On the forefront of hematology research, Mayo Clinic has contributed to the body of knowledge across the spectrum of hematologic malignancies and related disorders. Some advances that have been made include those listed below.
Mayo has shown that chemotherapy with high-dose melphalan followed by peripheral stem cell support is surprisingly effective in amyloidosis patients who are deemed eligible for the rigors of this high dose approach. Prior to that, Mayo Clinic trials showed that simple oral melphalan and prednisone, long known to be effective in myeloma, is the standard, and it still is for patients who cannot undergo the rigors of high-dose melphalan therapy.
Mayo Clinic hematologists joined together to publish consensus guidelines on a number of areas, including: recommendations for the definition of "high-risk multiple myeloma," guidelines for the use of bisphosphonates in treating patients with multiple myeloma, and treatment options based on risk stratification (branded as mSMART). These guidelines arose as a consequence of the translational research and clinical trials conducted by Hematologic Malignancies Program members.
Lymphocytic Leukemia, Chronic Lymphoproliferative Diseases
Mayo investigators defined a novel gene expression signature that differentiates chronic lymphomatic leukemia (CLL) B-cells from normal B-lymphocytes.
Mayo Clinic researchers have made important epidemiological connections between the risk of older women developing lymphoma and alcohol consumption, menstrual history, postmenopausal hormone therapy and previous blood transfusions. Mayo Clinic investigators pioneered radioactive monoclonal antibody therapy to specifically target and kill lymphoma cells. This therapy gives patients with lymphoma greater hope for survival.
Monoclonal Gammopathy of Undetermined Significance (MGUS), Smoldering Multiple Myeloma
Robert Kyle, M.D. and other researchers from Mayo Clinic discovered two significant hematologic entities, monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). MGUS and SMM are asymptomatic, pre-malignant blood disorders characterized by monoclonal plasma cell proliferation in the bone marrow and absence of end-organ damage such as osteolytic bone lesions, anemia, or renal failure. Both MGUS and SMM can progress to multiple myeloma, and Mayo Clinic researchers have continued to make strides in better defining these disorders and finding ways to combat that progression.
Mayo Clinic established that multiple myeloma is not one disease but a group of diseases, and treatment needs to be tailored to the specific underlying genetic and genomic aberrations.
Mayo also conclusively showed that monoclonal gammopathy of undetermined significance (MGUS) is in many cases an early form of myeloma, and progression of the disease is linked to the level of abnormal protein in the blood.
A Mayo clinical trial proved that the combination of the drugs thalidomide and dexamethasone is safe and effective as an initial treatment and still allows the safe harvesting of stem cells for transplant.
Non-Hodgkin Lymphoma (NHL) incidence and mortality rates have increased over the past 50 years, and these trends are largely unexplained. The five-year survival rates were approximately 50 percent during most of this time, and have only recently begun to improve. At present, we cannot accurately predict who will and will not do well after their NHL diagnosis. This study will ask the question of whether survival is in part determined by background genetic variation in immune function and metabolism of agents used to treat lymphoma patients. Mayo researchers are hopeful that identifying these genetic patterns will accomplish two goals: 1) help physicians decide which treatments a patient is most likely to respond to best, with minimal side effects; and 2) help researchers identify new drug targets for treatment.
In Project #5, Mayo investigators proposed to systematically test hypotheses that genetic differences (polymorphisms) related to immune function and regulation and to the metabolism and function of specific anti-cancer drugs may affect survival rates for NHL and a closely related cancer called chronic lymphocytic leukemia (CLL).
Specific aims were:
To test these hypotheses, the project is enrolling all newly diagnosed NHL and CLL patients seen at Mayo Clinic Rochester or University of Iowa within nine months of their diagnosis. The researchers are collecting blood (for DNA), treatment data, and other clinical and laboratory factors, and are following all patients after diagnosis in order to identify clinical outcomes. Genetic variability (polymorphisms) within the selected genes will be identified using the Mayo Clinic Cancer Center Genotyping Shared Resource. The results of the genotyping are then linked to treatment and outcome data to see if we can predict who has a better outcome after accounting for disease and treatment differences. The researchers completed the first round of genotyping in 2007, and should have early results in mid 2008.
As part of the SPORE renewal in 2007, this project became the Molecular Epidemiology Resource (MER), and is a core resource available to SPORE researchers. Through 2007, 2,450 participants have enrolled into the MER, 1,842 from Mayo Clinic and 608 from the University of Iowa. Some of the participants will be reaching their six-year follow-up in the summer of 2008.
The three most recent grants funded that use the MER:
Biology and Epidemiology of BLyS and APRIL in Follicular Lymphoma
Genetic Predictors of Prognosis in Mantle Cell Lymphoma
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