Recommendations

People have the right to be involved in discussions and make informed decisions about their care, as described in your care.

Making decisions using NICE guidelines explains how we use words to show the strength (or certainty) of our recommendations, and has information about prescribing medicines (including off‑label use), professional guidelines, standards and laws (including on consent and mental capacity), and safeguarding.

1.1 Diagnosis

Type of biopsy

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

1.1.2 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.

1.1.3 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.

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

Diagnosing B‑cell lymphomas: gene testing strategies

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

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

Stratifying high‑grade B‑cell lymphomas using laboratory techniques

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

1.1.8 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]).

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

1.2 Staging using FDG‑PET‑CT (fluorodeoxyglucose‑positron emission tomography‑CT)

Confirming staging

1.2.1 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.

1.2.2 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.

Assessing response to treatment for diffuse large B‑cell lymphoma

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

End‑of‑treatment assessment

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

  • diffuse large B‑cell lymphoma

  • Burkitt lymphoma.

1.2.5 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.

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

1.3 Management of follicular lymphoma

First‑line treatment for stage IIA follicular lymphoma

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

1.3.2 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.

1.3.3 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.

Treating advanced‑stage asymptomatic follicular lymphoma

1.3.4 Offer rituximab induction therapy[1] to people with advanced‑stage (stages III and IV) follicular lymphoma who are asymptomatic.

Treating advanced‑stage symptomatic follicular lymphoma

1.3.5 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 rituximab for the first-line treatment of stage III–IV follicular lymphoma (NICE technology appraisal guidance 243).]

1.3.6 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 rituximab for the first-line maintenance treatment of follicular non-Hodgkin's lymphoma (NICE technology appraisal guidance 226).]

The guideline committee did not assess evidence or develop recommendations on bendamustine for treating people with follicular lymphoma, because a NICE technology appraisal on 'the clinical and cost effectiveness of bendamustine in combination with rituximab within its licensed indication for the first‑line treatment of advanced indolent non‑Hodgkin's lymphoma' was in development. This technology appraisal is currently suspended.

Treating advanced‑stage relapsed or refractory follicular lymphoma

The recommendations in this section are from rituximab for the treatment of relapsed or refractory stage III or IV follicular non-Hodgkin's lymphoma (NICE technology appraisal guidance 137).

1.3.7 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.

1.3.8 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.

1.3.9 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).

Consolidation with stem cell transplantation

1.3.10 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.

1.3.11 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).

Treating transformed follicular lymphoma

1.3.12 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.

1.3.13 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.

1.3.14 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.

1.4 Management of MALT lymphoma

First‑line treatment

Gastric MALT lymphoma: localised disease

1.4.1 Offer 1 or more lines of Helicobacter pylori eradication therapy, without any concurrent therapy, to people with H. pylori‑positive gastric MALT lymphoma (see the NICE guideline on gastro-oesophageal reflux disease and dyspepsia in adults).

1.4.2 Consider H. pylori eradication therapy for people with H. pylori‑negative gastric MALT lymphoma (see the NICE guideline on gastro-oesophageal reflux disease and dyspepsia in adults).

1.4.3 Consider 'watch and wait' (observation without therapy) for people with gastric MALT lymphoma that responds clinically and endoscopically to H. pylori eradication therapy but who have residual disease shown by surveillance biopsies of the stomach, unless high‑risk features are present.

1.4.4 For people with residual MALT lymphoma after H. pylori eradication therapy who are at high risk of progression [H. pylori‑negative at initial presentation or t(11:18) translocation], consider a choice of the following, in discussion with the person:

  • chemotherapy (for example, chlorambucil or CVP) in combination with rituximab[2]or

  • gastric radiotherapy.

1.4.5 For people with progressive gastric MALT lymphoma, offer a choice of:

  • chemotherapy (for example, chlorambucil or CVP) in combination with rituximab[2]or

  • gastric radiotherapy.

Gastric MALT lymphoma: disseminated disease

1.4.6 Offer H. pylori eradication therapy to people with disseminated H. pylori‑positive gastric MALT lymphoma (see the NICE guideline on gastro-oesophageal reflux disease and dyspepsia in adults).

1.4.7 Offer chemotherapy (for example, chlorambucil or CVP) in combination with rituximab[2] to people with disseminated gastric MALT lymphoma who need treatment; for example, people who are symptomatic or with threatened vital organ function.

1.4.8 Consider 'watch and wait' (observation without therapy) for people with disseminated gastric MALT lymphoma who are asymptomatic and do not have threatened vital organ function.

Non‑gastric MALT lymphoma

1.4.9 For people with non‑gastric MALT lymphoma, take into account the following before recommending any treatment:

  • site of involvement and potential for organ dysfunction

  • whether it is localised or disseminated

  • the morbidity associated with any treatment proposed

  • the person's overall fitness.

1.4.10 Offer chemotherapy (for example, chlorambucil or CVP) in combination with rituximab[2] to people with non‑gastric MALT lymphoma for whom radiotherapy is not suitable or who have disseminated disease and need treatment.

1.4.11 Consider radiotherapy for people with localised disease sites of non‑gastric MALT lymphoma, irrespective of stage.

1.4.12 Consider 'watch and wait' (observation without therapy) for people with clinically non‑progressive localised non‑gastric MALT lymphoma that is unlikely to result in vital organ dysfunction, who are asymptomatic and for whom radiotherapy is not suitable.

1.5 Management of mantle cell lymphoma

First‑line treatment

1.5.1 Offer chemotherapy in combination with rituximab[2] 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.

1.5.2 Consider cytarabine[3]‑containing immunochemotherapy for people with advanced‑stage mantle cell lymphoma who are fit enough to tolerate an intensive approach.

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

1.5.4 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.

1.5.5 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 bortezomib for previously untreated mantle cell lymphoma (NICE technology appraisal guidance 370).]

The guideline committee did not assess evidence or develop recommendations on bendamustine for treating people with mantle cell lymphoma, because a NICE technology appraisal on 'the clinical and cost effectiveness of bendamustine in combination with rituximab within its licensed indication for the first‑line treatment of mantle cell lymphoma' was in development. This technology appraisal is currently suspended.

Consolidation with stem cell transplantation

1.5.6 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.

Maintenance strategies

1.5.7 Consider maintenance rituximab[4], 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.

1.5.8 Consider maintenance rituximab[5], 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.

1.6 Management of diffuse large B‑cell lymphoma

Radiotherapy in first‑line treatment

1.6.1 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.

Central nervous system prophylaxis

1.6.2 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.

1.6.3 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.

1.6.4 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.

1.6.5 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.

Salvage therapy and consolidation with stem cell transplantation

1.6.6 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.

1.6.7 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.

1.6.8 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.

1.7 Management of Burkitt lymphoma

First‑line treatment

1.7.1 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.

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

1.7.3 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.

1.8 Management of peripheral T‑cell lymphoma

First‑line treatment

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

Consolidation therapy

1.8.2 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.

1.9 Information and support

1.9.1 To help people with non‑Hodgkin's lymphoma (and their family members or carers as appropriate) to make decisions about care, follow the recommendations in the NICE guidelines on patient experience in adult NHS services, improving outcomes in haematological cancers – the manual (patient‑centred care), improving supportive and palliative care for adults with cancer and care of dying adults in the last days of life. Pay particular attention to the following areas:

  • establishing the best way of communicating with the person

  • timing and format of information

  • information about treatment, including benefits, short‑term risks and late effects

  • financial support and benefit advice

  • fertility issues

  • sexual function

  • support groups

  • access to wellbeing services and psychological support.

1.9.2 Give people with non‑Hodgkin's lymphoma (and their family members or carers as appropriate) detailed information about the nature and purpose of diagnostic and staging tests, including:

  • bone marrow biopsies

  • central line insertion

  • core and excision biopsies

  • CT and PET‑CT scans

  • lumbar punctures.

1.9.3 If 'watch and wait' (observation without therapy) is suggested for a person with non‑Hodgkin's lymphoma:

  • explain to them (and their family members or carers as appropriate) about what this involves and why it is being advised

  • address any increased anxiety that results from this approach.

1.9.4 Explain to people with low‑grade non‑Hodgkin's lymphoma about the possibility of transformation to high‑grade lymphoma, taking into account the person's needs and preferences. Involve family members or carers as appropriate.

1.9.5 Ensure that people with non‑Hodgkin's lymphoma have:

  • a named key worker at diagnosis and during treatment and

  • contact details for the specialist team after treatment.

1.9.6 Discuss exercise and lifestyle with people with non‑Hodgkin's lymphoma from diagnosis onwards.

1.10 Follow‑up for people with diffuse large B‑cell lymphoma

1.10.1 For people in complete remission after first‑line treatment with curative intent for diffuse large B‑cell lymphoma:

  • offer regular clinical assessment

  • consider stopping regular clinical assessment aimed at detecting relapse 3 years after completing treatment for people in ongoing complete remission

  • offer urgent appointments to people who experience a recurrence of lymphoma symptoms or new symptoms that suggest disease relapse

  • do not offer LDH surveillance for detecting relapse

  • do not offer routine surveillance imaging (including chest X‑ray, CT and PET‑CT) for detecting relapse in people who are asymptomatic.

1.11 Survivorship

1.11.1 Provide end‑of‑treatment summaries for people with non‑Hodgkin's lymphoma (and their GPs). Discuss these with the person, highlighting personal and general risk factors, including late effects related to their lymphoma subtype and/or its treatment.

1.11.2 Provide information to people with non‑Hodgkin's lymphoma when they complete treatment about how to recognise possible relapse and late effects of treatment.

1.11.3 At 3 years after a person with non‑Hodgkin's lymphoma completes a course of treatment, consider switching surveillance of late effects of treatment to nurse‑led or GP‑led services.



[1] 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.

[2] 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.

[3] 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.

[4] 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.

[5] 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.

  • National Institute for Health and Care Excellence (NICE)