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Meta-Analysis
. 2011 Oct 5;2011(10):CD008818.
doi: 10.1002/14651858.CD008818.pub2.

Allogeneic hematopoietic cell transplantation for adult acute lymphoblastic leukemia (ALL) in first complete remission

Joseph Pidala  1 , Benjamin Djulbegovic, Claudio Anasetti, Mohamed Kharfan-Dabaja, Ambuj Kumar
Affiliations
Meta-Analysis

Allogeneic hematopoietic cell transplantation for adult acute lymphoblastic leukemia (ALL) in first complete remission

Joseph Pidala et al. Cochrane Database Syst Rev. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

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.

Figures

1
1
PRISMA flow diagram for study review and inclusion
2
2
Forest plot of comparison: 1 Donor versus no donor, outcome: 1.1 Overall survival (overall sample).
3
3
Forest plot of comparison: 2 Subgroup analyses (donor versus no donor), outcome: 2.3 Overall survival.
4
4
Forest plot of comparison: 1 Donor versus no donor, outcome: 1.2 Disease‐free survival (overall sample).
5
5
Forest plot of comparison: 1 Donor versus no donor, outcome: 1.4 Relapse (overall sample).
6
6
Forest plot of comparison: 1 Donor versus no donor, outcome: 1.3 Non‐relapse mortality (overall sample).
7
7
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
8
8
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
9
9
Funnel plot of comparison: 1 Donor versus no donor, outcome: 1.1 Overall survival (overall sample).
1.1
1.1. Analysis
Comparison 1 Donor versus no donor, Outcome 1 Overall survival (overall sample).
1.2
1.2. Analysis
Comparison 1 Donor versus no donor, Outcome 2 Disease‐free survival (overall sample).
1.3
1.3. Analysis
Comparison 1 Donor versus no donor, Outcome 3 Non‐relapse mortality (overall sample).
1.4
1.4. Analysis
Comparison 1 Donor versus no donor, Outcome 4 Relapse (overall sample).
2.1
2.1. Analysis
Comparison 2 Subgroup analyses (donor versus no donor), Outcome 1 Overall survival.
2.2
2.2. Analysis
Comparison 2 Subgroup analyses (donor versus no donor), Outcome 2 Overall survival.
2.3
2.3. Analysis
Comparison 2 Subgroup analyses (donor versus no donor), Outcome 3 Overall survival.
2.4
2.4. Analysis
Comparison 2 Subgroup analyses (donor versus no donor), Outcome 4 Disease‐free survival.
2.5
2.5. Analysis
Comparison 2 Subgroup analyses (donor versus no donor), Outcome 5 Relapse.
2.6
2.6. Analysis
Comparison 2 Subgroup analyses (donor versus no donor), Outcome 6 Non‐relapse mortality.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD008818

References

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