PROLONGED ADMINISTRATION OF GRANULOCYTE-COLONY-STIMULATING FACTOR (FILGRASTIM) TO PATIENTS WITH FANCONI-ANEMIA - A PILOT-STUDY

This report examines the effect of filgrastim (granulocyte colony-stim ulating factor, [G-CSF] in 12 patients with neutropenia [absolute neut rophil count [ANC] <1,000/mm(3)]) caused by Fanconi anemia (FA). Two o f 14 patients who were evaluated for study entry were ineligible becau se of unsuspected cytogenetic abnormalities in their bone marrow (BM). G-CSF was started at 5 mu g/kg/d. All patients had an increase in the ir ANC at week 8 (mean increase = 15,664/ mm(3)). The median ANC durin g therapy was 5,030/mm(3). Eight of 10 patients who completed 40 weeks on study maintained an ANC >1,500/mm(3) on G-CSF given every-other-da y. Four patients had an increase in their platelet count by week 8 wit hout transfusion (maximum increase = 23,000 to 45,000/mm(3)); however, platelet counts fell toward baseline levels as the G-CSF dose was red uced. BM CFU-MK were increased at week 8 in three of four evaluable pa tients, Four patients who did not receive red blood cell transfusions had an increase in their hemoglobin level of at least 2.0 g/dL. A fift h patient had a red blood cell transfusion in week 2 and then had a si milar increase in hemoglobin level without subsequent transfusion. Eig ht of 10 patients who completed 40 weeks of treatment showed increases in the percentage of BM CD34(+) cells measured by flow cytometry, The same proportion showed increases in peripheral blood CD34(+) cells. I ncreased BM cellularity and myeloid hyperplasia were constant findings and were associated with increased expression of the proliferating ce ll nuclear antigen, Adverse experiences were mild fever (1 patient) an d a new BM cytogenetic abnormality at week 40 (1 patient), This study shows that prolonged administration of G-CSF exerts a stimulatory effe ct on the BM of FA patients and may be used to maintain a clinically a dequate ANC in these patients. G-CSF has beneficial effects on multipl e hematopoietic lineages in some patients and may be a good candidate for use in combination cytokine protocols for FA patients with progres sive aplastic anemia. G-CSF use results in an increase in circulating CD34(+) cells, a finding with important implications for future gene t ransfer protocols. (C) 1996 by The American Society of Hematology.