and D. Olde-Weghuis (Nijmegen), for the review of karyotypes.
Contents of this study are solely the responsibility of the authors and do not represent the official views of the National Cancer Institute (Bethesda, MD).
Mayer RJ, Davis RB, Schiffer CA, et al. Intensive post-remission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B.
Cassileth PA, Harrington DP, Appelbaum F, et al. Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission.
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Reiffers J, Gaspard MH, Maraninchi D, et al. Comparison of allogeneic or autologous bone marrow transplantation and chemotherapy in patients with acute myeloid leukemia in first remission: a prospective controlled trial.
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Reiffers J, Stoppa AM, Attal M, et al. Allogeneic vs autologous stem cell transplantation vs chemotherapy in patients with acute myeloid leukemia in first remission: the BGMT 87 study.
Harousseau JL, Cahn JY, Pignon B, et al. Comparison of autologous bone marrow transplantation and intensive chemotherapy as postremission therapy in adult acute myeloid leukemia. The Groupe Ouest Est Leucemies Aigues Myeloblastiques (GOELAM).
Zittoun RA, Mandelli F, Willemze R, et al. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia.
Lowenberg B, Verdonck LJ, Dekker AW, et al. Autologous bone marrow transplantation in acute myelogenous leukemia in first remission: results of a Dutch prospective study.
Mitus AJ, Miller KB, Schenkein DP, et al. Improved survival for patients with acute myelogeneous leukemia.
Sierra J, Brunet S, Granena A, et al. Feasibility and results of bone marrow transplantation after remission induction and intensification chemotherapy in de novo acute myeloid leukemia. Catalan Group for Bone Marrow Transplantation.
Burnett AK, Goldstone AH, Stevens R, et al. Randomised comparison of addition of autologous bone-marrow transplantation to intensive chemotherapy for acute myeloid leukaemia in first remission: results of MRC AML 10 trial.
Keating S, de Witte T, Suciu S, et al. The influence of HLA-matched sibling donor availability on treatment outcome for patients with AML: an analysis of the AML 8A study of the EORTC Leukemia Cooperative Group and GIMEMA.
Frassoni F. Commentary and randomised studies in acute myeloid leukaemia: the double truth.
Gale RP, Buchner T, Zhang M-J, et al. HLA-identical sibling bone marrow transplants vs chemotherapy for acute myelogenous leukaemia in first remission.
Gale RP, Horowitz MM, Weiner RS, et al. Impact of cytogenetic abnormalities on outcome of bone marrow transplants in acute myelogenous leukemia in first remission.
Gorin NC, Aegerter P, Auvert B. Autologous bone marrow transplantation for acute leukemia in remission: an analysis of 1322 cases.
Hamatol Bluttransfus
Hermans J, Suciu S, Stijnen T, et al. Treatment of acute myelogenous leukemia: an EBMT-EORTC retrospective analysis of chemotherapy versus allogeneic or autologous bone marrow transplantation.
Eur J Cancer Clin Oncol
de Witte T, Keating S, Suciu S, et al. A randomised comparison of the value of autologous BMT versus autologous PSCT for patients with AML in first CR in the AML 10 trial of the EORTC LCG and GIMEMA [abstract].
Gray R, Wheatley K. How to avoid bias when comparing bone marrow transplantation with chemotherapy.
Yates J, Glidewell O, Wiernik P, et al. Cytosine arabinoside with daunorubicin or adriamycin for therapy of acute myelocytic leukemia: a CALGB study.
Mitelman F, ed.
ISCN 1995: An International System for Human Cytogenetic Nomenclature
. Basel, Switzerland: S. Karger,
Bennett JM, Catovsky D, Daniel MT, et al. Proposed revised criteria for the classification of the acute myeloid leukemia: a report of the French-American-British Cooperative Group.
Bennett JM, Catovsky D, Daniel MT, et al. Proposal for the recognition of minimally differentiated acute myeloid leukaemias (AML-M0).
Klein JP, Moeschberger ML.
Survival Analysis: Techniques for Censored and Truncated Data. Statistics for Biology and Health
. New York: Springer-Verlag;
Gray RJ. A class of K-sample tests for comparing the cumulative incidence of a competing risk.
Ann Stat.
Burnett AK, Wheatley K, Goldstone AH, et al. The value of allogeneic bone marrow transplantation in patients with acute myeloid leukaemia at differing risk of relapse: results of the UK MRC AML 10 trial.
Burnett AK. Current controversies: which patients with acute myeloid leukaemia should receive a bone marrow transplantation? An adult treater's view.
Grimwade D, Walker H, Oliver F, et al. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1612 patients entered into the MRC AML 10 trial.
Slovak ML, Kopecky J, Casseleth PA, et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study.
Lowenberg B, Downing JR, Burnett A. Acute myeloid leukemia.
Slavin S, Aker M, Shapira MY, Panigrahi S, Gabriel C, Or R. Non-myeloablative stem cell transplantation for the treatment of cancer and life-threatening non-malignant disorders: past accomplishments and future goals.
Kolb HJ, Schattenberg A, Goldman JM, et al. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. European Group for Blood and Marrow Transplantation Working Party Chronic Leukemia.


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Home News ePayments has been blocked? Reasons, problems, alternatives
ePayments has been blocked? Reasons, problems, alternatives
On February 12th, 2020, ePayments electronic payment service has been blocked. Millions of customers around the world have been left without the opportunity to send or receive payments online or with ePayments debit/credit cards. Let's find out what's happened and check the alternative solutions.
ePayments is a widely used electronic payment system that's licensed in the UK and allows for issuing IBAN accounts and bank cards for regular users, businesses and online merchants. In July 2018, it has become the first company to use Passport authorization in Telegram messenger. The company fully protects users' funds, and many of them have to go through a complicated KYC procedure, which boosts the security.
However, that didn't save ePayments from serious legal problems.
1 No more payments?
2 Clients haven't been notified
3 Will ePayments come alive?
4 Any alternatives?
No more payments?
On February 11th, ePayments has agreed with the Financial Conduct Authority (British regulator) that it will suspend all activity on the customers' accounts. Such a decision was made after the regulator had found the signs of money-laundering operations.
Since January 10th, 2020, FCA turned into the United Kingdom's only AML authority in the field of crypto business. Evidently, ePayments wasn't able to prove its compliance with Anti Money-Laundering standards in the course of one month.
The regulator plans to introduce even harsher AML and a few other requirements, which means ePayments has a lot of work ahead, and they have to settle up all issues as soon as possible because it concerns millions of users and billiards of USD on their accounts.
Clients haven't been notified
The problem appeared out of nothing – ePayments didn't place any warnings on the official website. Email notifications haven't been sent either. That embarrassed millions of users from all over the world, especially in CIS countries.
ePayments was one of the most convenient and cost-efficient tools for fiat/crypto and crypto/fiat exchanged. The suspension of service is a real issue for freelance workers and businesses.
Will ePayments come alive?
It depends on FCA requirements and how long it will take ePayments to go through the compliance procedures. Most likely, debit and credit cards of regular users will be unblocked in a few weeks. The other functions will be available later – in several months, the requirements will get stricter. At the moment, the company is negotiating with the regulator.
Any alternatives?
The exact alternative options depend on the country of the user's residence. They include:
Payoneer allows for convenient invoicing, issues bank cards and supports several currencies;
Bitcoin, Litecoin, and Ethereum are the most widely used options for cryptocurrency payments;
PayPal is used for online transactions around the world (the transfers between PayPal accounts are free of charge);
WebMoney is a popular alternative among users from CIS countries – it supports various fiat currencies and has recently added a few instruments for cryptocurrency exchange;
Payeer is an international online payment platform and wallet that's available in 200+ countries;
Advcash also issues bank cards, allows for making online payments and exchanging fiat currencies instantly.
Paxum is a Canadian payment processing platform that allows for generating invoices and issuing a debit/credit payment card.
Capitalist allows making mass payments to bank accounts, electronic wallets, and credit cards without opening accounts in other payment systems.
While ePayments is solving the issues with AML compliance, customers are searching for other ways to send and receive payments. Most likely, the service will be available in March. Meanwhile, users are switching to other popular online payment systems and cryptocurrency exchange & trading platforms like Binance and Coinbase.
Diana Limanska	13.02.2020
About Diana Limanska
VP of Partnership integrations at AdSpyglass. She has 5+ years of experience in Adtech and Marktech industry, and more than 10 years of data analysis.
Bidvertizer Ad Network Review 2021
Ibizads Ad Network Review 2021

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Have you ever been annoyed when you wanted to see a document and the download popup appears which forces you to select an external application to view it?
This extension allows you to open the document directly in your browser.
Version 2.0 and later is rewriten using the WebExtensions API. A limitation is that the extension is not able to detect the type when the server does not specify an explicit Content-Type header. In this case, the extension will show the dialog even when it should not be shown. If you would rather see too few dialogs than too many, select the "Open with Firefox" option and remember the choice.
You can always force an "Open in Browser" dialog to be shown by using the "Tools" > "Open in Browser" menu.
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Modify browser.helperApps.neverAsk.saveToDisk by double-clicking on the row.
If you use Firefox 56 or earlier, install Open in Browser version 1.18.


text:
if which coverage > /dev/null; then
    coverage run tests/tests.py
    coverage report
else
    /usr/bin/env python tests/tests.py
fi

redpajama_set_name: RedPajamaGithub


We've been chatting to John Hulsman, the leading geo-political risk analyst and speaker. John's recently been talking to audiences and clients in Delhi, London and Zurich and "for the first time American economic and political problems were front and centre in terms of risk questions (both short term like the fiscal cliff and longer term like debt sustainability), with Iran, China, and Europe being secondary." John was struck by this unanimity, and the abrupt shift in the assessment of where primary risk lies which it represents. "It means the whole unquestioned basic stability of the world we have taken for granted for decades has now to be questioned." To find out more about John, or to book him for your event programme, contact Alex Hickman at alexh@chartwellpartners.co.uk.


Distribution: North Atlantic Ocean: temperate and arctic zones in northern hemisphere. In the western Atlantic, it ranges from western Greenland and the coastal drainages of Quebec, Canada, to Connecticut, USA. Landlocked stocks are present in North America. In the eastern Atlantic, it ranges from the White and Barents Sea basins through northeastern Europe to the Baltic and North Sea basins, including Iceland. Introduced to New Zealand, Chile, southern Argentina and Australia.
Biology: Amphihaline species, spending most of its life in freshwater. Some landlocked populations exist. Found in all rivers where temperature rises above 10° C for about 3 months per year and does not exceed 20° C for more than a few weeks in summer (preferred temperatures 4-12°C). Juveniles may live in cold lakes in northern Europe. Parr (i.e. juveniles) are territorial and are found in the upper reaches of rivers and streams, in riffle areas with strong current and rough gravel bottoms. During winter, parr seek refuge in small spaces or under stones during the day. Young remain in freshwater for 1 to 6 years, then migrate to coastal marine waters or even to open oceans where they remain for 1 to 4 years before returning to freshwater for spawning. Adults inhabit cooler waters with strong to moderate flow. The Atlantic salmon is reported to live up to 10 years, but most individuals only reach 4-6 years. Juveniles feed mainly on aquatic insects, mollusks, crustaceans and fish; adults at sea feed on squids, shrimps, and fish. Most populations depend mostly or exclusively on stocking due to degradations of environmental conditions. Fishing pressure on wild stocks has decreased due to intensive farming but other problems have increased. Farmed salmons escape in large numbers and move to any river and hybridize with wild stocks.


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It's not over yet. Hard to look worse than they did on Saturday but you don't get 2 or 3 losses no matter how bad the loss is. It's still just one game. Plenty of talent there, question is whether they play up to it or not. If they do, on to the next round (where who they face could be anyone as 2 of the top 4 seeds in the East lost their series openers), if they don't, then Brown will be let go pretty quickly and they'll have to see whether they choose to spend money on Harris, Butler, and Simmons. Still have to play Game 2 first though.
Joe says He is elite.
I sure hope a team with 2 elite players doesn't get bounced out of the playoffs in the 1st round.
Oh and BTW......I agree with 100% of your comments.
But you did forget one ELITE aspect concerning Simmons and it's the ONLY ELITE thing about him: The piece of tail He is currently hitting!!!!
Well if Joe says he's elite then he must be. Two things about Joe - 1- Joe says he's rarely wrong, but #2 - be prepared for his wrath when you TELL HIM he's wrong haha.
"How can you be an elite NBA player when you can't make shots that the 8th grade CYO team is expected to make on a routine basis and the CYO team shoots FT's better?"
Plus the team can't let you have the ball in your hands with 5 minutes to go because you are a liability with it at that time of the game??
I guess that is elite.
Oh and yeah.....that is sweet to look at!!!!
Very nice win last night. Simmons showed what he's capable of doing. Monroe had good minutes and our guy from the Clippers Harris showed up.
One of the best games the Sixers have played - they shot the lights out. Simmons, Redick, Harris all excelled. Even Boban was a force!


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Its amazing the number of guests that see the "northern lights" for the very first time while on their fall adventures to Little Duck. No urban sprawl or lighting up here to spoil the view!!
Trophy Lake Trout are a snapping on Neg!!!


Every homeowner should learn all they can to protect their home. However, pulling out the most helpful pieces of information from the irrelevant can be a challenge. Thus, it is wise to review the above information anytime you need advice about how to protect your home.


text:
DeSantis' education nominee backs school choice, comes from public and charter schools
Sen. Manny Diaz Jr., R-Hialeah, and Florida Gov. Ron DeSantis at William A. Kirlew Junior Academy, a Seventh-day Adventist K-8 school in Miami Gardens, in 2019. DAVID SANTIAGO dsantiago@elnuevoherald.com
Miami Herald | By Ana Ceballos Herald/Times Tallahassee Bureau | April 28, 2022
When Gov. Ron DeSantis was looking for the next person to run Florida's education department, he turned to one of the state's loudest school choice supporters: Manny Diaz Jr.
The 49-year-old Republican, a state senator from Hialeah and former teacher, had been the long-rumored pick to replace Richard Corcoran, a firebrand former House speaker who reshaped the job of Florida education commissioner during his four-year term.
Corcoran, with a take no prisoners attitude, carried out many aspects of DeSantis' education agenda. He fought to expand the charter school sector and school vouchers, which pay for students to attend private schools.
And in the pandemic era, he led the charge on reopening schools after briefly shutting them down, punished local school board members who supported strict mask mandates, publicly quarreled with President Joe Biden's administration and tackled head-on the classroom culture war fights that have become so emblematic of DeSantis' political persona.
Diaz, who is poised to be confirmed by the State Board of Education on Friday, will come into a Florida education system reshaped by the pandemic and now a wedge issue in politics as local school officials face increased scrutiny from Republican lawmakers, activists and some parent groups.
He will also enter the scene as DeSantis seeks re-election in November, and a potential run for the White House, with education as a main focus.
A husband and father of four — including three school-age daughters who attend charter schools and a 23-year-old son who graduated from Columbus High School and later Florida International University — Diaz was shaped by an education at Miami Springs Senior High. He received a bachelor's degree from St. Thomas University, a master's degree in education from Nova Southeastern and completed a Harvard Graduate School of Education program for principals.
In this May 9, 2019 file photo. Florida Gov. Ron DeSantis, center, speaks during a bill signing ceremony at the William J. Kirlew Junior Academy, in Miami Gardens. Lynne Sladky AP
Diaz, a mild-mannered lawmaker with deep-rooted ties to charter school operators, aligns with the governor's education agenda. He plans to continue advocating for the GOP mantra about school choice, greater parental control and the fight against what Republicans call the indoctrination of children in the classroom.
But he says his leadership style will probably be "a little different" than Corcoran's. He might not be in the public eye as much.
"Even though I haven't shied away from making comments to the media or anything like that, it's not my intent to be out in the forefront," Diaz said in an interview this week. "My intent is to fulfill the duties of the commissioner and do my job."
Behind the scenes, he expects the governor to be involved in actions taken by the Department of Education.
"He is the top executive of this state, he has had an agenda for education, and I am aligned with that agenda," Diaz said. "I am listening, and I will share my thoughts with him as well."
At the helm of the Department of Education, Diaz would be overseeing several contentious education laws passed by lawmakers this year that will need to be implemented in the next couple of years.
Those include an overhaul to Florida's K-12 testing system and a review and update of state standards and educator practices in relation to the new "parental rights in education" law that critics have called the "don't say gay" bill.
WHAT HISTORY SHOWS ABOUT DIAZ'S PHILOSOPHY
Diaz has served in the Legislature for a decade and since 2013,as avice president at Doral College, a private non-profit institution that offers advanced courses at charter schools. Doral College is affiliated with Academica, a Miami-based for-profit contractor that provides administrative services to charter schools.
Diaz said he plans to resign his post at Doral College to dedicate himself full-time to the commissioner's job.
Before coming into Doral College, Diaz taught social studies at Hialeah-Miami Lakes for four years starting in 1995 and went on to become an assistant principal there from 1999 to 2007.
In January 2021, Diaz was accused by several former students at Hialeah-Miami Lakes Senior High of acting inappropriately around girls while he was a teacher, including making comments on girls' appearances and talking to students about doing ecstasy at Miami clubs. Diaz denied the allegations and said the attacks were politically motivated, "baseless and defamatory." No further action came after the accusations were made.
In the Legislature, he first served in the Florida House and moved to the Senate in 2018. He chaired the Senate Education Committee for several years. And when he no longer did, he continued to sponsor education bills — many of them backed by DeSantis — that drew the praise of Republicans and the ire of Democrats.
In some cases, he found common ground with lawmakers of both parties. In 2020, for example, Diaz sponsored legislation that became the vehicle for a years-long effort to increase Florida teachers' minimum salaries to $47,500 — a priority for DeSantis since he took office.
"I have worked on amendments and bills with Manny that he has been very helpful — in the ones that we can agree on — and he met me in the middle with things that were extremely controversial," said Senate Education Committee Vice Chair Shevrin Jones, a West Park Democrat. "I hope he will take that same energy over to the Department of Education."
Florida Sen. Manny Diaz Jr., left, embraces Sen. Shevrin Jones after the passage of a bill during a legislative session at the Florida State Capitol, Thursday, March 10, 2022, in Tallahassee, Fla. Wilfredo Lee AP
Other Democrats are not too enthused he was picked for the state's top education post, noting his long history of advocating to expand school choice.
"Sen. Diaz is someone who has been a fervent leader in privatization of public education," said state Rep. Anna Eskamani, an Orlando Democrat. "I'm concerned it's going to be more of the same partisan weaponization of education."
Diaz's education philosophy is centered on choice. As commissioner, he said that will be the guiding post.
"I think our job as a state is not to push parents into any particular choice. It is to make those choices available and let them make those choices," he said. "And obviously, continue to strive to have the best public school system as a whole to provide parents with those options."
For years, Diaz has advocated for sweeping school choice measures in the Legislature. In the past two years, he sought to create publicly funded education savings accounts to help families pay for private tuition and other expenses and helped pass legislation that dramatically expanded the Florida Family Empowerment Scholarship voucher program, which DeSantis pushed to create shortly after taking office.
This year, he also carried a bill to overhaul the state's testing system, a process that will be overseen by the Department of Education, and legislation that created a new body within the department to make it potentially easier to get charter schools approved and renewed. It is the latest effort by Republican lawmakers to get more charter schools approved in the state by creating state-level authorization, a concept that was previously found unconstitutional in court.
"I wholeheartedly believe that we have a huge role for our public education and our public schools," Diaz said. "But where I think I have differing opinions from some others is that I do think that the parents should be able to make the choice regardless of ZIP code, regardless of their financial situation, or what best fits the child."
A FOCUS ON PARENTS AND INDOCTRINATION
As one of DeSantis' top allies in the Legislature, Diaz has embraced a message about prioritizing the rights of parents in schools, and about protecting children from indoctrination there.
Those issues go hand in hand, he says.
He defines indoctrination in the classroom as school employees "imposing or putting a student in a situation where they have to either accept or admit something they're not responsible for," or "pushing or imposing a specific view on a topic."
"There is a role for the family here, and there is a role for the parents, [for] social views, political view, religious views and those things," he added.
This year, he sponsored legislation that gets at the heart of the issue. The new law, signed by the governor last week, says schools must not teach lessons about race that foster hatred of the nation or that tell children they are inherently racist. Opponents say the measure is a GOP effort to rewrite history to ignore negative truths, and a federal lawsuit challenging the new law has already been filed.
DeSantis signed the bill in Hialeah Gardens, at an event where children were holding "Stop Woke" and anti-critical race theory signs, which were political in nature. Some Democrats criticized the governor's event as being the "real indoctrination."
But Diaz says the bill is about giving parents "a voice." And he disagrees that DeSantis and his administration's policies are giving more weight to parent groups who share the same conservative ideology.
"I think all parents are getting a voice," he said. "I mean, naturally, parents that agree with certain policies or philosophies are going to gravitate towards one side that supports that, but that doesn't mean that all parents aren't important."
On Friday, Diaz is not expected to face stiff resistance from the board, which is stocked with DeSantis appointees. The board did not conduct a search for the job and scheduled a confirmation hearing for Diaz a day after the governor recommended him for the job.
If confirmed, he would move from Hialeah to Tallahassee to start thejob on June 1. His legislativeteam says he would start transitioning into the role next month.
Diaz knows there is a lot of work to do. Among the tasks will be the implementation of a new testing system that will be rolled out in the 2022-23 academic year, a top priority for the governor.
He will also oversee the implementation of a new law thatprohibits classroom instruction on gender identity and sexual orientation in kindergarten through third grade in public schools, and could restrict the teaching of those topics in older grades if deemed not "age appropriate" by the state.
Diaz did not specify what he, personally, would find to be inappropriate instruction on those topics in grades 4 to 12. But he said the department would conduct a full review on the issue.
"I do expect to look at all that before I formulate any kind of final opinion on specifically what to do," he said. "But when we say age appropriate, what we mean is having those experts in child development … and make sure that we are in compliance with the pupil progression and the pacing plan, like we do with any other topic."
Then, Diaz said, he would like to include the Republican-dominated Legislature on the matter so that lawmakers "can make those decisions, if there are legislative decisions."
Florida approves more math books but provides no explanation
How social-emotional learning became a target for Ron DeSantis and conservatives


We are an 150 seat retro comedy club venue located in the heart of Manhattan's East Village. The club was founded by native New Yorkers who have years of experience in the comedy and bar businesses. Therefore, we pride ourselves in presenting the funniest and most experienced comedians featured on TV and film, and also providing a great environment for our patrons. We host special events, such as: fundraisers, bachelor & bachelorette parties, comedy classes, TV & movie shoots, singles nights, birthday parties, prom shows and New Year's Eve events. There is no age restriction for admission. Shows may contain adult content, but we're an all-ages under 21 comedy club and offer non-alcoholic beverages for our underage customers.
We are an 150 seat retro comedy club venue located in the heart of Manhattan's East Village.


Halloween's just around the corner! Are you frightened of a spooky ghost and ghoul invasion at your home?
Small children in costumes asking for candy is actually a pleasant site to many. But thieves and intruders aren't. Fortunately, you can keep your home and family protected with just one step: Installation of a home security system.
Read on to learn more about why a home security system will immediately boost your home's security and how you can pick out just the right system for your protective needs.
Not all theft and intruder prevention measures will protect you as a security alarm system will. It is the absolute best way to keep you and your family safe.
With a security system in place, the first thing you're doing is preventing burglars and would-be thieves. For example, burglars will be deterred from stealing delivered boxes and packages from your front doorstep. Moreover, they'll be less likely to break in when they think no one's home or steal something around your home (like a parked car or other vehicles or equipment).
When you are home, and possible intruders and other criminals are a threat, you'll be kept safe with an alarm system that will initially scare off intruders, or they'll be immediately caught when alarms blare, and lights flash at their entry. Some systems even contact authorities right away so the assailants can potentially be caught in the act and arrested.
Finally, use an alarm system with a monitoring app to keep an eye on your home while you're away. You can even have an alarm system protect other properties you own. Make sure investment properties, business buildings, or second homes are safe and secure without even having to visit physically.
The main difference you'll encounter with alarm or security systems is how the system is monitored: Centrally by a professional security service or by you, the homeowner.
There are benefits to both types of systems. For example, centrally-monitored systems take care of your security for you. Leave it up to them to monitor your home 24/7 for suspicious activity and breaches in security. It's a more comprehensive way of securing your home. The drawback is these systems tend to be more expensive.
Self-monitored systems can be beneficial because they offer you freedom and flexibility to monitor your home the way you want to do things. These are also less expensive systems for the most part.
The other main choice you'll need to make when getting a new security system is between a DYI installed system and a professionally installed system. The latter will certainly be easier on your time and energy, but not as easy on your pocketbook. They may also be more comprehensive. On the other hand, DIY systems are better than ever before, so some of them actually beat professionally-installed systems protection-wise, and they are simple to install.
Part of keeping your home and family safe is having adequate homeowners insurance coverage. Need help finding a plan that meets your security needs? Reis Insurance can help. Stop in to speak with one of our agents today, or give us a call at your convenience.


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Micro (M) Series: Manufactured to MIL-83513 standards, the M Series of metal and plastic connectors come in sizes ranging from 9 to 100 contacts---allowing customers to customize their termination methods.
microQUAD Series: Engineered to process LVDS (low-voltage differential signaling) bus signals such as Ethernet, IEEE 1394, and serial rapid IO, the microQUAD family of female and male connectors are MIL-83513 certified.
microSI Series: Manufactured out of metal, the microSI family of high-data connectors are ideal for when signal integrity is needed.
Nano (N) Series: Made to MIL-32139 standards, the N Series of metal and plastic connector are ideal for tight spaces.
R Series: Designed to meet MIL-55302 standard, the R Series of plastic connectors come in sizes ranging from 11 to 600 contacts.
RC Series: The RC family of connectors are stackable and perform high-density duties.
RCII Series: Deriving from the RC family, the RCII Series is also stackable and has an aligned contact field.
RZ Series: For applications needing a one-piece contact system, the RZ family of solder-less connectors is ideal.
verSISeries: Designed to work in extreme environments, the verSI family of open-pin connectors are ruggedized and come in male and female options.
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WeCharg has one two-fold mission: Improve developing economies while transitioning the world into alternative energies. This is done by offering the most advanced, automatic, and convenient electric vehicle and car charging technology at the lowest possible price. WeCharg believes everyone should be empowered to make money. Get onboard with WeCharg and together we can change the world.


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Trash travel plan gels
The city hopes to start shipping waste to the mainland next year
By Crystal Kua
ckua@starbulletin.com
» 20 more months for landfill sought
The city is finalizing plans to ship garbage to the mainland in early 2008.
The city plans to ask for bids from waste-shipping companies in August and hopes to reach a deal by Sept. 20, Martin Okabe, executive assistant to city Environmental Services Director Eric Takamura, told the City Council's Planning and Sustainability Committee yesterday.
"We've decided that we're going to be putting out a service agreement which would identify the types of waste that would be available, when the waste could be available ... and we'll be asking obviously for price," he said.
If costs are too high, the city would be able to pull back the contract and cancel it, but the three shippers the city spoke with said they could probably work within the city's $70 to $80 per ton price range, Okabe said.
The City Council has budgeted $5 million in next fiscal year's budget to pay for about six months worth of shipping.
A special committee meeting is scheduled for June 27, when Committee Chairman Gary Okino said he would like to see final plans and cost figures.
Okabe said the administration would not object to shipping garbage off island as long as the city maintains control over the flow of garbage in Oahu's waste stream.
Before the first piece of trash is shipped off island, several more steps are ahead for the city:
» City Council's Planning & Sustainability Committee will hold a special meeting
» Bids from shipping companies will be sought in late August.
» The goal is to reach an agreement with a company by Sept. 20.
» Companies interested must gear up -- including obtaining the necessary regulatory approvals, which could take three to six months.
» Could begin shipping by the first quarter of 2008.


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Pancit Bihon or Pansit Bihon Guisado is a type of noodle dish which makes use of thin rice noodles known as bihon. The Chinese introduced pancit to the Filipinos – from then on, it has been a favorite noodle dish among the locals. It is said that noodles symbolizes long life; for this reason, pancit bihon and other types of pancit are served during birthday parties and special gatherings.
The name Pancit bihon guisado pertains to how pancit bihon is cooked. Guisado or Gisado means to sauté; this describes the dish wherein the thin rice noodles are sautéed with pork or chicken, shrimp, vegetables (such as carrots, snow peas or snap peas, and cabbage), soy sauce, and other special ingredients.
Pancit bihon is best eaten with lemon or calamansi. Simply squeeze lemon or calamansi over the noodles and then toss. Some people have a small bowl with soy sauce and lemon mixture or fish sauce (patis) and lemon mixture.
Pansit Sinanta, Pancit Bato, Pancit Palabok, Pansit Sabaw, Pancit Canton,Pancit Lucban.
This method of cooking pancit involves the rice sticks or thin rice noodles to be soaked in water until it turns soft. Basically, the rice sticks absorbs the water in this process and eventually turns it into rice noodles.
Guisado is a word synonymous to ginisa. This means to saute. Then dish can also be called rice noodle with pork and vegateble saute.
(03:12) pour the water in and then add the chicken bouillon. simmer.
(03:42) cook the vegetable (cabbage, carrots, pea pod, and celery).
(06:02) add the rice noodle.
add the meat and vegetables back in.
(06:54) enjoy this delicious Filipino food.


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Business updates
Source 21
Source 21 Trade Fair and Business Summit kicks off in Nairobi
Regional Cooperation 17 Jul 2019
Next Business Update Previous Business Update
The Source 21 Common Market for Eastern and Southern Africa (COMESA) International Trade Fair and High-Level Business Summit, organized by the COMESA Business Council and hosted by the Government of Kenya in partnership with the Kenya Association of Manufacturers (KAM), has kicked off on Wednesday 17th July 2019 at Kenyatta International Convention Centre (KICC), Nairobi.
The event running under the theme "The Hallmark of Quality" brings together policymakers and the private sector from the 21 COMESA Member States who are the drivers of trade and economic development, to deliberate on how to promote and advance cross-border trade amongst the representative States. The event also includes a presidential public-private round table where Heads of States interact with business leaders on key strategies to enhance industry competitiveness and formulate strategies to enhance local sourcing and intra-regional trade.
HE Uhuru Kenyatta, President of Kenya, who officially opened the event, urged Member States to explore different products that they could trade with and encouraged them to trade amongst themselves. "We need to come up with innovative and practical strategies to promote industrialization and enhance trade in our region," Kenyatta said.
Speaking at the event, the President of the COMESA Business Council, Mr. Marday Venkatasamy, highlighted that this summit is a step towards more business partnerships in Africa and in particular in the COMESA region. He stated that intra-COMESA trade stands at only 6 to 7 percent of total trade and underlined that the potential stands at more than USD 83 Billion annually. ""It is also about working together in order to integrate the global value chain. Africa has the potential to becoming a manufacturing hub to America, Europe and Asia. The continent has the raw materials, and the human capital, and we should work together to tap into the global market at competitive rates..."", he said.
Participants comprised several heads of states, including the President of the Republic of Mauritius, HE Mr. Paramasivum Pillay Vyapoory, Presidents from Zambia and Uganda and several ministers from the African continent.
The COMESA Source 21 Business Facilitation Handbook was also launched to provide market information and investment for its members. Dr. Amany Asfour, immediate past Chairperson of COMESA Business Council, stated that the handbook is the first step in combating lack of knowledge in the region and limited access to trade information in order to promote cross-border trade.
A Mauritian public-private sector delegation, including representatives from EDB, MCCI and Business Mauritius, is currently in Nairobi to attend the Business Summit. A Mauritius Pavillion has also been set up to promote Mauritius as the ideal business hub between Africa and Asia as well to showcase the know-how of Mauritian SMEs.
View all Business Updates


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Aug 2, 2017 8:54PM PT
Aldo Group to Buy Camuto Group in Powerhouse Shoe Deal
By Katie Abel
Katie Abel
More Stories By Katie
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CREDIT: Rex/Shutterstock
The Aldo Group is buying Camuto Group in a deal that brings together two of the most storied names in shoes and creates a huge, new powerhouse.
The marriage will significantly increase both companies' capabilities and broaden their reach in a major way. Aldo derives most of its business from retail and international, while Camuto has robust wholesale and licensing operations and is focused mainly on the U.S market.
Terms of the agreement were not disclosed and the deal is subject to customary closing conditions. The new company will operate two distinct offices, one in Greenwich, Conn., where Camuto is based, and the other in Montreal, where Aldo is headquartered. (The Camuto family will continue to operate the company's apparel businesses.)
The Biggest Retail Predictions for 2021 From Top Execs at Saks, Aldo, Saucony + More
David Bensadoun, CEO of Aldo Group, told FN that his father, founder and company namesake Aldo Bensadoun first approached Camuto CEO Alex Del Cielo about a year ago to see "if the Camuto family might be ready to sell." Four months ago, talks intensified.
"One family business is acquiring another. We both have that entrepreneurial spirit," David Bensadoun said. "Both of our companies are heavily product-oriented, and they each evolved in different ways."
Del Cielo — who worked closely with the late Vince Camuto for decades — said Aldo was the kind of company the legendary executive would have been proud to partner with.
"It was very important that the company be operated the same way Vince would have operated it [and we found that in Aldo]," said Del Cielo, who will stay on board and report to David Bensadoun. "We weren't actively shopping the company, but the shareholders liked the idea and felt comfortable."
The two founders share an impressive achievement: they both won FN's coveted lifetime achievement award. Camuto took the honor home in 2013, while Bensadoun was fêted in 2016.
Both executives opened up to FN about their deep belief in surrounding themselves with great people and treating everyone with respect.
"If you look at the successes of the best companies in America, it was the culture that was built and remained long after the principals weren't there," Camuto told FN in 2013. "It's never about one person. It's about the teams you put in place. Without the right people, you're nowhere."
Bensadoun shared a similar sentiment in 2016 about his own vision: "When I started the company, I wanted to create a model of what I believed society should be," he explained. "To me, there are certain human values that are important. Yes, you can work hard and succeed, but you should not tramp on people. Everyone has the right to succeed, and you should enable them to reach their full potential."
Aldo's deal with Camuto will certainly alter the playing field in an industry that continues to undergo rapid consolidation. Just last week, Michael Kors said it was buying Jimmy Choo for $1.2 billion. That follows Coach's move to buy Kate Spade for $2.4 billion.


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Minister for Women
Senator the Hon Marise Payne
Statement on protests in Hong Kong
Australia has a substantial interest in Hong Kong's success, home to one of our biggest expatriate communities globally and our largest commercial presence in Asia.
There is intense public interest and international community concern at events in Hong Kong.
Australia supports the right of people to protest peacefully and to exercise their freedom of speech, and we urge all sides to show restraint and avoid violence.
The Australian Government believes it is important that any changes to Hong Kong's extradition arrangements are pursued in keeping with regular processes of government and resolved in a way that fully respects Hong Kong's high degree of autonomy and upholds the rights and freedoms enshrined in Hong Kong's Basic Law under the 'one country, two systems' framework.
The Australian Consul-General in Hong Kong has raised concerns about the proposed amendments at senior levels within the Hong Kong government and with the Executive and Legislative Councils.
DFAT keeps its travel advisories under close review. On 12 June, DFAT issued an update to the travel advice for Hong Kong advising Australian citizens that they may encounter demonstrations or protests in Hong Kong and to avoid large public gatherings.
Minister's office: (02) 6277 7500
DFAT Media Liaison: (02) 6261 1555
Download the official portrait of the Minister
Austrade
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Australian Centre for International Agricultural Research
Australian Secret Intelligence Service
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"He was wearing heavy shoes."
"I found a pair of dress shoes at the store."
"Be sure to bring your gym shoes."
"Put on your shoes before you go outside."
"Please take off your shoes before entering the house."
"He needs help tying his shoes."
"I need to break in these shoes."
"We need to buy some shoe polish."
"I like to save shoe boxes."
"Do you use a shoe rack?"