First-Line Therapy for Nodal T-cell Non-Hodgkin Lymphomas: an Unmet Need in Hematology.

PURPOSEOF REVIEW: The main aim of this review is to summarize first-line therapy of nodal T-cell non-Hodgkin lymphoma. RECENT FINDINGS: Current treatment with CHOP chemotherapy results in poor outcomes in the majority of patients. However, there are advances within the field. First breakthrough is the ECHELON-2 trial which showed that the addition of brentuximab vedotin improves outcomes in anaplastic large cell lymphoma. However, other types of peripheral T-cell non-Hodgkin lymphoma were underrepresented with optimal treatment not known. Second breakthrough is an increase of autologous stem cell transplantation usage in the first complete metabolic remission, except in ALK + anaplastic large cell lymphoma, offering better disease control. Despite advances in the field, CHOP remains the standard treatment for the majority of these lymphomas, but multiple trials are underway with the aim to improve this unmet need in hematology and, hopefully, leading us to a new era in the treatment of peripheral T-cell lymphomas.

[CURRENT APPROACH TO NON-HODGKIN MANTLE CELL LYMPHOMA: LITERATURE REVIEW].

Mantle cell lymphoma (MCL) represents the fourth most common type of non-Hodgkin lymphomas. It is characterized by aggressive course and frequent relapses. The main aim of this review is to evaluate current treatment approach towards this type of lymphoma. In younger patients the chemotherapy including high doses of cytarabine is the gold standard. In case of complete or partial remission, the consolidation with autologous stem cell transplantation is indicated as consolidation approach. In older patients CHOP-R regimen is not the treatment of choice. These patients should be treated with bendamustine in combination with rituximab. In case of complete or partial remission, further therapy with rituximab maintenance as consolidation represents an option. The vast majority of patients with MCL will ultimately relapse which poses a challenge in treatment approach. The approach in relapsed MCL can be divided in two types: chemotherapy or biologic therapy. In young fit patients chemotherapy based on bendamustine and cytarabine is a reasonable option. In patients with comorbidities or poor performance status biologic agents are reasonable options. Ibrutinib, Bruton kinase inhibitor, is characterized by highest overall response rate and the longest duration of response and should be offered to these patients. With the development of novel potent inhibitor of B cell receptor signaling pathway, these agents may become the gold standard in future and introduce the treatment of MCL in "chemo-free"era.

[AUTOLOGOUS STEM CELL TRANSPLANTATION IN REFRACTORY OR RELAPSED DIFFUSE LARGE B CELL LYMPHOMA - A SINGLE CENTRE EXPERIENCE]. / AUTOLOGNA TRANSPLANTACIJA PERIFERNIH MATICNIH STANICA U REFRAKTORNOM ILI RELAPSNOM NE-HODGKINOVU LIMFOMU DIFUZNOGA B-VELIKOSTANICNOG TIPA - ISKUSTVO JEDNOG CENTRA.

Autologous stem cell transplantation represents the gold standard in chemosensitive diffuse B large cell lymphoma in relapse or in refractory setting. The aim of this study was to present the outcome of peripheral autologous stem cell transplantation in patients with refractory or relapsed diffuse large B cell lymphoma. We retrospectively analysed the data of 62 patients, who underwent this procedure for the period 2000-2013. The majority of patients (71%) were treated with miniBEAM salvage chemotherapy and all received BEAM myeloablative protocol followed by the stem cell reinfusion. The overall response rate for autologous transplantation was 75.8%. Median overall survival was 37.2 months. Median event-free survival was 16.9 months. Factors associated with overall survival were state of disease prior to salvage chemotherapy, chemosensitivity of disease, International prognostic index, disease activity at the relapse, response to autologous transplantation and post-transplantation radiotherapy. The use of rituximab was not significantly correlated to the outcome. In this patient group autologous stem cell transplantation was found to be effective in achieving remission and survival showing the adequate role of this procedure in this clinical setting. We stress out that autologous stem cell transplantation was effective in 32.5% patients with chemorefractory disease after salvage therapy.

[Diagnostic approach and treatment of immune thrombocytopenia in adults]. / Dijagnosticki pristup i lijecenje imune trombocitopenije u odrasloj dobi.

The aim of this review is to provide the Croatian medical public with novel insights into the definition, pathogenesis, diagnostic algorithms and treatment approaches to immune thrombocytopenia (ITP) in adults. Recently, primary ITP has been uniformly defined as an autoimmune disorder characterized by an isolated platelet count lower than 100 x 10(9)/L without preexisting disease or conditions, which could lead to thrombocytopenia. The recognition of primary and secondary ITP is important because they require different treatment strategies. In secondary ITP, therapeutic approach oriented towards the underlying disorder. Unlike childhood onset ITP, which is a self-limited condition with high rates of spontaneous remissions, adulthood onset ITP usually has chronic course. Previously, the pathogenesis of ITP was considered to be immune mediated destruction of platelets in liver and spleen, while recent findings have shown a novel pathophysiological pathway based on the inhibition of thrombopoiesis, leading to novel treatment approaches. The diagnosis of ITP is based on exclusion of the possible underlying causes of thrombocytopenia and consists of simple diagnostic procedures. The decision to treat ITP should be based individually: platelets count (lower than 30 x 10(9)/L), various bleeding risk factors and patient's preference. The use of corticosteroids is the mainstay of first line therapy. Two most commonly used corticosteroids are prednisone and dexamethasone. Prednisone is administered continuously, while dexamethasone is applied in cycles. Due to the lack of randomized clinical trials, it is not possible to recommend certain class of corticosteroid therapy. Another two agents used as first line therapy in case of corticosteroid refractoriness or the need of rapid platelet elevation, are intravenous immunoglobulins and anti-D immunoglobulin (anti-D is not approved in Europe). They are characterized by rapid onset of platelet recovery and low long-term remission rates. Until recently, splenectomy, with adequate infectious and thromboprophylaxis, was the therapy of choice in patients who did not respond to corticosteroids due to high long-term remission rates and low relapse rates. This procedure can be offered to a younger patient without significant comorbidities after the first year of ITP duration. With advances in the understanding of ITP pathogenesis, a new class of drug has been established: thrombopoietin agonists (TPO). Eltrombopag and romiplostim, the TPO agonists currently approved for the management of ITP in patients who failed the first line therapy and are not suitable for splenectomy, are only two agents that have shown benefits in large clinical randomized trials. They are characterized by a high response rate and appropriate safety profile, but the need for continuous use, a high relapse rate after therapy withdrawal, and price limit their use in everyday practice. TPO agonists represent an appropriate treatment choice in patients who have relapse after splenectomy. Another agent, often used in everyday clinical practice, is rituximab with high response and relapse rates. Its use is based on small studies, and due to the lack of clinical randomized controlled trials, rituximab is not approved by the leading medical agencies for this indication. As shown in this review article, our understanding and therapy for ITP has improved, but further research is needed to implement evidence-based therapy in clinical practice.