T cell large granular lymphocyte leukemia and chronic NK lymphocytosis
Publication date: Available online 22 June 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Gregorio Barilà, Giulia Calabretto, Antonella Teramo, Cristina Vicenzetto, Vanessa Rebecca Gasparini, Gianpietro Semenzato, Renato ZambelloAbstractLarge Granular Lymphocyte Leukemia (LGLL) is a rare chronic lymphoproliferative disorder characterized by the clonal expansion of Large Granular Lymphocytes (LGLs). Among LGLL, the 2016 WHO classification recognizes two different entities, i.e. T-LGLL and the provisional entity Chronic Lymphoproliferative disorder of NK cells (CLPD-NK). In both subtypes neutr...
Source: Best Practice and Research Clinical Haematology - June 25, 2019 Category: Hematology Source Type: research

Index
Publication date: June 2019Source: Best Practice & Research Clinical Haematology, Volume 32, Issue 2Author(s): (Source: Best Practice and Research Clinical Haematology)
Source: Best Practice and Research Clinical Haematology - June 14, 2019 Category: Hematology Source Type: research

Editorial Board / Aims & Scope
Publication date: June 2019Source: Best Practice & Research Clinical Haematology, Volume 32, Issue 2Author(s): (Source: Best Practice and Research Clinical Haematology)
Source: Best Practice and Research Clinical Haematology - June 14, 2019 Category: Hematology Source Type: research

NK/T-cell lymphomas
Publication date: Available online 12 June 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Eric Tse, Yok-Lam KwongAbstractNK/T-cell lymphomas are extranodal EBV-related malignancies, mostly of NK-cell and occasionally of T-cell lineage. They are divided into nasal, non-nasal, and disseminated subtypes. Nasal NK/T-cell lymphomas involve the nose, nasopharynx and the upper aerodigestive tract. Non-nasal NK/T-cell lymphomas involve the skin, gastrointestinal tract, testis and other sites. Disseminated NK/T-cell lymphoma involves multiple organs, and may present with a leukemic phase. Initial evaluation...
Source: Best Practice and Research Clinical Haematology - June 13, 2019 Category: Hematology Source Type: research

Monoclonal B-cell lymphocytosis
Publication date: Available online 7 June 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Elsa Maitre, Xavier TroussardAbstractFlow cytometry diagnostic practices can detect very low levels of clonal B cells in the peripheral blood. In the absence of clinical symptoms, cytopenia or organomegaly, the small clones may correspond to monoclonal B-cell leukemia (MBL) diagnosis. Most MBLs harbor a chronic lymphocytic leukemia (CLL) phenotype (e.g., CD5+, CD23+) and are referred to as CLL-type MBL. The two other types are atypical CLL-type MBL and non-CLL-type MBL. In addition to the phenotypical classific...
Source: Best Practice and Research Clinical Haematology - June 8, 2019 Category: Hematology Source Type: research

B and T cell Prolymphocytic leukaemia
Publication date: Available online 6 June 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): M. Cross, C. DeardenAbstractProlymphocytic leukaemias B-PLL and T-PLL are rare disorders, typically with an aggressive clinical course and poor prognosis. Combining morphology, immunophenotyping, cytogenetic and molecular diagnostics reliably separates B-PLL and T-PLL from one another and other disorders. In T-PLL discovery of frequent mutations in the JAK-STAT pathway have increased understanding of disease pathogenesis. Alemtuzumab (anti-CD52) produces excellent response rates but long-term remissions are onl...
Source: Best Practice and Research Clinical Haematology - June 6, 2019 Category: Hematology Source Type: research

Genomics of LGL Leukemia and select other rare leukemia/lymphomas
We examined the linkage between these mutations and autoimmune symptoms and disorders, in cases of obvious and suspected LGL leukemia. We then summarized and compared mutations in a set of other rare leukemias that also have JAK/STAT signaling pathway activation brought about by genomic changes. These include T-cell acute lymphoblastic leukemia (T-ALL), T-cell prolymphocytic leukemia (T-PLL), cutaneous T-cell lymphoma (CTCL), select peripheral T-cell lymphoma (PTCL), and adult T-cell leukemia/lymphoma (ATLL). Though STAT3 activation is common in these leukemias, the way in which it is achieved, such as the activating cytok...
Source: Best Practice and Research Clinical Haematology - June 6, 2019 Category: Hematology Source Type: research

Leukaemic variants of cutaneous t-cell lymphoma: Erythrodermic mycosis fungoides and Sézary syndrome
Publication date: Available online 6 June 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Xochiquetzal U. Martinez, Cosimo Di Raimondo, Farah R. Abdulla, Jasmine Zain, Steven T. Rosen, Christiane QuerfeldAbstractMycosis fungoides (MF) and Sézary syndrome (SS) are the most common types of cutaneous lymphoma, accounting for approximately 60% of cutaneous T-cell lymphomas. Diagnosis requires correlation of clinical, histologic, and molecular features. A multitude of factors have been linked to the aetiopathogenesis, however, none have been definitively proven. Erythrodermic MF (E-MF) and SS shar...
Source: Best Practice and Research Clinical Haematology - June 6, 2019 Category: Hematology Source Type: research

AML: The Future is Now or was it Yesterday?
Publication date: Available online 25 May 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Naval Daver, Eytan Stein (Source: Best Practice and Research Clinical Haematology)
Source: Best Practice and Research Clinical Haematology - May 26, 2019 Category: Hematology Source Type: research

Venetoclax-based Therapies for Acute Myeloid Leukemia
Publication date: Available online 24 May 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Veronica A. Guerra, Courtney DiNardo, Marina KonoplevaAbstractThe prognosis of adult acute myeloid leukemia (AML) remains poor, with the long-term survival rate less than 50%. However, the current paradigms of treatment are changing through a better understanding of the disease genetics and pathophysiology. Since 2017, eight new drugs have been approved by the U.S. Food and Drug Administration for the treatment of AML, including the FLT3 inhibitors midostaurin and gilteritinib, the IDH inhibitors ivosidenib and...
Source: Best Practice and Research Clinical Haematology - May 25, 2019 Category: Hematology Source Type: research

Clonal Hematopoiesis and Risk of Acute Myeloid Leukemia
Publication date: Available online 24 May 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Pinkal Desai, Duane Hassane, Gail J. RobozAbstractAcute Myeloid Leukemia, the most common form of acute leukemia in adults, is an aggressive hematopoietic stem cell malignancy that is associated with significant morbidity and mortality. Though AML generally presents de novo, risk factors include exposure to chemotherapy and/or radiation, as well as both familial and acquired bone marrow failure syndromes. Clonal Hematopoiesis (CH) refers to an expansion of blood or marrow cells resulting from somatic mutations ...
Source: Best Practice and Research Clinical Haematology - May 25, 2019 Category: Hematology Source Type: research

Daunorubicin-Cytarabine Liposome (CPX-351) in the Management of Newly Diagnosed Secondary AML: A New Twist on an Old Cocktail
Publication date: Available online 13 May 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Joseph E. Maakaron, Alice S. MimsAbstractInitial therapy for acute myeloid leukemia (AML) remained stagnant for approximately four decades despite advances in improved understanding of pathogenesis and prognostication of the disease. The cornerstone of AML treatment has historically included three days of an anthracycline (daunorubicin or idarubicin) combined with continuous infusion of cytarabine for 7 days, the “7 + 3” regimen. Several attempts have been made to improve on this regimen by dose-int...
Source: Best Practice and Research Clinical Haematology - May 14, 2019 Category: Hematology Source Type: research

Incorporating FLT3 inhibitors in the frontline treatment of FLT3 mutant acute myeloid leukemia
Publication date: Available online 12 May 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Eunice S. WangAbstractFLT3 mutations occur in up to a third of newly diagnosed patients with acute myeloid leukemia (AML) and confer poor prognosis. Clinical development of FLT3 tyrosine kinase inhibitors for AML initially involved broad-spectrum inhibitors (midostaurin, sorafenib) targeting multiple kinases. Addition of midostaurin to upfront intensive chemotherapy for younger patients with FLT3 mutant AML significantly improved overall survival and validated FLT3 as a therapeutic target. Other regimens such a...
Source: Best Practice and Research Clinical Haematology - May 14, 2019 Category: Hematology Source Type: research

Can we incorporate MRD assessment into clinical practice in AML?
Publication date: Available online 10 May 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Gert Ossenkoppele, Gerrit Jan Schuurhuis, Arjan van de Loosdrecht, Jacqueline CloosAbstractMeasurable residual disease (MRD) can be assessed either by flow cytometry or molecular techniques. It has been proven to be highly prognostic in quite a number of prospective clinical studies. The recently published ELN MRD recommendations aim harmonize the approaches to MRD assessment in order to improve its overall quality. The predictive value leading to the usage as a surrogate endpoint for survival which would be in...
Source: Best Practice and Research Clinical Haematology - May 11, 2019 Category: Hematology Source Type: research

Current Status and New Treatment Approaches in TP53 Mutated AML
Publication date: Available online 11 May 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Anthony M. Hunter, David A. SallmanAbstractMutations in the essential tumor suppressor gene, TP53, are observed in only 5-10% of acute myeloid leukemia (AML) cases, but are highly associated with therapy-related AML and cases with complex karyotype. The mutational status of TP53 is a critical prognostic indicator, with dismal outcomes consistently observed across studies. Response rates to traditional cytotoxic chemotherapy are poor and long-term survival after allogeneic hematopoietic stem cell transplant is r...
Source: Best Practice and Research Clinical Haematology - May 11, 2019 Category: Hematology Source Type: research

Novel Monoclonal Antibody-based Therapies for Acute Myeloid Leukemia
Publication date: Available online 9 May 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Linde M. Morsink, Roland B. WalterABSTRACTThere has been long-standing interest in using monoclonal antibodies to improve outcomes of people with acute myeloid leukemia (AML). While several candidate therapeutics have failed at various stages of clinical testing, improved survival of some patients receiving the CD33 antibody-drug conjugate gemtuzumab ozogamicin has provided first evidence that monoclonal antibodies have a role in the armamentarium against AML. Over the last several years, work to improve the suc...
Source: Best Practice and Research Clinical Haematology - May 10, 2019 Category: Hematology Source Type: research

Hereditary Myeloid Malignancies
Publication date: Available online 3 May 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Hind Rafei, Courtney D. DiNardoAbstractMyelodysplastic syndromes and acute myeloid leukemia are sporadic for the majority of cases affecting the elderly population. Inherited cases, however, do occur. Genetic predispositions to myeloid malignancies can be classified into three categories: familial cancer syndromes associated with increased risk of various malignancies including myelodysplasia and acute myeloid leukemia such as Li-Fraumeni syndrome and constitutional mismatch repair deficiency (CMMRD); germline m...
Source: Best Practice and Research Clinical Haematology - May 5, 2019 Category: Hematology Source Type: research

Editorial Board / Aims & Scope
Publication date: March 2019Source: Best Practice & Research Clinical Haematology, Volume 32, Issue 1Author(s): (Source: Best Practice and Research Clinical Haematology)
Source: Best Practice and Research Clinical Haematology - March 28, 2019 Category: Hematology Source Type: research

Index
Publication date: March 2019Source: Best Practice & Research Clinical Haematology, Volume 32, Issue 1Author(s): (Source: Best Practice and Research Clinical Haematology)
Source: Best Practice and Research Clinical Haematology - March 28, 2019 Category: Hematology Source Type: research

Clinicopathological aspects of therapy-related acute myeloid leukemia and myelodysplastic syndrome
Publication date: Available online 27 February 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Chong Chyn Chua, Shaun Fleming, Andrew H. WeiABSTRACTTherapy-related myeloid neoplasm (t-MN) is a rare but devastating consequence of chemotherapy and/or radiotherapy used for the treatment of solid cancers and various hematologic malignancies. Our current understanding of the etiology is that hematopoietic clones that are contemporaneous with the primary cancer and resistant to the cytotoxic exposure have the potential to undergo selective expansion and transformation to t-MN. Consequently, a large propor...
Source: Best Practice and Research Clinical Haematology - February 27, 2019 Category: Hematology Source Type: research

Myeloid Malignancies after treatment for Solid Tumours
Publication date: Available online 26 February 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Guru Subramanian Guru Murthy, Sameem AbedinAbstractThe cure rate for several solid tumour malignancies including breast cancers, head and neck cancers, bone cancers, and sarcoma has improved remarkably with the advent of neoadjuvant and adjuvant therapies. Unfortunately, exposure to chemotherapy or radiation as a part of these treatments exposes patients to the risk of subsequent myeloid malignancies. Therapy related myeloid malignancies have certain characteristic findings. They typically arise within 10 ...
Source: Best Practice and Research Clinical Haematology - February 26, 2019 Category: Hematology Source Type: research

Can Allogeneic Hematopoietic Cell Transplant Cure Therapy-related Acute Leukemia?
Publication date: Available online 26 February 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Yazan F. Madanat, Aaron T. GerdsAbstractTherapy-related myeloid neoplasms (t-MN) include both therapy-related myelodysplastic syndromes as well as therapy-related acute myeloid leukemia. These two entities were grouped together in the World Health Organization classification of AML due to having similarly poor outcomes and disease biology. Exposure to prior radiation therapy or chemotherapy for other malignant or benign conditions, namely autoimmune diseases or solid organ transplants, constitutes the prin...
Source: Best Practice and Research Clinical Haematology - February 26, 2019 Category: Hematology Source Type: research

Choosing Induction Chemotherapy in Therapy-Related Acute Myeloid Leukemia
Publication date: Available online 26 February 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Lauren K. Shea, Geoffrey L. UyAbstractPatients with AML that develops after cytotoxic therapy (tAML) have overall inferior outcomes relative to de novo AML due to both patient-related factors and the intrinsic biology of the disease. Treatment of patients with tAML is challenging. The key initial clinical decision is whether a patient is a candidate for or likely to benefit from intensive induction chemotherapy, a determination which we argue should not be predicated on chronologic age alone. For those det...
Source: Best Practice and Research Clinical Haematology - February 26, 2019 Category: Hematology Source Type: research

Preface
Publication date: Available online 23 February 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Dr Laura C. Michaelis (Source: Best Practice and Research Clinical Haematology)
Source: Best Practice and Research Clinical Haematology - February 25, 2019 Category: Hematology Source Type: research

TP53 and Therapy-related Myeloid Neoplasms
Publication date: Available online 19 February 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Jae Chung, David A. Sallman, Eric PadronAbstractTherapy-related myeloid neoplasms (t-MNs) are the most serious late complications in patients treated with traditional cytotoxic chemotherapy and/or radiation. T-MNs are aggressive and chemorefractory hematologic malignancies, with a median survival of less than 6 months. TP53 mutations are highly enriched in t-MN patients, though the mechanism for this selective enrichment has only come to light over the past several years. In this review, we discuss the his...
Source: Best Practice and Research Clinical Haematology - February 19, 2019 Category: Hematology Source Type: research

Therapy-Related Myeloid Neoplasms In Lymphoma Survivors: Reducing Risks
Publication date: Available online 16 February 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Taha Al-Juhaishi, Arushi Khurana, Danielle ShaferAbstract:Treatment for Hodgkin (HL) and non-Hodgkin’s lymphoma (NHL) has changed dramatically in the last fifty years. While there are increasing numbers of long-term survivors, there has been increasing recognition of the long-term toxicities of treatments, particularly therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML). The survival for t-MDS/AML is extremely poor. Multiple heterogeneous retrospective studies have reporte...
Source: Best Practice and Research Clinical Haematology - February 17, 2019 Category: Hematology Source Type: research

Clonal Hematopoiesis and therapy related MDS/AML
Publication date: Available online 15 February 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Pinkal Desai, Gail J. RobozAbstractClonal Hematopoiesis is defined as the presence of mutations in peripheral blood in the absence of myeloid malignancies and is thought to occur as a normal part of ageing due to the fitness advantage conferred by these mutations in an ageing hematopoietic compartment. Therapy related myeloid neoplasms are malignancies that occur after exposure to chemotherapy/radiation and are associated with poor survival. Clonal hematopoiesis mutations represent a pre malignant state th...
Source: Best Practice and Research Clinical Haematology - February 15, 2019 Category: Hematology Source Type: research

Germline polymorphisms and the risk of therapy-related myeloid neoplasms
Publication date: Available online 11 February 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Koichi TakahashiAbstractTherapy-related myeloid neoplasms (t-MNs) are one of the lethal complications from cytotoxic chemotherapy/radiation therapy. There is substantial variability in the risk of developing t-MNs among individuals who receive the same level of exposures and it has been widely suspected that germline polymorphisms may influence the risk and account for the variability. As the number of cancer survivors increases, effectively identifying an individual with a high risk of developing t-MNs is...
Source: Best Practice and Research Clinical Haematology - February 12, 2019 Category: Hematology Source Type: research

Therapy-related Myeloid Neoplasms after Treatment for Plasma-cell Disorders
Publication date: Available online 8 February 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Alfred Chung, Michaela LiedtkeAbstractTherapy-related myeloid neoplasms (t-MN), including therapy-related acute myeloid leukaemia and myelodysplastic syndrome, are second primary malignancies (SPM) that are of growing importance as patients with plasma cell disorders (PCD) such as multiple myeloma (MM) are living longer with more effective therapies. Both patient-specific and treatment-specific factors likely impact the risk of t-MN development after diagnosis and treatment of PCD. Alkylating chemotherapy, ...
Source: Best Practice and Research Clinical Haematology - February 9, 2019 Category: Hematology Source Type: research

Myeloid disorders after autoimmune disease
Publication date: Available online 7 February 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Prajwal Boddu, Amer M. ZeidanABSTRACTAutoimmune diseases (ADs) are associated with an increased risk not only of lymphoproliferative disorders but also of myeloid malignancies. The excess risk of myelodysplastic syndromes and/or acute myeloid leukemia is observed across several AD types, including systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disorders, multiple sclerosis, among others. The risk of developing myeloid neoplasms (MNs) is dependent on several variables, including the s...
Source: Best Practice and Research Clinical Haematology - February 8, 2019 Category: Hematology Source Type: research

Therapy-associated leukemic Transformation in Myeloproliferative Neoplasms – What do we know?
Publication date: Available online 8 February 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Danielle Cuthbert, Brady Lee SteinAbstractMyeloproliferative Neoplasms (MPNs) are a group of progressive diseases that share a common pathogenesis, clinical and laboratory features, as well as a spontaneous risk of secondary AML. Certain MPN therapies have been associated with an increased risk of leukemic conversion, with robust data highlighting the highest rates with 32P, chlorambucil, and pipobroman. Herein, we review risk factors for leukemic transformation, including therapy-related MPN-BP, with a foc...
Source: Best Practice and Research Clinical Haematology - February 8, 2019 Category: Hematology Source Type: research

Stem Cell Damage after Chemotherapy- Can We Do Better?
Publication date: Available online 6 February 2019Source: Best Practice & Research Clinical HaematologyAuthor(s): Joy Tang, Nan Zhu, Sridhar Rao, Karen-Sue CarlsonABSTRACTTherapy-related myeloid neoplasms are unintended and unwanted complications of cytotoxic chemotherapy and radiation. Unlike other environmental toxin-induced malignancies, exposure to the inciting agent is required to eradicate a primary and life-threatening cancer. In this review, we will focus on the biochemical mechanisms that lead to therapy-induced myeloid malignancy. This includes discussion of known mechanisms by which cytotoxic chemotherapy an...
Source: Best Practice and Research Clinical Haematology - February 6, 2019 Category: Hematology Source Type: research

Editorial Board / Aims & Scope
Publication date: December 2018Source: Best Practice & Research Clinical Haematology, Volume 31, Issue 4Author(s): (Source: Best Practice and Research Clinical Haematology)
Source: Best Practice and Research Clinical Haematology - November 21, 2018 Category: Hematology Source Type: research

What biologic factors predict for transformation to AML?
Publication date: Available online 23 October 2018Source: Best Practice & Research Clinical HaematologyAuthor(s): Rafael BejarTransformation 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...
Source: Best Practice and Research Clinical Haematology - October 24, 2018 Category: Hematology Source Type: research

Allogeneic transplantation for patients with Philadelphia chromosome positive acute lymphoblastic leukemia: Is it imperative in the tyrosine kinase inhibitor era?
Publication date: Available online 20 September 2018Source: Best Practice & Research Clinical HaematologyAuthor(s): Mark R. LitzowAbstractBefore 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 a...
Source: Best Practice and Research Clinical Haematology - October 17, 2018 Category: Hematology Source Type: research

Can one target T-cell ALL?
Publication date: Available online 17 October 2018Source: Best Practice & Research Clinical HaematologyAuthor(s): Adolfo FerrandoProgress 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 tar...
Source: Best Practice and Research Clinical Haematology - October 17, 2018 Category: Hematology Source Type: research

Can haploidentical transplantation meet all patients' needs?
Publication date: Available online 21 September 2018Source: Best Practice & Research Clinical HaematologyAuthor(s): Daniel WeisdorfAbstractAllotransplantation 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 superi...
Source: Best Practice and Research Clinical Haematology - October 16, 2018 Category: Hematology Source Type: research

Should immunologic strategies be incorporated into frontline ALL therapy?
Publication date: Available online 25 September 2018Source: Best Practice & Research Clinical HaematologyAuthor(s): Cecilie Utke Rank, Wendy StockAbstractSurvival 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...
Source: Best Practice and Research Clinical Haematology - October 5, 2018 Category: Hematology Source Type: research

Identifying patients with genetic predisposition to acute myeloid leukemia
Publication date: Available online 25 September 2018Source: Best Practice & Research Clinical HaematologyAuthor(s): Ellyn Obrochta, Lucy A. GodleyAbstractGermline 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 ma...
Source: Best Practice and Research Clinical Haematology - October 5, 2018 Category: Hematology Source Type: research

Is it time to routinely incorporate MRD into practice?
Publication date: Available online 21 September 2018Source: Best Practice & Research Clinical HaematologyAuthor(s): Farhad RavandiInterest 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. (Source: Best Practice and Re...
Source: Best Practice and Research Clinical Haematology - September 22, 2018 Category: Hematology Source Type: research

Why is a 3-year NRM following allogeneic transplantation still stuck at approximately 20%?
Publication date: Available online 21 September 2018Source: Best Practice & Research Clinical HaematologyAuthor(s): John BarrettWhether 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% ...
Source: Best Practice and Research Clinical Haematology - September 22, 2018 Category: Hematology Source Type: research

Can haploidentical transplantation meet all patients’ needs?
Publication date: Available online 21 September 2018Source: Best Practice & Research Clinical HaematologyAuthor(s): Daniel WeisdorfAllotransplantation 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...
Source: Best Practice and Research Clinical Haematology - September 22, 2018 Category: Hematology Source Type: research

Patterns of mutations in TP53 mutated AML
Publication date: Available online 20 September 2018Source: Best Practice & Research Clinical HaematologyAuthor(s): John S. WelchTP53 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 rem...
Source: Best Practice and Research Clinical Haematology - September 21, 2018 Category: Hematology Source Type: research

What FLT3 inhibitor holds the greatest promise?
Publication date: Available online 20 September 2018Source: Best Practice & Research Clinical HaematologyAuthor(s): Richard M. StoneAbstractDetermining 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...
Source: Best Practice and Research Clinical Haematology - September 21, 2018 Category: Hematology Source Type: research

Is there a standard of care for relapsed AML?
Publication date: Available online 20 September 2018Source: Best Practice & Research Clinical HaematologyAuthor(s): Bruno C. MedeirosAbstractDespite 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 mon...
Source: Best Practice and Research Clinical Haematology - September 21, 2018 Category: Hematology Source Type: research

The role of hypomethylating agents prior to hematopoietic cell transplantation in myelodysplastic syndromes
This article reviews the rationale for hypomethylating agents, their use or intensive chemotherapy pre-transplant, and data supporting pre-transplant MDS treatment. (Source: Best Practice and Research Clinical Haematology)
Source: Best Practice and Research Clinical Haematology - September 21, 2018 Category: Hematology Source Type: research

Progress and predictions: AML in 2018
Publication date: Available online 20 September 2018Source: Best Practice & Research Clinical HaematologyAuthor(s): Jacob M. RoweAbstractThe 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 d...
Source: Best Practice and Research Clinical Haematology - September 21, 2018 Category: Hematology Source Type: research

Hematopoietic cell transplantation as treatment of patients with acute myeloid leukemia with measurable residual disease after consolidation therapy
Publication date: Available online 20 September 2018Source: Best Practice & Research Clinical HaematologyAuthor(s): Frederick R. AppelbaumThe 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 thes...
Source: Best Practice and Research Clinical Haematology - September 21, 2018 Category: Hematology Source Type: research

Allogeneic transplantation among patients with Ph+ ALL: Is it imperative in the TKI era?
Publication date: Available online 20 September 2018Source: Best Practice & Research Clinical HaematologyAuthor(s): Mark R. LitzowAbstractBefore the advent of tyrosine kinase inhibitors (TKIs), Philadelphia 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 chemothe...
Source: Best Practice and Research Clinical Haematology - September 21, 2018 Category: Hematology Source Type: research

Is the overall survival for older adults with AML finally improving?
Publication date: Available online 20 September 2018Source: Best Practice & Research Clinical HaematologyAuthor(s): Jeffrey E. LancetAbstractOlder 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 liposom...
Source: Best Practice and Research Clinical Haematology - September 21, 2018 Category: Hematology Source Type: research