Granulocyte-macrophage colony-stimulating factor (GM-CSF), given concurrently with induction therapy for acute myelogenous leukemia (AML), augments the syndrome of T-lymphocyte recovery.
A transient lymphocytosis precedes myeloid recovery in many patients with AML treated with intensive chemotherapy. We describe the kinetics, clinical features, and immunology of lymphocyte recovery which is markedly augmented by the inclusion of GM-CSF in induction therapy. Lymphocyte recovery from 19 patients receiving GM-CSF as part of induction therapy was compared to a historical control of 25 patients treated with identical chemotherapy in the absence of cytokine. Kinetics and clinical features of lymphocyte recovery were analyzed. Peripheral blood was studied by flow cytometry, chromium release assays, and Southern analysis of the T-cell antigen receptor, beta chain gene. Patients treated with GM-CSF to recruit cells into cycle, exhibit markedly increased peaks of lymphocyte recovery. Recovering lymphocytes demonstrated an activated memory T-cell phenotype suggestive of a cytokine release syndrome. Lymphoid recovery was often associated with rash, fever, and lymphadenopathy. Study patients who developed peak lymphocyte counts > or = 1000 microliters were more likely to achieve remission than those with a lower peak. Recovery lymphocytes did not lyse pretreatment autologous bone marrow cells. Southern analysis demonstrated dominant potentially clonal rearrangements in the majority of patients studied. Lymphocyte recovery, which appears to include oligoclonal expansion of memory T cells is markedly augmented by administration of GM-CSF during chemotherapy. This may represent a non-specific response by a limited repertoire of T cells surviving therapy, or a specific clonal response to a powerful exogenous or endogenous antigen. Possible antileukemic activity of these cells remains to be elucidated.
Gore
S D
SD
Johns Hopkins Oncology Center, Baltimore, MD 21205.
Donnenberg
A D
AD
Zehnbauer
B A
BA
Weng
L J
LJ
Burke
P J
PJ
D000328:Adult; D003872:Dermatitis / Q000276:immunology; D005260:Female; D005334:Fever / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D007958:Leukocyte Count; D008218:Lymphocytosis / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D013577:Syndrome; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000276:immunology
D016178:Granulocyte-Macrophage Colony-Stimulating Factor