1,721,079 research outputs found
The role of transplantation in Hodgkin lymphoma
No full textAutologous stem cell transplantation is the standard salvage strategy for young and fit patients with Hodgkin lymphoma failing induction therapy, and is effective in nearly 50% of cases. The quality of response at transplantation is the most relevant prognostic aspect, as patients in complete response can obtain better outcomes. Therefore, first-line salvage treatments applied before transplantation need to produce high quality responses without excessive myelotoxicity and without affecting peripheral blood stem cell mobilisation. In this sense, the incorporation of new agents active in Hodgkin lymphoma, such as brentuximab vedotin and anti-programmed death 1 antibodies, in conventional regimens, may help to enhance complete remission rates. Working on conditioning regimen and applying a post-autologous consolidation treatment (for example with brentuximab vedotin) are two ways for improving transplant outcomes, particularly in patients displaying high-risk features for early relapse or progression. Allogeneic transplantation maintains its curative potential also in the era of new drugs, although its most correct timing and the most suitable sequence of post-autologous salvage treatments still remain to be determined
The unique biology and treatment of primary mediastinal B-cell lymphoma
No full textThe unique biological features of primary mediastinal large B-cell lymphoma are offering suggestions for the development and application of innovative drugs in patients who do not respond to first-line regimens or relapse. This lymphoma, in fact, is characterised by high rates of curability with standard anthracycline-containing chemoimmunotherapy regimens, but still displays a severe prognosis if adequate responses are not rapidly achieved or if the disease recurs. Radiotherapy has proved to be effective to consolidate responses after induction, but it may be safely avoided in certain cases, especially when a metabolic complete response is obtained, as to reduce the incidence of radiation-induced long-term sequelae. The current management of this lymphoma, both at diagnosis and at relapse, is reviewed in this paper, along with the description of its peculiar biological panorama
Peripheral T-cell lymphoma, not otherwise specified.
No full textPeripheral T-cell lymphoma, not otherwise specified, is a broad category of biologically and clinically heterogeneous diseases that cannot be further classified into any other of the existing entities defined by the World Health Organization classification. Anthracycline-containing regimens, namely cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), nowadays represent the standard first-line treatment; for patients who achieve a satisfactory response, a consolidation by means of autologous stem cell transplantation may offer a greater chance of long-term survival. Several patients, however, display treatment refractoriness or relapse soon after obtaining a response, and just a few of them are suitable transplant candidates. This is why several new agents, with innovative mechanisms of action, have been investigated in this context: pralatrexate, romidepsin, belinostat, and brentuximab vedotin have been approved for relapsed and refractory peripheral T-cell lymphomas based on their activity, although they do not significantly affect survival rates. The incorporation of such new drugs within a CHOP backbone is under investigation to enhance response rates, allow a higher proportion of patientsto be transplanted in remission, and prolong survival
Optimizing Outcomes in Primary Mediastinal B-cell Lymphoma
No full textPrimary mediastinal B-cell lymphoma is characterized by a high chance of cure, and cured patients have a long disease-free life-expectancy; however, prognosis is severe in the case of relapsed or refractory disease. The initial use of the most effective chemoimmunotherapy regimen is therefore crucial. Understanding who will benefit from postinduction radiotherapy is also of paramount importance; positron emission tomography may be a reliable guide for physicians in determining which patients will require consolidation. New drugs with mechanisms of action including the most relevant biologic features of the tumor may allow better disease control
Possible novel agents in marginal zone lymphoma
No full textEfficacy, safety and mechanisms of action of novel agents in marginal zone lymphoma patients, both with a nodal and extranodal presentation, are reviewed. Data on lenalidomide, bortezomib and 90yttrium-ibrutumomab tiuxetan are obtained from trials specifically designed for patients affected by marginal zone lymphoma and with various disease presentations. The role of targeted agents, such as obinutuzumab, ibrutinib and idelalisib, and of some very new drugs (venetoclax, copanlisib, ublituximab and TGR-1202) is also discussed, taking into account the most relevant experiences in patients with indolent non-Hodgkin's lymphomas. A glance to some possible drug combinations will also be provided, along with an update of the most relevant ongoing trials
Angioimmunoblastic T-Cell Lymphoma
No full textAngioimmunoblastic T-cell lymphoma is a follicular T-helper–derived neoplasm displaying a peculiar morphologic appearance and biological complexity. New mutations have been described that contribute to elucidating the underlying pathogenetic events. The disease behaves aggressively and typically affects elderly patients. The outcomes reported with anthracycline-containing regimens are poor; therefore autologous transplantation in first remission should be offered whenever possible. Newer approaches are urgently needed for relapsed and refractory patients. Newly approved agents show activity in pretreated patients but response durations are short. Innovative induction strategies (CHOP + biologic agent) should be designed to enhance response quality, facilitate transplantation, and prolong survival
Covalent Bruton tyrosine kinase inhibitors across generations: A focus on zanubrutinib
Full text linkBruton tyrosine kinase (BTK), the primary target of BTK inhibitors, is a key enzyme in the proliferation and survival pathway of neoplastic B-cells. BTK inhibitors are approved in many hematologic malignancies: chronic lymphocytic leukaemia, mantle cell lymphoma, marginal zone lymphoma, Waldenström macroglobulinaemia and follicular lymphoma. Second-generation BTK inhibitors display high target selectivity thus resulting in a reduction in off-target and off-tissue effects, better therapeutic index and improved tolerability. This paper summarizes the mechanisms of action of first and second generation BTK inhibitors and elucidates results in any disease setting, with a precise focus on zanubrutinib
Corso di malattie del sangue e degli organi emolinfopoietici
No full textQuesta nuova edizione del Corso di Malattie del Sangue e degli Organi Emolinfopoietici incorpora tutti gli aggiornamenti dell'ultima revisione della classificazione delle neoplasie del tessuto emopoietico e linfoide edita dall'Organizzazione Mondiale della Sanità. Inoltre, presenta in modo completo le più recenti acquisizioni biologiche e terapeutiche nell'ambito delle patologie dell'eritropoiesi, della piastrinopoiesi e della coagulazione del sangue, con particolare enfasi sia su molecole recentemente approvate, sia su farmaci in sperimentazione.
Sono passati 5 anni dalla stesura dell’ultima edizione di questo Manuale e a giudicare dalla mole di nuove acquisizioni di biologia, prognosi e terapia delle malattie del sangue sembra che sia passato un secolo. Le nuove conoscenze, nella maggior parte dei casi, hanno un impiego clinico che ha modificato il decorso di molte emopatie, la “qualità” della vita durante la terapia, la sopravvivenza e la percentuale di guarigioni. Lo studente di medicina deve sapere che, oggi, la maggior parte dei pazienti, compresi quelli a peggiore prognosi, possono essere curati ambulatorialmente con grandi vantaggi per la qualità della loro vita. Tutto questo è il frutto d’importanti acquisizioni di biologia molecolare, cellulare e di farmacologia che hanno portato alla sintesi di nuovi farmaci che vengono messi sul mercato con incredibile frequenza e mirati a distruggere le cellule patologiche risparmiando quelle sane. Sono farmaci ben tollerati e molto spesso somministrati per via orale
Cutaneous T-cell lymphomas: Focusing on novel agents in relapsed and refractory disease
No full textPatients with relapsed or refractory cutaneous T-cell lymphoma (CTCL) display a dismal prognosis and their therapy represents an unmet medical need, as the best treatment strategy is yet to be determined. Exciting data on novel targeted agents are now emerging from recently concluded and ongoing clinical trials in patients with relapsed and refractory CTCL. Three FDA approved compounds are used as single agents including the oral retinoid bexarotene and histone deacetylase inhibitors romidepsin and vorinostat. Brentuximab vedotin, an anti-CD30 drug-conjugated monoclonal antibody, has received from European Commission the orphan designation but has not been approved by EMA yet. Several other molecules have demonstrated their activity in the same context and combination strategies are being explored. Participation in a well designed clinical trial is encouraged, as the introduction of novel agents will continue to expand the therapeutics options available in the management of CTCL
Peripheral T-cell lymphomas: Focusing on novel agents in relapsed and refractory disease
No full textPatients with relapsed or refractory peripheral T-cell lymphoma display a dismal prognosis and their therapy represents an unmet medical need, as the best treatment strategy is yet to be determined. Exciting data on novel targeted agents are now emerging from recently concluded and ongoing clinical trials in patients with relapsed and refractory PTCL. Four recently approved compounds are used as single agents: pralatrexate, a novel antifolate agent; romidepsin and belinostat, both histone deacetylase (HDAC) inhibitors; brentuximab vedotin, an anti-CD30 drug-conjugated monoclonal antibody. Several other molecules have demonstrated their activity in the same context: gemcitabine, bendamustine, lenalidomide, duvelisib, copanlisib, alisertib, mogamulizumab, selinexor and ARGX-110. Robust preclinical observations strongly support chemo-free combinations, which are expected to enhance the quality and duration of responses in pretreated patients and in those who are unable to receive a stem cell transplantation
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