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Unrelated donor hematopoietic stem cell transplantation for the treatment of non‐malignant genetic diseases: An alemtuzumab based regimen is associated with cure of clinical disease; earlier clearance of alemtuzumab may be associated with graft rejection
Author(s) -
AbdelAzim Hisham,
Mahadeo Kris Michael,
Zhao Quan,
Khazal Sajad,
Kohn Donald B.,
Crooks Gay M.,
Shah Ami J.,
Kapoor Neena
Publication year - 2015
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.24141
Subject(s) - alemtuzumab , medicine , hematopoietic stem cell transplantation , busulfan , cyclophosphamide , regimen , transplantation , fludarabine , gastroenterology , oncology , immunology , surgery , chemotherapy
Hematopoietic stem cell transplantation (HSCT) with matched unrelated donors (MUD), offers potentially curative therapy for patients with non‐malignant genetic diseases. In this pilot study conducted from 2006 to 2014, we report the outcomes of 15 patients with non‐malignant genetic diseases who received a myeloablative regimen with a reduced cyclophosphamide dose, adjunctive serotherapy and MUD HSCT [intravenous alemtuzumab (52 mg/m 2 ), busulfan (16 mg/kg), fludarabine (140mg/m 2 ), and cyclophosphamide (105 mg/kg)]. Graft‐versus‐host‐disease (GVHD) prophylaxis consisted of tacrolimus/cyclosporine and methylprednisolone. Median (range) time to neutrophil engraftment (>500 cells/µL) and platelet engraftment (>20,000/mm 3 ) were 15 (12–28) and 25 (17–30) days, respectively. At a median follow‐up of 2 (0.2–5.4) years, the overall survival (OS) was 93.3% (95% CI: 0.61–0.99) and disease‐free survival (DFS) was 73.3% (95% CI: 0.44–0.89). Among this small sample, earlier alemtuzumab clearance was significantly associated with graft rejection ( P = 0.047), earlier PHA response ( P = 0.009) and a trend toward earlier recovery of recent thymic emigrants (RTE) ( P = 0.06). This regimen was associated with durable donor engraftment and relatively low rates of regimen related toxicity (RRT); future alemtuzumab pharmacokinetic studies may improve outcomes, by allowing targeted alemtuzumab clearance to reduce graft rejection and promote more rapid immune reconstitution. Am. J. Hematol. 90:1021–1026, 2015. © 2015 Wiley Periodicals, Inc.