Journal of Hematopoietic Cell Transplantation
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Volume 5 , Issue 3
Showing 1-7 articles out of 7 articles from the selected issue
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Review
  • Yasushi Ishida
    Volume 5 (2016) Issue 3 Pages 51-63
    Released: July 15, 2016
    JOURNALS FREE ACCESS
     The quality of life (QOL) of pediatric patients that undergo stem cell transplantation (SCT) and the late effects they experience have become more important issues because of improvements in the survival of such patients. The late effects seen in such cases were attributed to 2 major causes: conditioning treatment and chronic graft-versus-host disease (GVHD). More than 40% of the surviving SCT-treated patients were underweight and of short stature, which was twice as high as the equivalent value for the no SCT group. Late effects were observed in 78% of the patients in the SCT group and 45% of those in the no SCT group. Lung toxicity was found to be a common cause of morbidity and mortality after SCT. Many of the children that underwent SCT developed endocrinological dysfunction, including growth hormone and thyroid hormone deficiencies, and gonadal damage and infertility occurred frequently after myeloablative SCT. Persistent secondary immunodeficiency was observed in all of the children with SCT; therefore, post-transplantation re-immunization is indispensable in such patients. The cumulative probability of secondary solid tumors increases after SCT, and the incidence of such tumors is associated with chronic GVHD and radiotherapy. The number of studies examining the QOL of pediatric survivors of SCT is growing. The results of the present study confirm that children that receive SCT should undergo long-term follow-up.
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  • Junichi Sugita
    Volume 5 (2016) Issue 3 Pages 64-73
    Released: July 15, 2016
    JOURNALS FREE ACCESS
     Allogeneic hematopoietic stem cell transplantation is a potentially curative treatment for patients with hematological malignancies and nonmalignant diseases. HLA-matched related or unrelated donors are the first choice but are not always available for all patients. Alternative donors who share a single HLA haplotype (HLA-haploidentical donors) with recipients are nearly always available, but HLA-haploidentical stem cell transplantation is associated with high incidences of graft-versus-host disease (GVHD) and graft rejection. Over the last few decades, several strategies have been developed to overcome HLA barriers.
     The most popular strategy has been T cell depletion of stem cell grafts; ex vivo T-cell depletion by CliniMACS®; in vivo T-cell depletion by antithymocyte globulin or alemtuzumab. However, these strategies are associated with an increased risk of severe opportunistic infections and nonrelapse mortality. More recently, T cell replete haploidentical transplantation has been developed by using post-transplant cyclophosphamide. The rationale of this strategy is selective depletion of alloreactive T cells. The incidence of acute GVHD, chronic GVHD, and NRM after PTCy-based haploidentical stem cell transplantation appears to be equivalent to those after HLA-matched stem cell transplantation.
     Together with progress of these platforms, HLA-haploidentical transplantation is becoming a novel breakthrough.
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  • Masanori Matsumoto
    Volume 5 (2016) Issue 3 Pages 74-81
    Released: July 15, 2016
    JOURNALS FREE ACCESS
     Thrombotic microangiopathy (TMA) is microvascular occlusive disorder characterized by thrombocytopenia, hemolytic anemia, and systemic or intrarenal platelet-rich thrombi. In addition to the two major forms of TMA, thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), transplantation-associated TMA (TA-TMA) is a well-recognized complication of hematopoietic stem cell transplantation. Acquired TTP is associated with a deficiency in ADAMTS13 caused by the production of autoantibodies. Despite the initial identification of TA-TMA as TTP, it is not associated with ADAMTS13 deficiency and it is largely unresponsive to plasma exchange compared to TTP. Currently, the pathogenesis of TA-TMA is not well understood. However, endothelial cell injury caused by graft-versus-host disease, chemoradiotherapy, infection, and calcineurin inhibitors were all implicated for their crucial roles in pathogenesis of this disease. Although a standard treatment strategy of TA-TMA has not yet been established, it is clear that early diagnosis and treatment improve prognosis. There is a consensus that calcineurin inhibitors should be discontinued and replaced with an alternate immunotherapy. In a small retrospective study to identify novel therapies for TA-TMA, recombinant soluble thrombomodulin, rituximab, and eculizumab were reported as putative alternative treatments.
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Original Article
  • Rie Goi, Katsutsugu Umeda, Koji Kawaguchi, Atsushi Iwai, Masamitsu Mik ...
    Volume 5 (2016) Issue 3 Pages 82-86
    Released: July 15, 2016
    JOURNALS FREE ACCESS
     We retrospectively analyzed the arrangement of human leukocyte antigen (HLA) testing, the final decision about donation, and the clinical outcome of allogeneic hematopoietic stem cell transplantation (HSCT), which was planned to be performed from a related donor as the first candidate between 1995 and 2015 in our hospital. Of fifty-nine candidates (35 siblings and 24 parents), 54 were eventually selected as HSCT donors. However, HSCT was not performed from four siblings (11.4%) and one parents (4.2%). Four candidates were replaced by alternative donors due to the donor health problems, intention of the donors or their family members, or to avoid HSCT from a carrier of a congenital disease. HSCT from the other candidate was canceled because the patient did not consent to HSCT. Peripheral blood stem cell harvesting was performed instead of bone marrow harvesting in two other donors due to their health problems. The physical and psychological eligibility of donor candidates, appropriate for their age, should be sufficiently examined. Furthermore, informed consent should be obtained from pediatric donor candidates and their family before HLA testing to avoid the unnecessary pain.
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  • Masahiro Sekiguchi, Yuki Arakawa, Tomoo Osumi, Kiyotaka Isobe, Junko T ...
    Volume 5 (2016) Issue 3 Pages 87-92
    Released: July 15, 2016
    JOURNALS FREE ACCESS
     Tacrolimus is usually administered continuously through one lumen of a double-lumen central venous catheter (CVC) in allogeneic hematopoietic stem cell transplantation. Although blood samples for therapeutic drug monitoring are taken through the other CVC lumen in children, the drug-concentration result is often falsely elevated. In order to reduce measurement errors obtained when collecting blood samples through a CVC, we retrospectively compared two blood-sampling methods: the standard method and a “flushing method,” in which the lumen is flushed with 5 mL saline before drawing blood. The flushing method significantly reduced measurement errors (median Rc [the ratio of the drug concentration measured in the blood sample collected through the CVC to that collected using venipuncture], 1.019 vs 1.142; p=1.8×10−10). In conclusion, the flushing method was an effective and more accurate means of monitoring blood concentration without the need for frequent venipuncture.
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  • Akihiro Ohmoto, Shigeo Fuji, Akiko Miyagi-Maeshima, Kinuko Tajima, Tak ...
    Volume 5 (2016) Issue 3 Pages 93-101
    Released: July 15, 2016
    JOURNALS FREE ACCESS
     It is still unclear what factors are associated with a poor prognosis after ASCT for relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The study cohort included 43 patients with relapsed or refractory DLBCL who underwent ASCT. Biopsy specimens were immunohistochemically analyzed for CD10, BCL6, MUM1, BCL2, and MYC. Thirty-seven patients (86%) received rituximab before ASCT, and the age-adjusted International Prognostic Index (aaIPI) at relapse was 2-3 in 18 patients (42%). Immunohistochemical analysis showed that 88% of samples were of the non-GCB type, and concurrent expression of BCL2 and MYC was observed in 59% of samples at diagnosis. The probability of 3-year overall survival (OS) was 65%. The poor prognostic factors for OS were aaIPI 2-3 at relapse (hazard ratio [HR], 4.1; 95% confidence interval [CI], 1.4-12.4) and no rituximab before ASCT (HR, 6.6; 95%CI, 2.1-20.9). The 3-year relapse incidence was 43%, and 2 factors were also significant risk factors for relapse (high aaIPI: HR, 3.0; 95%CI, 1.1-7.9 and no rituximab before ASCT: HR, 9.2; 95%CI, 3.6-23.3). In the rituximab era, novel treatment strategies might be required in DLBCL patients with high aaIPI at relapse.
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Case Report
  • Minako Tokunaga, Takuro Nishikawa, Takanari Abematsu, Shunsuke Nakagaw ...
    Volume 5 (2016) Issue 3 Pages 102-106
    Released: July 15, 2016
    JOURNALS FREE ACCESS
     We herein describe a 7-year-old male with refractory acute myeloid leukemia who relapsed 9 months after bone marrow transplantation from human leukocyte antigen (HLA) -identical sibling. He received 2 cycles of FLAG chemotherapy, however, complete remission was not obtained. In addition, sepsis due to viridans group streptococci occurred in 2 of 2 courses of chemotherapy. He underwent haploidentical peripheral blood stem cell transplantation (haploPBSCT) from his father. The conditioning regimen consisted of fractionated total body irradiation (9.9 Gy) and fludarabine (120 mg/m2). Tacrolimus, mycophenolate mofetil, and posttransplant cyclophosphamide (PTCy) (50 mg/kg×2) were administered for the prophylaxis of graft versus host disease (GVHD). The patient developed a fever on day 1, which was promptly resolved with PTCy. On day 18, myeloid engraftment was achieved. The patient developed grade I acute GVHD and mucositis. A fourth CR was obtained for 1 month after haploPBSCT. On day 180, he has been in continuous remission while maintaining his quality of life (QOL). Although the use of haploPBSCT with PTCy has been limited in children, this strategy may be potentially less toxic and helpful to maintain or improve the QOL of patients.
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