Better Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation with Reduced-Intensity Conditioning in Elderly Patients with Hematological Malignancies

Introduction: The prognosis of elderly patients with hematological malignancies by chemotherapy is poor. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can increase disease-free survival (DFS) for this setting, but transplant-related mortality (TRM) is high due to older age and comorbidities. Reduced-intensity conditioning (RIC) has resulted in lower TRM and provided a potential curative modality via graft-versus-tumor effect which may benefit for elderly patients.

Objective: In present study, the safety and efficacy of allo-HSCT in elderly patients with hematological malignancies with either RIC or myeloablative conditioning (MAC) were evaluated.

Methods: Between May 2019 and June 2021, 19 patients over 55 years with hematological malignancieswho underwent allo-HSCT in our hospital were enrolled. The median age was 61 (55-70) years old. Eleven cases were female and 8 were male. The diagnosis were myelodysplastic syndrome (MDS,n=8), acute myeloid leukemia (AML,n=7), acute lymphoblastic leukemia (ALL,n=3)and diffuse large B-cell lymphoma (DLBCL,n=1).The disease status before transplant was complete remission (CR) in 11 (57.9%) (minimal residual disease (MRD) negative in 6; MRD positive in 5) and non-remission (NR) in 8 (42.1%). Two cases were second allo-HSCT. The types of transplant included haploidentical (n=11, 57.8%), unrelated (n=4, 21.1%), and identical siblings (n=4, 21.1%). Either RIC (n=6, 31.6%) or MAC (n=13, 68.4%) regimens were applied. For RIC cohort, the regimen with total body irradiation (TBI, 6-7Gy, fractionated,n=6) /fludarabine (30mg/m ², 5 days)/cytarabine (1g/m ², 3 days)/Me-CCNU (250mg/m ², 1 day)/rabbit anti-T-cell globulin was used. For MAC cohort, the regimen with TBI (8Gy, fractionated, n=3)/TMI(10Gy, fractionated, n=1, second allo-HSCT) or busulfan (0.8mg/kg q6h, 3days, n=9)/fludarabine (30mg/m ², 5days)/cytarabine (1g/m ², 3 days)/Me-CCNU (250mg/m ², 1 day)/rabbit anti-T-cell globulin was used. Decitabine (20mg/m ², 3 days)or etoposide (200mg/m ², 2 days) were administrated in some patients in NR or MRD positive. Some patients received maintenance therapy post-transplant with targeted medicine based on their fusion genes or gene mutations.

Results: Seventeen evaluable patients achieved full donor chimerism because two patients (AML 1, MDS 1) in NR who underwent salvaged transplants were still with active disease at the first disease evaluation post-HSCT. The median time for neutrophil recovery was 14 (8-22) days, and the median time for platelet recovery was 14 (8-28) days. With a median follow-up of 11.5(1-23) months, overall survival (OS) and DFS were 14/19 (73.6%), 13/19(68.4%), respectively. Two (10.5%) patients relapsed and 5 (26.3%) patients died. The causes of death included graft-versus-host disease (GVHD, n=2), infections (n=2), and disease progress (n=1). TRM was 21.1%. There was a trend of better OS (100% vs. 61.5%) and DFS (83.3% vs. 61.5%), lower TRM (0% vs. 30.8%), lower acute GVHD (aGVHD) (0% vs. 38.5%), and lower CMV reactivation (16.7% vs. 53.8%) in RIC cohort compared with MAC cohort. The incidences of chronic GVHD (cGVHD) were similar in RIC (33.3%) and MAC (36.4%) cohorts.

Conclusions: Under our protocol, OS (73.3%) and DFS (68.4%) has been improved remarkably by allo-HSCT in elderly patients with hematological malignancies even 42.1% cases in NR before transplant. Our preliminary data have shown that RIC regimen has resulted in better OS and DFS, lower TRM, lower aGVHD, lower CMV reactivation and similar cGVHD. More patients and longer follow-up are warranted.