title: Multicenter prospective study of clonal complications in adult aplastic anemia patients following recombinant human granulocyte colony-stimulating factor (lenograstim) administration.
abstract: To elucidate the relationship between treatment with granulocyte colony-stimulating factor (G-CSF) and the development of chromosomal abnormalities and clonal evolution in adult aplastic anemia (AA) patients, we performed a prospective multicenter study. Of the 104 registered patients, 91 were found by the central review committee to have the diagnosis of AA. Of the 91 patients, 84 were determined to be evaluable in this study and were treated with regimens including G-CSF (lenograstim). A time-course study (at registration and 6 and 12 months after registration) of G-banded chromosomes, fluorescence in situ hybridization (FISH) analysis for monosomy 7, and morphological assessment of bone marrow was performed with these patients during the 1-year follow-up period. G-banding analysis demonstrated the development of cytogenetic abnormalities in 10 (16.1%) of the 62 evaluable patients. The most common aberration was monosomy 7. FISH analysis demonstrated monosomy 7 in 7 (10.4%) of the 67 evaluable patients. Evolution into myelodysplastic syndrome (MDS) was observed in 5 (7.7%) of the 65 patients who underwent morphological assessment of bone marrow. All patients who developed cytogenetic abnormalities or MDS received immunosuppressive agents and/or steroids with G-CSF. This study demonstrated that some adult AA patients exhibit evolution into MDS and development of chromosomal abnormalities such as monosomy 7. Although the incidence seems to be comparable with that found in previous studies, further long-term follow-up will be necessary to confirm the relationship between G-CSF and the development of chromosomal abnormalities and MDS.
authors.affiliation: First Department of Internal Medicine, Saitama Medical School, Iruma-gun, Saitama, Japan. hbesshoo@saitama-med.ac.jp
authors.forename: Masami
authors.initials: M
authors.lastname: Bessho
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Hotta
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ohyashiki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Mizoguchi
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Asano
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Masaharu
authors.initials: M
authors.lastname: Sakurai
authors.forename: Arinobu
authors.initials: A
authors.lastname: Tojo
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kizaki
authors.forename: Masako
authors.initials: M
authors.lastname: Iwanaga
authors.forename: Masao
authors.initials: M
authors.lastname: Tomonaga
authors.forename: Kunitake
authors.initials: K
authors.lastname: Hirashima
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000741:Anemia, Aplastic / Q000188:drug therapy / Q000473:pathology*; D002869:Chromosome Aberrations; D002897:Chromosomes, Human, Pair 7; D002999:Clone Cells / Q000187:drug effects / Q000473:pathology; D020732:Cytogenetic Analysis; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000633:toxicity*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009006:Monosomy; D009190:Myelodysplastic Syndromes / Q000139:chemically induced; D011446:Prospective Studies; D011994:Recombinant Proteins; D013997:Time Factors
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor