Recombinant interferon-alpha therapy of Philadelphia chromosome-negative myeloproliferative disorders with thrombocytosis.
OBJECTIVE
The clinical course of patients with myeloproliferative disorders and excessive thrombocytosis may be complicated by serious hemorrhagic or thrombotic events. We have previously reported that interferon-alpha can control severe refractory thrombocytosis in patients with advanced chronic myelogenous leukemia. Therefore, we treated a group of thrombocythemic patients with Ph-negative myeloproliferative disorders, including polycythemia vera and essential thrombocythemia, with recombinant interferon-alpha (rIFN-alpha 2a).


METHODS
Eight patients with profound elevations in platelet counts received a median induction dose of 5.4 X 10(6) U/day (range, 5.0 to 10.0 X 10(6) U/day) of rIFN-alpha 2a administered intramuscularly or subcutaneously.


RESULTS
We observed a significant decline in platelet counts from a median baseline value of 1,929 X 10(9)/L (range, 960 to 2,960 X 10(9)/L) to a median posttreatment value of 431 X 10(9)/L (range, 71 to 1,150 X 10(9)/L) (p less than 0.01). Concomitantly, white blood cell counts declined from a median baseline value of 20.8 X 10(9)/L (range, 10.5 to 40.8 X 10(9)/L) to a median posttreatment value of 6.1 X 10(9)/L (range, 2.9 to 29.0 X 10(9)/L) (p less than 0.02). Correction of thrombocytosis was rapid, with a median of only eight days from the start of therapy to the achievement of a platelet count less than 1,000 X 10(9)/L. Six of eight patients have shown an ongoing response with a median follow-up period of 11 months (range, one to 30 months). There have been no bleeding or thrombotic events during the study. Side effects of rIFN-alpha 2a therapy consisted of fever and flu-like symptoms, with tachyphylaxis developing after one to two weeks of therapy.


CONCLUSIONS
Our observations suggest that alpha interferon may be a promising therapeutic agent for myeloproliferative disorders characterized by thrombocytosis.
Talpaz
M
M
Department of Clinical Immunology and Biological Therapy, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Kurzrock
R
R
Kantarjian
H
H
O'Brien
S
S
Gutterman
J U
JU
D000328:Adult; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000009:adverse effects / Q000627:therapeutic use*; D007958:Leukocyte Count; D008214:Lymphocytes / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000188:drug therapy*; D010976:Platelet Count; D011087:Polycythemia Vera / Q000188:drug therapy; D011994:Recombinant Proteins; D013920:Thrombocythemia, Essential / Q000188:drug therapy
D007370:Interferon Type I; D011994:Recombinant Proteins