Lineage-specific engraftment and outcomes after T-cell-depleted peripheral blood stem cell transplant with Flu/Cy/TBI conditioning.
Sixty patients with haematological malignancies received a myeloablative regimen of total body irradiation, cyclophosphamide and fludarabine followed by a T-cell-depleted peripheral blood stem cell transplant from a human leucocyte antigen identical sibling. To improve donor immune function, 1 x 10(7) CD3+ cells/kg were added-back between d 45 and 100. T-cell and myeloid chimaerism were monitored regularly to evaluate the effect of T-cell chimaerism on outcome. The major factor affecting outcome was disease risk, with significantly lower relapse and higher survival in 29 standard risk (SR) patients compared with 31 patients at high risk (HR) for treatment failure (relapse 4.8 +/- 5% vs. 59 +/- 11%, P < 0.0001, and overall survival 93 +/- 5% vs. 39 +/- 10%, P < 0.0001, respectively). Donor myeloid chimaerism reached > or = 95% within 14 d of transplant, but in the first several months, donor T-cell chimaerism was frequently mixed. Full T-cell chimaerism was significantly more frequent in HR vs. SR patients. Landmark analysis at days 30 and 90 in HR patients with mixed versus full T-cell chimaerism, showed relapse probabilities of 50.5 +/- 14% vs. 70 +/- 16% (P = 0.62) and 34.4 +/- 20% vs. 58.8 +/- 15% (P = 0.32) respectively. Early full T-cell engraftment correlated with development of severe acute graft-versus-host disease (GVHD). However, mixed T-cell chimaerism was favourable for reducing GVHD, and did not affect relapse in this small series.
Montero
Aldemar
A
Stem Cell Allogeneic Transplantation Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1202, USA.
Savani
Bipin N
BN
Kurlander
Roger
R
Read
Elizabeth J
EJ
Leitman
Susan F
SF
Childs
Richard
R
Solomon
Scott R
SR
Barrett
A John
AJ
D000293:Adolescent; D000328:Adult; D002648:Child; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008212:Lymphocyte Depletion; D017710:Lymphocyte Transfusion; D008297:Male; D036102:Peripheral Blood Stem Cell Transplantation; D016016:Proportional Hazards Models; D015996:Survival Rate; D013601:T-Lymphocytes; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014916:Whole-Body Irradiation
D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine