A Comparison of Conditioning Regimens with or without Alemtuzumab for Sibling RIC Transplants for AML: Study from the British Society for Blood and Marrow Transplantation.
Authors: Malladi Ram K. , Peniket Andrew J. , Littlewood Timothy James , Towlson Keiren E. , Pearce Rachel , Yin John , Cavanagh Jamie D. , Craddock Charles , Orchard Kim H. , Marks David I. 
Published: October 2019

Abstract
The use of in vivo Alemtuzumab in reduced intensity conditioning (RIC) stem cell transplantation for AML has been reported to be associated with low non-relapse mortality (NRM) and favourable survival outcomes. However, Alemtuzumab depletes the alloreactive donor T cells and recipient antigen presenting cells that mediate graft versus leukaemia (GvL) and graft versus host disease (GvHD). We report the analysis of 90 patients from the British Society for Blood and Marrow Transplantation (BSBMT) registry comparing T-cell replete and Alemtuzumab-containing protocols in HLA-identical sibling RIC transplants for AML. Patient characteristics were: median age at diagnosis-50 years; 46%-male, 54%-female; diagnostic karyotypes according to MRC AML criteria-13% good risk, 76% standard risk, 11% poor risk; 67%-CR1, 24%-CR2, 9-refractory/relapsed disease/PR. Conditioning protocols were: fludarabine/melphalan (66%), fludarabine/busulphan (17%), fludarabine/cyclophosphamide (11%), others (6%). 51 patients (57%) received in vivo Alemtuzumab and 37 patients (41%) did not receive any T-depleting antibodies. 2 patients (2%) received ALG/ATG and were excluded from subsequent analyses comparing the effect of Alemtuzumab with T-replete transplants. The median CD34 cell dose was 4.41x106/kg (0.77–15.8). The actuarial overall survival (OS) and progression-free survival (PFS) at 5 years for all patients were 53% and 47% respectively. The NRM and relapse risk (RR) at 5 years were 16% and 49% respectively. The majority of the relapses were within 2 years of transplant. Acute GvHD was either absent or Grade I in 75 patients (84%). Grade II-IV acute GvHD developed in 15 patients (16%). Extensive chronic GvHD occurred in 18/65 surviving ≥100 days (28%). A complete hematological remission(CR) at transplant predicted for OS at 3 years with 54% survival for CR1, 57% survival for CR≥2 and 0% survival for PR/relapse/refractory disease (p<0.05). The OS at 3 years for standard and poor risk karyotype were 55% and 38%, respectively (non-significant (NS)). OS at 3 years between the Alemtuzumab and non-Alemtuzumab groups were similar at 53% and 60%. There was a trend towards a higher NRM for the non-alemtuzumab patients compared to the alemtuzumab group (20% vs. 12% at 3 years) but this was offset by a trend for lower RR in the non-Alemtuzumab group compared to the Alemtuzumab group (30% vs. 38% at 3-years) (all NS). Acute GvHD rates were similar in the two groups (Alemtuzumab vs non-Alemtuzumab: 35% vs. 32%). Chronic GvHD was significantly lower in the Alemtuzumab group (19% vs. 91% at 3-years, p<0.05). We conclude that RIC allogeneic stem cell transplantation is an effective treatment for AML in patients with an HLA-identical sibling. There may be important differences between conditioning regimens containing Alemtuzumab and those that do not T-deplete which are highlighted by this study. Further larger randomized studies may be indicated to evaluate these differences further.