Best Practice & Research Clinical Haematology RSS feed: Current Issue. In practical paperback format, each 200 page topic-based issue of Best Practice & Research Clinical Haematology will provide a comprehensive review of current clinical practice and thinking within the specialty of haematology. All chapters are commissioned and written by an international team of practising clinicians with the Guest Editors for each issue drawn from a pool of renowned experts and opinion leaders. Reference is made to: • the latest original research • Cochrane Reviews • audits and confidential enquiries • national and international conferences • national and international guidelines • personal communications All chapters take the form of practical, evidence-based reviews that seek to address key clinical issues of diagnosis, treatment and patient management. Each issue follows a problem-orientated approach that focuses on the key questions to be addressed, clearly defining what is known and not known. Management will be described in practical terms so that it can be applied to the individual patient. Boxed and bulleted Learning Objectives and Practice Points are features within each chapter and will highlight the core and essential knowledge that will help the physician to provide the best care to their patients. The series' objective is to provide a continuous update for the busy clinician and researcher. http://www.bprch.com/?rss=yesElsevier Inc.en © 2011 Published by Elsevier Inc. All rights reserved. Best Practice & Research Clinical Haematology1521-6926244December 2011 © 2011 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.bprch.com/article/PIIS1521692611000983/abstract?rss=yesEditorial Board / Aims & Scope10.1016/S1521-6926(11)00098-3Best Practice & Research Clinical Haematology 24, 4 (2011)2011-12-01Best Practice & Research Clinical Haematology2011-12-01244S1521-6926(11)X0005-1iiiiiihttp://www.bprch.com/article/PIIS1521692611000831/abstract?rss=yesOver the past decade and a half, a virtual explosion in the identification of genes and mutations has enhanced our understanding of the biology of acute myeloid leukemia (AML) as well as offered potential targets for therapy. We are a long way from the early 1970s and, by now, quite far away from the sole use of cytogenetics for prognosis in AML. Molecular genetics is now dominant, especially among the patients with a normal karyotype. Most recently, we are moving toward a further refinement, namely, interaction between genes. Not a month goes by without another mutation that seems to have independent prognosis.Evaluation of prognostic factors in AMLJacob M. Rowe10.1016/j.beha.2011.09.003Best Practice & Research Clinical Haematology 24, 4 (2011)2011-12-01Best Practice & Research Clinical Haematology2011-12-01244S1521-6926(11)X0005-1485488http://www.bprch.com/article/PIIS1521692611000843/abstract?rss=yesChildhood acute lymphoblastic leukemia (ALL) is comprised of multiple subtypes defined by recurring chromosomal alterations that are important events in leukemogenesis and are widely used in diagnosis and risk stratification, yet fail to fully explain the biology of this disease. In the last 5 years, genome-wide profiling of gene expression, structural DNA alterations and sequence variations has yielded important insights into the nature of submicroscopic genetic alterations that define novel subgroups of acute lymphoblastic leukemia and cooperate with known cytogenetic alterations in leukemogenesis. Importantly, several of these alterations are important determinants of risk of relapse and are potential targets for therapeutic intervention. Here, these advances and future directions in the genomic analysis of ALL are discussed.Genomic profiling of B-progenitor acute lymphoblastic leukemiaCharles G. Mullighan10.1016/j.beha.2011.09.004Best Practice & Research Clinical Haematology 24, 4 (2011)2011-12-01Best Practice & Research Clinical Haematology2011-12-01244S1521-6926(11)X0005-1489503http://www.bprch.com/article/PIIS1521692611000855/abstract?rss=yesWhile flow cytometry once enabled researchers to examine 10–-15 cell surface parameters, new mass flow cytometry technology enables interrogation of up to 45 parameters on a single cell. This new technology has increased understanding of cell expression and how cells differentiate during hematopoiesis. Using this information, knowledge of leukemia cell biology has also increased. Other new technologies, such as SPADE analysis and single cell network profiling (SCNP), are enabling researchers to put different cancers into more biologically similar categories and have the potential to enable more personalized medicine.Flow cytometry in the post fluorescence eraGarry P. Nolan10.1016/j.beha.2011.09.005Best Practice & Research Clinical Haematology 24, 4 (2011)2011-12-01Best Practice & Research Clinical Haematology2011-12-01244S1521-6926(11)X0005-1505508http://www.bprch.com/article/PIIS1521692611000867/abstract?rss=yesMinimal residual disease (MRD) monitoring, particularly via multiparameter flow (MPF) cytometry assessed after chemotherapy, has been very useful in the prognostic and therapeutic approach for children with acute lymphoblastic leukemia. While many studies suggest that MRD monitoring (using MPF or other techniques that are more sensitive than morphologic examination) might be able to accurately predict patient outcome, there is very little data suggesting that treatment decisions should be altered based on such measurements. Proving that MPF-defined MRD should prompt a change in treatment plan optimally requires a contemporaneous control group or at least a historical control treated in standard fashion.Should the presence of minimal residual disease (MRD) in morphologic complete remission alter post-remission strategy in AML?Richard M. Stone10.1016/j.beha.2011.09.006Best Practice & Research Clinical Haematology 24, 4 (2011)2011-12-01Best Practice & Research Clinical Haematology2011-12-01244S1521-6926(11)X0005-1509514http://www.bprch.com/article/PIIS1521692611000879/abstract?rss=yesPrognoses of older patients (age ≥60 years) vary greatly following use of standard therapy, such as 3 + 7: 3 days of daunorubicin or idarubicin + 7 days of cytarabine (ara-C). Although most older patients receive only supportive care, the principal prognostic factor among the presumably healthier treated patients is cytogenetics, with a monosomal karyotype conferring a particularly poor prognosis. However other factors are also informative and several systems incorporating multiple factors have been devised to help guide the fundamental decision as to whether a patient should receive standard therapy or, much more frequently, investigational therapy. Although physicians may be reluctant to await results of cytogenetic analysis and molecular markers (NPM, FLT3), data suggest no harm is done by waiting for these results to become available; certainly the risk of delaying therapy is less than the risk of giving a patient 3 + 7 when the risk of treatment-related mortality (TRM) is greater than the chance of a beneficial response. Nonetheless, in general the risk of TRM is less than that of resistance to therapy, even in patients aged ≥75 years. Perhaps, however, focusing on the former, there is an increasing tendency to administer azacitidine or decitabine to older patients. However there is little to suggest that on average these drugs by themselves convey what many patients would consider medically meaningful improvements in survival. Hence these drugs should not reduce the imperative of putting older patients on trials involving new drugs. Finally, confirming everyday observation, age alone is a very inadequate predictor of outcome and is likely a surrogate for other covariates. Accordingly, the common practice of assigning patients to treatment protocols based solely on age leaves much to be desired.What is the optimal induction strategy for older patients?Elihu Estey10.1016/j.beha.2011.09.007Best Practice & Research Clinical Haematology 24, 4 (2011)2011-12-01Best Practice & Research Clinical Haematology2011-12-01244S1521-6926(11)X0005-1515522http://www.bprch.com/article/PIIS1521692611000880/abstract?rss=yesDo patients with therapy-related acute myeloid leukemia (t-AML) have a poor prognosis independent of other predictive variables such as cytogenetics or molecular determinants? Limited data exist to answer this question in part because t-AML is often considered together with AML following myelodysplastic syndromes (MDS) in the category of secondary AML. This discussion provides some insight, based primarily on two published retrospective reviews of the German cooperative groups, into the question of whether t-AML is an independent adverse variable.Does therapy-related AML have a poor prognosis, independent of the cytogenetic/molecular determinants?Eric J. Feldman10.1016/j.beha.2011.09.008Best Practice & Research Clinical Haematology 24, 4 (2011)2011-12-01Best Practice & Research Clinical Haematology2011-12-01244S1521-6926(11)X0005-1523526http://www.bprch.com/article/PIIS1521692611000892/abstract?rss=yesCurrent National Comprehensive Cancer Network guidelines for acute myeloid leukemia (AML) treatment state that bone marrow biopsies should be completed 7–10 days after completion of chemotherapy. Treatment decisions change based on cellularity of that biopsy. Several studies show that bone marrow aspirates at nadir can be used to predict complete remission (CR) and overall survival. Many groups have attempted to modify induction regimens based on results of bone marrow biopsies with mixed results. This paper will review the current literature on using bone marrow biopsy to prognosticate and guide treatment for AML patients.Is a nadir bone marrow required and, if so, what to do with residual disease?Selina M. Luger10.1016/j.beha.2011.09.009Best Practice & Research Clinical Haematology 24, 4 (2011)2011-12-01Best Practice & Research Clinical Haematology2011-12-01244S1521-6926(11)X0005-1527532http://www.bprch.com/article/PIIS1521692611000818/abstract?rss=yesAllogeneic hematopoietic stem cell transplantation (HSCT) demonstrated convincingly the potential of allogeneic T cells in causing sustained remissions in high-risk hematologic malignancies. However toxicity of allogeneic HSCT limits its application to a broader group of patients. An improved understanding of NK biology along with mechanisms of natural killer (NK) cell and T-cell-mediated alloreactivity against leukemia has led to several clinical immunotherapeutic strategies that preserve graft versus leukemia (GVL) while minimizing the toxicity of HSCT. Here we review strategies being explored both in HSCT and non-HSCT settings that include an emphasis on two key aspects: (a) Maximizing cytotoxicity of alloreactive cells, ie, NK cells and T cells, and (b) Targeted manipulation of critical pathways in T and NK cells contributing to sustained anti-leukemia effects.Targeted immunotherapy for acute myeloid leukemiaSumithira Vasu, Michael A. Caligiuri10.1016/j.beha.2011.09.001Best Practice & Research Clinical Haematology 24, 4 (2011)2011-12-01Best Practice & Research Clinical Haematology2011-12-01244S1521-6926(11)X0005-1533540http://www.bprch.com/article/PIIS1521692611000909/abstract?rss=yesA recent American Society of Blood and Marrow Transplantation (ASBMT) position paper concluded that allogeneic hematopoietic cell transplantation (HCT) is recommended for patients with myelodysplastic syndromes (MDS) with an International Prognostic Scoring System (IPSS) score of INT-2 at diagnosis who have a suitable donor and meet the transplant center’s eligibility criteria and for selected patients at low risk at diagnosis who have poor prognostic features not included in the IPSS. While the ASBMT position is generally reasonable, given available data, physicians caring for MDS patients should be aware of the limitations of these conclusions. The position of the ASBMT is largely based on studies relying on the IPSS, which is imprecise, only applies to patients at diagnosis, ignores the impact of recent therapeutic advances, excludes patients with treatment-related MDS and certain subtypes of chronic myelomonocytic leukemia (CMML), and does not consider the influence of age and comorbidities on the decision-making process. The development of a revised IPSS for MDS provides us with an opportunity to reconsider the role of HCT in the treatment of MDS.The role of hematopoietic cell transplantation as therapy for myelodysplasiaFrederick R. Appelbaum10.1016/j.beha.2011.09.010Best Practice & Research Clinical Haematology 24, 4 (2011)2011-12-01Best Practice & Research Clinical Haematology2011-12-01244S1521-6926(11)X0005-1541547http://www.bprch.com/article/PIIS1521692611000910/abstract?rss=yesTransplantation of hematopoietic cells to treat acute leukemia can offer disease control and extended survival for a sizeable fraction of patients, but because alternative approaches may also be effective, the decision about transplant timing remains uncertain. For those transplanted in first complete remission (CR1), outcomes are the best, but some fraction of those might have had extended leukemia-free survival in the absence of a transplant. In later remission, outcomes are variable but promising—and markedly better than any nontransplant approach. Risks of relapse may differ based on the depth of remission, measurable minimal residual disease (MRD), or patient’s performance status.Transplants for leukemia in relapse: When is the best time?Daniel Weisdorf10.1016/j.beha.2011.09.011Best Practice & Research Clinical Haematology 24, 4 (2011)2011-12-01Best Practice & Research Clinical Haematology2011-12-01244S1521-6926(11)X0005-1549552http://www.bprch.com/article/PIIS152169261100082X/abstract?rss=yesIn the 16 years since thrombopoietin was identified and cloned, much has been learned about its biochemistry, how it is regulated, and its involvement in a wide range of functions in a variety of cell lineages. The first generation of recombinant human thrombopoietins, rHuTPO and pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), were shown to increase platelet counts in patients with immune thrombocytopenia, in platelet apheresis donors, and in patients receiving nonmyeloablative chemotherapy. Their effects in patients with acute myeloid leukemia (AML) showed no benefit at a wide range of doses and schedules. The two second-generation TPO mimetics approved by the US Food and Drug Administration (FDA) for the treatment of ITP, romiplostim and eltrombopag, are now being studied in a number of thrombocytopenic disorders including those due to chemotherapy and hepatitis C. Since romiplostim is comparable to the first-generation recombinant thrombopoietins, it may not be beneficial in AML treatment; however, given its novel mechanism of action, eltrombopag may be a TPO potentiator and if given at the proper time during chemotherapy, may enable AML patients to recover platelet counts sooner.What is the potential for thrombopoietic agents in acute leukemia?David J. Kuter10.1016/j.beha.2011.09.002Best Practice & Research Clinical Haematology 24, 4 (2011)2011-12-01Best Practice & Research Clinical Haematology2011-12-01244S1521-6926(11)X0005-1553558http://www.bprch.com/article/PIIS1521692611000922/abstract?rss=yesHuman T-cell lymphoma virus (HTLV)-1 was the first human retrovirus to be discovered. It has been recognized as the cause of adult T-cell leukemia (ATL). In addition to giving a historical perspective on HTLV-1 and other retrovirus research, this paper discusses the origin of HTLV-1; the modes of transmission and global epidemiology of HTLV-1 infection; the genome of HTLV-1 and the mechanism of HTLV-1-induced leukemogenesis; the role of HTLV-1 in other diseases, and recent breakthroughs in ATL therapy.Research and discovery of the first human cancer virus, HTLV-1Robert C. Gallo10.1016/j.beha.2011.09.012Best Practice & Research Clinical Haematology 24, 4 (2011)2011-12-01Best Practice & Research Clinical Haematology2011-12-01244S1521-6926(11)X0005-1559565http://www.bprch.com/article/PIIS1521692611001022/abstract?rss=yesIndex10.1016/S1521-6926(11)00102-2Best Practice & Research Clinical Haematology 24, 4 (2011)2011-12-01Best Practice & Research Clinical Haematology2011-12-01244S1521-6926(11)X0005-1II