High-dose peripheral blood stem cell infusion: a strategy to induce donor-specific hyporesponsiveness to allografts in pediatric renal transplant recipients.
We designed and implemented a clinical trial to achieve zero-rejection status in pediatric renal allograft recipients, using granulocyte-macrophage colony-stimulating factor (GM-CSF)-stimulated peripheral blood stem cell (PBSC) infusion. We studied 44 consecutive patients: 24 volunteers in a treated group (Tn) and 20 in a control group (Cn). Both groups were comparable with respect to clinical and laboratory parameters. The Tn group had 70.8% one haplo-match donors and the Cn group had 80% one haplo-match donors. Patients in the Tn group received cyclosporin A (CsA) and 0.4 mg/kg body weight prednisolone as immunosuppressants; azathioprine was added for patients of the Cn group, who received 1 mg/kg body weight prednisolone together with CsA. Living-related donors (LRD) of patients in the Tn group received GM-CSF 450 microg on four consecutive days followed by leucopheresis and immediate transfusion of unmodified PBSC into the recipient. This procedure was repeated once/twice, with one portal and one/two systemic infusions. Our aim was to maximize the dose of PBSC. The total average dose was 22 x 10(8) cells/kg body weight. Lymphocyte cross-match (LCM) was performed before GM-CSF injection and after the last PBSC infusion. Follow-up over an 18-month period revealed 100% graft survival with sustained low serum creatinine (SCr) values in patients of the Tn group as compared with 80% graft survival in patients of the control group who had marginally higher SCr levels. Absence of graft vs. host disease (GvHD), acute rejection episodes, and low incidence of cytomegalovirus (CMV) disease were the principal benefits of this protocol.
Trivedi
Hargovind L
HL
Department of Nephrology and Transplantation, Institute of Kidney Diseases & Research Center (IKDRC), Ahmedabad, Gujarat, India. ikdrc@vsnl.com
Shah
Veena R
VR
Vanikar
Aruna V
AV
Gera
Dinesh
D
Shah
Pankaj R
PR
Trivedi
Varsha B
VB
Khemchandani
Sajani
S
Mehta
AsiT
A
Dalal
Sonal S
SS
Shah
Shailesh A
SA
Shah
Tejanshu P
TP
Visana
Kirtipal V
KV
D000293:Adolescent; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007262:Infusions, Intravenous; D007676:Kidney Failure, Chronic / Q000601:surgery; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000379:methods; D008297:Male; D011300:Preoperative Care; D011446:Prospective Studies; D019172:Transplantation Conditioning; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology; D016896:Treatment Outcome
D016178:Granulocyte-Macrophage Colony-Stimulating Factor