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Best Practice & Research. Clinical Haematology

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https://www.readbyqxmd.com/read/30466759/why-is-a-3-year-nrm-following-allogeneic-transplantation-still-stuck-at-approximately-20
#1
REVIEW
John Barrett
Whether and when to recommend an allogeneic stem cell transplant (SCT) for a patient with leukemia is a treatment decision that rests on determining whether the transplant or non-transplant option carries the greatest probability of 3-5-year survival. While SCT confers a greater possibility of leukemia cure, the decision to transplant has to be made in the light of the high chance of treatment-related mortality (TRM) that follows the allograft. Here we identify that current estimates of a 20% 3-year TRM hold largely true for a variety of leukemias, diverse types of conditioning regimen, and varied donor-recipient compatibility across a wide age-range...
December 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30466758/can-haploidentical-transplantation-meet-all-patients-needs
#2
REVIEW
Daniel Weisdorf
Allotransplantation in the absence of an HLA-matched sibling donor can offer numerous donor options including unrelated donor and umbilical cord blood grafting. Recently, haploidentical transplantation has exploded in popularity and worldwide use following the application of post-transplant cyclophosphamide (PTCy) for GVHD prophylaxis. Various approaches, disease states, conditioning intensities and supportive care advances have improved all these choices without demonstrable superiority of one approach versus the others...
December 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30466757/hematopoietic-cell-transplantation-as-treatment-of-patients-with-acute-myeloid-leukemia-with-measurable-residual-disease-after-consolidation-therapy
#3
REVIEW
Frederick R Appelbaum
The persistence of measurable residual disease (MRD) following induction chemotherapy is the single most powerful prognostic factor available to clinicians treating patients with acute myeloid leukemia (AML). How to use this information to guide subsequent therapy is complex, and influenced by the category of AML being treated, the assays used to measure MRD, MRD levels and kinetics, and the spectrum of therapies available to the patient. In this literature-based review, each of these issues will be discussed, with a particular emphasis on the role of hematopoietic cell transplantation in the treatment of MRD-positive patients...
December 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30466756/what-flt3-inhibitor-holds-the-greatest-promise
#4
REVIEW
Richard M Stone
Determining which FLT3 inhibitor holds the greatest promise is a difficult task, as the drugs vary according to potency, specificity, protein-binding, drug interactions, and side effect profile. The best choice depends on when in the course of the disease the inhibitor will be used. Moreover, as the results of ongoing trials become available, newer agents could supplant former 'best' drugs. This paper reviews FLT3 inhibitors in combination with chemotherapy early in the disease in FLT3 mutant patients, as single agents or in combination in advanced disease, or in the post-transplant setting to provide separate answers to the main question...
December 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30466755/is-it-time-to-routinely-incorporate-mrd-into-practice
#5
REVIEW
Farhad Ravandi
Interest in detecting minimal/measurable residual disease (MRD) in acute myeloid leukemia (AML) has been increasing, but numerous issues need to be addressed if MRD assessment is to be routinely incorporated into practice. Assays, their reliability, standardization, and availability all must be considered, and a strategy developed to eradicate residual leukemia. This paper reviews some issues surrounding the routine incorporation of MRD assessment into practice.
December 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30466754/which-novel-agents-for-acute-myeloid-leukemia-are-likely-to-change-practice
#6
REVIEW
Daniel A Pollyea
There has been little progress in drug development in acute myeloid leukemia (AML) in the recent past. This recently changed with the approval of several therapies for patients with this disease and prompts one to consider which therapies may change practice for patients with AML. To change practice, a therapy must be adopted as a standard of care intervention based on its efficacy and safety profile and must endure as the accepted treatment for a particular indication for a significant period of time. Here I attempt to determine which therapies, approved or in development, may change practice in the field of AML...
December 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30466753/is-the-overall-survival-for-older-adults-with-aml-finally-improving
#7
REVIEW
Jeffrey E Lancet
Older adults with acute myeloid leukemia (AML) traditionally have very poor survival outcomes. Those who receive only supportive care have worse overall survival than those who undergo treatment, regardless of treatment type, and improvements in overall survival in the last several decades are largely attributable to the increasing decision to treat rather than offer only supportive care. However, there are a few newer agents that appear promising; these include CPX-351 (a liposomal product with cytarabine and daunorubicin), glasdegib (a selective Hedgehog signaling pathway inhibitor), and venetoclax (potent small molecule inhibitor of BCL2)...
December 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30466752/is-there-a-standard-of-care-for-relapsed-aml
#8
REVIEW
Bruno C Medeiros
Despite advances in treatment for acute myeloid leukemia (AML), the prognosis for patients with relapsed disease is extremely poor. The median overall survival for patients with relapsed AML ranges from 4-6 months and long-term survival from the time of relapse ranges from 5%-20%. Much of the difficulty in establishing a standard of care for relapsed AML is that the disease is clinically and genomically diverse. Nevertheless, significant progress has been made over the past 12 months with the approval of several agents, and the expectation is that additional therapies will be available soon...
December 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30466751/patterns-of-mutations-in-tp53-mutated-aml
#9
REVIEW
John S Welch
TP53 mutated acute myeloid leukemia (AML) responds poorly to chemotherapy and has a short overall survival rate with a median of 5-9 months. Poor outcomes in TP53 mutated AML following chemotherapy have been observed and treatment options remain limited, although the presence of TP53 mutations alone should not be a barrier to therapy. Decitabine is emerging as an alternative treatment option for patients with TP53 mutated AML, although the agent has not been associated with deep molecular remissions and requires additional consolidation...
December 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30466750/identifying-patients-with-genetic-predisposition-to-acute-myeloid-leukemia
#10
REVIEW
Ellyn Obrochta, Lucy A Godley
Germline syndromes in myeloid leukemias are being discovered increasingly in patients, and their identification is essential for proper medical management to yield positive health outcomes for patients and their families. There needs to be a greater appreciation of germline predisposition driving the development of hematologic malignancies within the field of myeloid malignancies. Characterization of the influence of germline mutations on the development of myeloid malignancies is ongoing by utilization of next generation sequencing data and prognostic panels...
December 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30466749/should-immunologic-strategies-be-incorporated-into-frontline-all-therapy
#11
REVIEW
Cecilie Utke Rank, Wendy Stock
Survival rates in adult patients with acute lymphoblastic leukemia (ALL) have markedly improved during the past decade. The one-size-fits-all-ages approach has been replaced with adaptation of pediatric-inspired treatment protocols for younger adults. Yet different treatment strategies for older patients are needed due to chemotherapy-related toxicities. A new era of immunotherapy has arrived, offering opportunities for targeted treatments for ALL subtypes. While CD20 targeting with rituximab has been demonstrated to improve survival when combined with chemotherapy, it has little activity as a single agent in ALL...
December 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30466748/can-one-target-t-cell-all
#12
REVIEW
Adolfo Ferrando
Progress in our understanding of the central genes, pathways, and mechanisms in the pathobiology of T-cell acute lymphoblastic leukemia (T-ALL) has identified key drivers of the disease, opening new opportunities for therapy. Drugs targeting highly prevalent genetic alterations in NOTCH1 and CDKN2A are being explored, and multiple other targets with readily available therapeutic agents, and immunotherapies are being investigated. The molecular basis of T-ALL is reviewed here and potential targets and therapeutic targets discussed...
December 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30466747/allogeneic-transplantation-for-patients-with-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-is-it-imperative-in-the-tyrosine-kinase-inhibitor-era
#13
REVIEW
Mark R Litzow
Before the advent of tyrosine kinase inhibitors (TKIs), Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) was associated with dismal survival without allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recent evidence has demonstrated that the combination of TKI and chemotherapy can result in a high rate of complete remission, thereby enabling more patients to proceed to allo-HSCT. However, with more studies reporting non-inferior outcomes with TKI and chemotherapy combination without allo-HSCT, the need for allo-HSCT in Ph+ ALL has become less certain...
December 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30466746/why-and-how-to-treat-ph-like-all
#14
REVIEW
Kathryn G Roberts
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL), or BCR-ABL1-like ALL, is a high-risk subtype of B-cell precursor ALL characterized by a gene expression profile similar to Ph-positive ALL, a high frequency of IKZF1 alterations, and poor outcome. The prevalence of Ph-like ALL is common among all ages, ranging from 10% to 15% in children to over 25% in young adults. Patients with Ph-like ALL harbor a diverse range of genetic alterations that activate cytokine receptor and kinase signaling and can be targeted with tyrosine kinase inhibitors...
December 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30466745/the-role-of-hypomethylating-agents-prior-to-hematopoietic-cell-transplantation-in-myelodysplastic-syndromes
#15
REVIEW
Mikkael A Sekeres
Therapies for myelodysplastic syndromes (MDS) are chosen depending on whether a patient has lower- or higher-risk disease. Hypomethylating agents are recommended as up-front therapy for all higher-risk patients, and lower-risk patients with multiple cytopenias. This article reviews the rationale for hypomethylating agents, their use or intensive chemotherapy pre-transplant, and data supporting pre-transplant MDS treatment.
December 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30466744/what-biologic-factors-predict-for-transformation-to-aml
#16
REVIEW
Rafael Bejar
Transformation of myelodysplastic syndromes (MDS) into secondary acute myeloid leukemia (sAML) is defined by an arbitrary boundary of ≥20% bone marrow blasts but does not necessarily reflect a defined biological transition. The more obvious distinction lies between MDS patients that have an isolated bone marrow failure phenotype and those with excess blasts. Subtyping of MDS might be more accurately stratified into clonal cytopenias and oligoblastic leukemias, using the degree of dysplasia and blast percentage as risk features, respectively, rather than as diagnostic criteria...
December 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30466743/progress-and-predictions-aml-in-2018
#17
REVIEW
Jacob M Rowe
The FLT3 inhibitor midostaurin, the antibody-drug conjugate gemtuzumab ozogamicin, CPX-351 (liposomal daunorubicin and cytarabine), and the IDH2 inhibitor enasidenib are among the novel agents approved for use in the clinic this past year. This year, 2018, already has seen the regulatory approval of the BCL2 inhibitor venetoclax in the form of breakthrough designation and the IDH1 inhibitor ivosidenib received full FDA approval. Much remains to be learned about how best to use these drugs to improve patient outcomes and how best to employ and interpret next-generation sequencing to determine measurable residual disease (MRD) levels that can more accurately predict risk of relapse...
December 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30213403/integrating-novel-systemic-therapies-for-the-treatment-of-mycosis-fungoides-and-s%C3%A3-zary-syndrome
#18
REVIEW
H Miles Prince, Christiane Querfeld
Novel systemic therapies are generally prescribed to patients with advanced-stage disease or those with early-stage disease refractory to skin-directed therapies. In general, systemic chemotherapy should be reserved for patients who fail to respond to biological agents. Such biological agents include interferon alfa, bexarotene, histone deacetylase inhibitors (vorinostat, romidepsin), brentuximab vedotin and mogamulizumab. Extracorporeal photopheresis is particularly effective for patients with Sézary Syndrome...
September 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30213402/extranodal-nk-t-cell-lymphoma-updates-in-biology-and-management-strategies
#19
REVIEW
Motoko Yamaguchi, Masahiko Oguchi, Ritsuro Suzuki
Extranodal NK/T-cell lymphoma, nasal type (ENKL), is a rare lymphoma subtype of peripheral T/NK-cell lymphoma that is very common in East Asia and Latin America. Two-thirds of patients have localized disease in the nasal cavity or adjacent sites. Large retrospective studies have revealed the clinicopathologic features of ENKL patients, identified risk factors for short survival time, and developed prognostic models. Next-generation sequencing studies have provided a comprehensive list of recurrent mutations in ENKL...
September 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/30213401/peripheral-t-cell-lymphoma-are-we-making-progress
#20
REVIEW
Niloufer Khan, Neval Ozkaya, Alison Moskowitz, Ahmet Dogan, Steven Horwitz
Peripheral T cell lymphoma (PTCL) is a rare subtype of non-Hodgkin lymphoma. PTCLs are heterogeneous in terms of biology, but generally have more aggressive features and poorer outcomes than aggressive B-cell lymphomas when treated with combination chemotherapy. While the best long-term results are still seen with intensive chemotherapeutic approaches, significant progress has been made with molecular profiling identifying genetic drivers of PTCL that could serve as therapeutic targets. Tailoring therapy to different subtypes of PTCL may lead to more individualized approaches with the hope of improved outcomes...
September 2018: Best Practice & Research. Clinical Haematology
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