OBJECTIVETo explore the clinical significance of evolution of paroxysmal nocturnal hemoglobinuria (PNH) clones in aplastic anemia (AA) patients.

METHODSThe positive rate of PNH clones in 678 AA cases at first diagnosis from January 2002 to December 2009 were analyzed, and to compare the response rate and overall survival (OS) between AA patients with or without PNH clones. All patients were sequentially followed-up to assess the incidence rate and risk factors for AA evolving to overt PNH.

RESULTS(1) Of 119/678 (17.6%) AA patients at initial diagnosis presented with PNH clones,the positive rates of PNH clones among non-severe AA (NSAA), severe AA (SAA) and very severe AA (VSAA) were 16.7% (37/ 222), 17.3% (45/260) and 18.9% (37/196), respectively. There was no statistical difference among the three groups. (Chi2 = 0.369; P = 0.832); (2) 678 newly diagnosed AA cases were divided into 5 subgroups according to PNH clones, severity of disease and treatment regimens. There was no statistical difference among the five subgroups regarding 6m-response rate (RR) and OS. (3) Serial follow-up revealed that persistent PNH negative clones were found in 516 (76.1%) cases, and evolved to PNH positive clones after therapy in 43 (6.3%) cases. Persistent PNH positive clones were found in 72 (10.6%) cases, and disappeared the clones after treatment in 47 (6.9%) cases. There was no statistical difference among the four subgroups in terms of the 6m RR (Chi2 = 2.489,P = 0.426) and OS (P = 0.477); (4) 17 out of 678 AA cases (2.5%) evolved to overt PNH and the estimated incidence of evolution to overt PNH was (3.7 +/- 0.9)% at 10 years. The incidences of AA patients with or without PNH clones at initial diagnosis evolved to overt PNH were 3.4% and 2.3%, respectively. There was no statistical difference between the two groups, (Chi2 = 0.111; P = 0.739); and so was found in OS by Kaplan-Meier analysis (P = 0.868). Cox regression model analysis showed that none of the severity of AA, with or without PNH clone at initial diagnosis, treatment regimen and 6m RR was the risk factor for evolution to overt PNH.

CONCLUSIONThere is no difference between AA patients presented with or without PNH clones at initial diagnosis regarding the RR and prognosis. The appearance of PNH clones in AA is not identified as a risk factor for developing into overt PNH.