International Journal of Hematologic Oncology最新文献

Donna E Reece speaks to Laura Dormer, Commissioning Editor: Dr Donna E Reece is a Professor of Medicine and Director of the Program for Multiple Myeloma and Related Diseases in the Department of Medical Oncology and Hematology at Princess Margaret Hospital/University of Toronto. She earned a Bachelor of Arts degree at the University of Texas, Austin, and graduated as valedictorian with a medical degree from Baylor College of Medicine, Houston, Texas. She completed an internship in Internal Medicine at the University of Colorado Affiliated Hospitals, a residency and Chief Residency in Internal Medicine at Jewish Hospital, St Louis, and a Fellowship in Hematology/Oncology at Barnes Hospital, Washington University, St Louis, Missouri. She was a fellow and later a leukemia/stem cell transplant staff physician at Vancouver General Hospital/University of British Columbia for over 10 years. She then served as Director of the Outpatient Leukemia/Stem Cell Transplant Program, and later interim director, of the Blood and Marrow Transplant Program of the Markey Cancer Center at the University of Kentucky, Lexington, Kentucky until her appointment to Princess Margaret Hospital in Toronto in 2001. Dr Reece received the David and Molly Bloom Chair in Myeloma Research in 2009. She is currently the co-chair of the Multiple Myeloma Clinical Trials Group of the National Cancer Institute of Canada, member of the Scientific Advisory Board of the International Myeloma Foundation, and member of the Project Review Committee of the MMRC (Multiple Myeloma Research Consortium). She is also the Chief Medical Officer of the Myeloma Canada Research Network and serves on the board of directors of Myeloma Canada. Her career focus has been in the areas of hematopoietic stem cell transplantation, lymphoid malignancies and plasma cell dyscrasias. She has published numerous articles in these areas.

Aim: To assess the 5-year healthcare resource utilization (HRU) and direct payer costs following allogeneic hematopoietic stem cell transplants (HSCTs) in acute lymphoblastic leukemia pediatric patients using data from two large US administrative databases.

Patients & methods: Among the 209 patients with acute lymphoblastic leukemia, HRU and costs were described over the up to 5 years after the HSCT.

Results: HRU and costs following the HSCTs were substantial. The highest average costs and most intensive HRU were observed within the first year following the HSCTs (49 outpatient visits; 29 laboratory service visits; 68 inpatient days), with a first year cost of US$683,099 and substantial costs over the following years.

Conclusion: HRU and direct costs associated with allogeneic HSCTs are substantial.

Limited data are available on the treatment of older adults with cancer. Comorbidities may preclude the administration of effective therapies, particularly in the extreme elderly. Comprehensive geriatric assessment can identify specific weaknesses of the patient and predict unexpected toxicities, thus enabling an optimized treatment strategy in this population. We report a case of the successful management of a 99-year-old female lymphoma patient with a strong wish for active treatment to improve quality of life and prolong survival past her 100th birthday. This case demonstrates that cancer treatment in the extreme elderly is possible and highlights the need for a formalized treatment plan based on geriatric assessment, frank discussion with patients and families, and defined goals of therapy.

The outcome of adult patients with Philadelphia chromosome-positive (Ph⁺) acute lymphoblastic leukemia (ALL) has improved substantially with the introduction of tyrosine kinase inhibitors (TKIs). TKIs are now integral components of therapy for Ph⁺ ALL. The current consensus is that they improve patient outcomes compared with historical control patients treated with chemotherapy alone, and increase the number of patients able to receive stem cell transplant. New challenges have emerged with respect to induction of resistance mainly via Abelson tyrosine kinase mutations. Several novel kinase inhibitors with significantly more potent antileukemic activity are currently being developed. Furthermore novel immune therapies, which recruit or modify patient's own T cells to fight leukemic cells, are being developed and could find an important place in Ph⁺ ALL therapy by few years. In this article, we reviewed treatment approaches in adults with Ph⁺ ALL with a focus on TKIs and combined chemotherapy regimens.

l-asparaginase, an enzyme originally derived from Escherichia coli, represents a major drug in the treatment of acute lymphoblastic leukemia. However, the occurrence of major adverse effects often leads to early withdrawal of the enzyme. Main side effects include immune-allergic reactions, coagulopathy, pancreatitis and hepatic disorders. Novel asparaginase formulations and alternative sources have been developed to address this issue, but the results were not totally satisfactory. l-asparaginase loaded red blood cells (RBCs; GRASPA) represent a new asparaginase presentation with reduced immunological adverse reactions. RBCs protect l-asparaginase, enhance its half-life and reduce the occurrence of adverse events. We reviewed the history, biology and clinical experiences with l-asparaginase, and the characteristics and first clinical experiences with GRASPA in the treatment of acute leukemia.

B-lymphocytes are dependent on B-cell receptor (BCR) signaling for the constant maintenance of their physiological function, and in many B-cell malignancies this signaling pathway is prone to aberrant activation. This understanding has led to an ever-increasing interest in the signaling networks activated following ligation of the BCR in both normal and malignant cells, and has been critical in establishing an array of small molecule inhibitors targeting BCR-induced signaling. By dissecting how different malignancies signal through BCR, researchers are contributing to the design of more customized therapeutics which have greater efficacy and lower toxicity than previous therapies. This allows clinicians access to an array of approaches to best treat patients whose malignancies have BCR signaling as a driver of pathogenesis.

High-dose melphalan has been the drug of choice for preparative regimens for autologous stem cell transplantation in multiple myeloma. Propylene-free melphalan (Evomela™) is a newer formulation of melphalan, which incorporates Captisol^® to produce a stable product upon reconstitution. In addition to avoiding propylene glycol with its' potential side effects, this approach improves the overall stability of reconstituted melphalan and can ensure intended dose delivery. In this paper, we review the published literature regarding this formulation. We focus on its' chemistry, pharmacokinetics and clinically available data for its use in myeloma autologous stem cell transplantation setting.

Aim: Circulating cell free (ccf) DNA contains information about mutations affecting chronic lymphocytic leukemia (CLL). The complexity of isolating DNA from plasma inhibits the development of point-of-care diagnostics. Here, we introduce an electrokinetic method that enables rapid recovery of DNA from plasma.

Materials & methods: ccf-DNA was isolated from 25 µl of CLL plasma using dielectrophoresis. The DNA was used for PCR amplification, sequencing and analysis.

Results: The ccf-DNA collected from plasma of 5 CLL patients revealed identical mutations to those previously identified by extracting DNA from CLL cells from the same patients.

Conclusion: Rapid dielectrophoresis isolation of ccf-DNA directly from plasma provides sufficient amounts of DNA to use for identification of point mutations in genes associated with CLL progression.