Current Hematologic Malignancy Reports最新文献

{"title":"Differential Diagnosis and Workup of Monocytosis: A Systematic Approach to a Common Hematologic Finding.","authors":"Abhishek A Mangaonkar,&nbsp;Aaron J Tande,&nbsp;Delamo I Bekele","doi":"10.1007/s11899-021-00618-4","DOIUrl":"https://doi.org/10.1007/s11899-021-00618-4","url":null,"abstract":"<p><strong>Purpose of review: </strong>Monocytosis is a frequently encountered clinical condition that needs appropriate investigation due to a broad range of differential diagnoses. This review is meant to summarize the latest literature in the diagnostic testing and interpretation and offer a stepwise diagnostic approach for a patient presenting with monocytosis.</p><p><strong>Recent findings: </strong>Basic studies have highlighted the phenotypic and functional heterogeneity in the monocyte compartment. Studies, both translational and clinical, have provided insights into why monocytosis occurs and how to distinguish the different etiologies. Flow cytometry studies have illustrated that monocyte repartitioning can distinguish chronic myelomonocytic leukemia, a prototypical neoplasm with monocytosis from other reactive or neoplastic causes. In summary, we provide an algorithmic approach to the diagnosis of a patient presenting with monocytosis and expect this document to serve as a reference guide for clinicians.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11899-021-00618-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38893514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pediatric Neoplasms Presenting with Monocytosis.","authors":"Jacob R Greenmyer,&nbsp;Mira Kohorst","doi":"10.1007/s11899-021-00611-x","DOIUrl":"https://doi.org/10.1007/s11899-021-00611-x","url":null,"abstract":"<p><strong>Purpose of review: </strong>Juvenile myelomonocytic leukemia (JMML) is a rare but severe pediatric neoplasm with hematopoietic stem cell transplant as its only established curative option. The development of targeted therapeutics for JMML is being guided by an understanding of the pathobiology of this condition. Here, we review JMML with an emphasis on genetics in order to (i) demonstrate the relationship between JMML genotype and clinical phenotype and (ii) explore potential genetic targets of novel JMML therapies.</p><p><strong>Recent findings: </strong>DNA hypermethylation studies have demonstrated consistently that methylation is related to disease severity. Increasing understanding of methylation in JMML may open the door to novel therapies, such as DNA methyltransferase inhibitors. The PI3K/AKT/MTOR, JAK/STAT, and RAF/MEK/ERK pathways are being investigated as therapeutic targets for JMML. Future therapy for JMML will be driven by an increased understanding of pathobiology. Targeted therapeutic approaches hold potential for improving outcomes in patients with JMML.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11899-021-00611-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25403028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pegaspargase in Practice: Minimizing Toxicity, Maximizing Benefit.","authors":"David O Riley,&nbsp;Jenna M Schlefman,&nbsp;Hans Christoph Vitzthum Von Eckstaedt V,&nbsp;Amy L Morris,&nbsp;Michael K Keng,&nbsp;Firas El Chaer","doi":"10.1007/s11899-021-00638-0","DOIUrl":"https://doi.org/10.1007/s11899-021-00638-0","url":null,"abstract":"<p><strong>Purpose of review: </strong>The incorporation of pegaspargase in chemotherapy regimens has significantly improved the prognosis of ALL in adults. However, pegaspargase use poses many challenges due to its unique toxicity profile. Here, we review pegaspargase's most clinically significant toxicities, and provide guidance for their prevention and management in order to avoid unnecessary drug discontinuation and achieve maximum clinical benefit.</p><p><strong>Recent findings: </strong>Clinically significant toxicities of pegaspargase include thrombosis, hypersensitivity and inactivation, hepatotoxicity, pancreatitis, and hypertriglyceridemia. The majority of these toxicities are temporary, nonfatal, and can be managed supportively without permanent pegaspargase discontinuation. Special attention should be paid to inactivation, which can lead to treatment failure, as well as pancreatitis, which necessitates complete cessation of asparaginase therapy. The question of how to best proceed in patients who cannot tolerate pegaspargase remains unanswered, and is an important area of future investigation. Pegaspargase is an essential component of the pediatric-inspired regimens that have improved survival in adult ALL. Although pegaspargase's toxicity profile is unique, it is also highly manageable and should not be a barrier to achieving maximum clinical benefit using this drug.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11899-021-00638-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38973673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Laboratory Evaluation and Pathological Workup of Neoplastic Monocytosis - Chronic Myelomonocytic Leukemia and Beyond.","authors":"Siba El Hussein,&nbsp;Joseph D Khoury,&nbsp;L Jeffrey Medeiros,&nbsp;Sanam Loghavi","doi":"10.1007/s11899-021-00625-5","DOIUrl":"https://doi.org/10.1007/s11899-021-00625-5","url":null,"abstract":"<p><strong>Purpose of review: </strong>Monocytosis is a distinct but non-specific manifestation of various physiologic and pathologic conditions. Among hematopoietic stem cell neoplasms, depending on the criteria used for disease classification, monocytosis may be a consistent and integral component of diseases such as chronic myelomonocytic leukemia or acute myeloid leukemia with monocytic differentiation, or it may represent an inconsistent finding that often provides a clue to the underlying genetic changes driving the neoplasm. The purpose of this review is to provide the readers with a laboratory-based approach to neoplastic monocytosis.</p><p><strong>Recent findings: </strong>In-depth elucidation of the genomic landscape of myeloid neoplasms within the past few years has broadened our understanding of monocytosis and its implications for diagnosis and prognosis. Genetic findings also shed light on potential disease response - or lack thereof - to various therapeutic agents used in the setting of myeloid neoplasms. In this review, we provide our approach to diagnose neoplastic monocytosis in the context of case-based studies while incorporating the most recent literature on this topic.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11899-021-00625-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38947329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progress in the Management of Smoldering Multiple Myeloma.","authors":"Timothy M Schmidt,&nbsp;Natalie S Callander","doi":"10.1007/s11899-021-00623-7","DOIUrl":"https://doi.org/10.1007/s11899-021-00623-7","url":null,"abstract":"<p><strong>Purpose of review: </strong>Smoldering multiple myeloma (SMM) is defined as an asymptomatic clonal proliferation of pre-malignant plasma cells and an increased risk of progression to multiple myeloma (MM) relative to monoclonal gammopathy of undetermined significance. Whether patients with SMM should be treated prior to development of symptomatic disease is fiercely debated and is a highly active area of research.</p><p><strong>Recent findings: </strong>The ECOG E3A06 study demonstrated that early treatment with lenalidomide significantly reduced the risk of progression to MM compared to observation in patients with high risk SMM. The IMWG recently validated a risk stratification model to include cytogenetics and a personalized risk calculator for individual patients. Beyond this, molecular genomic aberrations and immunological phenomena that promote progression from asymptomatic disease to MM have been recently characterized and may help to more precisely identify patients who are most suitable for early intervention. As highly effective and tolerable therapies for plasma cell disorders evolve, the field is approaching a paradigm shift that involves the adoption of intervention for patients with SMM who are at high risk for progression to symptomatic myeloma in order to prevent morbidity and mortality. This review highlights our current understanding of the biology of patients with SMM, clarifies the rationale for early intervention, and summarizes early results of various treatment strategies for patients with high-risk smoldering myeloma.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11899-021-00623-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38977661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Targeted Therapeutics in Acute Myeloid Leukemia: an Embarrassment of Riches.","authors":"Nicole R Grieselhuber,&nbsp;Alice S Mims","doi":"10.1007/s11899-021-00621-9","DOIUrl":"https://doi.org/10.1007/s11899-021-00621-9","url":null,"abstract":"<p><strong>Purpose of review: </strong>Acute myeloid leukemia (AML) is an aggressive malignancy of the bone marrow that has a poor prognosis with traditional cytotoxic chemotherapy, especially in elderly patients. In recent years, small molecule inhibitors targeting AML-associated IDH1, IDH2, and FLT3 mutations have been FDA approved. However, the majority of AML cases do not have a targetable mutation. A variety of novel agents targeting both previously untargetable mutations and general pathways in AML are currently being investigated. Herein, we review selected new targeted therapies currently in early-phase clinical investigation in AML.</p><p><strong>Recent findings: </strong>The DOT1L inhibitor pinometostat in KMT2A-rearranged AML, the menin inhibitors KO-539 and SYNDX-5613 in KMT2Ar and NPM1-mutated AML, and the mutant TP53 inhibitor APR-246 are examples of novel agents targeting specific mutations in AML. In addition, BET inhibitors, polo-like kinase inhibitors, and MDM2 inhibitors are promising new drug classes for AML which do not depend on the presence of a particular mutation. AML remains in incurable disease for many patients but advances in genomics, epigenetics, and drug discovery have led to the development of many potential novel therapeutic agents, many of which are being investigated in ongoing clinical trials. Additional studies will be necessary to determine how best to incorporate these novel agents into routine clinical treatment of AML.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11899-021-00621-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9771277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Approach to Managing Patients with Newly Diagnosed High-Risk Multiple Myeloma.","authors":"Naimisha Marneni,&nbsp;Rajshekhar Chakraborty","doi":"10.1007/s11899-021-00631-7","DOIUrl":"https://doi.org/10.1007/s11899-021-00631-7","url":null,"abstract":"<p><strong>Purpose of review: </strong>With rapid advances in the therapeutic landscape and biological insights in multiple myeloma, it is critical to identify and strategically manage high-risk patients to achieve best outcomes with currently available drugs. The purpose of this review is to summarize the management of high-risk myeloma with a focus on recent advances in the field.</p><p><strong>Recent findings: </strong>The most widely accepted definition of \"high-risk\" is the Revised International Staging System (R-ISS) stage 3 disease, which includes high tumor burden (ISS stage 3) and high-risk FISH cytogenetics or an elevated lactate dehydrogenase level. A major advance in the management of high-risk patients is insight into the importance of achieving and sustaining minimal residual disease (MRD) negativity, which is an influential equalizer for long-term outcomes. Quadruplet pre-transplant induction regimens incorporating an anti-CD38 monoclonal antibody (mAb), proteasome inhibitor (PI: bortezomib or carfilzomib), lenalidomide, and dexamethasone should be strongly considered in high-risk patients given higher odds of getting to MRD negativity with these regimens compared to triplets. In transplant-eligible patients, upfront transplant does lead to a higher rate of sustained MRD negativity and superior PFS compared to delayed transplant. The role of tandem transplant in the context of bortezomib-lenalidomide-dexamethasone (VRD) induction therapy is unclear. Post-transplant maintenance therapy should include lenalidomide in combination with either bortezomib or carfilzomib until progression. For transplant-ineligible patients, VRD or daratumumab-lenalidomide-dexamethasone (DRD) until progressions are both reasonable and choice should be individualized based on patient-related factors. Outcomes of high-risk myeloma patients have improved in the last decade with the use of modern 3-drug induction regimens incorporating a PI and an immunomodulatory drug, with potential for further improvement as we bring anti-CD38 mAb upfront. MRD assessment will play a major role in treatment modification at several key time-points in the future such as pre-transplant, pre-maintenance, and yearly on maintenance therapy.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11899-021-00631-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38890523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MRD Assessment in Multiple Myeloma: Progress and Challenges.","authors":"Luca Bertamini,&nbsp;Mattia D'Agostino,&nbsp;Francesca Gay","doi":"10.1007/s11899-021-00633-5","DOIUrl":"https://doi.org/10.1007/s11899-021-00633-5","url":null,"abstract":"<p><strong>Purpose of review: </strong>Over the last decade, the development of effective treatment approaches for multiple myeloma (MM) has been associated with higher response rates and longer survival. In patients who achieve complete response, several high sensitivity techniques have been studied to assess minimal residual disease (MRD) and detect residual neoplastic cells within the bone marrow (by flow cytometry or molecular biology techniques) or outside the bone marrow (by imaging or circulating disease markers in the peripheral blood). This is of utmost importance, since residual disease can drive clinical relapse. This review focuses on the progress made in the assessment of MRD in MM.</p><p><strong>Recent findings: </strong>The achievement of MRD negativity after therapy is considered prognostically important for MM patients, and data from clinical trials and meta-analyses have confirmed that it is strongly associated with better survival. Along with well-known techniques, such as next-generation sequencing (NGS), next-generation flow (NGF), and positron emission tomography/computed tomography (PET/CT), other methods such as mass spectrometry (MS) and circulating tumor cells are under study. Intensive treatment regimens at diagnosis can lead up to 70% of MRD negativity in MM patients, although the current proportion of curable patients is still unknown. Today, clinicians who treat MM deal with MRD assessment in routine clinical practice. Its appropriate use in therapeutic decision making may be the most fascinating and challenging issue to be addressed over the next few years.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11899-021-00633-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38950172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enteropathy-Associated T cell Lymphoma.","authors":"Zakiah Al Somali,&nbsp;Mehdi Hamadani,&nbsp;Mohamed Kharfan-Dabaja,&nbsp;Ana Sureda,&nbsp;Riad El Fakih,&nbsp;Mahmoud Aljurf","doi":"10.1007/s11899-021-00634-4","DOIUrl":"https://doi.org/10.1007/s11899-021-00634-4","url":null,"abstract":"<p><strong>Purpose of review: </strong>Enteropathy-associated T cell lymphoma (EATL) is a rare subtype of mature T cell lymphoma. The available literature about this rare type T cell lymphoma is relatively limited. This article provides a summary and review of the available literature addressing this entity in terms of risk factors, pathogenesis, diagnostic, and therapeutic options.</p><p><strong>Recent findings: </strong>EATL has two distinct subtypes. Type I EATL, now known as EATL, is closely, but not exclusively linked to celiac disease (CD), and it is primarily a disease of Northern European origin. It accounts for < 5% of peripheral T cell lymphoma (PTCL). Risk factors for EATL include advanced age, male sex, and most importantly, genetic susceptibility in the form of HLA-DQ2 homozygosity. The pathogenesis of EATL is closely related to celiac disease as it shares common pathogenic features with refractory celiac disease. The gold standard of diagnosis is histological diagnosis. EATL carries an aggressive course and a poor prognosis. Treatment of EATL includes surgery, induction chemotherapy, and consolidation in first complete remission and autologous stem cell transplant. The role of targeted and biologic therapies in newly diagnosed EATL patients along with relapsed, refractory cases is evolving and discussed in this review. EATL is an aggressive peripheral T cell lymphoma with poor overall treatment outcome using currently available therapy options. Clinical trials are considered the best approach for treatment of EATL. Early diagnosis and early referral to specialized centers would be the best way to deal with such patients. Development of new prognostic models and early surgical intervention are warranted. Prevention is where all the efforts should be spent, by counseling patients with CD regarding the importance of adherence to gluten-free diet and development of periodic surveillance programs in celiac disease patients for early detection of pre-lymphoma lesions.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11899-021-00634-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38915718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution of Hematology Clinical Trial Adverse Event Reporting to Improve Care Delivery.","authors":"Tamara P Miller,&nbsp;Richard Aplenc","doi":"10.1007/s11899-021-00627-3","DOIUrl":"https://doi.org/10.1007/s11899-021-00627-3","url":null,"abstract":"<p><strong>Purpose of review: </strong>Reporting of adverse events on hematology clinical trials is crucial to understanding the safety of standard treatments and novel agents. However, despite the importance of understanding toxicities, challenges in capturing and reporting accurate adverse event data exist.</p><p><strong>Recent findings: </strong>Currently, adverse events are reported manually on most hematology clinical trials. Especially on phase III trials, the highest grade of each adverse event during a reporting period is typically reported. Despite the effort committed to AE reporting, studies have identified underreporting of adverse events on hematologic malignancy clinical trials, which raises concern about the true understanding of safety of treatment that clinicians have in order to guide patients about what to expect during therapy. In order to address these concerns, recent studies have piloted alternative methods for identification of adverse events. These methods include automated extraction of adverse event data from the electronic health record, implementation of trigger or alert tools into the medical record, and analytic tools to evaluate duration of adverse events rather than only the highest adverse event grade. Adverse event reporting is a crucial component of clinical trials. Novel tools for identifying and reporting adverse events provide opportunities for honing and refining methods of toxicity capture and improving understanding of toxicities patients experience while enrolled on clinical trials.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11899-021-00627-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25535026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}