Objective: To evaluate the efficacy and safety of HLA-haploidentical hematopoietic stem cell transplantation (allo-HSCT) for hepatitis-related aplastic anemia (HRAA) patients. Methods: Retrospective analysis was performed on hepatitis-associated aplastic anemia patients who received haplo-HSCT at our center between January 2012 and June 2022. October 30, 2022 was the final date of follow-up. Results: This study included 28 HRAA patients receiving allo-HSCT, including 18 males (64.3% ) and 10 females (35.7% ), with a median age of 25.5 (9-44) years. About 17 cases of severe aplastic anemia (SAA), 10 cases of very severe aplastic anemia (VSAA), and 1 case of transfusion-dependent aplastic anemia (TD-NSAA) were identified. Among 28 patients, 15 patients received haplo-HSCT, and 13 received MSD-HSCT. The 2-year overall survival (OS) rate, the 2-year failure-free survival (FFS) rate, the 2-year transplant-related mortality (TRM) rate, the 100-day grade Ⅱ-Ⅳ acute graft-versus-host disease (aGVHD) cumulative incidence rate, and the 2-year chronic graft-versus-host disease (cGVHD) cumulative incidence rate were 81.4%, 81.4% (95% CI 10.5% -20.6% ), 14.6% (95% CI 5.7% -34.3% ), 25.0% (95% CI 12.8% -45.4% ), and 4.2% (95% CI 0.6% -25.4% ), respectively. After transplantation, all patients had no significant liver function damage. Compared with the MSD-HSCT group, only the incidence of cytomegaloviremia was significantly higher in the haplo-HSCT group [60.0% (95% CI 35.2% -84.8% ) vs 7.7% (95% CI 0-22.2% ), P=0.004]. No statistically significant difference in the Epstein-Barr virus was found in the 2-year OS, 2-year FFS, 2-year TRM, and 100-day grade Ⅱ-Ⅳ aGVHD cumulative incidence rates and 2-year cGVHD cumulative incidence rate. Conclusion: Allo-HSCT is safe and effective for HRAA, and haplo-HSCT can be used as a safe and effective alternative for newly diagnosed HRAA patients who cannot obtain HLA-matched sibling donors.
Male ; Female ; Humans ; Adult ; Treatment Outcome ; Anemia, Aplastic/therapy* ; Retrospective Studies ; Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Graft vs Host Disease/etiology* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Hepatitis/etiology* ; Bronchiolitis Obliterans Syndrome ; Transplantation Conditioning

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

The defectiveness of bone marrow mesenchymal stem cells (BM-MSCs) in acquired aplastic anemia (AA) has been a frequent research topic in recent years. This review summarizes the defectiveness of BM-MSCs which is responsible for the mechanism of acquired AA and the prospective application of BM-MSCs in the treatment of acquired AA. An increasingly number of laboratory statistics has demonstrated that the defectiveness of BM-MSCs is more likely to play an important role in the pathogenesis of AA, namely, the apparently different biological characteristics and gene expression profiles, the decreased ability of supporting hematopoiesis as well as self-renewal and differentiation, and the exhaustion of regulating immune response of hematopoietic environment. Those abnormalities continuously prompt AA to become irreversible bone marrow failure along with the imbalanced immunity. With deepening research on MSCs, infusion of MSCs for the primary purpose of recovering hematopoietic microenvironment may become a new approach for the treatment of AA.
Anemia, Aplastic ; etiology ; immunology ; therapy ; Bone Marrow ; Cell Differentiation ; Cell Proliferation ; Cytokines ; analysis ; Humans ; Lymphocyte Activation ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; physiology ; T-Lymphocytes, Regulatory ; immunology

OBJECTIVETo study the expression of Foxp3 and NFAT1 protein in peripheral blood (PB) in children with aplastic anemia (AA) and their roles in the pathogenesis of AA.

METHODSThe expression levels of Foxp3 and NFAT1 protein of mononuclear cells in PB were measured by Western blot in 68 children with AA before and after treatment and in 60 normal children (control group). The correlation between Foxp3 and NFAT1 protein expression and the correlation of the Foxp3 and NFAT1 protein expression with blood Hb, WBC and platelet levels were analyzed.

RESULTSThe expression levels of Foxp3 and NFAT1 protein in PB in the acute phase in the AA group were significantly lower than in the control group (P<0.05). After treatment (recovery phase) the expression levels of Foxp3 and NFAT1 protein increased obviously compared with those in the acute phase (P<0.05). The Foxp3 protein level was positively correlated with the NFAT1 protein level (r=0.812, P<0.05). Both the Foxp3 and NFAT1 protein levels were positively correlated with blood Hb, WBC and platelet levels in children with AA in the recovery phase (r=0.537, 0.579, 0.655 respectively; P<0.05).

CONCLUSIONSThe Foxp3 and NFAT1 protein levels in PB are reduced in children with AA, suggesting that they are involved in the pathogenesis of AA. The measurement of Foxp3 and NFAT1 protein levels may be useful in the severity evaluation of AA.

Adolescent ; Anemia, Aplastic ; blood ; etiology ; Child ; Child, Preschool ; Female ; Forkhead Transcription Factors ; blood ; Humans ; Male ; NFATC Transcription Factors ; blood

OBJECTIVETo determine the effect of combined treatment with Chinese medicine (CM) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) on patients with severe aplastic anemia (SAA).

METHODSEleven patients were treated with CM plus allo-HSCT. Nine patients received a conditioning regimen consisting of fludarabine (Flu), anti-thymocyte globulin (pig ALG), or anti-lymphocyte globulin (Rabbit ATG) and cyclophosphamide (CY), and two patients received pig ALG and CY. All patients were treated with Kidney (Shen)-reinforcing, blood-activating, and stasis-removing (KBS) herbal preparation beginning at 1 week before transplantation and ending at 8 weeks after transplantation. Chimerism status was assessed by analyzing short tandem repeat (STR) polymorphisms.

RESULTSAll patients recovered hematopoietic function and none had graft failure. The median number of days required for the absolute neutrophil count (ANC) increased to >0.5×10(9)/L was 15 days (12-22 days) and for spontaneous platelet recovery to >20×10(9)/L without post-transplantation transfusion was 17 days (15-27 days). Nine patients were long-term survivors and achieved full donor chimerism. The overall cumulative incidence of acute graft versus host disease (GVHD) grades I-II and III-IV was 18.2% (2/11) and 9.1% (1/11), respectively. The overall accumulated incidence of chronic GVHD was 27.3% and all patients had limited chronic GVHD. At a median follow-up time of 32 months (range: 12-97 months), 9 patients were still alive. The estimated 5-year overall survival (OS) rate was 81.8%. The incidence of treatment-related mortality, 2-year post-transplantation, was 18.2%. Two patients died from GVHD after transplantation.

CONCLUSIONTreatment with the KBS formulation may reduce the rate of graft failure and treatment-related mortality and improve the rate of OS in SAA patients with allo-HSCT.

Adolescent ; Adult ; Anemia, Aplastic ; therapy ; Animals ; Child ; Combined Modality Therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Graft Rejection ; etiology ; Graft vs Host Disease ; etiology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Rabbits ; Sus scrofa ; Syndrome ; Transplantation, Homologous ; Treatment Outcome ; Young Adult

OBJECTIVETo elucidate the clinical features, response rate, prognosis and clonal evolution of aplastic anemia (AA) with macrocytic anemia (mAA).

METHODSThe clinical features at initial diagnosis and data in follow up of mAA hospitalized from January 2000 to October 2011 were analyzed retrospectively.

RESULTS(1) Of 153/568 (26.9%) cases of mAA at initial diagnosis, 114(74.5%)were non-severe AA (NSAA), 39(25.5%)severe AA (SAA) and 0 very severe AA (VSAA), while the proportion was 16.2%, 45.2%, and 38.6% in 376 normocytic anemia AA (nAA), and the difference is statistically significant(χ(2) = 181.390; P = 0.000). The median age of mAA was significantly higher than that of nAA \[30(4 - 70)years vs 19 (3 - 68) years, P = 0.001\]. (2) There were no statistical difference in hemoglobin, absolute neutrophil count (ANC), platelet count (PLT), response rate after 6 months treatment and overall survival (OS) between mAA and nAA grouped in SAA and NSAA respectively. In SAA, the reticulocyte count (Ret) of mAA was significantly higher than that of nAA \[23.90(2.99 - 61.00)×10(9)/L vs 13.1(0 - 70.60)×10(9)/L, P = 0.000\] and the proportion of erythroid cells in bone marrow of mAA was also higher \[23.5 (0 - 58) vs 14.5 (0 - 65), P = 0.043\], while they did not differ significantly in NSAA. (3) The proportion of AA with PNH clones or abnormal cytogenetics did not differ significantly in mAA and nAA groups before treatment. The incidences of AA evolved to PNH in mAA and nAA was not statistically significant (7/153 vs 9/376, χ(2) = 1.099, P = 0.294) and so was the incidence of evolution to MDS/AML(3/153 vs 13/376, χ(2) = 0.399, P = 0.528).

CONCLUSIONIn presented with macrocytic anemia at initial diagnosis of AA, higher proportion of NSAA, elderly age, higher Ret and proportion of erythroid cells are features, but being no statistical difference in the response rate, OS, and proportion of clonal evolution.

Adolescent ; Adult ; Age of Onset ; Aged ; Anemia, Aplastic ; complications ; genetics ; therapy ; Anemia, Macrocytic ; etiology ; Child ; Child, Preschool ; Cloning, Molecular ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Treatment Outcome ; Young Adult

Anemia, Aplastic ; diagnosis ; etiology ; Benzene ; poisoning ; Expert Testimony ; Humans ; Male ; Occupational Diseases ; diagnosis

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

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

OBJECTIVETo explore the bone marrow feature of hemopoietic system injured by benzene through analyzing 56 benzolism cases.

METHODSThe 56 benzolism cases were divided into mild poisoning group, midrange poisoning group, aplastic anemia group, pancytopenia group and leukemia group. All cases progressed bone marrow aspiration and smear, and counted hundred karyocytes by Wright-Giemsa tinct bone marrow smear to classification and observe the cells' feature.

RESULTSThe megakaryocytes and the extent of bone marrow hyperplasia were decreased by turns of mild poisoning group, midrange poisoning group and aplastic anemia group. The archaeocytes and juvenile cells proliferation in mild poisoning group and midrange poisoning group were inhibited and occurred cell paramorphia which related to intoxication. Comparing with the other groups and normal reference value, the pancytopenia group's percentage of bone marrow cells in karyocytes was significantly decreased (P < 0.01, P < 0.05) and the leukemia group's percentage of bone marrow cells in karyocytes was significantly increased (P < 0.01). The proportion of cell paramorphia and nucleus malformation of granulocytes and red blood cells in pancytopenia group and leukemia group were increased, especially in leukemia group.

CONCLUSIONWe saw the inhibition of archaeocytes and juvenile cells proliferation and some cell paramorphia appearances in mild poisoning and midrange poisoning cases of chronic benzolism. The abnormality changes which can be seen in bone marrow of severe benzolism cases were corresponding with the clinical classification.

Adult ; Anemia ; etiology ; pathology ; Anemia, Aplastic ; etiology ; pathology ; Benzene ; poisoning ; Bone Marrow ; pathology ; Bone Marrow Cells ; cytology ; Bone Marrow Examination ; Female ; Humans ; Leukemia ; etiology ; pathology ; Male ; Middle Aged