Outcomes of Melphalan Versus Busulfan with Fludarabine Reduced Intensity Conditioning Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis

• Published in: Blood 2024-11, Vol.144 (Supplement 1), p.7426-7426
• Main Authors: Shahzad, Moazzam, Khan, Abat, Amin, Muhammad Kashif, Rehman, Gohar, Akram, Umar, Nihar, Kainat, Ishaq, Muhammad Uzair, Ismail, Areeba, Sadiq, Muhammad Hamza, Shamoon, Sheena, Mannan, Muhammad Shaheer, Singh, Pramod, Faisal, Abdul Rafae, Chaudhary, Sibgha Gull, Anwar, Iqra, Nelson, Maggie, Abdelhakim, Haitham, McGuirk, Joseph P., Mushtaq, Muhammad Umair
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2024-199400

Background: An optimal conditioning regimen before hematopoietic cell infusion is essential for improved outcomes after allogeneic hematopoietic cell transplantation (allo-HCT). Historically, myeloablative conditioning was used to eradicate disease, followed by allograft infusion to restore hematopoiesis. However, many patients with acute myeloid leukemia (AML) are elderly, with a median age of diagnosis of 69 years. Reduced-intensity conditioning (RIC) is used in elderly and less fit patients undergoing allo-HCT, and outcomes for these patients have improved over the years. We aimed to compare the outcomes after two commonly used RIC regimens, Melphalan versus Busulfan with Fludarabine (FluMel vs. BuFlu), in AML patients undergoing allo-HCT.Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a comprehensive literature search was performed on five databases (PubMed, Cochrane Library, ClinicalTrials.gov, Medline, and Embase) from date of inception through June 2024 using the MeSH and entry terms for (“acute myeloid leukemia”) AND (“allogeneic stem cell transplantation” OR “Stem cell transplantation”) AND “reduced intensity conditioning chemotherapy”). A total of 5957 studies were identified, and primary and secondary screening was performed. After excluding reviews, editorials, opinion pieces, animal studies, and duplicate and non-relevant articles, we included six studies (five retrospective, one trial) reporting outcomes following RIC with either FluMel or BuFlu. The Joanna Briggs Institute critical appraisal checklist for studies reporting the prevalence data and randomized control trials was used for quality assessment, and all studies were reported as good. Review Manager (RevMan, version 5.4; The Cochrane Collaboration, Copenhagen, Denmark) was used for statistical analysis. We used a DerSimonian and Laird random effects model, with the Mantel-Haenszel method for dichotomous outcomes to calculate risk ratios (RR) and corresponding 95% CI. The random-effects model was used because of the estimated heterogeneity of the actual effect sizes. We used the Higgins I2 values to evaluate statistical heterogeneity, and a value above 50% was considered a cause for concern. Multiple arms were combined when two or more groups were present in intervention and control groups.Results: Our study included 4365 patients with the median ages in the late 50s to mid-60s (range 19-76 years). Male patients were 55-65