Outcomes after Bone Marrow Versus Peripheral Blood Stem Cells Haploidentical Hematopoietic Cell Transplantation: A Systematic Review and Meta-Analysis
Authors: Shahzad Moazzam , Rehman Gohar , Khan Abat , Amin Muhammad Kashif , Ishaq Muhammad Uzair , Akram Umar , Sadiq Muhammad Hamza , Choudhary Umar Iqbal Javid Iqbal , Shamoon Sheena , Khan Bilal Yasin , Chaudhary Sibgha Gull , Anwar Iqra , Singh Anurag , McGuirk Joseph P. , Mushtaq Muhammad Umair 
Published: December 2024

Background: Allogenic hematopoietic cell transplantation (allo-HCT) is used to treat various hematological disorders. The allograft can be harvested using peripheral blood stem cells (PBSC) or bone marrow (BM). Recently, the trend has shifted towards PBSC allograft due to easy logistics and comparable clinical outcomes. In this meta-analysis, we aimed to compare the real-world outcomes of these two graft sources in patients undergoing haploidentical (haplo) 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 (“Hematopoietic Stem Cell Transplantation”) OR (“Haploidentical Transplantation” AND “ peripheral blood stem cell”) AND “ bone marrow”). A total of 5830 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 12 studies (11 retrospectives, one trial) reporting outcomes following BM vs. PBSC allo-HCT. 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; a value above 50% was considered a cause for concern. Results: The analysis of 12 studies comparing the outcomes between BM and PBSC haplo HCT showed a mixed picture. Our study included 11604 patients, including 4811 BM (41.46%) and 6793 PBSC (58.54%) grafts. The median age was 46 (range 18-76) years, male to female ratio was approximately 49% male and 51% female, and across these studies, most patients had good performance status (ECOG 0-1 or KPS ≥90%). Hematologic diseases included acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, lymphoma, and others. Conditioning regimens varied across studies with the use of both myeloablative and reduced-intensity conditioning with or without the use of total body irradiation. Stem cell doses also varied, with PBSCT groups receiving higher CD34+ cell doses than BMT groups. When reported, neutrophil engraftment typically occurred between 14-19 days post-transplantation, with PBSCT often showing slightly faster engraftment compared to BMT. Platelet engraftment typically occurred later than neutrophil engraftment, 20-28 days post-transplantation, with PBSCT often slightly faster engraftment than BMT. Between the BM and PBSC groups, there was no discernible difference in overall survival (OS) at one year following transplantation. PBSC, however, demonstrated statistically significant improved OS at two years (RR 1.14, 95% CI 1.04-1.25, P=0.005) and five years (RR 1.17, 95% CI 1.02-1.34, P=0.02) after transplant. The PBSC group has statistically significant reduced relapse rates compared to the BM group at one year (RR 1.31, 95% CI 1.01-1.71, P=0.04) and two years (RR 1.27 95% CI 1.03-1.57, P=0.02) but it was not significant at three years (RR 1.13, 95% CI 0.49-2.61, P=0.78). The two groups had no statistically significant difference in disease-free survival or transplant-related mortality. Grades II-IV acute graft versus host disease (aGVHD) rates were somewhat lower with BM, but there was no statistically significant difference (RR 0.85, 95% CI 0.73-0.98, P=0.03), and a similar trend was seen for grade III-IV aGVHD (RR 0.86, 95% CI 0.20-3.66, P=0.84). Conclusion: Our findings suggest that while PBSCT may offer some advantages in long-term survival and relapse prevention, the choice between BMT and PBSCT should be carefully considered in patients undergoing haplo HCT. It is crucial to consider individual patient factors and specific clinical contexts, as this personalized approach can lead to the best possible outcomes for each patient.