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

Hisham Abdel-Azim, Kris Michael Mahadeo, Quan Zhao, Sajad Khazal, Donald B. Kohn, Gay M. Crooks, Ami J. Shah, Neena Kapoor

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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/m2), busulfan (16 mg/kg), fludarabine (140mg/m2), 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/mm3) 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.

Original languageEnglish (US)
Pages (from-to)1021-1026
Number of pages6
JournalAmerican Journal of Hematology
Volume90
Issue number11
DOIs
StatePublished - Nov 1 2015
Externally publishedYes

Fingerprint

Unrelated Donors
Inborn Genetic Diseases
Hematopoietic Stem Cell Transplantation
Graft Rejection
Cyclophosphamide
Busulfan
Passive Immunization
Methylprednisolone
Tacrolimus
Graft vs Host Disease
Therapeutics
Cyclosporine
Disease-Free Survival
Neutrophils
Blood Platelets
Pharmacokinetics
Tissue Donors
Survival
alemtuzumab

ASJC Scopus subject areas

  • Hematology

Cite this

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. / Abdel-Azim, Hisham; Mahadeo, Kris Michael; Zhao, Quan; Khazal, Sajad; Kohn, Donald B.; Crooks, Gay M.; Shah, Ami J.; Kapoor, Neena.

In: American Journal of Hematology, Vol. 90, No. 11, 01.11.2015, p. 1021-1026.

Research output: Contribution to journalArticle

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abstract = "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/m2), busulfan (16 mg/kg), fludarabine (140mg/m2), 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/mm3) 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.",
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