Non-Hodgkin’s lymphoma: diagnosis and management

Consider an excision biopsy as the first diagnostic procedure for people with suspected non‑Hodgkin's lymphoma at first presentation.

In people with suspected non‑Hodgkin's lymphoma for whom the risk of a surgical procedure outweighs the potential benefits of an excision biopsy, consider a needle core biopsy procedure. Take the maximum number of cores of the largest possible calibre.

For people with suspected non‑Hodgkin's lymphoma in whom a diagnosis is not possible after a needle core biopsy procedure, offer an excision biopsy (if surgically feasible) in preference to a second needle core biopsy procedure.

Pathology departments should ensure that tissue is conserved when handling needle core biopsies, so that further analysis can be carried out if needed.

Consider using FISH (fluorescence in situ hybridisation) to identify a MYC rearrangement in all people newly presenting with histologically high‑grade B‑cell lymphoma.

If a MYC rearrangement is found, use FISH to identify the immunoglobulin partner and the presence of BCL2 and BCL6 rearrangements.

Do not use immunohistochemistry to assess the prognostic value associated with cell of origin in people with diffuse large B‑cell lymphoma.

Interpret FISH results (MYC, BCL2 and BCL6 rearrangements) in the context of other prognostic factors (particularly the person's age and International Prognostic Index [IPI]).

Explain FISH results and their potential prognostic value to people with B‑cell lymphoma.

Offer FDG‑PET‑CT imaging to confirm staging for people diagnosed with:

• stage I diffuse large B‑cell lymphoma by clinical and CT criteria

• stage I or localised stage II follicular lymphoma if disease is thought to be encompassable within a radiotherapy field

• stage I or II Burkitt lymphoma with other low‑risk features.

For people diagnosed with other subtypes or stages of non‑Hodgkin's lymphoma not listed in recommendation 1.2.1, consider FDG‑PET‑CT imaging to confirm staging if the results will alter management.

Do not routinely offer FDG‑PET‑CT imaging for interim assessment during treatment for diffuse large B‑cell lymphoma.

Offer FDG‑PET‑CT imaging to assess response at completion of planned treatment for people with:

• diffuse large B‑cell lymphoma

• Burkitt lymphoma.

For people with other subtypes of non‑Hodgkin's lymphoma not listed in recommendation 1.2.4, do not routinely offer FDG‑PET‑CT imaging to assess response at completion of planned treatment unless the results will alter management.

Consider FDG‑PET‑CT imaging to assess response to treatment before autologous stem cell transplantation for people with high‑grade non‑Hodgkin's lymphoma.

Offer local radiotherapy as first‑line treatment to people with localised stage IIA follicular lymphoma.

Consider 'watch and wait' (observation without therapy) as first‑line treatment for people with stage IIA follicular lymphoma who are asymptomatic and for whom treatment with a single radiotherapy volume is not suitable.

Offer the same treatments that might be offered to people with advanced‑stage (stages III and IV) symptomatic follicular lymphoma to people with stage IIA follicular lymphoma who are symptomatic and for whom radiotherapy is not suitable.

Offer rituximab induction therapy to people with advanced‑stage (stages III and IV) follicular lymphoma who are asymptomatic.

At the time of publication (July 2016) rituximab did not have a UK marketing authorisation for this indication. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council's Prescribing guidance: prescribing unlicensed medicines for further information. The evidence reviewed for the guideline supports the standard monotherapy dosage of 4 doses of 375 mg/m² at weekly intervals.

Rituximab, in combination with:

• cyclophosphamide, vincristine and prednisolone (CVP)

• cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP)

• mitoxantrone, chlorambucil and prednisolone (MCP)

• cyclophosphamide, doxorubicin, etoposide, prednisolone and interferon‑α (CHVPi) or

• chlorambucil
  
  is recommended as an option for the treatment of symptomatic stage III and IV follicular lymphoma in previously untreated people. [This recommendation is from NICE's technology appraisal guidance on rituximab for the first-line treatment of stage III–IV follicular lymphoma.]

Rituximab maintenance therapy is recommended as an option for the treatment of people with follicular non‑Hodgkin's lymphoma that has responded to first‑line induction therapy with rituximab in combination with chemotherapy. [This recommendation is from NICE's technology appraisal guidance on rituximab for the first-line maintenance treatment of follicular non-Hodgkin's lymphoma.]

Rituximab, within its marketing authorisation, in combination with chemotherapy, is recommended as an option for the induction of remission in people with relapsed stage III or IV follicular non‑Hodgkin's lymphoma.

Rituximab monotherapy as maintenance therapy, within its marketing authorisation, is recommended as an option for the treatment of people with relapsed stage III or IV follicular non‑Hodgkin's lymphoma in remission induced with chemotherapy with or without rituximab.

Rituximab monotherapy, within its marketing authorisation, is recommended as an option for the treatment of people with relapsed or refractory stage III or IV follicular non‑Hodgkin's lymphoma, when all alternative treatment options have been exhausted (that is, if there is resistance to or intolerance of chemotherapy).

Offer consolidation with autologous stem cell transplantation for people with follicular lymphoma in second or subsequent remission (complete or partial) who have not already had a transplant and who are fit enough for transplantation.

Consider consolidation with allogeneic stem cell transplantation for people with follicular lymphoma in second or subsequent remission (complete or partial):

• who are fit enough for transplantation and

• for whom a suitable donor can be found and

• when autologous stem cell transplantation has not resulted in remission or is inappropriate (for example, because stem cell harvesting is not possible).

Consider consolidation with autologous stem cell transplantation for people with transformation of previously diagnosed follicular lymphoma that has responded to treatment and who are fit enough for transplantation.

Consider consolidation with autologous or allogeneic stem cell transplantation for people with transformation of follicular lymphoma who need more than 1 line of treatment for a response and who are fit enough for transplantation.

Do not offer consolidation with high‑dose therapy and autologous or allogeneic stem cell transplantation to people presenting with concurrent diagnoses of follicular lymphoma and diffuse large B‑cell lymphoma that have responded to first‑line treatment.

Offer chemotherapy in combination with rituximab as first‑line treatment for people with advanced‑stage mantle cell lymphoma who are symptomatic. Take the person's fitness into account when deciding on the intensity of chemotherapy.

At the time of publication (July 2016) rituximab did not have a UK marketing authorisation for this indication. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council's Prescribing guidance: prescribing unlicensed medicines for further information.

Consider cytarabine‑containing immunochemotherapy for people with advanced‑stage mantle cell lymphoma who are fit enough to tolerate an intensive approach.

At the time of publication (July 2016) cytarabine did not have a UK marketing authorisation for this indication. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council's Prescribing guidance: prescribing unlicensed medicines for further information.

Consider radiotherapy for people with localised stage I or II mantle cell lymphoma.

Consider 'watch and wait' (observation without therapy) until disease progression for people with clinically non‑progressive mantle cell lymphoma who are asymptomatic and for whom radiotherapy is not suitable.

Bortezomib is recommended, within its marketing authorisation, as an option for previously untreated mantle cell lymphoma in adults for whom haematopoietic stem cell transplantation is unsuitable. [This recommendation is from NICE's technology appraisal guidance on bortezomib for previously untreated mantle cell lymphoma.]

Consider consolidation with autologous stem cell transplantation for people with chemosensitive mantle cell lymphoma (that is, there has been at least a partial response to induction chemotherapy) who are fit enough for transplantation.

Consider maintenance rituximab, every 2 months until disease progression, for people with newly diagnosed mantle cell lymphoma who are not fit enough for high‑dose chemotherapy and where there has been a response to R‑CHOP‑based immunochemotherapy.

At the time of publication (July 2016) rituximab did not have a UK marketing authorisation for this indication. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council's Prescribing guidance: prescribing unlicensed medicines for further information. The evidence reviewed for the guideline supports a dosage of 375 mg/m² every 2 months until disease progression.

Consider maintenance rituximab, every 2 months for 3 years, for people with newly diagnosed mantle cell lymphoma who are in remission after cytarabine‑based induction and high‑dose chemotherapy.

At the time of publication (July 2016) rituximab did not have a UK marketing authorisation for this indication. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council's Prescribing guidance: prescribing unlicensed medicines for further information. The evidence reviewed for the guideline supports a dosage of 375 mg/m² every 2 months for 3 years.

Consider consolidation radiotherapy delivering 30 Gy to sites involved with bulk disease at diagnosis for people with advanced‑stage diffuse large B‑cell lymphoma that has responded to first‑line immunochemotherapy. For each person, balance the possible late effects of radiotherapy with the possible increased need for salvage therapy if it is omitted, and discuss the options with them.

Explain to people with diffuse large B‑cell lymphoma that they have an increased risk of central nervous system lymphoma if the testis, breast, adrenal gland or kidney is affected.

Explain to people with diffuse large B‑cell lymphoma that they may have an increased risk of central nervous system lymphoma if they have 2 or more of the following factors:

• elevated lactate dehydrogenase (LDH)

• age over 60 years

• poor performance status (ECOG score of 2 or more)

• more than one extranodal site involved

• stage III or IV disease.
  
  Explain that the level of risk increases with the number of factors involved.

Offer central nervous system‑directed prophylactic therapy to people with diffuse large B‑cell lymphoma:

• that involves the testis, breast, adrenal gland or kidney or

• who have 4 or 5 of the factors associated with increased risk of central nervous system relapse listed in recommendation 1.6.3.

Consider central nervous system‑directed prophylactic therapy for people with diffuse large B‑cell lymphoma who have 2 or 3 of the factors associated with increased risk of central nervous system relapse listed in recommendation 1.6.3.

Offer salvage therapy with multi‑agent immunochemotherapy to people with relapsed or refractory diffuse large B‑cell lymphoma who are fit enough to tolerate intensive therapy:

• explain that this is primarily to obtain sufficient response to allow consolidation with autologous or allogeneic stem cell transplantation, but is also beneficial even if not followed by transplantation

• consider R‑GDP immunochemotherapy, which is as effective as other commonly used salvage regimens and less toxic.

Offer consolidation with autologous stem cell transplantation to people with chemosensitive diffuse large B‑cell lymphoma (that is, there has been at least a partial response to chemotherapy) who are fit enough for transplantation.

Consider consolidation with allogeneic stem cell transplantation for people with chemosensitive diffuse large B‑cell lymphoma (that is, there has been at least a partial response to chemotherapy):

• that relapses after autologous stem cell transplantation or

• in whom stem cell harvesting is not possible.

Offer intensive immunochemotherapy to people with Burkitt lymphoma who are fit enough to tolerate it. Consider using one of the following:

• R‑BFM

• R‑CODOX‑M/R‑IVAC

• R‑HyperCVAD (HDMTX)

• R‑LMB.

For people with low‑risk Burkitt lymphoma, consider using the less intensive DA‑EPOCH‑R regimen supplemented with intravenous and/or intrathecal methotrexate.

Offer less intensive immunochemotherapy to people with Burkitt lymphoma who are not fit enough to tolerate intensive chemotherapy. Consider using one of the following, alone or supplemented with intravenous and/or intrathecal methotrexate:

• R‑CHOP

• R‑CHEOP

• DA‑EPOCH‑R.

Consider CHOP chemotherapy as first‑line treatment for people with peripheral T‑cell lymphoma.

Consider consolidation with autologous stem cell transplantation for people with chemosensitive peripheral T‑cell lymphoma (that is, there has been at least a partial response to first‑line chemotherapy) who are fit enough for transplantation.