Hematology AND Aplastic anemia [keywords]
- [Antithymocyte/Antilymphocyte globulin plus cyclosporine A therapy for the treatment of older patients with severe aplastic anemia]. [English Abstract, Journal Article]
- Zhonghua Xue Ye Xue Za Zhi 2016 Jul; 37(7):607-10.
To evaluate the efficacy and safety of intensive immunosupressive therapy (IST) with antithymocyte/antilymphocyte globulin plus cyclosporine A in the treatment of older patients (≥60 years) with severe aplastic anemia (SAA).The hematologic response and safety of sixteen older SAA patients treated with IST regimen in our hospital were retrospectively analyzed , and the factors affecting response were also explored.A total of 16 older SAA patients were involved, the median age was 63.5 (60-79) years. Among them, 7 were VSAA and 9 were SAA; 9 patients received Rabbit anti- human thymocyte globulin (rATG), and 7 patients porcine anti- human lymphocyte globulin (pALG). Two patients died within 3 months after IST; at the 6 months after IST, 9 patients achieved hematology response and 5 patients had no response; overall response rate was 56.3%. Two (22%) of the 9 patients treated with rATG achieved hematology response; However, all 7 patients (100.0%) treated with pALG achieved hematology response. rATG/pALG associated adverse reactions were mild and easily managed.The older patients with SAA could still benefit from IST consisting of standard dose rATG/pALG with CsA, and the patients with VSAA had worse prognosis, pALG was inferior to rATG as a first treatment for SAA.
- Successful treatment of aplastic anemia-paroxysmal nocturnal hemoglobinuria associated with eosinophilic fasciitis with matched unrelated donor allogeneic peripheral blood stem cell transplantation. [Journal Article]
- Clin Case Rep 2016 Aug; 4(8):765-7.
We report the first patient case of successful treatment intervention for both eosinophilic fasciitis and aplastic anemia with allogeneic peripheral blood stem cell transplantation from a matched unrelated donor after multiple immunosuppressant failure.
- Abnormal histone acetylation of CD8(+) T cells in patients with severe aplastic anemia. [JOURNAL ARTICLE]
- Int J Hematol 2016 Aug 2.
Severe aplastic anemia (SAA) is a rare autoimmune disease characterized by severe pancytopenia and bone marrow failure, which is caused by activated T lymphocytes. In the present study, we evaluated histone H3 acetylation levels of bone marrow CD8(+) T cells in SAA patients, and analyzed its correlation with clinical condition parameters. We found that the percentages of CD8(+) T cell histone H3 acetylation in patients with untreated SAA, recovering SAA (R-SAA) and normal control, were 1.21 ± 0.08, 1.05 ± 0.36, and 1.00 ± 0.41, respectively, with no significant statistical differences. However, the amount of CD8(+) T cell histone H3 acetylation from untreated SAA was 176.21 ± 32.22 μg/mg protein, which was significantly higher than that of complete response (CR)-SAA (104.29 ± 62.06 μg/mg protein) and normal control (133.94 ± 56.27 μg/mg protein) (P < 0.05) groups. Moreover, histone H3 acetylation amount of CD8(+) T cell was significantly and negatively correlated with absolute neutrophil count, proportion of reticulocytes, ratio of CD4(+) to CD8(+) T cell in peripheral blood, and percentage of bone marrow erythroid (P < 0.05). To some extent, it also negatively correlated with hemoglobin level, platelet count, percentage of bone marrow granulocyte, and megakaryocyte count. Abnormal histone H3 acetylation of CD8(+) T cells may thus play a role in the immune pathogenesis of SAA.
- Marrow grafts from HLA-identical siblings for severe aplastic anemia: does limiting the number of transplanted marrow cells reduce the risk of chronic GvHD? [JOURNAL ARTICLE]
- Bone Marrow Transplant 2016 Aug 1.
A total of 21 patients with severe aplastic anemia (SAA) underwent marrow transplantation from HLA-identical siblings following a standard conditioning regimen with cyclophosphamide (50 mg/kg/day × 4 days) and horse antithymocyte globulin (30 mg/kg/day × 3 days). Post-grafting immunosuppression consisted of a short course of methotrexate (MTX) combined with cyclosporine (CSP). The transplant protocol tested the hypothesis that the incidence of chronic GvHD could be reduced by limiting the marrow grafts to ⩽2.5 × 10(8) nucleated marrow cells/kg. None of the patients rejected the graft, all had sustained engraftment and all are surviving at a median of 4 (range 1-8) years after transplantation. Chronic GvHD developed in 16% of patients given ⩽2.5 × 10(8) nucleated marrow cells/kg. Post-grafting immunosuppression has been discontinued in 20 of the 21 patients. In conclusion, limiting the number of transplanted marrow cells may have resulted in minimal improvement in the incidence and severity of chronic GvHD.Bone Marrow Transplantation advance online publication, 1 August 2016; doi:10.1038/bmt.2016.198.
- Autoimmune Hepatitis and Seronegative Hepatitis Associated With Myelodysplastic Syndrome in Children. [JOURNAL ARTICLE]
- J Pediatr Hematol Oncol 2016 Jul 27.
An association between hepatitis and aplastic anemia (AA) is known as hepatitis-associated AA, and is characterized by an acute attack of hepatitis followed by the development of AA. We report 2 clinical cases of acute seronegative hepatitis in which pancytopenia with mild dysplasia developed after 3 months; however, neither of our cases fulfilled the histological criteria of AA, but rather myelodysplastic syndrome. This novel association bears considerable resemblance to hepatitis-associated AA, and raises the question of whether hepatitis-associated dysmyelopoiesis should be included in the spectrum of hypocellular myelodysplastic syndrome.
- High-dose Cyclophosphamide is Effective Therapy for Pediatric Severe Aplastic Anemia. [JOURNAL ARTICLE]
- J Pediatr Hematol Oncol 2016 Jul 27.
Use of high-dose cyclophosphamide without hematopoietic stem cell transplant to treat severe aplastic anemia (SAA) has been controversial due to concern for increased infectious toxicity as compared with antithymocyte globulin and cyclosporine A. As children often tolerate dose-intensive therapy better than adults, we sought to perform a detailed retrospective analysis of both treatment response and toxicity in 28 patients younger than 22 years of age treated with 29 courses of high-dose cyclophosphamide as the sole form of immunosuppression.Children and adolescents with SAA who lacked an human leukocyte antigen-matched sibling donor were treated with cyclophosphamide 50 mg/kg/d for 4 consecutive days then received daily granulocyte colony stimulating factor until neutrophil recovery, transfusion support, and antimicrobial prophylaxis.Overall survival was 85%, with hematologic response of 79% and complete response of 66%. Cumulative incidences of bacterial infection (86%) and fungal infection (62%) were high but deaths due to infection were rare, as were clonal evolution (1/28), clinically relevant paroxysmal nocturnal (1/28), and relapse (2/28).Response rates and survival following high-dose cyclophosphamide in pediatric patients with SAA exceed those seen in adults and compare favorably to antithymocyte globulin/cyclosporine A with manageable infectious toxicity.
- [Efficacy and security of matched unrelated donor hematopoietic stem cell transplant with transfusion of multipotent mesenchymal cells in pediatric severe aplastic anemia]. [English Abstract, Journal Article]
- Zhonghua Xue Ye Xue Za Zhi 2016 Jun 14; 37(6):453-7.
To observe the efficacy of matched unrelated donor hematopoietic stem cell transplant (HSCT) with transfusion of multipotent mesenchymal cells (MSC) in pediatric severe aplastic anemia (SAA).19 children with SAA received matched unrelated donor HSCT with MSC, and the hematopoietic recovery and transplant-associated complications of these children were monitored.All patients achieved rapid hematopoietic reconstruction after HSCT, and the median durations to neutrophil and platelet recovery were 12 (9-21) days and 14 (8-24) days respectively, but delayed rejection occurred in one case four months after HSCT. 9 cases developed grade Ⅰ acute graft-versus-host (aGVHD), and one case grade Ⅲ aGVHD and diffuse chronic graft-versus-host. Cytomegalovirus viremias were observed in 15 patients. 2 cases developed hemorrhagic cystitis, 10 children experienced infections. All the children were alive during a median following-up time of 27(8-70) months, one of them developed LPD and received rituximab and chemotherapy, delayed rejection occurred in this patient four months after HSCT, Haplo-identical HSCT from his father as the donor was performed and achieved successful engraftment.The matched unrelated donor HSCT with MSC in pediatric SAA was safe and effective.
- Evaluation of the Hemostatic Disorders in Adolescent Girls with Menorrhagia: Experiences from a Tertiary Referral Hospital. [Journal Article]
- Indian J Hematol Blood Transfus 2016 Sep; 32(3):356-61.
Bleeding disorders are a common cause of menorrhagia in the adolescent age group. We aimed to evaluate the incidence of hemostatic disorders, using clinical and laboratory findings of bleeding disorders in adolescent girls with menorrhagia. A retrospective chart review used to evaluate adolescent girls with menorrhagia who were referred to Yuzuncu Yil University Pediatric Hematology clinic between January 2010 and December 2014. Out of 52 patients referred for investigation, 50 patients were included in the study. The mean age and mean menarche age were 14.8 ± 1.42 (range: 12-17) and 12.47 ± 0.55, respectively. In 42 % (n = 21) of patients, anemia was detected. In 22 % (n = 11) of patients, a bleeding disorder was detected: five cases with von Willebrand disease, two cases with acute immune thrombocytopenic purpura, one case with Bernard-Soulier syndrome, one case with Glanzmann thrombasthenia, one case with aplastic anemia and one case with factor X deficiency. The remaining 39 out of the 50 patients were finally diagnosed with dysfunctional uterine bleeding. When compared the patients with bleeding disorders and without bleeding disorders, bleeding from other sites, including gingival bleeding or epistaxis, low platelet counts and prolonged activated partial thromboplastin time were found statistically more frequent in patients with bleeding disorders (p < 0.05). Menorrhagia in adolescents is frequently associated with underlying bleeding disorders. Adolescents with heavy menstrual bleeding and a history of nose or gingival bleeding should be evaluated for congenital bleeding disorders.
- Recurrent trichosporonosis with central nervous system involvement in an allogeneic hematopoietic stem cell transplant recipient. [CASE REPORTS]
- Transpl Infect Dis 2016 Jul 18.
Trichosporon is an ubiquitous yeast that has emerged as an opportunistic pathogen in the immunocompromised host. We describe a case of invasive trichosporonosis in an allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipient while on caspofungin antifungal prophylaxis. She developed disseminated trichosporonosis in the pre-engraftment period and was successfully treated with voriconazole. She later developed 2 further episodes of invasive trichosporonosis involving the central nervous system. This case highlights the challenges of managing trichosporonosis in allo-HSCT recipients and suggests the need for lifelong therapy in some patients. This article is protected by copyright. All rights reserved.
- Genetic features of myelodysplastic syndrome and aplastic anemia in pediatric and young adult patients. [JOURNAL ARTICLE]
- Haematologica 2016 Jul 14.
Clinical and histopathological distinction between the inherited versus acquired bone marrow failure or myelodysplastic syndromes is challenging. The identification of inherited bone marrow failure/ myelodysplastic syndromes is critical to inform appropriate clinical management. To investigate whether a subset of pediatric and young adults undergoing transplant for aplastic anemia or myelodysplastic syndrome have germline mutations in bone marrow failure/myelodysplastic syndrome genes, we performed a targeted genetic screen of samples obtained between 1990-2012 from children and young adults with aplastic anemia or myelodysplastic syndrome transplanted at the Fred Hutchinson Cancer Research Center. Mutations in inherited bone marrow failure/myelodysplastic syndrome genes were found in 5.1%(5/98) of aplastic anemia patients and 13.6%(15/110) of myelodysplastic syndrome patients. While the majority of mutations were constitutional, a RUNX1 mutation present in the peripheral blood at a fifty-percent variant allele fraction was confirmed to be somatically acquired in one myelodysplastic syndrome patient. This highlights the importance of distinguishing germline versus somatic mutations by sequencing DNA from a second tissue or from parents. Pathologic mutations were present in DKC1, MPL, and TP53 among the aplastic anemia cohort, and in FANCA, GATA2, MPL, RTEL1, RUNX1, SBDS, TERT, TINF2, and TP53 among the myelodysplastic syndrome cohort. Family history or physical examination failed to reliably predict the presence of germline mutations. This study shows that while any single specific bone marrow failure/myelodysplastic syndrome genetic disorder is rare, screening for these disorders in aggregate identifies a significant subset of patients with inherited bone marrow failure/myelodysplastic syndrome.