Deciding on Therapy for Follicular Lymphoma

Loretta J. Nastoupil, MD:At the initial presentation, we’re recommending bone marrow biopsies for all patients with indolent lymphoma. The most recent Lugano criteria suggest that if there is uptake within the bone marrow on the PET scan, you may forgo the bone marrow biopsy. I think this is more applicable in the aggressive histology, such as large-cell lymphoma or Hodgkin lymphoma. There’s still valuable information in follicular lymphoma specifically as to whether or not there’s bone marrow involvement and the extent of bone marrow involvement. This has implications not only for prognosis, but in terms of what to expect with our treatment in regards to side effects and management of those side effects. Cytopenias, including prolonged cytopenias, though infrequent, are something that we will address in the management of follicular lymphoma, and knowing whether or not there is extensive bone marrow involvement at the initial presentation is valuable information.

I will repeat the bone marrow biopsy if I’m trying to confirm whether or not a patient has achieved a complete response, meaning if they have a negate PET. If they had bone marrow involvement at presentation, we will repeat that bone marrow to assess whether or not they’ve cleared the marrow. And I can tell you my personal experiences. There are times where the PET is negative, but there’s residual lymphoma in that bone marrow. I do not routinely repeat the bone marrow beyond the 2 time points. If I have a patient who has achieved a complete response and they’re coming in—and they may have evidence of progression or they may be in remission—I don’t routinely repeat the bone marrow biopsy in the absence of a clinical indication. I am investigating for etiology of cytopenias.

To summarize this case, we have a 71-year-old female with an underlying autoimmune condition, who has been on immunosuppressive therapy, who presents with bilateral small volume axillary adenopathy. The largest lymph node was approximately 4 cm in size and was in the groin. It was excised, and we rendered a diagnosis of follicular lymphoma based on the phenotype and the morphology, with the confirmation of the translocation 14:18. So, I am confident that this is a diagnosis of follicular lymphoma. We have a low—tumor burden patient based on the GELF criteria. I would complete the staging assessment with a bone marrow biopsy. But I believe this patient to be an appropriate candidate for observation.

The staging system we use for follicular lymphoma is the Ann Arbor Staging System. What has changed recently with the inguinal criteria is we’re no longer making the distinction between stage 1 or 2 or stage 3 or 4. So, we are now classifying patients as “limited stage” if they’re stage 1 or 2, and “advanced stage” if they’re stage 3 or 4. The vast majority of patients will be advanced stage based on the natural history of this disease. It’s still pertinent to distinguish those stage 2 bulky patients, because those are oftentimes not candidates for radiation or definitive therapy for limited stage disease. But I think this is a simpler classification system, and oftentimes patients will be quite frustrated when they hear they have stage 4 disease, whereas stage 3, or advance stage, sounds less ominous at times. So, I think this is a helpful classification system that we’re currently employing.

In regard to a newly diagnosed follicular lymphoma patient, we are recommending PET as the initial workup, primarily for 2 reasons. First, this disease is usually PET-avid and it can be helpful to know the extent of the extra nodal involvement. But secondly, I think it’s also important to make sure that we’re confident about the diagnosis because we rarely sample more than one site outside of a lymph node and a bone marrow and there may be 2 lymphomas at the same time at presentation. So, if you have a discordance in the PET uptake, that may prompt us to sample an additional lymph node to ensure we’ve excluded the possibility of an aggressive lymphoma as well.

Based on the available information, which is primarily derived from the physical exam, the labs, and the CTs, we know this patient is at least stage 3 because she has abnormally sized lymph nodes above and below the diaphragm. In the absence of PET, we do not know if there’re any signs of extranodal involvement. So, at this time, I would recommend a bone marrow biopsy and a PET to complete the staging.

Transcript edited for clarity.

January 2014

• A 71-year-old female reports having symptoms of bilateral axillary swelling of 1.5 years’ duration and presents with diffuse inguinal and cervical adenopathy.
• Past medical History: 15-year history of treatment for rheumatoid arthritis with methotrexate
• Physical examination:
  • The patient is generally well-appearing; temperature, pulse, blood pressure, and HEENT are all WNL; extremities show no edema.
  • Cardiac exam is normal; chest is clear
  • Abdomen shows no abnormal hepatosplenomegaly
  • Lymph nodes: left axillary 1.5 cm, right axillary 2 cm; cervical and inguinal nodes <1 cm bilaterally; non-tender
• Notable laboratory findings:
  • CBC with diff, WNL
  • LDH, 148
• Right groin excisional node biopsy shows small lymphocytes with nuclear indentations (centrocytes) and large lymphocytes without indentations (centroblasts).
  • Pathology: t(14;18); co-expression of Bcl2, CD10, CD20.
• CT shows scattered adenopathy in the cervical, axillary, mesenteric, and pelvic regions. The largest lymph node measures 4.5 cm. The remaining lymph nodes are smaller than 3 cm.