[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.

[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.

Greater impact of oral fluconazole on drug interaction with intravenous calcineurin inhibitors as compared with intravenous fluconazole.

OBJECTIVE: Although the drug interaction between fluconazole and calcineurin inhibitors has been established, the influence of the route of fluconazole administration on its drug interaction with calcineurin inhibitors has yet to be fully examined. The aim of the present study is to examine whether different routes of fluconazole administration alter its drug interactions with intravenous calcineurin inhibitors. METHODS: In 53 recipients of allogeneic hematopoietic cell transplantation receiving calcineurin inhibitors intravenously, steady-state whole-blood levels of cyclosporine A (CsA) or tacrolimus were measured after the route of fluconazole (200 mg/day) administration was switched from intravenous to oral. RESULTS: The mean steady-state whole-blood level of CsA or tacrolimus significantly increased after the route of fluconazole administration was switched from intravenous to oral (CsA: to 394 +/- 28.4 from 362 +/- 17.8 ng/mL; tacrolimus: to 18.8 +/- 0.64 from 17.4 +/- 0.39 ng/mL, P < 0.05). CONCLUSION: This finding strongly suggests that oral fluconazole has a greater impact on its drug interactions with intravenous calcineurin inhibitors than intravenous fluconazole. Monitoring of blood levels of intravenous calcineurin inhibitors is recommended when the route of fluconazole administration is switched from intravenous to oral.

[Successful treatment with L-asparaginase-based combination chemotherapy for refractory T-cell post-transplant lymphoproliferative disorder].

A 31-year-old man underwent kidney transplantation in 1996, and had been on immunosuppressants. In 2005, he presented with discomfort on swallowing. Swelling of the left tonsil and a mediastinal mass were observed. A biopsy of the left tonsil showed a monotonous proliferation of atypical lymphocytes suggesting post-transplant lymphoproliferative disorder (PTLD). The reduction of immunosuppressants did not result in any clinical improvements, and he developed bilateral cervical lymphadenopathy. A biopsy of the cervical lymph node also showed monotonous proliferation of TdT, CD3, CD5, CD7, CD10, and CD34-positive immature cells. T-cell receptor rearrangement, but not EBER, was detected. Based on these findings, monomorphic T-cell PTLD was diagnosed. He was treated with four different chemotherapeutic regimens without any clinical improvements, and the PTLD became leukemic. Chemotherapy consisting of L-asparaginase, vincristine, and dexamethasone (LVD) was then given, which resulted in massive tumor lysis. However, after two courses of LVD, complete remission was achieved. T-cell PTLD is a rare disorder, characterized by its refractoriness to chemotherapy as opposed to B-cell PTLD. Our experience suggests that L-asparaginase-based chemotherapy may improve the prognosis of T-cell PTLD.

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.

Myelitis associated with human herpes virus 6 (HHV-6) after allogeneic cord blood transplantation.

Human herpes virus 6 (HHV-6) has been recognized as 1 of the pathogens causing central nervous system diseases such as encephalitis after hematopoietic stem cell transplantation. We here report 2 patients who developed HHV-6-associated myelitis soon after allogeneic cord blood transplantation.

Hepatic veno-occlusive disease after tranexamic acid administration in patients undergoing allogeneic hematopoietic stem cell transplantation.

Tranexamic acid is one of the widely used antifibrinolytic agents. In spite of its effective inhibitory activity against plasminogen, thromboembolic adverse events caused by tranexamic acid are rare. We encountered three recipients of allogeneic hematopoietic stem cell transplantation (HSCT) who developed hepatic veno-occlusive disease (VOD) shortly after the administration of tranexamic acid. Hepatic VOD was resolved completely in all patients with the discontinuation of the drug, and with supportive measures with or without intravenous tissue plasminogen activator administration. These findings suggest that administration of tranexamic acid could be one of the possible risk factors for developing hepatic VOD in HSCT recipients.