On the following pages you will find information about the various types of indolent NHL and what their particular characteristics are. In many cases we have provided links to other web sites that give more detail. Low-grade is another term that refers to indolent lymphoma. Before discussing the individual types it is important to review some of the characteristics common to all indolent lymphomas. First, here are the main types of indolent lymphoma.
- Marginal zone
- Splenic marginal zone
- Anaplastic Large Cell Lymphoma
- Cutaneous T-cell
- Full classification system
Indolent lymphomas are usually not considered curable because the cancer grows too slowly to be targeted accurately by most modern treatments. Nonetheless they actually do respond very well to treatment in most cases. People with indolent lymphomas usually survive for many years. Statistics say the median is around 10-15 years, but that is very misleading because the "median" only means that half the patients have not survived past 10-15 years, and the other half have survived. Don't try to apply a median statistic to yourself since it cannot by its very nature apply. Suffice it to say that most patients can look forward to many years of productive life, and quite possibly a cure in the not too distant future. Rituxan, and other biologic therapies are bringing us closer all the time.
In many cases it is totally appropriate to defer treatment altogether in favour of a watch and wait approach. This is usually done when the patient has no symptoms, and there are no major organs at risk. When treatment is required there is a variety of choices, none of which has any clear advantage in all cases. The single most common chemotherapy regimen for lymphoma is CHOP and it is frequently used for indolent lymphomas, but it is also a fairly aggressive treatment which many believe should be saved for later. A recent study presented at the ASH 2010 convention shows treatment with Rituximab alone folowed by maintenence Rituximab prolongs the length of time before real chemotherapy is required, over just watching and waiting. But it does not show an overal survival advantage, and you have to balance the inconvenience of going for Rituxan every few months and the very low risk of side effects, against the desire to delay using chemotherapy. It really boils down to what each patient feels most comfortable with. Click the link below to read the study.
An Intergroup Randomised Trial of Rituximab Versus a Watch and Wait Strategy In Patients with Stage II, III, IV, Asymptomatic, Non-Bulky Follicular Lymphoma (Grades 1, 2 and 3a). A Preliminary Analysis
Since indolent lymphomas cannot usually be cured the main goal of treatment is to keep the patient in good health as long as possible. Virtually all the low grade or indolent lymphomas are characterized by a pattern of treatment-remission-relapse with each remission being shorter than the previous one. This means using the least toxic options first, and saving the "big guns" as we call it, until later.
Click here to read an in-depth discussion of low-grade lymphoma: Biologic characteristics, pathology, treatment selection options, and transplant outcomes. This article is a comprehensive discussion by leading experts from the American Society of Hematology (ASH)
It is not unusual for some indolent cells to transform into a more aggressive form, resulting in two clones. Statistically the risk of transformation is about 30% after ten years, but this may be low since the figure is based on confirmed second biopsies, which often are not performed since the priority at such time is to treat. Historically transformation has been associated with a worse prognosis but with modern therapies this is not always the case. Recent data suggests that maintenance Rituxan may lower the risk of transformation. Furthermore the use of Rituxan would appear to be significantly improving the outcome when transformation occurs. The first 2 studies below are recent ones that shows this trend.
Here are some articles about transformation.
Transformed follicular non-Hodgkin lymphoma
Transformation of follicular lymphoma in the era of
immunochemotherapy: A population-based study from
Rates and Outcomes of Follicular Lymphoma
Transformation in the Immunochemotherapy Era: A Report
From the University of Iowa/Mayo Clinic Specialized
Program of Research Excellence Molecular Epidemiology
- Risk Factors and Prognosis of Transformation in Follicular Lymphoma: a Multicentre Retrospective Analysis of 1763 Patients from the Geltamo Spanish Lymphoma Cooperative Group
There is much controversy about whether to reserve use of anthracyclines such as doxorubicin until transformation occurs. It is thought by some that the anthracyclines are the more potent drugs and should be saved until that happens. Therefore other options should be used first. But at least one study shows that upfront use of anthracyclines might actually lower the risk of transformation. Below are two studies that look at the risk factors for transformation. The first looks at the use of anthracyclines.
The impact of initial treatment of advanced stage
indolent lymphoma on the risk of transformation
The use of anthracycline at first-line compared to
alkylating agents or nucleoside analogs improves the
outcome of salvage treatments after relapse in
follicular lymphoma The REFOLL study by the Fondazione
Risk Factors for Early Transformation of Follicular
Lymphoma (FL): Report From the National LymphoCare Study
- The architectural pattern of FOXP3-positive T cells in follicular lymphoma is an independent predictor of survival and histologic transformation
Autologous stem cell transplants are highly successful in treating transformed indolent lymphoma. One study shows that the results are comparable to using SCT for de novo diffuse large B-cell lymphoma. See the study below.
High rate of survival in transformed lymphoma after
autologous stem cell transplant: pathologic analysis and
comparison with de novo diffuse large B-cell lymphoma
- High-dose therapy and autologous stem cell transplant for transformed non-Hodgkin lymphoma in the rituximab era
In this type of lymphoma it is an overproduction of the immunoglobulin protein IgM by the plasma cells that produces the malignancy. This increase in paraprotein causes hyperviscosity (thickening of the blood), which can cause many problems.
There is evidence to suggest that when treatment is needed Fludarabine has significant benefits over Chlorambucil. Read the study below.