Abstract A preparative regimen of fludarabine, cyclophosphamide (Cy) and low dose TBI 200cGy (FC-TBI) followed by post-transplant Cy (PTCy) is one of the most widely utilized conditioning platforms for nonmyeloablative peripheral blood stem cell transplantation (PBSCT). It provides reliable engraftment in patients receiving HLA-mismatched transplants, manageable regimen-related toxicity and low non-relapse mortality (NRM), even in older and less fit patients. However, relapse represents a major source of treatment failure, particularly in patients with higher risk myeloid malignancies and those with measurable residual disease (MRD) pre-transplant. To help mitigate the relapse risk, we substituted melphalan 100mg/m2 for pre-transplant Cy in the fludarabine/TBI 200cGy backbone (FM-TBI) followed by PTCy, tacrolimus and MMF. Twenty-eight consecutive patients with hematologic malignancy receiving PBSCT following FM-TBI from June '21 to Dec '24 was compared to 127 consecutive patients receiving FC-TBI from Feb '13 to Dec '24. The donor type was Haplo, MUD and MRD in 91%, 8% and 1% respectively. Of the 155 total patients, median age was 63 years (range, 19-77), comorbidity index was 3 (range, 0-10), DRI was high/very high in 25%, and most common transplanted diseases were AML 47, MDS 31 and ALL 24, and were similar between FC-TBI and FM-TBI patients. In contrast, FM-TBI patients were statistically more likely to receive MRD/MUD (29% vs. 5%, p0.001) and have younger donors (median age 29 vs. 41 years, p0.001). Median follow-up was 13.5 months and 67 months for FM-TBI and FC-TBI patients, respectively. Compared to FC-TBI patients, FM-TBI resulted in slower ANC and PLT engraftment (19 vs. 17 days, p=0.07 and 33 vs 27 days, p=0.032) with similar incidence of graft rejection (0 vs. 4%, p=0.59). No differences were seen in the incidence of acute or chronic GVHD or CMV reactivation. FM-TBI was associated with a significantly higher 1-yr NRM (36% vs. 7%, p0.001) and lower 1-yr survival (67% vs. 82%, p=0.029), while 1-year relapse incidence was reduced (7% vs. 23%, p=0.031). Furthermore, the number of hospital days through day +100 was significantly longer following FM-TBI (20 vs. 11 days). In multivariable analysis, controlled for diagnosis and DRI, the use of FM-TBI was associated with higher NRM (HR 4.24, p=0.002) and a trend towards inferior survival (HR 1.92, p=0.08). In the context of reduced intensity PBSCT in older transplant recipients, substitution of melphalan for pre-transplant Cy resulted in higher regimen-related toxicity, resulting in increased NRM and requirement for inpatient hospitalization. Despite lower relapse incidence with FM-TBI, 1-yr survival favored FC-TBI. The use of FM-TBI RIC PBSCT should be reserved for younger, healthier transplant recipients. Alternative strategies are required to reduce relapse incidence in older, less fit PBSCT recipients with higher risk disease.
Asad Bashey (Mon,) studied this question.