Thrombocytopenia during immunotherapy with interleukin-2 by constant infusion.
OBJECTIVE
To elucidate some of the possible mechanisms that lead to interleukin-2 (IL2)-induced thrombocytopenia.


METHODS
We evaluated retrospectively the effects of immunotherapy with IL2 in 76 patients with disseminated cancer. The lymphokine was administered by constant infusion, daily for 6 days a week for 4 consecutive weeks.


RESULTS
A significant decrease in platelet counts was seen after the first 6 days of therapy in all but two patients: 14 patients experienced grade 2 or 3 toxicity, 21 had grade 1 toxicity, and although the decrease in platelet counts could not be graded as toxicity in the remaining 41 patients, there was an average decrease of 32% from baseline platelet counts in 39 (p less than 0.0001). Thrombocytopenia appeared to be secondary to peripheral platelet destruction, since bone marrow biopsy specimens obtained during thrombocytopenia showed hyperplastic megakaryocytopoiesis. IL2 is inactivated by tubular resorption, and severity of thrombocytopenia was strongly correlated with IL2-induced renal dysfunction (p = 0.0004). Additionally, both renal dysfunction and thrombocytopenia were related to total dose of IL2 and were more pronounced in patients with worse baseline renal function and lower baseline platelet counts. The incidence of thrombocytopenia increased with subsequent IL2 therapy: life-threatening thrombocytopenia (less than 25,000/microL) was seen in nine of 57 patients, five of whom required transfusional platelet support.


CONCLUSIONS
On the basis of preliminary observations, we hypothesize that thrombocytopenia induced by IL2 is caused by accelerated clearance of platelets by the reticuloendothelial system.
Paciucci
P A
PA
Department of Neoplastic Diseases, Derald Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New York.
Mandeli
J
J
Oleksowicz
L
L
Ameglio
F
F
Holland
J F
JF
D000293:Adolescent; D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects* / Q000032:analysis; D007674:Kidney Diseases / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy; D010976:Platelet Count / Q000187:drug effects; D011994:Recombinant Proteins; D012189:Retrospective Studies; D013921:Thrombocytopenia / Q000209:etiology*
D007376:Interleukin-2; D011994:Recombinant Proteins; D003404:Creatinine