Dose-reduced conditioning and allogeneic hematopoietic stem cell transplantation from unrelated donors in 42 patients.
OBJECTIVE
A fludarabine-based "nonmyeloablative" preparative regimen was investigated in 42 patients with hematological malignancies receiving hematopoietic stem cell grafts from unrelated volunteer donors.


METHODS
Recipient conditioning consisted of fludarabine 30 mg/m(2) on days -6 to -2 and i.v. busulfan 3.3 mg/kg on days -6 to -5. Antithymocyte globuline was added at 2.5 mg/kg i.v. on days -5 to -2. The patients were grafted with bone marrow (n = 13) or peripheral blood stem cells either unmanipulated (n = 20) or CD34+ selected (n = 9). Graft-versus-host disease prophylaxis was performed with cyclosporine A (CsA, n = 12), CsA/methotrexate (n = 12), or CsA/mycophenolate mofetil (n = 18).


RESULTS
With a median follow-up of 13 months (range, 5-26 months), the actuarial disease-free survival is 64% and 38% for patients with lymphoid malignancies and standard-risk leukemia compared with only 14% for patients with high-risk disease. The main cause of treatment failure was relapse of disease in high-risk patients (n = 14). An increased incidence of primary (n = 1) or secondary graft-failure (n = 8) was observed (21%). Chimerism analysis of CD56+/CD3--sorted natural killer (NK) cells, available in 10 patients, showed an impaired increase of donor NK cell chimerism between day 10 and 30 after transplantation in three of four patients with graft failure, whereas the percentage of donor NK cells surpassed 75% in all of the six patients with stable engraftment.


CONCLUSIONS
Unrelated transplants after dose-reduced conditioning are associated with a higher risk of graft-failure. Pretransplant host immunosuppression has to be optimized to overcome resistance to grafts from unrelated donors after nonmyeloablative conditioning therapy.
Bornhäuser
M
M
Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden, Germany. bornhaeuser@oncocenter.de
Thiede
C
C
Platzbecker
U
U
Jenke
A
A
Helwig
A
A
Plettig
R
R
Freiberg-Richter
J
J
Röllig
C
C
Geissler
G
G
Lutterbeck
K
K
Oelschlagel
U
U
Ehninger
G
G
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007694:Killer Cells, Natural / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy; D011014:Pneumonia / Q000209:etiology; D016019:Survival Analysis; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000009:adverse effects; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
D000961:Antilymphocyte Serum; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine