Emergence of antitumor cytolytic T cells is associated with maintenance of hematologic remission in children with acute myeloid leukemia.
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.
Montagna
Daniela
D
Dipartimento di Scienze Pediatriche, Università di Pavia, IRCCS Policlinico San Matteo, P.le Golgi 2, 27100 Pavia, Italy. d.montagna@smatteo.pv.it
Maccario
Rita
R
Locatelli
Franco
F
Montini
Enrica
E
Pagani
Sara
S
Bonetti
Federico
F
Daudt
Liane
L
Turin
Ilaria
I
Lisini
Daniela
D
Garavaglia
Claudio
C
Dellabona
Paolo
P
Casorati
Giulia
G
D000293:Adolescent; D016026:Bone Marrow Transplantation / Q000379:methods; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D006801:Humans; D007157:Immunologic Surveillance; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000628:therapy; D008297:Male; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D012008:Recurrence; D012074:Remission Induction; D012307:Risk Factors; D013234:Stem Cells / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014182:Transplantation, Autologous
D016693:Receptors, Antigen, T-Cell, alpha-beta