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Br J Haematol. 2019 Feb;184(4):547-557. doi: 10.1111/bjh.15685. Epub 2018 Nov 22.

Impact of graft-versus-lymphoma effect on outcomes after reduced intensity conditioned-alemtuzumab allogeneic haematopoietic stem cell transplantation for patients with mature lymphoid malignancies.

Author information

1
Department of Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
2
Centre for Clinical Haematology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
3
Department of Haematology, Beatson West of Scotland Cancer Centre, Glasgow, UK.
4
Department of Haematology, Plymouth Hospitals NHS Trust, Plymouth, UK.
5
Serviço de Hematologia, Hemoterapia e Terapia Celular, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.

Abstract

Allogeneic haematopoietic stem cell transplant (allo-HSCT) offers potentially curative therapy for patients with relapsed/refractory lymphoid malignancies. Reduced-intensity conditioning (RIC) with Alemtuzumab reduces transplant-related mortality and graft-versus-host disease (GvHD), but may be associated with increased risk of relapse. With the aim of studying the effect of GVHD and donor lymphocyte infusions (DLI) on relapse, we performed a retrospective study of 288 patients (57% non-Hodgkin lymphoma, 24% Hodgkin lymphoma and 19% chronic lymphocytic leukaemia; 58% were relapsed/refractory) who underwent RIC-Alemtuzumab-HSCT between 2000 and 2012. Median follow-up time for survivors was 64 months. Five-year overall survival, relapse incidence, GvHD/relapse-free survival and non-relapse mortality were 47%, 33%, 37% and 28% respectively. Cumulative incidence of grade II-IV acute and extensive chronic GvHD was 22% and 21% at 100 days and 5 years respectively. On multivariate analysis, presence of GvHD (P = 0·03) and unrelated donor type (P = 0·03) were protective of relapse. 62/288 patients received DLI for either mixed donor chimerism (prophylactic DLI, n = 37) or clinical relapse (therapeutic DLI, n = 25). Prophylactic and therapeutic DLI successfully converted the patient to full or stable mixed donor chimerism in 78% and 56% of patients respectively. These data demonstrate good long-term outcomes and support the concept of the graft-vs-lymphoma effect as a key protective factor against relapse following RIC-Alemtuzumab allo-HSCT for patients with mature lymphoid malignancies.

KEYWORDS:

alemtuzumab; donor lymphocyte infusions; reduced intensity conditioning

PMID:
30467838
DOI:
10.1111/bjh.15685

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