Outcomes and Impact of Donor Lymphocyte Infusion after Reduced Intensity Conditioned-Alemtuzumab Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Mature Lymphoid Malignancies

• Published in: Blood 2016-12, Vol.128 (22), p.3500-3500
• Main Authors: Brierley, Charlotte K., Jones, Francesca M, Hanlon, Katherine, Peniket, Andrew, Medd, Patrick, Clark, Andrew, Parker, Anne, Chaganti, Sridhar, Malladi, Ram, Craddock, Charles, Danby, Robert, Rocha, Vanderson
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V128.22.3500.3500

Allogeneic hematopoetic stem cell transplantation (allo-HSCT) offers long-term remission for patients with lymphoid malignancies. In particular, reduced intensity conditioned (RIC) protocols with Alemtuzumab T-cell depletion lead to durable engraftment and reduced graft versus host disease (GvHD). However, such regimens may be associated with reduced graft-versus-lymphoma (GvL) effect and higher incidence of disease progression, leading to increased use of donor lymphocyte infusion (DLI). This study examined transplant outcomes and use of DLI in a large UK RIC-Alemtuzumab conditioned HSCT cohort. 288 consecutive adult patients from three UK transplant centres (Birmingham, Glasgow, Oxford) undergoing first Alemtuzumab-based RIC HSCT for Hodgkin's lymphoma (57%), Non-Hodgkin's lymphoma (24%) and chronic lymphocytic leukemia (19%) between 2000 and 2012 were included. Overall survival (OS), current progression-free survival (CPFS), relapse incidence (RI), transplant-related mortality (TRM), incidence of GvHD and effects of DLI were analyzed. Median age was 49y (range 17-68) and 60% were male. Patients were heavily pre-treated with 58% having received ≥3 prior lines of treatment and 49% having failed a previous autograft. 55% received stem cells from an HLA-matched unrelated donor and 94% received a peripheral blood stem cell harvest. The most frequent conditioning regimen was Fludarabine, Melphalan and Alemtuzumab (FMC) (70%) and the median total Alemtuzumab dose was 50mg (range 30-100). Median duration of follow-up for survivors was 64 months. 3y OS and CPFS were 53% and 50%, respectively. Factors negatively associated with OS in univariate (UV) analysis were previous autograft (p=0.01), no requirement for DLI (p=0.05), disease status not CR (p=0.05), previous treatment number ≥3 (p=0.007) and failure to engraft plts (p=0.001). On multivariate (MV) analysis, only previous autograft (HR 1.58 p=0.01) and failure to engraft plts (HR 2.3 p=0.0001) retained significance. Factors negatively associated with CPFS on UV analysis were no requirement for DLI (p=0.006), failure to engraft plts (p=0.0003) and previous treatment lines ≥3 (p=0.04). On MV analysis, no DLI remained a significant predictor of adverse CPFS (HR 1.8 p=0.01), as did failure to engraft plts (HR 1.77 p=0.005) and ≥3 treatment lines (HR 1.46 p=0.04). At 3y, the cumulative incidence of relapse and TRM was both 27%. The incidence of grade 2-4 acute GvHD (aGvHD) and extensive chronic GvHD (cGvHD) was 22