Oncology Case Study: A Dog with Epistaxis

I will post the Day 3 answers below so we can move on to the next part of the case:

Question 1: Describe the main findings on the CT images.

• There are multifocal, irregular, osteolytic lesions affecting the vertebral body, pelvis and left femur. The lysis involves medullary and cortical bone.

Question 2: Interpret the SPE trace.

• The main findings on SPE include a reduction in albumin and a large sharp peak in the gamma globulin region, consistent with a monoclonal gammopathy.
• See the image attached that show a normal SPE result and a polyclonal gammopathy.

Question 3: What is your diagnosis in Barney’s case, and why?

• Multiple myeloma. The presence of a monoclonal gammopathy, in absence of any obvious infectious cause, alongside the multifocal lytic bony lesions (in bone regions involved with haematopoiesis) is consistent with multiple myeloma. The coagulopathy, azotaemia, ionised hypercalcaemia and cytopenias also fit with the clinical presentation of multiple myeloma.

DAY 4

Based on your investigations, Barney has been diagnosed with multiple myeloma (MM).

Question 1: What are the specific criteria for diagnosing MM in dogs? What other tests can help diagnose MM in dogs, not used in Barney’s case?

Question 2: In light of Barney’s diagnosis, explain the underlying pathophysiology behind the coagulopathy, neutropenia, thrombocytopenia, azotaemia, and ionised hypercalcaemia.

I will post the answers below so we can move on to the final part of the case:

Question 1: What are the specific criteria for diagnosing MM in dogs? What other tests can help diagnose MM in dogs, not used in Barney’s case?

• A definitive diagnosis of MM comes from demonstrating two or more of:
  • Osteolytic bone lesions
  • M-component (e.g. monoclonal gammopathy on SPE, or detection of urine Bence Jones proteins – note, hyperglobulinaemia alone not sufficient)
  • Bone marrow plasmacytosis (bone marrow biopsy demonstrating >20% plasma cells)
• If, for example, Barney did not have any bony changes on CT scan then a bone marrow biopsy would be required to definitively diagnose him with MM. Sometimes we will be happy with documentation of plasmacytosis in other organs such as the spleen instead, if bone marrow biopsy is not possible.

Question 2: In light of Barney’s diagnosis, explain the underlying pathophysiology behind the coagulopathy, neutropenia, thrombocytopenia, azotaemia, and ionised hypercalcaemia.

• Coagulopathy has many possible underlying causes in patients with MM. Around 50% of MM patients have abnormal PT/APTT, and up to 30% have clinical signs of bleeding. The M-component (secreted immunoglobulin) can:
  • Inhibit platelet aggregation
  • Inhibit tissue factor
  • Inhibit proteins S + C
  • Cause abnormal fibrin polymerisation
  • Reduce available calcium
• Neutropenia and thrombocytopenia likely due to myelophthisis
• Renal disease is present in up to 50% of dogs with MM. The pathogenesis can be multifactorial and due to:
  • Bence Jones (light chain) proteinuria
  • Tumour infiltration into kidneys
  • Hypercalcaemia
  • Amyloidosis
  • Reduced perfusion (hyperviscosity syndrome)
  • Pyelonephritis (MM patients are often immunocompromised and prone to infection)
• Ionised hypercalcaemia is present in up to 50% of dogs with MM and is mostly due to tumour cell production of osteoclast activating factor (OAF), but they can also secrete TNF-a, IL-1 and IL-6.

DAY 5

Barney’s owner is currently trying to decide whether to treat his MM or not.

Question 1: What would you advise them regarding treatment options and associated prognosis? Think about Barney’s immediate treatment requirements/options as well as the longer-term management of MM.

Question 2: What would you advise Barney’s owner regarding monitoring response to treatment (both in terms of efficacy and adverse effects). What possible adverse effects should his owner’s be aware of with treatment?

Here are the answers for the final post:

Question 1: What would you advise them regarding treatment options and associated prognosis? Think about Barney’s immediate treatment requirements/options as well as the longer-term management of MM.

• Acute management:
  • Analgesia: paracetamol, opioids +/- gabapentin/amantadine +/- bisphosphonates (e.g. pamidronate/zoledronate – these can be very good for bone pain associated with lytic bone lesions)
  • Management of azotaemia: IVFT (4ml/kg/hr initially)
  • Management of hypercalcaemia: as the hypercalcaemia is mild-moderate you can initially assess response to IVFT at 4ml/kg/hr (lactated Ringer’s) initially. Other options if needed include corticosteroids and bisphosphonates, but often the hypercalcaemia will improve when managing the underlying MM
  • Monitor PCV/transfusion triggers if ongoing bleeding
• Treating MM:
  • Optimum chemotherapy protocol is melphalan + prednisolone
    • Melphalan 0.1mg/kg PO SID for 10d, then 0.05mg/kg PO SID ongoing
    • Prednisolone 0.5mg/kg PO SID for 10d, then 0.5mg/kg PO EOD for 60d
  • MM can be rewarding to treat with a 79 – 94% response rate to treatment, and median survival time between 1.5 – 2.5 years. Treatment is required long-term as long as it is tolerated, and is not curative – relapse will eventually occur, but rescue chemotherapy can be considered at this time
  • As melphalan can take a bit of time to start working, other alkylating agents such as cyclophosphamide (250mg/m² IV) can be given at the same time as starting oral melphalan, to try and resolve clinical signs quicker – this would be the recommended approach in Barney’s case due to his bleeding diatheses and hypercalcaemia/azotaemia, which should be managed as quickly as possible.

Question 2: What would you advise Barney’s owner regarding monitoring response to treatment (both in terms of efficacy and adverse effects). What possible adverse effects should his owner’s be aware of with treatment?

• Melphalan is often very well tolerated in most dogs, with minimal adverse effects. The main considering is a cumulative myelosuppression, particularly thrombocytopenia, with the risk increasing with continued use. Adverse effects can include:
  • Myelosuppression (particularly thrombocytopenia)
  • Gastrointestinal toxicity
• An ideal monitoring plan for dogs with MM treated with melphalan is outlined below. It is important to note that measuring globulins only is a relatively crude method for monitoring response to treatment, and repeating SPE is most accurate. This approach assesses for adverse effects of treatment as well as assessing treatment efficacy:
  • 2 weeks after starting treatment: Haematology, globulins
  • 4 weeks after starting treatment: Haematology, full biochemistry
  • 8 weeks after starting treatment: Haematology, globulins
  • 12 weeks after starting treatment: Haematology, biochemistry, SPE +/- repeat imaging
  • Then:
    • Every 4 – 6 weeks: Haematology, globulins
    • Every 3 – 4 months: Haematology, biochemistry, SPE +/- imaging as indicated