LAUSR

Introduction Reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) has been shown to be successful; however, the ideal RIC regimen is not known. In this study, we report the pooled results of three separate prospective studies utilizing cladribine (2CdA) and melphalan (Mel) based conditioning in patients undergoing allogeneic HCT. Objectives To determine the feasibility, toxicity, and efficacy of a 2Cda/Mel based regimen in patients requiring RIC HCT. Methods 63 adult patients were treated with 2Cda/Mel and included for analysis (84% greater than 50 years of age). 40 men and 23 women received HCT between 1999 and 2014 at Scripps Clinic. 17 patients had previously undergone autologous HCT. All patients received 2CdA 0.14 mg/kg/day for either 4 or 5 days and Mel at either 100 mg/m2 or 180mg/m2 total dose. All patients received rabbit-derived anti-thymocyte globulin (ATG). 22 unrelated recipients received Methotrexate. 41 related recipients received oral cyclosporine as GVHD prophylaxis. 22 patients received tacrolimus as GVHD prophylaxis. Donor lymphocyte infusions (DLI) were allowed but not scheduled. Results Two patients expired prior to neutrophil engraftment; for the remaining 61 the median time to recovery of absolute neutrophil count > 0.5 × 109/L was 12 days (range 9-21). 7 patients expired prior to platelet engraftment; for the remaining 56 the median time to platelets >20 × 109/L without transfusion support was 19 days (12-55). Median overall survival for all 63 patients was 17 months (11 days to 16 years). 10 patients expired prior to day 100, 19 between day 101 and 365, and 14 greater than one year. Diseases included AML (18), Lymphoma (15), MDS (8), Multiple Myeloma (5) and others (17). Non-relapse mortality (NRM) at 100 days, NRM at 365 days, and 1 year OS were 18%, 53%, and 26% for AML, 0%, 37%, and 63% for MDS, and 13%, 27%, and 73% for Lymphoma. In evaluable patients, Grade 2-4 acute GVHD was seen in 47%. Grade 3-4 acute GVHD was seen in 34%. Chronic GVHD was seen in 45% of patients. For 2 patients, acute GVHD was the primary cause of death. 18 patients received DLI; reasons for DLI were relapse (11), mixed chimerism (5), post-transplant lymphoproliferative disorder (PTLD) (1), and idiopathic hemolytic anemia (1). Several patients developed second malignancies after HCT including non-melanoma skin cancers (8), melanoma (1), PTLD (4), myeloproliferative disorder (1), breast cancer (1), cervical cancer (1), and tonsillar squamous cell carcinoma (1). Conclusion 2CdA and Mel are effective agents for RIC HCT. This is the largest study of this regimen published to date. Though it is difficult to fully compare the results from different non-randomized trials, rates of NRM, OS, and GVHD appear similar to other published RIC regimens.