- Targeted Therapy in Lymphoproliferative Disorders (Excluding CAR T Cells)January 20, 2015
More than 70,000 new cases of non-Hodgkin lymphoma were diagnosed in the United States during the past year. Despite the introduction of rituximab nearly two decades ago, the majority of patients with lymphoma and chronic lymphocytic leukemia (CLL) who require treatment receive cytotoxic chemotherapy. Recent advances in the understanding of the pathobiology of B-cell lymphoproliferative disorders have led to the identification of multiple therapeutic targets and the development of rational novel agents.
- CAR T Cells in Acute Lymphoblastic LeukemiaJanuary 13, 2015
After decades of work, the last two to three years have brought about a successful translation of basic immunology that gave rise to two promising strategies to modify the immune system to treat cancer. One approach involves antibodies targeting immune checkpoints, CTLA-4 and PD-1, to release the brake on T cells to attack tumor cells. Another strategy involves infusion of T cells genetically modified to express a chimeric antigen receptor (CAR) to target a specific tumor antigen.
- Erythroferrone: A Missing Link in Iron RegulationJanuary 13, 2015 | Mark J. Koury, MD
Among the most important discoveries for hematologists in 2014 is the report of Dr. Leon Kautz and colleagues, from the laboratory of Dr. Tomas Ganz, that identified erythroferrone (ERFE) as a hormone produced by erythroblasts that suppresses hepcidin transcription in the liver.
- Gene Therapy for Blood DisordersJanuary 13, 2015 | Pamela S. Becker, MD, PhD
Based largely on vector innovation, gene therapy for hematologic disorders has advanced tremendously in the past decade, with 2014 witnessing sustained improvement in selected inherited diseases.
- Meta-analysis of Bleeding Complications with Direct Oral AnticoagulantsJanuary 13, 2015 | David Garcia, MD
Looking back at 2014, several published articles related to nonmalignant
hematology were significant because of their potential to influence
clinical practice. Leading the way is the report by Dr. Chatree
Chai-Adisaksopha and colleagues, “The Impact of Bleeding Complications
in Patients Receiving Target-Specific Oral Anticoagulants: A Systematic
Review and Meta-Analysis.”
- Myeloma Highlights of 2014January 13, 2015 | A. Keith Stewart, MB, ChB
A number of publications from 2014 that impact our understanding and treatment of multiple myeloma (MM) stand out. First, insights into the mechanism of action of thalidomide and its analogues came fast and frequently. With more direct therapeutic relevance, the results of the Phase III ASPIRE clinical trial were published. This trial tested the hypothesis that three drugs would be better than two in relapsed MM. Finally, a randomized trial reconfirmed the role of transplantation in MM patients younger than 65 years.
- Pre-Leukemic Hematopoietic Stem Cells in Human Acute Myeloid LeukemiaJanuary 13, 2015 | Ravindra Majeti, MD, PhD
Patients with de novo acute myeloid leukemia (AML) typically come to clinical attention with symptoms of bone marrow failure in the absence of any prior hematologic condition. In many such patients, the diagnosis is sudden and unexpected, without any significant prodrome. The generally poor prognosis of AML and the decades-long impasse in generating effective therapeutic strategies other than conventional antracycline and cytarabine-based (“3+7”) induction chemotherapy has spurred intense investigation of its molecular and cellular origins. Pioneering work by numerous investigators led to an early understanding of the genetics of AML, particularly the identification of recurrent chromosomal abnormalities and mutations in the genes FLT3 and NPM1. However, it is only with the recent implementation of massively parallel next-generation DNA sequencing that the full spectrum of mutations in AML has been defined.
- The Year's Best in Sickle Cell Disease (2014)January 09, 2015 | Charles T. Quinn, MD, MS
Among the most important clinical advances for hematologists in 2014,
especially those who care for patients with sickle cell disease, is the report by Dr.
Michael DeBaun and colleagues of the results of the Silent Cerebral Infarct Transfusion Trial (SIT Trial).
- Long-Acting Factor Concentrates for Hemophilia January 08, 2015 | Adam Cuker, MD, MS
Regular prophylactic factor infusion reduces bleeding, improves joint
health, and has become standard of care in the management of patients
with severe hemophilia A and B. However, the inconvenience of frequent
intravenous administration is an important source of patient
dissatisfaction and nonadherence. Most patients must infuse two to three
times weekly to maintain hemostatic trough levels due to the relatively
short half-lives of factor VIII (~12 hours) and factor IX (~20 hours).
The arrival of long-acting factor concentrate has been anxiously
anticipated as a means of enhancing the convenience of, and adherence
to, therapy. In 2014, long-acting factor IX concentrate arrived.
- Mutation of the Calreticulin (CALR) Gene in Myeloproliferative NeoplasmsJanuary 08, 2015 | Jason Gotlib, MD, MS
The discovery of mutations in exon 9 of the calreticulin (CALR) gene in the majority of cases of JAK2 wild-type essential thrombocythemia (ET) and primary myelofibrosis (PMF) came out of left field. This
breakthrough dominated the landscape of myeloproliferative neoplasms
(MPN) in 2014 and imbued investigators with a similar scholarly frenzy
that followed the identification of JAK2 V617F in 2005.
- The Year's Best in Hematology 2014: Looking Backward, Moving ForwardJanuary 08, 2015 | Jason Gotlib, MD, MS
Dr. Jason Gotlib, Editor-in-Chief of The Hematologist, discusses the “Year’s Best” review of 2014 in the January/February 2015 issue of The Hematologist.