***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Between August 1990 and August 1995 , 231 patients ( median age 51 , 53 % Durie-Salmon stage III , median serum beta-2-microglobulin 3.1 g/L , median C-reactive protein 4 g/L ) with symptomatic multiple myeloma were enrolled in a program that used a series of induction regimens and two cycles of high-dose therapy ( " Total Therapy " ) . Remission induction utilized non-cross-resistant regimens ( vincristine-doxorubicin-dexamethasone [ VAD ] , high-dose cyclophosphamide and granulocyte-macrophage colony-stimulating factor with peripheral blood stem cell collection , and etoposide-dexamethasone-cytarabine-cisplatin ) . The first high-dose treatment comprised melphalan 200 mg/m2 and was repeated if complete ( CR ) or partial ( PR ) remission was maintained after the first transplant ; in case of less than PR , total body irradiation or cyclophosphamide was added . Interferon--2b maintenance was used after the second autotransplant . Fourteen patients with HLA-compatible donors underwent an allograft as their second high-dose therapy cycle . Eighty-eight percent completed induction therapy whereas first and second transplants were performed in 84 % and 71 % ( the majority within 8 and 15 months , respectively ) . Eight patients ( 3 % ) died of toxicity during induction , and 2 ( 1 % ) and 6 ( 4 % ) during the two transplants . True CR and at least a PR ( PR plus CR ) were obtained in 5 % ( 34 % ) after VAD , 15 % ( 65 % ) at the end of induction , and 26 % ( 75 % ) after the first and 41 % ( 83 % ) after the second transplants ( intent-to-treat ) . Median overall ( OS ) and event-free ( EFS ) survival duration s were 68 and 43 months , respectively . Actuarial 5-year OS and EFS rates were 58 % and 42 % , respectively . The median time to disease progression or relapse was 52 months . Among the 94 patients achieving CR , the median CR duration was 50 months . On multivariate analysis , superior EFS and OS were observed in the absence of unfavorable karyotypes ( 11q breakpoint abnormalities , -13 or 13-q ) and with low beta-2-microglobulin at diagnosis . CR duration was significantly longer with early onset of CR and favorable karyotypes . Time-dependent covariate analysis suggested that timely application of a second transplant extended both EFS and OS significantly , independent of cytogenetics and beta-2-microglobulin . Total Therapy represents a comprehensive treatment approach for newly diagnosed myeloma patients , using multi-regimen induction and t and em transplantation followed by interferon maintenance . As a result , the proportion of patients attaining CR increased progressively with continuing therapy . This observation is particularly important because CR is a sine qua non for long-term disease control and , eventually , cure BACKGROUND AND OBJECTIVES The Dutch-Belgian HOVON group performed a r and omized phase 3 trial to compare single non-myeloablative intensive treatment with double , intensive treatment in previously untreated patients with multiple myeloma ( MM ) . DESIGN AND METHODS Three hundred and three patients with stage II/III MM were r and omized after VAD induction chemotherapy  to receive two cycles of non-myeloablative intermediate-dose melphalan ( 70 mg/m2 ) ( single treatment ) or the same regimen followed by cyclophosphamide 120 mg/kg iv plus total body irradiation ( TBI ) 9 Gy and autologous stem cell transplantation ( double , intensive treatment ) . In both treatment arms interferon .IIa was given as maintenance until relapse/progression . RESULTS A significantly higher proportion of patients achieved a complete remission ( CR ) on protocol treatment with double , intensive therapy ( 32 % vs 13 % , p<0.001 ) . Double treatment produced better outcome in terms of event-free survival ( median 22 vs 21 months , 28 % vs 14 % at 4 years and 15 % vs 7 % at 6 years after r and omization ; logrank p=0.013 ; univariate HR 0.74 , 95 % CI , 0.58 - 0.94 ) , progression-free survival ( median 27 vs 24 months , 33 % vs 16 % at 4 years , and 17 % vs 9 % at 6 years after r and omization ; logrank p=0.006 ; HR=0.71 , 95 % CI 0.56 - 0.91 ) , but not overall survival ( median 50 vs 55 months , 52 % vs 56 % at 4 years and 39 % vs 36 % at 6 years after r and omization ; logrank p=0.51 ; HR=1.10 , 95 % CI 0.83 - 1.46 ) . The achievement of a CR had a favorable prognostic impact on event-free survival ( HR=0.60 , 95 % CI=0.44 -0.82 , p=0.001 ) and progression-free survival ( HR=0.62 , 95 % CI=0.45 -0.84 , p=0.002 ) . INTERPRETATION AND CONCLUSIONS Double , intensive treatment result ed in a better CR rate , event-free survival and progression-free survival but not overall survival compared to single non-myeloablative treatment in previously untreated patients with multiple myeloma Fluorescence in situ hybridization ( FISH ) has become a powerful technique for prognostic assessment in multiple myeloma ( MM ) . However , the existence of associations between cytogenetic abnormalities compels us to re-assess the value of each abnormality . A total of 260 patients with MM at the time of diagnosis , enrolled in the GEM-2000 Spanish transplant protocol , have been analyzed by FISH in order to ascertain the independent influence on myeloma prognosis of IGH translocations , as well as RB and P53 deletions . Survival analyses showed that patients with t(4;14 ) , RB or P53 deletions had a significantly shorter survival than patients without these abnormalities . However , patients with RB deletions without other abnormalities in FISH analysis , displayed a similar outcome to those patients without genetic changes by FISH ( 46 vs 54 months , P=0.3 ) . In the multivariate analysis the presence of t(4;14 ) , RB deletion associated with other abnormalities , age > 60 years , high proportion of S-phase cells and advanced stage of the disease according to the International Staging System retained their independent prognostic influence . In summary , RB deletion as a sole abnormality does not lead to a shortening in the survival of MM patients , whereas t(4;14 ) confers the worst prognosis in MM patients treated with high-dose chemotherapy Virtually no progress has been made during more than 2 decades of clinical trials for multiple myeloma ( MM ) involving st and ard therapy ( ST ) . Recent studies suggest that dose intensification requiring hematopoietic stem cell support results in higher complete response ( CR ) rates and extended disease control .  " Total Therapy " ( TT ) consisting of noncross-resistant induction regimens , followed by a double autotransplant ( AT ) procedure , was administered to 123 untreated patients with symptomatic MM . Upon hematologic recovery , interferon ( IFN ) maintenance ( 3 million units [MU]/m2 subcutaneously thrice weekly ) was given until disease recurrence/progression . Results were compared with the outcome of untreated patients receiving ST according to Southwest Oncology Group ( SWOG ) trials . One hundred sixteen pair mates were selected from both TT and among 1,123 patients to match for the major prognostic features . TT induced CR in 40 % of all 123 patients ( intent-to-treat ) . By 12 months , 7 % had died , including 4 % from treatment-related complications . With a median follow-up of 31 months , median duration s of event-free survival ( EFS ) and overall survival ( OS ) are 49 and 62 + months , respectively . Abnormalities of chromosomes 11q and 13 were associated with inferior outcome , whereas CR within 6 months after induction was a favorable prognostic feature for both EFS and OS . In comparison to ST , TT induced higher PR rates ( 85 % v 52 % , P < .0001 ) ( CR rates not available on SWOG trials ) and extended EFS ( 49 v 22 months , P = .0001 ) and OS ( 62 + v 48 months , P = .01 ) . Compared to ST , dose intensification with double AT markedly augments tumor cytoreduction , effecting not only higher CR rates but also significantly extending EFS and OS in previously untreated patients with MM PURPOSE We performed a prospect i ve , r and omized study of single ( arm A ) versus double ( arm B ) autologous stem-cell transplantation ( ASCT ) for younger patients with newly diagnosed multiple myeloma ( MM ) . PATIENTS AND METHODS A total of 321 patients were enrolled onto the study and were r and omly assigned to receive either a single course of high-dose melphalan at 200 mg/m2 ( arm A ) or melphalan at 200 mg/m2 followed , after 3 to 6 months , by melphalan at 120 mg/m2 and busulfan at 12 mg/kilogram ( arm B ) . RESULTS As compared with assignment to the single-transplantation group ( n = 163 patients ) , r and om assignment to receive double ASCT ( n = 158 patients ) significantly increased the probability to attain at least a near complete response ( nCR ; 33 % v 47 % , respectively ; P = .008 ) , prolonged relapse-free survival ( RFS ) duration of 18 months ( median , 24 v 42 months , respectively ; P < .001 ) , and significantly extended event-free survival ( EFS ; median , 23 v 35 months , respectively ; P = .001 ) . Administration of a second transplantation and of novel agents for treating sequential relapses in up to 50 % of patients r and omly assigned to receive a single ASCT likely contributed to prolong the survival duration of the whole group , whose 7-year rate ( 46 % ) was similar to that of the double-transplantation group ( 43 % ; P = .90 ) . Transplantation-related mortality was 3 % in arm A and 4 % in arm B ( P = .70 ) . CONCLUSION In comparison with a single ASCT as up-front therapy for newly diagnosed MM , double ASCT effected superior CR or nCR rate , RFS , and EFS , but failed to significantly prolong overall survival . Benefits offered by double ASCT were particularly evident among patients who failed at least nCR after one autotransplantation BACKGROUND We conducted a r and omized trial of the treatment of multiple myeloma with high-dose chemotherapy followed by either one or two successive autologous stem-cell transplantations . METHODS At the time of diagnosis , 399 previously untreated patients under the age of 60 years were r and omly assigned to receive a single or double transplant . RESULTS A complete or a very good partial response was achieved by 42 percent of patients in the single-transplant group and 50 percent of patients in the double-transplant group ( P=0.10 ) . The probability of surviving event-free for seven years after the diagnosis was 10 percent in the single-transplant group and 20 percent in the double-transplant group ( P=0.03 ) . The estimated overall seven-year survival rate was 21 percent in the single-transplant group and 42 percent in the double-transplant group ( P=0.01 ) . Among patients who did not have a very good partial response within three months after one transplantation , the probability of surviving seven years was 11 percent in the single-transplant group and 43 percent in the double-transplant group ( P<0.001 ) . Four factors were significantly related to survival : base-line serum levels of beta2-microglobulin ( P<0.01 ) and lactate dehydrogenase ( P<0.01 ) , age ( P<0.05 ) , and treatment group ( P<0.01 ) . CONCLUSIONS As compared with a single autologous stem-cell transplantation after high-dose chemotherapy , double transplantation improves overall survival among patients with myeloma , especially those who do not have a very good partial response after undergoing one transplantation The prognostic value of chromosomal abnormalities was studied in untreated multiple myeloma patients who were registered into a prospect i ve r and omised multicentre phase 3 study for intensified treatment ( HOVON24 ) . A total of 453 patients aged less than 66 years with stage II and III A/B disease were registered in the clinical study .  Cytogenetic analysis was introduced as a st and ard diagnostic assay in 1998 . It was performed at diagnosis in 160 patients and was successful in 137/160 patients ( 86 % ) . An abnormal karyotype was observed in 53/137 ( 39 % ) of the patients . Abnormalities of chromosome 1p and 1q were found in 19 ( 36 % of patients with an abnormal karyotype ) and 21 patients ( 40 % ) . There was a strong association between chromosome 1p and /or 1q abnormalities and deletion of chromos 
    Output:
    
CONCLUSION In previously untreated MM patients , use of t and em AHCT did not result in improved OS or EFS .
We conclude that t and em AHCT is associated with improved response rates but at risk of clinical ly significant increase in TRM