title: Long-term follow-up of clonal evolutions in 802 aplastic anemia patients: a single-center experience.
abstract: To assess the incidence rates and risk factors for clonal evolutions in aplastic anemia (AA) patients, we studied 802 hospitalization cases from January 1991 through December 2007 by using the cumulative incidence curves and the Cox proportional hazards mode. We found that the case of 19 patients had evolved to myelodysplastic syndrome or acute myeloid leukemia (MDS/AML), while 21 patients (two of them with concurrent MDS) developed paroxysmal nocturnal hemoglobinuria (PNH). The cumulative incidence of clonal evolutions was assessed as 3.7%, whereas the incidences of MDS/AML and PNH were 1.7% and 2.1%, respectively, at 5 years. By multivariate analysis, age, severity of the disease, and the number of days of rhuG-CSF therapy were the risk factors for AA evolution to MDS/AML. The relative risk (RR) for very severe AA was approximately seven times higher than that for severe AA (SAA) and non-SAA (NSAA) (P = 0.001), but the latter two did not differ significantly (P = 0.743). PNH clone was monitored sequentially in 237 patients; positive clones were detected in 41% of the patients, but more than half of them were transient or instable. White blood cell count at initial diagnosis was identified as the only significant risk factor for AA evolution to PNH (P = 0.007). Our results suggest that the transformation to PNH for subpopulations of AA patients may be natural evolution as the clinical manifestation and pathogenesis between AA and PNH were closely related. Furthermore, normalizing hematopoiesis of AA may represent a viable approach to prevent clone evolutions, especially to MDS/AML.
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, People's Republic of China.
authors.forename: Yingmei
authors.initials: Y
authors.lastname: Li
authors.forename: Xingxin
authors.initials: X
authors.lastname: Li
authors.forename: Meili
authors.initials: M
authors.lastname: Ge
authors.forename: Jun
authors.initials: J
authors.lastname: Shi
authors.forename: Linsheng
authors.initials: L
authors.lastname: Qian
authors.forename: Yizhou
authors.initials: Y
authors.lastname: Zheng
authors.forename: Jianxiang
authors.initials: J
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use; D006457:Hemoglobinuria, Paroxysmal / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D015994:Incidence; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology / Q000209:etiology*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000453:epidemiology / Q000209:etiology*; D011994:Recombinant Proteins; D012307:Risk Factors; D012720:Severity of Illness Index; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor