The value of granulocyte colony-stimulating factor (G-CSF) in the treatment of conditions associated with bone marrow aplasia/suppression is well appreciated. However, accruing experience is bringing to light adverse side effects that appear to be associated with long-term administration of G-CSF. We report 2 siblings with severe congenital neutropenia (SCN) (Kostmann's disease) who featured G-CSF (Filgrastim) -induced major renal and hematological complications. FA, a 12yr old girl and AA, her 17yr old brother, received daily G-CSF therapy for the last 9yrs. Both patients developed persistent microscopic hematuria with normal kidney function 2 mo after starting G-CSF. However, 4 yrs later, FA showed proteinuria, macroscopic hematuria and reduced kidney function. Renal biopsy revealed membranoproliferative glomerulonephritis type I. Discontinuation of G-CSF therapy for 4 months resulted in improvement of renal function. Persistent severe neutropenia and bacterial infections required resumption of G-CSF, which has led to deterioration of renal function and partially steroid-responsive hematuria and proteinuria. AA, who continues to show microscopic hematuria, has lately developed pancytopenia, with positive Coombs test and antiplatelet antibodies. Serology for parvovirus B19 was negative. Bone-marrow aspirates revealed maturation arrest of neutrophil precursors at the promyelocyte/myelocyte stage, and also megaloblastic changes and diminution of red cell progenitors and of megakaryocytes. Myeloid dysplasia or acute myeloid leukemia were not found. Each attempt to increase G-CSF dosage failed to raise the neutrophil count but aggravated the pancytopenia, requiring blood transfusions. In contrast, discontinuation of G-CSF resulted each time in a prompt reversal of pancytopenia and in disappearance of the Coombs and antiplatelet antibodies. AA was scheduled for bone marrow transplant and received during 33 days a glycosylated G-CSF (Lenograstim) preparation without adverse hematological phenomena.

We postulate that the observed hematological and renal derangements of long-term G-CSF therapy are immunologically mediated. Long term G-CSF therapy should be used with great caution under close surveillance of the hemotopoietic system and kidney function. It remains to be established whether Lenograstim might prove to be a suitable alternative.