Article

Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem-cell transplantation.

University of Michigan, Ann Arbor, MI, USA.
Journal of Clinical Oncology (impact factor: 18.37). 02/2002; 20(2):405-12. pp.405-12
Source: PubMed

ABSTRACT 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.
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.
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.
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.

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Keywords

57 assessable patients
 
6 months
 
adequate cellular responses
 
chemotherapy strategy
 
complete response
 
debulk disease
 
different approaches
 
difficult clinical problem
 
fast-growing disease
 
G-CSF)-primed DLIs
 
G-CSF-primed DLIs
 
Graft-versus-host disease
 
granulocyte colony-stimulating factor
 
HLA-matched sibling BMT
 
median follow-up
 
myeloid malignancy
 
poor prognosis
 
posttransplant remission lasting
 
significant treatment-related mortality
 
Treatment-related mortality