Abstract
Friends, colleagues, readers of Therapeutic Advances in Hematology,
Welcome to the first issue of 2013 for the journal! With the New Year we bring you much wisdom and guidance from this month’s submissions. As well we continue to have plans and expectations for Therapeutic Advances for 2013 and hope to continue to peak your interest and encourage you to consider submission of original articles or review/summary pieces for consideration. The journal is ours to shape and populate, all of us committed to the advance of therapy for all hematologic disorders, benign and malignant, so please do not hesitate to contact me or the editorial team. Enjoy!
We begin this issue with a review of clofarabine and its place in the treatment of AML in older adults, from S. Tiley of East Carolina University in South Carolina and D. Claxon from Hershey Cancer Institute, Pennsylvania. They walk us through the trials of clofarabine alone, in combination (eg with LDAC) and conclude this ‘second-generation’ purine nucleoside analogue performs well with comparable induction response and lower toxicity versus 7+3, in trials including patients of older age, significant comorbidites and poor risk cytogenetics. This is followed by a very comprehensive overview of JAK inhibitors in myeloproliferative neoplasms, a disease group near and dear to my own interests, from R. Tiu and colleagues of the Taussig Cancer Institute, Cleveland Clinic. Starting with an overview of the JAK-STAT signaling changes currently understood, the array of mutations in JAK, MPL, and LNK are summarized. A full summary of clinical trial data for not only ruxolitinib but for all available JAK inhibitors is then presented to use with comparative data on spleen reduction included; a primer on JAK inhibition in MPNs for 2013 indeed!
We then move on to a very enlightening description of the current and potential role of serum free light chain measurement in B-cell neoplasms from P. Tosi and others from Infermi Hospital, Rimini, Italy. They describe the diagnostic approach to myeloma and related diseases with focus on atypical forms not producing monoclonal immunoglobulin (M protein). As a broadly detectable and correlative marker the free light chain assay (sFLC) and its development, including current use in nonsecretory/oligosecretory states, ‘pre-myeloma’ state, and in myeloma kidney disease are summarized. The prognostic value of sFLC in all of the B-cell neoplasms and other disease states such as HIV are described, with the conclusion that this assay may have broad clinical use, be less burdensome then timed urine collections and may be a better diagnostic and prognostic tool.
We then continue in the area of improving diagnostic acumen with a paper from K. Dunleavy and colleagues from the National Cancer Institute in Bethesda, Maryland, unravelling the group of diffuse large B-cell lymphoma (DLBCL) based on molecular subtyping. The group describes what now may be three distinct groups within the category of DLBCL: a germinal center B-cell like type (GCB), an activated B-cell like type (ABC) and a primary mediastinal B-Cell lymphoma type (PMBL). Microarray and response data are presented and juxtaposed for the groups, showing the clear differences. ‘Targetable’ differences are then described, such as chronic B-cell receptor activation and moreover NF-kB in ABC type; bcl-6 in GCB type; BCL-2 and MYC in both ABC and GBC type; and the potential for Jak inhibition for PMBL type. With the emergence of novel targeted therapies useful in DLBCL such as ibrutinib, such understanding and further classification in this disease group will be paramount.
We close the issue with a review of hemophilia A and factor VIII inhibitors from C. Witmer from the Children’s Hospital of Philadelphia and G. Young from the Children’s Hospital Los Angeles / USC Keck School of Medicine. Starting with defining and identifying an inhibitor, they then review the epidemiology and presentation as well as risk factors for development of factor VIII inhibitors. The treatment related risk of inhibitor development and risk-stratification of patients with inhibitors is then covered, followed by review of immune tolerance induction. They close with sage advice on using the proper bypass product to overcome inhibitor effect and novel approaches to immune tolerance, including less antigenic replacement products and immune modulation of inhibitor patients.
As always, enjoy!