Hemoglobinuria, Paroxysmal ; therapy ; Humans

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

Antibodies, Monoclonal, Humanized ; therapeutic use ; Complement Inactivator Proteins ; therapeutic use ; Hemoglobinuria, Paroxysmal ; therapy ; Humans

Paroxysmal nocturnal hemoglobinuria (PNH) is a hemolytic disease of abnormally activated complement. FLAER diagnosis is a higher sensitive and specific method, which makes PNH patients to be early discovered and treated. Non-typical symptoms including thrombosis, pulmonary hypertension and chronic kidney disease in PNH have been caused increasing attention. Eculizumab monoclonal antibody has greatly improved the current treatment status of PNH. PNH can be cured thoroughly by allogeneic hematopoietic stem cell transplantation. In this article, the FLAER diagnosis, clinic symptoms and progress of treatment in patients with PNH are reviewed.
Antibodies, Monoclonal, Humanized ; therapeutic use ; Hematopoietic Stem Cell Transplantation ; Hemoglobinuria, Paroxysmal ; diagnosis ; therapy ; Humans

Through the applications of high-sensitivity flow cytometry of FLAER and the treatment of eculizumab, it is necessary to understand of paroxysmal nocturnal hemoglobinuria (PNH) from a new point of view. The results of studies demonstrate that treatment with eculizumab alters the natural history of PNH by virtually eradicating thromboembolic complications, inhibiting of intravascular hemolysis and reducing or eliminating transfusion requirements. Eculizumab treatment may also reduce disease-related mortality. This review focuses on the studies to define the relationship between PNH and bone marrow failure syndromes and to characterize the long-term outcome of patients with PNH treated with eculizumab. New therapeutic strategies aimed at controlling extravascular and intravascular hemolysis are discussed.
Antibodies, Monoclonal, Humanized ; therapeutic use ; Complement C5 ; immunology ; Hemoglobinuria, Paroxysmal ; diagnosis ; therapy ; Humans ; Prognosis

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder of hematopoiesis due to the inactivation of PIG-A gene. However, the presence of mutant PIG-A gene in a group of hematopoietic cells is not enough for the development of PNH, immunologic injury and apoptotic effects are considered to play an important role in clonal expansion. Knowledge of the molecular mechanisms leading to PNH has substantially increased in the past decades, which remarkably advances the diagnostic modalities and treatment approaches of patients with PNH. Though great progress has been made because of targeted therapy method, the challenges are still ahead. In this review the advances of studies on mechanism, laboratorial diagnosis and therapeutic protocols of PNH are summarized.
Complement System Proteins ; Hemoglobinuria, Paroxysmal ; diagnosis ; genetics ; pathology ; therapy ; Humans ; Membrane Proteins ; genetics ; T-Lymphocytes, Regulatory

OBJECTIVE: To investigate the clinical characteristics and prognosis of patients with acute myeloid leukemia(AML) combined with paroxysmal nocturnal hemoglobinuria(PNH). METHODS: The clinical data of 13 AML combined with PNH patients treated in our hospital from January 2017 to May 2019 were collected and retrospective analyzed. The complete remission(CR) rate for induction chemotherapy was analyzed. The level of PNH RESULTS: Among the 13 patients, 11 (84.6%) cases were CR after first induction chemotherapy. The median overall survival(OS) time was 17 months(0-30 months), the median progression-free survival(PFS) time was 16 months(2-26 months). There were no significant difference in the number of PNH CONCLUSION The patients of AML combined with PNH have higher CR rate after the first induction chemotherapy. The level of WBC and LDH at first diagnosed are the factors that affecting the OS of the patients. The OS of patients with WBC lower than 10×10
Hemoglobinuria, Paroxysmal ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute/drug therapy* ; Prognosis ; Remission Induction ; Retrospective Studies

OBJECTIVE: To analyze the clinical efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for paroxysmal nocturnal hemoglobinuria (PNH), and preliminarily explore the role of an improved post-transplantation cyclophosphamide (PTCy) based conditioning regimen in PNH patients receiving transplantation. METHODS: Clinical related data of PNH sufferers receiving allo-HSCT in Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were collected, and hematopoietic reconstitution, chimerism, PNH cloning, graft-versus-host disease (GVHD), infection, and survival were analyzed. RESULTS: Totally five PNH patients receiving allo-HSCT were enrolled, including 1 case with classic PNH, 3 cases with aplastic anemia-PNH syndrome, 1 case with myelodysplastic syndrome, three of them (case 1-3) received the improved PTCy based conditioning regimen before HSCT. All sufferers engrafted successfully within 28 days, the median time of neutrophil and platelet engraftment was 11 days and 12 days, respectively, no patient occurred acute or chronic GVHD, after a median follow-up of 16 months, all recipients survived and completely eliminated PNH cloning. CONCLUSION Allo-HSCT can completely clear PNH cloning and restore hematopoietic function with controllable complications, and the improved PTCy based conditioning regimen is proved to be effective in PNH transplantation.
Anemia, Aplastic/therapy* ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Hemoglobinuria, Paroxysmal/therapy* ; Humans ; Transplantation Conditioning

Objective: To compare the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for paroxysmal nocturnal hemoglobinuria (PNH) with paroxysmal nocturnal hemoglobinuria-aplastic anemia (PNH-AA) syndrome. Methods: The outcomes of 46 patients who received allo-HSCT (16 PNH patients, 30 PNH-AA patients) from July 10, 2007 to June 2, 2018 were analyzed retrospectively. The conditioning regimen was busulfan, cyclophosphoramide, and ATG in haploidentical donors and unrelated donors. Patients with matched sibling donors were treated with the fludarabine, cyclophosphamide, and ATG regimen. Results: There were no differences of baseline data between the 2 groups except gender distribution and the numbers of haploidentical donor transplantation. The median values of absolute nucleated cell counts were 10.58 (3.83-13.83) ×10(8)/kg in the PNH group and 10.81 (3.96-33.40) ×10(8)/kg in the PNH-AA group (P=0.668) . The median doses of CD34(+) cells infused were 5.00 (3.14-8.42) ×10(6)/kg and 3.57 (1.97-6.17) ×10(6)/kg (P=0.002) , respectively. All patients obtained complete engraftment. The median time for myeloid engraftment were 11 (7-14) days in the PNH group and 12 (10-26) days in the PNH-AA group (P=0.003) . The median time for platelet engraftment were 13 (11-16) days and 18 (12-75) days (P=0.002) , respectively, after a median follow-up of 36 (4-132) months in the PNH group and 26 (4-75) months in the PNH-AA group (P=0.428) . There were no differences of incidence rates of acute graft-versus-host disease (aGVHD) , chronic GVHD and infection between PNH and PNH-AA groups (P>0.05) . No patient occurred early death and relapse. The estimated 3-year overall survival (OS) of PNH and PNH-AA groups were (100.0±0.0) % and (85.7± 6.6) % (P=0.141) , GVHD-free and failure-free survival (GFFS) were (100.0±0.0) %, (78.7±7.7) % (P=0.067) . Conclusions: allo-HSCT is effective for patients with PNH and PNH-AA syndrome. The preliminary results indicate that myeloid and platelet engraftment in PNH group were faster than PNH-AA group. There were no differences in OS and GFFS between PNH group and PNH-AA group.
Anemia, Aplastic/therapy* ; Hematopoietic Stem Cell Transplantation ; Hemoglobinuria, Paroxysmal/therapy* ; Humans ; Retrospective Studies ; Transplantation, Homologous ; Treatment Outcome

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