Efficacy and safety profile of the MAP-kinase pathway inhibitors in hairy cell leukemia patients.

La leucemia a cellule capellute è una sindrome linfoproliferativa rara caratterizzata dalla mutazione V600E del gene B-raf, il cui prodotto proteico sostiene il processo di leucemogenesi. La lesione genica è stabilmente riscontrata in tutte le fasi della malattia, comprese le successive ricadute, e differenzia la leucemia a cellule capellute da sindromi linfoproliferative croniche con un’espressione clinica simile, ove risulta assente. Il ruolo centrale giocato dalla proteina B-Raf nella patogenesi della malattia fa di essa un potenziale efficace bersaglio terapeutico. Il farmaco inibitore di B-Raf mutato, vemurafenib, è stato impiegato come agente singolo in pazienti con malattia ricaduta o refrattaria e pesantemente pretrattati con analoghi purinici (il gold standard del trattamento di prima linea), mostrando un tasso di risposta globale del 96%, con risposte complete nel 35% dei casi circa. Una terapia di combinazione di vemurafenib con rituximab incrementa l’efficacia degli agenti singoli nel medesimo contesto di pazienti, con risposte complete fino al 100% dei casi. La specificità della lesione genetica B-raf V600E la rende inoltre un marcatore di neoplasia attiva in tutte le fasi di malattia. È possibile dunque misurare il burden allelico di B-raf V600E alla diagnosi (a scopo di diagnostica differenziale), al termine di qualsiasi linea di trattamento (per stabilire la profondità della remissione clinica integrando i criteri di risposta attualmente vigenti) e nel follow-up per confermare la diagnosi di ricaduta o per seguire l’andamento della malattia nel tempo (su sangue periferico). Un saggio molecolare allestito su campioni di sangue periferico e midollare, con ricerca della mutazione B-raf V600E mediante droplet digital PCR, correla strettamente con i dati clinici ed emocromocitometrici del paziente in ciascuna fase di malattia.Hairy cell leukemia (HCL) is a rare chronic lymphoproliferative disorder characterized by the V600E mutation of the B-raf gene, whose product is responsible of the leukemic transformation. This genetic lesion is invariably found at both disease diagnosis and relapse, and it helps distinguish HCL from other similar lymphoproliferative diseases in which the mutation is absent. Given the pivotal role of the B-Raf protein in the pathogenesis of HCL, this might appear as a suitable treatment target. Vemurafenib, a specific inhibitor of mutated B-Raf, has been tested in patients with HCL relapsed or refractory after previous treatment(s) with purine analogues (at present regarded as the front-line treatment standards): responses were seen in 96% of cases, with complete responses in 35% of treated patients. A combination of rituximab and vemurafenib was able to produce even higher response rates, with up to 100% of complete responses. The presence of the B-raf V600E mutation in HCL may also be regarded as a marker of disease activity. This means that the allelic burden of the mutation can be measured (in both peripheral blood and bone marrow) at disease onset, to rule out a differential diagnosis; at the end of any lines of treatment, thus integrating the histological criteria now applied to establish the depth of the response; and during follow-up, to confirm the response status or to early detect a disease relapse. A molecular assay based on droplet digital PCR analysis of the B-raf V600E mutation has been developed and directly correlates with clinical and hematological data of patients in each phase of the disease

Prolonged disease-free survival in elderly relapsed diffuse large B-cell lymphoma patients treated with lenalidomide plus rituximab

open4non/aopenZinzani, PIER LUIGI; Pellegrini, Cinzia; Argnani, Lisa; Broccoli, AlessandroZinzani, PIER LUIGI; Pellegrini, Cinzia; Argnani, Lisa; Broccoli, Alessandr

Stem Cell Transplantation in Chronic Lymphocytic Leukemia

N

Pharmacoutilization of epoetins in na\uc3\uafve patients with hematological malignancies in an unselected italian population under clinical practice setting: A comparative analysis between originator and biosimilars

Aim: The purpose of this study was to assess the prescription of epoetins and consumption of health care resources (in terms of drug treatments) in na\uc3\uafve patients with hematological malignancies in a real-world setting; in particular, we compared the results between reference product and biosimilar products. Methods: An observational retrospective study based on administrative and laboratory databases of three local health units was conducted. All adults diagnosed with hematological malignancies and who had received at least one epoetin (either reference product or biosimilars) prescription for the first time between 1 January 2010 and 30 April 2012 (enrollment period) were included. The date of the first prescription of epoetin within the enrollment period was defined as index date (ID). Patients were followed up for 4 weeks after ID (follow-up period) and were investigated for the 1-year period before the ID. The difference between the last hemoglobin (Hb) measurement after ID and the one prior to ID (\uce\u94Hb) was evaluated. The drug cost analysis was conducted from the perspective of the Italian National Health System. Results: Overall, 69 patients were included in the study; 48 of them received reference epoetin product and 21 received biosimilars as first prescription. Among reference product users, the mean \uc2\ub1 standard deviation (SD) age was 62.5\uc2\ub114.7 years; this cohort of patients was slightly significantly younger than the biosimilar users (71.8\uc2\ub111.8 years). The mean \uc2\ub1SD overall Hb level prior to treatment was lower among patients who started with biosimilar products (9.6\uc2\ub11.1 g/dL) compared to those who started with a reference product (10.1\uc2\ub12.1 g/dL). No significant differences in \uce\u94Hb were observed between biosimilar and originator groups during the followup period. The mean \uef\u82\u81\uef\u81\ubd\uef\u80 SD cost per patient was \ue2\u82\uac667.98\uc2\ub1573.93 and \ue2\u82\uac340.85\uc2\ub1235.73 for the reference product and biosimilar users, respectively (p=0.065). Conclusion: Our study showed that the use of biosimilar products might contribute to controlling health care costs (in terms of drug treatments) for patients with hematological malignancies being maintained by high-quality anemia therapy. Our findings also showed some discordances regarding the most appropriate therapeutic approach in daily clinical practice

Evaluation of an intervention aimed at supporting new parents: the Baby Newsletter project

Background: Anticipatory guidance for parents is commonly used to improve parenting skills. The objective of this pre/post-intervention controlled study was to evaluate the effectiveness of a periodic newsletter with advice on childcare and development in improving parenting self-efficacy. Methods: This was a non-randomized pre/post-intervention controlled study. All the parents of children born between September 2014 and December 2015 resident in the S. Ilario d’Enza municipality (Italy) received eight Baby Newsletters. Parents resident in other municipalities of the same Health District were the control. Parents with linguistic barriers or with preterm or hospitalized children were excluded. Improvement in parenting self-efficacy was measured through the TOPSE (Tool to Measure Parenting Self-Efficacy) questionnaire during the first week (t0) after delivery and at 5 (t1) and 12 months (t2) of life at two vaccination appointments. A score ranging from 0 to 60 was computed for each of the eight domains investigated by the TOPSE. Variations of each TOPSE score between delivery and 12 months in the two groups were compared, adjusting for parity, education, age of parents, and child’s sex, and stratifying by parity and education. Results /findings: One hundred thirty-six families accepted to participate in the study. Scores at 12 months were higher than 1 week after delivery in both groups for all TOPSE domains. The improvement was slightly stronger in the Newsletter group for almost all the skills except learning and knowledge [difference in the mean of variation: -0.48 (95% CI: − 3.17; 2.21)]; the difference was significant only for play and enjoyment [2.18 (95% CI: 0.12; 4.25)]. The increase in scores in almost all domains was more pronounced for parents with high education level at first child. Conclusions: The intervention was effective in improving parents’ ability to play. However, it risks worsening existing differences between parents with high and with low education levels

Prolonged Complete Response with Lenalidomide in a Relapsed Diffuse Large B-cell Lymphoma, Leg-type: A Case Report

Introduction: For primary cutaneous diffuse large B-cell lymphoma, leg-type (PC DLBCL-LT) there are no uniform recommendations for second-line treatment in case of relapse. Case presentation: Here we present the case of an elderly relapsed/refractory PC DLBCL-LT patient who obtained a prolonged clinical complete remission with lenalidomide. Conclusion: Lenalidomide as single agent led to an unexpected long complete response with manageable toxicity

BRAF V600E-positive monomorphic epitheliotropic intestinal T-cell lymphoma complicating the course of hairy cell leukemia

Hairy cell leukemia (HCL) is an uncommon B-cell chronic lymphoproliferative disorder whose pathogenesis and recurrence are strictly dependent on the presence of the BRAF V600E mutant. A 65-year-old male presented a monomorphic epitheliotropic intestinal T-cell lymphoma (formerly enteropathy-associated T-cell lymphoma, type II) with HCL not responding to first-line induction with cladribine. The intestinal lymphoma bears the BRAF V600E mutant, which is the molecular hallmark of HCL, being implicated in its pathogenesis. The case is of interest, as it provides the first description of a BRAF V600E-positive intestinal T-cell lymphoma, along with immunohistochemical and molecular demonstration, occurring in concomitance with HCL. A novel digital PCR-base method for HCL disease assessment is also suggested

90-yttrium-ibritumomab tiuxetan consolidation of fludarabine, mitoxantrone, rituximab in intermediate/high-risk follicular lymphoma: updated long-term results after a median follow-up of 7\ua0years

Radioimmunotherapy (RIT) after an induction phase with conventional chemoimmunotherapy became an attractive strategy of consolidation for patients with advanced follicular lymphoma: in particular, in many studies RIT was represented by yttrium-90-ibritumomab tiuxetan (90Y-IT). Independently by the different front-line treatment, updates on the long-term follow-up of these studies are needed because the disease course of follicular lymphoma is characterised by multiple relapses and progressively shorter durations of response. We report updated long-term efficacy and toxicity results of a multicenter phase II study on sequential treatment with four cycles of fludarabine, mitoxantrone, and rituximab followed by 90Y-IT as front-line therapy for untreated patients with intermediate/high-risk follicular lymphoma. With a median follow-up of 84 months, only 19/49 (38.8%) complete response patients relapsed, yielding an estimated long-term disease-free survival of 62.6%. The 7-year overall survival was 72.7%. Four (7.3%) second acute myeloid leukemia occurred, with a median time following RIT of 42 months. A relevant patients' responsiveness to subsequent therapies occurred: approximately 65% of relapsed patients obtained a good clinical response after the second-line treatment. These data represented the first evidence of a real role even in the long period of 90Y-IT after a fludarabine-containing regimen plus rituximab in the treatment of high-risk follicular lymphoma

PEERS’ ANATOMY: teaching among students as an original approach to learning anatomy – a project made in Alma Mater

Anatomy is an ancient discipline which benefited greatly from technological improvements. Those very same technologies, along with a shift towards more clinically relevant topics, might be endangering anatomy’s central role as a cornerstone of medical education. A review of local realities showed anatomy to be quite uniformly taught by means of lectures alone. On the basis of our own experience, and comforted by references in literature (Day et al. [1]), we propose a revaluation of the teaching approach to anatomy, which includes an integration between different available resources and, above all, introduces peer-to-peer activity. Over the course of the last decade, based on a proposal from the Anatomy Department, more and more medical students took part to gross anatomy workshops abroad, thus consolidating what today is a large group of tutors. Working in parallel with the lectures, back home these students organize activities where notions are not a mere tool to pass the exam, but are aimed at giving younger students solid foundations on which to build their future competence. On the grounds of the experiences acquired in these years, we managed to divide the tutoring activities into six areas: surface and topographic anatomy, muscles and skeleton, heart and thorax, neuroanatomy, abdomen and pelvis, didactic coordination. Each group is based on the equal division of tasks and on respecting each tutor’s expertise, attitudes and skills. These workshops have proved to be highly effective both for students, as a chance to experience anatomy “hands-on”, and for tutors, as an opportunity of mastering the subject. Being appointed a tutor outlines a shift from a deductive learning method, typical of the pre-exam phase, to an inductive one, more useful in the future as medicine doctors. To sum up, the availability of adequate facilities for cadaveric dissection certainly enhances the teaching of anatomy; what our experience shows, however, is that only direct involvement of students as tutors brings out the full potential of these activities. We therefore propose abandoning a pure “learning-to-do” approach, in favour of a more effective “learning-by- doing” strategy

Single-agent rituximab is an effective salvage therapy in pretreated patients with hairy cell leukemia

No abstract availabl