title: Reduced-intensity conditioning using fludarabine, melphalan and thiotepa for adult patients undergoing haploidentical SCT.
abstract: Haploidentical SCT (HaploSCT) has been most commonly performed using a myeloablative, TBI-based preparative regimen; however, the toxicity with this approach remains very high. We studied the feasibility of a reduced-intensity conditioning regimen in a phase II clinical trial using fludarabine, melphalan and thiotepa and antithymocyte globulin (ATG) for patients with advanced hematological malignancies undergoing T-cell depleted HaploSCT. Twenty-eight patients were entered in the study. Engraftment with donor-derived hematopoiesis was achieved in 78% of patients after a median of 13 days. Six patients experienced primary graft failure, three out of four tested patients had donor-specific anti-HLA antibodies (DSA) (P=0.001). Toxicity included mostly infections. A total of 21 out of 22 patients with AML/myelodysplastic syndrome (MDS) achieved remission after transplant (16 with relapsed/refractory AML). Five out of the 12 patients (42%) with AML/MDS with <15% BM blasts survived long term as compared with none with more advanced disease (P=0.03). HaploSCT with this fludarabine, melphalan and thiotepa and ATG RIC is an effective, well-tolerated conditioning regimen for patients with AML/MDS with low disease burden at the time of transplant and allowed a high rate of engraftment in patients without DSA. Patients with overt relapse fared poorly and require novel treatment strategies.
authors: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. sciurea@mdanderson.org
authors: S O
authors: SO
authors: Ciurea
authors: R
authors: R
authors: Saliba
authors: G
authors: G
authors: Rondon
authors: S
authors: S
authors: Pesoa
authors: P
authors: P
authors: Cano
authors: M
authors: M
authors: Fernandez-Vina
authors: S
authors: S
authors: Qureshi
authors: L L
authors: LL
authors: Worth
authors: J
authors: J
authors: McMannis
authors: P
authors: P
authors: Kebriaei
authors: R B
authors: RB
authors: Jones
authors: M
authors: M
authors: Korbling
authors: M
authors: M
authors: Qazilbash
authors: E J
authors: EJ
authors: Shpall
authors: S
authors: S
authors: Giralt
authors: M
authors: M
authors: de Lima
authors: R E
authors: RE
authors: Champlin
authors: J
authors: J
authors: Gajewski
mesh_terms: D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D002648:Child; D005260:Female; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007239:Infections / Q000209:etiology; D015470:Leukemia, Myeloid, Acute / Q000628:therapy; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage*; D009190:Myelodysplastic Syndromes / Q000628:therapy; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology; D013852:Thiotepa / Q000008:administration & dosage; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; D019653:Myeloablative Agonists; D013852:Thiotepa; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan