Detection of myelodysplastic syndrome/ acute myeloid leukemia evolving from aplastic anemia in children, treated with recombinant human G-CSF.
OBJECTIVE
Recombinant human granulocyte colony-stimulating factor (G-CSF) has clear benefits in patients with severe neutropenia. However, recent reports of myelodysplastic syndrome/acute myeloid leukemia (t-MDS/AML) developing after treatment with immunosuppressants and G-CSF has raised concern over the use of this agent in patients with aplastic anemia.


METHODS
We undertook a multi-institutional, non-randomized study of 112 children given a diagnosis of aplastic anemia, and then treated with different immunosuppressants with or without G-CSF. In each case, bone marrow specimens were tested at study entry and every 6 months for 3 years to detect t-MDS/AML, defined by stringent morphological and molecular/cytogenetic criteria. Incidence rates were calculated by the person-years statistical method.


RESULTS
As of December 2001, all eligible patients had been followed for a median of 3 years, and the G-CSF (+) group had received a median total G-CSF dose of 30,100 micrograms altogether, administered over a median of 4 months. Only one case of MDS developed among the G-CSF (+) patients (n=81), compared with three in the group receiving other agents (n=31). This isolated case was not associated with monosomy 7, the cytogenetic abnormality most often linked to G-CSF treatment. Incidence rates of MDS in the two groups were not significantly different (3.8 vs. 22.4 per 1,000 patient-years at risk, p=0.125). There were no cases of overt AML in either cohort.


CONCLUSIONS
G-CSF therapy did not increase the risk of t-MDS/AML development in children with aplastic anemia over a median follow-up of 3.7 years
Imashuku
Shinsaku
S
Kyoto City Institute of Health and Environmental Sciences, Kyoto, Japan.
Hibi
Shigeyoshi
S
Bessho
Fumio
F
Tsuchida
Masahiro
M
Nakahata
Tatsutoshi
T
Miyazaki
Sumio
S
Tsukimoto
Ichiro
I
Hamajima
Nobuyuki
N
D000208:Acute Disease; D000741:Anemia, Aplastic / Q000188:drug therapy*; D002648:Child; D002897:Chromosomes, Human, Pair 7; D018450:Disease Progression; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015994:Incidence; D007951:Leukemia, Myeloid / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics; D009006:Monosomy; D009190:Myelodysplastic Syndromes / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics / Q000628:therapy; D009503:Neutropenia / Q000188:drug therapy; D011446:Prospective Studies; D011994:Recombinant Proteins
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim