Originally published as JCO Early Release 10.1200/JCO.2005.09.117 on March 7 2005

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Aversa, F. Articles by Martelli, M. F. Search for Related Content PubMed PubMed Citation Articles by Aversa, F. Articles by Martelli, M. F. Social Bookmarking                            What's this?

Full Haplotype-Mismatched Hematopoietic Stem-Cell Transplantation: A Phase II Study in Patients With Acute Leukemia at High Risk of Relapse

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.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				A. N. Hasan, W. J. Kollen, D. Trivedi, A. Selvakumar, B. Dupont, M. Sadelain, and R. J. O'Reilly A Panel of Artificial APCs Expressing Prevalent HLA Alleles Permits Generation of Cytotoxic T Cells Specific for Both Dominant and Subdominant Viral Epitopes for Adoptive Therapy J. Immunol., August 15, 2009; 183(4): 2837 - 2850. [Abstract] [Full Text] [PDF]

				L. Vago, S. K. Perna, M. Zanussi, B. Mazzi, C. Barlassina, M. T. L. Stanghellini, N. F. Perrelli, C. Cosentino, F. Torri, A. Angius, et al. Loss of Mismatched HLA in Leukemia after Stem-Cell Transplantation N. Engl. J. Med., July 30, 2009; 361(5): 478 - 488. [Abstract] [Full Text] [PDF]

				A. Dodero, C. Carniti, A. Raganato, A. Vendramin, L. Farina, F. Spina, C. Carlo-Stella, S. Di Terlizzi, M. Milanesi, P. Longoni, et al. Haploidentical stem cell transplantation after a reduced-intensity conditioning regimen for the treatment of advanced hematologic malignancies: posttransplantation CD8-depleted donor lymphocyte infusions contribute to improve T-cell recovery Blood, May 7, 2009; 113(19): 4771 - 4779. [Abstract] [Full Text] [PDF]

				M. Arora, D. J. Weisdorf, S. R. Spellman, M. D. Haagenson, J. P. Klein, C. K. Hurley, G. B. Selby, J. H. Antin, N. A. Kernan, C. Kollman, et al. HLA-Identical Sibling Compared With 8/8 Matched and Mismatched Unrelated Donor Bone Marrow Transplant for Chronic Phase Chronic Myeloid Leukemia J. Clin. Oncol., April 1, 2009; 27(10): 1644 - 1652. [Abstract] [Full Text] [PDF]

				E. Morra, G. Barosi, A. Bosi, F. Ferrara, F. Locatelli, M. Marchetti, G. Martinelli, C. Mecucci, M. Vignetti, and S. Tura Clinical management of primary non-acute promyelocytic leukemia acute myeloid leukemia: practice Guidelines by the Italian Society of Hematology, the Italian Society of Experimental Hematology and the Italian Group for Bone Marrow Transplantation Haematologica, January 1, 2009; 94(1): 102 - 112. [Abstract] [Full Text] [PDF]

				L Moretta, F Locatelli, and A Moretta Alloreactive natural killer cells in targeting high-risk leukaemias Ann Rheum Dis, December 1, 2008; 67(Suppl_3): iii39 - iii43. [Abstract] [Full Text] [PDF]

				F. Ciceri, M. Labopin, F. Aversa, J. M. Rowe, D. Bunjes, P. Lewalle, A. Nagler, P. Di Bartolomeo, J. F. Lacerda, M. T. Lupo Stanghellini, et al. A survey of fully haploidentical hematopoietic stem cell transplantation in adults with high-risk acute leukemia: a risk factor analysis of outcomes for patients in remission at transplantation Blood, November 1, 2008; 112(9): 3574 - 3581. [Abstract] [Full Text] [PDF]

				L. Vago, B. Forno, M. P. Sormani, R. Crocchiolo, E. Zino, S. Di Terlizzi, M. T. Lupo Stanghellini, B. Mazzi, S. K. Perna, A. Bondanza, et al. Temporal, quantitative, and functional characteristics of single-KIR-positive alloreactive natural killer cell recovery account for impaired graft-versus-leukemia activity after haploidentical hematopoietic stem cell transplantation Blood, October 15, 2008; 112(8): 3488 - 3499. [Abstract] [Full Text] [PDF]

				M. Stern, L. Ruggeri, A. Mancusi, M. E. Bernardo, C. de Angelis, C. Bucher, F. Locatelli, F. Aversa, and A. Velardi Survival after T cell-depleted haploidentical stem cell transplantation is improved using the mother as donor Blood, October 1, 2008; 112(7): 2990 - 2995. [Abstract] [Full Text] [PDF]

				J. K. Davies, J. G. Gribben, L. L. Brennan, D. Yuk, L. M. Nadler, and E. C. Guinan Outcome of alloanergized haploidentical bone marrow transplantation after ex vivo costimulatory blockade: results of 2 phase 1 studies Blood, September 15, 2008; 112(6): 2232 - 2241. [Abstract] [Full Text] [PDF]

				F. R. Appelbaum Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia When a Matched Related Donor Is Not Available Hematology, January 1, 2008; 2008(1): 412 - 417. [Abstract] [Full Text] [PDF]

				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]

				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]