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Autologous stem cell transplant (ASCT) has been an important component of therapy for myeloma patients eligible for high-dose chemotherapy. Recent studies comparing early transplant to low-dose chemotherapy support the continued use of ASCT as consolidation following induction therapy, even in the era of immunomodulatory drugs, proteasome inhibitors, and other novel agents. Despite the marked improvements in outcomes with this approach, most patients will eventually experience disease progression. Thus, inclusion of post-ASCT consolidation/maintenance strategies is used to improve long-term disease control. Multiple randomized studies support the use of lenalidomide maintenance therapy following ASCT. The next generation of clinical trials will incorporate novel agents such as monoclonal antibodies, proteasome inhibitors, and other novel pathway modulatory agents into post-ASCT treatment strategies with the goal of achieving even deeper responses and longer durations of disease control., (© 2016 by The American Society of Hematology. All rights reserved.)

Multiple myeloma remains a highly treatable but incurable disease. New agents with improved efficacy have increased the response to induction treatment. These agents have been adapted for use in maintenance therapy strategies to improve responses and delay relapse/progression with the ultimate goal of improved overall survival. Recent trials have shown that the immunomodulatory drugs thalidomide and lenalidomide; the proteasome inhibitor bortezomib; and the bisphosphonate zoledronate improve time to progression and overall survival. Introduction of new therapies, alone or in combination with existing agents, may lead to increased improvement and prolongation of disease control after autologous hematopoietic stem cell transplantation for transplant-eligible patients.

Background: Data are lacking on whether lenalidomide maintenance therapy prolongs the time to disease progression after autologous hematopoietic stem-cell transplantation in patients with multiple myeloma., Methods: Between April 2005 and July 2009, we randomly assigned 460 patients who were younger than 71 years of age and had stable disease or a marginal, partial, or complete response 100 days after undergoing stem-cell transplantation to lenalidomide or placebo, which was administered until disease progression. The starting dose of lenalidomide was 10 mg per day (range, 5 to 15)., Results: The study-drug assignments were unblinded in 2009, when a planned interim analysis showed a significantly longer time to disease progression in the lenalidomide group. At unblinding, 20% of patients who received lenalidomide and 44% of patients who received placebo had progressive disease or had died (P<0.001); of the remaining 128 patients who received placebo and who did not have progressive disease, 86 crossed over to lenalidomide. At a median follow-up of 34 months, 86 of 231 patients who received lenalidomide (37%) and 132 of 229 patients who received placebo (58%) had disease progression or had died. The median time to progression was 46 months in the lenalidomide group and 27 months in the placebo group (P<0.001). A total of 35 patients who received lenalidomide (15%) and 53 patients who received placebo (23%) died (P=0.03). More grade 3 or 4 hematologic adverse events and grade 3 nonhematologic adverse events occurred in patients who received lenalidomide (P<0.001 for both comparisons). Second primary cancers occurred in 18 patients who received lenalidomide (8%) and 6 patients who received placebo (3%)., Conclusions: Lenalidomide maintenance therapy, initiated at day 100 after hematopoietic stem-cell transplantation, was associated with more toxicity and second cancers but a significantly longer time to disease progression and significantly improved overall survival among patients with myeloma. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00114101.).

Clinical research published since the first evidence-based review on the role of hematopoietic stem cell transplantation (SCT) in the treatment of pediatric acute lymphoblastic leukemia (ALL) is presented and critically evaluated in this update. Treatment recommendations are provided by an expert panel. Allogeneic SCT is recommended for children who: are in second complete remission (CR2) after experiencing an early marrow relapse for precursor-B ALL; experienced primary induction failure, but subsequently achieved a CR1; have T-lineage ALL in CR2; or have ALL in third or greater remission. Although the 2005 pediatric ALL evidence-based review (EBR) recommended allogeneic SCT for children with Philadelphia chromosome positive (Ph+) ALL in CR1, preliminary tyrosine kinase inhibitor (TKI) data demonstrate that early outcomes are comparable for allogeneic SCT and chemotherapy + imatinib. Based on the evidence, autologous SCT is not recommended for ALL in CR1. Allogeneic SCT is not recommended for: T-lineage ALL in CR1; mixed-lineage leukemia (MLL)+ ALL when it is the sole adverse risk factor; isolated central nervous system (CNS) relapse in precursor-B ALL. Based on expert opinion, allogeneic SCT may be considered for hypodiploid ALL and persistent minimal residual disease [corrected] (MRD) positivity in ALL in CR1 or greater, although these are areas that need further study. Treatment recommendations pertaining to various transplantation techniques are also provided, as are areas of needed future research., (Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Objective: In 1999, three randomized controlled trials concluded that high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HDC/HCT) is no better than conventional chemotherapy for women with breast cancer. This study documents the impact of the trials on use of HDC/HCT and describes how hospitals reacted to the trials., Data Source: We used patient-level data on 15,847 HDC/HCTs reported to the Center for International Blood and Marrow Transplant Research between 1994 and 2005., Study Design: We report trends in total HDC/HCT procedure volume, compare the time to hospitals' exit from the HDC/HCT market between research and nonresearch hospitals, and document trends in hospital-specific volumes in the 2 years before exit., Principal Findings: HDC/HCT volume declined from 3,108 in 1998 to 1,363 the year after trial results were released. In 2002, only 76 procedures were performed. Teaching hospitals and the hospitals that participated in the trials were no slower to discontinue the procedure compared with nonteaching, nonparticipating hospitals. At the hospital level, volume declined steadily in the months before abandonment., Conclusion: The results suggest that comparative effectiveness research studies that report negative results can reduce spending, but specialists may be reluctant to relinquish cutting-edge technologies., (© Health Research and Educational Trust.)

Imatinib mesylate (IM, Gleevec) has largely supplanted allogeneic hematopoietic cell transplantation (HCT) as first line therapy for chronic myeloid leukemia (CML). Nevertheless, many people with CML eventually undergo HCT, raising the question of whether prior IM therapy impacts HCT success. Data from the Center for International Blood and Marrow Transplant Research on 409 subjects treated with IM before HCT (IM(+)) and 900 subjects who did not receive IM before HCT (IM(-)) were analyzed. Among patients in first chronic phase, IM therapy before HCT was associated with better survival but no statistically significant differences in treatment-related mortality, relapse, and leukemia-free survival. Better HLA-matched donors, use of bone marrow, and transplantation within one year of diagnosis were also associated with better survival. A matched-pairs analysis was performed and confirmed a higher survival rate among first chronic phase patients receiving IM. Among patients transplanted with advanced CML, use of IM before HCT was not associated with treatment-related mortality, relapse, leukemia-free survival, or survival. Acute graft-versus-host disease rates were similar between IM(+) and IM(-) groups regardless of leukemia phase. These results should be reassuring to patients receiving IM before HCT.

Clinical research examining the role of hematopoietic stem cell transplantation (HSCT) in the therapy of acute myelogenous leukemia (AML) in adults is presented and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the treatment recommendations. Treatment recommendations based on the evidence are presented in Table 3, entitled Summary of Treatment Recommendations Made by the Expert Panel for Adult Acute Myelogenous Leukemia, and were reached unanimously by a panel of AML experts. The identified priority areas of needed future research in adult AML include: (1) What is the role of HSCT in treating patients with specific molecular markers (eg, FLT3, NPM1, CEBPA, BAALC, MLL, NRAS, etc.) especially in patients with normal cytogenetics? (2) What is the benefit of using HSCT to treat different cytogenetic subgroups? (3) What is the impact on survival outcomes of reduced intensity or nonmyeloablative versus conventional conditioning in older (>60 years) and intermediate (40-60 years) aged adults? (4) What is the impact on survival outcomes of unrelated donor HSCT vesus chemotherapy in younger (<40 years) adults with high risk disease?

The discovery and approval of imatinib drastically changed the therapeutic algorithm for chronic myeloid leukaemia (CML). Imatinib is now considered the therapy of choice for patients with newly diagnosed CML, including those previously considered candidates for allogeneic haematopoietic cell transplantation (HCT). We compared numbers and types of allogeneic HCTs performed for CML in North America before and after the introduction of imatinib, and publication of the International Randomized Trial of Interferon and STI571 (IRIS) using transplants reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). The number of HCTs for CML registered with the CIBMTR in 1998 was 617; 62% were performed in first chronic phase (CP1). Only 1% of patients had received imatinib prior to transplantation. In 2003, the number of HCTs reported was 223; 44% were performed in CP1 and 77% of patients received imatinib prior to transplantation. The introduction of imatinib therapy has had a profound impact on the use of allogeneic transplantation for CML, with a marked decrease in the number of transplants for CML and an accompanying decrease in the proportion done in CP1. Most patients now receive a trial of imatinib before proceeding to HCT.

Recent improved treatments for lymphoid malignancies produce more long-term survivors, yet increase the risk for secondary malignancies. Therapy-related myelodysplasia and acute myeloid leukemia are well described, but secondary chronic myeloid leukemia (CML) has only rarely been reported. We report three patients with CML diagnosed 8, 10 and 2.5 years following Hodgkin's disease, non-Hodgkin's lymphoma and chronic lymphocytic leukemia therapy, respectively. BCR-ABL transcripts were not detected after completion of primary therapy in two cases. All three patients received imatinib therapy, with one patient subsequently undergoing allogeneic hematopoietic stem cell transplantation. All three patients have ongoing favorable responses to CML therapy.

Evidence supporting the role of hematopoietic stem cell transplantation (SCT) in the therapy of acute lymphoblastic leukemia (ALL) in children is presented and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the treatment recommendations. Treatment recommendations based on the evidence are presented in a table in this review (Summary of Treatment Recommendations Made by the Expert Panel for Pediatric Acute Lymphoblastic Leukemia) and were reached unanimously by a panel of ALL experts. The priority areas of needed future research in pediatric ALL are unrelated marrow or blood donor versus unrelated cord blood donor allogeneic SCT; alternative, nonfamily allogeneic donor versus autologous SCT; better methods for identifying high-relapse-risk patients; assessments of the effect of current chemotherapy regimens on early relapse; and use of pre-SCT detection of minimal residual disease to predict post-SCT outcomes.

Evidence supporting the role of hematopoietic stem cell transplantation (SCT) in the therapy of multiple myeloma (MM) is presented and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published medical literature and for grading the quality of the evidence, the strength of the evidence, and the strength of the treatment recommendations. Treatment recommendations based on the evidence presented in the review were made unanimously by a panel of MM experts. Recommendations for SCT as an effective therapy for MM include the following: SCT is preferred to standard chemotherapy as de novo therapy; SCT is preferred as de novo rather than salvage therapy; autologous peripheral blood stem cell transplantation (PBSCT) is preferred to bone marrow transplantation (BMT); and melphalan is preferred to melphalan plus total body irradiation as the conditioning regimen for autologous SCT. Recommendations that SCT is not effective include the following: current purging techniques of bone marrow. Recommendations of equivalence include the following: PBSCT using CD34+ selected or unselected stem cells. No recommendation is made for indications or transplantation techniques that have not been adequately studied, including the following: SCT versus standard chemotherapy as salvage therapy, tandem autologous SCT, autologous or allogeneic SCT as a high-dose sequential regimen, allogeneic BMT versus PBSCT, a preferred allogeneic myeloablative or non-myeloablative conditioning regimen, and maintenance therapy post-autologous SCT with interferon alpha post-SCT. The priority area of needed future research is maintenance therapy posttransplantation with nothing versus interferon alpha versus other agents such as corticosteroids or thalidomide or its derivatives., (Copyright 2003 American Society for Blood and Marrow Transplantation)