This phase I/II multicenter study evaluated romidepsin treatment in Japanese patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL). Patients aged ae<yen>20 years received romidepsin via a 4-h intravenous infusion on days 1, 8, and 15 of each 28-day cycle. Phase I used a 3 + 3 design to identify any dose-limiting toxicity (DLT) for regimens of romidepsin 9 and 14 mg/m(2). The primary endpoints for phase I and II were DLT and overall response rate (ORR), respectively. Intent-to-treat patients were those who received ae<yen>1 romidepsin dose (PTCL, n = 48; CTCL, n = 2). In phase I, none of the patients (n = 3, 9 mg/m(2); n = 6, 14 mg/m(2)) exhibited DLT. In phase II, 40 patients with PTCL were treated with 14 mg/m(2) romidepsin. The most common treatment-emergent grade ae<yen>3 adverse events were lymphopenia (74%), neutropenia (54%), leukopenia (46%), and thrombocytopenia (38%). Patients in phase II showed a 43% ORR, including 25% complete responses. Median progression-free survival was 5.6 months and median duration of response was 11.1 months. This phase I/II study identified a well-tolerated dose of romidepsin, with an acceptable toxicity profile and clinically meaningful efficacy in Japanese patients with relapsed/refractory PTCL. ClinicalTrials.gov Identifier NCT01456039.

Immunosuppressive therapy after solid organ transplantation is known to be a risk factor for the development of myelodysplastic syndromes (MDS). Herein, we report 2 patients, both of whom developed low-risk MDS after solid organ transplantation and were successfully treated with azacitidine (AZA). The 1st case was a 74-year-old man who had received liver transplantation. The initial immunosuppressive therapy consisted of cyclosporine and prednisolone. Nine years after transplantation, he was diagnosed as having MDS (RCMD). The 2nd case was a 47-year-old woman who had received cadaveric renal transplantation. The initial immunosuppressive therapy was comprised of cyclosporine, azathioprine, and prednisolone. Twenty-seven years after transplantation, she developed MDS (RA). Both patients received 75 mg/m2 AZA once daily for five consecutive days on a 28-day cycle. After 2 courses of therapy, both patients achieved hematological improvement (IWG 2006 criteria) without severe (grade 3/4) non-hematological adverse events. Moreover, AZA did not affect the status of organ transplantation in terms of engraftment and function of the graft. In conclusion, AZA would be a safe and effective agent for patients with MDS after solid organ transplantation. However, long-term follow-up is needed to confirm the safety and efficacy of AZA for patients undergoing solid organ transplantations.

Background: The purpose of this study was to quantitatively evaluate the tumor accumulation and heterogeneity of In-111-ibritumomab tiuxetan (Zevalin (R)) and tumor accumulation of F-18-fluoro-deoxyglucose (FDG) and compare them to the tumor response in B-cell non-Hodgkin's lymphoma patients receiving Y-90-ibritumomab tiuxetan (Zevalin (R)) therapy. Methods: Sixteen patients with histologically confirmed non-Hodgkin's B-cell lymphoma who underwent Y-90-ibritumomab tiuxetan therapy along with In-111-ibritumomab tiuxetan single-photon emission computerized tomography (SPECT)/CT and FDG positron emission tomography (PET)/CT were enrolled in this retrospective study. On pretherapeutic FDG PET/CT images, the maximum standardized uptake value (SUVmax) was measured. On SPECT/CT images, a percentage of the injected dose per gram (%ID/g) and SUVmax of In-111-ibritumomab tiuxetan were measured at 48 h after its administration. The skewness and kurtosis of the voxel distribution were calculated to evaluate the intratumoral heterogeneity of tumor accumulation. As another intratumoral heterogeneity index, cumulative SUV-volume histograms describing the percentage of the total tumor volume above the percentage thresholds of pretherapeutic FDG and In-111-ibritumomab tiuxetan SUVmax (area under the curve of the cumulative SUV histograms (AUC-CSH)) were calculated. All lesions (n = 42) were classified into responders and non-responders lesion-by-lesion on pre- and post-therapeutic CT images. Results: A positive correlation was observed between the FDG SUVmax and accumulation of In-111-ibritumomab tiuxetan in lesions. A significant difference in pretherapeutic FDG SUVmax was observed between responders and non-responders, while no significant difference in In-111-ibritumomab tiuxetan SUVmax was observed between the two groups. In contrast, voxel distribution of FDG demonstrated no significant differences in the three heterogeneity indices between responders and non-responders, while In-111-ibritumomab tiuxetan demonstrated skewness of 0.58 +/- 0.16 and 0.73 +/- 0.24 (p < 0.05), kurtosis of 2.39 +/- 0.32 and 2.78 +/- 0.53 (p < 0.02), and AUC-CSH of 0.37 +/- 0.04 and 0.34 +/- 0.05 (p < 0.05) for responders and non-responders. Conclusions: Pretherapeutic FDG accumulation was predictive of the tumor response in Y-90-ibritumomab tiuxetan therapy. The heterogeneity of the intratumoral distribution rather than the absolute level of In-111-ibritumomab tiuxetan was correlated with the tumor response.

A 68-year-old man was referred to our hospital due to a high fever and pancytopenia. Neither tumors nor infectious lesions were detected. Hemophagocytosis was observed on the bone marrow (BM) smear, although without abnormal cells. Prednisolone therapy was ineffective for the patient's high fever. Later on, we obtained the results of a BM biopsy indicating the presence of infiltration of atypical Reed-Sternberg cells, leading to a diagnosis of HIV-negative primary bone marrow Hodgkin lymphoma (PBMHL). However, the patient died of multiple organ failure before receiving chemotherapy. As the clinical course of PBMHL is rapid, physicians must keep in mind its possibility in similar cases.

Primary effusion lymphoma (PEL) is a rare type of non-Hodgkin lymphoma that usually develops in immunosuppressed patients infected with human herpes virus-8 (HHV-8) in conjunction with human immunodeficiency virus (HIV) infection. However, there are several reports of HHV-8-related HIV-negative cases and HHV-8-unrelated HIV-negative cases, mainly in immunodeficient and elderly patients. Here, we report one case of HHV-8-related HIV-negative PEL with gastric cancer (case 1) and one case of HHV-8-unrelated HIV-negative effusion-based lymphoma (case 2), both in elderly men. A 73-year-old man and a 79-year-old man were admitted because of lymphomatous effusions, and no mass was detectable in both cases. They were diagnosed as having malignant effusion lymphoma on the basis of cytological findings indicating atypical lymphoid cells and the expression of CD20 and CD79a. To detect evidence of HHV-8 infection in neoplastic cells, immunocytochemical staining for ORF73/latent nuclear antigen-1 (LNA-1) was performed. The results revealed that case 1 was ORF73-positive, and case 2 was ORF73-negative. Rituximab-based chemotherapy (R-THPCOP: rituximab, pirarubicin, cyclophosphamide, vincristine, prednisolone) was administered to both patients and complete remission was achieved in both. Compared to most HIV-positive PEL cases, these two cases showed a good response to chemotherapy. In cases of PEL, we should focus on HHV-8 infection and HIV status for determining prognosis.

Patients with acquired haemophilia A usually show widespread subcutaneous bleeding. We describe an 86-year-old man with acquired haemophilia A associated with prostate carcinoma, showing initial localised giant haematoma and subsequent widespread subcutaneous bleeding. A localised giant haematoma may present as a first and important sign of acquired haemophilia A.

今回，単一施設における輸血後鉄過剰症の実態を検討した。2009年と2010年の2年間に年間10単位以上の輸血を受けていた血液疾患患者は合計163例で，およそ半数が骨髄異形成症候群（61例）と再生不良性貧血（18例）であった。赤血球輸血が20単位施行された時点で血清フェリチン値が測定されていた65症例中血清フェリチン値が500 ng/ml以上，1,000 ng/ml以上であった症例の比率はそれぞれ90.8%, 66.2%であった。鉄過剰症に関連すると推測される臓器障害の比率は，全体で56.9%, 血清フェリチンが500～999 ng/mlでは43.8%, 1,000 ng/ml以上では67.4%であった。今回の解析により，「輸血後鉄過剰症の全国実態調査」の結果より早期に輸血後鉄過剰症が起こり，臓器障害も出現することが明らかになった。したがって，赤血球輸血40単位，血清フェリチン値1,000 ng/mlを除鉄療法の開始基準とするわが国のガイドラインより早期に除鉄療法を開始する必要がある可能性が示唆された。

A 32-year-old woman was referred to our hospital due to systemic lymphadenopathy. The patient's peripheral blood showed expansion of CD5+CD20+CD38+CD23- mature lymphocytes. However, the axillary lymph nodes were infiltrated by both CD23+ large lymphocytes and CD23- small lymphocytes. Because the pattern of the rearranged immunoglobulin heavy chain gene was different between the peripheral blood and lymph node samples in a Southern blot analysis, the patient was diagnosed with Richter syndrome, in which diffuse large B-cell lymphoma develops from a clone distinct from B-cell chronic lymphocytic leukemia. After undergoing rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) therapy, the patient was successfully treated with allogeneic hematopoietic transplantation, and no relapse was observed for three years. © 2013 The Japanese Society of Internal Medicine.

Aims: To evaluate the role of tumour-associated macrophages (TAMs) of the M1 and M2 types in the behaviour of diffuse large B-cell lymphoma (DLBCL). Methods and results: Double immunohistochemical staining of HLA-DR/CD68 (M1) or CD163/CD68 (M2) was performed in 101 cases of DLBCL. CD68+ cells represent the total number of TAMs. The average number of double-positive cells was counted, and the cut-off value was set at the mean number of counts, i. e. 30.7 and 27.0 for M1 TAMs and M2 TAMs, respectively. That for total TAMs was set at the 90th percentile number of total counts, i. e. 132.3. Cases were categorized into three pairs: high (34 cases) and low (67 cases) M1 TAM groups, high (39 cases) and low (62 cases) M2 TAM groups, and high (10 cases) and low (91 cases) total TAM groups. The difference in overall survival rates was statistically significant between the high and low M2 TAM groups (P < 0.01) and between the high and low total TAM groups (P < 0.05). Multivariate analysis revealed that the presence of a bulky mass and a higher number of M2 TAMs were significant factors for poor prognosis (P < 0.05). Conclusions: Estimation of specific type of macrophages, of the M1 and M2 types, is superior to the estimation of TAMs as a whole (CD68+ cells) for prediction of the prognosis of DLBCL patients.

Patients with hematologic malignancies are immunosuppressive and may develop cutaneous or invasive infections as a primary sign of immune suppression. Acute promyelocytic leukemia (acute myeloid leukemia M3) is caused by translocation of reciprocal chromosomal rearrangement t(15 17), which produces an oncogenic protein. We herein describe a 71-year-old man having cellulitis with leukocytopenia as a first sign of acute promyelocytic leukemia. Dermatologists and hematologists should keep in mind that patients with a hematologic malignancy, such as acute promyelocytic leukemia, can develop cellulitis with leukocytopenia. Copyright © 2012 S. Karger AG, Basel.

To evaluate roles of tumor-associated macrophages (TAMs) for prognosis of classical Hodgkin lymphoma (CHL). Expression of markers for TAMs, CD68, HLA-DR, CD163, HLA-DR/CD68 (M1), and CD163/CD68 (M2) was immunohistochemically examined in 82 cases with CHL. Positively stained cells were counted and correlation of number of TAMs and patients' survival time was analyzed. Number of CD163+ cells and M2 cells was significantly correlated with shorter overall survival (P < 0.05), while it was marginally significant for CD68+ cells (P = 0.0827). HLA-DR + cells and M1 cells showed no significant correlation with overall survival. When confined to mixed cellularity subtype, number of M1 cells was correlated with favorable prognosis (P < 0.05), while M2 did not (P = 0.7). Older age and male sex were unfavorable factors for prognosis. At multivariate analysis, number of CD163+ cells, M2+ cells, and age were independent factors for poor overall survival (P = 0.03, 0.02, and 0.01, respectively). CD163+ cells and M2 cells might work to be tumor promotive in CHL. M1 cells might be tumor suppressive in mixed cellularity type.

Purpose To clarify the change in the fluorodeoxyglucose (FDG) uptake by the bone marrow over time after administration of granulocyte colony-stimulating factor (G-CSF), we evaluated the correlation between the interval from the last day of administration of G-CSF to positron emission tomography/computed tomography (PET/CT) study and spinal bone marrow accumulation in patients with non-Hodgkin's lymphoma. Methods A total of 127 patients with confirmed non-Hodgkin's lymphoma who underwent FDG PET within 60 days from the last administration of G-CSF were retrospectively reviewed. Thirty age-matched and sex-matched healthy controls were also included to evaluate physiological FDG uptake. PET/CT examinations were retrospectively reviewed, and maximum standardized uptake value (SUV(max)) was measured by placing volumetric regions of interest over each thoracic and lumbar vertebra on PET images referring to CT images. Bone marrow SUV was defined as the mean SUV(max) of the vertebra. The correlation between the interval after G-CSF and the bone marrow SUV was plotted and analyzed with polynomial approximation. Results In controls, physiological bone marrow SUV of the spine was determined. In patients with lymphoma, bone marrow SUV decreased over time and reached a plateau at about 14 days after G-CSF administration, and this was higher by 5% than the plateau at 10 days. SUV declined to the 'physiological range', that is, mean+ 1 standard deviation of patients, at about 7 days. Conclusion For a PET/CT study, an interval of 10 days after G-CSF administration is recommended to minimize the influence of G-CSF on the bone marrow when evaluating treatment response in patients with non-Hodgkin's lymphoma. Nucl Med Commun 32:678-683 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

We report a rare case of chronic myelomonocytic leukemia (CMML) with pericardial effusion. After receving the diagnosis of CMML, she had been successfully treated with hydroxycarbamide (HU). However, she was admitted to our hospital due to pericardial effusion. The majority of the cells in the pericardial fluid were monocytes. We made the diagnosis of pericardial involvement with CMML cells and intravenously administered etoposide (100 mg/body daily for 5 days). Although CMML cells disappeared from the peripheral blood, the pericardial effusion still persisted. This case indicates that pericardial effusion is a possible and life-threatening complication in CMML patients despite stably controlled leukocytes.

Fournier's gangrene is a life-threatening disorder caused by aerobic and anaerobic bacterial infection. We report a case of genital infection as the initial warning sign of acute myeloid leukemia. We were able to prevent progression to Fournier's gangrene in our patient by immediate intensive therapy with incision, blood transfusions and intravenous administration of antibiotics. This case suggests that hematologists and dermatologists should keep in mind that genital infection can be a first sign of hematologic malignancy. Copyright © 2010 S. Karger AG, Basel.

We report a case of primary cardiac lymphoma (PCL) occurring in a 76-year-old man during maintenance hemodialysis. Chest computed tomography (CT) revealed a tumor with pericardial effusion in the left ventricular posterior wall. Cytological examination of the pericardial fluid revealed monotonous lymphoid cells positive for B-cell markers, and clonal immunoglobulin heavy chain gene rearrangement was detected, indicating B-cell lymphoma. Rituximab monotherapy was administered biweekly at the therapeutic level on hemodialysis. The follow-up chest CT showed tumor disappearance with pericardial fluid after two courses of therapy. Rituximab monotherapy was effective for an elderly hemodialysis patient with PCL.

Change of CD20 expression was examined in cases of diffuse large B-cell lymphoma (DLBCL). CD20 expression after treatment with anti-CD20 antibody (rituximab, Rx) for DLBCL was examined in 23 cases who received serial biopsy by immunohistochemistry (IHC) and flow cytometry (FCM). CD20- by IHC and/or FCM was defined as CD20-. Four cases were CD20- at initial biopsy but became CD20+ after chemotherapy with Rx (CH-R) (group A). Recurrent tumors in three group A cases became resistant to CH-R. Initial and recurrent tumors were CD20+ before and after CH-R in 17 cases (group B). Tumors before CH-R were CD20- in two cases (group C) and continued to be CD20- in one and turned CD20+ in the other with survival time after the relapse of 8 and 23 months, respectively. Evaluation of CD20 expression with immunohistochemical and flow cytometric methods is used for the prediction of responsiveness of relapsed DLBCL for CH-R.

We previously reported mRNA expression of glutathione S-transferases theta (GSTT)-1, wild type (623 bp) and mutant (500 bp), in patients with myelodysplastic syndrome (MDS). The deletion of 123 bp creates a sequence that is homologous to the mammalian target of rapamycin (mTOR). To analyze the function of mutant GSTT-1 gene, stable transformants for the mutant and wild-type GSTT-1 gene, respectively, were established. In this study, the expression of the wild and mutant type of the GSTT-1 gene of those stable transformants in cell lines and in bone marrow cells from MDS patients by reverse-transcription polymerase chain reaction (RT-PCR) was observed in the presence or absence of rapamycin. Significant growth inhibition by rapamycin was observed among stable transformants for the mutant GSTT-1 gene, but not wild type GSTT-1 gene, and was indicative of typical apoptosis.

The pharmacokinetics (PK) and pharmacodynamics (PD) of the once-daily, oral ironchelating agent, deferasirox (Exjade (R), ICL670), have been evaluated further in a Phase I, openlabel, multicenter, dose-escalation study in Japanese patients with myelodysplastic syndromes, aplastic anemia, and other anemias. Deferasirox was initially administered as a single dose of 5 (n = 6), 10 (n = 7), 20 (n = 6) or 30 (n = 7) mg/(kg day) and then after 7 days seven daily doses were administered. Linear PK (C (max) and AUC) were observed at all doses after a single dose and at steady state, and dose-dependent iron excretion was observed. Pharmacokinetic/pharmacodynamic parameters were similar to those reported in a Caucasian beta-thalassemia cohort. Following the single- and multiple-dose phases, 21 of 26 patients progressed to a 3-year extension phase of the study, where dose reductions and increases [5-30 mg/(kg day)] were allowed following safety and efficacy assessments. In the interim, 1-year data show that deferasirox was well tolerated, with generally infrequent and mild adverse events. Reductions in serum ferritin levels were observed and a negative iron balance achieved at doses of 20-30 mg/(kg day). These data suggest that deferasirox has a stable and predictable PK/PD profile, irrespective of underlying disease or race, and a predictable and manageable safety profile suitable for chronic administration.

Purpose We previously reported that all-trans retinoic acid (ATRA) inhibited growth in human T-cell leukemia virus type I (HTLV-I)-positive T-cell lines and in fresh cells from patients with adult T cell leukemia (ATL). Here, we confirmed the clinical effects of ATRA in 20 patients with ATL. Materials and methods The 20 patients (n = 20) with a median age of 56 (range 35-73) years who were diagnosed with ATL received ATRA orally. Results The efficacy of treatment was as follows: no complete response (CR), a partial response (PR) in 40% of the patients, no change (NC) in 45% of the patients, and a progressive disease (PD) in 15% of the patients. In seven acute-type ATL patients, a PR was achieved in two (28.5%), NC was observed in two (28.5%), and a PD was observed in three (42.8%). In three lymphoma-type ATL patients, a PR (100%) was achieved. Among four chronic-type ATL patients, a PR was achieved in one (25%) and NC was observed in the remaining three (75%). In six smoldering-type ATL patients, a PR was achieved in two (33.3%) and NC was observed in four (66.6%). The major side effects were headache (n = 5), transient liver dysfunction (n = 2), hyperlipidemia (n = 2), and anorexia (n = 1). Conclusions These results indicated that ATRA might be a useful agent for the safe treatment of ATL.

3年生および4年生の学生を対象として、英語教材を用いてClinical Pathological Conference(CPC)を実施した。最後のCPCを終了し、学生および教員を対象としアンケートを実施した。回収率は学生100%、教員78.5%であった。英語教材によるCPCの順序として、和訳、問題点の列挙、検査結果の解析、画像診断などがあり、3年生および4年生にとっては少しレベルが高すぎた可能性がある。しかし、教員は確実に学生の学習意欲を感じ取っており、学生の準備状況も良好であった。教員の熱意も学生は評価しており、両者にとっても有意義であった。

We previously reported that all-trans retinoic acid (ATRA) inhibited growth in HTLV-1-positive T-cell lines and fresh cells from patients with adult T-cell leukemia. Interestingly, ATRA significantly inhibited reverse transcriptase (RT) activity similar to azidothimidine (AZT) in HTLV-1-positive T-cell lines. To clarify whether ATRA has an inhibitory effect on the replication of HIV, we examined HIV proviral DNA in a HIV-1-positive cell line (8E5) using real time PCR. ATRA as well as AZT reduced the proviral DNA load of 8E5 in a dose- dependent manner. These results suggest that there is a common element of ATRA signaling in both HTLV-1 and HIV. Furthermore, we examined the effects of ATRA on viral replication in primary lymphocytes of three individuals infected with HIV. ATRA reduced viral replication significantly similar to AZT. These findings suggested that ATRA acts as a RT inhibitor, reducing the HIV-1 proviral DNA load. Finally, we conclude that ATRA may be a potential therapeutic agent for HIV infection.

血液疾患に合併する難知性細菌感染症の原因菌の変遷と使用抗生剤戸の相関について報告した。

白血病治療中の感染症原因菌の変遷と使用抗生剤の傾向との関係について報告した。

A 53-year-old male with myelodysplastic syndrome developed Sweet's syndrome extensively over his left iliac and inguinal regions that was refractory to standard treatment with corticosteroids and chemotherapy, received a stem cell transplant from an HLA-matched unrelated donor, conditioned by reduced-intensity regimen. The patient achieved complete hematological remission, and the cutaneous lesions improved gradually and then disappeared completely despite the patient receiving granulocyte colony-stimulating factor after transplantation and developing acute graft-versus-host disease.

The authors previously reported the mRNA expression of Glutathione S-transferases theta (GSTT)-1, wild type ( 623 bp) and mutant ( 500 bp) in MDS patients. The deletion of 123 bp creates a sequence that is homologues to mammalian target of repamycin ( mTOR). To analyse the function of mutant GSTT-1 gene, stable transformants for the mutant and wild-type GSTT-1 gene, respectively, were established. In this study, the expression of wild and mutant type GSTT-1 gene of those stable tramsformants and bone marrow cells from MDS patients by RT-PCR was observed in the presence or absence of rapamycin. In result, exposure of rapamycin led to the disappearance of just the mutant gene band. This phenomenon possibly indicates that rapamycin only attacked the mutant GSTT-1 expressing clone.

紅皮症を呈したAnaplastic Large Cell Lymphomaについて免疫組織学的に検討した。

We describe a patient with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) who developed an extramedullary blast crisis in the central nervous system (CNS) and then a subcutaneous tumor of the neck during treatment with imatinib mesylate. Administered 400 mg of imatinib mesylate after the diagnosis of chronic-phase CML, the patient achieved a complete cytogenetic remission 4 months later. However, he developed a mixed myeloid/B-cell blast crisis with additional karyotype abnormalities only in the CNS during a complete cytogenetic remission in the bone marrow. Several doses of intrathecal chemotherapy and whole-brain irradiation were effective in treating the blast crisis in the CNS. After 7 months of complete cytogenetic remission, the patient experienced a subcutaneous tumor in the right neck. A biopsy of the tumor revealed a mixed myeloid/T-cell blast crisis. The cytogenetic analysis showed that the blast crisis clone in the neck tumor was different from that of the CNS. An increased dose of imatinib mesylate was ineffective in treating the neck tumor. Irradiation to the right neck was therefore undertaken. This case suggests that the development of a clone resistant to imatinib mesylate is not always detected in the bone marrow and that multiple Ph-positive clones have the potential to become transformed into a blast crisis. (c) 2005 The Japanese Society of Hematology.

Fractalkine (CX3CL1) and its receptor CX3CR1 play an important role in natural killer (NK) cell- and cytotoxic T cell-mediated endothelium damage. Here we describe the cytotoxicity of myelodysplastic syndrome (MDS)-derived T cell line, K2-MDS, through the fractalkine-CX3CR1 system. K2-MDS cells induced apoptosis against CD34(+) cells from normal bone marrow (BM) in a direct cell contact manner. K2-MDS cells expressed perforin and granzyme B, but they lacked Fas ligand expression. A specific inhibitor for perforin, concanamycin A, blocked K2-MDS-dependent cytotoxicity. Furthermore, a CX3C-chemokine, fractalkine, was expressed in CD34(+) cells, and its receptor, CX3CR1, was expressed on K2-MDS cells. The neutralizing monoclonal antibody (MoAb) for fractalkine and soluble fractalkine significantly inhibited K2-MDS-dependent cytotoxicity. K2-MDS cells also induced the cytotoxicity against human umbilical cord endothelial cells (HUVECs) expressing fractalkine. These data indicate that K2-MDS may be a perforin-granzyme-positive T cell line that exerts a cytotoxic effect on CD34(+) cells mediated through the fractalkine-CX3CR1 system. (C) 2004 Elsevier Inc. All rights reserved.

The frequency of NK-cell related neoplasms was estimated among lymphoproliferative diseases diagnosed and treated in Osaka, Japan, from 1999 to 2003. The total number of registered cases was 1,400, among which 1,092 patients were diagnosed as having malignant lymphomas. There were 987 cases of non-Hodgkin's lymphoma (NHL) and 105 (9.6%) of Hodgkin's lymphoma. Immunophenotypic analysis revealed that 743 patients had B-cell lymphomas and 209 T/NK-cell lymphomas. Among the T/NK-cell lymphomas, 40 showed positive immunoreactivity for CD56, and thus they were judged to be NK/T-cell lymphomas. They included one blastic NK-cell lymphoma and 39 NK/Tcell lymphomas. NK/T-cell lymphomas were further divided into three categories based on the main site of lesions: nasal type (23 cases), non-nasal extranodal type (11 cases), and nodal type (5 cases). The positive rate of infection with the Epstein-Barr virus determined by in situ hybridization was 83%, 36%, and 25% in the nasal, non-nasal, and nodal type, respectively. A mosquito allergy was found in one patient with EBV-positive non-nasal NK/T-cell lymphoma. The present study showed that the frequency of NK-cell related neoplasms among all NHLs was 4% in an ATL-non-endemic area of Japan. (C) 2004 Wiley-Liss, Inc.

Classical Hodgkin's disease (HD) is characterized by rare neoplastic Hodgkin and Reed-Sternberg (H-RS) cells within abundant reactive cellular backgrounds. In most cases, H-RS cells originate from the B-cell lineage, but their immunophenotypes are unusual. Here we newly found frequent expression of chemokine receptors CXCR6 and CCR10 and their respective ligands CXCL16 and CCL28 in RD-derived cell lines. CCR10 is known to be selectively expressed by plasma cells, whereas CCL28 attracts eosinophils via CCR3 and plasma cells via CCR10 and CCR3. Therefore, we examined their expression in HD tissues by immunohistochemistry. We found that H-RS cells in 15 of 19 cases were positive for CCL28. Among them, seven cases were also positive for CCR10, suggesting a potential autocrine effect. In situ hybridization confirmed the expression of CCL28 mRNA in H-RS cells. The CCL28 positivity in H-RS cells did not significantly correlate with that of LMP-1, CCL17, CCL22, or CCL11. However, it significantly correlated with the background accumulation of eosinophils, plasma cells, and CCR10(+) cells. Thus, the production of CCL28 by H-RS cells may play a major role in tissue accumulation of eosinophils and/or plasma cells in classical HD. The frequent expression of CCR10 in H-RS cells themselves also supports their close relationship to plasma cells.

We systematically examined the repertoire of chemokine receptors expressed by human plasma cells. Fresh bone marrow plasma cells and myeloma cells consistently expressed CXCR4, CXCR6, CCR10, and CCR3. Accordingly, plasma cells responded to. their respective ligands in chemotaxis and very late Ag-4-dependent cell adhesion to fibronectin. Immobilized CXC chemokine ligand (CXCL)16, a novel transmembrane-type chemokine and CXCR6 ligand, also directly induced adhesion of plasma cells without requiring G(alphai) signaling or divalent cations. Furthermore, we revealed consistent expression of CXCL12 (CXCR4 ligand), CXCL16 (CXCR6 ligand), and CC chemokine ligand 28 (CCR10 and CCR3 ligand) in tissues enriched with plasma cells including bone marrow, and constitutive expression. of CXCL12, CXCL16, and CC chemokine ligand 28 by cultured human bone marrow stromal cells. Collectively, plasma cells are likely to be recruited to bone marrow and other target tissues via CXCR4, CXCR6, CCR10, and CCR3. CXCR6 may also contribute to tissue localization of plasma cells through its direct binding to membrane-anchored CXCL16.

Follicular lymphoma (FL) is defined as a neoplastic proliferation of follicle center cells with varying follicular areas. To learn the time trend of FL in the Osaka area, an adult T-cell leukemia/lymphoma (ATL) nonendemic area of Japan, we examined the frequency of FL among all non-Hodgkin's lymphomas (NHLs) during the period 1964 to 1987 (n = 1000) and 1999 to 2001 (n = 659). The frequency of FL with varying follicular areas increased from 1964-1987 to 1999-2001. There was a significant difference in frequency of total cases of FL (14.2% versus 18.8%) (P <.05) and FL with no to 25% follicular area (2.3% versus 5.0%.) (P <.01). According to the Berard criteria, cytologic grade of FL was defined by counting the number of centroblasts (CB) in 10 neoplastic follicles as follow: less than or equal to5 CB; per high power field (HPF), grade 1; 6-15 CB, grade 2; >15 CB, grade 3. Immunohistochemical staining with monoclonal antibodies for bcl-2 and CD10 was performed. There was an inverse correlation between follicular area and cytological grade (P <.0001) and bcl-2 expression and cytological grade (P <.01). That is, the larger the follicular area in cases with a lower cytological grade, the stronger was bcl-2 expression in a lower cytological grade. There was a significant correlation between follicular area and stage of disease (P <.05). That is, the follicular area was larger in cases in an advanced stage. This study showed the increase in frequency of FL in Osaka, Japan. Change of lifestyle in Japan may be one of the causative factors for the increase.

汎血球減少で発症し、特異な経過をとった慢性骨髄性白血病の一例を報告した。発症は、フィラデルフィア染色体を有し、その後約2カ月でリンパ性急性転化をした。一時的に化学療法が奏功したが、その後再発し、死亡した。（英文）

Chemokines and chemokine receptors play important roles In migration and tissue localization of various lymphocyte subsets. Here, we report the highly frequent expression of CCR4 In adult T-cell leukemia (ATL) and human T-cell leukemia virus type 1 (HTLV-1)-immortalized T cells. Flow cytometric analysis revealed that ATL and HTLV-1-immortalized T-cell lines consistently expressed CCR4. Inducible expression of HTLV-1 transcriptional activator tax in a human T-cell line Jurkat did not, however, up-regulate CCR4 mRNA. In vitro Immortalization of peripheral blood T cells led to preferential outgrowth of CD4(+) T cells expressing CCR4. We further demonstrated highly frequent expression of CCR4 in fresh ATL cells by (1) reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of CCR4 expression in peripheral blood mononuclear cells (PBMCs) from patients with ATL and healthy controls; (2) flow cytometric analysis of CCR4-expressing cells in PBMCs from patients with ATL and healthy controls; (3) CCR4 staining of routine blood smears from patients with ATL; and (4) an efficient migration of fresh ATL cells to the CCR4 ligands, TARC/CCL17 and MDC/CCL22, in chemotaxis assays. Furthermore, we detected strong signals for CCR4, TARC, and MDC in ATL skin lesions by RT-PCR. Collectively, most ATL cases have apparently derived from CD4+ T cells expressing CCR4. It is now known that circulating CCR4(+) T cells are mostly polarized to Th2 and also contain essentially all skin-seeking memory T cells. Thus, HTLV-1-infected CCR4+ T cells may have growth advantages by deviating host immune responses to Th2. CCR4 expression may also account for frequent infiltration of ATL into tissues such as skin and lymph nodes. (C) 2002 by The American Society of Hematology.

AML-MOによる顆粒細胞肉腫では、ミエロペルオキシダーゼ蛋白の発現が少なく診断が困難であるが、ミエロペルオキシダーゼ遺伝子の発現をin situ hybridization を使って検出することにより骨髄球系腫瘍であることを証明することができる。（英文）

グルコースによる腹膜中皮細胞の増殖能抑制の機序としてTGF-β1の発現の亢進と、そのRb蛋白質のリン酸化抑制による細胞周期制御異常の関与が考えられる。腹膜機能低下発症の機序としてTGF-β1が重要な役割を担っている可能性が示唆された。

Multicentric Castleman's Diseaseは非定型リンパ球増殖性疾患の1つであり, 多クローン性形質細胞性リンパ腫の組織像を呈し, 臨床像としては発熱, 貧血, 高ガンマグロブリン血症等の急性炎症性変化を来す疾患群である.またその臨床経過中免疫異常を来し, 感染症や悪性疾患を合併するものもあるが, その原因は不明である.本研究では, Multicentric Castleman's Disease患者血清中にレクチン誘導性T細胞芽球化を著明に抑制する分画を見いだし, 分離後検討を加えた.患者血清より分離精製されてきたT細胞芽球化抑制因子の候補として, IL-6依存性急性炎症性タンパクであるα2マクログロブリンが考えられた.同分子は以前より免役機構への関与が考えられている720kDの巨大分子である.この患者由来のα2マクログロブリンは健常人由来のそれと比較して強い芽球化抑制能を示し, また一方ではペプチドマッピングにおいて泳動パターンの相違を認め, 両者間の質的差異が示唆された.これらのことから, 患者由来のα2マクログロブリンが何らかの修飾を受けることによって, より強い芽球化抑制能を獲得していると考えられた.

We have established a T lymphoid cell line, K2-MDS, from the peripheral blood mononuclear cells (PBMC) of a patient with acute myeloblastic leukemia (AML) transformed myelodysplastic syndrome (MDS). K2-MDS cells are positive for the expression of CD4, CD5, CD13, CD25, CD71, CD95, HLA-DR and cytoplasmic CD3. Southern blotting analysis shows T cell receptor (TCR) β chain genes rearrangements, whereas immunoglobulin heavy chain (IgH) genes are not rearranged. Further, the patient PBMC contains TCR β chain genes rearrangements in the same manner as K2-MDS cells. The data indicate that K2-MDS is a T lymphoid cell line derived from a myelodysplastic clone in the patient PBMC. This new MDS-derived cell line K2-MDS may be a useful in vitro model for studies on the pathogenetic mechanisms leading to MDS. Copyright (C) 2000 Elsevier Science Ltd.

Left cervical lymphadenopathy developed in a 50-year-old male who had a history of adult-onset Still's disease for the preceding 18 months. Still's disease is characterized by rash, fever, and leukocytosis. Lymphadenopathy has been reported in about 60% of the patients, and most histopathologic studies have shown non-specific reactive hyperplasia. However, in this case, an open biopsy of the cervical node revealed a histology of diffuse large B-cell lymphoma. The B-cell malignant lymphoma that developed may have resulted from a sequential progression of a previous stage of benign lymphoproliferative lesion. Our case suggests that the pathophysiology of adult-onset Still's disease involves the stimulation of lymphoid systems to the point of progression towards lymphoma. Malignant lymphoma should be added to the list of life-threatening complications which, although rare, are associated with this disease.

細胞生物学から分子生物学レベルまで、現在では蛋白の分離精製は必須のテクニックとなりつつある。免疫沈降法はこのうちで最も基礎的かつ応用範囲の極めて広いテクニックである。本稿で我々は免疫沈降法について実際のプロトコールとともに解説した。

We observed the effects of the retinoic acid (13-cis retinoic acid; 13-cis RA, and all-trans retinoic acid; ATRA) for the cell growth and the expression of CD 25 on peripheral blood mononuclear cells (PBMC) from 17 patients with adult T cell leukemia (ATL). Fourteen had acute type, 1 had chronic type, and 2 had smoldering type of ATL. We divided those patient into 3 groups (hyper-sensitive, sensitive and resistant group) by determined with reduction rate of [3H]-thymidine incorporation obtained before and after treatment with 13-cis RA or ATRA respectively. Growth inhibition was not observed in normal PBMC by 13-cis RA or ATRA. However, no down-regulation of CD 25 expression was observed on PBMC in all patients and normal individuals after treratment with 13-cis RA or ATRA. In the aspect of growth inhibition on PBMC in ATL patients, we tried to clarify the mechanism of the phenomenon. In agarose gel electrophoresis, extracted genomic DNA from retinoic acid treated PBMC in hyper-sensitive and sensitive ATL patients showed multimer DNA fragmentation pattem. On the other hand, genomic DNA from PBMC after treatment with retinoic acid in resistant ATL patients and normal individuals showed high molecular DNA pattern. without fragmentation. Taken together, it is suggested that retinoic acid could induce growth inhibition of PBMC in some ATL patients resulting in DNA fragmentation, apoptosis. We deeply consider that retinoic acid may be an useful agent for ATL patients in clinical aspect.

The author investigated the capacity of our established thymic stromal cell clone (MRL 104.8a) or its derived factor(s) to induce differentiation of immature thymocytes. One-day culturing of purified adult murine double negative (CD4^-8^-) thymocytes on the MRL 104.8a thymic stromal cell monolayer resulted in the induction of an appreciable per cent of CD4^-8^+ thymocytes. A bone marrow-derived stromal cell or L929 fibroblast monolayer failed to generate CD4^-8^+ cells. This differentiation could also be induced by a semi-purified sample of the MRL 104.8a culture supernatant that contained thymic stroma-derived T cell growth factor (TSTGF) capable of contributing to the growth of double-negative immature thymocytes. CD4^-8^+ thymocytes generated one day after co-culturing with the MRL 104.8a cells or the TSTGF-containing sample were found to be CD3^- J11d^+, excluding a possibility of expansion of mature (CD3^+4^-8^+) thymocytes present in the thymus. More importantly, when the culture period was extended to 2 or 3 days, an appreciable number of CD4^+8^+ and single positive (CD4^+) cells were generated on the MRL 104.8a monolayer. Thus, these results the directly demonstrate that CD3^-4^-8^- immature thymocytes are promoted to differentiate through a rapidly cycling intermediate (CD3^-4^-8^+) into double- and single-positive cells by a specialized thymic stromal component.

難治性B細胞リンパ腫に対する放射免疫療法の使用の実態につき、当院の成績をもとに提示した。

発熱性好中球減少症における当院での起炎菌の変遷および抗生剤選択について解説した。

近畿大学におけるFebrile neutropenia（FN）における起因菌の変遷について検討した。カルバペネム系抗生剤の頻用以降、G陰性菌の頻度およびMRSAの頻度が増加しており、抗生剤使用の方法に一考を要することが示唆された。

【背景と目的】人工透析業務には、迅速な対応が必要とされる場面が多く、医師の指示を待たずに看護師や臨床工学技士の判断で対応することがある。今回、医師の透析継続指示に反し、患者の終了希望を優先し透析を終了するという事例が発生した。医師の指示に従うことは業務上重要であるが、透析続行により患者の安全が保たれない可能性もあり得る。医師と看護師の間に確執を残さず、かつ、看護師・技師が安易に透析終了の判断を下す傾向にないよう、TeamSTEPPSにのっとっりコミュニケーション上の問題点や改善策をチームで再検討した。【取り組み】透析終了業務時に起こった事例について、TeamSTEPPSの考え方をもとに振り返りを行った。【結果】患者が透析終了を希望した際、他患者の透析終了時間が重なっており、担当看護師が一人で医師への連絡や患者の対応をしていた。医師に透析を終了したい事を電話で報告するが、SBARで報告ができず、医師から「何の情報もなく、困

北陸がんプロフェッショナル養成プログラムの要請を受け、一般患者向けに悪性リンパ腫治療の現状を解説した。

放射免疫療法による悪性リンパ腫治療時の安全性とその適応について報告した

グループ・ネクサス・第19回医療セミナーとして、患者向けに悪性リンパ腫の病態および治療につき解説した。

血管免疫芽球型T細胞性リンパ腫（ATIL）治療中に赤芽球癆（PRCA）を合併し、化学療法とともに改善した一例について報告し、当科のケモカイン研究の結果と併せ報告した。

放射免疫療法による再発難治B細胞リンパ腫治療の実際とその問題点について解説した。

輸血後鉄化過剰症に対する鉄キレート療法施行時の効果、副作用とその対応について報告した。

鉄過剰症の現状と新規鉄キレート療法の効果と問題点について解説した。

59歳，女性。2007年11月末から39度台の発熱を伴って体幹に皮下結節が出現した。初診時，左頸部および体幹に径3cmまでの皮下硬結が計8個みられ，一部は潰瘍化していた。生検組織像は，主に皮下脂肪組織内に異型リンパ球の稠密な浸潤があり，一部ではlace－like patternがみられた。真皮内にも異型リンパ球の浸潤がみられた。異型リンパ球の表面マーカーはCD3陽性，CD4陰性，CD8陰性，CD20陰性，CD56陽性であり，TCRβ鎖の遺伝子再構成は認められなかった。血液内科でCHOP－E療法を開始し腫瘍は消退したが，3クール終了後，皮下結節が出現し，骨髄検査では血球貪食像が認められた。種々の化学療法を施行したが効果なく2008年7月末に永眠された。腫瘍細胞におけるγδ型リンパ球の形質については検索できなかったが，他の所見から皮膚γδ型T細胞リンパ腫が考えられた。

造血幹細胞移植患者において、骨粗鬆症の診療として利用される骨代謝マーカーを測定し、移植後の骨量に対する影響と骨量減少に対するビスフォスフォネート製剤介入の有効性の検討を前方視的に行った。

第9回NPOグループ・ネクサス悪性リンパ腫医療セミナーにおいてリンパ腫の病理病態および最近の治療について報告した。

＜現病歴＞ 平成20年1月に右鼡径部の皮下腫瘤に気付き増大傾向となったため、大阪労災病院皮膚科受診し生検の結果、び慢性大細胞リンパ腫(DLBCL)と診断され紹介となる。PET-CTでは両腋下・右鼡径部にFDGの集積を認めた。骨髄穿刺ではDLBCL細胞の浸潤を認めなかったことよりStage Ⅲと診断した（IPIはH-I）。4月2日からR-THP-COP療法開始し副作用なく終了し2回目より外来治療となる。6月20日に４回目の同療法後、7月4日に肝障害(GOT 131IU/l, GPT 153IU/l, T-bil 0.8mg/dl, ALP 227IU/l,)を認め、7月20日にはGOT 4625IU/l, GPT 1647IU/l, T-bil 9.3mg/dl, D-bil 7.0mg/dl, ALP 283IU/lと著増し黄疸も認められた。腹部CT・超音波所見でも肝腫大・胆嚢壁肥厚あり急性肝炎で入院となる。 ＜入院後経過＞ HBs抗原 98.97IU/ml, HBs抗体陰性、Hbe抗原陰性、HBe抗体 99％、HBc抗体 10.4S/CO、HBV-DNA定量で8.7LGE/mlと上昇しており、平成15年のHBs抗原は陰性で輸血歴もないことより急性B型肝炎の再活性化(reactivation)と診断した。なおDLBCLは寛解状態を持

血液疾患における感染症治療-Febrile Neutropeniaに対するサイクリング療法の効果について報告した

発熱性好中球減少症における抗菌剤サイクリング療法の臨床的有用性について報告した。 サイクリング療法により治療効果、耐性菌発症についてその有用性が示された。

当科において1回目の同種造血幹細胞移植(HSCT1)後の再発または生着不全に対する2回目の同種造血幹細胞移植(HSCT2)の移植成績について後方視的に解析した。

同種骨髄移植拒絶後に臍帯血ミニ移植が奏効した異形性を伴う急性骨髄性白血病の一例を経験した。 移植後拒絶に対し、再移植の選択肢として臍帯血ミニ移植の有用性が示された。

診断困難であった濾胞性リンパ腫についてのMulti dimensional flow cytometry解析によりabberant lineageを検出することにより確定診断が可能となり、その有用性が検証された。

当科で施行した母児間免疫寛容理念に基づくHLA不一致造血幹細胞移植9例の安全性と有用性について検討した。全例が進行期の症例であったが，3年3ヶ月の長期生存例もあり，フルマッチドナーが存在しない場合でも，母児間免疫寛容理念に基づくHLA不一致血縁者間造血幹細胞移植が有用な選択枝になり得ると考えられた。

For patients with hematological disease who had fever caused by an unknown pathogen, including febrile neutropenic patients, we performed antimicrobial cycling and assessed changes over time in the isolation rates of MRSA, Pseudomonas aeruginosa, etc.We concluded that cycling of four classes of antibiotics used in this study was effective in patients with fever of unknown origin, including febrile neutropenic (FN) patients, since it could decrease the isolation rates of MRSA and P. aeruginosa.

骨髄異形成症候群（以下MDS）における無効造血は過剰なアポトーシスが病態とされているが、詳細は不明である。一方、近年、SDF-1/CXCR4系が造血幹細胞における分化、増殖および生存に関するケモカインとして注目されている。今回われわれは、低リスクMDS患者のCD34陽性細胞において、アポトーシスとSDF-1/CXCR4系が有意に相関関係を示す結果を報告した。（英文）

症例：46歳 男性。平成14年6月に白血球増多を主訴に来院され骨髄穿刺を施行の結果AML(M5b)と診断された。JALG97プロトコールに従い寛解導入療法を施行することにより完全寛解を得た。地固め２コース終了後にカリニ肺炎を合併し人工呼吸器管理中に再発を認めCA療法、地固め３コース等施行するも完全寛解には至らず、非寛解状態で骨髄バンクドナーから骨髄移植を施行し生着、完全寛解を確認すもday+79に再発を認めた。同ドナーからのDLTを施行することにより再度寛解に至るも急性GVHDの悪化を認め（Grade Ⅳ）、急性膵炎も合併し蛋白分解酵素阻害剤等による治療が必要であった。day+160頃から急激な腹部膨満と腫瘤触知を認め、CT上巨大膵仮性のう胞が確認された。その頃よりGVHDによる肝不全も合併し腹部イレウスも悪化、またAMLの再発も認められ血栓性血小板減少性紫斑病(TTP)も合併し血漿交換を施行するも脳出血で死亡された。急性GVHDによる急性膵炎後に発症した仮性膵のう胞の急激

We tried to study the clinical effect of R-MECP therapy for non-Hodgkin B-cell lymphoma, and domonstrated the safety and efficasy for even relapsed and reflactory cases.

56歳女性、seronegative RAの患者。その経過中にサラゾスルファピリジン内服により、薬剤性間質性肺炎と皮疹を合併した報告例は極めて文献的にも稀であることから、その一例を報告した。

症例は72歳女性MDS overt M6。初回治療としてAra-C、IDRを投与し、問題なく経過したが寛解に至らず持続Ara-C、MITの併用で再寛解導入療法を行った。治療開始13日目、上下肢の痙攣を認め、頭部MRI上びまん性に信号異常を検出し、PLESと診断した。

第80回近畿血液学地方会シンポジウムにおいて、血液疾患における感染病及びその治療について、当科の感染症発症の経過を併せて最新の知見を報告した。

マントル細胞リンパ腫は、低悪性度グループに数えられてはいるものの、再発が多く予後不良である事が知られている。1994年から現在まで当科における成績を発表した。

26歳の女性に多関節炎・耳介の炎症で発症した、比較的稀な再発性多発軟骨炎について報告した。

MDS由来T細胞株K2-MDS細胞はCD34陽性細胞に対して細胞障害を示し、細胞株はperfernin/ gronzyneを有することから細胞障害系路が同定された。抗原認識においてfractalkine/CX3CR1システムが重要であることが判明した。

ホジキン病におけるケモカインの発現解析する為に細胞株を使用しケモカインについてRT-PCRを行い、MECの発現を新たに認めた。次にMECと好酸球、形質細胞の組織浸潤についての相関を調べた所、有意差を持って相関関係を認めた。

骨髄異形成症候群の無効造血にはアポトーシスが関与しているとされるが、詳細は不明である。近年SDF-1/CXCR4システムの造血幹細胞の増殖や分化への関与が注目されている。我々は骨髄異形成症候群におけるSDF-1/CXCR4システム異常の関与を明らかにしたので、報告した。

我々は1999～2003年に大阪リンパ腫研究会に登録されたNK細胞関連リンパ腫について検討を行った。39例中全てにCD5、TIA-1を認め、EBERはnasal type 83%で最も高かった。non-Masal typeは予後においても極めて不良であった。

MDS由来T細胞株K2-MDS細胞のCD34陽性細胞に対する細胞障害について検討した。共培養系でCD34陽性細胞に細胞障害を示し、fractalkine/CX3CR1システムを介して標的細胞を認識することが判明した。

症例はCML1st.CPで血縁間で骨髄移植を施行。以後も特に大きな合併症を認めなかったが、d90あたりから発熱、呼吸苦が出現。各種抗生剤、抗真菌剤投与するも軽快せず死亡された。剖検結果から気管支肺アスペルギルス症と診断し得た症例であった。

これまでにCXCL13は濾胞樹状細胞に発現することのみが報告されているが、ホジキンリンパ腫内ではT細胞に発現することが確認された。そのレセプターであるCXCR5はHRS細胞に陽性像を示したがこれは今回の調査した症例の約半数であった。

MDS由来細胞株、K2-MDSのCD34陽性前駆細胞に対するアポトーシス誘導機序を解析した結果、ケモカインシステムのフラクタルカインとCX3CR1を介して、パーフォリン、グランザイムB分子に基づく細胞死であることが判明した。

骨髄異形成症候群(MDS)においてのシクロスポリンによるT細胞を介する免疫抑制療法の機序をMDS由来T細胞株K2-MDSのCD34陽性細胞へのアポトーシス誘導モデルを用いて解析した。

血液透析歴2年の58歳の女性。BHLと頚部リンパ節生検からサルコイドーシスと診断し、ステロイドを投与開始したが、漸減中に粟粒結核を合併した。結核の危険因子について文献的考察を加え報告した。

CHOP抵抗性CD20陽性低悪性度悪性リンパ腫に対し、salvage protocolとしてRituximab＋mitoxantrone, etoposide, carboplatin, and prednisolone(MECP)療法の有効性を検討した。結果として、CRが4例/6例、PRが1例/6例と良好な結果を得ている。

MECP-R療法により寛解を得た治療抵抗性濾胞性リンパ腫の1例および当科におけるMECP-R療法の治療成績をあわせて報告した。

CHOP抵抗性CD20陽性低悪性度悪性リンパ腫に対し、Rituximab＋mitoxantrone, etoposide, arboplatin, and prednisolone(MECP)療法を用いたpilot studyを施行しその有効性を検討した。結果として、CRが4例/6例、PRが1例/6例と良好な結果を得ている。

MDSの血球減少にはT細胞による免疫学的機序が関与しており、免疫抑制剤シクロスポリンA(CsA)が効果を示す。今回我々は、MDS由来T細胞株K2-MDSの骨髄CD34陽性細胞への影響とCsAによるK2-MDSへの細胞障害活性検討した。

急性骨髄性白血病加療中、突然の発熱、CRP上昇をきたし、マイコドットにて診断し得、加療により結核の改善を認めた。結核加療中、白血病病勢増悪を認めず現在も経過良好である。

PNHではPIG-A遺伝子変異以外のなんらかの異常がPNHクローンの増大に関わっている可能性がある。我々はPIG-A遺伝子異常以外の要因を検出するためPNHクローンと非PNHクローン間で、発現量に差のある遺伝子のスクリーニングを試みた。

濾胞性リンパ腫の頻度は日本ではアメリカに比較し少ないが、大阪地区で1999-2001に発症した非ホジキンリンパ腫に対する割合は増加傾向にあった。加えて濾胞形成率、cytological grade、bcl-2、CD10の発現と病期についての関係を検討した。

非寛解期症例に対し、骨髄非破壊的造血幹細胞移植を施行した。9例中2例はⅡ度のGVHDを来したのみで寛解状態が持続しており、GVL効果が期待できた症例と推察された。本検討から再発難治性症例にも骨髄非破壊的造血幹細胞移植が有用と考えられた。

当科および関連施設において、慢性骨髄性白血病に対する、新しい分子標的療法として、開発されたチロシンキナーゼ阻害剤グリベックの治療成績を、有害事象を含めて紹介した。

光顕的ペルオキシダ－ゼ陰性骨髄系腫瘍における鑑別診断確定の一助となるべく、MPO-PNAを用いたフローサイトメトリーによるMPO-RNA検出法を確立し、この感度及び特異性について検討を加えた。

MDSの血球減少にはT細胞による免疫学的機序が関与しており、免疫抑制剤シクロスポリンA(CsA)が効果を示す。今回我々は、MDS由来T細胞株K2-MDSの骨髄CD34陽性細胞への影響とCsAによるK2-MDSへの細胞障害活性を検討した。

Follicular Lymphomaにおける濾胞形成率、cytological gradeの間では、相関関係がみられた。濾胞形成率と病期の間にも相関関係が認められ、濾胞形成率が高いものなど病期が進んでいる傾向がみられた。

骨髄造血幹細胞の異常である骨髄異形成症候群(MDS)における、Tリンパ球の異常の詳細は不明であり、適切な細胞株も存在しない。今回、われわれは、MDS患者の末梢血から、特異なT細胞株を樹立したので報告した。

光顕的ペルオキシダ－ゼ陰性骨髄系腫瘍におけるMPO-RNAの検出をMPO-PNAを用いフローサイトメーターで検出する方法を確立した。この方法は細胞株のみならず臨床検体に対しても応用可能である事が明らかになった。

骨髄非破壊性末梢血幹細胞移植により治癒したsweet病による難治性皮膚潰瘍を合併したMDS overt症例を経験したので発表した。

CD3、CD50陽性でTCRの再構成を認めるNK/T cell lymphomaを経験した。本症例はMaconらの提唱したNK-like T-cell lymphomaと考えられ、十二指腸に原発したものは非常に稀である。今回、本症例を剖検結果を踏まえて報告した。

ANCA関連血管炎症候群、肝腫瘍、敗血症など多彩な合併症を呈し、急激に悪化した骨髄異形成症候群（5q-症候群）の一例を報告した。

種々の化学療法に対し抵抗性を示した、多臓器に浸潤を認めた症例に対して、化学療法単独では治癒を期待できなかったため、血縁者間末梢血幹細胞移植を行い、graft-versuslymphoma効果を出現させることによって治癒をもたらした貴重な症例である。

PNHクロ－ンに特異的に発現する遺伝子群をクローニングするためPNH患者のCD59－顆粒球とCD59＋顆粒球または健常者のCD59＋顆粒球との間でCDNAサブトラクションを行った。１０個以上の候補遺伝子断片がクローニングされた。

アトピ－性皮膚炎の治療への骨髄移植の適応について、アトピ－性皮膚炎モデルマウス（NC/Nga)を用い検討した。正常骨髄をアトピーマウスに移植する事により、皮膚所見、サイトカイン異常の改善を認め、重症アトピ－性皮膚炎の選択肢となると考えた。

約8年の経過で骨髄線維症様の病態を呈し、出血傾向及び硬膜の髄外造血が出現した過好酸球症候群の一例を経験した。この疾患の病態生理については、不明の点が多いが、ステロイドをはじめ各種化学療法抵抗性を示す骨髄増殖性疾患の一型と考えられた。

現在成人ALL,特にL3は予後が悪く、効果的な標準的治療法が存在しないことが問題となっていたが、今回JALSG-B-ALL97プロトコールが奏功した2例を経験した。本プロトコールの特徴を交えて考察する。

53歳女性。汎血球減少で発症し、2カ月後にdouble PH'と付加的染色体異常を伴い、急性転化(Blymphoid crisis)を起こし、VP療法により寛解状態を得ることができた慢性骨髄性白血病の一例である。

骨髄に形態異常を認めないが染色体異常inv(8)(p21;q22)を認め、再生不良性貧血と骨髄異形成症候群との鑑別が困難であった症例。染色体異常の存在は腫瘍化への関与を想起させ、今後の注意深い経過観察が必要である。

ステロイド抵抗性Weber-Christian病に非アルコール性脂肪肝炎（NASH）を合併しCyAが著効した症例を経験した。NASHはW-CDに起因すると考えられ、W-CDにCyAが著効したことよりT細胞系の異常が強くWeber-Christian病に考えられる。

長期のリンパ球性間質性肺病変に合併したホジキン病を経験し、同時に慢性活動性EBV感染症を伴っていた。び慢性肺疾患と縦隔リンパ節腫大に対しABVD療法とステロイドが著効を示した。EBER1の検索を行ったところ、肺では陽性の所見を認めた。

AML-MOと診断され寛解導入療法施行し完全寛解となったが骨髄回復期に突然の呼吸困難と胸痛を訴え肺梗塞と心超音波にて診断した。右心室に巨大血栓を認めICUにて体外循環管理下にて＋－PAによる血栓溶解療法により血栓が完全消失を認めた。

骨髄での再発に先立って白血病細胞の皮膚浸潤を認めた急性骨髄性白血病（M2）の1例の臨床経過、及び、急性骨髄性白血病（特にM2）の皮膚浸潤の頻度についての文献的検討に関して発表した。

Granulocytic sarcomaは限局性リンパ節腫脹を形成することが多いが、AML-MOにより全身リンパ節にgranulocytic sarcomaを形成した2症例を組織形態学的、免疫学的、臨床的に検討した。

MDS患者骨髄よりRNAを抽出し、GSTT-1 cDNAを観察したところ、623bpの症例と500bpの症例に分けられた。500bpの症例では白血化症例の頻度が高かった。