Chronic myelogenous leukemia in the chronic phase with lymph node swelling which represented extramedullary involvement composed of cells at different stages of maturation.

In chronic myelogenous leukemia (CML), lymph node swelling is generally considered an early sign of blast crisis. We encountered a rare case of CML showing marked lymph node swelling, which represented extramedullary involvement composed of cells at different stages of maturation but not showing blast crisis. In 1996, a 60-year-old Japanese male was diagnosed with CML in the chronic phase, and imatinib mesylate was prescribed following interferon-alpha treatment in 2004. However, the patient chose to discontinue out patient treatment 1 year later. He was referred to our hospital because of severe fatigue in August 2006, and laboratory tests showed a WBC count of 347.9 x 10(9)/l with 6.5% blasts. On bone marrow tests, Ph chromosome presence was found in all cells examined, but there was no additional chromosomal abnormality. Cytogenetic analysis revealed that 82% of cells in on employing FISH showed BCR/ABL. The patient had swelling of the left cervical and both inguinal lymph nodes. A lymph node biopsy showed proliferation in three lineages of hematological cells at different stages of maturation. He was diagnosed with CML in the chronic phase. He was given imatinib mesylate and hydroxyurea, and achieved hematological remission. Sixteen months later, he developed blast crisis and died of cerebral hemorrhage. Such a case of extramedullary involvement composed of cells at different stages of maturation is rare, and suggests the need to biopsy extramedullary tumors in order to evaluate the clinical phase.

[Combination therapy with rituximab and cladribine for patients with follicular lymphoma].

Treatment strategies for follicular lymphoma have not been established. We report the outcome after combination therapy with rituximab and cladribine (RC) for 8 patients with follicular lymphoma treated between January 2005 and December 2006 in our hospitals. Median patient age was 57 (range 42 approximately 73) years. There were 4 males and 4 females. Only 1 patient had refractory disease, while the others had untreated disease. On the follicular lymphoma international prognostic index, 4 patients were in the low-risk group, 3 in the intermediate-risk group and 1 in the high-risk group. The median follow-up period was 36 (range 22 approximately 90) weeks. The RC protocol consisted of intravenous rituximab at a dose of 375 mg/m (2) on day 1 and cladribine at a dose of 0.1 mg /kg per day for 2-hours on day 1 through 5. The median number of RC courses was 5 (range 3 approximately 8). The median interval between the 2 courses was 7 (range 3 approximately 26) weeks. The overall response rate was 87.5%. Grade 3 neutropenia was observed in 50% patients, although G-CSF was not needed. There was no apparent thrombocytopenia or anemia. Herpes zoster was observed after treatment in 1 patient. RC is considered highly effective and well tolerated.

Diffuse large B-cell lymphoma presenting with central pontine myelinolysis: a case report.

INTRODUCTION: The most common cause of central pontine myelinolysis is an overly rapid correction of hyponatremia, although it can also occur in patients with any condition leading to nutritional or electrolyte stress. We report a case of diffuse large B-cell lymphoma with central pontine myelinolysis developing at the onset of disease. To the best of our knowledge, hematological malignancies presenting with central pontine myelinolysis have been rarely reported, especially in previously untreated patients, as in our case report. CASE PRESENTATION: A 78-year-old Japanese woman presented to a neighborhood clinic with persistent high fever, edema, and general weakness. Despite the absence of specific neurological findings, brain magnetic resonance imaging showed an abnormal lesion in the central pons area of her brain (hyperintense on T2-weighted and hypointense on T1-weighted sequences), compatible with central pontine myelinolysis. She was admitted to our emergency department in a state of shock one month later. The results of her blood tests showed greatly elevated C-reactive protein and lactate dehydrogenase levels. She had severe hypoalbuminemia and mild hyponatremia, and showed signs of disseminated intravascular coagulation. Mild bilateral pleural effusion, prominent subcutaneous edema, and splenomegaly were detected on her systemic computed tomography scan. Her body fluid cultures did not show signs of infection and her spinal aspiration did not show pleocytosis or abnormal cells. A diagnosis of diffuse large B-cell lymphoma was made based on the results of her bone marrow examination. As she was critically ill before the diagnosis was made, she was treated with methylprednisolone pulse therapy, followed by systemic chemotherapy (rituximab with modified THP-COP regimen, including cyclophosphamide, pirarubicin, vindesine, and prednisolone), which resulted in complete remission and recovery without any neurological defects, and resolution of her abnormal findings on magnetic resonance imaging. CONCLUSIONS: Central pontine myelinolysis is a serious condition that may result in neuropathological sequelae and mortality, and clinicians should be aware of its potential presence in patients with malignancies.

Multifocal fibrosclerosis: retroperitoneal fibrosis associated with a suprasellar tumor and pachymeningitis.

A 42 year-old man with lumbago and fever had hydronephrosis due to a mass surrounding the abdominal aorta, associated with pachymeningitis and a suprasellar tumor. He was given a diagnosis of multifocal fibrosclerosis, involving both retroperitoneal and intracranial fibrosis. He responded to treatment with corticosteroid and cyclophosphamide. The intracranial lesions seemed to be rare, but important manifestations of the systemic disease, and were clearly visualized by magnetic resonance imaging. The phenotype of the infiltrated lymphocytes was CD4+, supporting the hypothesis that autoimmunity was involved pathogenetically. We propose a comprehensive category termed "inflammatory fibrotic disease" including both systemic and localized diseases.

The response to second-line induction with bortezomib and dexamethasone is predictive of long-term outcomes prior to high-dose chemotherapy with autologous stem cell transplantation for multiple myeloma.

OBJECTIVE: We retrospectively investigated the efficacy and predictive factors for the treatment outcomes of bortezomib plus dexamethasone (BD) as second-line induction therapy prior to high-dose chemotherapy supported by autologous stem cell transplantation (HDT/ASCT) in multiple myeloma (MM) patients. METHODS: Sixty-six transplant eligible MM patients treated by the Kyoto Clinical Hematology Study Group between 2006 and 2011 were investigated. Conventional induction chemotherapy, including vincristine, doxorubicin and dexamethasone (VAD) and high-dose dexamethasone (HDD), was used as first-line induction therapy in all patients, seven (10.6%) of whom attained a very good partial response (VGPR). Of the 59 patients who did not attain VGPR with VAD or HDD, 33 were given BD as second-line induction therapy prior to HDT/ASCT. RESULTS: Patients not treated with BD induction showed an overall response rate (ORR, i.e., better than partial response) of 85.3% after induction therapy, while the ORR of patients treated with BD induction improved from 42.4% after conventional induction therapy to 84.8% after BD. The overall survival (OS) and progression-free survival (PFS) of patients not treated with BD induction were not significantly influenced by the response to induction therapy. Among the patients treated with BD, failure in attaining VGPR prior to ASCT was associated with a significantly shorter PFS and it also tended to show a shorter OS, while the disease stage and achievement of a complete response after HDT/ASCT had no impact on OS or PFS. CONCLUSION: The achievement of at least VGPR with second-line BD induction therapy is a prerequisite for attaining longer OS and PFS after HDT/ASCT.

Bortezomib plus dexamethasone for relapsed or treatment refractory multiple myeloma: the collaborative study at six institutes in Kyoto and Osaka.

We conducted a retrospective collaborative investigation of bortezomib (Bor) plus dexamethasone (Dex) therapy (BD Tx) for 88 relapsed or refractory (Rel/Ref) MM patients at six institutes. One cycle BD Tx comprised of Bor (1.3 mg/m²/day) on days 1, 4, 8 and 11, and Dex on days 1, 2, 4, 5, 8, 9, 11 and 12, every 21 days, and the mean number of BD Tx cycles was 3. The overall response rate was 66.9%, the median overall survival (OS) was 510 days, and the median progression-free survival (PFS) was 113 days. Attainment of partial response (PR) with the first course of BD Tx associated with the longer OS and PFS and late good responder, while no patient who did not achieve PR with the first cycle attained better than very good PR (VGPR) with the subsequent BD Tx. Patient age of less than 64 years old also associated with the longer OS and PFS. In addition, both an earlier disease stage and Dex dosage had a significant impact on OS, while the attainment of VGPR within 2 cycles had a significantly longer PFS. Earlier BD Tx courses may be predictive for the subsequent therapeutic pathway of Rel/Ref MM.

Malnutrition and disease progression in patients with rheumatoid arthritis.

To examine the changes in nutritional status during the progression of rheumatoid arthritis (RA), we studied anthropometric and biochemical variables in 97 Japanese patients with RA. Anthropometric data included body mass index (BMI), triceps skinfold thickness (TSF), and arm muscle area (AMA). Levels of albumin and cholesterol in serum, and lymphocyte count were studied as biochemical variables. The prevalence of malnutrition defined as hypoalbuminemia less than 3.4 g/dl was 24.7%, similar to the reports in other countries. Analysis of the data according to disease stage showed that malnutrition in RA was characterized by a progressive reduction in body protein. Body mass index and TSF were increased in patients with stage 1 disease, whereas serum albumin and AMA were within normal range. Stage 2 patients had normal BMI with decreased body protein, albumin, and AMA. Progression to stages 3 and 4 was associated with a stepwise decrease in AMA; serum albumin and BMI remained in the same range as stage 2. Albumin values and AMA were significantly lower in patients with poor functional class and high C-reactive protein. The characteristic progression of malnutrition in RA is attributed to excessive protein catabolism evoked by inflammatory cytokines and by disuse atrophy due to functional impairment.