The aggressive B-cell lymphomas are a diverse collection of cancers grouped together based on clinical behavior and derivation from B lymphocytes. Genomic analyses on these tumours are now translating into improved classification systems and identification of underpinning targetable biology. Simple karyotyping revealed key translocations involving MYC, BCL2, and BCL6 that have impacted lymphoma classification in the World Health Organization classification scheme. Subsequently, gene expression profiling identified molecular subgroups within the most common lymphoma, diffuse large B-cell lymphoma (DLBCL): activated B-cell-like and germinal centre B-cell-like. Finally, next generation sequencing has revealed a modest number of frequently mutated genes and a long list of infrequent mutations. The mutational landscapes involve diverse genes associated with dysregulated signalling, epigenetic modification, blockade of cellular differentiation, and immune evasion. These mutational "signatures" are enriched in the different aggressive lymphoma subtypes impacting phenotypes and identifying therapeutic targets. Challenges to implementing genomic assays into clinical practice remain.

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 developments in this area.

The discovery of the activating mutation JAK2 V617F ushered a new era in MPN which included new diagnostic and prognostic criteria as well as a potential therapeutic target. JAK2 inhibition became a reality with first patients receiving drugs that targeted JAK2 in 2007 and was marked by the first approval in 2011 of Ruxolitinib a JAK 1 and 2-inhibitor to treat myelofibrosis (MF). In this article entitled "How many JAK inhibitors for myelofibrosis" we discuss JAK2 as a target, review briefly the benefits to patients with MF of JAK inhibition and highlight some of the differences between the number of JAK inhibitors currently being evaluated. Reflecting upon what we have learnt from the chronic myeloid leukaemia field and for MF regarding disease complexity as well as individual patient factors including resistance we discuss why it is likely we will need several different agents with JAK inhibitory activity. The next chapter discusses combination therapies for myelofibrosis which is a logical step in both trying to cure this disease and improve patient outcome and toxicities with JAK inhibitors.

This year marked the occurrence of several important milestones in the treatment of acute leukemias. First, the standard 7 + 3 protocol for acute myeloid leukemia (AML) was developed 40 years ago, and with some adaptations, has stood the test of time. Second, the 1 millionth hematopoietic cell transplant was recorded this year. Stem cell transplant, the first reported by Dr E. Donnall Thomas in 1957, had been considered a rare procedure until about a decade ago. Today, it has become a proven and often life-saving therapy for patients with acute leukemia. Advances in the treatment of patients with AML continue to take place, many of which relate to an increased understanding of the clinical heterogeneity of known subtypes. Forty years ago, the regimen that has come to be known as 7+3 for acute myeloid leukemia (AML) was born [1,2]. Cytosine arabinoside, or arabinosylcytosine as it was then called, was given as a continuous intravenous infusion of 100 mg/m(2) for 7 days, and the anthracycline, daunorubicin, was administered at 45 mg/m(2) intravenously for 3 days. Sixteen patients were originally treated on this protocol, and 5 of 8 previously untreated and 2 of 8 previously treated patients achieved a complete response (CR). This regimen has withstood the test of time. Attempts to add or substitute other agents have not yielded superior results. The only major contemporary change is that a higher dose of daunorubicin is safe and has become the standard of care [3].

Although acute leukaemia was not a principal research interest of Ernie’s, he did establish the haematopoietic stem cell transplantation programme at the City of Hope Medical Center in 1975 and recruited Karl Blume to develop it. He and Karl and other colleagues at the City of Hope published one of the early papers establishing the utility of transplantation in first remission for patients with AML [2]. Karl went on to establish the haematopoietic stem cell transplantation programme at Stanford, and his disciples have scattered throughout the land to establish or lead other transplantation programmes. Thus, according to Karl, this made Ernie the father, grandfather and great-grandfather of transplant programmes throughout the United States, a contribution integral to the interests of the attendees of this forum. It is fitting that Drs. Rowe and Tallman have named the keynote lecture in Ernie’s memory. And I am confident that Ernie would be very pleased that Joseph Bertino was the inaugural speaker, a fellow physician-scientist of distinction and accomplishment. Ernie Beutler was the quintessential physician scientist. His knowledge of genetics, biochemistry, molecular biology, nutrition, cell physiology, medicine, haematology and other fields was unparalleled and allowed him to apply his experience and keen insights into a remarkable array of human disorders. There is a German proverb, which translated states: ‘‘Much is known, but unfortunately in different heads.’’ Ernie was an exception to this adage. He had it all in one head, and he had so many other characteristics that made him a great scientist. Two that stood out were that he chose important problems, and he stayed with them. At the time of his death, Ernie was still involved with a malaria

Invasive fungal infections (IFIs) are a common problem in immunocompromised patients. Patients with leukemia, especially those undergoing stem cell transplantation, are at increased risk for IFIs, particularly invasive aspergillosis (IA). Serial monitoring with the recently approved Aspergillus galactomannan antigen test has helped to improve the diagnosis and the monitoring of treatment of IA in cancer patients. There are several new options to treat cancer patients with fungal infections. These include new antifungal agents, such as the mould-active triazoles (itraconazole, voriconazole, and posaconazole), the echinocandins (anidulafungin, caspofungin and micafungin), and the lipid formulations of amphotericin B. Immunotherapy with hematopoietic growth factors and interferon-gamma has been effective in some patients. Finally, donor-stimulated granulocyte transfusions may be useful in this patient population, but further research is required.

Despite significant improvements in survival for multiple myeloma patients through autologous stem-cell transplantation (SCT) and the introduction of novel drugs, the disease remains incurable for all but a small fraction of patients. Only allogeneic SCT is potentially curative, due in part to a graft-versus-myeloma effect. High transplant-related mortality with allogeneic SCT is currently the major limitation to wider use of this potentially curative modality. Mortality can be reduced through the use of lower-intensity conditioning regimens which allow engraftment of allogeneic stem cells, but this comes at a cost of higher rates of disease progression and relapse. Promising studies to improve outcomes of allogeneic transplants include the use of more intensive non-myeloablative conditioning regimens, tandem transplants, peripheral blood cells, graft engineering to improve the graft-versus-myeloma activity while reducing graft-versus-host disease (GVHD), post-transplant maintenance, and targeted conditioning therapies such as bone-seeking radioisotopes.

Because of the lack of a curative treatment for chronic lymphocytic leukemia (CLL) and the poor prognosis of patients refractory to the newer and more effective therapies for this disease, stem-cell transplantation (SCT) is being increasingly performed in patients with CLL. The available evidence indicates that autologous SCT may prolong survival in highly selected patients, but does not result in cure. Conversely, allogeneic SCT may cure a proportion of patients, including those who are refractory to purine-analog-based therapy or with other unfavorable risk parameters, but at the cost of high morbidity and mortality. Reduced-intensity conditioning (non-myeloablative) regimens may contribute to reducing toxic deaths while preserving the antileukemic effect of the allograft, and results are encouraging in patients with chemosensitive disease. Ongoing randomized studies will hopefully contribute to clarification of the role of SCT in the management of CLL. Meanwhile, SCT in patients with CLL should be performed only within clinical studies.

Patients with liver dysfunction have an increased risk of developing early and late complications after haematopoietic stem-cell transplantation (HSCT). That's why it is mandatory to evaluate liver status before transplantation in all cases. This evaluation should allow us to decide whether HSCT can be performed or whether we should adopt measures focused on preventing these complications. The evaluation of the liver in an HSCT candidate requires the collection of information by history-taking, physical examination, liver-function tests and, occasionally, imaging tests and liver biopsy. Additionally, as infection by hepatitis B or C viruses represents the most relevant cause of hepatic dysfunction after HSCT, the serological status of the patient should be carefully evaluated. This chapter tries to analyse and systematise the most important aspects in the patient's evaluation. Finally, as some liver dysfunctions in the stem-cell donor can have a negative impact for the donor during the harvest and/or for the recipient during HSCT, the methodology to evaluate the donors will also be analysed.