Alemtuzumab markedly reduces chronic GVHD without affecting overall survival in reduced-intensity conditioning sibling allo-SCT for adults with AML

被引:0
作者
R K Malladi
A J Peniket
T J Littlewood
K E Towlson
R Pearce
J Yin
J D Cavenagh
C Craddock
K H Orchard
E Olavarria
G McQuaker
M Collin
D I Marks
机构
[1] John Radcliffe Hospital,Department of Haematology
[2] BSBMT Data Registry,Department of Haematology
[3] Guy's Hospital,Department of Haematology
[4] Manchester Royal Infirmary,Department of Haematology
[5] St Bartholomew's Hospital,undefined
[6] Haematology,undefined
[7] Queen Elizabeth Hospital,undefined
[8] Southampton General Hospital,undefined
[9] Hammersmith Hospital,undefined
[10] Glasgow Royal Infirmary,undefined
[11] Newcastle upon Tyne Hospitals NHS Trust,undefined
[12] Bone Marrow Transplant Unit,undefined
[13] Bristol Children's Hospital,undefined
来源
Bone Marrow Transplantation | 2009年 / 43卷
关键词
alemtuzumab; AML; allograft; GVHD;
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学科分类号
摘要
By retrospective analysis of 88 patients from the British Society of Blood and Marrow Transplantation registry, we investigated the effect of in vivo T-cell depletion in HLA-identical sibling reduced-intensity conditioning (RIC) allografts for adult AML by comparing patients who received alemtuzumab with those without alemtuzumab conditioning. Both groups were equivalent for age, sex, karyotype and disease status at transplant. With a median follow-up of 27 months (3–72 months) and 48 months (7–72 months), the 2- and 5-year overall survival, with or without alemtuzumab, is 60 and 60% (P=0.80) and 61 and 53%, respectively (P=0.85). The 2-year non-relapse mortality is 12% with alemtuzumab, and 17% without alemtuzumab (P=0.49). The 2-year relapse rate is 35% with alemtuzumab compared with 19% without alemtuzumab (P=0.28). Grades II–IV acute GVHD occurred in 22% (8/37) without alemtuzumab compared with 14% (7/51) given alemtuzumab (P=0.25). Extensive chronic GVHD occurred in 47% (14/30) not given alemtuzumab compared with 4% (2/45) who were given alemtuzumab (P=0.001). Among evaluable patients, the risk of infections was higher in those treated with alemtuzumab compared with those not treated with alemtuzumab (79 vs 57%, respectively, P=0.02). In conclusion, alemtuzumab has a beneficial effect by reducing chronic GVHD without affecting overall survival. Further studies are warranted before alemtuzumab can be recommended as standard in RIC allografts for AML.
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页码:709 / 715
页数:6
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共 216 条
[1]  
Dick JE(2005)Biology of normal and acute myeloid leukemia stem cells Int J Hematol 82 389-396
[2]  
Lapidot T(1997)Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell Nat Med 3 730-737
[3]  
Bonnet D(1998)The importance of diagnostic cytogenetics on outcome in AML: analysis of 1612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Working Parties Blood 92 2322-2333
[4]  
Dick JE(2002)The value of allogeneic bone marrow transplant in patients with acute myeloid leukaemia at differing risk of relapse: results of the UK MRC AML 10 trial Br J Haematol 118 385-400
[5]  
Grimwade D(2006)A phase 2 trial of the FLT3 inhibitor lestaurtinib (CEP701) as first-line treatment for older patients with acute myeloid leukemia not considered fit for intensive chemotherapy Blood 108 3262-3270
[6]  
Walker H(2007)A phase 2 study of the farnesyltransferase inhibitor tipifarnib in poor-risk and elderly patients with previously untreated acute myelogenous leukemia Blood 109 1387-1394
[7]  
Oliver F(2005)Results of a phase 1–2 study of clofarabine in combination with cytarabine (ara-C) in relapsed and refractory acute leukemias Blood 105 940-947
[8]  
Wheatley K(2005)Pulmonary complications in adult blood and marrow transplant recipients: autopsy findings Chest 128 1385-1392
[9]  
Harrison C(1998)Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases Blood 91 756-763
[10]  
Harrison G(1997)Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy Blood 89 4531-4536