Diffuse Large B-CellDLBC is the most common of all the lymphomas, and by far the most common of the aggressive types of lymphoma. It comprises about 35% of all NHL cases in North America, and about 60% of all aggressive cases. The term diffuse refers to the fact that the cancer cells are spread around and not concentrated in one particular part of the node or in clusters within a part of the node. In other words the cancer cells don't clump together very well. This is the opposite behaviour of follicular lymphoma, which is an indolent variety.
This diffuse pattern of growth contributes to the aggressive behaviour of DLBC. These patients are more likely to experience "B" symptoms which includes fever, recurrent night sweats, fatigue or weight loss. However their aggressive natures is also what contributes to their high cure rate because chemotherapy is most effective at targeting rapidly dividing cells. The International Prognostic Index, is highly predictive of those who are at risk of early relapse.
Diagnosis and PrognosisSee our diagnosis page for more detailed information how how NHL is diagnosed. The prognosis for patients with DLBC varies widely according to the number of risk factors on the International Prognostic Index (IPI). With combination chemotherapy with or without radiation DLBC can be cured in about 50-80% of patients, and as high as 90% of patients with no risk factors can be cured. Most relapses if they occur, occur within the first two years. After two years a relapse is unlikely but doctors will generally not use the "cure" word until 5 years. See the section below on relapsed DLBC for more information.
In addition to the IPI current studies show that the absolute lymphocyte count at diagnosis is a strong predictor of outcome. A low absolute lymphocyte count predicts for worse outcomes. Below are two recent studies on this.
Low absolute lymphocyte count is a poor prognostic factor in diffuse-large-B-cell-lymphoma.
Here is another study that looks at which genetic features predict for outcome.
Additional information about what genetic features may affect the prognosis are found at the bottom of this page in the Other information section. It is a complex topic which is really still in its infancy. Every day they are discovering new information.
TreatmentsDLBC is usually treated with R-CHOP (CHOP with Rituxan) chemotherapy or other Doxorubicin containing regimens. Many patients will be cured using this chemotherapy regimen. A "cure" is generally defined as 5 year disease free survival. The aggressive nature of DLBC means that if it has not relapsed within 5 years it is statistically highly unlikely that it ever will. In fact the vast majority of relapses occur within the first 2 years following treatment. While a relapse after 5 years is unlikely it does occur in a small subset of patients.
There is ongoing study about the best schedule for R-CHOP. Traditionally CHOP was given every 3 weeks (CHOP-21). But studies using a dose dense schedule CHOP-14 (every 2 weeks) showed superior outcomes for patients over the age of 60. However with the addition of Rituxan to this combination there is still some question of whether the 14 or 21 day schedule is superior. Below is the link to the latest update for that particular study (Feb 2008)
An earlier study showed that adding Rituxan to CHOP-14 (making it R-CHOP-14) for only 6 cycles was superior to using standard CHOP-21 for eight cycles. Therefore there is little reason to continue CHOP for 8 cycles and expose the patient to excessive anthracyclines. Below is the link to that study.
Now the question that needs to be answer is whether or not R-CHOP-14 is superior to R-CHOP-21. As yet that is an unanswered question that needs to be studied in a Phase III trial.
Here is the link to an analysis of these studies from Dr. Andrew Zelenetz
Even with R-CHOP being the current Gold Standard, there is still no consensus on the optimal frontline treatment for all DLBC patients. There are many genetic features, risk factors and other factors that influence the outcome for each patient. Below is a link to an excellent Medscape article that reviews the current knowledge, ongoing studies and future directions for DLBC treatment.
Read the original article directly from Medscape
Here is another study that discusses the optimal front-line treatment for DLBC. First-line therapy of CD20+ diffuse large B-cell lymphoma: facts and open questions
CNS involvement is not common but it does occur with DLBC. Of greater concern is the risk of having a relapse with central nervous system involvement. To prevent this from happening some physicians will give high risk patients CNS prophylaxis treatment. Usually that will be high dose Methotrexate, or ARA-C.
Of greater concern however is, how high is the risk of CNS relapse, and is it necessary to give this additional treatment in the absence of evidence there is any CNS involvement at diagnosis. Below is one study that looks at the issue of CNS relapse and whether CNS prophylaxis is necessary for newly diagnosed high risk patients.
Here is a letter to the editor from another expert in the field with his comments on the above study.
Natural History of CNS Relapse in Aggressive Non-Hodgkin's Lymphoma: What Have We Learned?
Relapsed aggressive NHLRelapses are unlikely to occur after two years of remission. But unlikely does not mean impossible and doctors generally don't use the cure word until 5 years of remission. Even after 5 years rare relapses do occur. Often a relapse this late is considered a whole new case of lymphoma and not really a relapse. Only a biopsy can really distinguish whether this is true. The study below discusses the characteristics and prognosis of relapses past the 5 year point.
If a relapse occurs a more potent salvage therapy will be used. In most cases if the patient is under 70 and in good general health a Stem Cell Transplant will be the treatment of choice for a relapse. Stem Cell transplants are highly effective and can cure a significant percentage of patients who undergo them. The patients who had a good response to their initial therapy are the ones who are most likely to have a good outcome from a stem cell transplant. There are two basic types of Stem Cell Transplant.
Allogeneic - where someone else is the donor. This type has a very high probability of curing the patient, but is also very risky. About 20-30% of patients die during this procedure.
Autologous - where the patient donates their own stem cells. This type is very safe (2% death rate) but does not produce the high rate of cures that allogeneic transplants to.
Not everyone is a candidate for a stem cell transplant. Other treatment options are available with varying degrees of success. For a list of alternative treatments to SCT click on the relapsed DLBC menu choice at the top left of this page.
Other informationRecent research has identified two distinct types of DLBC. Using modern techniques such as DNA Microarray analysis, and Flow Cytometry, researchers have discovered that DLBC can be divided into Germinal B-Cell (GBC) and Activated B-Cell (ABC) types of diffuse large B-cell lymphoma. The GBC variant has a very favourable prognosis with a 5 year survival rate around 70-80% in most studies. The ABC variant is a poor prognosis with only about 30-40% 5 year survival.
It still remains a challenge for researchers and doctors to find ways to use this information to develop treatments that make use of the knowledge and help boost the ABC survival rate. It is hoped that in the future they will be able to tailor the treatment to the subtype. Here is a list of medical studies on this subject.
Click here to run a focused Medline search for more abstracts on this topic
Furthermore, additional studies are beginning to show that the GBC and ABC variant is not the deciding factor in the prognosis. They are finding other genetic features that are perhaps of more prognostic value. This is an ongoing area of research so much of the information is contradictory. Here are some studies looking at this topic.
T-cell rich B-cell lymphomaAnother variant of DLBC is T-cell/Histiocyte - Rich B-cell Lymphoma. Despite the name this not a T-cell lymphoma, but a form of DLBC. It derives its name from the fact that the tumour environment is populated by a high percentage (over 50%) of normal healthy T-cells. The links below takes you to an excellent article on this type of NHL
A general overview of the features of T-cell histiocyte rich B-cell lymphoma from Haematologica
Biology, Diagnosis and Management of T-cell Histiocyte-Rich DLBC
T-cell rich B-cell lymphoma from Blood Journal
To read more about diffuse large b-cell lymphoma check out the following links.
National Cancer Institute aggressive NHL information
(Note, follow the links on the left side of this page for additional information since it is all categorized.) Because this type of lymphoma is the most common type there is an abundance of information about it on the Internet. But for the average person who is looking for treatment options the best place to look is likely going to the be American Society of Hematology) ASH abstracts. These abstracts represent the ground breaking work of the worlds leading haematologists as presented at their annual convention.
|