About Lymphoma | Advocacy | Art | CAM | Clinical trials | Doctors - Experts - Centers | Guidelines at Diagnosis | News
Risk Factors | Side Effects | Statistics | Support | Symptoms | Tests | Treatments | Types of Lymphoma

Search Site         Guidelines at Diagnosis | About Clinical Trials            How to Help!

Patients Against Lymphoma

 

AdvocacySnap Freezing Lymphoid Tissue

Last update: 08/19/2012

TOPICS
Overview  | Objectives | Rationale | About snap freezing |
Proposed actions References | Resources

Before you have the biopsy to determine if you have a lymphoma or to evaluate tissue to see if you've had a relapse, contact your surgeon or oncologist and specify that you want a portion of the extra tissue snap frozen using CLIA standards

bullet

to determine if you are eligible for a clinical trial (now or in the future)
testing an agent that targets a pathway that might be present in the tumor)

bullet

to produce a patient-specific cancer vaccine, should one of the three 
vaccines coming up for approval within the year wins approval.

bullet

to do advanced diagnostics, to determine if you have high or low risk lymphoma 
(or as control tissue if negative for lymphoma!)

bullet

to determine your eligibility to use approved targeted agents in future.

NOTE: Keep in mind that having your tissue stored in this way is unlikely to provide clinical benefit.  Clinical use of the tissue (such as to guide medical decisions) may depend on which studies utilize the tissue ... such as if the tissue is used to guide patient selection in a therapeutic trial or not. The general expectation is that the insights from the use of biospecimen in clinical trials will take many years to become useful in clinical practice. 

That said, we do think this is wise practice, even if the potential for you to benefit clinically seems small at this time. Further, such centers will likely have higher levels of expertise in the diagnosis of lymphoma.

WHERE / HOW can I have this done?

bullet
One way: Participate in the Genome Expression Study 
(highly recommended when it's time for a biopsy)

Rationale: The observed variability in the clinical course of follicular lymphoma, along with 
the diverse range of therapeutic options available, necessitates accurate prognostic 
stratification of the individual patient.


Conditions: Lymphoma; Leukemia; Multiple Myeloma; Lymphoid Malignancies

Locations: 
  
Nebraska Medical Center in Omaha,  
  Southwest Oncology Group centers- see for MANY centers in USA: swog.org 
  the British Columbia Cancer Agency in Vancouver, Canada; 
  the Norwegian Radium Hospital in Oslo, Norway; 
  the University of Würzburg in Würzburg, Germany; 
  the University of Barcelona in Barcelona, Spain; and 
  St. Bartholomew's Hospital in London, England.


Background:  The Leukemia and Lymphoma Molecular Profiling Project (LLMPP), 
a collaboration of researchers in the United States, Canada, and Europe NCI investigators 
are working with researchers at the University of Nebraska Medical Center in Omaha 
to define the gene expression profiles of all types of human lymphoid malignancies. 

The project is supported by an international collaboration ...  The LLMPP uses 
"Lymphochip" cDNA (complementary DNA) microarrays, which are enriched in genes 
that are expressed in and/or function in lymphocytes. Lymphochip microarrays allow 
measurement of the RNA expression levels of the represented genes. Gene expression 
profiles developed as a result of this project may someday be used for disease classification
 (diagnosis), prognosis, and therapy selection. Already, results from the LLMPP indicate 
that these profiles can improve diagnostic accuracy and provide prognostic information. 

The LLMPP is initiating a multicenter clinical trial to evaluate a lymphoma diagnostic chip, 
called LymphDX, which was designed by the company Affymetrix in collaboration with 
NCI researchers using LLMPP data. The study will demonstrate the feasibility of 
disseminating the LymphDX microarray technology to all of the participating sites and 
will also evaluate the diagnostic utility of the LymphDX chip in a prospective study.
Source: cancer.gov  

IMPORTANT:  Be sure to request a CLIA Certified Laboratory  - "defined as clinical diagnostic laboratories certified by the DHHS Health Care Financing Administration ... as revised by the Clinical Laboratory Improvement Amendments (CLIA)". http://ohsr.od.nih.gov/info/sheet17.html 

Also see Rationale, below. 


Centers that are more likely to snap freeze tissue at biopsy:

bullet
See The Cooperative Human Tissue Network  
bullet
See NCI-designated cancer centers - Cancer.gov  (in state order. Scroll down to list)
bullet
SWOG centers in USA: swog.org 
bullet
Locate CLIA accredited laboratories by state:  cms.hhs.gov  pdf 
bullet
Locations participating in LLMPP:
  
Nebraska Medical Center in Omaha,
   
Southwest Oncology Group centers- see for MANY centers in USA: swog.org 
 
the British Columbia Cancer Agency in Vancouver, Canada; 
 
the Norwegian Radium Hospital in Oslo, Norway; 
 
the University of Würzburg in Würzburg, Germany; 
 
the University of Barcelona in Barcelona, Spain; 
 
St. Bartholomew's Hospital in London, England.

Send comments by clicking here


Objectives 

bullet Advocate for the routine snap freezing of lymphoid tissue at each patient biopsy.
 
Provide the rationale and notification of expectation to: 
 
bullet

treating physicians who refer patients for biopsies, 

bullet

clinical investigators and scientists who can advise us about where to put our efforts.

bullet

cancer centers that must store the tissue, or package and ship the tissue elsewhere,

bullet

surgeons who perform the procedures,

bullet

pathologists who first receive the tissue,

bullet

and the public who must inquire and know what to ask for when scheduled for lymphoid tissue biopsies. 

We will develop and distribute educational material so that the public and our representatives can understand the potential of this technology and the need to fund and support it. 

bullet Identify research centers that will receive the tissue, or perform genetic testing on it.
  
bullet Identify methods to safeguard the privacy of patients who donate lymphoid tissue and provide clinical history.
  
bullet Identify and provide incentives for patients to donate lymphoid tissue and provide clinical history.
  
bullet Advocate for the creation of a centralized lymphoid tissue data bank at the NCI that will receive and evaluate tissue from outside sources.
  
bullet Advocate for open access to tissue and related data to help advance clinical progress.


Rationale 

The reasons to routinely snap freeze and store lymphoid  tissue at biopsies so that the tissue can be profiled at a genetic level are numerous and compelling:

bullet Enables scientist to more rapidly identify the gene expressions that distinguish normal from malignant cells and assist in the "development of molecularly targeted therapies that have specificity and potency for defined cancer types." 4
   
bullet Enables scientists to link clinical behavior (how aggressive or indolent the cancer is likely to be ) to gene expression, and thus better advise patients about treatment selection and timing. Currently, the variable clinical course of patients given the same diagnosis stems, in part, from the underlying molecular diversity among their tumors. 4
  
bullet Enables identification of viral factors that may be present and may contribute to causing, promoting, or maintaining malignant behavior of lymphoma cells.
  
bullet Enables scientists to discover how genes function in immune cells and apply to the treatment of numerous diseases.
  
bullet Enables retrospective testing to correlate genetic expression with individual responses to treatments. The potential benefits will enable doctors or researchers to:
 
bullet select treatments that are far more likely to benefit the patients
bullet spare patients from the side effects of ineffective treatments
bullet identify patients in need of experimental approaches to treatment 1
bullet reduce health costs by enabling rational treatment selection, instead of by wasteful trial and error
bullet identify genes in tumors that lead to treatment resistance
bullet select patients most likely to benefit from investigational drugs in clinical trials

“Presently we are overlooking effective treatments for some people, while administering ineffective and toxic treatments to others based on studies conducted with ill-defined aggregates of patients.” – DF.
 
  

bullet Multiple samples from the same patient, 
 
bullet enable the identification of changes to gene expression and other tumor characteristics in response to treatments and over time.
bullet enable the identification of changes to gene expression and other tumor characteristics that correlate to refractory disease, or transformation to aggressive disease, or the lack thereof.
   
bullet Enable identification of tumor-associated antigens that can form the basis for therapeutic cancer vaccines.
   
bullet Enable discovery of cells in the lymphoid microenvironment that may be promoting or inhibiting lymphomas.
   
bullet Enable production of patient-specific therapeutics, such as cancer vaccines or therapeutic antibodies.

“The inadequacy of the current diagnostic methods is evident in the heterogeneous treatment responses of cancer patients within a diagnostic category. The importance of establishing a new molecular diagnosis of cancer is two fold. First, the assignment of cancer patients to molecularly diagnostic categories will often provide prognostic information that can guide patients to the most appropriate treatments. Second, a molecular diagnosis of cancer provides a detailed blue print of the abnormal  molecular circuitry of the cancer cell, which will lead to the development  of molecularly targeted therapies that have specificity and potency for defined cancer types.” – Louis M. Staudt, Annu.Rev.Med.2002.53:303–18


Snap-freezing of lymphoid tissue at biopsies

At the time of biopsy a portion of the tumor removed by surgery – not used for histology testing – can be snap frozen in liquid nitrogen and stored at -80 C degrees for later processing (DNA or RNA extraction). Storing the material is very simple. It only takes a few seconds or minutes. In short, it is required to have liquid nitrogen at the local were the biopsy is being done. All hospitals have liquid nitrogen, which is not expensive.  

Immediately after removing the tissue, it has to be introduced into a tube and then into liquid nitrogen. After that the tubes can be securely transported to an -80 C degrees freezer.  We estimate that the cost of the initial storing of the material in the freezer will be modest.

IMPORTANT:  Be sure to request a “CLIA Certified Laboratories”  - "defined as clinical diagnostic laboratories certified by the DHHS Health Care Financing Administration ... as revised by the Clinical Laboratory Improvement Amendments (CLIA)". http://ohsr.od.nih.gov/info/sheet17.html 

 


Notification of Expectation

For Patients: How to inquire and what to ask for when scheduled for lymphoid tissue biopsies.

How will extra tissue be stored at this center?

Will it be snap frozen?

Will it be accessible for research, including clinical research I may participate in later?

May I review your consent document on the use and storage of extra biospecimen?

"If so, I would like to have the lymphoid tissue taken at my biopsy snap frozen so that DNA analysis can be done, and so that I have the option to use a portion of it for therapeutic purposes in future, such as identifying molecular targets that may be targeted by recently approved or investigational therapies, or for making a tumor-specific cancer vaccine.

For Treating Physicians, Surgeons, and Hospital Centers

We believe that the benefits of participating in this program will far exceed the costs, which we estimate to be approximately $?? per patient.  Costs are probably modest and relate to storage and supervision of tissue.

History tells us that difficult problems can only be solved only by taking proactive steps, and by coordinating our efforts.  

The potential benefits of this program are twofold: It can potentially help patients living with the disease today, and it will help future patients by assisting in advancing the science.


References:

[1] Rosenwald, et al., The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jun 20;346(25):1937-47. - PubMed | Related abstracts

[2] Specific Gene Patterns Linked to Treatment with EGFR Drugs,  Cedars-Sinai Medical Center 3-Jun-03  - Abstract 763, ASCO

[3] Clinical translation of gene expression profiling in lymphomas and leukemias. Semin Oncol. 2002 Jun;29(3):258-63. Review. PMID: 12063678 - PubMed

[4] Staudt, Gene Expression Profiling of Lymphoid Malignancies -  Annu.Rev.Med.2002.53:303–18 - PubMed


Resources: 

  • Molecular Targeting in the Treatment of Cancer: An Interview With Brian Druker, MD - Medscape (free login req.)
  • Molecular Diagnosis of the Hematologic Cancers, Staudt - NEJM May 1, 2003
  • Hematological Tumor Profiling, Kris Novak, PhD Clinical Editor: Sara M Mariani, MD, PhD - Medscape
  • Clinical pharmacology - mja.com.au
  • DNA arrays diagnose, predict survival for Sezary syndrome cancer patients - 
    New technology validated, dozens of potential drug targets identified - Eurekalert.org Jun_03
  • Bioinformatics and microarray gene expression profiles -  PDF 
  • The LymphoChip - Staudt Lab 
  • Application of tissue microarray technology to the study of non-Hodgkin's and Hodgkin's lymphoma. Hum Pathol. 2002 Oct;33(10):968-974. PMID: 12395368 - PubMed
  • Drug response linked to genes in lymphoma patients - GNN 2_21_03
    "The researchers identified about 150 genes in lymph tumors that could help predict the drug response. The activity of these genes differed significantly between patients who responded to treatment and those who did not. "
  • Gene profiles predict survival - NCS Infoservices, 04_02
    The activity of as few as 17 genes can be used to predict lymphoma patients' response to treatment, scientists reported at the 18th UICC International Cancer Congress in Oslo this week.
  • Recommendations for the Reporting of Lymphoid Neoplasms - Medscape (free  login req.)
    A checklist for pathologists and surgeons on how to evaluate and store lymphoid tissue at biopsy.
 
Disclaimer:  The information on Lymphomation.org is not intended to be a substitute for 
professional medical advice or to replace your relationship with a physician.
For all medical concerns,  you should always consult your doctor. 
Patients Against Lymphoma, Copyright © 2004,  All Rights Reserved.