Can only partial T-cell depletion of the graft before hematopoietic stem cell transplantation mitigate graft-versus-host disease while preserving a graft-versus-leukemia reaction? A prospective phase II study.
The study comprised 37 consecutive patients who underwent transplantation with a Campath-1H in vitro T cell-depleted granulocyte colony-stimulating factor-mobilized peripheral blood stem cell graft from an HLA-identical sibling, followed 24 hours later by an unmanipulated graft. Acute graft-versus-host disease (GVHD) was limited to grade I to II, whereas chronic graft-versus-host disease occurred in 9 patients, mostly (n = 7) with limited disease. Molecular relapses (8 chronic myeloid leukemia [CML] and 1 non-Hodgkin lymphoma) that occurred not earlier than the sixth month after transplantation were treated with donor lymphocyte infusion (DLI), which induced complete remission in all but 1 CML patient with persistent very low BCR-ABL molecular levels. With a median follow-up of 54 months (range, 29-84 months), the actuarial 5-year overall survival, disease-free survival, and transplant-related mortality are 78% (95% confidence interval [CI], 52%-88%), 78% (95% CI, 52%-86%), and 6% (95% CI, 1.5%-32%), respectively. All CML patients are alive and free of disease. The results of this prospective, nonrandomized study show that incomplete T-cell depletion in vitro with Campath-1H (in combination with DLI for molecular relapses in CML) may decrease the incidence of GVHD and transplant-related mortality with no adverse effect on disease-free survival. The described method decreases the number of T cells to an extent that severe GVHD is prevented while relapse is postponed to a time when the patient can be treated with DLI without severe side effects.
Chalandon
Yves
Y
Hematology Service, Department of Internal Medicine University Hospital, Geneva, Switzerland. yves.chalandon@hcuge.ch
Roosnek
Eddy
E
Mermillod
Bernadette
B
Waelchli
Laurent
L
Helg
Claudine
C
Chapuis
Bernard
B
D000293:Adolescent; D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D020544:Graft vs Leukemia Effect; D019650:Hematopoietic Stem Cell Mobilization; D006650:Histocompatibility Testing; D006801:Humans; D047589:Leukocyte Reduction Procedures; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D012008:Recurrence; D016019:Survival Analysis; D013601:T-Lymphocytes
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000074323:Alemtuzumab