Hiroaki Shimizu

Gunma University, Maebashi, Gunma Prefecture, Japan

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Publications (10)18.76 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Although the introduction of imatinib dramatically improved the outcomes for patients with Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukemia (Ph+BCP-ALL), the survival benefit of imatinib has not been assessed in the context of Ph+ mixed phenotype acute leukemia (Ph+MPAL). To clarify this important issue, we studied 42 Ph+ acute leukemia (Ph+AL) patients who received intensive chemotherapy and concurrent administration of imatinib. Of the 42 Ph+AL patients, 13 (31%) patients were categorized as Ph+MPAL (positive for both myeloid and B-cell lineage), 27 (64%) were categorized as Ph+BCP-ALL, and two (5%) were categorized as Ph+ acute myeloid leukemia. The complete remission rates after the initial induction therapy were not significantly different when comparing Ph+MPAL and Ph+BCP-ALL patients (100% vs. 85%, respectively, p = 0.14). Likewise, there were no significant differences in the 5-year overall survival (OS) or disease-free survival (DFS) rates when comparing the MPAL and BCP-ALL groups (OS: 55% vs. 53%, respectively, p = 0.87, DFS: 46% vs. 42%, respectively, p = 0.94). These findings suggest that concurrent imatinib administration with chemotherapy improved the outcomes of Ph+MPAL patients to the level seen in Ph+BCP-ALL patients and should, therefore, be considered as the standard therapy for these patients.This article is protected by copyright. All rights reserved.
    European Journal Of Haematology 04/2014; · 2.41 Impact Factor
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    ABSTRACT: Although studies have demonstrated a high prevalence of extramedullary (EM) relapse after allogeneic stem cell transplantation (allo-SCT) in patients with acute myeloid leukemia (AML), the prevalence of EM relapse has not been compared with that after chemotherapy. This study investigated the prevalence of EM relapse among 498 adult AML patients (median age, 57 years; range, 15-82 years) who underwent intensive chemotherapy. A total of 281 relapses occurred in 210 patients (36 after allo-SCT; 245 after chemotherapy), and 33 relapses (11.7%) were accompanied by EM disease. Among these relapses, EM disease was more frequently observed at relapse after allo-SCT than after chemotherapy (25% vs. 9%, respectively; p=0.008). Eight of 33 relapses after the first allo-SCT had EM disease, and only presence of extensive chronic graft-versus-host disease (GVHD) was identified as a predisposing factor for EM relapse. Additionally, the 1-year overall survival rate after relapse was not significantly different when comparing those with EM relapse and those with BM relapse (38% vs. 16%, respectively; p=0.279). These data suggest that AML patients undergoing allo-SCT should be closely followed for signs of EM relapse, especially those with extensive chronic GVHD.
    Leukemia research 09/2013; · 2.36 Impact Factor
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    ABSTRACT: The presence of pre-transplant anti-HLA antibodies in recipients of cord blood transplantation (CBT) is associated with failed engraftment. However, only a small number of studies have reported that recipient-derived anti-HLA antibodies persist after CBT and have potential impact on the outcome. Of 61 patients who underwent HLA-mismatched CBT at Saiseikai Maebashi Hospital, three patients were identified as having anti-HLA antibodies not corresponding to HLA antigens in the transplanted CB. All patients achieved successful engraftment. However, the three patients with the pre-transplant anti-HLA antibodies not corresponding to HLA antigens in the transplanted CB continued to produce these antibodies even after engraftment; the persistence of these antibodies served as a sensitive minimal residual disease (MRD) marker. In contrast, donor HLA-specific and newly produced third party antibodies were not detectable even after relapse. The persistence of anti-HLA antibodies even after engraftment may be a potential marker for MRD, but is not a significant factor in secondary humoral engraftment failure.
    International journal of hematology 03/2013; · 1.17 Impact Factor
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    ABSTRACT: OBJECTIVES: The categorization of T-cell acute lymphoblastic leukemia (T-ALL) into four subgroups according to the degree of thymic differentiation was proposed in 1995, and this categorization scheme has been described in the World Health Organization classification 4th edition with minor changes. The aim of this study is to explore the clinical significance of leukemia cell differentiation stages in patients with T-ALL. METHODS: We analyzed 36 adult T-ALL patients, including six patients (17%) in pro-T stage, 16 (44%) in pre-T stage, three (8%) in cortical-T stage, and 11 (31%) in medullary-T stage. Pro-T and pre-T stages were arbitrarily clustered as the immature group, and cortical-T and medullary-T stages as the mature group. RESULTS: Patients in the immature group had unique presentations, including lower lactate dehydrogenase levels, lower frequency of mediastinal tumor, and higher expression of myeloid antigens than the mature group. There was no difference in the treatment strategies between both groups. Although patients in the immature group had a lower complete remission (CR) rate when compared with the mature group (45% vs. 79%, respectively; P = 0.04), the 3-yr overall survival (OS) for both groups was comparable (27% vs. 38%, respectively; P = 0.66). Such discrepancy between the CR rates and the OS could be partially explained by survival benefit of allogeneic transplantation observed in the immature group but not in the mature group. CONCLUSIONS: These findings indicate that T-ALL patients can be categorized into two biologically distinctive subgroups according to the differentiation stages, and this stratification might enable prospective identification of patients with poor chemotherapy response.
    European Journal Of Haematology 02/2013; · 2.41 Impact Factor
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    ABSTRACT: To investigate the clinical significance of granulocytic sarcoma (GS) in adults with acute myeloid leukemia (AML), 434 consecutive patients with AML were analyzed retrospectively. Forty-five patients (10.4%) with GS at diagnosis were younger (P < 0.001), presented with higher white blood cell counts (P = 0.03) and were more likely to conform to French-American-British M4 (P = 0.001) and M5 (P = 0.045) classifications than those without GS. In contrast, no significant difference in frequency of cytogenetic abnormalities was found between the GS and non-GS groups. Treatment outcomes in 260 patients (40 with GS) who underwent intensive chemotherapy, excluding patients with acute promyelocytic leukemia, were investigated. Complete remission rates did not differ significantly between the GS and non-GS groups (75.0% vs 79.1%; P = 0.192, respectively) or the 5-year overall survival (OS) rates (39.9% vs 38.7%; P = 0.749, respectively). However, the GS group had a significantly higher relapse rate than the non-GS group (74.2% vs 55.3%; P = 0.048) and a significantly lower 5-year disease-free survival rate (8.2% vs 25.7%, respectively; P = 0.005). When considered together with the results of multivariate analysis, which identified the presence of GS as an independent predictor for disease-free survival time, these findings indicate that GS might identify a high-risk subset of patients with AML.
    Cancer Science 05/2012; 103(8):1513-7. · 3.53 Impact Factor
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    ABSTRACT: Post-transplant lymphoproliferative disorder (PTLD) is a fatal complication of allogeneic hematopoietic stem cell transplantation (HSCT) that is caused by reactivation of Epstein-Barr virus (EBV). A successful approach, monitoring EBV-DNA load in peripheral blood (PB) accompanied by preemptive rituximab therapy, has recently been reported. Here, we describe a 29-year-old woman who developed isolated central nervous system (CNS) PTLD. She received HSCT against acute myelogenous leukemia from a related human leukocyte antigen-haploidentical donor, following a conditioning regimen that included antithymocyte globulin. Tacrolimus and methylprednisolone were given as prophylaxis for graft-versus-host disease. On day +172, the patient's consciousness deteriorated. Magnetic resonance imaging showed six ring-enhanced lesions in the cerebral hemispheres. These tumors were diagnosed, via a craniotomy and tumorectomy, as PTLD. EBV-DNA load was elevated in the cerebrospinal fluid (CSF) but not detected in PB. She was treated with whole-brain irradiation and rituximab, and achieved partial remission of the tumors. This case serves as a reminder that vigilance is required regarding the development of isolated CNS PTLD; it is worth examining EBV-DNA replication in CSF for diagnosis even when the EBV-DNA load is negative in PB.
    International journal of hematology 11/2011; 94(5):495-8. · 1.17 Impact Factor
  • European Journal Of Haematology 09/2011; 88(2):181-2. · 2.41 Impact Factor
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    ABSTRACT: Antibody (Ab)-mediated pure red cell aplasia (PRCA) is a rare but important side effect in patients with chronic kidney disease who receive recombinant human erythropoietin (rhEPO). Ab-mediated PRCA was first reported in the 1990s, and the incidence subsequently increased and reached a peak in 2001. After improvements in rhEPO products and the administration route, the incidence was reduced by 90%, and now Ab-mediated PRCA only develops in a limited number of patients who receive rhEPO subcutaneously for a long period. We describe here the clinical course of one such rare patient with Ab-mediated PRCA. The patient was a 70-year-old man with chronic renal failure secondary to diabetic nephropathy. He had not received rhEPO therapy before the initiation of hemodialysis. He started hemodialysis and began to receive rhEPO therapy intravenously. Three months later, his hemoglobin level started declining and he became transfusion dependent. A diagnosis of Ab-mediated PRCA was made by bone marrow examination and detection of anti-EPO Abs. He was successfully treated with cyclosporine and became independent of blood transfusions. This case is a reminder that vigilance is required regarding the development of Ab-mediated PRCA upon rhEPO therapy, regardless of the administration route.
    Acta Haematologica 06/2011; 126(2):114-8. · 0.89 Impact Factor
  • Annals of Hematology 10/2007; 86(9):697-8. · 2.40 Impact Factor
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    ABSTRACT: We present a case of a 74-year-old male, who had a relapse of minimal change nephrotic syndrome (MCNS) as the initial presentation of acquired hemophilia A. MCNS had been maintained in remission with prednisolone 10 mg for 15 years. In early December 2005, the patient developed edema of the right leg, was admitted to a local general hospital, and was diagnosed as having a relapse of MCNS based on massive proteinuria (urine protein 6.1 g/day). One week later, severe anemia (hemoglobin 4.4 g/dl) and acute renal failure (creatinine 2.0 mg/dl) developed, and a CT scan of the abdomen revealed a hematoma in the left iliopsoas muscle. He was referred to our hospital with bleeding tendency. Laboratory examination revealed prolonged APTT 80.5 seconds), reduced factor VIII activity (<1%) and thepresence of factor VIII inhibitor at a titer of 19 Bethesda units/ml, based on which he was diagnosed as having acquired hemophilia A. With recombinant activated FVII, hemostasis was obtained and prednisolone administration 60 mg/day (1 mg/kg) was started. Both the acquired hemophilia A and MCNS responded well to the treatment with prednisolone. Six weeks after initiation of the treatment, factor VIII inhibitor and urine protein disappeared. This patient is considered to be a rare case; to the best of our knowledge, this is the third report of acquired hemophilia A with nephrotic syndrome.
    [Rinshō ketsueki] The Japanese journal of clinical hematology 07/2007; 48(6):514-7.

Publication Stats

24 Citations
18.76 Total Impact Points


  • 2007–2014
    • Gunma University
      • Graduate School of Medicine
      Maebashi, Gunma Prefecture, Japan
  • 2011–2013
    • Saiseikai Maebashi Hospital
      Edo, Tōkyō, Japan
    • Dokkyo Medical University
      • Department of Anatomic and Diagnostic Pathology
      Totigi, Tochigi, Japan