Our case concentrated on presentation, investigation and management of DLBCL.
This 42 year old gentleman had presented with a history of B-symptoms and palpable lymphadenopathy. Bloods tests revealed an acute kidney injury highlighting the need for urgent treatment.
CT scanning demonstrated bulky disease with an intrabdominal mass measuring 1ocm. It also demonstrated widespread lymphadenopthy above and below the diaphragm as well as kidney and splenic involvement. His blood counts demonstrated an anaemia which may suggest marrow involvement also.
Biopsy is organised promptly, however PET is not available for a further 3 days. The decision to commence treatment was based on clinical deterioration and therefore PET was cancelled. The patient was treated appropriately to prevent tumour lysis given he had bulky disease and acute kidney injury.
The patients treatment was discussed at MDT and the decision to commence R-CHOP chemotherapy was based on confimation of histology ensuring the biopsy was negative for c-myc, BCL6, BCL2, which would be associated with a poorer prognosis and indicate escalation of therapy in this young, previously fit patients. Our patient had an IPI of 4.
Intrathecal prophylaxis was also considered.
Diffuse large B-cell lymphoma is the most common non-hodgkins lymphoma accounting for 30-40% of cases.
- Hepatitis B and C
- ECHO – in patients > 65 or previous cardiac history
- Consider sperm banking
- staging CT – neck, chest, abdo, pelvis
- if CNS involvement – CT/MRI head + LP + intrathecal
- surgical excision or incisional biopsy
PET vs Staging BM
Current guidelines suggest a staging bone marrow at diagnosis. However this practice is a topic for debate and a number of hospitals no longer perform staging bone marrows. Studies have suggested PET is more sensitive than bone marrow for DLBCL and although low level disease <10-20% may be missed, this is unlikely to affect prognosis.
International IPI should be calculated for all patients.
- >60years of age
- stage III or IV disease
- elevated LDH
- ECOG > 1
- More than 1 extranodal site
0-1 points – low risk – 5 year survival 73%
2 points – low intermediate risk 5 yr survival 51%
3 points – 5 year survival 43%
4-5 points – 5 year survival 26%
Histology samples should be tested for MYC rearrangements by FISH. If present this confers a poorer prognsis. Samples should then also be tested for BCL2 and/or BCL6 (double-hit or triple- hit) lymphoma. Double HIT lymphoma is clinically aggressive and has a prognosis of <12 months. Therefore the presence of these rearrangments may prompt escalation of therapy.
As per BCSH guidelines high risk of CNS relapse according to anatomical sites include; testicular, cranial air sinuses, bone, breast, renal and epidural space. Guidelines suggest CNS directed therapy should be offered to all patients with DLBCL with an elevated LDH and more than one extranodal site (not including spleen), or anatomical sites -testicular, breast and epidural.
The patient in this case certainly qualifies for CNS prophylaxis. The form of prohylaxis needs to be discussed within the clinical team. Options of intrathecal methotraxate versus high does intravenous prophylaxis need to be considered.
Calculating the CNS-IPI may facilitate this decision. For further reading on this see references below!
Guidelines recommend R-CHOP chemotherapy. However patients with poor risk IPI can be consider for escalated therapy of R-CHOEP-14 or R-CODOX-M/IVAC.
Radiotherapy should also be consider for our patients. It is recommended that patients receive IFRT to sites of >7.5cm and extranodal disease following completion of chemotherapy therefore this management plan should have been discussed at the MDT for this patient. An end of treatment PET would be strongly recommended and biopsy of any PET positive lesion at this stage.
CNS international prognostic index: A risk model for CNS relapse in patients with diffuse large B-cell lymphoma treated with R-CHOP. Schmitz, N et al. Journal of clinical oncology, volume 34, number 26, september 10 2016.
Staging DLBCL: bone marrow biopsy or PET-CT? Avigdor, A. Blood 2013, 122:4-5
Guidelines for the management of diffuse large B cell lymphoma. Changanti, S et al 2016
CNS prophylaxis in NHL. McMilan, A et al. 2013