High Overall Survival in Patients Aged 70 Years and Older Submitted to Allogeneic Hematopoietic Stem Cell Transplantation in São Paulo, Brazil

Introduction: Many hematological diseases like myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) have a median age of diagnosis above the sixth decade and can be cured with allogeneic hematopoietic stem cell transplantation (HSCT). However, elderly patients are commonly considered ineligible for the procedure due to high rates of morbimortality. Recent advances in supportive care and new conditioning regimens have made HSCT in elderly patients more feasible and safe. There are few reports in Brazil about HSCT in patients aged 70 years or older.

Methods: This retrospective observational study analyzed 44 patients aged 65 years or older who underwent their first allogeneic HSCT for myeloproliferative neoplasms: acute myelogenous leukemia (AML, n=27), myelodysplastic syndrome (MDS, n=12), or myelofibrosis (MF, n=5), at two Brazilian centers in São Paulo between December 2013 and March 2024. Clinical data were collected using standardized forms based on information from medical records.

Results: The median age was 70 years (range: 65-81), with most patients being male (64%). The majority had haploidentical donors (59%), followed by matched unrelated donors (30%) and matched sibling donors (11%). All patients received reduced-intensity conditioning (RIC) regimens, with the vast majority using mobilized peripheral blood as the stem cell source (n=40, 91%), and only four (9%) receiving bone marrow cells. Among the 27 patients with AML, seven (26%) were not in complete remission before transplant. The main graft-versus-host disease (GVHD) prophylaxis was the combination of mycophenolate mofetil and cyclosporine or sirolimus. T-cell depletion with either post-transplant cyclophosphamide was used in 26 patients (59%) or antithymocyte globulin (ATG) in 15 patients (34%). The median follow-up was 18 months (range: 4-138). The cumulative incidence (CI) of acute GVHD grade II-IV was 28% and grade III-IV was 9%. The CI of chronic GVHD at 2 years was 39%, but only 4 patients (9%) required prolonged immunosuppression. Progression-free survival (PFS) and overall survival (OS) at two years were 54% and 64%, respectively. The CI of non-relapse mortality (NRM) was 11% at 100 days and 19% at two years. The main causes of death were infections (33%), followed by relapse or progression (29%).

Conclusions: This retrospective study demonstrates that allogeneic HSCT is an effective and safe curative option for myeloproliferative neoplasms in patients aged 65 years and older. Despite the use of RIC regimens and the inclusion of patients not in remission before transplantation, we observed a low relapse rate and a median PFS and OS that were not reached within two years of follow-up. Additionally, the rates of NRM and chronic extensive GVHD were relatively low. Although the study has limitations, including its retrospective nature and lack of comparison with other specific therapies, the findings suggest HSCT is viable treatment option for elderly patients.

Szor:Janssen Cilag: Research Funding.