Junki Inamura

Severe Hepatic Injury Caused by Imatinib Mesylate Administered for the Treatment of Chronic Myeloid Leukemia and the Efficacy of Prednisolone for its Management

Imatinib mesylate is a specific inhibitor of BCR-ABL tyrosine kinase, which is now widely used for the treatment of chronic myeloid leukemia (CML) with a high efficacy. Although severe hepatic injury caused by imatinib mesylate is rare, such a side effect may force patients to discontinue taking imatinib mesylate. In the present paper, we report on the case of a 51-year-old woman with CML who experienced hepatic injury with severe hyperbilirubinemia caused by imatinib mesylate. The findings from a liver biopsy specimen and her clinical course suggested the hepatic injury to presumably have been caused by an allergic mechanism. The co-administration of prednisolone was thus tried, and she has been able to continue imatinib mesylate administration without any liver dysfunction and finally was able to obtain a complete cytogenetic response. We therefore recommend that prednisolone should be tried when severe hepatic injury caused by imatinib mesylate is observed, since it might enable such patients to continue imatinib mesylate treatment and thereby improve the prognosis in such cases.

A novel five-way chromosomal translocation observed in chronic myelogenous leukemia

Most patients with chronic myelogenous leukemia (CML) show a Philadelphia (Ph) chromosome with a characteristic translocation between chromosomes 9 and 22. However, there are variant complex translocations involving other chromosomes in addition to the standard translocation. We describe a case of CML showing a complex and novel chromosomal translocation involving five chromosomes, t(4;12;7;9;22).

Development of POEMS syndrome after an initial manifestation of solitary plasmacytoma

A 44-year-old male was admitted for numbness in the left arm. CT showed a tumor impacting on the spinal cord with an adjacent thoracic vertebral osteosclerotic lesion. The histopathology of the tumor showed diffuse proliferation of atypical plasma cells with expressed vascular endothelial growth factor (VEGF), which is a known etiological factor in POEMS syndrome. Though serum VEGF (sVEGF) level was elevated, a diagnosis of solitary plasmacytoma with an osteosclerotic lesion was made as the patient presented no polyneuropathy, organomegaly, endocrinopathy, or skin changes. The patient experienced muscle weakness of the lower limbs and skin pigmentation/hemangioma one year after irradiation of the osteosclerotic lesion. Laboratory tests revealed hypothyroidism, hyperglycemia, serum monoclonal gammopathy, further elevation of sVEGF, and increased atypical bone marrow plasma cells. CT imaging showed splenomegaly, and a nerve conduction test revealed demyelinating motor peripheral neuropathy. The patient was therefore diagnosed with POEMS syndrome. Plasmacytoma is very rare as an initial manifestation of POEMS syndrome. Patients presenting with plasmacytoma with an osteosclerotic lesion should be carefully observed and evaluated for the expression of sVEGF and development of POEMS syndrome, as most bone plasmacytomas in POEMS syndrome patients are reported to be osteosclerotic. This is to our knowledge the first case of osteosclerotic plasmacytoma that progressed to POEMS syndrome, with an increase of sVEGF.

Combined use of dendritic cells enhances specific antileukemia immunity by leukemia cell-derived heat shock protein 70 in a mouse model with minimal residual leukemia cells.

We have reported that immunotherapy using leukemia cell-derived heat shock proteins (HSPs) is effective against minimal residual disease (MRD) after syngeneic stem cell transplantation (SCT) in mice. However, leukemia patients after SCT are usually immunocompromised and immunologically tolerant to leukemia cells.We investigated whether the use of dendritic cells (DCs) in combination with HSP70 enhances cytotoxicity against B-cell leukemia cell line A20 in mice after syngeneic SCT. All unimmunized mice died of leukemia early after A20 cell inoculation, whereas mice immunized with HSP70 or HSP70-pulsed DCs survived significantly longer. Although only 60% of the HSP70-immunized mice survived, all mice immunized with HSP70-pulsed DCs survived without MRD. In addition, the cytotoxicities against A20 cells for splenocytes from mice immunized with HSP70-pulsed DCs were significantly higher than those of HSP70-immunized mice, and the cytotoxicities against A20 cells were significantly blocked by anti-CD8 antibody and by major histocompatibility complex class I antibody, but not by anti-CD4 antibody. Moreover, abnormalities were detected in neither the biochemical data nor the histopathologic findings. These findings indicate that the combined use of DCs and leukemia cell-derived HSP70 enhances the antileukemia effect by inducing the specific cytotoxicities of CD8+ cytotoxic T-cells, thereby eradicating MRD effectively and safely, even in an immunocompromised state after syngeneic SCT. This approach may thus be useful for further application of HSP in leukemia patients after autologous SCT.

The Detection of Pancreatic and Retroperitoneal Plasmacytoma Helped to Diagnose Multiple Myeloma: A Case Report.

AbstractMultiple myeloma is characterized by the neoplastic proliferation of a single clone of plasma cells producing a monoclonal protein. However, the involvement of pancreas is a rare event. We herein report a rare case of pancreatic plasmacytoma, which was detected before the diagnosis of multiple myeloma.An 83-year-old male was referred to our hospital for further evaluation of obstructive jaundice and a pancreatic mass. A contrast-enhanced computed tomography (CT) scan revealed solid masses with homogenous enhancement in the pancreatic head and retroperitoneum. The histological findings of the retroperitoneal mass obtained by CT-guided biopsy showed multiple sheets of atypical plasma cells, which were positively immunostained for CD79a, CD138, and the &kgr; light chain. Serum immunoelectrophoresis detected M-component of immunoglobulin A-&kgr;, and the histological findings of the bone marrow revealed an abnormally increased number of atypical plasma cells with irregular nuclei and cytoplasmic vacuolation. The patient was therefore diagnosed to have multiple myeloma involving the pancreas and retroperitoneum. Although chemotherapy was performed, the patient died 6 months after the diagnosis.The pancreatic plasmacytoma was detected before the multiple myeloma in the present case. It is difficult to diagnose a pancreatic plasmacytoma without a history of multiple myeloma and related disease.

B-cell Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, without the development of Richter's Syndrome, with Neoplastic Cells Lacking CD20 Antigen Expression after Rituximab Treatment

A 40-year-old man was admitted to our hospital with systemic swelling of the lymphnodes (LNs). The histopathological findings of the neck LNs revealed a diffuse proliferation of neoplastic small lymphocytes. LN and bone marrow (BM) cells were subjected to immunostaining and flow cytometric analysis of the cell surface, showing CD5, CD19, CD20, and CD23 positivity and CD3, CD10, and cyclin D1 negativity. The patient was diagnosed with B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL). He received a cycle of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) and 6 cycles of RFC (rituximab, fludarabine, and cyclophosphamide), after which complete remission was obtained. Fifteen months after the diagnosis, the lymphoma relapsed and massive systemic LN swelling and BM infiltration were observed, characterized by a lack of CD20 antigen expression in the neoplastic cells. Two salvage chemotherapy regimens proved ineffective and the lymphoma progressed. The patient died two months after the relapse. The pathological findings at autopsy revealed the multiple organ infiltration of CLL/SLL cells which lacked CD20 expression. There were no evidence of Richter’s syndrome. Patients with relapsed B-CLL/SLL who are undergoing rituximab-containing therapy should be monitored for the loss of CD20 antigen expression in the neoplastic cells.