title: 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.
abstract: 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.
authors.affiliation: Experimental Immunology Unit, Cancer Immunotherapy and Gene Therapy Program, DIBIT, H. San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Casorati
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Sara
authors.initials: S
authors.lastname: Pagani
authors.forename: Claudio
authors.initials: C
authors.lastname: Garavaglia
authors.forename: Enrica
authors.initials: E
authors.lastname: Montini
authors.forename: Daniela
authors.initials: D
authors.lastname: Lisini
authors.forename: Ilaria
authors.initials: I
authors.lastname: Turin
authors.forename: Francesca
authors.initials: F
authors.lastname: Rossi
authors.forename: Paolo
authors.initials: P
authors.lastname: Dellabona
authors.forename: Rita
authors.initials: R
authors.lastname: Maccario
authors.forename: Daniela
authors.initials: D
authors.lastname: Montagna
mesh_terms: 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
chemical_list: D000276:Adjuvants, Immunologic; C048341:mafosfamide; D003520:Cyclophosphamide