***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Summary : A prospect i ve r and omized trial was conducted to study the timing of high-dose intravenous melphalan and autologous stem cell transplantation ( HDM/SCT ) in AL amyloidosis . In all , 100 newly diagnosed patients were r and omized to receive  HDM/SCT  , either as initial therapy ( Arm-1 ) or following two cycles of oral melphalan and prednisone ( Arm-2 ) . The objectives of the trial were to compare survival and hematologic and clinical responses . With a median follow-up of 45 months ( range 24–70 ) , the overall survival was not significantly different between the two treatment arms ( P=0.39 ) . The hematologic response and organ system improvements after treatment did not differ between the two groups . Fewer patients received HDM/SCT in Arm-2 because of disease progression during the oral chemotherapy phase of the study , rendering them ineligible for subsequent high-dose therapy . This affected patients with cardiac involvement particularly , and led to a trend for an early survival disadvantage in Arm-2 . Hence , newly diagnosed patients with AL amyloidosis eligible for HDM/SCT did not benefit from initial treatment with oral melphalan and prednisone , and there was a survival disadvantage for patients with cardiac involvement if HDM/SCT was delayed by initial oral chemotherapy One hundred sixty-eight patients with primary systemic amyloidosis ( AL ) were identified . Median survival after diagnosis was 12 months and ranged from 4 months for patients presenting with congestive heart failure to 50 months for those presenting with peripheral neuropathy only . Utilizing the proportional-hazards model in a stepwise multivariate fashion to evaluate the simultaneous influence of putative risk factors as of diagnosis revealed that congestive heart failure , urine light chain , hepatomegaly , and multiple myeloma were the major factors adversely affecting survival during the first year after diagnosis . Serum creatinine , multiple myeloma , orthostatic hypotension , and monoclonal serum protein were the most important variables adversely affecting survival for patients surviving 1 year . These models were used to categorize patients according to the variables in the models into low- , moderate- , and high-risk groups for the first year after diagnosis and separately for subsequent years . The influence of these variables on survival is important in stratification of patients r and omized to prospect i ve clinical trials High‐dose melphalan ( MEL ) with autologous stem cell transplant ( SCT ) is an effective therapy for systemic AL amyloidosis ( AL ) , but treatment‐related mortality ( TRM ) has historically been high . We performed a phase II trial of risk‐adapted SCT followed by adjuvant dexamethasone ( dex ) and thalidomide ( thal ) in an attempt to reduce TRM and improve response rates . Patients ( n = 45 ) with newly diagnosed AL involving ≤2 organ systems were assigned to MEL 100 , 140 , or 200 mg/m2 with SCT , based on age , renal function and cardiac involvement . Patients with persistent clonal plasma cell disease 3 months post‐SCT received 9 months of adjuvant thal/dex ( or dex if there was a history of deep vein thrombosis or neuropathy ) . Organ involvement was kidney ( 67 % ) , heart ( 24 % ) , liver/GI ( 22 % ) and peripheral nervous system ( 18 % ) , with 31 % having two organs involved . TRM was 4·4 % . Thirty‐one patients began adjuvant therapy , with 16 ( 52 % ) completing 9 months of treatment and 13 ( 42 % ) achieving an improvement in haematological response . By intention‐to‐treat , overall haematological response rate was 71 % ( 36 % complete response ) , with 44 % having organ responses . With a median follow‐up of 31 months , 2‐year survival was 84 % ( 95 % confidence interval : 73 % , 94 % ) . Risk‐adapted SCT with adjuvant thal/dex is feasible and results in low TRM and high haematological and organ response rates in AL patients PURPOSE Based on the success of hematopoietic stem-cell transplantation ( HSCT ) for multiple myeloma , HSCT is being used to treat patients with primary systemic amyloidosis ( AL ) . This article addresses the extent to which eligibility to undergo HSCT is a favorable prognostic feature and explores prognostic factors within the subset of eligible patients . PATIENTS AND METHODS The Mayo Clinic amyloid data base was queried for all patients with AL seen at the Mayo Clinic from 1983 through 1997 who would have been eligible for peripheral-blood stem-cell transplantation . Inclusion criteria included biopsy-proven amyloid , symptomatic disease , absence of a clinical diagnosis of multiple myeloma , age < or = 70 years , cardiac interventricular septal thickness < or = 15 mm , cardiac ejection fraction more than 55 % , serum creatinine < or = 2 mg/dL , and direct bilirubin < or = 2.0 mg/dL. RESULTS Median age was 56 years ( range , 25 to 70 ) with 79 ( 34 % ) older than 60 years . One hundred patients had early cardiac involvement ; 41 , hepatic involvement ; 167 , renal involvement ; and 39 , nerve involvement . The 229 patients have had a median follow-up of 52 months , and 151 have died . The median survival was 42 months with 5- and 10-year survival rates of 36 % and 15 % , respectively . Important predictors of survival were size of M-component in 24-hour urine , number of involved organs , alkaline phosphatase , performance score , and weight loss . CONCLUSION The same patients who are eligible for HSCT are a good-risk population who do relatively well with chemotherapy ( median survival , 42 months ) , substantially better than the expected median survival of 18 months for all patients with AL . A r and omized trial is needed to assess the true effect of HSCT Current therapy of primary systemic ( AL ) amyloidosis with oral melphalan and prednisone remains unsatisfactory , with a median survival of only 13 months . Between 1996 and 2003 , 93 patients with biopsy-proven AL amyloidosis were enrolled in a prospect i ve US national cooperative group trial . Treatment schema consisted of induction therapy with pulse dexamethasone ( DEX ) , followed by maintenance therapy with DEX and alpha interferon .  Hematologic complete remissions were observed in 24 % and improvement in AL amyloidosis-related organ dysfunction occurred in 45 % of patients evaluable for response . Median survival of the entire cohort is 31 months , with an estimated 2-year overall survival ( OS ) and event-free survival ( EFS ) of 60 % and 52 % , respectively . Presence of congestive heart failure and increased level of serum beta2 microglobulin ( > /= 0.0035 g/L [ 3.5 mg/L ] ) were dominant predictors of adverse outcome . Estimated 2-year OS in patients who are eligible to receive transplants with this approach was 78 % . These data demonstrate for the first time in the context of a US multicenter prospect i ve clinical trial that front-line therapy with a DEX-based regimen in AL amyloidosis can lead to durable reversal of AL amyloidosis-related organ dysfunction and prolonged survival This study investigated the response rate and toxicity of blood cell transplantation as treatment for primary amyloidosis ( AL ) . Twenty-three patients had stem cells collected between November 1995 and September 1998 . Conditioning included melphalan and total body irradiation in 16 and melphalan alone in 4 . Three patients did not undergo stem cell infusion because of poor performance status . Two died of progressive amyloid at 1 and 3 months . One patient is alive on hemodialysis . Fourteen males and six females ( median age , 57 years ) underwent  transplantation . Renal , cardiac ( by echocardiography ) , peripheral neuropathy or liver amyloidosis occurred in 14 , 12 , 3 , and 1 , respectively . Echocardiography demonstrated an interventricular septal thickness ⩾15 mm in six patients , five of whom died post transplantation . Three patients died of progressive amyloidosis at 7 , 7 , and 21 months . Thirteen patients are alive with a follow-up of 3 to 26 months . Twelve ( 60 % ) fulfilled the criteria of a hematologic or organ response . Severe gastrointestinal tract toxicity was seen in five ( 25 % ) . We conclude that blood cell transplantation for amyloidosis had a much higher morbidity and mortality compared with transplantation for myeloma . The best results appear to occur in patients with nephrotic syndrome as the only manifestation of their disease . Bone Marrow Transplantation ( 2000 ) 26 , 963–969 Context AL amyloidosis responds poorly to oral chemotherapy and rarely leads to elimination of plasma cell dyscrasia . Amyloid cardiomyopathy is a particularly fatal complication of the disease . Contribution Analysis of consecutive patients with AL amyloidosis from 6 separate trials over 8 years shows that high-dose intravenous melphalan therapy combined with autologous stem-cell transplantation greatly improves duration of survival and ameliorates organ dysfunction . Implication s Intravenous melphalan therapy combined with stem-cell transplantation represents a clinical ly significant improvement in treating AL amyloidosis and shows promise in reversing amyloid cardiomyopathy . The Editors The most common form of systemic amyloidosis in the United States is AL ( or primary ) amyloidosis . In this disease , amyloid fibrils are derived from monoclonal immunoglobulin light chains that are produced by an underlying clonal plasma cell dyscrasia . Although the burden of plasma cells is generally low , accumulation of amyloid deposits in vital organs leads to progressive disability and death . The median survival of untreated patients after diagnosis is 12 months and less than 5 months for those with cardiomyopathy ( 1 - 5 ) . AL amyloidosis is reported to occur in 5 to 12 persons per million per year in the United States ; however , death records and autopsy results suggest that the incidence may be higher ( 6 , 7 ) . Treatment with oral melphalan results in a modest increase in median survival but rarely eliminates the plasma cell dyscrasia and is not effective for rapidly progressive disease ( 8 - 10 ) . Alternative chemotherapy regimens have not improved survival further ( 11 - 15 ) . Promising treatment outcomes observed with high-dose intravenous melphalan and autologous stem-cell transplantation in multiple myeloma ( 16 - 19 ) provided a rationale for testing the hypothesis that this treatment would improve survival for patients with AL amyloidosis . Favorable responses to high-dose melphalan and stem-cell transplantation in patients with AL amyloidosis have been reported in case reports and in small series ; however , treatment-related mortality was high in multicenter trials ( 20 - 28 ) . Our initial experience with treatment in AL amyloidosis indicated that selected patients can tolerate treatment and that hematologic responses and reversal of amyloid-related organ dysfunction can be achieved ( 29 - 32 ) . Since 1994 , we have evaluated 701 patients with AL amyloidosis , 312 of whom initiated high-dose melphalan treatment and stem-cell transplantation .  This longitudinal study examines survival , hematologic response , and improvement of amyloid-related organ disease in patients who were treated with high-dose melphalan and stem-cell transplantation .  We contrast these data with features and survival of a simultaneous cohort of patients who were not eligible for treatment . Methods Patients Between July 1994 and June 2002 , 701 consecutive patients with AL amyloidosis were evaluated and clinical data were collected with the approval of the Institutional Review Board of Boston University Medical Center . All patients had biopsy-proven amyloid disease and a documented plasma cell dyscrasia , which was diagnosed by the presence of clonal plasma cells in the bone marrow or a monoclonal gammopathy detected by immunofixation electrophoresis of serum or urine proteins ( Figure 1 ) . To exclude another type of systemic amyloidosis and a monoclonal gammopathy of unknown significance , all patients with findings compatible with familial or secondary ( AA ) amyloidosis were tested by DNA analysis for gene mutations in transthyretin , apolipoprotein A1 , fibrinogen , and lysozyme known to be associated with amyloidosis and by immunohistochemistry of the biopsy tissue for AA amyloid fibril deposits ( 33 ) . Patients with multiple myeloma ( bone marrow plasmacytosis 30 % or lytic bone lesions ) were excluded . In patients older than 70 years of age with cardiomyopathy only , a diagnosis of senile cardiac amyloidosis ( caused by wild-type transthyretin ) was excluded by immunohistochemical examination of a tissue biopsy specimen using antiserum to transthyretin . All patients were evaluated for degree of organ involvement by physical examination , st 
    Output:
    
In the controlled studies , there was no heterogeneity for any outcome ; however , in the single-arm studies , there was a significant heterogeneity for the outcomes of OS , CHR , renal response , and partial hematologic response .
Our findings indicate that AHCT does not appear to be superior to CC in improving OS in patients with AL amyloidosis .