Blood, 15 June 2001, Vol. 97, No. 12, pp. 3682-3682
Adverse effects of G-CSF in sickle cell syndromes
Though likely past kindergarten, it was nevertheless
early on when I learned that sickle cell anemia is a disease of the red cell. In view of this simple principle, it was a nasty surprise to find
that administering G-CSF to patients with sickle cell disease, a
maneuver designed to affect white cells, can lead to disastrous
consequences, as described in 3 case reports, 2 of which appear as
letters to the editor in this issue (Wei and Grigg, page 3998) and the
May 15 issue (Adler and colleagues. Blood. 2001;97:3313); the third
report is by Abboud et al (Lancet. 1998;351:959). All 3 reports
describe severe pain and multiorgan failure occurring within 4 days of
starting G-CSF, and in one case the patient died. From these 3 isolated
clinical observations, much can be learned. First, patients with any of
the sickle cell syndromes should be considered at risk for
G-CSF-induced complications, since the 3 reports encompass a patient
with hemoglobin SS disease, a patient with hemoglobin SC disease, and a
patient with hemoglobin S/
+ thalassemia. Importantly, a
prior study suggests that G-CSF causes no ill effects in patients with
sickle cell trait (Kang et al. Blood. 2000;96:14a). Second, the lack of
a prior history of sickle cell-related symptoms should not be viewed
as reassuring, since the patients presented here were relatively
asymptomatic prior to starting the hematopoietic growth factor. Third,
G-CSF-induced complications may arise in the absence of
granulocytosis, since the patient reported by Wei and Grigg developed
life-threatening complications despite a normal neutrophil count. This
observation suggests that the deleterious consequences of G-CSF may be
partly attributable to effects on neutrophil function.
These case reports have a number of implications. They substantially
contribute to a growing body of epidemiological evidence showing an
association between leukocytosis and poor outcome in patients with
sickle cell disease. While prior epidemiological studies demonstrated a
clear association between leukocytosis and poor outcome, the
present case reports suggest that this association may be causal. As
such, they raise the possibility that interventions targeting
neutrophils may be useful in interdicting some of the complications of
sickle cell disease. Additionally, there is considerable interest in
mobilizing stem cells and progenitors in patients with sickle cell
disease for the eventual application of gene therapy. These cases
demonstrate that alternatives to G-CSF for achieving mobilization need
to be identified. Ultimately of most immediate relevance is the
conclusion that G-CSF administration is contraindicated in patients
with sickle cell disease.
C. Anthony Blau
University of Washington
