Yuzuru Kuriyama

Imatinib mesylate-induced hepato-toxicity in chronic myeloid leukemia demonstrated focal necrosis resembling acute viral hepatitis.

Imatinib mesylate-induced hepato-toxicity in chronic myeloid leukemia demonstrated focal necrosis resembling acute viral hepatitis

Can eradication therapy for Helicobacter pylori really improve the thrombocytopenia in idiopathic thrombocytopenic purpura? Our experience and a literature review

Helicobacter pylori has recently been postulated to play a role in the pathogenesis of autoimmune diseases, including idiopathic thrombocytopenic purpura (ITP). We investigated the prevalence ofH pylori infection and the effects of its eradication in 61 patients with ITP.H pylori infection was found in 50 patients (83%), an incidence significantly higher than not only healthy volunteers in Japan (60%) but also subjects in other reported ITP series (approximately 43%–71%). In our study, the mean age ofH pylori-positive ITP patients (58.0 years) was significantly higher than that ofH pylori-negative ITP patients (40.5 years). Bacterium eradication efforts were performed in 29 infected ITP patients and succeeded in 27 patients (93%). The 29 patients with eradicatedH pylori infections showed significant increases in platelet counts compared with patients with uneradicated infections or who wereH pylori-negative. During the follow-up period (median, 11.0 months), 16 (55%) of 29 patients achieved a major or a minor response. The patients who achieved a major response had not received previous prednisolone therapy, suggesting a relationship between prednisolone therapy and the response to eradication efforts.The assessment ofH pylori infection and its eradication should be attempted in cases of ITP, because this approach may be a good new strategy for treating some ITP patients, especially elderly Japanese patients. Some regional factors have been suggested as causes ofH pylori-associated ITP.

Pulmonary alveolar proteinosis as a terminal complication in myelodysplastic syndromes: a report of four cases detected on autopsy.

Secondary pulmonary alveolar proteinosis (PAP) is one of the complications of hematologic malignancy and immunosuppressive diseases. We encountered four cases of myelodysplastic syndrome (MDS) associated with PAP detected on autopsy. They consisted of two refractory anemia (RA) and two patients with refractory anemia with excess blasts in transformation (RAEBt) at the time of MDS diagnosis, but all of them developed leukemic phase and were resistant to chemotherapy at the time of pulmonary episodes. Of the four MDS patients, two also had pulmonary aspergillosis. Previously, 69 patients with PAP associated with hematologic disorders have been reported, but there have been only seven cases with MDS, including our four patients. Of the 69 reported cases of PAP in hematologic malignancies, 24/63 (38%) informative patients with infection had fungal infections of the lung; 2/7 (29%) MDS cases had fungal infection. We should, therefore, pay careful attention to this possibility in cases of MDS with lung complications, including PAP, especially in patients in the leukemic phase of MDS.

Thrombocytopenia induced by imatinib mesylate (Glivec) in patients with chronic myelogenous leukemia: is 400 mg daily of imatinib mesylate an optimal starting dose for Japanese patients?

Imatinib mesylate (Glivec) is a potent and selective inhibitor of the tyrosine kinase activity of BCR-ABL. Because the mechanism of action of imatinib mesylate is inhibition of BCR-ABL tyrosine kinase, it seems likely that to achieve maximum therapeutic benefit for chronic myelogenous leukemia (CML), imatinib mesylate must be administered at a dose that maximally inhibits BCR-ABL kinase activity or, alternatively, that inhibits sufficient BCR-ABL kinase activity to induce apoptosis. According to in vitro study results, 1 M levels of imatinib mesylate are optimal for inducing cell death, and 1 M trough levels are achieved in patients using imatinib mesylate at a daily dose of more than 300 mg [1]. In a phase I/II study in which the dose-response curve in chronic-phase CML patients was examined, the therapeutic effect was reported to plateau at a dose at or slightly above 300 mg. In addition, there was no convincing evidence of dose-limiting toxicity in patients receiving a maximum dose of 1000 mg [2]. These data were used to set the standard therapeutic dose of imatinib mesylate for chronicphase patients at 400 mg daily, and thereafter, the therapeutic benefits for CML patients of imatinib mesylate at this dose were demonstrated in clinical trials [2,3]. This standard therapeutic dose has been used in administering imatinib mesylate to Japanese patients as well as patients in the United States and Europe. At our institute, however, a series of CML patients treated with 400 mg of imatinib mesylate showed thrombocytopenia, and imatinib mesylate adminisThrombocytopenia Induced by Imatinib Mesylate (Glivec) in Patients with Chronic Myelogenous Leukemia: Is 400 mg Daily of Imatinib Mesylate an Optimal Starting Dose for Japanese Patients?

MALT lymphoma originating in breast and uvula.

A case of marginal zone B cell lymphoma of MALT type arising in the uvula and breast is reported. The patient, a 30-year-old woman who delivered a child and lactated in 1997, was suffering from Sjögren syndrome (SS). She was diagnosed with MALT lymphoma after a biopsy of the right breast and uvula. To investigate the relationship of the delivery, lactation and MALT lymphoma, we examined the immunohistochemical analysis of hormone receptors. As a result, lymphoid cells of the breast were stained with anti-progesterone receptor antibodies in the cytoplasm. Consequently, the MALT lymphoma of the uvula appeared to be associated with SS. Moreover, hormones such as progesterone may have influenced the breast involvement of MALT lymphoma in our case.

Hemophagocytic syndrome associated with CD8 positive T-cell chronic lymphocytic leukemia.

We describe a case of hemophagocytic syndrome (HPS) associated with CD8-positive T-cell chronic lymphocytic leukemia (CD8 + T-CLL). A 68-year-old man with CD8 + T-CLL presented with fever, progressive pancytopenia, and lymphadenopathy. Laboratory findings showed a hyper-ferritinemia, abnormalities of coagulation tests, and liver and renal dysfunction with hypoproteinemia. He did not respond to any treatments and died of respiratory failure 10 days after the admission and 14 months after the onset of CD8 + T-CLL. Pathological findings of the autopsy demonstrated infiltration of CD8 + T-CLL cells in multiple organs along with the increase of histiocytes with prominent hemophagocytosis. Serum concentration levels of IL-6, soluble IL-2 receptor and VEGF were all elevated at admission. These findings revealed that he had a secondary HPS. It was suggested that HPS should be considered in patients with an unexplained cytopenia and a fever during the clinical course of CD8 + T-CLL.

Circulating and Tumor-Infiltrating γδ T Cells in Patients with B-Cell Lymphomas

In order to analyze the involvement of γδ T cells in the immune surveillance against B cell lymphomas (BCL), we investigated the proportion of circulating γδ T cells in 52 BCL patients using two-color flow cytometry, together with tumor-infiltrating γδ T cells in 22 of those patients. We found that the proportion of tumor-infiltrating γδ T cells in BCL patients was not different from that of lymph node γδ T cells in reactive hyperplasia patients. However, a decreased percentage of circulating γδ T cells were observed in indolent lymphoma (IL) and limited aggressive lymphoma (AL) patients when compared with normal controls. In contrast, as a result of a histogram. advanced AL patients were divided into two subgroups: the patients with increased circulating γδ T cells anti those without any increase. However, there was no difference in the clinical features of between the two AL subgroups.

Spontaneous reduction of leukemic lymphoma cells possibly by anti-tumor antibody-mediated phagocytosis; a κ λ-dual-positive b cell lymphoma

We have investigated the possible role of anti-tumor antibody detected in a case of follicular lymphoma which demonstrated the spontaneous reduction of leukemic tumor cells. The tumor cells genotypically had monoclonal rearrangements of the immunoglobulin J H and C κ genes, but phenotypically exhibited surface IgG, A, κ and λ (κ λ dual positivity). The culture study revealed that IgGλ, at least, was derived from the serum, and IgAκ was expressed intrinsically. Furthermore, the positive correlation between the densities of both surface light chains on two-color flow cytometry, the rosette formation study and its inhibition test by the Fcγ fragment suggested that the serum IgGλ combined with some antigens on the tumor-cell surface via its Fab portion and with the Fcγ receptor of macrophages via its Fc portion. From these findings, we regarded the present case as an anti-tumor antibody-coated lymphoma. In addition, the phagocytic study disclosed that the serum-derived IgGλ, at least, might have induced the phagocytosis of circulating lymphoma cells by macrophages. In conclusion, the existence of the anti-tumor antibody-coated lymphoma may be helpful in clarifying the immunological mechanism of the spontaneous regression occasionally seen in lymphomas.

Breast MALT lymphoma: potential relationship between hormonal environment and female sex hormone receptor expression in lymphoma cells.

Breast involvement by malignant lymphoma is a rare event. It accounts for 0.04% to 0.5% of all malignant diseases of the breast, 0.07% of all non-Hodgkin’s lymphomas and 1.7% of extranodal non-Hodgkin’s lymphoma (1,2). We have recently reported a case of mucosa-associated lymphoid tissue (MALT) lymphoma originating in the breast and uvula. In this case, the lymphoma cells expressed progesterone receptors (PR) but not estrogen receptors (ER) (3). Another case of breast MALT lymphoma will be presented here which showed a different reactivity to anti-female sex hormone receptor antibodies.

Clinical Implication and Prognostic Significance of Small Lymphoma Cells in the Peripheral Blood and Bone Marrow of B-Cell Non-Hodgkin's Lymphomas

It seems possible that small lymphoma cells (SLC) may have a role even in aggressive B-cell non-Hodgkins lymphoma (B-NHL) such as large-cell lymphoma. However, SLC are often difficult to distinguish morphologically from normal or reactive small lymphocytes. In this study, we used a flowcytometric technique (kappa-lambda imaging; KLI) for detection of SLC. Peripheral blood (PB) and bone marrow (BM) samples taken from 41 patients with surface immunoglobulin positive (sIg+) B-NHL were analysed. SLC were detected in about 90% (37/41) of the untreated patients when either PB or BM was analysed by KLI. The presence of SLC correlated well with disease activity. However, a few SLC were present even in the PB (16%) or BM (27%) of the 31 patients who achieved complete remission, indicating that minimal residual disease (MRD) was present. In some cases, the reappearance of SLC in the PB or BM preceded clinical relapse. Furthermore, the initial volume of SLC, particularly in the BM, tended to be related to the prognosis (P = .068). These results suggest that the detection of SLC by KLI may be helpful not only for the screening and clinical staging of sIg+ B-NHL, but also for monitoring disease activity and detecting MRD. Moreover, the volume of SLC in the BM may be a useful predictor of prognosis.