Acute myeloid leukemia (AML) is one of the hematologic malignancies, for which patients typically undergo chemotherapy to achieve complete remission. However, approximately 30% of patients fail to respond to initial treatment, and many experience relapse after achieving remission. For patients with relapsed or refractory AML, allogeneic hematopoietic stem cell transplantation (HSCT) offers a potentially curative option. Sibling-matched HSCT has demonstrated a disease-free survival rate of 20-30%, while unrelated donor transplants yield an overall survival rate of approximately 22%. Haploidentical transplantation is a viable alternative for patients lacking a sibling donor. A 2019 study involving 1,693 patients with relapsed/refractory (R/R) AML revealed that haploidentical transplants yielded outcomes comparable to other transplant modalities, including HLA-matched and 9/10 matched unrelated donor transplants, thus supporting haploidentical transplantation as a viable therapeutic option.
The conditioning regimen is a critical component of the transplantation. In China, the modified BU/CY conditioning regimen, which combines busulfan (BU) and cyclophosphamide (CTX), is widely utilized for tumor cytoreduction and immunosuppression. Some centers also employ post-transplant cyclophosphamide (PTCy) to mitigate the risk of graft-versus-host disease (GVHD). Despite advances, relapse remains a significant challenge. Optimizing conditioning regimens to enhance tumor cell targeting and achieve deeper remission is crucial. Additionally, many patients are unfit due to prior chemotherapy, infections, and organ dysfunction, which may make them unable to tolerate high-intensity conditioning.
Recent studies suggest that melphalan (MEL)-based conditioning regimens may offer advantages over CTX-based protocols. While total body irradiation (TBI) has been traditionally used in conditioning for HSCT, it is associated with considerable organ toxicity.
A low-dose TBI regimen combined with BU+MEL represents a promising conditioning regimen for R/R AML. In preliminary studies, 7 patients treated with this regimen successfully achieved hematopoietic stem cell engraftment. Building on these results, a clinical study is planned to evaluate further the safety and efficacy of the TBI+BUMEL (IBM) conditioning regimen in relapsed/refractory AML, with a focus on improving engraftment rates, reducing relapse rates, minimizing GVHD incidence, and enhancing overall survival outcomes.
Age between 14 and 70 years (inclusive of the age limits);
Availability of a suitable allogeneic donor;
Life expectancy of ≥3 months;
Karnofsky Performance Status (KPS) ≥ 60%, Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
Patients had serious adverse reactions to investigational drugs such as allergies;
Patients with a history of immunodeficiency, or other acquired or congenital diseases, immunodeficiency diseases, and a history of organ transplantation;
Patients with hypertension, ventricular arrhythmia requiring clinical intervention, acute coronary syndrome, congestive heart failure, stroke, or other grade III or higher cardiovascular events within 6 months;
Patients received Class II or higher surgery within 4 weeks prior to enrollment;
Single group
Salvage Allogeneic Hematopoietic Stem Cell Transplantation
Procedure/Surgery1. TBI+BUMEL (IBM) Conditioning Regimen Day -7: Semustine (Me-CCNU) 250mg/m², orally, Day -7; Day -6: Total Body Irradiation (TBI) 4Gy, in two parts, Day -6; Day -5 to Day -4: Busulfan (Bu) 3.2mg/kg/day, administered in four divided doses, IV infusion; Day -3 to Day -2: Melphalan (Mel) 50mg/m²/day, IV infusion 2. Donor Stem Cell Infusion (Hematopoietic Stem Cell Transplantation) Day 0: Intravenous infusion of donor hematopoietic stem cells (MNC ≥ 8×10⁸/kg, CD34+ cells ≥ 4×10⁶/kg).
The cumulative incidence of neutrophil engraftment and platelet engraftment
Neutrophil and platelet engraftment is defined as the first occurrence of 3 consecutive days with an absolute neutrophil count of at least 0.5×109/L and a platelet count of over 20×109/L for 7 consecutive days without transfusion support.
The time to reconstitution of hematopoiesis
recovery of hemopoietic function after treatment
The cumulative incidence of transplant-related mortality (TRM)
Transplant-related mortality was defined as mortality due to any cause other than disease progression within 100 days of transplantation.
The cumulative incidence and grade of graft-versus-host disease (GVHD)
Graft-versus-host disease (GVHD) is a medical complication following the receipt of transplanted tissue from a genetically different person.
The cumulative incidence of relapse
We defined relapse as any clinical evidence of progression or recurrence of original diseases.
Overall survival rate
We estimated OS from the time of transplant until the date of death of any cause or last follow-up for patients still alive.
The cumulative incidence of adverse events
Following extraction of the tumor, a blood vessel burst causing increased blood loss during the procedure, an adverse event the surgeon did not expect.
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