Deoxycoformycin-induced immunosuppression in patients with hairy cell leukemia.
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.
Program Resources, National Cancer Institute-Frederick Cancer Researh Facility, MD 21701.
W J
WJ
Urba
M W
MW
Baseler
W C
WC
Kopp
R G
RG
Steis
J W
JW
Clark
J W
JW
Smith
D L
DL
Coggin
D L
DL
Longo
D003070:Coformycin / Q000031:analogs & derivatives / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006562:Herpes Zoster / Q000139:chemically induced; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007370:Interferon Type I / Q000627:therapeutic use; D007943:Leukemia, Hairy Cell / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D007958:Leukocyte Count / Q000187:drug effects; D008213:Lymphocyte Activation; D008297:Male; D015649:Pentostatin; D011994:Recombinant Proteins; D012263:Ribonucleosides / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects
D007166:Immunosuppressive Agents; D007370:Interferon Type I; D011994:Recombinant Proteins; D012263:Ribonucleosides; D003070:Coformycin; D015649:Pentostatin