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Blood, 1 December 2006, Vol. 108, No. 12, pp. 3843-3850.
Prepublished online as a Blood First Edition Paper on July 25, 2006; DOI 10.1182/blood-2006-05-021535.


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IMMUNOBIOLOGY

Emergence of antitumor cytolytic T cells is associated with maintenance of hematologic remission in children with acute myeloid leukemia

Daniela Montagna, Rita Maccario, Franco Locatelli, Enrica Montini, Sara Pagani, Federico Bonetti, Liane Daudt, Ilaria Turin, Daniela Lisini, Claudio Garavaglia, Paolo Dellabona, and Giulia Casorati

From the Department of Pediatrics, Laboratory of Immunology, University of Pavia, Italy; Pediatric Hematology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy; and Experimental Immunology Unit, Cancer Immunotherapy and Gene Therapy Program, Department of Oncology, Department of Biological and Technological Research (DIBIT), Hospital San Raffaele Scientific Institute, Milan, Italy.

Although the graft-versus-leukemia effect of allogeneic bone marrow transplantation (BMT) is of paramount importance in the maintenance of disease remission, the role played by the autologous T-cell response in antitumor immune surveillance is less defined. We evaluated the emergence of antileukemia cytotoxic T-lymphocyte precursors (CTLp's) and the correlation of this phenomenon with maintenance of hematologic remission in 16 children with acute myeloid leukemia (AML), treated with either chemotherapy alone (5 patients) or with autologous BMT (A-BMT, 11 patients). Antileukemia CTLp's were detectable in 8 patients in remission after induction chemotherapy; none of them subsequently had a relapse. Of the 8 patients who did not show detectable CTLp frequency while in remission after induction chemotherapy, 7 subsequently experienced leukemia relapse. In patients undergoing A-BMT, molecular fingerprinting of the TCR-Vbeta repertoire, performed on antileukemia lines, demonstrated that selected antileukemia T-cell clonotypes, detectable in bone marrow before transplantation, survived ex vivo pharmacologic purging and were found in the recipient after A-BMT. These data provide evidence for an active role of autologous T cells in the maintenance of hematologic remission and also suggest that quantification of antileukemia CTLp frequency may be a useful tool to identify patients at high risk for relapse, thus potentially benefiting from an allogeneic antitumor effect.


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