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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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Submitted May 9, 2006
Accepted July 16, 2006
Emergence of anti-tumor cytolytic T cells is associated
with maintenance of hematological 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
University of Pavia, IRCCS Pol. San Matteo, Pavia
IRCCS Pol San Matteo, Pavia
University of Pavia, IRCCS Pol san Matteo, Pavia
IRCCS Pol. San Matteo, Pavia
University of Pavia, Pavia
DIBIT, ospedale San Raffaele
DIBIT, Ospedale San Raffaele
* Corresponding author; email: d.montagna{at}smatteo.pv.it.
Whilst 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 anti-tumor immune-surveillance is less defined. We evaluated the emergence of anti-leukemia cytotoxic T-lymphocyte precursors (CTLp) and the correlation of this phenomenon with maintenance of hematological remission in 16 children with acute myeloid leukemia (AML), treated with either chemotherapy alone (5 patients) or given also autologous BMT (A-BMT, 11 patients). Anti-leukemia CTLp were detectable in 8 patients in remission after induction chemotherapy; none of them subsequently relapsed. Of the 8 patients who did not show detectable CTLp frequency while in remission after induction chemotherapy, 7 subsequently experienced leukemia relapse. In patients receiving A-BMT, molecular fingerprinting of the TCR-V repertoire, performed on anti-leukemia lines, demonstrated that selected anti-leukemia T-cell clonotypes, detectable in BM before transplantation, survived ex-vivo pharmacological 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 hematological remission and also suggest that quantification of anti-leukemia CTLp frequency may be a useful tool to identify patients at high relapse risk , thus potentially benefiting from an allogeneic anti-tumor effect.
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