Reduced Intensity Conditioning Regimens with Alemtuzumab Result in Low Treatment-Related Mortality and Low Relapse Rate in Unrelated and Related Allotransplantation Recipients.
Authors: Bigelow Carolyn L. , Elkins Stephanie , Herrin Vincent , Hardy Cheryl L. , Files Joe Clark 
Published: October 2019

Abstract
From September, 2003, to July, 2006, 29 adult patients with hematological malignancies received reduced intensity conditioning (RIC) instead of standard conditioning for allogeneic transplant. The RIC regimens used in our program employ an ablative dose of melphalan and patients become cytopenic and transfusion-dependent. Patients were transplanted for a variety of malignancies including multiple myeloma, AML, CML, NHL, MDS, one renal cell carcinoma and one CLL. Eleven (38%) were in CR at time of transplant while 18 (62%) had relapsed or refractory disease. With a median follow-up of 8 mon (range 1–27 mon) we have completed a retrospective analysis of treatment-related mortality, d+100 and overall survival, engraftment, grades I-II and III-IV acute GVHD, and relapse rate. Two RIC regimens were used consecutively, consisting of either: fludarabine 30 mg/m2 × 5 d and melphalan 140 mg/m2 × 1 d in both groups, and Alemtuzumab 20 mg/d × 3d (Group 1) and × 2d (Group 2). Group 1 was 10 patients and Group 2 was 19. Median age was 53, range 24–66. Median age of Group 1 was 47 (range 24–59) and of Group 2 was 54 (range 34–66). Seventeen patients received MUD products (4 in Group 1 and 13 in Group 2) and twelve received MRD products. Cell source was bone marrow (8 patients), PBSC (18 patients) cord blood (2 patients) and combined products in 2 transplants (2 patients). All patients received an adequate C34+ cell dose or TNC dose (cord blood) and none of the products was manipulated. HLA matches were 6/6 antigen matches or better in Group 1 except for a 4/6 allele matched cord blood. All products were 6/6 or better in Group 2 except for two who were 8/10 allele matches, one 5/6 antigen match and a 4/6 serological match (cord). GVH prophylaxis was tacrolimus tapering after d+100 and MMF tapering after d+30. All patients except one achieved a WBC graft, and the ANC >500/dl occurred at a median of 12 d (range 10–48 d). The graft failure was a CML in Group 2 who received the 8/10 marrow product followed by a cord blood transplant that also failed. Eight (28%) of the cohort developed acute GVHD grades I-II (one from Group 1, 7 from Group 2) and two developed grades III-IV (one from each group). Five (17%) went on to develop chronic GVHD (one from Group 1, 4 from Group 2). Relapse or disease progression occurred in only 38% (4 in Group 1 and 7 in Group 2). Seven from the cohort were treated with one or more DLI to accelerate conversion to full chimerism and two from each group developed acute GVHD following the treatment. Incidence of treatment-related mortality by d+100 was low at 21%, with two patients in Group 1 and 4 in Group 2. Overall survival was 41%, 3 in Group 1 and 9 in Group 2. Most surprising was the overall survival of MUD patients, 41%, all from Group 2, which is higher than that reported by NMDP for unrelated transplants. In summary, we plan to continue accruing patients to both Alemtuzumab dosing regimens in order to compare the incidence of GVHD and relapse rate in each treatment arm. We conclude that a RIC regimen utilizing Alemtuzumab allows for a relatively low treatment-related mortality (21%), a low relapse rate (38%) and a superior survival (41%), especially in MUD transplants.