Adult ; Hemoglobinuria, Paroxysmal ; complications ; pathology ; Humans ; Male ; Moyamoya Disease ; diagnosis ; etiology ; pathology ; Young Adult

OBJECTIVES: To study the association between paroxysmal nocturnal hemoglobinuria (PNH) clone and immunosuppressive therapy (IST) in children with severe aplastic anemia (SAA). METHODS: A retrospective analysis was performed on the medical data of 151 children with SAA who were admitted and received IST from January 2012 to May 2020. According to the status of PNH clone, these children were divided into a negative PNH clone group (n=135) and a positive PNH clone group (n=16). Propensity score matching was used to balance the confounding factors, and the impact of PNH clone on the therapeutic effect of IST was analyzed. RESULTS: The children with positive PNH clone accounted for 10.6% (16/151), and the median granulocyte clone size was 1.8%. The children with positive PNH clone had an older age and a higher reticulocyte count at diagnosis (P<0.05). After propensity score matching, there were no significant differences in baseline features between the negative PNH clone and positive PNH clone groups (P>0.05). The positive PNH clone group had a significantly lower overall response rate than the negative PNH clone group at 6, 12, and 24 months after IST (P<0.05). The evolution of PNH clone was heterogeneous after IST, and the children with PNH clone showed an increase in the 3-year cumulative incidence rate of aplastic anemia-PNH syndrome (P<0.05). CONCLUSIONS SAA children with positive PNH clone at diagnosis tend to have poor response to IST and are more likely to develop aplastic anemia-PNH syndrome.
Anemia, Aplastic/drug therapy* ; Child ; Clone Cells ; Hemoglobinuria, Paroxysmal/etiology* ; Humans ; Immunosuppression Therapy ; Retrospective Studies

Adolescent ; Adult ; Anemia, Iron-Deficiency ; diagnosis ; etiology ; Child ; Female ; Hemoglobinuria, Paroxysmal ; complications ; diagnosis ; Humans ; Male ; Middle Aged ; Young Adult

Adult ; Graft vs Host Disease ; etiology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; methods ; Hemoglobinuria, Paroxysmal ; therapy ; Humans ; Male

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.

Adolescent ; Adult ; Aged ; Anemia, Aplastic ; complications ; pathology ; Child ; Child, Preschool ; Clone Cells ; Female ; Hemoglobinuria, Paroxysmal ; etiology ; pathology ; Humans ; Incidence ; Male ; Middle Aged ; Risk Factors ; Young Adult

In recent years, there have been lots of progresses in the studies on red cell diseases in China, especially bone marrow failure diseases including immuno-related pancytopenia, aplastic anemia, myelodysplastic syndrome, and paroxymal nocturnal hemoglobinuria. Numerous laboratory experiments as well as clinical researches have been carried out by Chinese hematologists, which brought about much clearer pathogenesis, more rational diagnosis methods and more effective therapies for red cell diseases.
Anemia, Aplastic ; diagnosis ; epidemiology ; etiology ; metabolism ; China ; Hematologic Diseases ; diagnosis ; epidemiology ; etiology ; metabolism ; Hemoglobinuria, Paroxysmal ; diagnosis ; epidemiology ; etiology ; metabolism ; Humans ; Myelodysplastic Syndromes ; diagnosis ; epidemiology ; etiology ; metabolism ; Pancytopenia ; diagnosis ; epidemiology ; etiology ; metabolism

Allogeneic stem cell transplantation (allo-SCT) using related or unrelated donor could eradicate paroxysmal nocturnal hemoglobinuria (PNH) clones and may cure the disease. Chronic graft-versus host disease (GVHD) is a major complication of patients who have undergone allo-SCT. Nephrotic syndrome has been described as one of the rare manifestations of chronic GVHD following the usual myeloablative allo-SCT. We report a case of nephrotic syndrome that developed 25 months after non-myeloablative allo-SCT for PNH. The patient had grade II acute GVHD and extensive chronic GVHD after non-myeloablative allo-SCT. Typically the patient presented with preserved renal function and full nephrotic syndrome including generalized edema, proteinuria, hypoalbuminemia, and hypercholesterolemia. Renal biopsy revealed findings of membranous glomerulopathy (MG). The patient is alive with a stable engraftment and full donor chimerism under the administration of tacrolimus for control of chronic GVHD and MG without refractory hemolysis and cytopenia.
Adult ; Diagnosis, Differential ; Female ; Glomerulonephritis, Membranous/drug therapy/*etiology/pathology ; Graft vs Host Disease/drug therapy/*etiology/pathology ; Hemoglobinuria, Paroxysmal/*therapy ; Human ; *Stem Cell Transplantation/*adverse effects ; Treatment Outcome

Paroxysmal nocturnal hemoglobinuria (PNH) is a progressive, systemic, life-threatening disease, characterized by chronic uncontrolled complement activation. A retrospective analysis of 301 Korean PNH patients who had not received eculizumab was performed to systematically identify the clinical symptoms and signs predictive of mortality. PNH patients with hemolysis (lactate dehydrogenase [LDH] > or = 1.5 x the upper limit of normal [ULN]) have a 4.8-fold higher mortality rate compared with the age- and sex-matched general population (P < 0.001). In contrast, patients with LDH < 1.5 x ULN have a similar mortality rate as the general population (P = 0.824). Thromboembolism (TE) (odds ratio [OR] 7.11; 95% confidence interval [CI] (3.052-16.562), renal impairment (OR, 2.953; 95% CI, 1.116-7.818) and PNH-cytopenia (OR, 2.547; 95% CI, 1.159-5.597) are independent risk factors for mortality, with mortality rates 14-fold (P < 0.001), 8-fold (P < 0.001), and 6.2-fold (P < 0.001) greater than that of the age- and sex-matched general population, respectively. The combination of hemolysis and 1 or more of the clinical symptoms such as abdominal pain, chest pain, or dyspnea, resulted in a much greater increased mortality rate when compared with patients with just the individual symptom alone or just hemolysis. Early identification of risk factors related to mortality is crucial for the management of PNH. This trial was registered at www.clinicaltrials.gov as NCT01224483.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized/therapeutic use ; Area Under Curve ; Child ; Dyspnea/etiology ; Female ; Hemoglobinuria, Paroxysmal/*diagnosis/drug therapy/mortality ; Hemolysis ; Humans ; Kaplan-Meier Estimate ; Kidney Diseases/complications/diagnosis ; L-Lactate Dehydrogenase/metabolism ; Male ; Middle Aged ; Odds Ratio ; ROC Curve ; Registries ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Thromboembolism/complications/diagnosis ; Young Adult