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Case study (24) – Multiple Myeloma

Case study (24) – Multiple Myeloma

A 76-year-old man had a history of abdominal pain, polyuria, and nocturia for 2 weeks.

He also noticed that the size of skin nodules was increasing.

Laboratory Investigation:

1. CBC:

Hemoglobin (Hb) 71 g/L

White blood cells (WBC) 4.6 X 109/L

Platelets 112 X 109/L

2. Other Investigations:

Urea 46 mmol/L

Creatinine 905 mmol/L

Ca2+ 3.60 mmol/L (N 2.1–2.6 mmol/L)

Albumin 26 g/L (N 35–42 g/L)

Total protein 120 g/L (N 65–80 g/L)

Alkaline phosphatase 143 U/L (N 30–130 U/L)

Uric acid 0.48 mmol/L (N 0.3–0.4 mmol/L)

3. Bone marrow aspiration smear:


Q1. Comment on the above Laboratory investigations results.

Q2. Comment on the bone marrow aspirate smear.


A 1: The results indicate anemia and thrombocytopenia with marked renal failure. Hypercalcemia with normal alkaline phosphatase suggests primary bone marrow malignancy. 

The suppression of serum albumin and raised total protein suggests myeloma.

A2: The bone marrow is infiltrated by plasma cells, confirming myeloma. 

Plasma cell leukemia is an aggressive form of myeloma characterized by large numbers of circulating plasma cells.

Q3: Comment on the skull x-ray.

Q4: What is the diagnosis?

Q5: How should he be treated?

A3: The skull x-ray shows multiple lytic lesions, a characteristic finding in myeloma.

A4: Multiple Myeloma.

A5: The hypercalcemia and renal failure require urgent therapy with rehydration to promote diuresis. 

Intravenous urogram (IVU) should not be performed because the patient should not be dehydrated. However, abdominal ultrasound scanning to rule out renal obstruction is valuable in acute renal failure.

The baseline test should include quantification of paraproteins in serum and urine (Bence Jones protein), skeletal survey, beta-2 microglobulin, and C-reactive protein.

Other baseline tests should contain a coagulation profile, culture of mid-stream urine, and assessment of antibodies to hepatitis A, B, and C.

Serum-free light chains should be estimated as they are elaborated by the tumor cells and are often the principal cause of the renal toxicity. 

A kidney biopsy should be considered, and the nephrologist wants to perform a series of tests to rule out other causes of acute renal insufficiency. 

A complete cardiac assessment including echocardiography is very important, and the presence of amyloid deposits, such as in the heart and kidneys, should be considered.

Baseline assessment should also cover the genetic analysis of the cells by fluorescent in situ hybridization (FISH) and/or chromosome analysis. The International Staging

System (ISS) for myeloma is given in the table.

Molecular changes in myeloma

1. Translocations should involve immunoglobulin heavy chain (lgh) locus, e.g. t(11;14) (translocation of CCNDI), t(4;14) (misregulation of fibroblast growth Factor III

and multiple myeloma SET [MMSET] domain)

2. Copy number alterations, e.g. hyperdiploidy, deletion 13, gains of 1q, trisomies, 17p deletion

3. Mutation – e.g. in the ERK pathway

4. Methylation modification

5. Late events are signs of cloning progress, such as RAS activation, MYC dysregulation

ERK, extracellular signal-related kinases.

International Staging System

Stage I

Stage I Beta-2 microglobulin <5.3 mg/dL, albumin >35 mg/dL

Stage II

Stage II Remainder

Stage III

Stage III Beta-2 microglobulin >5.5 mg/dL


Imaging techniques are important for the detection of skeletal and neurologic involvement.

The patient should receive allopurinol (at a reduced dose of 100 mg/day because of his renal failure) followed by steroid therapy for hypercalcemia. 

If the calcium remains raised, consider bisphosphonates, for example, zoledronic acid or pamidronate, given by intravenous (IV) infusion, dose adjusted for renal impairment. 
Renal failure may warrant the institution of dialysis.

Chemotherapy should be commenced once he is stabilized. Bortezomib is a proteosome inhibitor that is administered subcutaneously alongside dexamethasone. 

The addition of an anthracycline drug, for example, Adriamycin should be considered; it can be given as an infusional regime with the bortezomib and dexamethasone.

Cyclophosphamide may be added as a weekly bolus; it is preferred in renal failure, as it is metabolized by the liver. 

Thalidomide is an immunomodulatory agent that also has direct anti-myeloma effects; side effects include drowsiness, constipation, neuropathy, and a critical need to avoid pregnancy (self or partner). 

A stable phase of the disease is typically achieved after four to six cycles of chemotherapy.

Long-term bisphosphonate therapy (e.g. sodium clodronate) may slow the progress of skeletal disease in myeloma. 

The typical course of myeloma is that patients relapse but will counter to the reinstitution of chemotherapy.

Older regimes which may have a role in relapsed patients include vincristine, adriamycin, both by IV infusion, and dexamethasone (VAD), and the combination of idarubicin and dexamethasone.

Younger patients (those under 65) with myeloma may benefit from intensive therapy, including autologous transplants of peripheral blood stem cells. 

Patients under 50 with human leukocyte antigen (HLA)- matching sibling may be considered for allogeneic hemopoietic stem cell transplantation, although this method has higher toxicity and lower efficacy than conventional methods than in acute leukemia and relapsed lymphoma.

A monoclonal antibody specific for CD38 has recently been licensed and has activity as a single agent and in combination with pomalidomide.