Reliable engraftment, low toxicity, and durable remissions following allogeneic blood stem cell transplantation with minimal conditioning.
OBJECTIVE
Allogeneic blood stem cell transplantation (BSCT) can cure patients with hematologic malignancies by high-dose chemotherapy and allogeneic graft-vs-tumor (GvT) reactions. To avoid high-dose conditioning and evaluate engraftment, toxicity, and GvT reactions, we treated a group of high-risk patients with a minimal intensive conditioning regimen followed by allogeneic BSCT.


METHODS
Thirty-four patients with lymphoma (11), myeloma (10), chronic myeloid leukemia (4), myelodysplastic syndrome (5), and acute myeloid leukemia (4) were treated with fludarabine (3 x 30 mg/m(2)) and 200 cGy total-body irradiation followed by the infusion of peripheral blood stem cells from related (28) or unrelated (6) donors. Cyclosporine or tacrolimus and mycophenolate mofetile were given posttransplant. Most patients had advanced disease, were intensively pretreated, and had contraindications against conventional myeloablative transplantation.


RESULTS
Thirty-two patients (94%) had engraftment of donor cells. Patients with lymphatic malignancies developed complete donor chimerism significantly faster than patients with myeloid malignancies (p < 0.05). Clinical responses were observed in 16 of 27 patients (59%) who had active disease at transplantation. Of 7 patients who were treated in remission, 5 remain free of disease. After a median follow-up of 325 days (range 100-844) 22 patients are alive (65%, 14 CR, 4 PR, 4 PD). Two patients (6%) died of treatment-related complications and 10 patients (29%) died of progressive disease. Acute graft-vs-host-disease (GvHD) of grade II or more developed in 17 patients (50%). Chronic GvHD is present in 10 of 22 patients (45%) who are alive beyond day 100.


CONCLUSIONS
Toxicity and survival in this group of high-risk patients are superior to those expected with conventional allogeneic transplantation. GvT reactions frequently occur in conjunction with GvHD and can induce durable remissions in patients with advanced hematologic malignancies.
Kobbe
Guido
G
Department of Hematology, Oncology and Clinical Immunology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. kobbe@med.uni-duesseldorf.de
Schneider
Peter
P
Aivado
Manuel
M
Zohren
Fabian
F
Schubert
Dominique
D
Fenk
Roland
R
Neumann
Frank
F
Kronenwett
Ralf
R
Pape
Hildegard
H
Rong
Astrid
A
Royer-Pokora
Brigitte
B
Hildebrandt
Barbara
B
Germing
Ulrich
U
Gattermann
Norbert
N
Heyll
Axel
A
Haas
Rainer
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D005240:Feasibility Studies; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000209:etiology; D020544:Graft vs Leukemia Effect; D020350:Graft vs Tumor Effect; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007951:Leukemia, Myeloid / Q000628:therapy; D008223:Lymphoma / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy; D009190:Myelodysplastic Syndromes / Q000628:therapy; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D012074:Remission Induction; D012306:Risk; D016879:Salvage Therapy; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000401:mortality; D016896:Treatment Outcome; D014916:Whole-Body Irradiation / Q000009:adverse effects