title: Rapid hematopoietic engraftment following fractionated TBI conditioning and transplantation with CD34(+) enriched hematopoietic progenitor cells from partially mismatched related donors.
abstract: Nineteen adult patients with poor-risk hematologic malignancy received T cell-depleted (TCD) hematopoietic progenitor cell (HPC) transplant from partially mismatched related donors (PMRD). The preparative regimen (FITFA) included fractionated TBI, thiotepa, fludarabine, and horse (n = 3) or rabbit (n = 16) anti-thymocyte anti-sera (ATG). GVHD prophylaxis consisted of TCD by positive/negative selection using the Isolex 300i system and pre-transplant ATG with no post-transplant immunosuppression. The mean number (+/-s.d.) of transplanted CD34(+) and CD3(+) cells were 8.9 x 10(6)/kg +/-4.3 (range 2.6-19.3) and 1.4 x 10(4)/kg +/-1.2 (range 0.3-4.6) respectively. Seventeen patients evaluable for neutrophil engraftment achieved an ANC >0.5 x 10(9)/l at a median of 12 days (range 9-27), with evidence of full donor chimerism. Thirteen patients died of the following causes: relapse (n = 6), infections (n = 5), interstitial pneumonia (n = 1), and unknown causes (n = 1) None of the recipients of rabbit ATG required therapy for acute or chronic GVHD. Five patients are alive and disease-free at a median time of 303 days post transplant (range 100-660). The FITFA preparative regimen using fractionated TBI is well tolerated and is sufficiently immunosuppressive to allow rapid and stable donor origin hematopoietic engraftment without 'mega' doses of CD34(+) cells. Combination of stringent ex vivo TCD and pre-transplant ATG is effective GVHD prophylaxis.
authors.affiliation: Emory University School of Medicine, Winship Cancer Institute, Department of Hematology and Oncology, Bone Marrow and Stem Cell Transplant Center, Emory University, Atlanta, GA, USA.
authors.forename: I
authors.initials: I
authors.lastname: Redei
authors.forename: A A
authors.initials: AA
authors.lastname: Langston
authors.forename: S
authors.initials: S
authors.lastname: Lonial
authors.forename: J K
authors.initials: JK
authors.lastname: Cherry
authors.forename: A J
authors.initials: AJ
authors.lastname: Allen
authors.forename: E
authors.initials: E
authors.lastname: Hamilton
authors.forename: M
authors.initials: M
authors.lastname: Jones
authors.forename: V M
authors.initials: VM
authors.lastname: Bartlett
authors.forename: E K
authors.initials: EK
authors.lastname: Waller
mesh_terms: D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D002423:Cause of Death; D002648:Child; D003131:Combined Modality Therapy; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006648:Histocompatibility / Q000276:immunology*; D006801:Humans; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods* / Q000401:mortality; D014184:Transplantation, Homologous / Q000276:immunology; D014916:Whole-Body Irradiation / Q000379:methods*
chemical_list: D018952:Antigens, CD34