Sonbol, Mohamad B

Mantle cell lymphoma (MCL) is a unique type of lymphoma with a prognosis intermediate between indolent and aggressive types. The purpose of this study was to study blood cytokine levels in newly diagnosed and relapsed MCL patients with respect to patterns of abnormalities and relationship to the MCL International Prognostic Index (MIPI) score. We analyzed blood levels of 30 cytokines using a multiplex ELISA in 88 patients with newly diagnosed MCL (pre‐treatment levels) and 20 with relapsed MCL and compared them with controls without known lymphoma. Elevated cytokine levels were compared with clinical outcome and the MIPI score. In the 88 newly diagnosed MCL patients, we found significantly elevated levels compared with controls of IL‐12, IP‐10, sIL‐2Rα, MIG, IL‐1RA, IL‐8, MIP‐1α, and MIP‐1β (all P < 0.05). Of these elevated cytokines, sIL‐2Rα, IL‐8, MIG, MIP‐1α, and MIP‐1β were predictive of inferior event‐free survival, and sIL‐2Rα (HR = 1.94; P = 0.038), IL‐8 (HR = 2.17; P = 0.015), and MIP‐1β (HR = 2.10; P = 0.016) were independent of MIPI score; only sIL‐2Rα (HR = 2.35; P = 0.041) was associated with overall survival after adjustment for MIPI. In the relapsed MCL patient group, the only significantly elevated plasma cytokines that predicted EFS were sIL‐2Rα (HR = 2.90; P = 0.04) and IL‐8 (HR = 3.75; P = 0.02). Elevated blood levels of sIL‐2Rα and the pro‐inflammatory cytokines IL‐8 and MIP‐1β are poor prognostic factors in MCL patients and independent of MIPI score. These factors, if validated, will provide important additions to the MIPI and guide the development of new therapies for patients with elevated levels of these cytokines. Am. J. Hematol. 89:E223–E227, 2014. © 2014 Wiley Periodicals, Inc.

Abstract Background: Palestinian refugees have been a displaced group of people since 1948, many of whom are living in refugee camps in the Middle East. They are entitled to free health care from the United Nations Relief and Work Agency (UNRWA). They show a higher prevalence of diabetes than the population in their host countries in the Middle East. This study examined the realities of care for diabetic patients in UNRWA health clinics in Damascus, Syria. The aim was three‑fold: To investigate the level of diabetes care, to probe patients′ level of general understanding of their disease and its management, and to search for areas of potential improvement. Methods: Data on patient education and care was gathered over a 1 month period from August 4, 2008 to September 4, 2008 using questionnaires and direct observation of the workflow at the clinics. Clinic‑led care was observed by the study team using checklists during patient visits. All of the clinic staff and sampled patients were interviewed. The main areas of care assessed were: Patient follow‑up; examination of eyes and feet; availability of medications; and patient education. A total of 154 people with diabetes were sampled from three refugee camps situated around Damascus. Results: A total of 154 patients, three doctors and seven nurses composed the sample of the study. Foot examinations were almost always neglected by health staff and eye examinations were not offered by the UNRWA clinics. Interviews with patients showed that: 67% (95% confidence intervals [CI]: 0.59‑0.70) had to buy their medication at their own expense at least once due to medication shortage in the UNRWA clinics, 48% (95% CI: 0.40‑0.55) displayed poor knowledge regarding the cause and exacerbating factors of diabetes, 65% (95% CI: 0.56‑0.72) had not heard of insulin, and 43% (95% CI: 0.35‑0.51) did not know for how long they needed to take their medications.

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem-cell disorders, characterized phenotypically by the abnormal accumulation of mature-appearing myeloid cells. Polycythemia vera, essential thrombocythemia, primary myelofibrosis (also known as ‘ BCR-ABL1-negative’ MPNs), and chronic myeloid leukemia (CML) are the primary types of MPNs. After the discovery of the BCR-ABL1 fusion protein in CML, several oncogenic tyrosine kinases have been identified in ‘ BCR-ABL1-negative’ MPNs, most importantly, JAK2V617F mutation. The similarity in the clinical characteristics of the BCR-ABL1-negative MPN patients along with the prevalence of the Janus kinase mutation in this patient population provided a strong rationale for the development of a new class of pharmacologic inhibitors that target this pathway. The first of its class, ruxolitinib, has now been approved by the food and drug administration (FDA) for the management of patients with intermediate- to high-risk myelofibrosis. Ruxolitinib provides significant and sustained improvements in spleen related and constitutional symptoms secondary to the disease. Although noncurative, ruxolitinib represents a milestone in the treatment of myelofibrosis patients. Other types of JAK2 inhibitors are being tested in various clinical trials at this point and may provide better efficacy data and safety profile than its predecessor. In this article, we comprehensively reviewed and summarized the available preclinical and clinical trials pertaining to JAK inhibitors.