Efficacy and safety of cladribine in combination with busulfan and cyclophosphamide as an intensive conditioning regimen preceding allogeneic hematopoietic stem cell transplantation in relapsed or refractory acute myeloid leukemia

Abstract

Background

Cladribine, an analogue of deoxyadenosine, is used for therapy of hematological malignancies. Cladribine-containing regimen has been recommended as a rescue therapy for relapsed or refractory (R/R) acute myeloid leukemia (AML). Its combination with busulfan plus cyclophosphamide (BuCy), as an intensive conditioning regimen prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT), requires more clinical evidence. This study aimed to explore the efficacy and safety of cladribine plus BuCy administered as an intensive conditioning regimen before allo-HSCT in R/R AML patients.

Methods

Twenty-three R/R AML patients, who underwent cladribine plus BuCy intensive conditioning regimen before allo-HSCT, were retrospectively analyzed. The median (range) follow-up duration time of observation was 0.73 (0.08–2.69) years.

Results

The median (range) returned levels of mononuclear cells were 11.5 (6.1–18.5) x 108/kg and CD34+ cells were 5.5 (3.5–9.3) x 106/kg. The median (range) time of platelet reconstitution was 13.0 (9.0–21.0) days and neutrophil reconstitution was 14.0 (11.0–26.0) days. The incidence of conditioning regimen related toxicity (CRRT) affected 69.6% of patients; all CRRT-affected patients had grade I-II symptoms, including gastrointestinal tract (39.1%), oral cavity (26.1%), liver (8.7%), and kidney (4.3%) CRRTs. The incidence of acute graft-versus-host disease (GVDH) included 30.4% among all patients with 4.3% of grade III-IV acute GVHD, and 34.8% of chronic GVHD. During the follow-up period, 4 (17.4%) patients relapsed, and 6 (26.1%) patients died (cause of death: disease relapse, n = 3; infection, n = 2; GVHD, n = 1). The 1-year and 2-year accumulating event-free survival rates were 66.3% and 53.1%, respectively. The 1-year accumulating overall survival rate was 74.7% and 2-year survival rate was 64.0%.

Conclusion

Cladribine plus BuCy intensive conditioning regimen before allo-HSCT exhibits favorable treatment efficacy with acceptable toxicity in R/R AML patients.