Leukemia Research 35 (2011) 998–1000 Contents lists available at ScienceDirect Leukemia Research jou rnal h omepa g e: www.elsevier.com/locate/leukres Alemtuzumab based reduced intensity conditioning allogeneic haematopoietic stem cell transplantation for myelofibrosis W. Nagi, Z.Y. Lim ∗ , P. Krishnamurthy, V. Potter, V. Tindell, L. Reiff-Zall, A. Abdullah, N. Lea, M. Kenyon, J. Marsh, A.Y.L. Ho, G.J. Mufti, A. Pagliuca Department of Haematological Medicine, Kings College Hospital NHS Foundation Trust, Kings College London, Denmark Hill, London, UK a r t i c l e i n f o Article history: Received 7 January 2011 Received in revised form 10 February 2011 Accepted 14 February 2011 Available online 24 June 2011 Keywords: Myelofibrosis Allogeneic Alemtuzumab a b s t r a c t We report the results of 11 patients myelofibrosis, who have received a uniform alemtuzumab-based RIC HSCT. The median recipient age was 51 years. Stem cells were obtained from 8 full HLA-matched and 3 HLA-mismatched donors. The 2-year OS and TRM at 2-years was 46% and 54% with no disease relapse observed. For patients with a full HLA-matched donor, the 2-year TRM and OS was 37.5% and 62.5%. All 4 JAK2 V617F mutant positive patients achieved molecular remission after a median of 90 days post-transplant, and the median time to regression of bone marrow fibrosis was 180 days. © 2011 Elsevier Ltd. All rights reserved. 1. Introduction Advanced stages of chronic idiopathic myelofibrosis (CIMF) are characterised by marrow failure, extramedullary haemopoiesis with splenomegaly, bone marrow collagen fibrosis and osteoscle- rosis. Allogeneic HSCT is the only potentially curative treatment option for CIMF. Recently several groups have demonstrated the feasibility of RIC HSCT to significantly lower transplant related toxicity particularly in elderly CIMF patients with co-morbid conditions [1]. We report herein the results of 11 patients diag- nosed to have primary or secondary myelofibrosis, who have undergone allogeneic stem cell transplantation using a uniform fludarabine–busulphan–alemtuzumab (FBC) RIC HSCT protocol. 2. Patients and methods All patients were transplanted between November 2002 and June 2006. The median recipient age was 51 years (range: 46–62 years). Patients had a diagnosis of either primary (n = 6) or secondary myelofibrosis (n = 5). Patients with secondary myelofibrosis had an antecedent diagnosis of essential thrombocythaemia (n = 3) and polycythemia rubra vera (n = 2). Three patients with primary myelofibrosis had progressed to secondary AML and were pre-treated with a course of inten- sive chemotherapy prior to transplantation. All 3 patients were in morphological remission at the time of transplantation. The transplant regimen consisted of busulphan orally 4 mg/kg daily in 4 divided doses for 2 days, fludarabine intravenously 30 mg/m 2 daily for 5 days and alem- tuzumab (CAMPATH-1H) intravenously 20 mg daily for 5 days with post-transplant immunosuppression using cyclosporine as previously described [2]. The protocol ∗ Corresponding author. Tel.: +44 0203 2995289; fax: +44 0203 2993514. E-mail addresses: ziyi.lim@nhs.net, ziyi.lim@kch.nhs.uk (Z.Y. Lim). was approved by the local institutional ethics committee, and all patients gave informed consent prior to participation in this study. The stem cell source was bone marrow in 3 patients and peripheral blood pro- genitor cells in 8 patients. The median CD34 stem cell dose infused was 8.77 × 10 6 CD34/kg (range: 3.43–24.45). Donor and recipients were tissue typed using high resolution typing at HLA A, B, C, DR and DQ loci. There were 2 sibling HLA-matched donors, 6 HLA-matched unrelated donors, and 3 9/10 HLA-mismatched unrelated donors (DRB1, A and CW loci respectively). Based on the Lille scoring system [3], 4 patients had a score of 0, and 7 patients had a score of 1–2. Bone marrow fibrosis at the time of transplantation was grade 2 (n = 2), grade 3 (n = 3) and grade 4 (n = 6). On the basis of the IWG-MRT myelofibrosis prognostic scoring system [4], 7 patients had a score of 0–1, 4 had a score of 2–4. JAK2 V617F mutation analysis was performed using primers and probes as described previously [5]. JAK2 V617F allele burden was determined by real-time PCR using MGB-hydrolysis probes (Applied Biosystems) [6]. Overall survival (OS) was measured from day 0 to death from any cause or last known follow-up; disease-free survival (DFS) from day 0 to the first indicator of relapse (morphological or cytogenetic), death of any cause, or last known follow- up; Survival curves were estimated using Kaplan–Meier methodology, and log-rank test was used to assess differences between groups. 3. Results The median follow-up for survivors was 739 days (range: 453–1680 days). Neutrophil and platelet engraftment occurred at a median of 14 days and 15 days respectively. One patient had primary graft failure at 43 days post-transplant and subsequently died of haemorrhagic complications. Acute GvHD was observed in 3 patients. Two patients had grade II–III acute cutaneous GvHD. One patient developed grade IV acute GvHD of gastrointestinal tract, and eventually died of complications related to GvHD at 9 months post-transplant. Only 1 patient had chronic extensive cutaneous GvHD and remains in remission. Transplant related mortality was 0145-2126/$ – see front matter © 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.leukres.2011.02.012