Future therapeutic options for patients with Waldenstr öm Macroglobulinemia
Publication date: Available online 14 September 2016 Source:Best Practice & Research Clinical Haematology Author(s): Jorge J. Castillo, Zachary R. Hunter, Guang Yang, Kimon Argyropoulos, M. Lia Palomba, Steven P. Treon Waldenström macroglobulinemia (WM) is a rare lymphoma characterized by the accumulation of IgM-producing lymphoplasmacytic cells. Although WM patients can experience prolonged remissions, the disease invariably recurs. Therefore, novel treatments associated with higher success rates and lower toxicity profiles are needed. The discovery of recurrent mutations in the MYD88 and CXCR4 genes has unr...
Source: Best Practice and Research Clinical Haematology - September 14, 2016 Category: Hematology Source Type: research

Bone marrow microenvironment in Waldenstrom's Macroglobulinemia
Publication date: Available online 4 September 2016 Source:Best Practice & Research Clinical Haematology Author(s): Shahrzad Jalali, Stephen M. Ansell Waldenstrom Macroglobulinemia (WM) is a low-grade B-cell lymphoma defined firstly by infiltration of lymphoplasmacytic cells into the bone marrow (BM), the milieu where the cells acquire signals that promote malignant growth and proliferation. A second characteristic associated with WM is the increased synthesis of monoclonal immunoglobulin M (IgM) by lymphoplasmacytic cells, which is secreted in the serum and often results in hyperviscosity. Advanced genomic tools ...
Source: Best Practice and Research Clinical Haematology - September 12, 2016 Category: Hematology Source Type: research

Novel therapeutic targets in Waldenstrom macroglobulinemia
Publication date: Available online 7 September 2016 Source:Best Practice & Research Clinical Haematology Author(s): Aneel Paulus, Sikander Ailawadhi, Asher Chanan-Khan Understanding of molecular mechanisms that drive Waldenstrom macroglobulinemia (WM) cell survival are rapidly evolving. This review briefly highlights emerging “WM-relevant” targets; for which therapeutic strategies are currently being investigated in preclinical and clinical studies. With the discovery of MYD88L265P signaling and remarkable activity of ibrutinib in WM, other targets within the B-cell receptor pathway are now being focus...
Source: Best Practice and Research Clinical Haematology - September 8, 2016 Category: Hematology Source Type: research

Targeting cell adhesion and homing as strategy to cure Waldenstr öm’s macroglobulinemia
Publication date: Available online 7 September 2016 Source:Best Practice & Research Clinical Haematology Author(s): Steven T. Pals, Marie José Kersten, Marcel Spaargaren Most B-cell malignancies strictly depend on signals from the microenvironment for their survival and proliferation. This niche-dependency can be regarded as their Achilles’ heel and provides an excellent target for therapy. Waldenström’s macroglobulinemia (WM) is characterized by the accumulation of neoplastic post-germinal center B cells within the bone marrow (BM). Interestingly, one third of the patients carry activating...
Source: Best Practice and Research Clinical Haematology - September 8, 2016 Category: Hematology Source Type: research

The role of stem cell transplantation in Waldenstrom ’s macroglobulinemia
Publication date: Available online 6 September 2016 Source:Best Practice & Research Clinical Haematology Author(s): Rajshekhar Chakraborty, Eli Muchtar, Morie A. Gertz Waldenstrom’s macroglobulinemia (WM) is an indolent B-cell lymphoma, which is highly chemosensitive, with an overall response rate over 90% to novel agents. However, most patients eventually relapse after response to first-line chemotherapy, necessitating further treatment. The possibility of long-lasting remission after high-dose cytotoxic chemotherapy followed by stem cell rescue is high in WM due to the chemosensitive nature of the disease ...
Source: Best Practice and Research Clinical Haematology - September 5, 2016 Category: Hematology Source Type: research

Prognostic factors and indications for treatment of Waldenstr öm's Macroglobulinemia
Publication date: Available online 23 August 2016 Source:Best Practice & Research Clinical Haematology Author(s): Robert A. Kyle, Stephen M. Ansell, Prashant Kapoor Waldenström's Macroglobulinemia (WM) is characterized by the presence of an IgM monoclonal protein regardless of its size, 10% or more bone marrow infiltration by small lymphocytes with a plasmacytoid or plasma cell differentiation. These cells usually have the following markers: IgM+, CD5−, CD10−, CD19+, CD20+ and CD23−. Chronic lymphocytic leukemia as well as other lymphoproliferative disorders such as mantle cell, marginal zon...
Source: Best Practice and Research Clinical Haematology - September 3, 2016 Category: Hematology Source Type: research

Bone Marrow Microenvironment in Waldenstrom ’s Macroglobulinemia
Publication date: Available online 4 September 2016 Source:Best Practice & Research Clinical Haematology Author(s): Shahrzad Jalali, Stephen M. Ansell Waldenstrom Macroglobulinemia (WM) is a low-grade B-cell lymphoma defined firstly by infiltration of lymphoplasmacytic cells into the bone marrow (BM), the milieu where the cells acquire signals that promote malignant growth and proliferation. A second characteristic associated with WM is the increased synthesis of monoclonal immunoglobulin M (IgM) by lymphoplasmacytic cells, which is secreted in the serum and often results in hyperviscosity. Advanced genomic tools ...
Source: Best Practice and Research Clinical Haematology - September 3, 2016 Category: Hematology Source Type: research

Preclinical Models of Waldenstr öm’s Macroglobulinemia and Drug Resistance
Publication date: Available online 4 September 2016 Source:Best Practice & Research Clinical Haematology Author(s): Sikander Ailawadhi, Aneel Paulus, Asher Chanan-Khan Newer therapeutic strategies are emerging in Waldenström’s Macroglobulinemia (WM), which has traditionally been an orphan disease diagnosis. Ibrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor was FDA-approved in 2015 as the first ever drug for the treatment of WM. This being a targeted therapy, has given rise to increased research into novel agents and pathways that can be exploited for clinical benefit in WM. In order to underst...
Source: Best Practice and Research Clinical Haematology - September 3, 2016 Category: Hematology Source Type: research

Monoclonal Gammopathy of Undetermined Significance and Waldenstr öm’s Macroglobulinemia
Publication date: Available online 4 September 2016 Source:Best Practice & Research Clinical Haematology Author(s): Sham Mailankody, Ola Landgren Since the initial identification of patients with monoclonal elevation of gamma globulin and associated clinical symptoms in 1944 by Jan Waldenström, several new insights have been gained using a range of approaches. For example, IgM monoclonal gammopathy of undetermined significance and smoldering Waldenström’s macroglobulinemia are defined clinical precursor states to symptomatic Waldenström’s macroglobulinemia. Epidemiologic studies have est...
Source: Best Practice and Research Clinical Haematology - September 3, 2016 Category: Hematology Source Type: research

Prognostic Factors and Indications for Treatment of Waldenstr öm’s Macroglobulinemia
Publication date: Available online 23 August 2016 Source:Best Practice & Research Clinical Haematology Author(s): Robert A. Kyle, Stephen M. Ansell, Prashant Kapoor Waldenström’s Macroglobulinemia (WM) is characterized by the presence of an IgM monoclonal protein regardless of its size, 10% or more bone marrow infiltration by small lymphocytes with a plasmacytoid or plasma cell differentiation. These cells usually have the following markers: IgM+, CD5-, CD10-, CD19+, CD20+ and CD23-. Chronic lymphocytic leukemia as well as other lymphoproliferative disorders such as mantle cell, marginal zone and mucosa...
Source: Best Practice and Research Clinical Haematology - August 23, 2016 Category: Hematology Source Type: research

Monoclonal IgM-related AL amyloidosis
Publication date: Available online 23 August 2016 Source:Best Practice & Research Clinical Haematology Author(s): Paolo Milani, Giampaolo Merlini Monoclonal immunoglobulin M (IgM)-related light chain (AL) amyloidosis, which accounts for 5% to 7% of all AL amyloidosis cases, is a distinct clinical entity that poses specific challenges to clinicians. Several studies reported that although there is a substantial overlap, the pattern of organ involvement is peculiar, with higher frequencies of lung, lymph nodes, and peripheral nervous system involvement. A recent collaborative study from three European referral center...
Source: Best Practice and Research Clinical Haematology - August 23, 2016 Category: Hematology Source Type: research

Adoptive cellular therapy for chronic lymphocytic leukemia and b cell malignancies. Cars and more
Publication date: Available online 20 August 2016 Source:Best Practice & Research Clinical Haematology Author(s): Januario E. Castro, Thomas J. Kipps Treatment of patients with chronic lymphocytic leukemia and other B cell malignancies is evolving very rapidly. We have observed the rapid transition during the last couple of years, from chemo-immunotherapy based treatments to oral targeted therapies based on B cell receptor signaling and Bcl-2 inhibitors and the use of second generation glyco-engineered antibodies. The next wave of revolution in treatment for this conditions is approaching and it will be based on s...
Source: Best Practice and Research Clinical Haematology - August 20, 2016 Category: Hematology Source Type: research

Special Volume “Chronic Lymphocytic Leukemia”
Publication date: Available online 17 August 2016 Source:Best Practice & Research Clinical Haematology Author(s): Januario E. Castro (Source: Best Practice and Research Clinical Haematology)
Source: Best Practice and Research Clinical Haematology - August 17, 2016 Category: Hematology Source Type: research

Present and future of personalized medicine in CLL
Publication date: Available online 12 August 2016 Source:Best Practice & Research Clinical Haematology Author(s): Emili Montserrat, Tycho Bauman, Julio Delgado Medicine has been ‘personalized’ (i.e. centred in persons) since its foundation. Recently, however, the term ‘personalized medicine’ (or, better, ‘precision medicine’) has been introduced to define ‘a form of medicine that uses information about a person’s genes, proteins, and environment to prevent, diagnose, and treat disease’. This concept has gained momentum thanks to next-generation-sequencing (NGS)...
Source: Best Practice and Research Clinical Haematology - August 13, 2016 Category: Hematology Source Type: research

“Current strategies to create tailored and risk-adapted therapies for CLL patients”
This article gives an update of the most interesting novel drugs. The strategy of the German CLL Study Group to use these agents in combinations is described in detail, highlighting the strategy and first results of a recently started series of phase II combination trials, the BXX series using agents such as bendamustine, idelalisib, ibrutinib, obinutuzumab, ofatumumab and venetoclax. (Source: Best Practice and Research Clinical Haematology)
Source: Best Practice and Research Clinical Haematology - August 11, 2016 Category: Hematology Source Type: research

Richter's syndrome: novel and promising therapeutic alternatives
Publication date: Available online 11 August 2016 Source:Best Practice & Research Clinical Haematology Author(s): Davide Rossi Richter’s syndrome (RS) is the development of an aggressive lymphoma in patients with a previous or concomitant diagnosis of chronic lymphocytic leukemia (CLL). The incidence rate for RS is ∼0.5% per year of observation. In the presence of clinical suspicious of RS, diagnosis of transformation and choice of the site of biopsy may take advantage of 18FDG PET/CT. Molecular lesions of tumor suppression regulators (TP53), cell cycle (CDKN2A) and cell proliferation (NOTCH1, MYC) overa...
Source: Best Practice and Research Clinical Haematology - August 10, 2016 Category: Hematology Source Type: research

The Chronic Lymphocytic Leukemia Microenvironment: Beyond the B-cell Receptor
Publication date: Available online 11 August 2016 Source:Best Practice & Research Clinical Haematology Author(s): Michael Y. Choi, Manoj Kumar Kashyap, Deepak Kumar Malignant B cells accumulate in the peripheral blood, bone marrow, and lymphoid organs of patients with chronic lymphocytic leukemia (CLL). In the tissue compartments, CLL shape a protective microenvironment by coopting normal elements. The efficacy of drugs that target these interactions further underscores their importance in the pathogenesis of CLL. While the B cell receptor (BCR) pathway clearly plays a central role in the CLL microenvironment, the...
Source: Best Practice and Research Clinical Haematology - August 10, 2016 Category: Hematology Source Type: research

TP53 Dysfunction in CLL: Implications for Prognosis and Treatment
Publication date: Available online 11 August 2016 Source:Best Practice & Research Clinical Haematology Author(s): Gera D. te Raa, Arnon P. Kater Despite the availability of novel targeted agents, TP53 defects remain the most important adverse prognostic factor in chronic lymphocytic leukemia (CLL). Detection of deletion of TP53 locus (17p deletion) by fluorescent in situ hybridization (FISH) has become standard and performed prior to every line of treatment as the incidence dramatically increases as relapses occur. As monoallelic mutations of TP53 equally affect outcome, novel methods are being developed to improv...
Source: Best Practice and Research Clinical Haematology - August 10, 2016 Category: Hematology Source Type: research

Current state of hematopoietic cell transplantation in CLL as smart therapies emerge
Publication date: Available online 11 August 2016 Source:Best Practice & Research Clinical Haematology Author(s): Mohamed A. Kharfan-Dabaja, Jessica El-Asmar, Farrukh T. Awan, Mehdi Hamadani, Ernesto Ayala Novel therapies targeting various kinases downstream of the B-cell receptor have emerged along with monoclonal antibodies and BCL-2 antagonists, and are changing the therapeutic landscape of chronic lymphocytic leukemia. However, cure remains unattainable unless eligible patients are offered an allogeneic hematopoietic cell transplant. Access to allogeneic hematopoietic cell transplantation has expanded consider...
Source: Best Practice and Research Clinical Haematology - August 10, 2016 Category: Hematology Source Type: research

B cell receptor inhibition as a target for CLL therapy
Publication date: Available online 11 August 2016 Source:Best Practice & Research Clinical Haematology Author(s): Deepa Jeyakumar, Susan O’Brien Inhibitors of the B cell receptor (BCR) represent an attractive therapeutic option for patients with chronic lymphocytic leukemia. Recently approved inhibitors of Bruton’s tyrosine kinase (ibrutinib) and phosphatidylinositol 3-kinase (idelalisib), are promising agents because they are generally well tolerated and highly effective. These agents may be particularly important in the treatment of older patients who are less able to tolerate the myelosuppression (a...
Source: Best Practice and Research Clinical Haematology - August 10, 2016 Category: Hematology Source Type: research

The 21st century revolution in CLL: why this matters to patients
Publication date: Available online 11 August 2016 Source:Best Practice & Research Clinical Haematology Author(s): Brian Koffman, Andrew Schorr The 21st century has seen rapid, positive changes in the management of chronic lymphocytic leukaemia from the patient’s perspective. New prognostic and predictive markers have ushered in the start of more precise and individualized therapy. For the first time, combined therapy [fludarabine, cyclophosphamide and rituximab] has been shown to prolong life significantly. Clinical trials have become more adaptive, faster and more patient friendly. Perhaps the greatest chan...
Source: Best Practice and Research Clinical Haematology - August 10, 2016 Category: Hematology Source Type: research

Genetic evolution in chronic lymphocytic leukaemia
Publication date: Available online 11 August 2016 Source:Best Practice & Research Clinical Haematology Author(s): Julio Delgado, Neus Villamor, Armando López-Guillermo, Elías Campo Next-generation sequencing provides a comprehensive understanding of the genomic, epigenomic and transcriptomic underpinnings of chronic lymphocytic leukaemia. Recent studies have uncovered new drivers, including mutations in non-coding regions, and signalling pathways whose role in cancer was previously unknown or poorly understood. Moreover, massive scale epigenomics and transcriptomics have supplied the foundations for ...
Source: Best Practice and Research Clinical Haematology - August 10, 2016 Category: Hematology Source Type: research

Biomarkers in Chronic Lymphocytic Leukemia: Clinical applications and Prognostic Markers
Publication date: Available online 10 August 2016 Source:Best Practice & Research Clinical Haematology Author(s): Carlos I. Amaya-Chanaga, Laura Z. Rassenti Chronic lymphocytic leukemia is a heterogeneous disease with a variable clinical course. The Rai and Binet staging systems are often used to predict survival. However, they do not take into account other biological characteristics of CLL cells that may influence the disease course and response to treatment. Prognostic factors such as chromosome abnormalities (trisomy 12, 11q deletions and 17p deletions), β2 microglobulin, thymidine kinase, CD38 and ZAP-70...
Source: Best Practice and Research Clinical Haematology - August 9, 2016 Category: Hematology Source Type: research

Corrigendum to “Advances in T-cell therapy for ALL” [Best Pract Res Clin Haematol 27 (2014) 222–228]
Publication date: Available online 16 July 2016 Source:Best Practice & Research Clinical Haematology Author(s): Stephan A. Grupp (Source: Best Practice and Research Clinical Haematology)
Source: Best Practice and Research Clinical Haematology - July 28, 2016 Category: Hematology Source Type: research

Optimal dose and schedule of consolidation in  AML: Is there a standard?
Publication date: September–December 2014 Source:Best Practice & Research Clinical Haematology, Volume 27, Issues 3–4 Author(s): Charles A. Schiffer Approximately 35%–40% of younger adults with acute myeloid leukemia (AML) can be cured using higher doses of cytosine arabinoside (ara-C) as post remission consolidation. Earlier studies focused on higher doses of 3 gms/m2, but since then numerous studies evaluating differences in dose, schedule, number of courses, and the addition of other agents, suggest that an intermediate-dose of ara-C may offer the greatest benefit to most patients with ...
Source: Best Practice and Research Clinical Haematology - June 17, 2016 Category: Hematology Source Type: research

Fanconi anemia and the development of  leukemia
Publication date: September–December 2014 Source:Best Practice & Research Clinical Haematology, Volume 27, Issues 3–4 Author(s): Blanche P. Alter Fanconi anemia (FA) is a rare autosomal recessive cancer-prone inherited bone marrow failure syndrome, due to mutations in 16 genes, whose protein products collaborate in a DNA repair pathway. The major complications are aplastic anemia, acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and specific solid tumors. A severe subset, due to mutations in FANCD1/BRCA2, has a cumulative incidence of cancer of 97% by age 7 years; the cancers are AML, br...
Source: Best Practice and Research Clinical Haematology - June 17, 2016 Category: Hematology Source Type: research

Editorial Board / Aims & amp; Scope
Publication date: December 2015 Source:Best Practice & Research Clinical Haematology, Volume 28, Issue 4 (Source: Best Practice and Research Clinical Haematology)
Source: Best Practice and Research Clinical Haematology - June 17, 2016 Category: Hematology Source Type: research

Hairy cell leukemia: Uncommon clinical features, unusual sites of involvement and some rare associations
Publication date: Available online 11 November 2015 Source:Best Practice & Research Clinical Haematology Author(s): Tamar Tadmor, Aaron Polliack Unusual clinical manifestations and associations with auto-immunity or other systemic disorders are uncommon clinical features of hairy cell leukemia (HCL). The exact prevalence of these rare associations is difficult to determine as they are mostly published as anecdotal case reports and generally not included in larger published series. This chapter deals with uncommon clinical manifestations and rare sites of involvement in HCL. It also summarizes the association wi...
Source: Best Practice and Research Clinical Haematology - November 12, 2015 Category: Hematology Source Type: research

Hairy cell leukemia
Publication date: Available online 11 November 2015 Source:Best Practice & Research Clinical Haematology Author(s): Claire Dearden (Source: Best Practice and Research Clinical Haematology)
Source: Best Practice and Research Clinical Haematology - November 12, 2015 Category: Hematology Source Type: research

Hairy cell leukaemia-variant: Disease features and treatment
Publication date: Available online 8 October 2015 Source:Best Practice & Research Clinical Haematology Author(s): Estella Matutes, Alejandra Martínez-Trillos, Elias Campo Hairy cell leukaemia-variant (HCL-V) is a rare B-cell malignancy that affects elderly males and manifests with splenomegaly, lymphocytosis and cytopenias without monocytopenia. The neoplastic cells have morphological features of prolymphocytes and hairy cells. The immunophenotype is that of a clonal B-cell CD11c and CD103 positive but, unlike classical HCL, CD25, CD123 and CD200 negative. The spleen histology is similar to classical HC...
Source: Best Practice and Research Clinical Haematology - October 27, 2015 Category: Hematology Source Type: research

Historical overview of hairy cell leukemia
Publication date: Available online 26 October 2015 Source:Best Practice & Research Clinical Haematology Author(s): Leslie A. Andritsos, Michael R. Grever Since its discovery in 1923 and further characterization in 1958, hairy cell leukemia (HCL) has undergone enormous advances in the understanding of the biology and treatment of the disease. Initially a uniformly fatal disease, new therapies in rapid succession transformed HCL into a chronic disease with a normal life expectancy in many cases. More recently, the identification of BRAFV600E mutations in the majority of patients with classic HCL have enabled targ...
Source: Best Practice and Research Clinical Haematology - October 27, 2015 Category: Hematology Source Type: research

Clinical features and diagnosis of hairy cell leukemia
Publication date: Available online 26 October 2015 Source:Best Practice & Research Clinical Haematology Author(s): Graeme R. Quest, James B. Johnston Significant advances in the diagnosis and treatment of hairy cell leukemia (HCL) have recently been made. Improved distinction of HCL from its mimics though clinical presentations, morphologic and immunophenotypic features, and more recently molecular biology, has highlighted marked differences in treatment response and overall prognosis between these disorders. As our understanding of the unique pathobiology of HCL has grown, exciting new avenues of treatment as ...
Source: Best Practice and Research Clinical Haematology - October 26, 2015 Category: Hematology Source Type: research

Bone marrow and splenic histology in hairy cell leukaemia
Publication date: Available online 24 October 2015 Source:Best Practice & Research Clinical Haematology Author(s): Andrew Wotherspoon, Ayoma Attygalle, Larissa Sena T. Mendes Hairy cell leukaemia is a rare chronic neoplastic B-cell lymphoproliferation that characteristically involves blood, bone marrow and spleen with liver, lymph node and skin less commonly involved. Histologically the cells have a characteristic appearance with pale/clear cytoplasm and round or reniform nuclei. In the spleen the infiltrate involves the red pulp and is frequently associated with areas of haemorrhage (blood lakes). The cells s...
Source: Best Practice and Research Clinical Haematology - October 25, 2015 Category: Hematology Source Type: research

The importance of the tissue microenvironment in hairy cell leukemia
Publication date: Available online 9 October 2015 Source:Best Practice & Research Clinical Haematology Author(s): Mariela Sivina, Jan A. Burger Hairy cell leukemia (HCL) cells engage in complex cellular and molecular interactions with accessory cells, matrix proteins, and various cytokines in the bone marrow and spleen, collectively referred to as the tissue microenvironment. Chemokine receptors and adhesion molecules are critical players for homing and retention within these microenvironments. Engagement of B cell antigen receptors and CD40 on HCL cells promote survival and proliferation. In this chapter, we s...
Source: Best Practice and Research Clinical Haematology - October 23, 2015 Category: Hematology Source Type: research

Hairy cell leukemia: Past, present and future
Publication date: Available online 21 October 2015 Source:Best Practice & Research Clinical Haematology Author(s): Bartlomiej M. Getta, Jae H. Park, Martin S. Tallman This brief review highlights the sequence of therapeutic milestones and advances in our understanding of the biology of hairy cell leukemia (HCL) with a focus on recent molecular findings and how these may be applied to improve disease outcomes in the future. Targeted therapy is discussed in the context of the recently identified BRAF mutation and other genetic findings. (Source: Best Practice and Research Clinical Haematology)
Source: Best Practice and Research Clinical Haematology - October 23, 2015 Category: Hematology Source Type: research

Antibodies: Immunoconjugates and autologous cellular therapy in acute lymphoblastic leukemia
Publication date: Available online 22 October 2015 Source:Best Practice & Research Clinical Haematology Author(s): Anjali Advani Using a case study of a 57-year-old man with relapsed/refractory precursor-B (pre-B) acute lymphoblastic leukemia (ALL), this review discusses treatment with immunoconjugates and autologous therapy in acute ALL. Three therapies—blinatumomab, inotuzumab, and CAR T cells—are considered here, each with advantages in specific clinical situations. These therapies represent some of the exciting advances that have been made in the treatment of ALL over the last several years. (Sou...
Source: Best Practice and Research Clinical Haematology - October 23, 2015 Category: Hematology Source Type: research

Plasticity of hematopoietic stem cells
Publication date: Available online 22 October 2015 Source:Best Practice & Research Clinical Haematology Author(s): Makio Ogawa, Amanda C. LaRue, Meenal Mehrotra Almost two decades ago, a number of cell culture and preclinical transplantation studies suggested the striking concept of the tissue-reconstituting ability of hematopoietic stem cells (HSCs). While this heralded an exciting time of radically new therapies for disorders of many organs and tissues, the concept was soon mired by controversy and remained dormant. This chapter provides a brief review of evidence for HSC plasticity including our findings ba...
Source: Best Practice and Research Clinical Haematology - October 23, 2015 Category: Hematology Source Type: research

Role of intestinal microbiota in transplantation outcomes
Publication date: Available online 22 October 2015 Source:Best Practice & Research Clinical Haematology Author(s): Ying Taur, Rob Jenq, Carles Ubeda, Marcel van den Brink, Eric G. Pamer While allogeneic hematopoietic stem cell transplantations have a curative potential, infections and graft-versus-host disease remain significant problems. The intestinal microbiota can influence responses to cancer chemotherapy and the role of the microbiota in affecting allogeneic hematopoietic stem cell transplantation outcomes is increasingly appreciated. The following paper discusses the most recent developments in this a...
Source: Best Practice and Research Clinical Haematology - October 23, 2015 Category: Hematology Source Type: research

Recent developments in HLA-haploidentical transplantations
Publication date: Available online 22 October 2015 Source:Best Practice & Research Clinical Haematology Author(s): Margaret Showel, Ephraim J. Fuchs While allogeneic hematopoietic stem cell transplantations have a curative potential, several patients with hematologic malignancies cannot avail themselves of this therapeutic option due to lack of matched donor availability. Although HLA-haploidentical transplantations were previously associated with poor outcomes, recent evidence with use of post transplantation cyclophosphamide indicate improved safety and efficacy. The following paper discusses the most recent ...
Source: Best Practice and Research Clinical Haematology - October 23, 2015 Category: Hematology Source Type: research

Should minimal residual disease guide therapy in AML?
Publication date: Available online 22 October 2015 Source:Best Practice & Research Clinical Haematology Author(s): Elisabeth Paietta The prognostic power of minimal residual disease after therapy for acute leukemias is not in question. It is only logical that the finding of leukemic blast cells after therapy predicts for impending relapse or at least the need for additional treatment. Which level of what is called minimal residual disease (MRD) is clinically relevant, however, depends on the efficacy of the initial treatment as well as the treatment strategies available to target MRD. There are a multitude of ad...
Source: Best Practice and Research Clinical Haematology - October 23, 2015 Category: Hematology Source Type: research

Is there a role for therapy after transplant?
Publication date: Available online 22 October 2015 Source:Best Practice & Research Clinical Haematology Author(s): Betül Oran Despite the steady increase in the number of stem cell transplants performed since 1980 and improvements in survival rates, disease relapse remains the major cause of death after HLA matched sibling and unrelated donor transplants for acute myeloid leukemia (AML). Given this situation, maintenance therapy after transplant may be an appropriate strategy to reduce the relapse rate and prolong survival. A number of agents are being investigated as maintenance therapy after stem cell tra...
Source: Best Practice and Research Clinical Haematology - October 23, 2015 Category: Hematology Source Type: research

Impact of genomics in the clinical management of patients with cytogenetically normal acute myeloid leukemia
Publication date: Available online 22 October 2015 Source:Best Practice & Research Clinical Haematology Author(s): Brunangelo Falini, Maria Paola Martelli Acute myeloid leukemia (AML) is a clinically and molecularly heterogeneous disease. Cytogenetics and FISH have contributed to the stratification of AML patients into favourable, intermediate, and unfavourable risk categories. However, until recently, the prognostic stratification and treatment decision for the intermediate risk category, mostly comprising AML patients with normal cytogenetics (CN-AML), has been difficult due to the scarce knowledge of the mol...
Source: Best Practice and Research Clinical Haematology - October 23, 2015 Category: Hematology Source Type: research

Reasons for optimism in the therapy of acute leukemia
Publication date: Available online 22 October 2015 Source:Best Practice & Research Clinical Haematology Author(s): Jacob M. Rowe Distinct progress has been made in recent years in the therapy of acute leukemia. For acute myeloid leukemia (AML), this progress has been anchored in the increased understanding of genomic complexity. Multiple targets and the relationships among them pose new challenges along with new possibilities for the development of targeted therapies. A number of new drugs are in early clinical development for AML, one of which centers on the role of isocitrate dehydrogenase (IDH) in malignancy....
Source: Best Practice and Research Clinical Haematology - October 23, 2015 Category: Hematology Source Type: research

AML evolution from preleukemia to leukemia and relapse
Publication date: Available online 22 October 2015 Source:Best Practice & Research Clinical Haematology Author(s): Liran I. Shlush, Amanda Mitchell Dismal outcomes of acute myeloid leukemia (AML), especially in the elderly, are mainly associated with leukemia relapse and primary no response to initial therapy. This review will focus on AML relapse, and how a better understanding of the evolutionary stages that lead to relapse might help us improve disease outcome. The fact that the relapse rate for some AMLs is so high indicates that we do not truly understand the biology of relapse or possibly that we are not ...
Source: Best Practice and Research Clinical Haematology - October 23, 2015 Category: Hematology Source Type: research

Hematopoietic cell transplantation for adults with acute myeloid leukemia with minimal residual disease
Publication date: Available online 22 October 2015 Source:Best Practice & Research Clinical Haematology Author(s): Frederick R. Appelbaum Early trials of hematopoietic cell transplantation (HCT) for adults with acute myeloid leukemia (AML) did not generally include measurement of minimal residual disease (MRD) at the time of remission. However, the presence of MRD is now considered to be a powerful predictor of outcome for adults with AML in first complete remission. This raises the question of whether MRD positivity in first remission changes the indications for transplant or the transplant approach itself if p...
Source: Best Practice and Research Clinical Haematology - October 23, 2015 Category: Hematology Source Type: research

Epidemiology and environmental risk in hairy cell leukemia
Publication date: Available online 23 October 2015 Source:Best Practice & Research Clinical Haematology Author(s): Tamar Tadmor, Aaron Polliack Hairy cell leukaemia (HCL) is an orphan subtype of leukaemia which constitutes less than 2% of all leukaemia's, with an incidence of less than 1 per 100,000 persons per annum. Median age at presentation is 55 years and it is 3-4 times more frequent in males. It is also more frequently encountered in whites and less in Asians, Africans and Arabs. The epidemiologic data are multi-factorial and influenced by ethnicity and geographical factors. Other reported associations r...
Source: Best Practice and Research Clinical Haematology - October 23, 2015 Category: Hematology Source Type: research

BRAF inhibitor therapy in HCL
Publication date: Available online 20 October 2015 Source:Best Practice & Research Clinical Haematology Author(s): Sascha Dietrich, Thorsten Zenz Targeted treatment approaches are transforming the therapeutic landscape of cancer care. The discovery of the BRAF V600E mutation in most cases of classical hairy cell leukemia opens up unique opportunities for tumor specific treatment of HCL targeting the MEK/ERK signaling pathway. The discovery and biological implications of BRAF V600E in HCL are summarized to form a basis for our current understanding of the potential for clinical exploitation. There is overwhelmin...
Source: Best Practice and Research Clinical Haematology - October 21, 2015 Category: Hematology Source Type: research

IDH2 inhibition in AML: Finally progress?
Publication date: Available online 19 October 2015 Source:Best Practice & Research Clinical Haematology Author(s): Eytan M. Stein Isocitrate dehydrogenase (IDH) catalyzes the conversion of isocitrate to alpha ketoglutarate. IDH occurs in three isoforms, IDH1, located in the cytoplasm, IDH2 located in the mitochondria, and IDH3, which functions as part of the TCA cycle. Mutations in the active site of IDH1 at position R132 and an analogous mutation in the IDH2 gene at position R172 have been discovered. Notably, many cases of acute myeloid leukemia (AML) have mutations in R172 and R140. The impact of these mutati...
Source: Best Practice and Research Clinical Haematology - October 20, 2015 Category: Hematology Source Type: research

Is there a best graft source of transplantation in acute myeloid leukemia?
Publication date: Available online 20 October 2015 Source:Best Practice & Research Clinical Haematology Author(s): Karen K. Ballen Only 30% of patients in the US who require an allogeneic hematopoietic cell transplant will have a fully HLA matched sibling donor. The National Marrow Donor Program/Be the Match has grown to over 25 million unrelated donors. However, a fully matched unrelated donor may not be available for many patients, particularly for patients of diverse racial and ethnic backgrounds. Over the last 10 years, considerable progress has been made in alternative donor transplant with improvements in ...
Source: Best Practice and Research Clinical Haematology - October 20, 2015 Category: Hematology Source Type: research

Should older adults with AML receive post-remission therapy?
Publication date: Available online 20 October 2015 Source:Best Practice & Research Clinical Haematology Author(s): Richard M. Stone The evolution of post-remission therapy in older adults has for the most part mirrored that for younger adults. However, the suitability of those regimens for an older population is less clear-cut, mainly due to poorer tolerance of therapy and a relatively higher level of disease resistance. Not only is intensive post-remission therapy not appropriate for the majority of older adults, but the role of intensive induction therapy is also unclear. Treatment goals in patients over 55-65...
Source: Best Practice and Research Clinical Haematology - October 20, 2015 Category: Hematology Source Type: research