Comparable survival outcomes after myeloablative allogeneic stem cell transplantation in secondary and de novo Acute Myeloid Leukemia in first complete remission: A propensity Score–Matched study Free

Secondary acute myeloid leukemia (sAML) is a distinct subtype of AML characterized by poor prognosis, arising either from a pre-existing hematologic disorder—primarily myelodysplastic syndromes (MDS) or myeloproliferative neoplasms (MPNs)—or as a consequence of prior cytotoxic chemotherapy or radiation therapy. Patients with secondary acute myeloid leukemia (sAML) generally have poorer outcomes—including lower remission rates and overall survival—compared to de novo AML, largely due to a higher prevalence of adverse molecular mutations, high-risk cytogenetics, older age, and antecedent hematologic disorders.

This was a retrospective, single-center analysis using the dataset of the HSCT Center of the Blood Diseases Hospital, Chinese Academy of Medical Sciences (CAMS). Eligible patients were adults (≥18 years) diagnosed with de novo or secondary AML who received a first allogeneic hematopoietic stem cell transplantation (HSCT) with a myeloablative conditioning (MAC) regimen between 2013 and 2024, no ex vivo T-cell depletion, and no posttransplant cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis. A haploidentical donor was defined as having ≥2 HLA mismatches between donor and recipient. Exclusion criteria included transplantation from other donor types (matched sibling, unrelated, or cord blood), prior history of HSCT, use of T cell–depleted grafts, unknown or favorable cytogenetic risk, and unknown antecedent hematologic disorder. Collected data encompassed recipient and donor characteristics (age, sex, Karnofsky Performance Status [KPS], and Hematopoietic Cell Transplantation–Specific Comorbidity Index [HCT-CI]); disease characteristics; antecedent hematologic disorder; year of diagnosis and transplantation; stem cell source; and GVHD prophylaxis. All patients received myeloablative conditioning (MAC), defined as regimens containing either total body irradiation (TBI) >6 Gy or a cumulative busulfan dose >8 mg/kg orally or >6.4 mg/kg intravenously. Grading of acute graft-versus-host disease (aGVHD) was performed based on standard consensus criteria(26). Classification of chronic graft-versus-host disease (cGVHD) was performed according to published consensus criteria. Complete remission (CR) is defined as having less than 5% bone marrow blasts, no circulating blasts, and no extramedullary disease. Relapse is defined as having more than 5% bone marrow blasts or the reappearance of circulating blasts after a documented CR.

Engraftment rates and incidence of GVHD did not differ significantly between the sAML and de novo AML groups, as shown in Table 2. Neutrophil recovery, defined as an absolute neutrophil count (ANC) > 0.5 × 10⁹/L, was achieved in 100% of both cohorts. Platelet engraftment is usually defined as independence from platelet transfusion for at least 7 days with a platelet count of more than ＞20×10⁹/L， which was achieved in 95.6% of de novo AML and 87.8% of sAML. By day +100, the incidence of grade II–IV and grade III–IV acute GVHD was16.1% (95% CI: 9.01-25.0%) versus 18.0% (95% CI:7.74-31.6%) (p =0.38) and 7.24% (95% CI:2.94-14.2%) versus18.0% (95% CI:7.74-31.6%) (p=0.96) in de novo and sAML patients, respectively. At two years, the cumulative incidence of limited and extensive chronic GVHD was 16.4% (95% CI:8.89-25.8%) versus 13.1% (95% CI:4.62-26.2%) (p=0.78) and 2.3% (95% CI:0.4-7.4%) versus 12.2% (95% CI:4.3-24.4%) (p =0.011), respectively. No significant differences were observed between sAML and de novo AML groups in two-year outcomes, including non-relapse mortality (NRM), relapse incidence (RI), leukemia-free survival (LFS), overall survival (OS), and GVHD-free, relapse-free survival (GRFS). Two-year NRM was 15.7%(95% CI,9.0-24.0%) versus 9.3%(95%CI,2.9-20.5%) (p=0.75), and RI was 18.7%(95%CI,11.2-27.7%) versus 20.8%(95%CI,10.0-34.2%) (p =0.49) for de novo and sAML, respectively (Table 3A). The two-year LFS, OS, and GRFS were 65.8% (95%CI,56.5-76.6) versus 54.4% (95%CI,39.6,74.7)(p =0.84), 67.9% (95%CI,58.7-78.5) versus 66.6% (95%CI,52.1-85.1)(p =0.84), and 56.6%(95%CI,47.1-68.2) versus 36.0%(95%CI,22.6-57.5) (p=0.35), respectively (Table 3A). Similarly, no outcome differences were found when comparing sAML post-MDS or sAML post other malignant hematological disorders (OMHD)/solid tumors (ST)/bone marrow failure syndrome(BMFS) to de novo AML.