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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 rare....
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 success...
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 mutat...
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 proportion...
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 year...
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 principa...
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 determi...
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 history...
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 reported risk f...
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 that c...
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 cru...
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, espe...
Source: Best Practice and Research Clinical Haematology - February 9, 2019 Category: Hematology Source Type: research