Case 102 – The Summary

 

Thank you for all the contributions to the case this week!

This week we discussed a 29 year old lady who presented with an extensive left arm DVT. She had been on the COCP for 2 years. Further investigations detected a large mediastinal mass that was confirmed to be Stage 2 Primary Mediastinal B cell Lymphoma. From our discussions we covered the following topics that will be discussed further below:

  • Upper extremity DVT
  • Cancer-associated thrombosis
  • Primary mediastinal B cell lymphoma

Upper Extremity DVT1,2

  • Account for upto 10% of all DVTs. The incidence is increasing predominantly due to the increasing use of central venous catheters and pacemakers.
  • Include radial, ulnar, brachial, axillary, subclavian, brachiocephalic and jugular veins.
  • Aetiology
    • Primary
      • Idiopathic
      • Thoracic outlet syndrome (compression of neurovascular bundle secondary to first rib, clavicle or muscle bulk)
      • Paget-Schroetter syndrome (vigorous effort causes microtrauma to the vessel resulting in thrombosis)
    • Secondary
      • Foreign body within vascular system i.e central venous catheter, pacemaker (most common risk factor)
      • Malignancy
      • Surgery, immobilisation
      • Acquired thrombophilia i.e anti-phospholipid syndrome
      • Inherited thrombophilia i.e anti-thrombin deficiency
      • Others (extensive list as for lower limb DVT / PE although Combined oral contraceptive pill / hormonal replacement therapy have not been convincingly found to be risk factors but no RCTs).

Clinical presentation:

  • Venous congestion e.g swelling, pain, dilation of the superficial veins

Investigations:

  • Compression ultrasound / venography
  • Investigations of underlying cause (directed by history / examination)

NB: DDimer has NOT been validated for the use of upper limb DVT

Complications:

  • PE
  • Post thrombotic syndrome
  • Superior vena cava syndrome
  • Recurrence

Management:

  • Anticoagulation
    • Various options regarding the type of anticoagulation exist including
      • LMWH
      • LMWH for 5 days followed by warfarin
      • DOACs are being increasing used (note studies regarding the efficacy of DOACs were not specific for upper limb DVT)
    • The optimal duration of anticoagulation is unknown. Periods of anticoagulation of 3-6 months tend to be associated with low risk of recurrence (<5%) but the risk needs to be individually assessed.
  • Catheter directed thrombolysis / thrombectomy can be considered in specific circumstances
  • Treatment of risk factor e.g resection of cervical rib, scalenotomy

 

Cancer-associated Thrombosis3,4:

  • Initial anticoagulation should be for 6 months if tolerated. In on-going active malignancy anticoagulation should be continued (with consideration of patient preference, bleeding risk etc)
  • Anticoagulation options
    • LMWH (lower VTE recurrence rate vs warfarin -7.9% vs 15%)
    • DOACs4
      • 2 RCTs for edoxaban and rivaroxaban (HOKUSAI Cancer and SELECT-D respectively) demonstrated non-inferiority vs LMWH in recurrence of VTE in cancer patients. However there was increased risk of bleeding especially in gastrointestinal and urological malignancies. Therefore in setting of thrombocytopenia one may opt for LMWH.
      • The effects of cancer treatment needs to also be considered when deciding re use of edoxaban or rivaroxaban in this setting. For example, whether will be absorbed and drug-drug interactions.
  • Anticoagulation in setting of thrombocytopenia3:
    • Platelets <50 x 109/l: Give plt transfusions to elevate plt >50 to allow full dose anticoagulation (especially in acute period 4-6 weeks)
    • Platelets 25-50 x 109/l: Frequent assessment of anticoagulation should occur
    • Platelets <25 x 109/l: Avoid full dose anticoagulation.

 

Primary Mediastinal B Cell Lymphoma (PMBCL)5

  • Subtype of DLBCL (~10%), derived from a thymic B cell
  • Females > males
  • Typically presents in 3rd and 4th decades

Clinical presentation

  • Bulky anterior mediastinal mass
  • 75% stage 1 or 2
  • Symptoms relating to local compression e.g airway compromise, superior vena cava obstruction
  • Symptoms relating to local invasion
  • B symptoms
  • 50% have pleural or pericardial effusions. CNS / bone marrow involvement not uncommon.

Investigations:

  • FBC, U+Es, LFTs, bone profile, LDH, urate
  • HIV, hepatitis B+C
  • CT neck/chest/abdo/pelvis
  • PET CT
  • Biopsy
    • Significant histopathological overlap between PMBCL and nodular sclerosing Hodgkin lymphoma
    • Morphology: Medium-large lymphoid cells, often sclerosis and some cells can resemble Reed-Sternberg cells. Often extensive fibrosis.
    • Immunophenotype: CD20+, CD22+, CD79a+, sIg-, CD30weak, CD15-, CD5-.

Management:

There is no single approach to treatment currently and the need for consolidative radiotherapy and role of PETCT after R-chemo remains controversial. It is important to optimise upfront therapy as salvage treatment once disease has relapsed is rarely curative. However, the longer-term toxicities need to be considered in this young patient cohort.

Chemo-immunotherapy options:

  • DA-EPOCH-R (6 cycles)

3 year PFS 83-93% (Dunleavy 2013, Kryachok 2016 ESMO). May be able to omit radiotherapy if end of treatment PET shows complete metabolic remission but ongoing IELSG 37 trial to assess this. Would currently recommend discussion with oncologist to discuss potential options. Note this regime contains high anthracycline doses.

  • R-CHOP (6 cycles)

3 year PFS ~70% (Rieger 2011 MInT, Kryachok 2016 ESMO). Typically require radiotherapy.

  • (R-)V/MACOP/B – less commonly used.

Thromboprophylaxis

  • To be considered as high risk of thrombotic complications (28.2% – Roth 2017, Lugano) including upper extremity DVT, superior vena cava, intracardiac etc.

Supportive therapies:

  • Blood product support
  • Antimicrobial support
  • Pyschological

References

  1. Tait C et al. Guidelines on the investigation and management of venous thrombosis at unusual sites. British Journal of Haematology. 2012. 159(1): 28-38.
  2. Heil J et al. Deep Vein Thrombosis of Upper Extremity. Deutsches Arzteblatt International. 2017. 114(14): 244-249.
  3. Watson H et al. Guideline on aspects of cancer-related venous thrombosis. British Journal of Haematology. 2015. 170(5): 640-648.
  4. Khorana A et al. Role of Direct Oral Anticoagulants in the treatment of cancer-associated venous thromboembolism: guidance from the SSC of the ISTH. Journal of Thrombosis and Haemostasis. 2018. 16:1891-1894.
  5. Giulino-Roth L. How I treat Mediastinal B-cell Lymphoma. Blood. 2018. http://www.bloodjournal.org/content/bloodjournal/early/2018/07/05/blood-2018-04-791566.full.pdf?sso-checked=true

 

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