Journal•ISSN: 1558-8211
Current Hematologic Malignancy Reports
Springer Science+Business Media
About: Current Hematologic Malignancy Reports is an academic journal published by Springer Science+Business Media. The journal publishes majorly in the area(s): Transplantation & Myeloid leukemia. It has an ISSN identifier of 1558-8211. Over the lifetime, 787 publications have been published receiving 12462 citations. The journal is also known as: Curr. Hermatol. malig. rep.
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TL;DR: Post-transplant lymphoproliferative diseases (PTLD) are heterogeneous lymphoid disorders ranging from indolent polyclonal proliferations to aggressive lymphomas that complicate solid organ or hematopoietic transplantation.
Abstract: Post-transplant lymphoproliferative diseases (PTLD) are heterogeneous lymphoid disorders ranging from indolent polyclonal proliferations to aggressive lymphomas that complicate solid organ or hematopoietic transplantation. Risk factors for PTLD include viral infections, degree of immunosuppression, recipient age and race, allograft type, and host genetic variations. Clinically, extra-nodal disease is common including 10–15 % presenting with central nervous system (CNS) disease. Most PTLD cases are B cell (5-10 % T/NK cell or Hodgkin lymphoma), while over one-third are EBV-negative. World Health Organization (WHO) diagnostic categories are: early lesions, polymorphic, and monomorphic PTLD; although in practice, a clear separation is not always possible. Therapeutically, reduction in immunosuppression remains a mainstay, and recent data has documented the importance of rituximab +/- combination chemotherapy. Therapy for primary CNS PTLD should be managed according to immunocompetent CNS paradigms. Finally, novel treatment strategies for PTLD have emerged, including adoptive immunotherapy and rational targeted therapeutics (e.g., anti-CD30 based therapy and downstream signaling pathways of latent membrane protein-2A).
232 citations
TL;DR: The universal association of ENKTL-NT with Epstein-Barr virus across all ethnic groups suggests a common pathogenesis and the poor response of this neoplasm to anthracycline-based therapy is consistent across all geographic areas.
Abstract: Extranodal NK/T cell lymphoma, nasal type (ENKTL-NT) is an aggressive extranodal non-Hodgkin lymphoma most commonly occurring in East Asia and Latin America but with increasing incidence in the United States. Data on epidemiology, disease presentation, and outcome for European and North American (“Western”) cases are very limited. We review published landmark clinical studies on ENKTL-NT in the West and report in detail recent data, including our institutional experience. We highlight key observations in its epidemiology, natural history, and trends in clinical management. In the USA, ENKTL-NT is more common among Asian Pacific Islanders (API) and Hispanics compared to non-Hispanic whites. Published studies indicate less heterogeneity in clinical presentation in Western ENKTL-NT compared to Asian patients. While there is variation in age at diagnosis, presence of antecedent lymphoproliferative disorders, and outcomes among racial/ethnic groups, the universal association of ENKTL-NT with EBV and the poor response of this neoplasm to anthracycline-based therapy is consistent across all geographic areas. Data on epidemiology, disease presentation, and clinical outcomes in mature T cell and NK cell (T/NK cell) neoplasms, including ENKTL-NT, in Europe and North America are very limited. As the classification and diagnostic characterization of the currently recognized T/NK cell lymphoma disease entities continue to evolve, gaps and inconsistencies in data reporting across different studies are being recognized. Despite these limitations, several studies from the USA suggest that the incidence of ENKTL-NT is higher in Asian Pacific Islanders (API) and non-white Hispanics and that outcomes may be worse in non-whites. However, the universal association of ENKTL-NT with Epstein-Barr virus (EBV) across all ethnic groups suggests a common pathogenesis. Given the overlap between the entities included in the category of T/NK cell neoplasms, there is a need to further define biological and clinical differences that may affect diagnosis, treatment, and outcome.
136 citations
TL;DR: There is increasing evidence that patients whose disease is controlled by TKIs will have greater impact on their quality of life from comorbidities or drug adverse events than from the disease itself.
Abstract: Most patients with chronic myeloid leukemia have deep and durable responses when treated with BCR-ABL1 tyrosine kinase inhibitors (TKIs). Imatinib (the first approved TKI), nilotinib, and dasatinib are used in newly diagnosed, relapsed or intolerant patients, while bosutinib and ponatinib are used only in relapsed or intolerant patients. Previously the drug of choice was related to the likelihood of response and, to a small extent, patient comorbidities. The long-term toxicities, particularly cardiopulmonary side effects, are now impacting treatment choice, making patient comorbidities of significant concern. About 10 % of patients do not tolerate their initial BCR-ABL1 TKI and an increasing number are developing long-term side effects, particularly with the second generation drugs. Side effects of the five drugs reviewed here highlight the differences between cardiovascular, pulmonary, gastrointestinal, and endocrine toxicities, as well as possible second malignancies. There is increasing evidence that patients whose disease is controlled by TKI's will have greater impact on their quality of life from comorbidities or drug adverse events than from the disease itself. Research into management of long-term toxicities is needed.
108 citations
TL;DR: CAR-T cells are a feasible, effective, and rapidly evolving therapy for patients with relapsed and refractory B cell malignancies.
Abstract: Genetically engineered T cells expressing a chimeric antigen receptor (CAR-T) targeting specific antigens present on acute lymphoblastic leukemia (ALL) blasts have generated promising results in children and adults with relapsed and refractory disease. We review the current evidence for CAR-T cell therapy in ALL, associated toxicities, and efforts to improve durable response to therapy. CD19-directed CAR-T cells have recently been approved by the FDA for use in children and young adults with ALL and in adults with diffuse large B cell lymphoma (DLBCL) in the relapsed/refractory setting. CD22-directed CAR-T cells have shown efficacy against leukemia as well in a recent clinical trial, representing the first alternative CAR target to approach comparable efficacy to CD19 CAR-T cells. Standardization of toxicity grading and management, strategies to combat significant relapse rates after CAR-T therapy, and applicability of CAR-T cells to treat central nervous system (CNS) disease remain challenges in the field and represent priorities for continued research. CAR-T cells are a feasible, effective, and rapidly evolving therapy for patients with relapsed and refractory B cell malignancies.
106 citations
TL;DR: The clinical advances with BTK inhibitor therapy are discussed, as well as its pathophysiological basis, and perspectives for future use of BTK inhibitors are outlined.
Abstract: BTK is a cytoplasmic, non-receptor tyrosine kinase that transmits signals from a variety of cell-surface molecules, including the B-cell receptor (BCR) and tissue homing receptors Genetic BTK deletion causes B-cell immunodeficiency in humans and mice, making this kinase an attractive therapeutic target for B-cell disorders The BTK inhibitor ibrutinib (PCI-32765, brand name: Imbruvica) demonstrated high clinical activity in B-cell malignancies, especially in patients with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and Waldenstrom's macroglobulinemia (WM) Therefore, ibrutinib was granted a ‘breakthrough therapy’ designation for these indications and was recently approved for the treatment of relapsed MCL by the US Food and Drug Administration Other BTK inhibitors in earlier clinical development include CC-292 (AVL-292), and ONO-4059 In CLL and MCL, ibrutinib characteristically induces redistribution of malignant B cells from tissue sites into the peripheral blood, along with rapid resolution of enlarged lymph nodes and a surge in lymphocytosis With continuous ibrutinib therapy, growth- and survival-inhibitory activities of ibrutinib result in the normalization of lymphocyte counts and remissions in a majority of patients This review discusses the clinical advances with BTK inhibitor therapy, as well as its pathophysiological basis, and outlines perspectives for future use of BTK inhibitors
104 citations