Bone marrow-resident memory T cells survive pretransplant chemotherapy and contribute to early immune reconstitution of patients with acute myeloid leukemia given mafosfamide-purged autologous bone marrow transplantation.
OBJECTIVE
Studies of memory T cells transferred with the graft are relevant to better understand the early immune reconstitution of patients given autologous bone marrow transplantation (A-BMT). A critical question is whether memory T cells resident in bone marrow (BM) of patients with hematological malignancies are resistant to either pretransplant chemotherapy or ex vivo pharmacological purging.


METHODS
To address these issues, we evaluated the frequency of tetanus-toxoid (TT)-specific proliferating T-cell precursors (TT-PTCp) in BM and peripheral blood (PB) of eight patients with acute myeloid leukemia (AML) given A-BMT after in vitro purging of BM with mafosfamide. Patients were studied at the time of BM harvesting and five of them also after A-BMT.


RESULTS
The range of TT-PTCp frequencies found after A-BMT were comparable with those observed in PB and in BM at the time of harvesting and did not differ significantly from those of eight age-matched healthy subjects who donated BM for a human leukocyte antigen-identical sibling. TT-PTCp frequencies in BM, studied before and after ex vivo purging, appeared not to be affected by incubation with mafosfamide. We also compared the T-cell receptor (TCR)-Vbeta-repertoire usage of TT-specific T-cell lines (TT-TCL) in BM of patients at the time of harvesting and in their PB 2 months after transplantation. The same TCR-clonotypes were detected in TT-TCL at time of harvesting and after A-BMT.


CONCLUSIONS
These data indicate that BM-resident memory T cells of patients with AML are resistant to both pretransplant chemotherapy and ex vivo pharmacological purging and may contribute to immune reconstitution after A-BMT.
Casorati
Giulia
G
Experimental Immunology Unit, Cancer Immunotherapy and Gene Therapy Program, DIBIT, H. San Raffaele Scientific Institute, Milan, Italy.
Locatelli
Franco
F
Pagani
Sara
S
Garavaglia
Claudio
C
Montini
Enrica
E
Lisini
Daniela
D
Turin
Ilaria
I
Rossi
Francesca
F
Dellabona
Paolo
P
Maccario
Rita
R
Montagna
Daniela
D
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000293:Adolescent; D001853:Bone Marrow / Q000276:immunology*; D016465:Bone Marrow Purging / Q000379:methods*; D016026:Bone Marrow Transplantation / Q000379:methods*; D002648:Child; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology*; D014182:Transplantation, Autologous
D000276:Adjuvants, Immunologic; C048341:mafosfamide; D003520:Cyclophosphamide