Expert review of hematology
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B-cell receptor (BCR) signaling plays a vital role in B-cell malignancies; Bruton tyrosine kinase is a critical mediator of this signaling. BCR signaling, either constitutively or following antigen binding, leads to activation of several downstream pathways involved in cell survival, proliferation and migration. The efficacy observed in studies of the Bruton tyrosine kinase inhibitor, ibrutinib, confirms that BCR signaling is critical for the growth of B-cell malignancies. ⋯ Ibrutinib has been shown to have an excellent safety profile and does not cause myelosuppression. Early data from combination studies of ibrutinib with anti-CD20 monoclonal antibodies have shown more rapid responses compared to those seen with ibrutinib monotherapy. Current data strongly support continued clinical evaluation of ibrutinib in B-cell malignancies.
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Mantle cell lymphoma (MCL) is a rare and aggressive form of non-Hodgkin's lymphoma. It can follow a heterogeneous clinical course but generally patients relapse early after standard immunochemotherapy regimens and develop resistance to subsequent therapies. For younger patients, intensive approaches followed by autologous stem cell transplantation offer excellent long-term disease control but with the possible exception of an allogenic stem cell transplant, MCL is an incurable condition. ⋯ It inhibits signaling pathways downstream of Bruton's tyrosine kinase that appear critical for the proliferation and survival of MCL. As a single agent it has shown extremely promising activity in relapsed and refractory MCL patients with an excellent side-effect profile. The exact role for ibrutinib in the treatment of MCL is yet to be established; however, it is likely to fundamentally change the way we treat this disease.
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Editorial
Calreticulin: a new horizon for the testing and treatment of myeloproliferative neoplasms.
The recent discovery of mutations of the gene calreticulin has allowed raising the proportion of patients with essential thrombocythemia and primary myelofibrosis with known mutational abnormality up to 85-90%. Knowledge of the mechanisms by which mutated calreticulin underlie a myeloproliferative neoplasm as well as the clinical and therapeutic implications is just at the very beginning, and exciting times await research in this field.
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Thrombocytopenia is a very common hematological abnormality found in newborns, especially in preterm neonates. Two subgroups can be distinguished: early thrombocytopenia, occurring within the first 72 hours of life, and late thrombocytopenia, occurring after the first 72 hours of life. Early thrombocytopenia is associated with intrauterine growth restriction, whereas late thrombocytopenia is caused mainly by sepsis and necrotizing enterocolitis (NEC). ⋯ In addition, risks of platelet transfusion seem to be more pronounced in preterm neonates. Because of lack of data, platelet transfusion guidelines differ widely between countries. This review summarizes the current understanding of etiology and management of neonatal thrombocytopenia.
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In spite of significant advances in the management of multiple myeloma (MM), the disease remains incurable and nearly all patients ultimately relapse and require salvage chemotherapy. As such, relapsed and relapsed-refractory MM remains a critical area of research pertaining to biological mechanisms of progression and chemotherapy resistance, as well as to the development of new pharmacologic agents and immunologic approaches for the disease. The immunomodulatory agents and proteasome inhibitors represent the cornerstone of treatment in this setting, with combination regimens incorporating these drugs demonstrating encouraging rates and duration of response, including the newer agents, pomalidomide and carfilzomib. In addition, novel drug classes have shown promising activity in RR MM, including the orally-administered proteasome inhibitors ixazomib and oprozomib; monoclonal antibodies such as the anti-CS1 monoclonal antibody elotuzumab and anti-CD38 monoclonal antibody daratumumab; and histone deacetylase inhibitors such as panobinostat and rocilinostat.