Imatinib-Related Neutropenia in Chronic-Phase Chronic Myelogenous Leukaemia: Safety and Efficacy of Granulocyte-Colony-Stimulating Factor (Filgrastim) Use.
Authors: Lazzaro Antonio , Bernuzzi Patrizia , Trabacchi Elena , Vallisa Daniele , Arcari Annalisa , Bertè Raffaella , Moroni Carlo F. , Anselmi Elisa , Cavanna Luigi 
Published: April 2020

Abstract
Hematological toxicity during imatinib therapy in patients with chronic myelogenous leukaemia (CML) is common occurring in about 30–50% of cases. Grade 3 or 4 neutropenia occurs in 35–45% of patients with CML in chronic phase that receive imatinib. Often myelosuppression results in treatment interruption or dose reduction producing a negative effect on the efficacy of therapy. To reverse neutropenia induced by imatinib therapy in a patient with chronic-phase CML we used granulocyte-colony-stimulating factor (filgrastim) evaluating the response and the safety. A chronic-phase CML Philadelphia positive was diagnosed in a 42 years old woman presenting with elevated thrombocytosis (platelets 1082 x10E9/L), splenomegaly and mild leucocytosis (white cells 10.8 x10E9/L). Cytogenetic analysys showed a tipical bcl-abl rearrangement in 100% of mitoses. Hematological and clinical parameters were used to obtain a mild Sokal risk score (0.9). Imatinib was started at standard dose of 400 mg/day producing a partial cytogenetic response (bcl-abl in 30% of mitoses). After 8 weeks of therapy the patient showed a rapid decrease of platelets number to normal level but presented a grade 2 anemia (haemoglobin 9.6 gr/dl) and a grade 3 neutropenia (760 x10E9/L). The imatinib dose was first reduced to 300 mg/day without leucocytes number recovery. The therapy was then stopped and reintroduced at a dose of 200 mg/day after increase of total leucocytes number but the hematologic toxicity reappeared. A cytogenetic analysis performed after five months by the start of therapy showed a progression of leukemic clone (bcl-abl in 75% of mitoses). Granulocyte-colony-stimulating factor (filgrastim) was then introduced with a schedule of 300 microgr every seven days. The granulocyte-colony-stimulating factor therapy was well tolerated and the patient showed a disappearance of haematological toxicity after only 3 weeks. Neutrophils number was ever superior to 1.5 x10E9/L and haemoglobin level remained at a value of 11–11.5 gr/dl. The absence of hematologic toxicity permitted to increase the imatinib therapy at a standard dose of 400 mg/day. A cytogenetic analysis with fluorescent in situ hybridization (FISH) technique was performed after three months of standard dose (400 mg/day) and showed a complete cytogenetic response (bcl-abl rearrangement resulted absent in 100% of mitoses). Actually the patient is at the seventh months by the start of full dose of imatinib therapy and the neutrophils number is stable over 2.5 x10E9/L with a single dose of granulocyte-colony-stimulating factor every ten days. In conclusion, on the basis of the concept that the probability of response to imatinib is decreased for patients who developed myelosuppression and that needed a dose reduction of therapy, we believe that the use of granulocyte-colony-stimulating factor to reverse neutropenia represents a safe and efficacy method to contrast the hematologic toxicity and to permit an optimal imatinib terapeutic schedule.