Long-term results of frontline dasatinib in chronic myeloid leukemia.

BACKGROUND: Dasatinib is a second-generation tyrosine kinase inhibitor that, when used as frontline therapy, produces more and faster cytogenetic and molecular responses compared with imatinib. The authors report the long-term follow-up from the first study using dasatinib as initial therapy for chronic-phase chronic myeloid leukemia. METHODS: Between November 2005 and August 2014, patients were randomly assigned to receive 100 mg daily or 50 mg twice daily. After June 2009, all patients started with 100 mg daily. RESULTS: With a median follow-up of 6.5 years, 94 of 149 treated patients (63%) were still receiving dasatinib on study. The median patient age was 48 years (interquartile range, 37-55 years), and 9% of patients had a high risk Sokal risk score. The cumulative complete cytogenetic response rate at 11 years was 92.6%, the major molecular response (MR) rate was 88.2%, and the MR4.5 rate (indicating a ≥4.5-log reduction in BCR-ABL1 transcripts) was 79.5%. The median time to a major MR and MR4.5 was 6 and 23 months, respectively. A sustained MR4.5 (≥2 years) was achieved in 82 patients (55%). The 10-year overall survival, transformation-free survival, event-free survival, and failure-free survival rates were 89%, 95%, 86%, and 65%, respectively. Univariate analysis showed that the achievement of a complete MR was associated with improved overall survival. The most common reasons for treatment discontinuation were toxicity and elective discontinuation. The most common treatment-emergent grade 3 and 4 adverse events were fatigue, thrombocytopenia, and infections. CONCLUSIONS: After this long-term follow-up, dasatinib continues to show an excellent safety profile and produces rapid cytogenetic responses and MRs, durable deep MRs, and excellent long-term survival outcomes in patients with chronic-phase chronic myeloid leukemia.

Antiretroviral therapy maintenance among HIV-positive women in Ghana: the influence of poverty.

This study examines the role of poverty in the acquisition of and the adherence to antiretroviral therapy (ART) and prescribed clinical follow-up regimens among HIV-positive women. We conducted in-depth interviews with 40 women living with HIV (WLHIV) in Ghana and 15 stakeholders with a history of work in HIV-focused programs. Our findings indicate that financial difficulty contributed to limited ability to maintain treatment, the recommended nutrient-rich diet, and clinical follow-up schedules. However, enacted stigma and concurrent illness of family members also influenced the ability of the WLHIV to generate income; therefore, HIV infection itself contributed to poverty. To further examine the relation between finances, ART adherence, and the maintenance of recommended clinical follow-up, we present the perspectives of several HIV-positive peer counselor volunteers in Ghana's Models of Hope program. We recommend that programs to combat stigma continue to be implemented, as decreased stigma may reduce the financial difficulties of HIV-positive individuals. We also recommend enhancing current support programs to better assist peer counselor volunteers, as their role directly supports Ghana's national strategic HIV/AIDS plan. Finally, additional investment in poverty-reduction across Ghana, such as broadening meal assistance beyond the currently limited food programs, would lighten the load of those struggling to combat HIV and meet basic needs.

HIV antiretroviral medication stock-outs in Ghana: contributors and consequences.

Drug stock-outs are an unfortunate yet common reality for patients living in low and middle income countries, particularly in sub-Saharan Africa where trouble with consistent stock of antiretroviral medications (ARVs) continues. Our study takes a snapshot of this problem in Ghana. Although the country launched its antiretroviral therapy (ART) programme in 2003, progress toward realising the full benefit of ART for treated individuals has been limited, in part, because of stock-outs. In Ghana's Greater Accra region, we conducted semi-structured interviews with 40 women living with HIV (WLHIV) and 15 individuals with a history of HIV-related work in government or non-governmental organisations, or healthcare facilities. We used repeated review with coding and mapping techniques to analyse the transcripts and identify common themes. Stock-outs of ARVs result in inconsistent administration of therapy, increased indirect medical costs for WLHIV, and negative labelling of patients. Inefficiencies in drug supply, poor coordination with port authorities, inadequate government funding and dependence on international aid contribute to the stock-outs experienced in Ghana. Although using ARVs produced in-country could reduce supply problems, the domestically-manufactured product currently does not meet World Health Organization (WHO) standards. We recommend focused efforts to produce WHO standard ARVs in Ghana, and a review of current supply chain management to identify and mend pitfalls in the system.

Considerations for purposeful HIV status disclosure among women living with HIV in Ghana.

Although disclosure of positive HIV status has recognized benefits, enacted and perceived stigma is a continuing problem in Ghana, especially affecting women living with HIV (WLHIV). This qualitative study investigates how WLHIV make these decisions. We interviewed 40 WLHIV, analysing their transcripts using thematic content analysis. Four themes emerged from the data: selectivity in disclosure; disclosure for education, prevention and to provide support; concern for the potential confident, and safety in secrets. Women's awareness of and concerns about HIV-related stigma led them to seriously weigh the costs and benefits of disclosure decisions. Overall, our participants disclosed only when they believed that disclosure would benefit them or the confidant. They did not condone open disclosure, and preferred non-disclosure to minimize harm to themselves and loved ones. Though disclosure occurred for HIV education and prevention purposes, personal safety was the priority. We recommend revision of current post-HIV testing and pre-treatment counselling procedures to incorporate WLHIVs' judgements about disclosure and discussion of the perceived benefits of disclosure. Disclosure is an intricate process that involves support seeking and educating others while averting harm. Continued research of the factors related to disclosure is important to enhance understanding of the disclosure process.

Long-term durable remission by cladribine followed by rituximab in patients with hairy cell leukaemia: update of a phase II trial.

Nucleoside analogues are highly active in patients with hairy cell leukaemia (HCL); however, patients continue to relapse. This phase II study evaluated the efficacy and safety of cladribine followed by rituximab in patients with untreated HCL (N = 59), relapsed HCL (N = 14) and HCL variant (HCLv, N = 7). Cladribine 5·6 mg/m(2) was given intravenously (IV) daily for 5 d and was followed approximately 1 month later with rituximab 375 mg/m(2) IV weekly for 8 weeks. Complete response rate in patients with untreated HCL, relapsed HCL and HCLv was 100%, 100% and 86%, respectively. With a median follow up of 60 months, 5-year failure-free survival (FFS) in patients with untreated HCL, relapsed HCL and HCLv was 95%, 100% and 64%, respectively. Median duration of response to the cladribine followed by rituximab was significantly longer than the first-line cladribine single agent in patients who received this treatment as second-line treatment (72 months vs not reached, P = 0·004). Almost all patients (94%) achieved negative minimal residual disease (MRD) after the treatment. Positive MRD during the follow up did not necessarily result in clinically relevant relapse. Cladribine followed by rituximab is highly effective even in patients with relapsed disease and HCLv, and can achieve durable remission.