Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem-cell transplantation.
OBJECTIVE
Patients with advanced myeloid malignancies who experience relapse after allogeneic bone marrow transplantation (BMT) have a poor prognosis. Long-term survival after chemotherapy alone, second myeloablative transplant, or donor leukocyte infusions (DLIs) alone is unusual. DLIs may have minimal effectiveness in advanced disease because adequate cellular responses are not able to develop in the presence of bulky, fast-growing disease. A chemotherapy strategy was used to debulk disease before administration of granulocyte colony-stimulating factor (G-CSF)-primed DLIs.


METHODS
Sixty-five patients experiencing hematologic relapse of myeloid malignancy after HLA-matched sibling BMT were prospectively treated with cytarabine-based chemotherapy, then G-CSF-primed DLIs. No prophylactic immunosuppression was provided.


RESULTS
Twenty-seven of 57 assessable patients experienced a complete response. Graft-versus-host disease (GVHD) was observed in 56% of the patients. Treatment-related mortality was 23%. Overall survival at 2 years for the entire cohort was 19%. Patients with a complete response were more likely to survive, with 1- and 2-year survival rates of 51% and 41%, respectively, with a median follow-up of more than 2 years. The 1-year survival for nonresponders was 5%. A posttransplant remission lasting more than 6 months before relapse was associated with a higher likelihood of response. GVHD was not required for durable remission.


CONCLUSIONS
Salvage treatment with chemotherapy before DLI can help some patients with advanced myeloid relapse and is not dependent on GVHD. Patients with short remissions after BMT are unlikely to benefit from this approach, and the approach is associated with significant treatment-related mortality. Modifications of this approach or entirely different approaches will be required for most patients with this difficult clinical problem.
Levine
John E
JE
University of Michigan, Ann Arbor, MI, USA. jelevine@umich.edu
Braun
Thomas
T
Penza
Samuel L
SL
Beatty
Patrick
P
Cornetta
Kenneth
K
Martino
Rodrigo
R
Drobyski
William R
WR
Barrett
A John
AJ
Porter
David L
DL
Giralt
Sergio
S
Leis
Jose
J
Holmes
Houston E
HE
Johnson
Matthew
M
Horowitz
Mary
M
Collins
Robert H
RH
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001782:Blood Donors; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007223:Infant; D007279:Injections, Subcutaneous; D007951:Leukemia, Myeloid / Q000473:pathology / Q000628:therapy*; D007962:Leukocytes; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012008:Recurrence; D016879:Salvage Therapy; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D016179:Granulocyte Colony-Stimulating Factor