Nahoko Hatsumi

Steroid‐refractory chronic idiopathic thrombocytopenic purpura associated with hepatitis C virus infection

Abstract: Objectives: Hepatitis C virus infection has often been suggested as a possible cause of various kinds of autoimmune diseases. The aim of this study was to determine the relationship between chronic idiopathic thrombocytopenic purpura (ITP) and hepatitis C virus infection and to characterize the clinical features of anti‐HCV antibody (HCVab) positive chronic ITP patients. Subjects and methods: We studied HCVab in 79 patients with chronic ITP (25 males, 54 females, mean age 42.3 yr, range 11–86 yr) using the third‐generation ELISA method. Results: HCVab was detected in 11 of the 79 patients (13.9%). Quantitative HCV‐RNA studies showed a high serum concentration of HCV‐RNA in these patients. The platelet counts in these 11 HCVab‐positive patients (Group 1) were lower than in the 68 HCVab‐negative patients (Group 2)[(2.6 ± 0.9) versus (4.9 ± 3.0) × 1010/L, respectively; p<0.02]. Significantly more patients in Group 1 required prednisolone therapy (10/11, 90.9%) than in Group 2 (31/68, 45.6%) (P < 0.005). The response rate to prednisolone treatment was significantly higher in Group 2 (19/31, 61.3%) than in Group 1(0/10, 0%) (P < 0.001). There was no difference in the response to splenectomy between Groups 1 (4/7, 57.1%) and 2 (3/5, 60%). Conclusion: Given these findings, we recommend that HCVab is measured upon diagnosis of chronic ITP, and that splenectomy is planned in patients with HCVab in the event that prednisolone treatment is ineffective.

Fulminant, CMV-associated, haemophagocytic syndrome following unrelated bone marrow transplantation

We report a case of haemophagocytic syndrome (HPS) occurring after allogeneic bone marrow transplantation (BMT) for acute promyelocytic leukaemia (APL) in a patient in fourth complete remission (CR). Anti- cytomegalovirus (CMV) antibody (Ab) was negative in this patient before BMT. BMT was performed from an HLA-identical unrelated donor who was positive for CMV Ab. After bone marrow engraftment and haematological recovery, severe acute graft-versus-host disease (GVHD) developed. This patient was treated with methylprednisolone in addition to cyclosporin A (CsA). Acute GVHD showed partial improvement, but CMV antigenaemia was observed. Despite administration of gancyclovir and immunoglobulin, CMV antigenaemia showed no improvement and HPS developed. As no other infections or malignancies were observed, we suspect that CMV infection was the trigger for development of HPS.

Clinical significance of granulocytic sarcoma in adult patients with acute myeloid leukemia

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 Sci, doi: 10.1111/j.1349‐7006.2012.02324.x, 2012)

Discrepancy in EBV-DNA load between peripheral blood and cerebrospinal fluid in a patient with isolated CNS post-transplant lymphoproliferative disorder

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.

Philadelphia chromosome‐positive mixed phenotype acute leukemia in the imatinib era

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‐yr 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.

Prevalence of extramedullary relapses is higher after allogeneic stem cell transplantation than after chemotherapy in adult patients with acute myeloid leukemia

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.

Acute Basophilic Leukemia Lacking Basophil-Specific Antigens: The Importance of Cytokine Receptor Expression in Differential Diagnosis

De novo acute basophilic leukemia (ABL) is a rare form of myeloid leukemia. The low prevalence of ABL makes it difficult to define its clinical characteristics and to establish an effective therapeutic protocol. We present here a case of de novo ABL in a 64-year-old Japanese man. The diagnosis of ABL depended on the following: (1) metachromasia with toluidine blue stain, (2) intracytoplasmic theta granules identified by electron microscopy, and (3) findings obtained from extensive immunophenotypic analysis. Although blast cells lacked basophil-specific antigens such as CDw17, CD88, and FcεRI, an expression profile of cytokine receptors including CD116 (GM-CSF receptor), CD117 (c-kit), and CD123 (IL-3 receptor α) helped to define the cellular lineage in our case. The patient achieved complete remission with intensive chemotherapy composed of idarubicin and cytosine arabinoside and was disease free during the following 30 months. We propose that immunophenotyping, especially focusing on cytokine receptors, is useful in diagnosing ABL.

Multiple Myeloma Presenting High Fever and High Serum Levels of Lactic Dehydrogenase, CRP, and Interleukin-6

Two myeloma patients presented high fever with no signs or data indicating infection at diagnosis or relapse. Both patients had plasmablastic myeloma, and serum levels of lactic dehydrogenase (LDH) and CRP were extremely high. Plasmablastic morphology, high LDH, and CRP were recognized as poor prognostic factors, indicating a fulminant phase of multiple myeloma. Interleukin‐6 (IL‐6) was only high in measured cytokines. We proposed that IL‐6 caused high fever and induced the fulminant phase in these 2 cases. Am. J. Hematol. 64:76–77, 2000.

Three AML patients with existing or pre-existing intracerebral granulocytic sarcomas who were successfully treated with allogeneic bone marrow transplantations.

We report three acute myelogenous leukemia (AML) patients who developed intracerebral granulocytic sarcomas (GS) and were successfully treated with allogeneic BMT (allo-BMT). The diagnosis of one patient was AML M2 with myelofibrosis, and the other two patients were AML M4 with eosinophilia (AML M4 Eo), according to the FAB classification. Two patients first experienced a relapse in the brain that resulted in the formation of GS, followed by a relapse in the bone marrow. The remaining patient developed an optic nerve GS after suffering a bone marrow relapse. All three patients received irradiation for the GS and systemic chemotherapy before the allo-BMT. TBI was used for conditioning, and GVHD prophylaxis was with cyclo- sporine (CsA) and short-term MTX in all three cases. These patients are currently 9 to 37 months post-BMT without relapse. Thus, our experience suggests that allo-BMT is an effective treatment for AML patients with existing or pre-existing intracerebral GS.

Ribosome-lamella complex of leukemic cells in a patient with aggressive NK cell leukemia.

A 36-year-old male was admitted to the hospital with anemia and leukopenia. A bone marrow specimen revealed the proliferation of leukemic cells with flower-like nuclei observed in adult T-cell leukemia. The leukemic cells were positive for HLA-DR, CD2, CD7, and CD56. A diagnosis of aggressive NK cell leukemia was made, the patient was treated with induction chemotherapy and cord blood stem cell transplantation, and he is well now. Seen with electron microscopy, some leukemic cells had ribosome-lamella complexes (RLC). This is the first reported case of leukemic cells with flower-like nuclei seen with light microscopy and RLC seen with electron microscopy.