The Difference Between Relapsed Lymphoma and Refractory Lymphoma

In a perfect world, every case of cancer would respond to, and be cured by first-line therapy. Unfortunately, it is not often the case. This is especially true in lymphomas.

Although we often see the term "Relapsed/Refractory Lymphoma", there is a difference between a relapsed cancer and a refractory one:

Relapsed Cancer: "Relapsed" refers to a cancer that returns after a period of improvement. This applies whether the cancer was treated or untreated.

Refractory Cancer: "Refractory" refers to a cancer that proves resistant, or does not respond to, treatment. It doesn't matter whether the cancer is resistant to treatment immediately, or whether it develops a resistance during treatment, it is still called refractory.

Why It Happens

Despite the enormous amount of research that has gone into the causes, symptoms, and treatments of lymphomas, science can not currently say why any one patient will relapse or why his or her cancer will prove refractory.

At best, research has been able to identify certain prognostic indicators that help determine whether that patient's lymphoma may relapse. These indices are traditionally used to determine initial prognosis against first-line treatment, but can also be used to help determine risk of relapse.

In non-Hodgkins lymphoma, those relapse risk factors are found in the Revised International Prognostic Index and are as follows:

• Age
• Stage of disease
• Whether or not there are extranodal sites
• LDH level
• ECOG performance status

In Hodgkins lymphoma, those factors are found in the International Prognostic Score and are as follows:

• Later stage of disease (III or IV)
• Age
• Gender (men more commonly relapse than women)
• Hemoglobin level
• Albumin level
• Leukocytosis (white blood cell count)
• Lymphopenia (lymphocyte level)

Treatments and Outcomes

In general, relapsed or refractory Hodgkins lymphoma has a much better prognosis, and is considered significantly more treatable and curable, than relapsed or refractory non-Hodgkins lymphomas—regardless of the treatment modality involved.

When it does happen, the treatments for relapsed or refractory disease are variable, and which one each patient receives depends on certain factors, such as:

• Time of relapse
• Age of patient
• Stage or extent of relapsed disease
• General health
• What drugs or treatments the patient has already received

Second-Line Therapies

Second-line therapies generally involve some form of more intense chemotherapy. The term 'salvage therapy' is often used to dennote therapy that follows on the heels of a prior therapy that has failed.

Salvage chemotherapy regimens for relapsed or refractory Hodgkins lymphoma include MOPP, ChlIVPP, CBVD, PCVP, CEVD, CAPE / PALE and Dexa-BEAM.

Salvage chemotherapy regimens given prior to an allogenic or autologuos bone marrow transplantation for relapsed or refractory Hodgkins lymphoma include ASHAP, Mini-BEAM, High-dose Melphalan, and CBV.

Second-line therapies for non-Hodgkins lymphomas will differ depending on the factors listed above but also on the non-Hodgkins lymphoma subtype.

Second-line therapy examples:

Treating relapsed or refractory follicular lymphoma might involve:

• Combination chemotherapy such as R-CHOP
• Rituxan maintanence
• Radiation
• Radioimmunotherapy such as Zevalin or Bexxar

Treating more aggressive relapsed or refractory B-cell lymphomas such as diffuse large B-cell lymphoma might involve:

• Salvage chemotherapy regimens, such as EPOCH, ESHAP, DHAP, ICE, R-ICE or FN-D
• Allogenic or autologuous bone marrow transplantation

Treating relapsed or refractory mantle cell lymphoma might involve:

• Salvage chemotherapy regimens, such as Hyper-CVAD-MTX/AraC
• Velcade, Treanda, or Gemzar, alone or with other chemotherapy drugs
• Rituxan maintanence
• Allogenic or autologuous bone marrow transplantation

In most cases, there is no consensus on a 'third-line' therapy for treating lymphomas, unless it involves trying another second-line therapy. Generally if first and second-line therapies fail, oncologists are apt to recommend a clinical trial or giving palliative care only.

Outcomes of relapsed lymphoma / refractory lymphoma

The actual statistics on the chance of success on being treated for a relapsed or refreactory lymphoma vary, and can range from as high as 80% in some cases of Hodgkins lymphoma down to 2-4% in some non-Hodgkins lymphomas.

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