Mihoko Yotsumoto

Current status of treatment for primary effusion lymphoma

Primary effusion lymphoma (PEL) is a rare and aggressive B-cell non-Hodgkins lymphoma that usually presents with malignant effusions without tumor masses. An extracavitary or solid variant of PEL has also been described. Human herpes virus 8/Kaposi sarcoma-associated herpes virus (HHV-8/KSHV) is universally associated with the pathogenesis of PEL. More than 70% of cases occur with concurrent Epstein-Barr virus infection, but its relation to the pathogenesis is unknown. Patients are found in the context of immunosuppressive states (HIV-1 infection, post-organ transplantation). PEL is usually treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like chemotherapy with antiretroviral therapy if HIV-1 is positive. However, it is generally resistant to chemotherapy with a short median survival of less than 6 months. The optimal treatment for PEL has not been established yet. More intensive chemotherapy, such as dose-adjusted EPOCH (DA-EPOCH; etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin) and CDE (cyclophosphamide, doxorubicin, etoposide) are expected to show a favorable prognosis. Recently, the molecular steps in KSHV/HHV-8-driven oncogenesis have begun to be revealed, and molecular targeting therapies such as proteasome, NF-κB, cytokines and surface antigens would provide evidence for their clinical use.

Whole brain radiation alone produces favourable outcomes for AIDS‐related primary central nervous system lymphoma in the HAART era

Primary central nervous system lymphoma (PCNSL) related to acquired immunodeficiency syndrome (AIDS) is a lethal disorder, but the recent application of highly active antiretroviral therapy (HAART) has significantly improved prognosis. This retrospective cohort study of AIDS‐related PCNSL examined the actual clinical outcomes and prognostic variables affecting overall survival (OS) in the HAART era. Twenty‐three newly diagnosed AIDS‐related PCNSL at 12 regional centre hospitals for HIV/AIDS in Japan between 2002 and 2008 were consecutively enrolled. The estimated 3‐yr OS rate of the entire cohort was 64% (95%CI, 41.0–80.3%). Whole brain radiation therapy (WBRT) had an independent positive impact on survival (WBRT ≥30 Gy vs. others, P = 0.02). Nine of 10 patients with a good performance status (PS) (0–2) remained alive with complete response, whereas 10 (77%) of 13 of those with a poor PS (3–4) died mostly after a short period. The estimated 3‐yr OS rate of the groups with a good and poor PS was 100% and 38% (95%CI, 14–63%), respectively (P = 0.01). Leukoencephalopathy (grade ≥ 2) developed in 21% of those that survived more than 12 months after radiation. The patients receiving a curative intent radiation dose (≥30 Gy) of WBRT achieved prolonged survival while maintaining a good quality of life in the HAART era, especially among patients with a favourable PS.

Non-AIDS-defining hematological malignancies in HIV-infected patients: An epidemiological study in Japan

Objective:To clarify the incidence and clinical outcomes of non-AIDS-defining hematological malignancies (NADHMs), excluding non-Hodgkins lymphomas, in HIV-infected patients. Design:A nationwide epidemiological study was conducted to evaluate the incidence and clinical outcomes of NADHMs. Methods:Questionnaires were sent to 429 regional AIDS centers and 497 educational hospitals certified by the Japanese Society of Hematology. Data from 511 institutes were obtained. Results:From 1991 to 2010, 47 patients with NADHMs were detected (median age, 42.0 years; male, 93.6%). The median CD4-positive T-cell count was 255/&mgr;l, and the median duration from the diagnosis of HIV infection to development of hematological malignancy was 28.0 months. Most patients with acute leukemia were treated with standard induction chemotherapy. Complete remission rates and median overall survival periods for acute myeloblastic leukemia (AML) and acute lymphoblastic leukemia (ALL) were 70.0 and 85.7% and 13 and 16 months, respectively. Three of four patients with chronic-phase chronic myeloid leukemia (CML-CP) were well controlled with imatinib. Five patients (2 AML, 1 ALL, 1 accelerated-phase CML, and 1 myeloma) were treated with autologous or allogeneic stem-cell transplantation. Comparison of patients over the two periods (1991–2000 and 2001–2009) revealed a 4.5-fold increase in the incidence of hematological malignancies. Conclusion:The incidence of NADHMs has increased in the past decade. The prognosis of these patients was similar to that of HIV-negative patients; therefore, standard chemotherapy may be a feasible treatment option for HIV-infected patients with hematological malignancies.

Mutations to the probe of Cobas TaqMan HIV-1 ver. 1.0 assay causing undetectable viral load in a patient with acute HIV-1 infection

We encountered a human immunodeficiency virus (HIV)-1 in which the viral load was undetectable with the Cobas TaqMan HIV-1 ver. 1.0 (CTM v.1.0) in a patient with acute HIV-1 infection. The CTM v.1.0 assay showed more than 1,000-fold underestimation compared with the subsequent Cobas Amplicor Monitor v.1.5 assay. Because five mismatches to the CTM v.1.0 assay probe in the HIV-1 virus in the patient were disclosed by the manufacturer, partial gag regions of the HIV genome were directly sequenced from the patient’s plasma viral RNA. The detected single nucleotide point mutations were located near the 5′-end of the Cobas Amplicor Monitor probe. Clinicians should be very careful in making interpretations when indeterminate Western blot analysis results and a low or even undetectable HIV-1 viral load are encountered with the CTM HIV-1 ver. 1.0 assay in patients with suspected acute HIV infection. Repeating Western blot analysis is essential before considering a low HIV-1 viral load to be a false-positive result.

End-of-life care for HIV-infected patients with malignancies: A questionnaire-based survey

Background: The number of HIV-infected patients who require palliative or end-of-life care is increasing, and the status of end-of-life care for HIV patients with malignancies is unclear. Aim: This study aimed to evaluate the end-of-life care provided to HIV patients with malignancies in Japan. Design: National cross-sectional questionnaire-based survey. Setting/participants: Questionnaires were delivered to the medical staff of 378 regional core hospitals/core hospitals for AIDS and 285 palliative care units in Japan. Data were collected between August and October 2013. Results: Overall, 226 regional core hospitals/core hospitals for AIDS (59.8%) responded. A total of 55 institutions (24.3%) provided end-of-life care to HIV patients with malignancies. Regarding the place of death of the patients, 69.1% died at the institution whereas 18.2% were transferred to palliative care units. The requests of 16 (29.1%) institutions to transfer patients to palliative care units were rejected. Of the 378 palliative care units, 179 (62.8%) responded. While 13 palliative care units (4.6%) provided care to hospitalized HIV patients with malignancies, 20 (11.2%) refused to accept these patients for treatment because of a lack of experience in treating these patients and a lack of knowledge regarding HIV infection. Conclusion: Our findings suggest that in Japan, HIV patients with malignancies have difficulties obtaining hospitalization at a palliative care unit, which is likely due to a lack of experience among the professionals in treating such patients as well as a lack of knowledge about HIV.

HIV positivity may not have a negative impact on survival in Epstein‑Barr virus‑positive Hodgkin lymphoma: A Japanese nationwide retrospective survey

There has been no comparative clinical study focused on differences in the clinical features of Epstein-Barr virus (EBV)+ Hodgkin lymphoma (HL) between HIV-positive and -negative cases. In a nationwide survey from 511 institutions in Japan, the present study investigated 16 EBV+ HIVpositive HL patients. To further clarify their characteristics in comparison with EBV+ HIVnegative HL (n=34) in the combination antiretroviral therapy era in Japan, the present study was performed. Results indicated that EBV+ HIVpositive HL frequently occurred in a younger population compared with EBV+ HIVnegative HL (P=0.0295), and that the EBV+ HIVpositive HL group was not associated with the nodular sclerosis subtype in the population who were below the age of 40. Notably, the EBV+ HIVpositive HL group had a significantly higher frequency of extra-nodal involvement (P=0.0214), including marrow invasion. In the advanced stage, 80% of those with EBV+ HIVpositive HL did not require dose-reduction and in the majority of cases, chemotherapy was completed. There were no significant differences in the complete remission rate (P=0.1961), overall survival (P=0.200) and progression-free survival (P=0.245) between EBV+ HIVpositive HL (median observational period, 23.5 months) and EBV+ HIVnegative HL (median observational period, 64.5 months), suggesting that HIV positivity may not have a negative impact on the clinical outcome of EBV+ HL. Notably, standard chemotherapy is effective and tolerable for EBV+ HL, regardless of HIV infection.

1604Chronic Kidney Disease Is Associated with Bone Mineral Density Loss among Elderly HIV-infected Individuals in Japan

Loss among Elderly HIV-infected Individuals in Japan Takashi Muramatsu, MD; Yasuyuki Yamamoto, MD, PhD; Naoki Yanagisawa, MD; Ikuo Seita, MD, PhD; Mihoko Yotsumoto, MD, PhD; Manabu Otaki, MD, PhD; Takeshi Hagiwara, MD, PhD; Takashi Suzuki, MD, PhD; Kagehiro Amano, MD, PhD; Katsuyuki Fukutake, MD, PhD; Department of Laboratory Medicine, Tokyo Medical University Hospital, Tokyo, Japan; Department of Infectious Diseases, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan

1567PA MULTI-INSTITUTIONAL SURVEILLANCE OF CLINICOPATHOLOGICAL FEATURES AND MOLECULAR EPIDEMIOLOGY OF EGFR MUTATIONS IN LUNG CANCER PATIENTS LIVING WITH HUMAN IMMUNODEFICIENCY VIRUS INFECTION IN JAPAN

ABSTRACT Aim: Lung cancer has become a crucial problem among patients living with human immunodeficiency virus (HIV), causing high mortality in Western countries. Japan has an increasing number of newly infected HIV patients. However, the clinical entities in the East-Asian population are unclear given the identification of ethnic differences in lung cancer in the general population. Methods: Nationwide, retrospective surveillance of patients living with HIV diagnosed with lung cancer from 1986 to 2013 in Japan was performed. This study was supported by a Health and Labour Sciences Research Grant from the Ministry of Health, Labour, and Welfare of Japan (Grant number: H25-AIDS-I-002). Results: 43 lung cancer patients living with HIV were diagnosed (median age, 60.0 years; males, 97.7%; 37.2% early stage, 34.9% advanced stage), 41 of whom were in the antiretroviral therapy era. The median CD4-positive T-cell count was 326 cells/µL. Adenocarcinoma was the most frequent histology (55.8%), followed by squamous cell carcinoma (27.9%). Of the 14 patients in whom epidermal growth factor receptor (EGFR) status was examined, 5 (35.7%) had EGFR mutations. Median overall survival was 25.1 months for all stages and 7.9 months for the advanced stage. On univariate and multivariate analyses, the only prognostic factor for overall survival was stage (p=0.02). Conclusions: There appear to be ethnic differences in the prevalence of EGFR mutations even in the population living with HIV and the clinical characteristics or outcome may be provided in the regional differences. Disclosure: All authors have declared no conflicts of interest.

Central nervous system T-cell lymphoma in acquired immunodeficiency syndrome.

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