Risk factors for evolution of acquired aplastic anemia into myelodysplastic syndrome and acute myeloid leukemia after immunosuppressive therapy in children.
Long-term survivors of acquired aplastic anemia (AA) have an increased risk of developing myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) after immunosuppressive therapy (IST). It is uncertain whether the increased survival time simply discloses the natural history of AA as a premalignant disease or whether secondary disease is related to the therapy itself. Between November 1992 and September 1997, 113 AA children with normal cytogenetics at diagnosis were treated with IST using antithymocyte globulin, cyclosporin, and danazol with or without granulocyte colony-stimulating factor (G-CSF). We assessed risk factors for developing MDS/AML by Cox proportional hazards models. Twelve of 113 patients developed MDS between 9 and 81 months following the time of diagnosis, giving a cumulative incidence of 13.7 +/- 3.9%. The following cytogenetic abnormalities were observed at the time of diagnosis of MDS: monosomy 7 (6 patients), monosomy7/trisomy21 (1 patient), trisomy 11 (1 patient), del (11) (9?:14) (1 patient), add (9q) (1 patient), add 7 (q 32) (1 patient), and trisomy 9 (1 patient). The number of days of G-CSF therapy and nonresponse to therapy at 6 months were statistically significant risk factors by multivariate analysis. The present study suggests a close relationship between long-term use of G-CSF and secondary MDS in nonresponders to IST.
Department of Developmental Pediatrics, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. kojimas@med.nagoya-u.ac.jp
Seiji
S
Kojima
Akira
A
Ohara
Masahiro
M
Tsuchida
Toru
T
Kudoh
Ryoji
R
Hanada
Yuri
Y
Okimoto
Takashi
T
Kaneko
Toshikuni
T
Takano
Koichiro
K
Ikuta
Ichiro
I
Tsukimoto
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D002897:Chromosomes, Human, Pair 7; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015994:Incidence; D007223:Infant; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000139:chemically induced* / Q000209:etiology / Q000235:genetics; D008297:Male; D009006:Monosomy; D009190:Myelodysplastic Syndromes / Q000139:chemically induced* / Q000209:etiology / Q000235:genetics; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate
D007166:Immunosuppressive Agents; D016179:Granulocyte Colony-Stimulating Factor