Here we provide thoughts compiled by members of peer-to-peer support groups on the subject of what to do and consider when you relapse.  This is lay content.  Please be sure to discuss with your doctor!

Encouragement: Relapse after the first primary therapy for lymphoma can be particularly discouraging to patients and to their loved one. Please be aware that there are often many effective treatment options for lymphoma following the first relapse.  

For relapse of an aggressive lymphoma, also see Treating relapsed DLBCL - review article

Step 1:  Testing.  A biopsy is often done to see if what has recurred has changed in any significant way from the original diagnosis. This information can be vital to making informed treatment decisions. For example, it can help your doctors to determine if you have high- or low-risk disease.  Staging will also be done by using imaging tests to see where the lymphoma is, and how far and fast it has progressed since the last treatment.

Pathology experts often advise that the biopsy should be of the largest lymph node that can be safely resected (removed surgically) to maximize the chance of getting representative cells. 

Also see: Indolent, Recurrent Adult Non-Hodgkin’s Lymphoma ~ Best Practices - Cancer.gov

Step 2: consult lymphoma experts after you have the information they will need to help you make an informed decision.  At the consults, job one is to determining if the relapsed lymphoma is high- or low-risk disease and to choose the goal of treatment accordingly. Prepare for these consults by summarizing the relevant information and by having all pathology information at hand, particularly the latest biopsy and imaging reports and slides, and two copies of your questions (one for you and one for your doctor).

Indicators of of high- and low-risk disease include but are not limited to:  

1. Was the disease sensitive to initial treatment? 

2. How long was the response to initial treatment?

3. What is the growth rate before and after treatment? - is it stable, waxing and waning? 

4. Is the lymphoma causing symptoms? 

5. Is the lymphoma causing low blood counts?

6. Is it sensitive to subsequent biologic, single agent, or low dose chemotherapy treatment? 

7. Is there evidence of transformation (diffuse growth pattern) from pathology analysis of tissue? 
   

There are two basic goals of treatment:

Management - watch & wait, followed by judicious use of low toxic biologic*  and/or chemotherapy when treatment is indicated by symptoms, progressing disease, poor quality of life, low blood counts, or even patient preferences.  The general idea is to treat the lymphoma as a chronic condition,  to minimize toxicity, and to keep your future options open.

Examples of biologics are Rituxan, Interferon, Leukine, therapeutic cancer vaccines (investigational).  Chemotherapy may include Chlorambucil,  Cytoxan,  Low dose oral PEP-C, Prednisone and combinations of agents.

Curative Approaches / Complete and Durable Response* - use of combination or  sequential therapy at higher doses in order to eliminate the disease, or aggressive  components of the disease.  * While indolent lymphoma is not considered curable with standard approaches  there is encouraging data with Bexxar, Zevalin, CHOP+R that raise the question if   cure is not achieved at an increasing rate. Why not always try to cure *indolent* lymphomas?   The potential to obtain the goal has to be weighed against the toxicities and risks  of the treatment. For example, if the probability of obtaining a durable response is  low for an aggressive therapy, you may be exposing yourself to unnecessary  risks for minimal gain.

Evidence-based best practice:

	New: Dr. Cheson discusses factors that influence options at relapse for Follicular Lymphomas  LRF 2006 Education Forum webcast   Flash format
	Adult Lymphoblastic Lymphoma - Cancer.gov
	Aggressive, Recurrent Adult Non-Hodgkin’s Lymphoma - Cancer.gov
	Indolent, Recurrent Adult Non-Hodgkin’s Lymphoma - Cancer.gov
	Recurrent Adult Hodgkin’s Lymphoma - Cancer.gov
	Treatment Approach for Children and Adolescents with Hodgkin’s Lymphoma - Cancer.gov
	NCCN Clinical Practice Guidelines in Oncology™ Non-Hodgkin's Lymphoma, 2007 http://www.nccn.org/professionals/physician_gls/PDF/nhl. pdf

Resources: 

Managing Indolent Lymphomas in Relapse Working Our Way Through a Plethora of Options - asheducationbook full/2000  Fernando Cabanillas, (Chair), Sandra Horning, Mark Kaminski and Richard Champlin In this review of the alternative therapies a panel of three expert hemato-oncologists each discuss their approach to the management of a 49-year-old patient with a relapsed indolent follicular lymphoma.  "The most important issues to address are whether further treatment should be given based on the considerations above and the desires of the patient.  For patients with bulky disease, combination chemotherapy will yield a more rapid response  and is more likely to yield a complete or partial response than antibody treatments.  Patients who enjoyed a prolonged initial response to alkylating agent–based treatment may be retreated, whereas those with brief partial responses and active, progressive disease should move on to another treatment such as fludarabine.  Histologic evidence of transformation or clinical suspicion of more aggressive disease  indicate the need for more intensive treatment with doxorubicin-containing chemotherapy,  possibly as a prelude to transplantation. Infrequently, persistence or recurrence of disease  in an isolated anatomic region argues for the use of radiotherapy."  ~ Dr. Horning

Treatment options after relapse of indolent lymphoma  http://tinyurl.com/32jrpx Dr Leonard, Dr. Coleman, and Dr. O'Conner

Lay Comments: 

Limitations of pathology findings: The pathology reports can have limitations. Sometimes small cleaved indolent behaves aggressively. Sometimes mixed, large, and small cell lymphomas (sometimes called grade 2) behaves indolently.  The clinical behavior can be as important as the diagnostic tests, which do not yet account for all factors that contribute to malignant behavior.   

Staging: A second scan at two months following relapse could be appropriate to gauge how clinically aggressive the lymphoma is. If the clinical behavior is indolent,  watch & wait might be recommended ... just like many do when originally diagnosed.  It's not uncommon for a relapse to appear abruptly, but then slow down and stabilize.  It can take time to judge the true clinical behavior of the relapsed disease. 

Response to treatment evaluations: "Specifically, assessing response [with PET] may be useful in two possible situations: to evaluate tumor response at the end of a full course of treatment, or to predict tumor response early in the course of a prolonged treatment regimen. In the first instance, early detection of treatment failure may permit a physician to institute a second-line therapeutic approach. In the second instance, accurately predicting treatment failure may allow the physician to substitute an alternative regimen, without subjecting the patient to the toxicity of the full course. "  Peter E. Valk, MD

Keep abreast of clinical trials for agents that have low toxicity and little risk of precluding subsequent treatments.  These may be best tried when treatment is not required as an alternative to watch & wait.

If the lymphoma is refractory (resistant) to standard treatments, you might have to consider stronger measures or novel combinations of cancer therapies. Low dose chemo regimens like PEP-C, investigational targeted treatments (like antisense with rituxan, velcade, gallium nitrate, vaccines, etc.).  Talk to your doctor about collecting stem cells before or after the treatments you are considering as a further precaution and use in the future, particularly if you have high-risk disease.

Know what clinical trials are available and what seems promising and low toxic.  Consult with non-treating experts who have intimate knowledge of your disease, treatment history, and all available standard and emerging treatments. Educate yourself about the potential risks and benefits of new approaches.

More on honesty. It's important that patient and doctor pay attention to the "messages," or trends of the clinical course of your lymphoma.  Failing to see the "writing on the wall" can be a problem. Getting too bulky can be a problem. So too can be sticking with a treatment too long when it's failing to benefit you.  

Burning bridges: Try to avoid treatment agents that may preclude the use of other approaches, or undermine immunity too profoundly. However, when the goal of treatment is to cure or obtain a durable remission, meeting the goal can offset the risks and toxicities, and the risks must be seen in the context of the clinical situation and the risks of the disease. 

Important note:  Only your doctors have the clinical details necessary to help you to make informed decisions.  But do not limit your horizon to the perspectives of one doctor. It can be helpful to consult outside lymphoma experts as well.  Please do not rely on the anecdotes and theories of patients.

Communicating honestly with your doctor and becoming informed about the potential risks and benefits of all the treatments appropriate to your diagnosis are keys to managing lymphoma and treating it effectively in a timely manner.