Tomoe Nemoto

Clinicopathological analyses in patients with other iatrogenic immunodeficiency-associated lymphoproliferative diseases and rheumatoid arthritis

Abstract Despite numerous attempts to uncover the mechanism of other iatrogenic immunodeficiency-associated lymphoproliferative diseases (OIIA-LPDs), this mechanism remains poorly understood, especially in rheumatoid arthritis (RA) patients. We analyzed the data on 23 patients with LPDs and RA. Patients were categorized into three groups according to whether they had methotrexate (MTX); MTX-regressive LPDs, MTX-persistent LPDs or other drugs-mediated LPDs. The LPDs seen in OIIA-LPDs-RA might have a unique behavior to think about several rare phenotypes. The overall survival of all patients was 74% at 5 years, and those of the three groups were 100%, 64% and 60%, respectively. Among the 6 patients who died, 4 had LPDs that were detected late, and thus adequate treatment was not given. In addition, several patients with diffuse large B cell lymphoma with a complex karyotype achieved complete remission (CR). Only one among the 17 patients who achieved CR relapsed. OIIA-LPDs-RA appeared to have a better prognosis than other more common types of lymphomas. Regarding RA treatment, various anti-RA drugs were given to the patients after developing LPDs, including MTX, but no recurrent patients were documented.

Successful treatment with a modified bortezomib schedule of weekly and longer intervals for patients with refractory/resistance multiple myeloma

Bortezomib is a potent agent for multiple myeloma (MM); however, severe treatment-related toxicities such as peripheral neuropathy have been observed in conjunction with its use. In this study, we present the cases of 9 patients with refractory MM whose administration schedule was modified from twice weekly to an interval of once weekly or longer mainly due to adverse events. The average duration from diagnosis to the time of bortezomib induction was 56 months. The schedule was changed to the modified administration according to the physicians discretion. The average duration of modified treatment was 16 months. Six patients with IgG or IgA subtype showed more than a minor response. One patient with BJP had stable disease for 3 years, and the other BJP-type patient with extramedullary plasmacytomas showed remarkable tumor regression. The treatment-related toxicities of this strategy were mild and tolerable. To our knowledge, this is the first report of the administration of bortezomib at intervals longer than once weekly.

Severe degenerative change of multiple organs mediated by chronic active Epstein-Barr virus infection with infected T-cell expansion

We here report the case of a young Japanese woman diagnosed with chronic active Epstein–Barr virus (EBV) infection. Intensive therapy with the CHOP regimen was partially able to control virus expansion, but various central nervous system symptoms appeared and gradually progressed. EBV-encoded RNA, detected using in situ hybridization, disclosed the presence of EBV in liver and bone marrow tissue, and real-time PCR revealed the presence of EBV in the cerebrospinal fluid (CSF) and serum. CD3+CD4+CD8−CD56− T-cell expansion in the peripheral blood (PB) and CSF was also observed. Atrophic brain changes were progressive, and the patient died of central nervous system disturbance and pulmonary hemorrhage a year after diagnosis. Autopsy revealed that EBV-infected T lymphocytes with a phenotype similar to those seen in PB and CSF had infiltrated multiple organs: the lymph nodes, bone marrow, endocardium, pericardium, myocardium, spleen, liver, and spinal cord. There have been few previous reports of severe degenerative changes in the myocardium, liver, and spinal cord in patients with EBV infection. Although EBV occasionally infiltrates the central nervous system and brain, atrophic changes mediated by EBV are rare. The autopsy results of this case suggest the possibility of EBV-mediated, severe degenerative changes in multiple organs.

Co-existence of acute myeloid leukemia with multilineage dysplasia and Epstein-Barr virus-associated T-cell lymphoproliferative disorder in a patient with rheumatoid arthritis: a case report

Rheumatoid arthritis (RA) is an autoimmune disease mediated by inflammatory processes mainly at the joints. Recently, awareness of Epstein-Barr virus (EBV)-associated T-cell lymphoproliferative disorder (T-LPD) has been heightened for its association with methotraxate usage in RA patients. In the contrary, acute myeloid leukemia with multilineage dysplasia (AML-MLD) has never been documented to be present concomitantly with the above two conditions. In this report we present a case of an autopsy-proven co-existence of AML-MLD and EBV-associated T-LPD in a patient with RA.

[Cardiac and breast diffuse large B-cell lymphoma with pericardial effusion and AV-block].

Primary cardiac lymphoma is extremely rare and is associated with a poor prognosis. In most cases, cardiac involvement occurs as a late symptom and the diagnosis is thus delayed. We herein report a 35-year-old woman with cardiac diffuse large B-cell lymphoma (DLBCL) with breast infiltration. The patient was admitted to our hospital based on an initial presentation with dyspnea on exertion, chest pain, and a hard mass of the left breast. Echocardiography revealed a mass in the right atrium wall and interatrial septum, and massive pericardial effusion. ECG showed atrioventoricular block. We promptly performed a needle biopsy of the breast mass, which showed CD5-positive DLBCL, non-GCB type. The serum HIV reaction was negative. We thus diagnosed this patient as having cardiac and breast CD5-positive DLBCL, stage IVA, based on the massive pericardial effusion. The patients prognosis was apparently poor. Therefore, she received 3 cycles of R-CHOP chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT), resulting in a complete response. In general, cardiac lymphoma is associated with high mortality and has a poor prognosis. This case demonstrates that rapid and appropriate diagnosis, and immediate intensive chemotherapy followed by PBSCT might be necessary for the treatment of extranodal lymphoma indicative of a poor prognosis.