Feasibility and Efficacy of a Second Allogeneic Stem Cell Transplant for Acute Leukemias and Myelodysplastic Syndromes: Experience from Two Centers in São Paulo, Brazil

Introduction: Second allogeneic hematopoietic stem cell transplant (HSCT) is often the only curative treatment option for patients who relapse or fail after a first transplant for malignant diseases. Outcomes previously reported for this intervention are often dismal with high relapse incidence (RI), non-relapse mortality (NRM) and low overall survival (OS). Here we explore encouraging results from two centers in São Paulo performing second HSCT for acute leukemias and Myelodysplastic Syndromes (MDS).

Patients and Methods: A retrospective observational study of 18 patients, aged 18 years or older, who underwent second allogeneic HSCT for acute leukemias (AML=9, ALL=7) or MDS (n=2), in two Brazilian centers in the city of São Paulo (Brazil) between November 2012 and March 2024. Clinical data were collected using standardized forms based on information obtained from medical records.

Results: Median age was 37 years (range: 18 - 65), most patients were male (n=11, 61%). The majority was haploidentical donors (n=14, 78%), followed by matched sibling donors (n=3, 17%), and matched unrelated donors (n=1, 5%). The majority of patients (n=16, 89%) received reduced-intensity conditioning (RIC) regimens, and most with mobilized peripheral blood as stem cell sources (n=15, 83%), with only three receiving cells from the bone marrow. All patients but one patient had different donors from the first HSCT. Among all patients, there were 10 (55%) who were not in remission before transplant. Median follow-up was 19 months (range: 9 - 19). Cumulative incidence (CI) of acute GVHD grade II-IV was 36% and grade III-IV was 16% in 100 days. CI of chronic GVHD at 2 years time was 20%. OS and progression free survival (PFS) were 68% and 62% at two years respectively. CI of non-relapse mortality (NRM) was 12% at 100 days and the same (12%) at two years. CI of relapse was 18% in 100 days and 26% in 2 years. When stratified by diagnosis, 2-year OS were 27%, 89% and 100% for acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML) and MDS respectively.

Conclusions: In our multicenter retrospective cohort, both OS and PFS were higher than frequently reported, and NRM and chronic GVHD rates were relatively low. Despite the limitations of this retrospective cohort, such as the small sample and limited follow up, we observed that second HSCT is a feasible and safe curative option for malignant hematologic diseases in the challenging setting of relapse or failure after a first allogeneic HSCT. Those findings may reflect improvements in support therapies, growing use of RIC regimens, choice of different than previous donors and personalized time of immunosuppressive therapy. Superior 2-year OS observed in myeloid malignancies may reflect superior graft versus leukemia effect elicited by HSCT in these diseases, even in a setting of a previous relapse/failure after HSCT.

Szor:Janssen Cilag: Research Funding.