Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse.
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.
Aversa
Franco
F
HSCT Unit, Hematology Section, Department of Clinical and Experimental Medicine, University of Perugia, 06100 Perugia, Italy. aversa@unipg.it
Terenzi
Adelmo
A
Tabilio
Antonio
A
Falzetti
Franca
F
Carotti
Alessandra
A
Ballanti
Stelvio
S
Felicini
Rita
R
Falcinelli
Flavio
F
Velardi
Andrea
A
Ruggeri
Loredana
L
Aloisi
Teresa
T
Saab
Jean Pierre
JP
Santucci
Antonella
A
Perruccio
Katia
K
Martelli
Maria Paola
MP
Mecucci
Cristina
C
Reisner
Yair
Y
Martelli
Massimo F
MF
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