Hematology AND Aplastic anemia [keywords]
- [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.
- Comparable Allogeneic Hematopoietic Cell Transplantation Outcome of a Haplo-Identical Family Donor with an Alternative Donor in Adult Aplastic Anemia. [JOURNAL ARTICLE]
- Acta Haematol 2016 Jul 14; 136(3):129-139.
We performed a study on allogeneic hematopoietic cell transplantation (alloHCT) from an HLA-haplo-identical familial donor (haploFD) using a busulfan-fludarabine-antithymocyte globulin conditioning regimen for severe aplastic anemia (sAA) and hypoplastic myelodysplastic syndrome. For the comparison between a haploFD and an alternative donor (AD; matched unrelated or partially matched donor) for sAA in adults, we collected haploFD data retrospectively and prospectively. Forty-eight AD cases were selected for the comparison with 16 haploFD cases. All transplantation outcomes except for extensive chronic graft versus host disease (GvHD) were similar. The frequencies of hepatic sinusoidal obstruction syndrome (p = 1.000), acute GvHD (p = 0.769), grade 3/4 acute GvHD (p = 0.258), chronic GvHD (p = 0.173), extensive chronic GvHD (p = 0.099), primary neutrophil engraftment failure (p = 1.000), secondary graft failure (p = 1.000) and platelet engraftment failure (p = 0.505) were similar. Time to neutrophil engraftment was faster in haploFD (p = 0.003), while the cumulative incidence of platelet engraftment was similar (p = 0.505). Overall survival was also similar between AD and haploFD (p = 0.730). In conclusion, alloHCT from haploFD in sAA was comparable with alloHCT from AD, but extensive chronic GvHD seemed frequent in haploFD. Therefore alloHCT from haploFD could be an alternative approach for alloHCT from AD in adult sAA.
- Leukemic Transformation of Severe Aplastic Anemia Following Matched Allogenic Stem Cell Transplantation, Transplanted Again in CR 1. [Journal Article]
- Indian J Hematol Blood Transfus 2016 Jun; 32(Suppl 1):223-7.
Aplastic anemia (AA) is a life-threatening bone marrow failure disorder, if untreated, is associated with very high mortality. Allogenic bone marrow transplantation (BMT) is the standard of care for severe aplastic anemia (SAA) patients those who are younger than 40 years of age. The development of secondary malignancies in post-BMT setting for AA is a rare, however, well documented phenomenon. Among the secondary malignancies, development of acute myeloid leukemia is even rarer entity. Here we report a case of acute myeloid leukemia following human leucocyte antigen (HLA) matched sibling peripheral blood stem cell transplant (PBSCT) in a case of SAA. The patient achieved complete remission (CR) following chemotherapy and in CR1, a second HLA matched PBSCT from a different donor was offered. The patient is presently in remission at day +180 post-PBSCT.
- A Comparison of Outcomes for Cord Blood Transplant and Unrelated Bone Marrow Transplant in Adult Aplastic Anemia. [JOURNAL ARTICLE]
- Biol Blood Marrow Transplant 2016 Jul 8.
Earlier reports suggested that umbilical cord blood transplant (UCBT) for aplastic anemia (AA) was feasible in alternative transplantation. To identify differences in outcomes of UCBT and HLA-matched or mismatched unrelated bone marrow transplant (UBMT) in adults with AA, we analyzed registry data of the Japan Society for Hematopoietic Cell Transplantation and compared results of UCBT (n=69) to 8/8 (n=101), 7/8 (n=65) or 6/8 (n=37) matched UBMT. The transplant period was from 2002 to 2012, and patients 16 years or older with AA were eligible. Median ages were 49, 35, 28 and 30 years for UCBT, 8/8, 7/8 and 6/8 UBMT. In multivariate analysis, risk of mortality was lower for 8/8 UBMT compared to UCBT (HR 0.55, 95% CI 0.32-0.94, P=0.029), adjusted for age and GVHD prophylaxis that were other associated factors. Mortality risks of 7/8 UBMT (HR 0.55, 95% CI 0.29-1.02) or 6/8 UBMT (HR 0.67, 95% CI 0.32-1.39) were not significantly different from UCBT. Risks of grade 3-4 acute and chronic GVHD were not different among four groups. The most prevalent cause of death was graft failure in UCBT and 6/8 matched UBMT, and infection in 8/8 and 7/8 matched UBMT. Under 40 years old, survival of UCBT was similar to UBMT (76, 79, 83, and 83%, at 3 years), adjusted for transplant period that was another associated factor; but for over 40 years, that of UCBT tended to be lower (47, 64, 64, 75%, at 3 years). To conclude, these data suggest that UCBT could be an alternative treatment option for younger adults when matched sibling or adequate UBMT donors are not available.
- Efficacy of rabbit antithymocyte globulin as first-line treatment of severe aplastic anemia: an Asian multicenter retrospective study. [JOURNAL ARTICLE]
- Int J Hematol 2016 Jul 4.
Due to the unavailability of horse antithymocyte globulin (ATG) in many markets worldwide, patients with severe aplastic anemia (SAA) are limited to the use of rabbit ATG. We aimed to analyze hematologic response and overall survival (OS) of Asian patients treated with rabbit ATG as first-line therapy of SAA. We retrospectively reviewed the medical records of 97 consecutive patients who received rabbit ATG as first-line treatment of SAA from 2006 to 2012 at centers in four Asian countries. The primary endpoint was 6- and 12-month overall response rates (ORR) for patients receiving rabbit ATG within the recommended dose range (2.5-3.75 mg/kg/day). Secondary endpoints included ORR in patients receiving any dose of rabbit ATG and 2-year OS. For patients who received rabbit ATG within the recommended dose range, 6- and 12-month ORRs were 17.4 and 63.6 %, respectively. For patients who received any dose of rabbit ATG, 6- and 12-month ORRs were 24.3 and 68.6 %, respectively. The 2-year OS rate was 86.3 %. Rabbit ATG is effective for treatment of SAA in Asian patients. The 12-month ORR and 2-year OS with rabbit ATG were comparable to historical results obtained with horse ATG.
- [Target cells of cytotoxic T cells in severe aplastic anemia in vitro]. [English Abstract, Journal Article]
- Zhonghua Yi Xue Za Zhi 2016 Jun 14; 96(22):1728-32.
To clarify the specific target of severe aplastic anemia (SAA) immune attack via identifying the target cells of cytotoxic T cell attacks and the expression of apoptosis ligand on each department and each stage of bone marrow hematopoietic cells.A total of 15 SAA patients and 15 normal controls were recruited in the Department of Hematology, Tianjin Medical University General Hospital between March 2011 and March 2012. Factor associated suicide(Fas) protein expression of CD34(+) , CD14(+) , CD33(+) , and GlycoA(+) cells in bone marrow was detected by flow cytometry. The CD8(+) T cells of SAA patients and CD3(-) bone marrow mononuclear cells (BMMNC) of controls were sorted by immunomagnetic separation and co-cultured for 72 hours. The apoptosis rate of CD34(+) , CD14(+) , CD33(+) , and GlycoA(+) cells were measured with flow cytometry.The expression of Fas protein in CD34(+) cells in SAA patients (46.59%± 27.60%) was significantly higher than that in control group (8.89%±7.28%, P<0.01). The expressions of Fas protein in CD14(+) , CD33(+) and GlycoA(+) cells in SAA group(29.29%±9.23%, 46.88%±14.30%, 15.15%±9.26%) were lower than those in control group(51.25%±38.36%, 72.06%±39.88%, 50.38%±39.88%, all P<0.05). The apoptosis rates of CD34(+) , CD33(+) and CD14(+) cells in the experimental group (CD8(+) T cells of SAA patients co-cultured with CD3(-) BMMNC of controls: 55.43%±20.50%, 38.13%±20.10%, 61.87%±21.65%)were significantly higher than those of the control group (CD8(+) T cells of controls co-cultured with CD3(-) BMMNC of controls: 35.02%±13.95%, 23.44%±10.33%, 37.04%±22.41%, all P<0.05).Cytotoxic T cells in SAA patients may have a killing effect on hematopoietic stem/progenitor cells, and granulocytic and macrophagocytic cells from normal bone marrow. Moreover, Fas/Fas ligand-mediated apoptosis may play an important role in the immune pathogenesis of SAA. CD34(+) cells show markedly increased Fas protein expression, which may be the main target cells in the process of immune injury in SAA patients.
- Haplo-identical transplantation for acquired severe aplastic anaemia in a multicentre prospective study. [JOURNAL ARTICLE]
- Br J Haematol 2016 Jun 28.
We conducted a prospective, multicentre study to confirm the feasibility of haplo-identical transplantation in treatment of severe aplastic anaemia (SAA) as salvage therapy, by analysing the outcomes of 101 patients who received haplo-identical transplantation between June 2012 and October 2015. All cases surviving for more than 28 d achieved donor myeloid engraftment. The median time for myeloid engraftment was 12 (range, 9-25) days and 15 (range, 7-101) days for platelets, with a cumulative platelet engraftment incidence of 94·1 ± 0·1%. With a median follow-up of 18·3 (3·0-43·6) months, recipients from haplo-identical transplantation had more cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD, 33·7% vs. 4·2%, P < 0·001), more chronic GVHD (22·4% vs. 6·6%, P = 0·014) at 1 year, but similar grade III-IV aGVHD (7·9% vs. 2·1%, P = 0·157), 3-year estimated overall survival (OS, 89·0% vs. 91·0%, P = 0·555) and failure-free survival (FFS, 86·8% vs. 80·3%, P = 0·659) when compared with 48 patients who received contemporaneous transplantation from matched related donors. Multivariate analysis showed no significant difference in engraftment and survival between the two cohorts. Both OS and FFS for the entire population correlated significantly with grades III-IV aGVHD. In conclusion, haplo-identical transplantation is a feasible choice for SAA with favourable outcomes.