Reduced-intensity conditioning followed by allografting of hematopoietic cells can produce clinical and molecular remissions in patients with poor-risk hematologic malignancies.
A reduced-intensity conditioning regimen was investigated in 45 patients with hematologic malignancies who were considered poor candidates for conventional myeloablative regimens. Median patient age was 49 years. Twenty-six patients previously failed autologous transplantation, and 18 patients had a refractory disease at the time of transplantation. In order to decrease nonrelapse mortality, and enhance the graft-versus-tumor effect, a program was designed in which a reduced conditioning with thiotepa, fludarabine, and cyclophosphamide was associated with programmed reinfusions of donor lymphocytes for patients without graft-versus-host disease (GVHD), not achieving clinical and molecular remission after transplantation. GVHD prophylaxis consisted of cyclosporine A and methotrexate. Seventeen patients received marrow cells and 28 received mobilized hematopoietic cells. All patients engrafted. The probability of grades II-IV and III-IV acute GVHD were 47% and 13%, respectively. The probability of nonrelapse mortality, progression-free survival, and overall survival were 13%, 57%, and 53%, respectively. Thirteen patients in complete remission had a polymerase chain reaction marker for minimal disease monitoring; 10 achieved molecular remission after transplantation. Nine patients received donor lymphocytes: one patient with mantle cell lymphoma had a minimal response, one patient with refractory anemia with excess of blasts in transformation achieved complete remission, and 7 patients did not respond. At a median follow-up of 385 days (range, 24 to 820 days), 25 patients (55%) were alive in complete remission. Although longer follow-up is needed to evaluate the long-term outcome, the study shows that this regimen is associated with a durable engraftment, has a low nonrelapse mortality rate, and can induce clinical and molecular remissions.
Corradini
Paolo
P
Department of Hematology, Istituto Scientifico HS Raffaele, Milano, Italy. paolo.corradini@istitutotumori.mi.it
Tarella
Corrado
C
Olivieri
Attilio
A
Gianni
Alessandro M
AM
Voena
Claudia
C
Zallio
Francesco
F
Ladetto
Marco
M
Falda
Michele
M
Lucesole
Moira
M
Dodero
Anna
A
Ciceri
Fabio
F
Benedetti
Fabio
F
Rambaldi
Alessandro
A
Sajeva
Maria R
MR
Tresoldi
Moreno
M
Pileri
Alessandro
A
Bordignon
Claudio
C
Bregni
Marco
M
D000328:Adult; D000368:Aged; D000754:Anemia, Refractory, with Excess of Blasts / Q000628:therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control; D020350:Graft vs Tumor Effect; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D017710:Lymphocyte Transfusion; D020522:Lymphoma, Mantle-Cell / Q000628:therapy; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000235:genetics; D016133:Polymerase Chain Reaction; D012008:Recurrence; D012074:Remission Induction; D015996:Survival Rate; D013852:Thiotepa / Q000008:administration & dosage; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D016572:Cyclosporine; D003520:Cyclophosphamide; D013852:Thiotepa; D014740:Vidarabine; C024352:fludarabine; D008727:Methotrexate