Highlights of Our Program

LOCATION/AFFILIATION

MIRT is part of the University of Arkansas for Medical Sciences (UAMS) in Little Rock, Arkansas. It is closely affiliated with the Winthrop P. Rockefeller Cancer Institute, also at UAMS.

MISSION

Since its inception in 1989 and under Dr. Bart Barlogie’s leadership, MIRT’s goal has been to unravel the genetics and biology of multiple myeloma and to develop curative therapies.

ACCOMPLISHMENTS

MIRT’s myeloma program has served more than 7,400 patients afflicted with myeloma and related disorders (MGUS, plasmacytoma, Amyloidosis, Waldenstrom’s Macroglobulinemia, Castleman’s Disease).  Each year MIRT evaluates 600 new patients, 70% of whom come from outside the State of Arkansas, from all over the United States and from abroad.

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MIRT’s program distinguishes itself by its primary focus on one disease family and its pursuit of the most appropriate therapies, ranging from monoclonal antibody treatment for Castleman’s and Waldenstrom’s, to high-dose therapy with autologous or allogeneic transplantation for myeloma, and novel agents for advanced and high-risk disease.

These treatments are administered within the context of the most refined diagnostic tools in radiologic imaging (MRI, PET-CT)and in molecular genetics profiling (DNA micro-array, interphase FISH, PCR for residual disease).

MIRT-affiliated support services in Radiology, Pathology, Stem Cell Apheresis, Immunology, Orthopedics, Neurology, Neurosurgery, Nephrology, Endocrinology and Cardiology assure that even the most complex clinical scenario can be managed by myeloma-interested and myeloma-knowledgeable experts.

See PowerPoint Presentation.

SURVIVAL RATES

For newly diagnosed multiple myeloma patients between 1995 and 2001, the National Cancer Institute reports through its SEER program (http://seer.cancer.gov/), that 34 percent of such patients lived at least five years. At the Myeloma Institute for Research and Therapy, for the same time period, 57 percent of our newly diagnosed patients lived five years or more. Five-year survival rates at the Myeloma Institute are now greater than 65 percent.

DISTINGUISHING CHARACTERISTICS

1. Enormous patient data base with long-term follow-up and instantaneous access to outcome data in the context of unique patient characteristics, so that every new patient’s prognosis can be forecast based on actual treatment data.

2. Identification of myeloma subgroups, especially via genetic tools such as gene expression profiling, using random bone marrow samples obtained from the pelvic bone and also from focal tumors identified by MRI or PET, with the purpose of "identifying the enemy".

3. Closely monitored follow-up of patients when away from Arkansas, through mailed-in samples for myeloma protein analysis, by a dedicated team of “phone nurses”.

4. Comprehensive discussion of all newly referred patients and patients with ongoing treatment challenges with the entire health care team, including most senior faculty.

5. Weekly research/clinical conferences to interpret success/failure of ongoing programs and identify the most promising research/treatment avenues for high risk patients.

6. Warm, loving care provided by a dedicated nursing team with 10 to 15 years of myeloma management experience.

POINTS OF INTEREST

1. MIRT sees more patients with myeloma and related diseases per year than any other institution in the world.

2. On any given day there are 173 myeloma patients staying in Little Rock for diagnosis and treatment of their disease.

3. The number of faculty immediately involved in myeloma diagnosis and therapy at MIRT is higher than at any other facility in the world.  They have in-depth knowledge and unprecedented expertise in the management of myeloma.

4. Over 1,000 patients participated in clinical trials in Fiscal Year 2007.  Clinical trial participation at MIRT is higher than at other facilities.

5. MIRT performs significant numbers of diagnostic tests annually for myeloma patients.

Fiscal Year 2007 numbers

# of MRIs                          3,888

# of PETs                          3,738

# of Bone Marrows          5,168

# of Cytogenetics              5,476

6. MIRT is the only facility in the world that routinely offers gene array analysis for every newly referred patient and utilizes this information for patient management.

7. In Fiscal Year 2007, MIRT performed more stem cell transplants overall (633) and for myeloma in particular (569) than any other facility.

8. MIRT patients always have plenty of back-up frozen stem cells for future transplants.

9. In addition to tandem transplants, MIRT has performed more “third” (287) and “fourth” (24) transplants than any other institution.

10. MIRT has detailed long term follow-up on 6,744 patients with myeloma.  This is a larger patient population than at any other facility.  Length of follow-up ranges from 1 to 290 months, with a median of 36 months.

11. MIRT has followed 402 patients for more than 10 years.  Of these 402 patients, 296 have never experienced a relapse.

12. MIRT has a comprehensive data base on 6,744 patients with myeloma and related diseases.  Detailed baseline and follow-up information on 14,000 parameters and event-free and live/expired status is unsurpassed and is used effectively to model new patients’ predicted outcome.

13. MIRT is the only facility that has a dedicated supportive care service that monitors all inpatients and outpatients on a daily basis.

14. MIRT performs blood draws on patients in local hotels to maximize their comfort and provide greater convenience.

MIRT is the only facility in the world that routinely offers gene array analysis for newly referred patients and utilizes this information for patient management and planning of therapy.

The Myeloma Institute performs multiple gene arrays on every patient enrolled on a clinical protocol

Based on a study of  more than 500 newly diagnosed patients treated at the Myeloma Institute for multiple myeloma, MIRT researchers found that the expression of just 17 genes (out of the 25,000 genes in the human body) revealed which form of myeloma a patient had.  The expression level of those 17 genes serves as a powerful predictor of response to therapy.

This enables doctors to more accurately predict which patients  will not respond to standard therapy and thereby spare patients from undergoing treatments that will not be effective.  The discovery is also important to the development of new treatments that specifically target the 17 genes.

Complete findings are reported in plenary paper published in Blood.

Blood, 15 March 2007, Vol. 109, No. 6, pp. 2276-2284

A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1

Summary of Abstract

To molecularly define high-risk disease, Dr. Shaughnessy’s group performed microarray analysis on tumor cells from 532 newly diagnosed patients with multiple myeloma.

Seventy genes were found to be linked to early disease-related death.
Importantly, most up-regulated genes mapped to chromosome 1q, and down-regulated genes mapped to chromosome 1p. The ratio of mean expression levels of up-regulated to down-regulated genes defined a high-risk score present in 13% of patients with shorter durations of complete remission, event-free survival, and overall survival.
Shaughnessy’s data suggest that altered transcriptional regulation of genes mapping to chromosome 1 may contribute to disease progression, and that expression profiling can be used to identify high-risk disease and guide therapeutic interventions
A central hypothesis of the work presented in this paper was that expression extremes of a subset of genes correlating with survival might be representative of the effects of DNA copy changes in myeloma disease progression. Shaughnessy and colleagues were thus able to identify a set of 70 genes, the expression levels of which permitted the identification of a small cohort of 13% to 14% of patients at high risk for early disease-related death.
The marked increase in the frequency of high-risk designation from 13% at diagnosis to 76% at relapse provides molecular evidence of disease evolution that influences postrelapse outcome. With further refinement of the model, Shaughnessy expects to develop tools for quantitative risk assessment during the entire course of therapeutic management.
The findings may also shed important light on the underlying molecular mechanisms that drive disease progression.  This has the potential to translate into clinical applications that slow down or prevent disease progression. 
Through multivariate discriminant analyses, Shaughnessy found that of the original 70 genes, 17 probe sets could be used to detect high-risk myeloma. Assessment of the expression levels of these genes may provide a simple and powerful molecular-based prognostic test that would eliminate the need for testing many of the standard variables currently in use with limited prognostic implications. If these gene signatures are unique to myeloma tumor cells, such a test may be useful after treatment to assess minimal residual disease, possibly using peripheral blood as a sample source.

Click here for a list of representative publications.

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