Good report of secondary allogeneic hematopoietic stem cell transplantation in patients with refractory/relapsed Acute Myeloid Leukemia

Abstract Objective: Post-transplant relapse in AML was a challenging clinical issue, with limited intervention options currently available. In cases where patients are in good physical condition and suitable donors are available, secondary allogeneic HSCT has emerged as a powerful tool to address this challenge. Method: From April 2018 to April 2023, 43 patients with AML undergoing secondary allogeneic HSCT were enrolled. There were 20 males and 23 females. The age range was 3–49 years, with a median age of 24 years. Twenty-eight patients were in remission at the time of the first transplant, while the remaining 15 patients underwent salvage transplantation due to failure to achieve remission or loss of remission. Forty-one patients experienced leukemia relapse after the first transplant, with relapse occurring between 3 and 68 months (median relapse time of 12 months). One patient underwent a second transplant due to persistent mixed chimerism and poor engraftment post-transplant, while another patient underwent a second transplant due to persistent MRD post-transplant. Prior to the second transplant, 12 patients were in MRD-negative CR, 13 patients were in MRD-positive CR, and 18 patients were in a state of leukemia relapse. For the second transplant, 7 patients received transplants from unrelated donors, and 36 patients received transplants from related haploidentical donors. Thirty-five patients received a conditioning regimen primarily consisting of TBI plus fludarabine/cladribine, while 8 patients received a regimen primarily consisting of BU plus fludarabine/cladribine. GVHD prophylaxis was administered using the standard regimen of CSA plus MMF plus short-course MTX. Following transplantation, patients received maintenance therapy with demethylation therapy/pan-targeted drug therapy/adoptive cell immunotherapy as tolerated based on hematologic parameters. Results: In terms of hematopoietic reconstitution, the time to granulocyte engraftment ranged from +9 days to +22 days (median time +14 days), and the time to platelet engraftment ranged from +6 days to +69 days (median time +14 days). Two patients did not achieve hematopoietic reconstitution. Post-transplant complications included 8 cases of CMV infection, 1 case of EBV infection, 1 case of B19 viral encephalitis, 1 case of HBV reactivation, 1 case of HSV reactivation, 1 case of VZV reactivation, and 1 case of adenovirus infection. Thirteen patients developed pneumonia, including 2 cases of CMV pneumonia, 2 cases of COVID-19 pneumonia, and 1 case of Pneumocystis pneumonia. Three cases of TMA were reported. Two patients did not achieve CR post-transplantation, and 12 patients experienced leukemia relapse, with relapse occurring from +3 months to +27 months (median time +11 months). Regarding GVHD, 11 patients developed ≥2-grade acute GVHD, and 18 patients developed chronic GVHD (6 cases of localized mild, 12 cases of widespread severe). Follow-up was conducted until July 2025, with a follow-up period ranging from 0 to 87 months (median follow-up time of 25 months). Eighteen patients (42%) survived and were in a leukemia-free state, while 25 patients (58%) died, including 3 deaths due to severe cGVHD, 2 cases of TMA, 6 cases of severe pneumonia (including 1 case of COVID-19 pneumonia and 1 case of CMV pneumonia), 1 case of hip joint infection, 12 cases of leukemia, and 1 case of graft failure. According to statistical analysis using SPSS software, the 2-year OS rate of enrolled patients was 46.4%, the 2-year cumulative recurrence rate was 35.1%, and the 2-year TRM rate was 29.7%. Patients were divided into two groups based on their pre-transplant status: the salvage HSCT group (MRD-negative CR or MRD-positive CR) and the non-salvage HSCT group (relapsed status). The 2-year OS rates for patients in the salvage HSCT group and the non-salvage HSCT group were 23.7% vs. 48.6%, respectively. Although the non-salvage HSCT group had a higher OS rate, this difference was not statistically significant (P = 0.268). Summary: For patients with AML who relapse after transplantation, a second transplant is a powerful management measure. At our center, the 2-year OS rate for second allogeneic HSCT reaches 46.4%. The TRM rate associated with secondary HSCT is manageable. Achieving CR prior to secondary HSCT is associated with higher post-transplantation OS rates. In cases where CR cannot be achieved, salvage secondary HSCT is also a viable option.