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A 56-year-old woman with rheumatoid arthritis who had been taking methotrexate (MTX) for six years visited our hospital with dyspnea and dizziness. Abdominal ultrasonography revealed mild splenomegaly. Laboratory examinations showed a marked elevation in soluble interleukin-2 receptor and lactate dehydrogenase levels. These abnormalities revealed a spontaneous regression after MTX discontinuation, however, they worsened again four months later. Skin biopsies revealed a diagnosis of intravascular large B-cell lymphoma (IVLBCL), and we diagnosed MTX-associated IVLBCL (MTX-IVLBCL) based on its characteristic course. Despite the recurrence of IVLBCL, it showed a good response to chemotherapy. MTX-IVLBCL should therefore be treated with consideration since it has different characteristics from that of de novo IVLBCL.

OBJECTIVES: We describe a rare case of adult T-cell leukemia (ATL) presenting with dry mouth and swelling of bilateral parotid and submandibular glands. The unusual involvement of these exocrine glands by malignant cells prompted us to conduct a detail characterization of these infiltrating and circulating leukemic T cells, which may provide insight to the pathogenesis of exocrine involvement in ATL. METHODS: Immunophenotyping of peripheral ATL cells and microscopic examinations of various organs prepared by autopsy were performed. Analysis of the repertoire of T-cell receptor (TCR) of parotid gland-infiltrating ATL cells using molecular and immunohistochemical examinations were also performed. RESULTS: Microscopic examinations of various organs prepared by autopsy revealed the predominant and specific exocrine gland infiltration of ATL cells. Reverse transcription-polymerase chain reaction (RT-PCR) followed by both TCR spectratyping and complementary determining region (CDR)-3 sequencing analysis of TCR Vbeta of parotid gland-infiltrating T cells revealed a relatively restricted but not single usage of TCR Vbeta. Immunohistochemical analyses of parotid gland specimens detected only a small number of TCR Valphabeta-positive cells in parotid gland-infiltrating ATL cells. CONCLUSIONS: The predominant infiltration of ATL cells in exocrine glands implied that these T cells recognized exocrine gland-specific antigen. However, the absence of both TCR Vbeta mRNA transcripts and TCR Valphabeta protein expression in most ATL cells suggested that antigen recognition via TCR may not have played a major role in adhesion and subsequent infiltration into the exocrine glands in this patient. These results provide important background information to further elucidate the pathogenesis of exocrine gland-specific inflammation.

Adenovirus (AdV) infection is an important cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. We treated 16 patients with AdV hemorrhagic cystitis (HC) following HSCT with cidofovir (CDV; 1 mg/kg/day, three times weekly for 3 weeks). Patients included 10 males and six females with a median age of 50 years (range 10-62). Two of the 16 patients were unevaluable because of early death from nonadenoviral causes. CDV therapy cleared AdV from urine in 12 of 14 patients (86%). Of 14 patients, 10 (71%) showed clinical improvements in HC. Among 14 patients, seven (50%) had avoided renal damage, the most important CDV toxicity. One patient previously treated with foscarnet for cytomegalovirus (CMV) required hemodialysis, and CDV treatment was discontinued. In another patient, CDV treatment was discontinued because of grade 2 nephrotoxicity. Four patients became positive for CMV antigenemia while being treated with CDV, and two developed herpes simplex virus (HSV) stomatitis while being treated with CDV. CDV proved effective in treating AdV HC in transplant patients. However, CDV at 1 mg/kg/day given three times weekly failed to prevent breakthrough infection with CMV and HSV in some patients.

We describe a rare case of adult T-cell leukemia (ATL) presenting with dry mouth and swelling of bilateral parotid and submandibular glands. The unusual involvement of these exocrine glands by malignant cells prompted us to conduct a detail characterization of these infiltrating and circulating leukemic T cells, which may provide insight to the pathogenesis of exocrine involvement in ATL.Immunophenotyping of peripheral ATL cells and microscopic examinations of various organs prepared by autopsy were performed. Analysis of the repertoire of T-cell receptor (TCR) of parotid gland-infiltrating ATL cells using molecular and immunohistochemical examinations were also performed.Microscopic examinations of various organs prepared by autopsy revealed the predominant and specific exocrine gland infiltration of ATL cells. Reverse transcription-polymerase chain reaction (RT-PCR) followed by both TCR spectratyping and complementary determining region (CDR)-3 sequencing analysis of TCR Vbeta of parotid gland-infiltrating T cells revealed a relatively restricted but not single usage of TCR Vbeta. Immunohistochemical analyses of parotid gland specimens detected only a small number of TCR Valphabeta-positive cells in parotid gland-infiltrating ATL cells.The predominant infiltration of ATL cells in exocrine glands implied that these T cells recognized exocrine gland-specific antigen. However, the absence of both TCR Vbeta mRNA transcripts and TCR Valphabeta protein expression in most ATL cells suggested that antigen recognition via TCR may not have played a major role in adhesion and subsequent infiltration into the exocrine glands in this patient. These results provide important background information to further elucidate the pathogenesis of exocrine gland-specific inflammation.

We describe treatment of a patient with advanced extranodal NK/T-cell lymphoma, nasal type, with multiple subcutaneous lesions and hemophagocytic syndrome. Considering the projected poor outcome of conventional treatments, we designed an L-asparaginase-based induction therapy. L-asparaginase (4000 units/day, day 1 to day 7) combined with vincristine (1 mg, day 1) and prednisolone (100 mg/day, day 1 to day 5) was administered by intravenous infusion every 3 weeks. Within a week after treatment was started, excellent response was observed. Because of an allergic reaction to L-asparaginase, 6 courses of CHOP (adriamycin, cyclophosphamide, vincristine and prednisolone) therapy were administered as consolidation after 4 courses of L-asparaginase. The lymphoma was controlled with complete remission lasting longer than 2 years without additional treatment. These results and related reports may contribute to greater therapeutic efficacy against at least some cases of extranodal NK/T-cell lymphoma and other related diseases. Further evaluations based on clinical study are expected to clarify these results.

We have previously reported that the platelet count and an increase in platelet number reflect individual erythropoietic capacity in pre-operative autologous blood donation (PABD). We have examined the correlation between erythropoiesis and thrombopoiesis by quantitative in vitro determination of thrombopoietin (TPO), erythropoietin (EPO), and interleukin-6 (IL-6) in patients with PABD. A sequential increase in platelet count with donation could not be explained by an increase in TPO. TPO showed a tendency to be inversely related to the pre-donation platelet count, and to be related to the pre-donation hemoglobin level. There was an inverse relationship between the TPO and EPO levels. As seen with these results, a high erythropoietic state induces restraint of thrombopoiesis, and a low erythropoietic state induces an increase in thrombopoiesis. These effects modulate EPO and TPO via negative feedback. These results provide some practical important information for performing autologous blood donation. Further studies are needed to elucidate the details of these correlations

The erythropoietic capacity for preoperative autologous blood donation (ECPABD) shows marked inter individual variability. This study was performed to evaluate factors useful to predict individual ECPABD from data available before the first donation. The subjects consisted of 74 adult patients who received autologous blood donation, with a mean of 61 ± 12.8 yr (SD). We classified the patients into four groups using our criteria for evaluating the ECPABD and investigated the relationships among age, disease, pre-platelet count, and the rate of platelet increase. Results. (1) Advanced age and the status of disease were not distinctly correlated with low ECPABD. (2) Patients with a high pre-platelet levels had a low ECPABD regardless of the haemoglobin. (3) Patients in which the platelet count increased in accordance with the level of collection exhibited low pre-platelet counts and high ECPABD. Conclusion. In patients with high pre-platelet levels, we reduced the amount collected, considered early use of recombinant human erythropoietin and reevaluated the application of autologous blood donation.

A 30-year-old man was admitted to our hospital with subcutaneous tumors and a high fever. Based on biomicroscopic findings of the tumor, the patient was diagnosed as having diffuse, medium, well-differentiated malignant lymphoma. Immunochemical analysis showed that CD3, CD4, CD25, and TCR beta were positive, and in situ hybridization revealed Epstein-Barr virus-encoded small RNAs in the nuclei of the lymphoma cells. Despite the patient's resistance to multidrug therapy, complete remission was achieved using L-asparaginase. This case is unique because of its peculiar clinical course and a possible association with the Epstein-Barr virus. L-asparaginase may be an important treatment in other patients who exhibit some of these characteristics.

Allogeneic hematopoietic stem cell transplantation (SCT) following high-dose chemotherapy and total body irradiation (TBI) has improved the prognosis of advanced hematological diseases. In order to assess a patient’s suitability for SCT, a thorough pretransplantation survey is performed. However, patient eligibility has expanded because of the progress of supportive care, so it is difficult to define SCT eligibility limitations due to organ dysfunction. Moreover, recent progress in reduced-intensity stem cell transplantation (RIST) has facilitated the use of SCT in older patients and patients with various underlying diseases [1,2]. This article describes the case of a 65-year-old man with myelodysplastic syndrome (MDS), refractory anemia, and chronic obstructive pulmonary disease (COPD) (emphysema) who underwent SCT. The patient had a history of smoking for more than 40 years and had suffered from Burger’s disease since the age of 40 years. He occasionally complained of lower limb pain and was treated with prostaglandin. In 1998, he presented with anemia, and MDS (refractory anemia) was diagnosed. Two years prior to this report he required frequent red cell transfusions, the frequency of which gradually increased. In June 2004, he was admitted to our hospital for allogeneic hematopoietic SCT. Laboratory examinations confirmed bicytopenia: hemoglobin concentration, 5.7 g/dL; red blood cell count, 2010 109/L; white blood cell count, 3.3 109/L; platelet count, 183 109/L. The bone marrow survey demonstrated normocellular bone marrow with mild dysplasia and a small amount of blasts (

A 69-year-old male was admitted to our hospital complaining of skin pigmentation. Masses in bilateral adrenal glands were noted on computed tomography. An exploratory laparotomy revealed malignant lymphoma confined to the bilateral adrenal glands. Histological diagnosis was diffuse mixed-cell type, B-cell lymphoma. Laboratory tests disclosed an elevated ACTH level and decreased urinary 17KS and 170HCS secretion. Based on hypofunction of adrenal glands and skin pigmentation, the patient was diagnosed as having Addison's disease. After complete remission with combination chemotherapy, adrenal function recovered normal and pigmentation disappeared, Addison's disease is an extremely rare complication of primary malignant lymphoma of the adrenal gland.

[Introduction] Natural killer (NK) cells show cytotoxicity against virus-infected cells and some tumor cells. The highly polymorphic killer cell immunoglobulin-like receptors (KIRs) which recognize HLA class 1 molecules play a major role in these cytotoxic activities, and also express on some T-cells. Human T-lymphotrophic virus-1 (HTLV-1) is a caucassive agent for leukemia and some autoimmune diseases. We investigated the correlations between the KIR genotype and susceptibilities to HTLV-1 associated diseases i.e. adult T-cell leukemia (ATL) and HTLV-1 associated myelopathy (HAM). [Materials and Methods] Fifty six HTLV-1 carriers, fifty one ATL patients and fifty seven HAM patients were recruited in this study. Genotyping of six KIR genes (3DL1, 2DL5, 2DS1, 2DS2, 2DS3 and 3DS1) was performed using PCR amplification with sequence specific primers (Martin et al. J Immunol 2002). [Results and Conclusion] Frequencies of each KIR and genotype were analysed as described in Table. Genotype means the pattern of positive KIR combinations. Significant differences between carrier vs. HAM in genotype 2 (p=0.01), and ATL vs. HAM in genotype 4 (p=0.01) were observed. Increased frequencies of genotype 3 and 2DS3 allele in HAM compared to carrier were also observed although these tendencies were not statistically significant. These preliminary results suggest that KIR gene polymorphism may play a role in determining susceptibility to HTLV-1 associated diseases. KIR genetype and HTLV-1 associated diseases Genotype 3DL1 / 2DL5 2DS1 / 2DS2 2DS3 / 3DS1 Carrier (%) * ATL (%) * HAM (%) * * this measns the genotype frequency; Y, positive; N, negative 1 Y / N N / N N / N 51.8 47.1 63.2 2 Y / Y Y / N N / Y 26.8 21.6 8.8 3 Y / Y Y / N Y / Y 1.8 7.8 10.5 4 Y / N N / Y N / N 5.4 11.8 0 5 Y / Y N / Y Y / N 1.8 2.0 7.0 6 N / Y Y / N N / Y 1.8 2.0 3.5 7 Y / Y Y / Y N / Y 1.8 3.9 1.8 Others 8.9 3.9 3.5 Carrier (%) 96.5 / 42.9 39.3 / 16.1 10.7 / 35.7 ATL (%) 96.1 / 41.2 39.2 / 21.6 9.8 / 39.2 HAM (%) 94.7 / 36.8 29.8 / 14.0 22.8 / 28.1

In June 1994, a 39 year-old male with adult T-cell leukemia was admitted to our hospital and received combination chemotherapy including epipodophyllotoxin for approximately 1 year. The monocyte count increased gradually beginning in April 1995, accelerating to 100 × 10 9 /l in January 1996, when he was diagnosed with acute monocytic leukemia. Inv(11)(q21;q23) × 2 was recognized at that time by chromosome analysis, and rearrangement of the MLL gene was shown by Southern blot analysis. From the clinical course and subsequent examinations, the case was regarded as epipodophyllotoxin-related secondary leukemia. Recently, epipodophyllotoxin has frequently been used as a treatment agent for adult T-cell leukemia. It is valuable to note that secondary leukemia may follow even such an aggressive leukemia as adult T-cell leukemia.

We performed allogenic bone marrow transplantation (BMT) in two adult T-cell leukemia (ATL) patients with HLA-identical siblings as donors. One patient, with acute ATL, relapsed 3 months after BMT. The other, with chronic ATL, has become free of disease over 18 months after the BMT from his human T-cell lymphotropic virus type 1 (HTLV-1)-negative sibling, and we were unable to detect HTLV-1 in the patient's peripheral blood. Based on our results and those of others, although there have been limited numbers of patients, BMT may represent the only potentially curative treatment for ATL, and the presence of graft-vs.-host disease tends to be related to good results, which suggests the possibility that graft-vs.-leukemia effects may play an important role in allogenic BMT for ATL.

Concomitant chemoradiotherapy is established as the standard treatment to improve the prognosis of several types of solid tumor, but has not been the general practice for hematological malignancies. Here, I report two cases of adult T-cell leukemia (ATL) with a radiotherapy-resistant bulky disease treated with concomitant radiotherapy and two topoisomerase inhibitors: etoposide (VP-16) and irinotecan (CPT-11). Patient 1 was a 78-year-old man with chemotherapy-resistant inguinal bulky mass. Radiotherapy (total 40 Gy) for this inguinal lesion was started; however, the bulky disease was found to be resistant to radiotherapy and progressed. VP-16 and CPT-11 were administered in addition to radiotherapy (after a total of 20 Gy of radiotherapy). Patient 2 was a 71-year-old man with a solitary bulky mass in left cervical lesion. Various previous chemotherapy and radiotherapy approaches had not been able to control the disease. Six months after first radiotherapy, the bulky disease rapidly progressed with the occurrence of pain. Second radiotherapy (30 Gy) was started with simultaneous administration of CPT-11 and VP-16. In both cases, the bulky disease gradually regressed and completely disappeared by the end of radiotherapy. Thus, flexible adaptation of concomitant chemoradiotherapy including two topoisomerase inhibitors may offer a potential therapeutic option for radiotherapy-resistant bulky diseases, even in hematological malignancies.