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immuno-chemotherapy Using Repeated Vaccine Treatment Can Produce Successful Clinical Responses in Advanced Metastatic Melanoma

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Journal of Cancer Therapy 2010年第4期1卷 205-213页

作者： Brendon Coventry Peter Hersey Anne-Marie Halligan Antonio Michele Discipline of Surgery University of Adelaide Royal Adelaide Hospital Adelaide Australia

Advanced Stage IV and IIIc melanoma has a dismal survival, with or without, standard chemotherapy. New therapies are required to improve survival and reduce morbidity. Repeated vaccine dosing does not appear to have been explored, so Vaccinia Melanoma Cell Lysate (VMCL) vaccine repetitive therapy was tested, either alone, or combined with chemotherapy. 37 patients (31 Stage IV [M1a(6), b(7), c(18)] and 6 Stage IIIc) were studied using intra-dermal VMCL vaccine therapy. If disease progressed, vaccine was continued with standard chemotherapy (DTIC and/or Fotemustine). Overall survival was assessed and clinical responses were also recorded. From vaccine commencement, median overall follow-up was 10 months. Survivals ranged from 4 to 73 months. Median (mean) overall survival was 10 (23.5) months;overall survival at 1, 2 and 3 years was 40.5%, 21.6% and 10.8% respectively. CR and PR occurred in 18.9% (7) and 18.9% (7) of patients;these were durable for up to 6.1 years in 4 patients. Stable disease was noted in a further 17 patients (45.9%). In 6 patients (16.2%) no response to therapy was apparent. Repeated vaccinations with or without chemotherapy produced strong, durable clinical responses with overall survival > 23 months occurring in nearly 25% of advanced melanoma patients. The overall disease control rate (CR, PR and SD) was 83.7%, including CR in very advanced cases. These results, in a largely unselected population of advanced metastatic melanoma patients, compare very favourably with other regimens, and notably were associated with minimal, if any, toxicity. Further analysis of this approach appears warranted.

关键词： Vaccine Therapy Combined immuno-chemotherapy Repetitive Dosing Advanced Melanoma Clinical Responses Prolonged Survival

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Hepatitis C virus and diffuse large B-cell lymphoma: Pathogenesis, behavior and treatment

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World Journal of Gastroenterology 2014年第32期20卷 11054-11061页

作者： Carlo Visco Silvia Finotto Department of Hematology and Cell Therapy San Bortolo Hospital

A significant association between hepatitis C virus (HCV) infection and B-cell lymphoma has been reported by epidemiological studies, most of them describing a strong relationship between indolent lymphomas and HCV. Furthermore, the curative potential of antiviral therapy on HCV related indolent lymphomas supports a specific role for the virus in lymphomagenesis. These observations are reinforced by numerous laboratory experiments that led to several hypothetical models of B-cell transformation by HCV. Diffuse large B-cell lymphoma (DLBCL), the most common lymphoma subtype in the western countries, has been associated to HCV infection despite its aggressive nature. This association seems particularly prominent in some geographical areas. Clinical presentation of HCV-associated DLBCL has consistently been reported to differ from the HCV-negative counterpart. Nevertheless, histopathology, tolerance to standard-of-care chemo-immunotherapy (R-CHOP or CHOP-like regimens) and final outcome of HCV-positive DLBCL patients is still matter of debate. Addition of rituximab has been described to enhance viral replication but the probability of severe hepatic complications remains low, with some exceptions (i.e., hepatitis B virus or immune immunodeficiency virus co-infected patients, presence of grade > 2 transaminases elevation, cirrhosis or hepatocarcinoma). HCV viral load in this setting is not necessarily directly associated with liver damage. Overall, treatment of HCV associated DLBCL should be performed in an interdisciplinary approach with hepatologists and hematologists with close monitoring of liver function. Available reports reveal that the final outcome of HCV-positive DLBCL that receive standard immunochemotherapy is not inferior to their HCV-negative counterpart. This review summarizes data on epidemiology, pathogenesis and therapeutic approach on HCV-associated DLBCL. Several issues that are matter of debate like clinical management of patients with trans

关键词： Hepatitis C virus Non-Hodgkin lymphoma Liver Toxicity Diffuse large B-cell lymphoma Rituximab Cyclophosphamide Hydroxydaunorubicin Vincristine Prednisolone immuno-chemotherapy Antiviral treatment

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Management of adult Langerhans cell histiocytosis based on the characteristic clinical features

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World Journal of Hematology 2013年第3期2卷 89-98页

作者： Shinsaku Imashuku Chihiro Shimazaki Arinobu Tojo Toshihiko Imamura Akira Morimoto Division of Hematology Takasago-seibu HospitalTakasago 676-0812Japan the NPO for Japan Langerhans Cell Histiocytosis Study Group Kyoto 602-8566Japan Division of Hematology Social Insurance Kyoto HospitalKyoto 603-8151Japan Division of Stem Cell Therapy Center for Stem Cell Biology and Regenerative Medicinethe Institute of Medical Sciencethe University of TokyoTokyo 108-8639Japan Department of Pediatrics Kyoto Prefectural University of MedicineGraduate School of Medical ScienceKyoto 602-8566Japan Department of Pediatrics Jichi Medical University School of MedicineShimotsuke 329-0498Japan

To find out the most appropriate management,clinical features of 18 cases of adult multisystem langerhans cell histiocytosis(LCH) have been analyzed. The patients comprising of 9 males and 9 females were median age of 36 years,ranging from 18-53 years at diagnosis. Regarding the initial symptoms,7 patients(2 males and 5 females) showed central diabetes insipidus(CDI) and other endocrine symptoms with thickened pituitary stalk or a mass at the hypothalamic region. Additional 2 patients initiated the disease with CDI with no immediate diagnosis. In the remaining patients,the diseasebegun with single(n = 3) or multiple(n = 1) spinal bone lesion(s) in 4 patients(all males),with multiple bone lesions in 3 patients(1 male and 2 females),with single skull lesion in one female patient and with ambiguous symptoms including hypothyroidism in the remaining one male patient. We also recognized the correlation between pregnancy/childbirth and LCH in 4 patients. In terms of treatment,9 patients received systemic immuno-chemotherapy alone,of which the majority received vinblastine-based chemotherapy while 4 received 2-chlorodeoxyadenosine. Five had a combination of immuno-chemotherapy with surgical resection or radiotherapy,2 had immunotherapy alone,2 had surgical resection followed by observation alone to date. Three patients received hematopoietic stem cell transplantation after extensive chemotherapy. In terms of outcome,15 patients are alive(9 with active disease,6 without active disease),with a median of 66 mo(range 17-166 mo),two died of disease while the remaining 1 lost to follow-up. Based on these results,we think that early diagnosis and rapid introduction of appropriate treatment are essential,in order to overcome the problems relevant to adult LCH.

关键词： Langerhans cell histiocytosis Adult immuno-chemotherapy 2-chlorodeoxyadenosine Childbirth

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