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Relapsed or refractory follicular lymphoma (FL) is a condition that requires a careful selection of treatment options. It often occurs in older people, who may have significant comorbidities, or who may have more advanced grades or stages of the cancer.

Various treatment schedules are thus used in relapsed or refractory lymphoma, which must be evaluated for evidence and amplitude of response. This may begin with imaging, which should be carried out in the middle and at the completion of the chemotherapy. The midterm response will confirm whether the treatment efficacy is as desired. If there is less than a partial response, an early salvage regimen should be substituted if possible. On the other hand, if there is partial response, such patients may be put on rituximab for maintenance, which may produce a complete response.

PET for Evaluation

Positron emission tomography (PET) together with computerized tomography (CT) is helpful to assess the prognosis. Patients who remain PET positive for a long time are at a higher risk for refractory disease or early relapse. The uptake of the agent is higher as the histological grade rises and it also reflects tumor transformation into a large cell type with focal increases in the uptake.  The use of PET-CT is thus important as a potential way to evaluate the response to treatment and may predict an aggressive course for the disease.

MRD Analysis

Minimal residual disease (MRD) is another possible prognostic factor that is identified by the use of polymerase chain reaction after treatment is complete. It reflects the tumor sensitivity to treatment. It has been shown in trials to indicate long-term outcome with accuracy, but is not yet in clinical use, because a negative MRD is not associated with any survival advantage. Patients who have undergone stem cell transplantation, but have residual MRD have a poorer prognosis. For instance, when the polymerase chain reaction was negative at the end of treatment, it was termed complete molecular remission and was associated with a better outcome, the 7-year progression-free survival being 58% vs. only 36% in patients who had minimal residual disease. In fact, patients with MRD showed no difference whether or not they were on maintenance treatment.

Factors That Need to be Followed up During Treatment

Treatment with powerful and potentially toxic chemotherapeutic drugs requires that the patient be carefully evaluated periodically for signs of toxicity.

Indicators of Toxicity

The most frequent serious adverse effect is neutropenia, which complicates the course in about one fourth of patients. Others include anemia, cardiac and renal toxicity, infections, and secondary malignancies. Thus these organs and systems need to be followed up with regular testing.

Molecular Markers

Molecular markers have also been shown to be of use in patients undergoing treatment to evaluate the response. These include cytogenetic alterations, including karyotypic abnormalities, gene-expression profiling, and the host genetic environment.

FLIPI Scoring

The Follicular Lymphoma International Prognostic Index (FLIPI) score is an important prognostic tool in FL. Patients with a low or intermediate FLIPI score have been shown to have a longer progression-free survival and overall survival. This is of additive value along with molecular markers. For instance, one study has shown that the 7-year progression-free survival with intermediate or low FLIPI scores was 67%, but only 38% in those with high FLIPI scores. The overall survival after 7 years was 86% vs. 75% in these two groups.


  • http://www.esmo.org/Guidelines/Haematological-Malignancies/Newly-Diagnosed-and-Relapsed-Follicular-Lymphoma
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5111519/
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3239387/
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5224815/
  • http://www.bbmt.org/article/S1083-8791(11)00482-4/pdf

Further Reading

  • All Follicular Lymphoma Content
  • Follicular Lymphoma – What is Follicular Lymphoma?
  • Follicular Lymphoma Causes
  • Follicular Lymphoma Treatments
  • Relapsed/Refractory Follicular Lymphoma

Last Updated: Feb 26, 2019

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.

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