Case 95 – summary

Thankyou for all your help this week.

This week we had a look at mantle cell lymphoma (MCL). MCL is a type of none Hodgkin’s lymphoma, and comprises between 3 and 10% of NHL, and often has features of both high and low grade lymphomas.

It has the chromosomal abnormality t(11;14)(q13;q32) which results in an over expression of cyclin d1.

MCL is more common in men and usually presents in the older population. Patients will often present with widespread lymphadenopathy, which not infrequently involves extranodal sites. Bone marrow/peripheral blood/splenic involvement are common at diagnosis.

The clinical course for patients presenting with MCL is variable. In some cases the MCL may behave more aggressively from the outset, whereas others may have an initial more indolent course. Patients who have blastoid MCL histologically usually have a more aggressive lymphoma, with a shorter survival and a lower response rate to treatment.

Although CNS involvement is uncommon at presentation, CNS relapse can occur in in up to 7.8% of patients. This is more likely if the patient has blastoid MCL or MCL with a high Ki67 on histology. Patients with CNS involvement have a poor prognosis.

When working up a patient it is important to ensure they have certain investigations completed

  • FBC and film to look for evidence of involvement, this can be sent for flow cytometry if suspected.
  • LDH
  • Hep B (SA and core Ab), hep C status prior to immunotherapy
  • HIV
  • If no peripheral blood involvement bone marrow aspirate and trephine to help establish staging
  • CT N/C/A/P to establish baseline lymphadenopathy
  • LP with cytology and flow if suspicion of CNS disease
  • MRI brain can also be useful to assess CNS disease.

Scoring systems

The MIPI is used to prognosticate disease into low medium and high risk categories. A link to the calculator can be found below. But age, LDH,ECOG and peripheral blood white cell count all play a part. Ki67 can also be included if using MIPIc

http://www.european-mcl.net/en/clinical_mipi.php

Some studies have shown that up to 92% of patients may have GI involvement, upper and lower GI endoscopy can be performed to assess, although this may not affect treatment. However in a patient with what appear to be otherwise stage 1A disease, or with other GI symptoms/bleeding this should be considered.

Once tissue has be acquired for diagnosis, if through bone marrow or peripheral blood flow cytometry can be performed. MCL usually expresses – CD5+,CD19+,CD22+,CD79b+,FMC7+, light clonal light chain expression is usually moderate. CD10 is occasionally positive.

If using lymph node/other affected tissue/bone marrow trephine IHC can be performed to establish diagnosis. MCL is usually CD20+,CD5+,BCL2+,cyclinD1+,SOX1+ and CD10-,CD23-,BCL6-

Cytogenetics can also be used to establish diagnosis and some cytogenetic abnormalities may be able to predict a poorer prognosis.

t(11;14)(q13·3;q32·33) is the cytogenetic abnormality behind MCL cases and can be detected by FISH, however many patients may have other cytogenetic abnormalities. Complex karyotypes are usually associated with a poorer prognosis and, as with other disorders, TP53 mutations confer a poorer prognosis

Treatment

Each patient needs careful assessment to decide if treatment is needed. In patients with an indolant, fairly asymptomatic disease a watch and wait approach may be adopted. As with other low grade lymphomas, indications for treatment can include bone marrow failure, bulky disease, symptomatic organomegaly, B symptoms and GI bleeding from MCL involvement.

Clinical trials should be offered to patients where available when considering treatment.

Considerations for type/intensity of treatment include age,comorbidities and performance status.

For first line treatment, in fit patients who would be suitable for an autologous SCT, to ensure a greater chance of achieving an optimal response a regime containing high dose cytarabine plus rituximab should be used.

For first line treatment in those patients not fit for auto SCT RCHOP and R-bendamustine are commonly used. In those less fit patients other immunochemotherapy regimes such as R-chlorambucil can be considered.

Regardless of upfront treatment with or without auto SCT rituximab maintainence treatment can be used and aim to increase duration of response to treatment.

CT can be used to assess response to treatment. MRD for t(11;14) has also be shown to be helpful in prognosticating patients, but is not widely used.

Options for 2nd line treatment can include brutonkinase inhibitors, R-CHOP and R-BENDA+/-cytarabine. Auto SCT (following treatment) if not done at first line and patient fit can be done. Consideration for ALLO SCT in younger fitter patients can also be made following 2nd line treatment.

Other drugs including venetoclax (BCL2 inhibitor) are currently being trialed for use in MCL and look promising.

Thankyou for your participation this week. Is there anything you would like to ask/add/and knowledge you would like to share?

For further reading we would recommend the BSH guidelines

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