Thrombocytosis over 800 x 109/L Following the Use of Pegfilgrastim after Chemotherapy R-MegaCHOP in Patients with Diffuse Large B-Cell Lymphoma

The single administration of the long lasting pegylated recombinant human granulocyte colony-stimulating factor (rhuG-CSF) pegfilgrastim has shown comparable effects on reducing the duration of severe neutropenia after cytotoxic chemotherapy in comparison to repeated daily doses of non-pegylated rhuG-CSF (filgrastim). They both have become an important part of supportive therapy with a similar profile of positive and adverse effects. Recently we observed high thrombocytosis most probably related to the administration of pegfilgrastim in several patients with diffuse large B-cell lymphomas (DLBCL) treated with R-MegaCHOP cycles in the study of the Czech Lymphoma Study Group (CLSG). Patients with DLBCL were treated according to the CLSG study R-MegaCHOP/R-ESHAP/BEAM with a prephase AOP (doxorubicin 75 mg/sqm i.v. day 1, vincristine 2 mg i.v. day 1, prednisone 60 mg/sqm p.o. days 1-5) and in 21-day intervals with 3 cycles of R-MegaCHOP (rituximab 375 mg/sqm i.v. day 0, cyclophosphamide 3000 mg/sqm i.v. day 1, doxorubicin 75 mg/sqm i.v. day 1, vincristine 2 mg i.v. day 1, prednisone 60 mg/sqm p.o. days 1-5). Pegfilgrastim (Neulasta, Amgen) 6 mg s.c. has been administered on day 2 of the cycle since 2005 while filgrastim (Neupogen, Roche) 5 mcg/kg/d s.c. had been given since day 8 of cycles for 3-9 (median 5.5) days in years 2000-4 (Pytlik R, The Hematology J. 5, Suppl. 2, S308-9, 2004). Blood cell counts including platelet numbers (range of normal reference values: 135 - 400 x 10E9/L) were measured by Coulter LH 750 Hematology Analyzer. Three of four patients (35/m, 59/f, 46/f) after the 1^st cycle of R-MegaCHOP with pegfilgrastim exhibited trombocytosis with 866, 993, 1046 x 10E9/L on day 20, 660, 522, and 870 x 10E9/L after the 2^nd cycle, respectively. A previous splenectomy was the contributing factor to thrombocytosis in the third patient but no other causes of thrombocytosis were discovered in other two patients. Platelets were under 400 x 10E9/L during and after this therapy in the fourth patient, a 32-year old man. On the contrary, 8 patients, 4 females and 4 males, aged 22-57 (median 47) years old, receiving the same chemotherapy with filgrastim had platelet counts either under 400 x 10E9/L(4 cases) or only slightly elevated 520 571 x 10E9/L(4 cases). The 9^th patient treated with chemotherapy and filgrastim was a 36-year old man after splenectomy, exhibiting platelet counts 1095, 708, 810 x 10E9/L after the 1^st, 2^nd, and 3^rd cycle of MegaCHOP chemotherapy. To conclude: 1. Patients with DLBCL after splenectomy treated with intensive chemotherapy plus filgrastim or pegfilgrastim may exhibit platelet counts over 1000 x 10E9/L with risks of thrombosis. 2. Pegfilgrastim administered to patients with DLBCL after intensive chemotherapy may increase platelets over 800 x 10E9/L on day 20 of cycles in a proportion of patients in comparison to filgrastim showing an overshooting recovery of platelets. No thrombotic complications were observed in any of our patients with platelet counts over 800 x 10E9/L. Supported in part by the grant from IGA MH CR No. NR 8231-3/2004.