Outcomes with mismatched unrelated donor allogeneic hematopoietic stem cell transplantation in adults: A systematic review and meta-analysis

Abstract

BackgroundAllogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for various hematologic disorders. Alternative donor strategies such as mismatched unrelated donors (MMUD) offer the option of HSCT to patients lacking a human leukocyte antigen (HLA)-matched donor. We conducted a systematic review and meta-analysis to evaluate outcomes after MMUD-HSCT.MethodsA literature search was performed on PubMed, Cochrane Library, and ClinicalTrials.gov from the inception date through April 6, 2022. After screening 2477 manuscripts, 19 studies were included. Data was extracted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Pooled analysis was done using the meta-package by Schwarzer et al. Proportions with 95% confidence intervals (CI) were computed.ResultsA total of 3336 patients from 19 studies were included. The median age was 52.1 years, and 53% of recipients were males. The graft source was bone marrow in 19% and peripheral blood stem cells in 81% of recipients. The median time to transplant from hematologic diagnosis was 10 (1-247) months. Hematologic diagnoses included myeloid (82.9%), lymphoid (41.1%), and other disorders (3%). The reduced intensity and myeloablative conditioning were used in 65.6% and 32% of recipients, respectively. In-vivo T-cell depletion was performed in 56.7% of the patients. Most patients had one (87.9%) or two (11.4%) antigen HLA-mismatch. The pooled 1-year overall survival (OS) was 63.9% (95% CI 0.57-0.71, n=1426/2706), and the pooled 3-year OS was 42.1% (95% CI 0.34.2-0.50, n=907/2355). The pooled progression-free survival was 46.6% (95% CI 0.39-0.55, n=1295/3253) after a median follow-up of 1.8 (range 1-6) years. The pooled relapse rate was 26.8% (95% CI 0.22-0.32, n=972/3253) after a median follow-up of 2.25 (1-3) years. The pooled incidence of acute (grade II-IV) graft-versus-host disease (GVHD) and chronic GVHD was 36.4% (95% CI 0.31-0.42, n=1131/3030) and 41.2% (95% CI 0.35-0.48, n=1337/3228), respectively. The pooled non-relapse mortality was 22.6% (95% CI 0.17-0.29, n=888/3196) after a median follow-up of 2.6 (1-5) years.ConclusionMMUD-HSCT has demonstrated favorable outcomes with an acceptable toxicity profile. It represents a promising option in patients lacking an HLA-matched or haploidentical donor and may expand HSCT access to underrepresented racial and ethnic populations.

Allogeneic stem cell transplantation in the treatment of acute myeloid leukemia: An overview of obstacles and opportunities

“…In addition, the survival of individuals who have undergone allo-HSCT is also affected by the compatibility of specific HLA loci of the donor and recipient. A recent publication pointed out that HLA matching and the age of the recipient are simple factors that can accurately stratify subjects into prognostic groups as well as predict overall survival and non-relapse mortality in allo-HSCT[ 180 ]. However, a meta-analysis of 19 investigations with a patient sample of 3336 individuals concluded that mismatched allo-HSCT from unrelated donors remains a safe procedure that is linked with favorable outcomes[ 181 ].…”

Graft-versus-host-disease prophylaxis with ATG or PTCY in patients with lymphoproliferative disorders undergoing reduced intensity conditioning regimen HCT from one antigen mismatched unrelated donor

“…Previous published studies have reported a higher incidence of GvHD and non-relapse mortality (NRM) in the setting of MMUD HCT [ 12 ]. Recent improvements in supportive care, HLA typing and GvHD prophylaxis, including PTCY, have resulted in better survival outcomes and acceptable toxicity profile after MMUD [ 13 ]. In the last years the traditional use of ATG in combination with calcineurin inhibitor and mycophenolate mofetil for 9/10 MMUD HCT has been overtaken by the progressive use of PTCY in this platform in different European institutions.…”

Real-World Challenges of Haplo-Identical Hematopoietic Stem Cell Transplant in a Developing Country: A Single Center Experience

“…With the increasing advancement in diagnostic modalities and improvement in HSCT outcomes, an increasing number of patients are now being considered for HSCT [ 2 ]. Finding a human leukocyte antigen (HLA)-compatible donor remains one of the limiting factors, hampering the utilization of HSCT [ 3 ]. However, the advent of newer transplant strategies has resulted in a global increase in haplo-identical HSCT.…”