Guidelines for supportive care in multiple myeloma 2011

Supportive care plays an increasingly important role in the modern management of multiple myeloma. While modern treatments have significantly prolonged overall and progression free survival through improved disease control, the vast majority of patients remain incurable, and live with the burden of the disease itself and the cumulative side effects of treatments. Maintenance of quality of life presents challenges at all stages of the disease from diagnosis through the multiple phases of active treatment to the end of life. Written on behalf of the British Committee for Standards in Haematology (BCSH) and the UK Myeloma Forum (UKMF), these evidence based guidelines summarize the current national consensus for supportive and symptomatic care in multiple myeloma in the following areas; pain management, peripheral neuropathy, skeletal complications, infection, anaemia, haemostasis and thrombosis, sedation, fatigue, nausea, vomiting, anorexia, constipation, diarrhoea, mucositis, bisphosphonate-induced osteonecrosis of the jaw, complementary therapies, holistic needs assessment and end of life care. Although most aspects of supportive care can be supervised by haematology teams primarily responsible for patients with multiple myeloma, multidisciplinary collaboration involving specialists in palliative medicine, pain management, radiotherapy and surgical specialities is essential, and guidance is provided for appropriate interdisciplinary referral. These guidelines should be read in conjunction with the BCSH/UKMF Guidelines for the Diagnosis and Management of Multiple Myeloma 2011.     

Phase II trial of 2-chlorodeoxyadenosine for the treatment of cutaneous T-cell lymphoma [see comments]

We investigated the efficacy of 2-chlorodeoxyadenosine (2-CdA) therapy in patients with mycosis fungoides (MF) and the Sezary syndrome (SS). Between February 1991 and November 1993, 21 patients with relapsed or refractory MF/SS were treated with 2-CdA. 2-CdA was administered by continuous intravenous infusion at a dose of 0.1 mg/kg/d for 7 days initially (13 patients), but was subsequently reduced to 5 days (nine patients) due to hematologic toxicity. All patients had failed to respond to at least one prior treatment for MF/SS (median number of total prior therapies, five; median number of systemic prior therapies, three) and had an Eastern Cooperative Oncology Group performance status of two or better. Cycles were administered at 28-day intervals. Assessable patients received at least 5 days of 2-CdA. Fourteen patients received more than one cycle of 2-CdA. An overall response rate of 28% was achieved. Three patients (14%) had a complete response with a median duration of 4.5 months (range, 2.5 to 16). Three (14%) had a partial response with a median duration of 2 months (range, 2 to 4). Fifteen patients (72%) had no response. The most significant toxicities encountered were bone marrow suppression (62% of patients) and infectious complications (62% of patients). Thirty-eight percent of patients experienced no toxicity from 2-CdA. 2-CdA has activity as a single agent in patients with previously treated relapsed MF/SS. Studies in less heavily pretreated individuals with 2-CdA alone or in combination will be undertaken.     

Prevalence of cytomegalovirus antibody in hemophiliacs and homosexuals infected with human immunodeficiency virus type 1

We determined the prevalence of antibody to cytomegalovirus (CMV) in the sera of non-homosexual hemophilia patients and homosexual men infected with the human immunodeficiency virus type 1 (HIV-1). CMV antibody testing by latex agglutination revealed 33 of 58 HIV-1 infected hemophiliacs (57%) were antibody-positive compared with 54 of 54 HIV-1 infected asymptomatic non-hemophiliac homosexuals (100%) (p less than .001). Nine of 15 hemophiliacs (60%) with symptomatic HIV-1 infection were CMV antibody-positive. We also tested 22 HIV-1 antibody-negative hemophiliacs who had received non-heat treated factor concentrates. 14 of these 22 (64%) were CMV antibody-positive compared with 57% of HIV-1 antibody-positive hemophiliacs. We conclude 1) there is little correlation between transmission of HIV-1 and CMV by factor concentrates, 2) the presence of CMV antibody does not appear to be associated with clinical stage of HIV-1 infection in hemophiliacs, and 3) there may be a significant number of CMV antibody-negative hemophiliacs with HIV-1 infection at risk for primary infection and subsequent disease if CMV seronegative blood products are not provided for future transfusions.     

Increased expression of the G gamma and A gamma globin genes associated with a mutation in the A gamma enhancer

We have previously described a unique type of delta beta-thalassemia in a Chinese family characterized by increased expression of the G gamma and A gamma fetal globin genes in the absence of a large deletion in the beta-globlin gene cluster. Our earlier study of the beta-globin gene on this delta beta-thalassemia chromosome showed a promoter mutation in the TATA box. In this report, we describe the results of our study of the fetal globin domain of this delta beta-thalassemia chromosome. We have cloned a 13-kb DNA fragment that includes the G gamma and the A gamma genes and the 3' A gamma enhancer element of this delta beta-thalassemia chromosome. DNA sequence analysis of the G gamma and A gamma-globin genes including their promoters did not show any mutations, but analysis of the putative enhancer element downstream from the A gamma-globin gene showed a C to T substitution 2,401 nucleotides downstream from the A gamma cap site. We performed DNA linkage analysis to determine if this mutation is unique to this chromosome or represents a common polymorphism. Our linkage analysis showed that this mutation is not a common polymorphism and that it is also not an intrinsic part of the haplotype of the chromosome on which it was found. We also studied the interaction of nuclear proteins from erythroid and nonerythroid cells with the DNA sequences surrounding this mutation. We have shown by in vitro DNase I footprinting that this mutation falls within a region that is occupied by a novel DNA-binding protein that binds to this site in nuclear extracts from erythroid, but not nonerythroid cells. The binding of this nuclear protein to DNA appears to be dependent on GATA-1 binding to an adjacent GATA-1 site. We have also developed a new functional assay to compare the activity of the normal and mutant A gamma enhancer elements in erythroid cells. Analysis of the activity of the mutant enhancer shows that the mutation completely eliminates all enhancer activity in this assay. These findings suggest that this mutation of the A gamma enhancer on a chromosome that carries a partially inactivated beta-globin gene may be responsible for the increased expression of both gamma-globin genes seen in this condition.     

Mental Health Law of the People's Republic of China

The following document is a translation of the first national mental health law of the People''s Republic of China, which was adopted by the National People''s Congress on October 26, 2012. The original Chinese version of the law is available at the official government website: http://www.gov.cn/jrzg/2012-10/26/content_2252122.htm. The translation was completed by a team of translators at the Shanghai Mental Health Center at the Shanghai Jiao Tong University School of Medicine. The translators have added footnotes at the end of the document that explain their choices in sections where alternative translations are possible and that provide background information for sections that may be confusing to readers unfamiliar with China. This translation should be cited as follows:ChenHH, Phillips MR, Cheng H, Chen QQ, Chen XD, Fralick D, Zhang YE, Liu M, Huang J, Bueber M. Mental Health Law of the People''s Republic of China (English translation with annotations). Shanghai Archives of Psychiatry. 2012; 24(6):305-321. doi:10.3969/j.issn.1002-0829.2012.06.001Shanghai Archives of Psychiatry