[Immunodeficiency-associated Burkitt lymphoma developed in a patient receiving a long-term methotrexate therapy for rheumatoid arthritis].

An increased risk of lymphoproliferative disorders (LPD) has been demonstrated in patients treated with methotrexate (MTX) for rheumatoid arthritis (RA). The role of Epstein-Barr virus (EBV) has been discussed in the pathogenesis of immunodeficiency-associated LPDs. We herein present a RA patient, who developed Burkitt lymphoma during MTX treatment. The patient was a 61-year-old Japanese female with a 10-year history of weekly MTX therapy for RA. She presented with a one-month history of submandibular lymph node swelling and fever. Remarkable increases in serum lactate dehydrogenase and blood EBV DNA were observed. Serology for HIV was negative. Biopsy specimens demonstrated diffuse proliferation of medium-sized lymphoid cells. The cells were positive for CD10, CD20 and BCL6, and negative for BCL2, MUM1, terminal deoxynucleotidyl transferase and CD34. The MIB-1 index was almost 100%. EBV in the tumor cells was identified by using EBV-encoded RNA in situ hybridization. A chromosomal translocation t(8;14) was found and further confirmed by fluorescence in situ hybridization. Her condition improved following discontinuation of MTX and initiation of prednisolone. After three cycles of a dose-reduced CHOP-like regimen, chemotherapy was discontinued due to severe complications. However, there has been no sign of recurrence for six years to date without additional intensive chemotherapy.

[Risk assessment for outpatients for cancer chemotherapy].

Outpatient treatment in the cancer chemotherapy center was begun in April 2005 at the University of Occupational and Environmental Health Hospital. Drugs were prescribed 2,590 times during the past year. Times for intravenous drip for various regimens and outpatient chemotherapy desired by patients showed a rough. The number of incidents was three (0.12%) and no accidents occurred. There were 74 consultations with pharmacists about prescriptions (2.6%) and 286 (11.0%) with nurses. Both types of consultation decreased and their contents were different. The number of consultations about prescriptions by special staff at the cancer chemotherapy center was less than at other departments. Therefore, a system assuring safe management is critically required for the establishment of a system for outpatient cancer chemotherapy treatment.

Evaluation of the quality of life between inpatients and outpatients receiving cancer chemotherapy in Japan.

A quality of life (QOL) assessment has become increasingly common in cancer clinical trials. Seventy-four consecutive patients treated for cancer between August 2005 and January 2006 at the Cancer Chemotherapy Center in the University of Occupational and Environmental Health, Japan, were examined. The 8-Short form health survey (SF-8) was utilized as a comprehensive scale and quality of life questionnaire for cancer patients treated with anticancer drugs (QOL-ACD) as disease specific scale for the QOL evaluation. The QOL for outpatients was investigated in comparison with that for inpatients. All questionnaires were collected and baseline questionnaires were filled in by 98.1% of the subjects. The physical comprehensive score (PCS) of SF-8 for the outpatients was higher than that for the inpatients. The physical condition of the outpatients was better than that of inpatients. There was no difference in the baseline scores of the QOL-ACD scales in daily activity, psychological condition, social attitude, and face scale of the analyzed domains between the two groups. Furthermore, a longitudinal study from admission to outpatient was carried out on 27 patients who were treated on an outpatient basis in our clinic. No difference in the baseline scores of the SF-8 and QOL-ACD scales were observed in any of the analyzed domains. These data suggest that the present QOL study has a sufficient feasibility for the outpatients evaluated in our study, and QOL of outpatients after discharge is equal to that of inpatients receiving cancer chemotherapy.

Prediction of emergency hospitalization of outpatients receiving cancer chemotherapy.

The purpose of this study was to establish criteria to predict the need for emergency hospitalization of patients receiving chemotherapy, based on information at presentation. 158 consecutive patients treated for cancer at the Cancer Chemotherapy Center in the University of Occupational and Environmental Health were examined. The number of emergency hospitalization cases for outpatients undergoing cancer chemotherapy was 14 (8.9%) and including seven lung carcinomas, six hematological carcinomas, and one mediastinal tumor. The reason for emergency hospitalization in twelve (85.7%) of the cases was infection. No significant difference was observed between the cases with and without emergency hospitalization regarding age, gender, cancer type, previous treatment, objective of the chemotherapy, or line of chemotherapy. A significantly higher number of the emergency cases were associated with performance status 2, severe adverse events and comorbidity than with a performance status 0-1 where there were no or only mild adverse events and no comorbidity. Multiple logistic regression models indicated that severe adverse events and comorbidities were independent predictive factors for patients with emergency hospitalization. By combining selected clinical information for outpatients receiving cancer chemotherapy, the need for emergency hospitalization could be predicted.

[What do cancer chemotherapy outpatients want?--results of a questionnaire survey].

We conducted a questionnaire survey to evaluate patients at the cancer chemotherapy center of the university of occupational and environmental health hospital from January to March 2006. Thirty-three (61.1%) and 5 (9.2%) of 54 patients wished to receive chemotherapy on an outpatient basis and as inpatients, respectively. Among the reasons for wishing to be treated as outpatients were the following: Keeping in touch with family, not wanting to be hospitalized, a desire to work, and the wish to continue hobbies, at 45.5 (15/33), 36.4 (12/33), 24.2 (8/33), and 24.2 (8/33), respectively. Twenty-four (44.4%) patients voiced concerns about chemotherapy at an outpatient clinic in terms of associated adverse events, feeling bad about causing trouble to their family, and the desire to have consultations at night or on holidays. Thirty-eight (70.4%) patients wished to have chemotherapy within 3 hours, and 42 (77.7%) of them requested improvements in the examinations, time, duration of chemotherapy, and the effect of chemotherapy. These findings indicate that a major part of patients wish to receive cancer chemotherapy at an outpatient clinic within 3 hours. However, they also have serious reservations about any associate adverse events. We therefore need to improve the overall environment for cancer chemotherapy patients in order to allow them to feel safe when undergoing such treatments.

[Hormone therapy for breast cancer].

Breast cancer is a hormone responsive disease, and its proliferation and progression correlate with estrogen. Estrogen binds to estrogen receptor and induces various target genes, thus promoting proliferation of breast cancer cells. Therefore, the strategy of endocrine therapy is the blockade of estrogen action. We can use a luteinizing hormone releasing hormone agonist and aromatase inhibitor as an interruptor of supply, tamoxifen as an inhibitor of estrogen receptor, and medroxyprogesterone acetate with an anti-estrogen action. In this article, we review endocrine therapy for breast cancer patients based on recent clinical trials.

[A medical economic benefit of outpatient with cancer chemotherapy].

Recently, there is a worldwide tendency to decrease medical costs, and a medical insurance revolution, such as a diagnosis procedure combination system, has also been put forward in Japan. It is important to consider medical management healthily by shortening hospital stays and cutting the cost of admission therapies. In this background, outpatients' chemotherapy takes notice because of the improvement in quality of life, discovery of new drugs without severe adverse effects, use-effectiveness of hospital beds and medical cost-effectiveness. Cancer patients suffer from not only a major burden of the diseases such as their physical and mental state, but also an economic impact. In this article, we review the medical cost-benefit for outpatients undergoing cancer chemotherapy.

[Chemotherapy for lung cancer patients].

The number of lung cancer-related deaths has increased since the 1960 and has become the leading cause of cancer-related death in Japan. It is anticipated that the number will double in the next 20 years. Chemotherapy is a hopeful systemic therapy because of distant metastases due to lung cancer. Platinum based doublets remain the standard of care for the first-line treatment of metastatic NSCLC. As salvage chemotherapy for patients, the effectiveness of docetaxel has been confirmed. The standard chemotherapy for extensive SCLC is the combination of cisplatin and irinotecan or etoposide. Recently, randomized trials have shown that platinum-based chemotherapy has the potential to improve survival among patients with completely resected NSCLC. Recent advances in molecular biology and genetics have created new molecular targeted therapies for lung cancer. New anti-cancer agents, including gefitinib, erlotinib, bevacizumab, pemetrexed and amrubicin, are being developed currently.

[Out-patient treatment for cancer patients at cancer chemotherapy centers in university hospitals].

At present, one-third of people die of cancer and the number is still increasing in Japan. A safe and effective treatment system is critically required. Recently, the discovery of new drugs and the development of medical oncology promotes out-patient treatment for cancer patients. Out-patient treatment in the cancer chemotherapy center of the University of Occupational and Environmental Health Hospital has been started, and many chemotherapy regimens were verified in this center. Not only different organ-specific chemotherapies but also summarizing the oncology team are necessary for performance of the mission. We describe in this review the characteristics of the cancer chemotherapy center.

[Angioimmunoblastic T-cell lymphoma accompanied by pure red cell aplasia].

A 71-year-old woman was admitted in December 2002 because of lymphadenopathy, hepatosplenomegaly and pleural effusion. She had severe anemia with hemoglobin 5.9 g/dl and a reticulocyte count of 1% per hundred. Direct/indirect Coombs tests and anti-double stranded DNA antibody were positive, her serum CH50 level was reduced and an increase in serum LDH isoenzyme 3 was observed. Bone marrow aspiration showed an almost total absence of erythroblasts and no pathological cell proliferation. The diagnosis of angioimmunoblastic T-cell lymphoma (AILT) was made based on the lymph node histological findings. Proliferation of arborizing small vessels with hyperplastic endothelium and infiltration of atypical T-lymphocytes were observed. After combination chemotherapy (THP-COP), remission was achieved in both the pure red cell aplasia (PRCA) and AILT. Remission was also accompanied by normalization of the Coombs tests, suggesting that autoimmune mechanisms in AILT may contribute to the development of PRCA.

Imatinib mesylate-sensitive blast crisis immediately after discontinuation of imatinib mesylate therapy in chronic myelogenous leukemia: report of two cases.

Although imatinib mesylate has shown encouraging activity in chronic myelogenous leukemia (CML), disease progression during therapy has been observed, manifested by clonal expansion of imatinib mesylate-resistant leukemia cells. On the other hand, myelosuppression related to treatment of imatinib mesylate is often managed with temporary interruption of treatment or dose reduction. We here report two CML patients who had imatinib mesylate-sensitive blast crisis (BC) immediately after discontinuation of imatinib mesylate therapy. The patients discontinued therapy because of neutropenia. Although there was no evidence of blastic phase during therapy, BC occurred 2 weeks after the withdrawal of treatment in both cases. Interestingly, additional chromosomal abnormalities were detected following the withdrawal of imatinib mesylate and disappeared by re-introduction of this agent. The same doses of imatinib mesylate was still effective and remission was sustained with imatinib mesylate alone again. Our report suggests the possibility that withdrawal of imatinib mesylate may lead to proliferation of blast clones even in patients showing good responses to imatinib mesylate without signs of disease progression.

[Remission induction of refractory diffuse large B-cell lymphoma with allogeneic peripheral blood stem cell transplantation followed by interferon-alpha and donor lymphocyte infusion].

Graft-versus-lymphoma (GVL) effect has been described in patients with malignant lymphoma after allogeneic stem cell transplantation (alloSCT). The effect of interferon-alpha (IFN-alpha) on the GVL effect still remains unclear. Here we report on a 29-year-old woman with refractory diffuse large B-cell lymphoma (DLBL). Her clinical findings included multiple masses in the liver, stomach, bilateral kidneys, thyroid, vertebral bones and a bulky mediastinal mass. Since the patient did not respond to various combination chemotherapies and further developed superior vena cava syndrome, allogeneic peripheral blood stem cell transplantation (PBSCT) from a HLA-identical brother was carried out after a myeloablative TBI/CY-based conditioning regimen. DLIs have been also performed every 4 weeks since day +14. As a result, the lymphoma masses showed a partial response. In order to enhance the GVL effect, IFN-alpha was further given at a maximum of 3 MU four times per week. Although the patient only experienced graft-versus-host disease of the skin (grade II) even after both DLIs and IFN, complete clinical remission was observed. 200 days after transplantation, the patient is still disease-free and in good condition. This report suggests the curative potential of IFN-alpha combined with DLI after allogeneic SCT in refractory DLBL.