Recurrent disease may be discovered by the patient or by surveillance in the post-treatment period. Symptoms can often present as:

• a lump or mass in any organ
• lymphadenopathy, particularly lymphadenopathy that lasts more than two weeks
• splenomegaly with or without systemic symptoms in the absence of, or after resolution of, any infection
• one or more of these systemic symptoms even in the absence of lymphadenopathy: fever, drenching night sweats, unexplained weight loss, frequent infections, unexplained

Managing residual or relapsed disease is complex and should therefore involve all the appropriate specialties in a multidisciplinary team including palliative care where appropriate. From the time of diagnosis, the team should offer patients appropriate psychosocial care, supportive care, advance care planning and symptom-related interventions as part of their routine care. The approach should be personalised to meet the patient’s individual needs, values and preferences. The full complement of supportive care measures as described throughout the optimal care pathway and in Appendices A, B and C should be offered to assist patients and their families and carers to cope. These measures should be updated as the patient’s circumstances change.

Survivorship care should be considered and offered at an early stage. Many people live with advanced cancer for many months or years. As survival is improving in many patients, survivorship issues should be considered as part of routine care. Health professionals should therefore be ready to change and adapt treatment strategies according to disease status, prior treatment tolerance and toxicities and the patient’s quality of life, in addition to the patient’s priorities and life plans.

In a suspected relapse, consider conducting a biopsy to confirm the relapse. Also consider whether there are clinical features to suggest transformation to high-grade lymphoma or involvement by a different lymphoma or neoplasm. In the event of a re-biopsy, the appropriate tissue diagnostic and prognostic investigations can be undertaken again as necessary. Molecular tests may in the near future be able to guide use of novel therapies (e.g. EZH2 mutation in FL).

Re-staging of relapsed or refractory disease should be performed with CT-PET scan, or if indolent disease was previously PET-negative, with CT scan. Consider a repeat bone marrow biopsy to evaluate the cause of cytopenias.

In managing people with low-grade lymphomas, treatment may include these options according to the British Society of Haematology (2020) and ESMO guidelines general concepts:

• first: assess performance status and comorbidities
• options:
  • asymptomatic relapse – watch and wait
  • localised relapse – consider radiation therapy
  • widespread and systemic recurrence – consider systemic therapy +/− autologous transplantation
• pre-screen patient for any currently recruiting or imminent clinical trial
• consider palliation
• treatment decision: collaboration between patient and specialist.

If there is an indication that a patient’s cancer has returned, care should be provided under the guidance of a treating specialist. Each patient should be evaluated to determine if referral to the original multidisciplinary team is necessary. Often referral back to the original multidisciplinary team will not be necessary unless there are obvious aspects of care involving different therapeutic and supportive care disciplines not otherwise accessible. The multidisciplinary team may include new members such as palliative care specialists.

Treatment will depend on the location, extent of recurrent or residual disease, previous management and the patient’s preferences.

In managing people with a low-grade lymphoma, treatment may include these options:

• The choice of systemic salvage treatment generally depends on the efficacy of previous regimens and the duration since the end of the prior If fewer than 24 months have elapsed since the prior treatment, a treatment regimen containing different, non-cross-resistant agents is optimal
• With additional immunosuppressive effects of therapy, the risk of opportunistic infection Prophylaxis is important with antimicrobials and/or immunoglobulin replacement as appropriate. Similarly, consider G-CSF as a primary or secondary prophylaxis for periods of neutropenia.

Follicular and marginal zone lymphomas (ESMO 2020)

• Asymptomatic patients may be observed (watch and wait).
• Radiation therapy may be considered for those with localised relapse, to defer systemic immuno-chemotherapy.
• Low-dose radiation therapy should be considered to palliate symptomatic sites of
• If systemic treatment is required, refer to Australian, British and European
• Consolidation of chemoimmunotherapy with autologous transplantation may be considered in fit patients.
• With many promising novel therapies, such as BTK inhibitors, and bi-specific antibody and CAR T-cell therapies, screening of patients for clinical trials are strongly

Mantle cell lymphoma

• At relapse, a BTK inhibitor should be considered as a priority
• Enrolment in a clinical trial is strongly
• In younger patients with adequate performance status and comorbidities, consider reduced- intensity allogeneic haematopoietic stem cell

Advance care planning is important for all patients with a cancer diagnosis but especially those with relapsed disease. Patients should be encouraged to think and talk about their healthcare values and preferences with family or carers, appoint a substitute decision-maker and consider developing an advance care directive to convey their preferences for future health care in the event they become unable to communicate their wishes (Australian Government Department of Health 2021a).

More information

Refer to section 4.3 ‘More information’ for links to resources.

Refer patients and carers to Advance Care Planning Australia  or to the Advance Care Planning National Phone Advisory Service on 1300 208 582.

Early referral to palliative care can improve the quality of life for people with cancer and in some cases may be associated with survival benefits (Haines 2011; Temel et al. 2010; Zimmermann

et al. 2014). The treatment team should emphasise the value of palliative care in improving symptom management and quality of life to patients and their carers. Refer to section 4.3 for more detailed information.

The lead clinician should ensure timely and appropriate referral to palliative care services. Referral to palliative care services should be based on the patient’s need and potential for benefit, not prognosis.

More information

Refer to the end of section 4.3 ‘Palliative care’ for links to resources.

Novel therapies are substantially improving the overall survival and quality of life for patients with low-grade lymphomas. The treatment team should be aware of and support the patient to take part in research and clinical trials where available and appropriate.

For more information visit:

• Cancer Australia 
• Australian New Zealand Clinical Trials Registry
• Australasian Leukaemia and Lymphoma Group
• ClinTrial Refer 
• Clinical Trials for an international view.