PMID- 21975786 OWN - NLM STAT- MEDLINE DCOM- 20111102 LR - 20211020 IS - 1469-493X (Electronic) IS - 1361-6137 (Linking) VI - 2011 IP - 10 DP - 2011 Oct 5 TI - Allogeneic hematopoietic cell transplantation for adult acute lymphoblastic leukemia (ALL) in first complete remission. PG - CD008818 LID - 10.1002/14651858.CD008818.pub2 [doi] LID - CD008818 AB - BACKGROUND: Consolidation chemotherapy, autologous hematopoietic cell transplantation (HCT) and allogeneic HCT represent potential treatment alternatives for post-remission therapy in adult acute lymphoblastic leukemia (ALL), but there is genuine uncertainty regarding the optimal approach. OBJECTIVES: To assess the effect of matched sibling donor vs. no donor status for adults with ALL in first complete remission (CR1). SEARCH STRATEGY: We performed a search of CENTRAL, MEDLINE and EMBASE electronic databases in September 2010 along with handsearching of literature cited in relevant primary articles, search of abstracts from American Society of Hematology and American Society of Clinical Oncology meetings, as well as consultation with content experts in the field. SELECTION CRITERIA: Review was performed by two authors, and Inclusion criteria included the following: controlled trials with donor vs. no donor comparison with assignment by genetic randomizationin adults with ALL in CR1. DATA COLLECTION AND ANALYSIS: We extracted data on benefits (overall survival, progression-free survival) and harms (treatment-related mortality, relapse) of compared treatments. Adverse events were considered, but analysis of individual adverse events was not possible from the reported literature. We pooled summary results from each study using a random-effects model. We assessed heterogeneity. We performed subgroup analyses for disease risk categories. We performed sensitivity analyses according to methodological quality. MAIN RESULTS: A total of 14 relevant trials were identified, consisting of a total of 3157 patients. There was a statistically significant overall survival advantage in favor of the donor versus no donor group (HR 0.86; 95% CI 0.77 to 0.97; P = 0.01), as well as significant improvement in disease-free survival in the donor group(HR 0.82; 95% CI 0.72 to 0.94; P = 0.004). Those in the donor group had significant reduction in primary disease relapse(RR 0.53; 95% CI 0.37 to 0.76; P = 0.0004) and significant increase in non-relapse mortality(RR 2.8; 95% CI 1.66 to 4.73; P = 0.001). Significant heterogeneity was detected in analysis of relapse (Chi(2) 40.51, df = 6, P < 0.00001; I(2) = 85%). In regard to methodologic quality, the majority of included studies were free of selective reporting, and performed analyses according to intention to treat. Conversely, few reported sample size calculation that informed the study design. While blinding was considered as an important domain of methodological quality, none of the studies reported on whether any of the study personnel were blinded (e.g. subjects, personnel, outcome assessors, data analysts etc). Therefore, we did not consider blinding further in the analysis of methodological quality in this review. AUTHORS' CONCLUSIONS: The results of this systematic review and meta-analysis support matched sibling donor allogeneic hematopoietic cell transplantation as the optimal post-remission therapy in ALL patients aged 15 years or over. This therapy offers superior overall survival and disease-free survival, and significantly reduces the risk of disease relapse, but does impose an increased risk of non-relapse mortality. Importantly these data are based on adult ALL treated with largely total body irradiation-based myeloablative conditioning and sibling donor transplantation and, therefore, cannot be generalized to pediatric ALL, alternative donors including HLA (human leukocyte antigen) mismatched or unrelated donors, or reduced toxicity or non-myeloablative conditioning regimens. FAU - Pidala, Joseph AU - Pidala J AD - Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Division of Oncologic Sciences, University of South Florida, Tampa, Florida, USA. FAU - Djulbegovic, Benjamin AU - Djulbegovic B FAU - Anasetti, Claudio AU - Anasetti C FAU - Kharfan-Dabaja, Mohamed AU - Kharfan-Dabaja M FAU - Kumar, Ambuj AU - Kumar A LA - eng GR - R01 CA140408/CA/NCI NIH HHS/United States PT - Journal Article PT - Meta-Analysis PT - Review PT - Systematic Review DEP - 20111005 PL - England TA - Cochrane Database Syst Rev JT - The Cochrane database of systematic reviews JID - 100909747 SB - IM UOF - doi: 10.1002/14651858.CD008818 MH - Adult MH - Hematopoietic Stem Cell Transplantation/*methods/mortality MH - Histocompatibility MH - Humans MH - Living Donors MH - Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality/*surgery MH - Randomized Controlled Trials as Topic MH - Recurrence MH - Remission Induction MH - Siblings MH - Transplantation Conditioning/methods MH - Transplantation, Homologous/mortality PMC - PMC7386902 COIS- Dr. Kharfan-Dabaja has received payment for lectures from Genzyme and Bristol Myers Squibb. He has also received consultancy fees from Vical. These financial activities are not relevant to the submitted work. All other authors report no conflict of interest. EDAT- 2011/10/07 06:00 MHDA- 2011/11/04 06:00 PMCR- 2012/10/05 CRDT- 2011/10/07 06:00 PHST- 2011/10/07 06:00 [entrez] PHST- 2011/10/07 06:00 [pubmed] PHST- 2011/11/04 06:00 [medline] PHST- 2012/10/05 00:00 [pmc-release] AID - CD008818.pub2 [pii] AID - 10.1002/14651858.CD008818.pub2 [doi] PST - epublish SO - Cochrane Database Syst Rev. 2011 Oct 5;2011(10):CD008818. doi: 10.1002/14651858.CD008818.pub2.