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 language | English (US) |
|---|---|
| Pages (from-to) | 1021-1026 |
| Number of pages | 6 |
| Journal | American Journal of Hematology |
| Volume | 90 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 1 2015 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Unrelated donor hematopoietic stem cell transplantation for the treatment of non-malignant genetic diseases
T2 - An alemtuzumab based regimen is associated with cure of clinical disease; earlier clearance of alemtuzumab may be associated with graft rejection
AU - Abdel-Azim, Hisham
AU - Mahadeo, Kris Michael
AU - Zhao, Quan
AU - Khazal, Sajad
AU - Kohn, Donald B.
AU - Crooks, Gay M.
AU - Shah, Ami J.
AU - Kapoor, Neena
PY - 2015/11/1
Y1 - 2015/11/1
N2 - 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.
AB - 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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U2 - 10.1002/ajh.24141
DO - 10.1002/ajh.24141
M3 - Article
VL - 90
SP - 1021
EP - 1026
JO - American Journal of Hematology
JF - American Journal of Hematology
SN - 0361-8609
IS - 11
ER -