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Volume 57, Issue 4
Displaying 1-19 of 19 articles from this issue
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[in Japanese], [in Japanese], [in Japanese], [in Japanese], [in Japane ...2016 Volume 57 Issue 4 Pages 395
Published: 2016
Released on J-STAGE: May 07, 2016
JOURNAL RESTRICTED ACCESSDownload PDF (3402K)
The 77th Annual Meeting of the Japanese Society of Hematology
Symposium 7
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Hidesaku ASAKURA2016 Volume 57 Issue 4 Pages 397-404
Published: 2016
Released on J-STAGE: May 07, 2016
JOURNAL RESTRICTED ACCESSDisseminated intravascular coagulation (DIC) is a pathological state in which varying degrees of fibrinolytic activation are seen simultaneously as systemic, persistent, and marked coagulation activation in the presence of an underlying disease. Suppressed-fibrinolytic-type DIC usually develops in patients with sepsis. Coagulation activation is severe, while fibrinolytic activation is mild. Enhanced-fibrinolytic-type DIC usually occurs with acute promyelocytic leukemia (APL). Both coagulation activation and fibrinolytic activation are severe in affected patients. Balanced-fibrinolytic-type DIC is usually seen in patients with solid tumors, and has a pathogenesis intermediate between those of the two aforementioned types. In animal DIC models, lipopolysaccharide (LPS)-induced forms of DIC are similar to suppressed-fibrinolytic-type DIC, whereas models of tissue factor (TF)-induced DIC have features similar to those of enhanced-fibrinolytic/balanced-fibrinolytic DIC. We are moving in the direction of more appropriate selection of treatment based on DIC type.View full abstractDownload PDF (1077K) -
Takashi ITO2016 Volume 57 Issue 4 Pages 405-411
Published: 2016
Released on J-STAGE: May 07, 2016
JOURNAL RESTRICTED ACCESSThrombosis is generally considered to be harmful because it compromises the blood supply to organs. However, recent studies have suggested that thrombosis during infection might play a physiological role in the early immune defense against invading microorganisms. This defensive role of thrombosis is now referred to as immunothrombosis. Detection of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) by immune cells triggers tissue factor expression and neutrophil extracellular trap (NET) release, promoting immunothrombosis. Sepsis-associated disseminated intravascular coagulation (DIC) is considered to be an advanced stage of pathological immunothrombosis, in which the immune system is no longer able to restrict the spread of pathogens, inflammation, and coagulation. In this stage, thrombosis is detrimental in part because it causes multiple organ failure. Recombinant thrombomodulin (rTM) is a therapeutic option for the treatment of sepsis-associated DIC in Japan. rTM binds thrombin, and switches its substrate specificity from coagulation factors V, VIII, and XIII to anticoagulant protein C. In addition to the activated protein C (APC)-dependent anticoagulant action, rTM has APC-independent anti-inflammatory actions, i.e., the sequestration of PAMPs and DAMPs. Thus, rTM is useful for resolving PAMP-and DAMP-mediated DIC, although further studies are needed to confirm the effectiveness of rTM in terms of clinical outcomes.View full abstractDownload PDF (2270K)
Symposium 8
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Yoshikane KIKUSHIGE2016 Volume 57 Issue 4 Pages 412-416
Published: 2016
Released on J-STAGE: May 07, 2016
JOURNAL RESTRICTED ACCESSAcute myeloid leukemia (AML) originates from self-renewing leukemic stem cells (LSCs), an ultimate therapeutic target for AML. We previously reported that the T-cell immunoglobulin mucin-3 (TIM-3) is expressed on the LCS surface in most types of AML. Since only the TIM-3+, i.e. not the TIM-3-, fraction of human AML cells can reconstitute human AML in immunodeficient mice, we hypothesized that the TIM-3 has an essential function in maintaining AML LSCs. Herein, we show that TIM-3 and its ligand, galectin-9 (Gal-9), constitute an autocrine loop critical for human AML LSC development. Serum Gal-9 was significantly elevated in primary AML patients and in mice xenografted with human AML. Neutralization of Gal-9 inhibited xenogeneic reconstitution of human AML, as well as Gal-9 ligation of TIM-3 co-activated NF-κB and β-catenin signaling, suggesting that TIM-3 signaling is necessary for LSC self-renewal. Interestingly, identical changes were found to be involved in the progressive transformation of a variety of pre-leukemic disorders into myeloid leukemia. Thus, molecules constituting the TIM-3/Gal-9 autocrine loop are potential therapeutic targets applicable to most types of myeloid leukemia.View full abstractDownload PDF (715K)
The 76th Annual Meeting of the Japanese Society of Hematology
Young Investigator's Award of JSH
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Keisuke KATAOKA, Seishi OGAWA2016 Volume 57 Issue 4 Pages 417-424
Published: 2016
Released on J-STAGE: May 07, 2016
JOURNAL RESTRICTED ACCESSAdult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy associated with HTLV-1 infection. To decipher the genetic landscape of ATL, we performed an integrated molecular analysis, which included whole-genome, whole-exome, transcriptome and targeted sequencing, as well as array-based copy number and methylation analyses. The somatic alterations are highly enriched for T-cell receptor/NF-κB signaling, the G-protein coupled receptor associated with T-cell migration, and other T-cell-related pathways as well as immune surveillance related genes. Among these, PLCG1, PRKCB, CARD11, VAV1, IRF4, CCR4, and CCR7 activating mutations and CTLA4-CD28 and ICOS-CD28 fusion genes have been identified. In addition, these genes significantly overlap with HTLV-1 Tax interactome. These results provide an important basis for the development of new ATL diagnostics and therapeuticsregimens.View full abstractDownload PDF (2543K) -
Kazutoshi IIJIMA, Nobutaka KIYOKAWA2016 Volume 57 Issue 4 Pages 425-429
Published: 2016
Released on J-STAGE: May 07, 2016
JOURNAL RESTRICTED ACCESSThe 5-year survival rate of patients with childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) now exceeds 90%, though there are still patients who fail to achieve remission or relapse early. To improve the outcomes of these cases, new diagnostic markers for stratification of those with unfavorable outcomes and novel targets for treatment have been investigated based on data from the OMICs analysis. We performed gene expression analysis of leukemic cells from 91 near-diploid BCP-ALL cases without specific fusion genes enrolled in Tokyo Children's Cancer Study Group (TCCSG)-L0416 & L0616 clinical trials employing the Affymetrix Human Genome U133 Plus 2.0 Array. Among them, DNA methylation status was analyzed in 24 cases by using the Infinium HumanMethylation450 BeadChip. Herein, initially, the current situations of gene expression analysis and DNA methylation analysis of childhood BCP-ALL are reviewed. Then, our analyses of gene expressions and DNA methylation related to the prognosis of childhood ALL without fusion genes are presented.View full abstractDownload PDF (670K) -
Tetsuichi YOSHIZATO2016 Volume 57 Issue 4 Pages 430-439
Published: 2016
Released on J-STAGE: May 07, 2016
JOURNAL RESTRICTED ACCESSAcquired aplastic anemia (AA) is a prototype of idiopathic bone marrow failure, which is caused by immune-mediated destruction of hematopoietic progenitors but is also characterized by frequent evolution to clonal myeloid disorders, such as myelodysplastic syndromes or acute myeloid leukemia. However, the chronological behavior of the clonality and its link to myelodysplastic syndrome or acute myeloid leukemia has not been fully explored. To define the clonality and its chronological behavior in AA, we performed targeted sequencing (N=439) in cases with AA. Somatic mutations were detected in 1/3 of our cases. Mutations were most frequently found in DNMT3A, followed by BCOR, PIGA and ASXL1. The prevalence of mutations increased with age. The clone sizes in DNMT3A and ASXL1 were prone to increase, whereas those of BCOR and PIGA were more likely to decrease or remain stable. Mutations in PIGA, BCOR and BCORL1 correlated with a better response to immunosuppressive therapy and more favorable survival. On the other hand, other mutations were associated with worse outcomes. The chronological dynamics of clonality showed marked variability and were not necessarily associated with prognosis.View full abstractDownload PDF (2193K)
Case Reports
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Yasuhiro KAZUMA, Yuichiro ONO, Noboru YONETANI, Yukihiro IMAI, Manabu ...2016 Volume 57 Issue 4 Pages 440-444
Published: 2016
Released on J-STAGE: May 07, 2016
JOURNAL RESTRICTED ACCESSA 19-year-old woman complaining of fever and a sore throat was diagnosed with very severe aplastic anemia (AA) by bone marrow examination at a local hospital. Despite administration of antibiotics and granulocyte-colony stimulating factor to treat the soft tissue infection in her neck, her neutrophil count showed no increase. Because emergent allogeneic stem cell transplantation (SCT) was necessary, she was referred to our hospital. On admission, computed tomography revealed right-sided severe pharyngitis and lymphadenitis causing tracheal stenosis, and emergent intubation was required the next day. Granulocyte transfusion therapy (GTX) from related donors coupled with broad-spectrum antibiotic administration controlled the otherwise overwhelming infection. The patient received allogeneic peripheral blood SCT using a reduced-intensity conditioning regimen. After allogeneic SCT, successful engraftment was obtained. She was discharged from the hospital 59 days after allogeneic SCT. She remains alive and well, as of the latest follow up. This case clearly demonstrates that GTX is useful for controlling severe infection and enables patients with severe AA to receive allogeneic SCT safely.View full abstractDownload PDF (1688K) -
Taro KURIHARA, Masahiko SUMI, Hiroko KAIUME, Wataru TAKEDA, Takehiko K ...2016 Volume 57 Issue 4 Pages 445-450
Published: 2016
Released on J-STAGE: May 07, 2016
JOURNAL RESTRICTED ACCESSA 79-year-old woman was admitted with a 5-kg weight loss and anorexia. Computed tomography showed diffuse lymphadenopathy, and thickening of the duodenal and ileal walls. The patient then underwent biopsy of these sites. Pathological examination revealed duodenal Epstein-Barr virus (EBV)-positive peripheral T cell lymphoma-not otherwise specified (PTCL-NOS) and EBV-negative ileal diffuse large B-cell lymphoma (DLBCL) to be present simultaneously. Combination chemotherapy including rituximab produced a reduction of the duodenal EBV-positive PTCL-NOS lesion, but had no effect on the EBV-negative ileal DLBCL lesion. Thereafter, new lymphadenopathy, high fever, and lactate dehydrogenase (LD) elevation developed, complicated by pneumonia. The patient died due to rapid deterioration of the lymphoma and pneumonia on day 108 after initiation of treatment. EBV-positive PTCL-NOS is reportedly rare and the prognosis is poor. Moreover, EBV-negative ileal DLBCL was diagnosed simultaneously. This case is considered to have had an extremely rare discordant lymphoma, although the exact etiology of its development remains unknown. We speculate that age-related disorders of the immune system and HCV infection may have been associated with the pathogenic mechanism of lymphomagenesis in this case.View full abstractDownload PDF (2579K) -
Kunio YANAGISAWA, Yoshiyuki OGAWA, Takeki MITSUI, Hiroyuki NOGUCHI, Hi ...2016 Volume 57 Issue 4 Pages 451-455
Published: 2016
Released on J-STAGE: May 07, 2016
JOURNAL RESTRICTED ACCESSAlthough acquired hemophilia A (AHA) often develops in patients with neoplasms, there are few reports on the efficacy of radiation therapy during the bleeding phase of AHA in the prior literature. We herein present a case of AHA experiencing remission soon after radiation therapy for esophageal cancer. A man in his seventies, who had a history of radical nephrectomy for left renal cell carcinoma, received a diagnosis of esophageal cancer. Three months later, he noticed a right thigh hematoma, and was transferred to our hospital. Laboratory data revealed a marked reduction of coagulation factor VIII (FVIII) activity at 0.9% and the inhibitor to FVIII was detected in his serum at 21.8 BU/ml. Under a diagnosis of AHA, the patient received high-dose oral prednisolone, which failed to achieve disease remission. He then underwent radiation therapy to eradicate the underlying esophageal cancer. Despite tapering of the prednisolone dosage, FVIII inhibitor declined to undetectable levels. In this case, radiation therapy for the underlying cancer was associated with achieving complete remission of AHA.View full abstractDownload PDF (983K) -
Yoshiyuki OGAWA, Kunio YANAGISAWA, Takuma ISHIZAKI, Chiaki NAITO, Masa ...2016 Volume 57 Issue 4 Pages 456-460
Published: 2016
Released on J-STAGE: May 07, 2016
JOURNAL RESTRICTED ACCESSAcquired hemophilia A (AHA) is a rare coagulation disorder caused by autoantibodies against coagulation factor VIII (FVIII). We report herein a very rare case of AHA complicated by immune thrombocytopenia (ITP). A 30-year-old woman was hospitalized with severe thrombocytopenia. Her platelet count was 5,000/μl on admission, at which time APTT was normal. ITP was diagnosed and she was treated with γ-globulin, platelet transfusion, and prednisolone at 1 mg/kg/day. She was discharged after platelet count normalization and prednisolone was tapered to 5 mg/day. During the prednisolone tapering, purpura appeared on both thighs and in the left inguinal region, and APTT was found to be prolonged. She was referred to our hospital for examination of APTT prolongation. FVIII activity was markedly decreased to 7.7% and the FVIII inhibitor was positive (1.5 BU/ml), based on which AHA was diagnosed. We carefully followed this patient without intensification of immunosuppressive therapy for 7 weeks, but her platelet count decreased from 150,000/μl to 70,000/μl and the FVIII inhibitor increased to 4 BU/ml. We therefore increased prednisolone to 30 mg/day, after which her platelet count increased and complete remission of AHA was achieved by day 42. In addition, we examined the relationship of the FVIII inhibitor and FVIII binding antibody in this case.View full abstractDownload PDF (823K) -
Shuhei KUROSAWA, Noriko DOKI, Satoshi KAITO, Masahiro SAKAGUCHI, Kaito ...2016 Volume 57 Issue 4 Pages 461-466
Published: 2016
Released on J-STAGE: May 07, 2016
JOURNAL RESTRICTED ACCESSA 53-year-old woman was admitted with right upper-extremity pain and multiple subcutaneous masses. Bone marrow aspirate showed hypercellular marrow with increased myeloid components at all stages of maturation. Cytogenetic analysis of the bone marrow revealed 100% Philadelphia chromosome positivity along with BCR/ABL gene rearrangement, as demonstrated by polymerase chain reaction (PCR). A diagnosis of chronic phase of chronic myeloid leukemia (CML) was therefore made. Biopsy of one of the subcutaneous masses showed proliferation of granulocytes in various stages of differentiation. There were also erythroid cells and megakaryocytes, without p53 and CD34-positive blasts. These results suggested that the subcutaneous masses had developed from extramedullary hematopoiesis, not blastomas. The patient was administered dasatinib (DA) 140 mg, combined with radiation therapy for pain and peripheral neuropathy from the right axial extramedullary tumor. The patient showed complete hematological remission and the subcutaneous masses had disappeared 1 month after starting administration of DA. Because the patient did not achieve a cytogenetic response, the tyrosine kinase inhibitor nilotinib was administered. She will undergo allogeneic stem cell transplantation in the near future. Extramedullary hematopoiesis in the early stages of CML is uncommon. Our case emphasizes the need to elucidate the pathogenesis of extramedullary hematopoiesis in the early stages of CML.View full abstractDownload PDF (1634K) -
Megumi AKIYAMA, Kota YOSHIFUJI, Tetsuya FUKUDA, Shuji TOHDA, Tohru MIK ...2016 Volume 57 Issue 4 Pages 467-471
Published: 2016
Released on J-STAGE: May 07, 2016
JOURNAL RESTRICTED ACCESSAn 80-year-old man with autoimmune hemolytic anemia (AIHA) received immunosuppressive therapy with prednisolone (1 mg/kg). One month later, his hemoglobin level had normalized, and the prednisolone dose was tapered. The next day, he complained of acute and progressive back pain. He was admitted to our hospital for further examination approximately 24 h after the pain had started. Computed tomography revealed only localized pneumonia. However, he showed signs of severe disseminated intravascular coagulation (DIC), liver dysfunction, and respiratory failure. Empiric broad-spectrum antibacterial therapy was started with a presumptive diagnosis of severe bacterial infection. However, his condition rapidly deteriorated, and he died 17 h after admission. Varicella-zoster virus (VZV) was detected by quantitative PCR in the peripheral blood sample and by immunohistochemistry in all organs except for the brain at autopsy. Visceral VZV infection is a severe disease with a high mortality rate. Although appropriate diagnosis and treatment is crucial, in cases without the characteristic skin rash the diagnosis is difficult. The possibility of visceral VZV infection should be taken into consideration when administering prednisolone to patients with AIHA.View full abstractDownload PDF (1803K) -
Sakiko HARADA, Hiromi HAYASHI, Noriyuki TADERA, Kannichi IWAMA, Kouich ...2016 Volume 57 Issue 4 Pages 472-476
Published: 2016
Released on J-STAGE: May 07, 2016
JOURNAL RESTRICTED ACCESSWe experienced two cases of peripheral neuropathy in the early phase following cord blood transplantation. Case 1 was a 66-year-old man with recurrent T-ALL. On day 8, he experienced a sharp pain originating in both the palms and the soles, which worsened spreading to the knees, and was accompanied by muscle weakness. The neurological symptom progressed to the point of being unable to walk. A nerve conduction velocity test showed demyelination and axonopathy. In the CSF analysis, albuminocytologic dissociation and a rise in myelin basic protein were detected. These findings met the diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP). The symptoms improved with intravenous immunoglobulin (IVIG). He is now able to walk and continues to visit our department. Case 2 was a 42-year-old man with primary mediastinal large B-cell lymphoma. As the disease was refractory, he underwent reduced intensity cord blood transplantation (RICBT). Flare and numbness started in the palms and soles on day 26, with the symptoms progressing thereafter. A nerve conduction velocity test showed demyelination and axonopathy. The symptoms improved after IVIG administration. The diagnosis of peripheral neuropathy after transplantation is often difficult, but when an immunologic disorder is suspected to be the cause, early administration of IVIG may be effective.View full abstractDownload PDF (1803K) -
Keiki KAWAKAMI, Ryugo ITO, Yuki KAGEYAMA, Keiki NAGAHARU, Takanori YAM ...2016 Volume 57 Issue 4 Pages 477-482
Published: 2016
Released on J-STAGE: May 07, 2016
JOURNAL RESTRICTED ACCESSSuperior sagittal sinus thrombosis (SSST) is a very rare but life-threatening complication in leukemia patients. SSST is very rare in acute myeloid leukemia (AML). In leukemia patients, several risk factors for SSST have been reported such as administration of L-asparaginase, disseminated intravascular coagulation, congenital thrombophilia, meningeal leukemia, and intrathecal chemotherapy (IT). Lumbar puncture itself and corticosteroid administration have also been acknowledged as risk factors. We describe herein our clinical experience with SSST in a 29-year-old Japanese man suffering from AML with t(8;21)(q22;q22), who presented with abrupt onset of loss of consciousness, left hemiplegia, and seizure soon after IT and high-dose cytarabine (HD-AraC) with dexamethasone for post remission consolidation. Despite the presence of intracranial hemorrhage (ICH) due to SSST rupture, we conducted anticoagulant therapy with heparin. Although ICH worsened temporarily, his clinical condition gradually improved with resolution of the SSST, and he eventually became fully ambulatory. There were no deficiencies of natural anticoagulants. Three additional cycles of HD-AraC without IT therapy were conducted, but no neurological complications recurred with the concomitant use of warfarin. He was discharged free of neurological deficits. In our case, there is a possibility that IT and the administration of corticosteroids along with HD-AraC triggered SSST.View full abstractDownload PDF (967K) -
Mayumi HATSUSE, Shin-ichi FUCHIDA, Akira OKANO, Satoshi MURAKAMI, Chih ...2016 Volume 57 Issue 4 Pages 483-488
Published: 2016
Released on J-STAGE: May 07, 2016
JOURNAL RESTRICTED ACCESSCase: A 71-year-old woman had been diagnosed as having osteosclerotic myeloma (BJP-λ type) three years prior to the current presentation, based on tumor biopsy from the forehead showing plasmacytoma with systemic osteosclerotic lesions. At 71 years of age, she underwent transverse colectomy for a tumor in the hepatic flexure of the large intestine, and it was diagnosed as IgH/CCND-1-positive plasmacytoma of the large intestine. Although serum vascular endothelial cell growth factor (VEGF) was not elevated, the plasmacytoma was largely positive for VEGF staining. She subsequently experienced transformation to aggressive myeloma over a short period of time. Osteosclerotic myeloma is a rare disease that accounts for less than 3% of all myelomas, and requires differentiation from POEMS syndrome. In this case, peripheral nerve symptoms, which are necessary for the diagnosis of POEMS syndrome, were not confirmed. Thus, this case was diagnosed as having osteosclerotic myeloma. By contrast, abnormal IgH/CCND-1 is confirmed in 15% of patients with myeloma, and 25% of those with POEMS syndrome. While it is unclear whether this genetic abnormality is involved in the development of an osteosclerotic lesion, it is expected that data from patients with osteosclerotic myeloma and POEMS syndrome will be accumulated in the future, allowing clarification of the relationship between the genetic abnormality and osteosclerosis.View full abstractDownload PDF (3165K)
Short Reports
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Michiko YAMADA, Hiroyuki KURODA, Saori SHIMOYAMA, Ryo ITO, Yusuke SUGA ...2016 Volume 57 Issue 4 Pages 489-491
Published: 2016
Released on J-STAGE: May 07, 2016
JOURNAL RESTRICTED ACCESSMuscle cramps are side effects commonly associated with tyrosine kinase inhibitor (TKI) treatment. Patients suffering from muscle cramps are treated with various medications such as calcium, magnesium and vitamin supplements, but these therapies are often ineffective. We report two patients with chronic myelogenous leukemia who developed muscle cramps caused by TKI. These patients were treated successfully with levocarnitine. Both of our cases revealed the beneficial effects of levocarnitine treatment on TKI-induced muscle cramps.View full abstractDownload PDF (679K)
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2016 Volume 57 Issue 4 Pages 496-499
Published: 2016
Released on J-STAGE: May 07, 2016
JOURNAL RESTRICTED ACCESSDownload PDF (674K)
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2016 Volume 57 Issue 4 Pages 500-501
Published: 2016
Released on J-STAGE: May 07, 2016
JOURNAL RESTRICTED ACCESSDownload PDF (622K)
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