Originally published as JCO Early Release 10.1200/JCO.2005.09.117 on March 7 2005
Journal of Clinical Oncology, Vol 23, No 15 (May 20), 2005: pp. 3447-3454
© 2005 American Society of Clinical Oncology.
Full Haplotype-Mismatched Hematopoietic Stem-Cell Transplantation: A Phase II Study in Patients With Acute Leukemia at High Risk of Relapse
Franco Aversa,
Adelmo Terenzi,
Antonio Tabilio,
Franca Falzetti,
Alessandra Carotti,
Stelvio Ballanti,
Rita Felicini,
Flavio Falcinelli,
Andrea Velardi,
Loredana Ruggeri,
Teresa Aloisi,
Jean Pierre Saab,
Antonella Santucci,
Katia Perruccio,
Maria Paola Martelli,
Cristina Mecucci,
Yair Reisner,
Massimo F. Martelli
From the Hematology and Clinical Immunology Section, Department of Clinical and Experimental Medicine, University of Perugia, Italy; the Department of Immunology, Weizmann Institute, Rehovot, Israel
Address reprint requests to Franco Aversa, MD, HSCT Unit, Hematology Section, University of Perugia, 06100 Perugia, Italy; e-mail: aversa{at}unipg.it
PURPOSE: 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.
PATIENTS AND 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.
CONCLUSION: 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.
Supported in part from AIRC (Italian Cancer Association), Perugia Section of the AIL (Italian Leukaemia Association), AULL (Umbrian Leukaemia and Lymphoma Association), the Daniele Chianelli Foundation and the Perugia Cassa di Risparmio Foundation.
Presented at the Tandem Meeting 2003, Keystone Symposia, Keystone, CO, January 30-Feb 3, 2003; 19th Meeting of the Belgian Hematological Society, Brussels, Belgium, January 30-31, 2004; 4th International Workshop on Haploidentical Transplants. Naples, Italy, July 8-10, 2004.
Authors' disclosures of potential conflicts of interest are found at the end of this article.
This article has been cited by other articles:

|
 |

|
 |
 
A. Nonami, T. Miyamoto, M. Kuroiwa, Y. Kunisaki, K. Kamezaki, K. Takenaka, N. Harada, T. Teshima, M. Harada, and K. Nagafuji
Successful Treatment of Primary Plasma Cell Leukaemia by Allogeneic Stem Cell Transplantation from Haploidentical Sibling
Jpn. J. Clin. Oncol.,
December 1, 2007;
37(12):
969 - 972.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. M. Rowe and A. H. Goldstone
How I treat acute lymphocytic leukemia in adults
Blood,
October 1, 2007;
110(7):
2268 - 2275.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. E. King and J. M. Rowe
Recent Developments in Acute Myelogenous Leukemia Therapy
Oncologist,
October 1, 2007;
12(suppl_2):
14 - 21.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Ruggeri, A. Mancusi, M. Capanni, E. Urbani, A. Carotti, T. Aloisi, M. Stern, D. Pende, K. Perruccio, E. Burchielli, et al.
Donor natural killer cell allorecognition of missing self in haploidentical hematopoietic transplantation for acute myeloid leukemia: challenging its predictive value.
Blood,
July 1, 2007;
110(1):
433 - 440.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. HANDGRETINGER, X. CHEN, M. PFEIFFER, I. MUELLER, T. FEUCHTINGER, G. A. HALE, and P. LANG
Feasibility and Outcome of Reduced-Intensity Conditioning in Haploidentical Transplantation
Ann. N.Y. Acad. Sci.,
June 1, 2007;
1106(1):
279 - 289.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. A. Rizzieri, L. P. Koh, G. D. Long, C. Gasparetto, K. M. Sullivan, M. Horwitz, J. Chute, C. Smith, J. Z. Gong, A. Lagoo, et al.
Partially Matched, Nonmyeloablative Allogeneic Transplantation: Clinical Outcomes and Immune Reconstitution
J. Clin. Oncol.,
February 20, 2007;
25(6):
690 - 697.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Mullally and J. Ritz
Beyond HLA: the significance of genomic variation for allogeneic hematopoietic stem cell transplantation
Blood,
February 15, 2007;
109(4):
1355 - 1362.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. M. Lazarus and S. Luger
Which Patients with Adult Acute Lymphoblastic Leukemia Should Undergo a Hematopoietic Stem Cell Transplantation? Case-Based Discussion
Hematology,
January 1, 2007;
2007(1):
444 - 452.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. J. Amrolia, G. Muccioli-Casadei, H. Huls, S. Adams, A. Durett, A. Gee, E. Yvon, H. Weiss, M. Cobbold, H. B. Gaspar, et al.
Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation
Blood,
September 15, 2006;
108(6):
1797 - 1808.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Perruccio, A. Tosti, E. Burchielli, F. Topini, L. Ruggeri, A. Carotti, M. Capanni, E. Urbani, A. Mancusi, F. Aversa, et al.
Transferring functional immune responses to pathogens after haploidentical hematopoietic transplantation
Blood,
December 15, 2005;
106(13):
4397 - 4406.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. R. Spitzer
Haploidentical Stem Cell Transplantation: The Always Present but Overlooked Donor
Hematology,
January 1, 2005;
2005(1):
390 - 395.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|