Children's Oncology Group's 2013 blueprint for research: Non‐Hodgkin lymphoma

Non‐Hodgkin lymphomas account for approximately 7% of cancers diagnosed in patients less than 20 years of age, with approximately 800 cases diagnosed annually at COG institutions. With current therapies, cure rates range from 70% to over 90%, even for children with disseminated disease. However, two major challenges need to be overcome: (i) to optimize upfront treatment to prevent relapse since prognosis for patients with relapsed disease remains poor and (ii) minimize long‐term side effects in survivors. Hence, the future initiatives for the treatment of pediatric NHL are to utilize novel targeted therapies to not only improve outcomes but to decrease bystander organ toxicities and late effects. Pediatr Blood Cancer 2013; 60: 979–984. © 2012 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97477/1/24416_ftp.pd

Commentary on the 2008 WHO classification of mature T- and NK-cell neoplasms

In 2008, the World Health Organization (WHO) published a revised and updated edition of the classification of tumors of the hematopoietic and lymphoid tissues. The aims of the fourth edition of the WHO classification was to incorporate new scientific and clinical information in order to refine diagnostic criteria for previously described neoplasms and to introduce newly recognized disease entities. The recognition that T-cell lymphomas are related to the innate and adaptive immune system, as well as enhanced understanding of other T-cell subsets, such as the regulatory T-cell and follicular helper T-cells, has contributed to our understanding of the morphologic, histologic, and immunophenotypic features of T- and NK-cell neoplasms. The purpose of this review is to highlight major changes in the classification of T- and NK-cell neoplasms and to explain the rationale for these changes

Updates in pathobiological aspects of anaplastic large cell lymphoma

Anaplastic large cell lymphomas (ALCL) encompass several distinct subtypes of mature T-cell neoplasms that are unified by the expression of CD30 and anaplastic cytomorphology. Identification of the cytogenetic abnormality t(2;5)(p23;q35) led to the subclassification of ALCLs into ALK+ ALCL and ALK- ALCL. According to the most recent World Health Organization (WHO) Classification of Haematolymphoid Tumours as well as the International Consensus Classification (ICC) of Mature Lymphoid Neoplasms, ALCLs encompass ALK+ ALCL, ALK- ALCL, and breast implant-associated ALCL (BI-ALCL). Approximately 80% of systemic ALCLs harbor rearrangement of ALK, with NPM1 being the most common partner gene, although many other fusion partner genes have been identified to date. ALK- ALCLs represent a heterogeneous group of lymphomas with distinct clinical, immunophenotypic, and genetic features. A subset harbor recurrent rearrangement of genes, including TYK2, DUSP22, and TP63, with a proportion for which genetic aberrations have yet to be characterized. Although primary cutaneous ALCL (pc-ALCL) is currently classified as a subtype of primary cutaneous T-cell lymphoma, due to the large anaplastic and pleomorphic morphology together with CD30 expression in the malignant cells, this review also discusses the pathobiological features of this disease entity. Genomic and proteomic studies have contributed significant knowledge elucidating novel signaling pathways that are implicated in ALCL pathogenesis and represent candidate targets of therapeutic interventions. This review aims to offer perspectives on recent insights regarding the pathobiological and genetic features of ALCL

The B7 Homologues and their Receptors in Hematologic Malignancies

The B7 homologues and their receptors regulate both peripheral tolerance and adaptive immunity. This field is rapidly evolving as new ligands and receptors are being identified. Much of the work supporting their role in the regulation of host anti‐tumor immunity has been derived from experimental models and clinical trials in solid malignancies. However, a growing body of evidence demonstrates that the B7‐H family has important immunologic and non‐immunologic functions in a variety of hematologic malignancies. Herein, we will review recent evidence that supports the therapeutic targeting of the B7 homologues in hematologic malignancies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91338/1/ejh1766.pd

Treatment Options for Paediatric Anaplastic Large Cell Lymphoma (ALCL): Current Standard and beyond.

Anaplastic Lymphoma Kinase (ALK)-positive Anaplastic Large Cell Lymphoma (ALCL), remains one of the most curable cancers in the paediatric setting; multi-agent chemotherapy cures approximately 65-90% of patients. Over the last two decades, major efforts have focused on improving the survival rate by intensification of combination chemotherapy regimens and employing stem cell transplantation for chemotherapy-resistant patients. More recently, several new and 'renewed' agents have offered the opportunity for a change in the paradigm for the management of both chemo-sensitive and chemo-resistant forms of ALCL. The development of ALK inhibitors following the identification of the EML4-ALK fusion gene in Non-Small Cell Lung Cancer (NSCLC) has opened new possibilities for ALK-positive ALCL. The uniform expression of CD30 on the cell surface of ALCL has given the opportunity for anti-CD30 antibody therapy. The re-evaluation of vinblastine, which has shown remarkable activity as a single agent even in the face of relapsed disease, has led to the consideration of a revised approach to frontline therapy. The advent of immune therapies such as checkpoint inhibition has provided another option for the treatment of ALCL. In fact, the number of potential new agents now presents a real challenge to the clinical community that must prioritise those thought to offer the most promise for the future. In this review, we will focus on the current status of paediatric ALCL therapy, explore how new and 'renewed' agents are re-shaping the therapeutic landscape for ALCL, and identify the strategies being employed in the next generation of clinical trials

Incidence of unintended pregnancy among female sex workers in low-income and middle-income countries: a systematic review and meta-analysis

Objectives: To determine the incidence of unintended pregnancy among female sex workers (FSWs) in lowincome and middle-income countries (LMICs). Design: We searched MEDLINE, PsychInfo, Embase and Popline for papers published in English between January 2000 and January 2016, and Web of Science and Proquest for conference abstracts. Meta-analysis was performed on the primary outcomes using random effects models, with subgroup analysis used to explore heterogeneity. Participants: Eligible studies targeted FSWs aged 15–49 years living or working in an LMIC. Outcome measures: Studies were eligible if they provided data on one of two primary outcomes: incidence of unintended pregnancy and incidence of pregnancy where intention is undefined. Secondary outcomes were also extracted when they were reported in included studies: incidence of induced abortion; incidence of birth; and correlates/predictors of pregnancy or unintended pregnancy. Results: Twenty-five eligible studies were identified from 3866 articles. Methodological quality was low overall. Unintended pregnancy incidence showed high heterogeneity (I²\u3e95%), ranging from 7.2 to 59.6 per 100 person-years across 10 studies. Study design and duration were found to account for heterogeneity. On subgroup analysis, the three cohort studies in which no intervention was introduced had a pooled incidence of 27.1 per 100 person-years (95% CI 24.4 to 29.8; I2 =0%). Incidence of pregnancy (intention undefined) was also highly heterogeneous, ranging from 2.0 to 23.4 per 100 personyears (15 studies). Conclusions: Of the many studies examining FSWs’ sexual and reproductive health in LMICs, very few measured pregnancy and fewer assessed pregnancy intention. Incidence varied widely, likely due to differences in study design, duration and baseline population risk, but was high in most studies, representing a considerable concern for this key population. Evidence-based approaches that place greater importance on unintended pregnancy prevention need to be incorporated into existing sexual and reproductive health programmes for FSWs

Sexual and reproductive health knowledge, contraception uptake, and factors associated with unmet need for modern contraception among adolescent female sex workers in China

Objective: In China, policy and social taboo prevent unmarried adolescents from accessing sexual and reproductive health (SRH) services. Research is needed to determine the SRH needs of highly disadvantaged groups, such as adolescent female sex workers (FSWs). This study describes SRH knowledge, contraception use, pregnancy, and factors associated with unmet need for modern contraception among adolescent FSWs in Kunming, China. Methods: A cross-sectional study using a one-stage cluster sampling method was employed to recruit adolescents aged 15 to 20 years, and who self-reported having received money or gifts in exchange for sex in the past 6 months. A semi-structured questionnaire was administered by trained peer educators or health workers. Multivariable logistic regression was conducted to determine correlates of low knowledge and unmet need for modern contraception. Results: SRH knowledge was poor among the 310 adolescents surveyed; only 39% had heard of any long-acting reversible contraception (implant, injection or IUD). Despite 98% reporting not wanting to get pregnant, just 43% reported consistent condom use and 28% currently used another form of modern contraception. Unmet need for modern contraception was found in 35% of adolescents, and was associated with having a current non-paying partner, regular alcohol use, and having poorer SRH knowledge. Past abortion was common (136, 44%). In the past year, 76% had reported a contraception consultation but only 27% reported ever receiving SRH information from a health service. Conclusions: This study demonstrated a low level of SRH knowledge, a high unmet need for modern contraception and a high prevalence of unintended pregnancy among adolescent FSWs in Kunming. Most girls relied on condoms, emergency contraception, or traditional methods, putting them at risk of unwanted pregnancy. This study identifies an urgent need for Chinese adolescent FSWs to be able to access quality SRH information and effective modern contraceptio

WHISPER or SHOUT study: protocol of a cluster-randomised controlled trial assessing mHealth sexual reproductive health and nutrition interventions among female sex workers in Mombasa, Kenya

Introduction New interventions are required to reduce unintended pregnancies among female sex workers (FSWs) in low- and middle-income countries and to improve their nutritional health. Given sex workers’ high mobile phone usage, repeated exposure to short messaging service (SMS) messages could address individual and interpersonal barriers to contraceptive uptake and better nutrition. Methods In this two-arm cluster randomised trial, each arm constitutes an equal-attention control group for the other. SMS messages were developed systematically, participatory and theory-driven and cover either sexual and reproductive health (WHISPER) or nutrition (SHOUT). Messages are sent to participants 2–3 times/week for 12 months and include fact-based and motivational content as well as role model stories. Participants can send reply texts to obtain additional information. Sex work venues (clusters) in Mombasa, Kenya, were randomly sampled with a probability proportionate to venue size. Up to 10 women were recruited from each venue to enrol 860 women. FSWs aged 16–35 years, who owned a mobile phone and were not pregnant at enrolment were eligible. Structured questionnaires, pregnancy tests, HIV and syphilis rapid tests and full blood counts were performed at enrolment, with subsequent visits at 6 and 12 months. Analysis The primary outcomes of WHISPER and SHOUT are unintended pregnancy incidence and prevalence of anaemia at 12 months, respectively. Each will be compared between study groups using discrete-time survival analysis. Potential limitations Contamination may occur if participants discuss their intervention with those in the other trial arm. This is mitigated by cluster recruitment and only sampling a small proportion of sex work venues from the sampling frame. Conclusions The design allows for the simultaneous testing of two independent mHealth interventions for which messaging frequency and study procedures are identical. This trial may guide future mHealth initiatives and provide methodological insights into use of reciprocal control groups