Efficacy of a second allogeneic hematopoietic cell transplant in myeloid heematologic malignancies

Abstract Purpose To evaluate the efficacy and safety of second allogeneic hematopoietic cell transplant (allo-HCT) in patients with myeloid hematologic malignancies who relapsed or encountered graft failure after the first allo-HCT. Patients and Methods This retrospective analysis included 12 cases with acute myeloid leukemia or myelodysplastic syndrome who underwent a second allo-HCT at Shanghai Zhaxin Integrated Traditional Chinese and Western Medicine Hospital between January 2020 and May 2024. There were 8 male and 4 female, the median age at was 40.5 (18-56), 9 patients with acute myeloid leukemia and 3 cases with myelodysplastic syndrome. Donor at first allo-HCT: 10 from related haploidentical donor, and 2 from matched sibling donor. 7 cases used a different donor for second allo-HCT: 2 matched unrelated donor, 1 matched sibling donor, 4 related haploidentical donor. The performance status assessment by ECOG score were：1 case scored 0, 1 case scored 1, 6 cases scored 2, 3 cases scored 3, 1 case scored 4. As for Hematopoietic Cell Transplantation-Comorbidity Index(HCT-CI) score：10 cases scored 1，1 case scored 2 and 1 case scored 3. The time interval between two allo-HCT: 4 cases within 180 days，8 cases beyond 180 days. Strongly positive DSA were detected in 2 cases. The disease status assessment before second allo-HCT: only 4 cases were in complete remission. Conditioning regimen: 3 patients encountering graft failure received reduced intensity conditioning, while 9 relapsing patients received total body irradiation (8Gy) and thiotepa (5mg/kg for 2 days) based myeloablative conditioning. GVHD prophylaxis included porcine anti human lymphocyte immunoglobulins, tacrolimus, methotrexate and/or anti-CD25 antibody. Our primary endpoint was OS, defined as time from transplantation to 1 year and last follow-up post-HCT or date of death. Statistical analyses were performed using the statistical package SPSS version 17. Results Engraftment was achieved in 10 patients (including those 2 cases with strongly positive DSA), the median time of neutrophil engraftment was 10(9-16) days. 2 patients died on +4 and +8 day after second allo-HCT, were excluded from further analysis. 10 patients were in complete remission by day 30 post second allo-HCT, no relapse were detected during the follow up. The median follow up was 364 (72-1007) days. 5 patients died and the other 5 survived by 2024.9.30, causes of death including severe pneumonia, multiorgan failure, and severe GVHD. The median overall survival was 535(95%CI:339-730)days, the 1 year cumulative survival rate was 78%，and the 2 year cumulative survival rate was 35%. Univariate analyses suggested ECOG (＞2) and HCT-CI(＞1) score were correlated with patient survival after second allo-HCT. Conclusion The findings of our current study indicate that a second allo-HCT is a reasonable treatment choice for AML and MDS patients relapsing or encountering graft failure after a first allo-HCT, complete response and survival benefit may be anticipated particularly in those with better performance status and fewer comorbidities.