A case of proliferative glomerulonephritis with immunoglobulin A1-lambda deposits successfully treated by chemotherapy.

A 74-year-old man presented with nephrotic syndrome and kidney insufficiency. Laboratory tests revealed monoclonal gammopathy of immunoglobulin A-lambda. Renal biopsy revealed diffuse mesangial proliferation and double-contoured basement membranes. Immunofluorescent analyses showed granular deposition of immunoglobulin A and C3 at the capillary walls and mesangial regions. Immunohistochemistry suggested monoclonal deposition of immunoglobulin A1-lambda. Electron microscopic analyses showed finely granular electron-dense deposits at mesangial and subendothelial areas. These findings suggested immunoglobulin A-type proliferative glomerulonephritis with monoclonal immunoglobulin deposits. Based on the results of bone marrow aspiration, multiple myeloma was diagnosed. Because the renal manifestation was considered to be affected by monoclonal gammopathy, chemotherapy was initiated rather than immunomodulatory therapy. Although bortezomib and dexamethasone proved ineffective, second chemotherapy with elotuzumab, lenalidomide, and dexamethasone was successful, and kidney function recovered. Effective treatments for proliferative glomerulonephritis with monoclonal immunoglobulin deposits have not been established. This represents the first description of a patient successfully treated for proliferative glomerulonephritis with monoclonal immunoglobulin deposits by chemotherapy using elotuzumab.

Successful treatment with rituximab for angioimmunoblastic T-cell lymphoma.

We experienced a patient with angioimmunoblastic T-cell lymphoma (AITL) without Epstein-Barr virus-positive B (EBV-B) cells at initial presentation who progressed to AITL with expansion of EBV-B cells at relapse. Based on the results of repeated biopsy, the patient was successfully treated with rituximab in combination with chemotherapy at relapse. A repeat biopsy may be necessary to determine the optimum therapeutic strategy at relapse, particularly for patients with suspected expansion of B cell and/or EBV-B cells. Although a recent report found no significant prognostic advantage of rituximab, it is one of the active drugs for selected patients with AITL.

[Severe bortezomib-induced peripheral neuropathy in a patient with multiple myeloma].

A 59-year-old man was diagnosed with IgA-kappa multiple myeloma in October 2005. He was treated with 4 courses of VAD and autologous peripheral blood stem cell transplantation (auto-PBSCT) after 200 mg/m(2) melphalan in September 2006, followed by a second auto-PBSCT after 200 mg/m(2) melphalan in February 2007. However, he did not achieve a very good partial response (VGPR). Laboratory examinations showed increased serum IgA level and renal dysfunction gradually progressed. Bortezomib was then started at a dose of 1.3 mg/m(2) in November 2008. After three cycles of bortezomib, the patient developed numbness, pain and weakness of his upper and lower extremities. The sensation of position and vibration was diminished in the fingers and toes. He developed left foot drop and gait disturbance due to left peroneal nerve palsy. Autonomic dysfunction such as orthostatic hypotension and urinary retention also occurred. Nerve conduction studies showed severe sensorimotor polyneuropathy particularly in the lower extremities. He developed grade 4 motor neuropathy and severe painful neuralgia. Six months after the cessation of bortezomib, these symptoms gradually improved and he was able to walk with support and discharged. Close monitoring of neurological symptoms and prompt dose-reduction or cessation of bortezomib are important to prevent the progression of irreversible peripheral neuropathy.

[Intravascular large B-cell lymphoma with pontine involvement successfully treated with R-hyper-CVAD/R-MTX-Ara-C regimen].

A 47-year-old woman was admitted to our hospital complaining of persistent fever and dry cough in June 2007. CT scan showed hepatosplenomegaly. Laboratory data revealed pancytopenia and increased levels of LDH and soluble interleukin-2 receptor. Malignant lymphoma was suspected, but histological diagnosis was difficult because superficial lymph nodes could not be palpated. Histological examination of the bone marrow biopsy specimen demonstrated the proliferation of large atypical lymphoid cells positive for CD20 and CD79a in the small capillaries, leading to the diagnosis of intravascular large B-cell lymphoma (IVLBCL). Although the results of neurological examination and CSF analysis were normal, head MRI showed a T2-hyperintense lesion in the pons. We chose R-hyper-CVAD/R-MTX-Ara-C alternating therapy with MTX intrathecal injection because CNS involvement in IVLBCL was highly suspected, and she responded well. Head MRI showed the disappearance of the abnormal signal in the pons after one cycle of R-hyper-CVAD. Five cycles of R-hyper-CVAD/R-MTX-Ara-C were performed and complete remission was obtained. R-hyper-CVAD/R-MTX-Ara-C alternating therapy was effective in an IVLBCL patient with CNS involvement.

[Successful treatment with hyper-CVAD and highly active anti-retroviral therapy (HAART) for AIDS-related Burkitt lymphoma].

A 38-year-old man was admitted to our hospital because of continuous fever and right facial palsy. He was diagnosed as HIV positive. Abdominal CT scan showed a large mass in the ascending colon. Gallium scintigraphy demonstrated increased uptake in the ascending colon. Colonoscopy was performed and histological examination of the colon tumor revealed Burkitt's lymphoma (BL). He received highly active anti-retroviral therapy (HAART) and his facial palsy improved. Because CD4 count was significantly low at 31/microl, he was treated with dose-adjusted EPOCH (DA-EPOCH) combined with HAART. Although the tumor was decreased in size by DA-EPOCH, we changed to the combination of hyper-CVAD/MTX-Ara-C alternating therapy with HAART in order to increase dose intensity. Six cycles of hyper-CVAD/MTX-Ara-C were performed and complete remission was obtained. In the HAART era, the survival of patients with AIDS-related diffuse large cell lymphoma (DLCL) improved dramatically, whereas the survival of similarly treated patients with AIDS-related BL remained poor. Our case suggests that intensive chemotherapy with hyper-CVAD/MTX-Ara-C combined with HAART may be well tolerated and effective in AIDS-related BL.

[Successful induction of complete cytogenetic response with low-dose imatinib mesylate in an accelerated phase chronic myelogenous leukemia patient who developed severe bone marrow aplasia following standard-dose imatinib mesylate therapy].

A 58-year-old female presented with massive splenomegaly, leukocytosis and anemia. Bone marrow appearance was consistent with CML-AP, and t (9;22) (q34;q11) was detected on karyotyping. 600 mg daily imatinib mesylate (imatinib) was started and achieved complete hematological remission. However, pancytopenia was evident. Despite dose reduction and subsequent drug withdrawal, the pancytopenia worsened and she became transfusion dependent. Grade 4 pancytopenia persisted for 8 months after discontinuing imatinib. Bone marrow biopsy showed severe bone marrow aplasia with no morphological evidence of disease progression. Karyotyping showed minor cytogenetic response with no clonal evolution. Signs of hematological recovery appeared 8 months after stopping imatinib. The patient was re-started on imatinib at a dose of 100 mg/day. The dose was increased to 200 mg/day without hematological toxicity. Complete cytogenetic response (CCyR) was achieved 5 months after the re-administration of imatinib. The patient maintained CCyR with 200 mg of imatinib per day. Prolonged severe bone marrow aplasia has rarely been reported as a complication of imatinib therapy. This case also suggests that low-dose imatinib would be tolerable and effective for some CML patients who are intolerant of a standard dose of imatinib.

Refractory plasmablastic type myeloma with multiple extramedullary plasmacytomas and massive myelomatous effusion: remarkable response with a combination of thalidomide and dexamethasone.

A 74-year-old man with multiple myeloma was refractory to melphalan/prednisolone (MP), high-dose dexamethasone and VAD chemotherapy. He had the following poor prognostic factors: 1) multiple extramedullary plasmacytomas, 2) massive myelomatous effusion, 3) increasing immature myeloma cells with plasmablastic morphology, and 4) predominance of MPC1-CD49e-CD45+ phenotype immature myeloma cells. Combination therapy with thalidomide and dexamethasone resulted in a rapid response and a partial remission despite his multiple poor prognostic factors. The present case suggests that combination therapy with thalidomide and dexamethasone is still an alternative treatment regimen for resistant extramedullary plasmacytoma with a plasmablastic morphology.

[CD4-positive diffuse large B-cell lymphoma].

An 82-year-old man received right upper lobectomy for lung cancer in April 2006. In August, 2006, he was readmitted to our hospital due to left cervical and left inguinal lymph node swelling. A pathologic diagnosis of diffuse large B-cell lymphoma (DLBCL) was made from a biopsy specimen of the left cervical lymph node. The immunophenotype of the lymphoma cells was CD2-, sCD3-, cCD3-, CD4+, CD5+, CD7-, CD8-, CD10-, CD19+, CD20+, CD23+, CD25+, kappa+, lambda-, CD56-, and dual staining confirmed that the cells were positive for both CD4 and CD19. From these findings, he was diagnosed with CD4-positive DLBCL. Five cycles of R-CHOP were performed and complete remission was achieved. To our knowledge, this is the first report of CD4-positive DLBCL.