Hidenori Sasaki

Prognostic Index for Acute- and Lymphoma-Type Adult T-Cell Leukemia/Lymphoma

PURPOSE The prognosis of acute- and lymphoma-type adult T-cell leukemia/lymphoma (ATL) is poor, but there is marked diversity in survival outcomes. The aim of this study was to develop a prognostic index (PI) for acute- and lymphoma-type ATL (ATL-PI). PATIENTS AND METHODS In a retrospective review, data from 807 patients newly diagnosed with acute- and lymphoma-type ATL between January 2000 and May 2009 were evaluated. We randomly divided subjects into training (n = 404) and validation (n = 403) samples, and developed a PI using a multivariable fractional polynomial model. RESULTS Median overall survival time (MST) for the 807 patients was 7.7 months. The Ann Arbor stage (I and II v III and IV), performance status (0 to 1 v 2 to 4), and three continuous variables (age, serum albumin, and soluble interleukin-2 receptor [sIL-2R]) were identified as independent prognostic factors in the training sample. Using these variables, a prognostic model was devised to identify different levels of risk. In the validation sample, MSTs were 3.6, 7.3, and 16.2 months for patients at high, intermediate, and low risk, respectively (P < .001; χ(2) = 89.7, 2 df; log-rank test). We also simplified the original ATL-PI according to dichotomizing age at 70 years, serum albumin at 3.5 g/dL, and sIL-2R at 20,000 U/mL and developed an easily calculable PI with prognostic discrimination power (P < .001; χ(2) = 74.2, 2 df; log-rank test). CONCLUSION The ATL-PI is a promising new tool for identifying patients with acute- and lymphoma-type ATL at different risks.

Chromosomal and Comparative Genomic Analyses of HHV-8-Negative Primary Effusion Lymphoma in Five HIV-negative Japanese Patients

A rare subset of HIV lymphoma, known as primary effusion lymphoma (PEL), is a high-grade tumour carrying human herpes virus 8 (HHV-8). Very little is known about genomic aberration in PEL, and only a few HIV-negative PEL have been reported. Here we report the results of chromosomal analysis and comparative genomic hybridisation (CGH) conducted to detect regions of gain and loss, in five HIV-negative Japanese cases of HHV-8-negative PEL. All patients except one (35-year-old female) were elderly men and the morphologic examination showed large cell type. PEL expressed B-cell-associated and activation-associated antigens, and exhibited clonal immunoglobulin genes. No HHV-8 was detected in all four examined cases, but Epstein-Barr virus (EBV) was detected in one case. Genomic abnormalities and aberrations were identified in all HHV-8/HIV-negative PEL. CGH studies showed gain in 19 of 24 chromosomes. Gains of 3q13-27, 8q24, 10q21-23 and Yq were detected in two of the five cases, but other gains were noted in each case. Chromosomal analysis revealed complex abnormalities both in numbers and structures. Burkitt lymphoma-associated t(8;22) was detected in one case, but +8 chromosome and c-myc amplification were detected in the other three cases by Southern blot and/or fluorecence in situ hybridization (FISH). Abnormality of chromosome 8, which associates with c-myc, was detected in four of the five HHV-8/HIV-negative PEL. However, the other common genomic abnormalities of HHV-8/HIV-negative PEL were not detected in our study, but the complex abnormalities seemed to be true rather than the usual large B-cell lymphoma. Our results suggest that multi-step genomic abnormalities might be associated in HHV-8/HIV-negative PEL tumorigenesis.

Addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisolone therapy has a high risk of developing interstitial pneumonia in patients with non-Hodgkin lymphoma

There are a few reports suggesting that rituximab (RTX) might be a risk for interstitial pneumonitis (IP). We also experienced such patients in the era of RTX. Here, we reviewed all the patients with non-Hodgkin lymphoma who were treated with RTX-CHOP-like regimen (R-CHOP) to determine the risk of developing IP. One of 59 (1.7%) patients who received CHOP alone and 8 of 129 (6.2%) patients who were treated with R-CHOP experienced IP (p = 0.28). Furthermore, three of eight patients who have had IP during R-CHOP were confirmed having Pneumocystis jirovecii pneumonia (PCP). PCP occurred during the fourth, sixth, and seventh cycle of chemotherapy, respectively. Among the patients treated by R-CHOP, 3 of 32 (9%) patients whose lymphocyte counts were <1000/μL before chemotherapy developed PCP, while 70 patients whose lymphocyte counts were >1000/μL did not (p = 0.03). In four of eight patients, IP occurred during the administration of granulocyte-colony stimulating factor. RTX seems to have a certain risk to induce IP including PCP. Patients with lymphoma who were treated by R-CHOP regimen, might be considered as PCP prophylactic, especially if the number of lymphocytes is low at the beginning of chemotherapy.

Analysis of hepatitis C virus (HCV) RNA in the lesions of lichen planus in patients with chronic hepatitis C: detection of anti-genomic- as well as genomic-strand HCV RNAs in lichen planus lesions.

BACKGROUND Hepatitis C virus (HCV) is a single-strand RNA virus. The association of lichen planus with chronic HCV infection has been reported, as has been cryoglobulinemic purpura, psoriasis, urticaria, and porphyria cutanea tarda. However, the cause of lichen planus is unclear. OBJECTIVES To investigate whether genomic- and/or anti-genomic-strand HCV RNAs are present in the lichen planus lesions of chronic hepatitis C patients and to elucidate the pathogenesis of lichen planus. METHODS Reverse transcription-polymerase chain reaction (RT-PCR) followed by nested-PCR was carried out to detect HCV RNA using RNA samples from lichen planus lesions of three patients with chronic hepatitis C. Since it is well known that commonly there is relatively dense inflammatory cell infiltration mainly in the upper dermis in lichen planus, the same RT-PCR procedure was performed using RNA from peripheral blood leukocytes from the same patients. In addition, in one patient, the same procedure was also performed using an RNA sample from normal skin. RESULTS Bands of the appropriate size (161 base pairs corresponding to region 98-258 of HCV RNA) in the nested-PCR products for both genomic- and anti-genomic-strands were detected in lichen planus lesions as well as in peripheral blood leukocytes in all the cases. CONCLUSION To the best of our knowledge, this is the first report showing the presence of anti-genomic- as well as genomic-strand HCV RNAs in lichen planus lesions in patients with chronic hepatitis C; suggesting that HCV-associated lichen planus lesions may be sites of HCV replication.

Japanese Society of Clinical Oncology clinical practice guidelines 2010 for antiemesis in oncology: executive summary

The purpose of this article is to disseminate the standard of antiemetic therapy for Japanese clinical oncologists. On the basis of the Appraisal of Guidelines for Research and Evaluation II instrument, which reflects evidence-based clinical practice guidelines, a working group of the Japanese Society of Clinical Oncology (JSCO) reviewed clinical practice guidelines for antiemesis and performed a systematic review of evidence-based domestic practice guidelines for antiemetic therapy in Japan. In addition, because health-insurance systems in Japan are different from those in other countries, a consensus was reached regarding standard treatments for chemotherapy that induce nausea and vomiting. Current evidence was collected by use of MEDLINE, from materials from meetings of the American Society of Clinical Oncology National Comprehensive Cancer Network, and from European Society of Medical Oncology/Multinational Association of Supportive Care in Cancer guidelines for antiemesis. Initially, 21 clinical questions (CQ) were selected on the basis of CQs from other guidelines. Patients treated with highly emetic agents should receive a serotonin (5-hydroxytryptamine; 5HT3) receptor antagonist, dexamethasone, and a neurokinin 1 receptor antagonist. For patients with moderate emetic risk, 5HT3 receptor antagonists and dexamethasone were recommended, whereas for those receiving chemotherapy with low emetic risk dexamethasone only is recommended. Patients receiving high-emetic-risk radiation therapy should also receive a 5HT3 receptor antagonist. In this paper the 2010 JSCO clinical practice guidelines for antiemesis are presented in English; they reveal high concordance of Japanese medical circumstances with other antiemetic guidelines that are similarly based on evidence.

A patient with acute myeloid leukemia who developed fatal pneumonia caused by carbapenem-resistant Bacillus cereus

Bacillus cereus is known as a serious bacterial pathogen in neutropenic patients. B. cereus is often resistant to β-lactams, including penicillins and cephalosporins. We report a case of fatal pneumonia caused by B. cereus in a patient with newly diagnosed acute myeloid leukemia (AML) during remission induction therapy. Cefepime was started for febrile neutropenia (FN) initially and was switched to panipem/betamipron, when fulminant pneumonia supervened. The isolated strain was resistant not only to cefepime but also to panipenem/betamipron. This is the first report of fulminant infection caused by carbapenem-resistant B. cereus in a neutropenic patient. B. cereus should be kept in mind as a target of empirical treatment when neutropenic patients develop pneumonia

Interferon-α and zidovudine for relapsed/refractory adult T cell leukemia/lymphoma: case reports of Japanese patients

Combination therapy with interferon-α and zidovudine (IFN/AZT) has been regarded as standard care for acute and indolent (i.e., chronic and smouldering) ATL based on reports involving a limited number of patients. This treatment approach has not been evaluated in Japan, a major endemic area of this disease in the world. This is the first Japanese report of IFN/AZT for ATL. It is impossible to draw any definitive conclusion from this small study; however, IFN/AZT showed clear anti-ATL effects for refractory/relapsed ATL patients. This report would contribute for developing future ATL treatment in Japan.

Acute hepatic failure due to hepatic involvement by chronic lymphocytic leukemic cells in a patient with chronic hepatitis B

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Retrospective analysis of the efficacy and safety of eribulin therapy for metastatic breast cancer in daily practice

Evidence of eribulin therapy for metastatic breast cancer (MBC) in clinical practice is not well documented.

Patient perceptions of symptoms and concerns during cancer chemotherapy: ‘affects my family’ is the most important

BackgroundCancer chemotherapy is associated with a variety of side effects/adverse events. It is very important that patients adhere to the planned chemotherapy regimen, which necessitates a minimum of side effects and that these side effects be kept under control. We have investigated patients’ concerns and symptoms during chemotherapy with the aim to seek solutions that will improve patients’ quality of life during chemotherapy.MethodsForty-nine patients with malignant diseases on parenteral antineoplastic agents were sequentially enrolled in this study. These patients completed a questionnaire consisting of 42 items related to non-physical concerns and 52 items of physical symptoms related to chemotherapy. Each patient was also asked to select the three items among these 94 items which affected him/her the most. ResultsThe median age of the cancer patients was 62 years and the male-to-female ratio was 18:31. Among the non-physical concerns, the most frequently chosen concern was ‘affects my family or partner,’ followed by anxiety related to treatment. Regarding the physical symptoms, the most frequent complaints were fatigue, alopecia and constipation, while the most troublesome symptoms were nausea, poor taste and paresthesia. Overall, the most frequently expressed concerns were ‘affects my family or partner’ and anxiety related to treatment. Male patients suffered most from fever, fatigue and nausea, and female patients complained more of poor taste and gastrointestinal problems.ConclusionPatient perceptions of adverse events associated with cancer chemotherapy apparently have changed from physical symptoms to non-physical concerns. In our patient cohort ‘affects my family or partner’ was the most important concern. One important point to note is that female patients often complained of poor taste because this meant they were unable to cook well.