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Deoxycoformycin-induced immunosuppression in patients with hairy cell
leukemia
WJ Urba, MW Baseler, WC Kopp, RG Steis, JW Clark, JW Smith , DL Coggin and DL Longo
Program Resources, National Cancer Institute-Frederick Cancer Researh
Facility, MD 21701.
Immune function in patients with hairy cell leukemia (HCL) was examined
serially during treatment with alternating monthly cycles of recombinant
interferon alpha-2a and 2'-deoxycoformycin (dCF). At presentation, most
patients had normal numbers of T lymphocytes and their cells had normal
proliferative responses to mitogens [phytohemagglutinin (PHA) and
concanavalin A (Con A)] and alloantigens. Patients had severe
monocytopenia, decreased delayed-type hypersensitivity (DTH) reactions, and
decreased peripheral blood natural killer (NK) activity. Treatment caused a
profound decrease in all lymphocyte subpopulations. T cells were more
affected than B cells or NK cells. Numbers of CD4+ and CD8+ lymphocytes
decreased to levels less than 200 cells/microliters in all patients during
treatment. This decrease in T cell number was associated with a marked
decrease in proliferative responsiveness to PHA, Con A, and alloantigens.
These abnormalities persisted throughout the 14 months of treatment and
have continued for up to 6 months beyond discontinuation of treatment. NK
cell activity increased during treatment, but cycled depending on the phase
of treatment; highest activities were observed after interferon (IFN)-alpha
and lower levels of activity were observed after dCF. DTH responses
generally did not improve during therapy. Levels of IgM, IgG, IgA, and IgD
did not change during treatment, but IgE levels rose in most patients. All
immunosuppressive effects were attributable to dCF since patients receiving
IFN-alpha 2a alone did not exhibit these same immunosuppressive effects,
and patients receiving dCF alone after IFN failure exhibited similar
abnormalities. Despite this severe immunosuppression from dCF,
life-threatening opportunistic infections have not been observed in our
patient population. Six patients developed localized Herpes zoster
infection among 21 patients who had received dCF. Pending the results of
long-term follow-up, we recommend that dCF be reserved for patients who
have failed splenectomy and IFN therapy.
Volume 73,
Issue 1,
pp. 38-46,
01/01/1989
Copyright © 1989 by The American Society of Hematology
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