Unmanipulated Peripheral Blood Stem Cell Transplantation with non-TBI Myeloablative Conditioning Regimen from Haploidentical and Unrelated versus Related Donors for Acute Leukemia in Children, Adolescents and Young Adults (CAYA): A Competing Risk Analysis

Abstract BackgroundAllogeneic hematopoietic stem cell transplantation (HSCT) is the only potentially curative treatment for acute leukemia. Many different parameters have significant impact on the final results of HSCT such as donor type, stem cell source, and the implemented conditioning regimen. In the absence of an HLA-matched related donor, unrelated donors or haploidentical donors are possible alternatives for patients with an indication to HSCT. In order to compare the outcomes of HSCT from different donor types, in this single-center study, using a radiation-free MAC regimen, we compared the results of unmanipulated peripheral blood stem cell transplantation (PBSCT) from matched and mismatched related and unrelated donors with haploidentical donors in the children, adolescents and young adults (CAYA) affected by acute leukemia.MethodsIn this retrospective study, since 2014 to 2021, the outcome of CAYA patients with acute leukemia who had undergone peripheral blood T cell-replete HSCT from haploidentical donors versus unrelated donors (including 10/10 or 9/10 HLA-matched) versus related donors (including 10/10 or 9/10 HLA-matched) were evaluated. The HSCT was based on a radiation-free MAC regimen including Busulfan and Cyclophosphamide. The GvHD prophylaxis was based on the administration of Cyclosporine A in all patients, plus rabbit anti-human thymocytes globulins in unrelated and haploidentical donors and post transplantation cyclophosphamide in haploidentical donors. Adjusted multivariable proportional hazard Cox and competing risk analyses were performed.ResultsMedian follow up time was 28.7 months (95% CI: 21.9-34.9). Three-year overall survival rate (OS) and GvHD-free/relapse-free survival (GFRFS) rate was 68.81% (95% CI: 60.08%-76.01%) and 44.19% (95% CI: 35.52%-52.49%), respectively. Patients who had undergone HSCT from an unrelated donor had the lowest OS and GFRFS compared to other donor types. The 3-years NRM in all patients was 7.84% (95% CI 4.36-12.62). Adjusted multivariable modeling of OS showed that the hazard of death in patients who had undergone HSCT from an unrelated donor, was 3.6 times more than patients who underwent HSCT from their haploidentical donors (P=0.05). Likewise, the hazard of NRM after HSCT from unrelated donors was 6 times more than haploidentical donors (P=0.002). However, the relapse incidence was not significantly different between the two mentioned groups.ConclusionsIn this study, HSCT from haploidentical donors was associated with superior survival rates compared to HSCT from unrelated donors. So haploidentical peripheral blood derived HSCT could be a practical and valuable clinical option that offers CAYA patients with acute leukemia needing HSCT and lacking matched available donors, a reasonable opportunity for disease control.