title: Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse.
abstract: OBJECTIVE
  Establishment of hematopoietic stem-cell (HSC) transplantation from mismatched relatives is feasible for patients with acute leukemia. As our original method of graft processing was unsuitable for large-scale clinical studies, we use automated devices for CD34+ cell purification.
  
  
  METHODS
  Sixty-seven patients with acute myeloid leukemia (AML; 19 complete remission [CR] 1, 14 CR 2, nine CR > 2, 25 in relapse) and 37 with acute lymphoid leukemia (ALL; 14 CR 1, eight CR 2, two CR > 2, 13 in relapse) were conditioned with total-body irradiation, thiotepa, fludarabine, and antithymocyte globulin. Peripheral-blood progenitor cells were mobilized with recombinant human granulocyte colony-stimulating factor and depleted of T-cells using CD34+ cell immunoselection. No post-transplantation graft-versus-host disease (GvHD) prophylaxis was administered.
  
  
  RESULTS
  Primary engraftment was achieved in 94 of 101 assessable patients. Six of the seven patients who rejected the primary graft, engrafted after a second transplantation. Overall, 100 of 101 patients engrafted. Acute GvHD developed in eight of 100 patients, and chronic GvHD, in five of 70 assessable patients. Thirty-eight patients died of nonleukemic causes. Relapse occurred in nine of 66 patients receiving transplantation in remission and in 17 of 38 receiving transplantation in relapse. Median follow-up of the 40 patients who survived event-free was 22 months (range, 1 to 65 months). Event-free survival (+/- standard deviation) rate was 48% +/- 8% and 46% +/- 10%, respectively, for the 42 AML and 24 ALL patients receiving transplantation in remission.
  
  
  CONCLUSIONS
  Our transplantation procedure provides reliable, reproducible CD34+ cell purification, high engraftment rates, and prevention of GvHD. The mismatched-related transplant emerges as a viable, alternative source of stem cells for acute leukemia patients without matched donors and/or those who urgently need transplantation.
authors.affiliation: HSCT Unit, Hematology Section, Department of Clinical and Experimental Medicine, University of Perugia, 06100 Perugia, Italy. aversa@unipg.it
authors.forename: Franco
authors.initials: F
authors.lastname: Aversa
authors.forename: Adelmo
authors.initials: A
authors.lastname: Terenzi
authors.forename: Antonio
authors.initials: A
authors.lastname: Tabilio
authors.forename: Franca
authors.initials: F
authors.lastname: Falzetti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Carotti
authors.forename: Stelvio
authors.initials: S
authors.lastname: Ballanti
authors.forename: Rita
authors.initials: R
authors.lastname: Felicini
authors.forename: Flavio
authors.initials: F
authors.lastname: Falcinelli
authors.forename: Andrea
authors.initials: A
authors.lastname: Velardi
authors.forename: Loredana
authors.initials: L
authors.lastname: Ruggeri
authors.forename: Teresa
authors.initials: T
authors.lastname: Aloisi
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Saab
authors.forename: Antonella
authors.initials: A
authors.lastname: Santucci
authors.forename: Katia
authors.initials: K
authors.lastname: Perruccio
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Martelli
authors.forename: Cristina
authors.initials: C
authors.lastname: Mecucci
authors.forename: Yair
authors.initials: Y
authors.lastname: Reisner
authors.forename: Massimo F
authors.initials: MF
authors.lastname: Martelli
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D016001:Confidence Intervals; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000453:epidemiology; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006650:Histocompatibility Testing; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012008:Recurrence; D018570:Risk Assessment; D012720:Severity of Illness Index; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome