Current Hematologic Malignancy Reports最新文献

Purpose of review: The treatment of acute lymphoblastic leukemia (ALL) is one of the success stories of pediatric oncology, but challenges and questions remain, including the optimal approach to the treatment of central nervous system (CNS) leukemia. It is unclear why some children with ALL develop CNS leukemia and others do not, and there remains debate regarding optimal regimens for prophylaxis, upfront treatment, and the treatment of CNS relapses. These topics are especially important since both cranial radiation therapy (CRT) and intensive intrathecal therapy carry risks of both short- and long-term adverse effects. In this review, we aim to identify areas of ongoing debate on this topic, review the biology of CNS leukemia, and summarize clinical trial data that address some of these questions.

Recent findings: Both retrospective and meta-analyses have demonstrated that few patients with ALL benefit from CRT as a component of CNS-directed treatment for de novo disease, allowing cooperative groups to greatly limit the number of patients undergoing CRT as part of their initial ALL regimens. More recent efforts are focusing on how best to assay for low levels of CNS disease at the time of diagnosis, as well as the biological drivers that may result in CNS leukemia in certain patients. Progress remains to be made in the identification and treatment of CNS leukemia in pediatric ALL. Advancements have occurred to limit the number of children undergoing CRT, but much has yet to be learned to better understand the biology of and risk factors for CNS leukemia, and novel approaches are required to approach CNS relapse of ALL.

Purpose of review: The treatment landscape for relapsed chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) has changed substantially over the past decade and continues to evolve. Despite the emergence of targeted therapies that are well tolerated and prolong survival, the disease remains incurable and relapse is common particularly in individuals with high-risk features. Herein, we review the key literature about the current options for relapsed disease and explore the emerging role of cellular therapies.

Recent findings: Clinical trials have established the role of Bruton tyrosine kinase inhibitors, selective BCL-2 inhibition, and anti-CD20 monoclonal antibodies as treatment options for CLL/SLL. The role of chimeric antigen receptor T cells has shown promise in individuals with CLL/SLL in early phase clinical trials. Novel therapeutic approaches with targeted therapies have redefined the management of CLL/SLL in both the front-line and relapsed/refractory settings. Optimal management in terms of sequencing or combining therapies, especially in individuals with high-risk features, remains a challenge. The emerging role of cellular therapies has the potential to build upon and further improve the current treatment paradigm.

Hematologic malignancies are most likely to present in the seventh and eighth decades of life. Continued population growth will lead to increasing numbers of older adults with hematologic malignancies. Oncology care for older adults is complex and must account for the effect of aging on disease biology and treatment tolerance. Multidisciplinary oncology care has been utilized in solid tumor oncology for decades, initially driven by the need for multi-modality treatment. In this review, we make the case for multidisciplinary oncogeriatric care for older adults with hematologic malignancies in order to best navigate the intersection of aging and blood cancer.

Purpose of review: This review will focus on recent and emerging treatment paradigms in chronic phase CML. The discussion of each novel treatment or drug combination will include a brief overview of scientific rational and pre-clinical data, followed by recently published or ongoing clinical trial efforts. The review will be divided into three focus areas in CML treatment: new frontline approaches and approaches to deepen remission, second treatment-free remission studies, and the treatment of refractory disease.

Recent findings: The section on new frontline approaches will highlight several strategies of combination therapy. These can be grouped into immunomodulatory approaches with interferons and immune checkpoint inhibitors, targeting of leukemia stem cells with compounds such as venetoclax and pioglitazone, and BCR-ABL1-intrinsic combination therapy with asciminib. The chance at a second treatment-free remission is an important emerging clinical trial concept, and again combination approaches are under investigation. Lastly, in advanced disease, the development of novel tyrosine kinase inhibitors remains a major focus. This review will provide an overview and perspective of treatment strategies on the horizon for chronic phase CML. Despite the already excellent clinical outcomes for most patients, challenges remain with regard to deepening initial responses, prolonging treatment-free remission, and providing efficacious and tolerable options for patients with refractory disease and resistance mutations.

Purpose of review: Since the discovery of imatinib, an oral breakpoint cluster region-Abelson murine leukemia tyrosine kinase inhibitor, chronic myelogenous leukemia transformed from a hematologic malignancy primarily treated with intravenous chemotherapy to a disease almost solely managed with oral agents. While certainly there are benefits to taking a medication at home, this change in treatment modality also came with unique challenges, including patient adherence, medication acquisition and cost, and toxicity management.

Recent findings: Pharmacists are uniquely equipped to assist with educating patients, safe prescribing, and access to medications. Several studies have described the benefits of an integrated oral anticancer medication management program in the ambulatory setting, including improvements in patient adherence, side effect management, patient comprehension, and drug-interaction detection. Pharmacists are also specially trained to assist with medication dose adjustments, relative lab monitoring, and co-pay assistance. Here, we describe the multidisciplinary workflows established to manage oral therapies in chronic myelogenous leukemia patients in a malignant hematology clinic at a large academic medical center. By using the unique talents of the clinic pharmacist, clinic nurse, and specialty retail pharmacy group, patients can be triaged to help ensure the correct skill set is used to optimally care for patients. An acuity-based monitoring structure can improve the ability to reach and safely monitor a large volume of patients.

Purpose of review: Rare malignancies developing from lymphocyte precursor cells, lymphoblastic leukemia (LBL), and acute lymphoblastic lymphoma (ALL) have historically been viewed as different manifestations of the same disease process. This review examines data on their epidemiology, genetics, clinical presentation, and response to treatment while highlighting areas of similarity and divergence between these two clinical entities.

Recent findings: Pediatric-type ALL chemotherapy regimens, compared to both lymphoma-type chemotherapy and adult-type ALL regimens, have led to improved outcomes for children, adolescents, and young adults with ALL. BCR-ABL-targeting tyrosine kinase inhibitors (TKIs) have improved outcomes in Philadelphia chromosome-positive (Ph +) ALL and in rare cases of Ph + LBL. Newer therapies including blinatumomab, inotuzumab, CAR-T therapy, and nelarabine have improved outcomes in selected cases of ALL and have an emerging role in the management of LBL. Better understanding of ALL and LBL biology allows for the development of therapies that target immunophenotypic or genetic features found in subsets of both diseases. Novel therapies are leading to improved outcomes in Ph + and relapsed and refractory disease.

Purpose of review: Social media-based scientific journal clubs provide an opportunity to promote published literature to a broader audience and allow robust multi-disciplinary and inter-professional discussion. Hematopathology Journal Club (#HemepathJC) on Twitter has successfully conducted monthly sessions since November 2019, covering topics related to lymphoma and leukemia.

Recent findings: To enhance connectivity, multitasking, and productivity, we present our experience of leveraging the voice-based platform Clubhouse concurrent with Twitter. The Twitter and Clubhouse partnership for #hemepathJC holds the potential to increase dissemination of scientific knowledge and further promote journal club format discussion.

Purpose of review: Patients with systemic mastocytosis, a dangerous and rare myeloid neoplasm, have long had few therapies available to them and, historically, rarely achieved from significant disease control. However, research and translational developments over the last decade have led to promising new options for disease management. In this review, we briefly outline the history of treatment for systemic mastocytosis and subsequently focus on the clinical development and potential applications of avapritinib (previously known as BLU-285), a potent and selective oral inhibitor of the tyrosine kinase most commonly mutated in this condition.

Recent findings: Phase I data and recent phase II data have demonstrated both safety and efficacy of this agent used as monotherapy, even in patients who have progressed on other targeted therapy. Studies to date have focused on patients with the most aggressive disease, but new trials in indolent mastocytosis are accruing currently. Over the next several years, one may anticipate finalized, peer-reviewed, and formally published data for this agent in both advanced systemic and indolent mastocytosis. Evidence from these early studies will also likely highlight where more research is needed.

Purpose of review: Chronic myeloid leukemia (CML) management in developing countries has improved in the last years, but the availability of therapeutic resources, monitoring, reimbursement, and financial issues may be a challenge and interfere with the best practices and results of CML treatment. This review points out the main challenges in CML management in South America.

Recent findings: In this review, we describe the access to tyrosine kinase inhibitors and monitoring in different countries of South America. We also address the ongoing discontinuation trials, the progress, and limitations of hematopoietic stem cell transplantation in the last years. There are still many challenges for achieving the best outcomes for CML patients in South America. The continuous efforts to provide continuous education, access to tyrosine kinase inhibitors, and monitoring, providing reference centers for CML management and hematopoietic stem cell transplantation may improve patients' outcomes.

Purpose of review: Essential thrombocythemia (ET) and polycythemia vera (PV) are the most common myeloproliferative neoplasms (MPNs). Treatment of ET and PV is based on the risk for subsequent thrombosis. High-risk patients, defined as older than 60, JAK2 V617F-positive patients, or patients with a history of prior thrombosis, merit cytoreduction to control blood counts, whereas a watchful waiting paradigm is utilized in low-risk patients. However, low-risk patients have a host of other specific management issues that arise during their disease course. This review will discuss the most common management issues specific to the care of low-risk patients, including anti-platelet therapy dosing, pregnancy, and indications for early cytoreduction.

Recent findings: Although low-dose aspirin is well established in PV, its indications and dosing regimens are less clear in ET. Recent evidence has supported twice daily low-dose aspirin in ET and observation alone in very low-risk ET patients. Pregnancy is not contraindicated in MPNs, and we recommend aspirin throughout pregnancy with consideration for prophylactic postpartum anticoagulation. High phlebotomy needs, symptom burden, and extreme thrombocytosis are common reasons for initiation of cytoreduction in low-risk patients, although we typically do not start cytoreduction for an isolated high platelet count alone. Recent data has also demonstrated a potential disease-modifying effect of interferons in MPNs, with some experts now advocating the early use of interferon in low-risk patients, although more mature data is needed before practice guidelines change. We evaluate the literature to inform clinical decision-making regarding these controversies, including most recent data that has challenged the "watchful waiting" paradigm. Our discussion provides guidance on common clinical scenarios seen in low-risk ET and PV patients, who face a myriad of complex management decisions in their care.