BuCy combined with cladribine and medium-dose cytarabine as an intensified conditioning regimen for allogeneic hematopoietic stem cell transplantation in T-ALL/lbl patients

Abstract Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been regarded as the most effective curative therapy for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL), a highly aggressive hematological malignant. And the conditioning regimen is a crucial component of allo-HSCT. Exploring new conditioning regimens to reduce relapse without increasing transplant-related mortality is of great significance for improving the prognosis of T-ALL/LBL patients. In consideration of the synergistic anti-leukemia effect of cladribine (CLAD) and cytarabine (Ara-c), our center added CLAD and medium-dose Ara-C on the basis of busulfan plus cyclophosphamide to intensify the conditioning regimen (CBAC). Our previous clinical data have suggested that CBAC regimen may reduce relapse without increasing non-relapse mortality (NRM), improving the prognosis of high-risk B-ALL patients. In this study, we implemented the CBAC regimen in T-ALL/LBL transplantation to investigate its potential efficacy benefits, conducting a comparative retrospective study against the TBI-Cy based regimen. Methods: Clinical data of T-ALL/LBL patients underwent allo-HSCT after receiving CBAC conditioning regimen (CLAD (5mg/m2/d, days -8 to -4), Ara-C (2g/m2/d, days -8 to -4), Bu (0.8mg/kg, Q6h, days -8 to -5), cyclophosphamide (CTX) (1.8g/m2/d, days -3 to -2). The medication sequence involved intravenous infusion of CLAD over 3 hours, followed by Ara-C through continuous intravenous drip over 3 hours, with a 4-hour interval) at Xiangya Hospital, Central South University were retrospectively reviewed. Additionally, data of T-ALL/LBL patients received traditional TBI-Cy based conditioning regimen were collected as a control group. We then analyzed the engraftment, transplant-related complications, relapse, and survival outcomes among different conditioning regimen groups. Results: The data were collected for a total of 44 T-ALL/LBL patients, divided into CBAC group (20 patients) and TBI-Cy group (24 patients). The two groups were similar in terms of age, gender, MRD/CR status at HSCT, IPI score, infused mononuclear cell count, infused CD34+ cell count and donor source (p>0.05). There was also no significant difference in either incidence or severity of GVHD, median time of neutrophil/platelet engraftment, incidence of CMV/EBV reactivation and bacterial/ fungal infection between the two groups (p>0.05). The 3-year non-relapse mortality (NRM), cumulative incidence of relapse (CIR), disease-free survival (DFS) and overall survival (OS) of CBAC and TBI-Cy group were 25.0% vs. 21.1% (p=0.786), 15.8% vs. 21.8% (p= 0.557), 59.2% vs. 57.2% (p =0.796), 64.2% vs. 65.8% (p= 0.956), respectively. Conclusion: The CBAC regimen achieved comparable efficacy to TBI-Cy-based regimen and can serve as an alternative to some extent in T-ALL/LBL patients.