Impact of Allogeneic Hematopoietic Stem Cell Transplantation on Acute Myeloid Leukemia Patients without Complete Remission
Authors: Santos Azevedo Fernanda , Molla Vinicius Campos de , Shcolnik Szor Roberta , Moraes Pedro Henrique Arruda de , Rosa Eurides L. , Justino Caio Cesar , Liz Cainã Dabbous , Azevedo Roberta Santos , Fonseca Ana Marcela , Arrais-Rodrigues Celso 
Published: December 2024

Background: Allogenic hematopoietic stem cell transplant (Allo-HSCT) is the most potent post-remission treatment for acute myeloid leukemia (AML) to reduce relapse rates. However, complete remission and minimal residual disease before Allo-SCT are important predictors of relapse and mortality rates after consolidation therapy. This study aims to describe the characteristics and outcomes of AML patients (pts) who underwent Allo-HSCT without achieving complete remission (CR).
Methods: We conducted a retrospective analysis of all AML pts with active disease who underwent Allo-HSCT between 2010 and 2024 in two Brazilian institutions. Active AML was defined as more than 5% of blasts in the bone marrow (BM) (WHO 2017) before starting the Allo-HSCT conditioning or sequential conditioning regimen. Kaplan-Meier curves estimated progression-free survival (PFS) and overall survival (OS) using the log-rank test for subgroup analyses.
Results: A total of 28 AML pts with active disease at Allo-HSCT were included in the analysis; 23 pts (82.1%) had refractory disease after first-line AML treatment, and 5 (17.9%) had second or later relapsed/refractory disease. The median age at HSCT was 47 years (range, 19-83), 39.3% were male, and the median percentage of blasts in BM at the start of Allo-SCT was 11%. Nine of 19 assessed pts (47.3%) were high-risk based on the HCT-CI score.
Haploidentical bone marrow transplantation was performed in 15 pts (53.6%), followed by matched unrelated donors in 7 pts (25%) and matched related donors in 6 pts (21.4%). Regarding the conditioning regimen, reduced-intensity conditioning (RIC) was performed in 22 pts (78.6%), including FluCyTBI 2 or 4Gy in 16 pts (72.7%), FluBu6.4 in 5 pts (22.7%), and FluMel140 in 1 pt (4.5%). Myeloablative conditioning (MAC) was used in 6 pts (21.4%), including FluBu9.6 in 3 pts (50%), BuCy in 2 pts (33.3%), and FluTBI12Gy in 1 pt (16.7%). Mobilized peripheral blood stem cells were the most common cell source (21 pts - 75%), while bone marrow was used in 7 pts (25%). Graft-versus-host disease (GvHD) prophylaxis included post-transplant cyclophosphamide (PTCY), cyclosporin (CSA), and oral mycophenolate in 16 pts (59.3%), while 12 pts (40.7%) used CSA associated with mycophenolate or methotrexate backbone. Anti-thymocyte globulin (ATG) was used in 4 pts (16.6%) of these latter patients.
With a median follow-up of 42 months, the median OS was 9.25 months, and the median PFS was 6.4 months. The 12-month OS and PFS rates were 46% and 43.5%, respectively. The 3-month and 12-month relapse rates were 18% and 26%, respectively. The non-relapse mortality (NRM) rate was 14% at 3 months and 32% at 12 months, with 6 deaths attributed to infectious complications. The cumulative incidence (CI) of acute grade II-IV GVHD at 100 days was 21%, and the 12-month CI of chronic GVHD was 29%.
The percentage of blasts in BM at Allo-HSCT was an important prognostic marker, with pts having more than 10% of blasts experiencing worse outcomes, with a 12-month OS of 22% compared to 76% for pts with 10% or fewer blasts (p=0.015) and a 12-month PFS of 22% versus 65% (p=0.035).
Conclusion: Allo-HSCT is a viable procedure for pts who do not achieve CR after induction therapy for AML, especially in pts with 10% or fewer blasts in BM. The outcomes of these pts are poor, especially in underdeveloped countries with low access to clinical trials. However, prospective studies with a larger number of patients and longer follow-up are needed to define the role of Allo-HSCT in active AML.