What is the significance of the tests ordered in making the diagnosis of plasma cell myeloma?
The revised International Myeloma Working Group (IMWG) criteria for the diagnosis of plasma cell myeloma and related disorders are shown on Table 1. The diagnosis of plasma cell myeloma requires the presence of one or more myeloma defining events (MDE) in addition to evidence of either 10% or more clonal plasma cells on bone marrow examination or a biopsy-proven plasmacytoma.

MDE consist of established:
1. CRAB (hypercalcemia, renal failure, anemia, or lytic bone lesions) features
2. Three specific biomarkers: clonal bone marrow plasma cells ≥60%, serum free light chain (FLC) ratio ≥100 (provided involved FLC level is ≥100 mg/L), and more than one focal lesion on MRI. Each of the new biomarkers is associated with an approximately 80% risk of progression to symptomatic end-organ damage in two or more independent studies.

The updated criteria represent a paradigm shift since they allow early diagnosis and initiation of therapy before end-organ damage.

What are the typical features seen in this patient that are helpful in making the diagnosis of plasma cell myeloma?
1. The first approach to this patient is: what’s the cause of her shortness of breath (SOB). Once the pulmonary, cardiac, renal, hepatic, psychotic abnormality had been excluded for the cause of her SOB, then it is meant to be her anemia.
2. The next issue will be: what’s the etiology of her anemia. The formal first step of anemia survey is to calculate reticulocyte production index (RPI). If RPI<2%, it suggested a bone marrow underproduction and MCV would be used to further differential diagnosis, as the algorithm figure showed.

Δ Other causes of normocyticanemia include monoclonal gammopathies, androgen deficiency (male), MDS, clonalcytopenias, copper deficiency, and others. Multiple causes may be present. The risks of clonal disorders and hematologic malignancies generally increases with age or exposure to bone marrow toxins including certain chemotherapy drugs. Aplastic anemia and Diamond-Blackfan anemia are less age dependent.
(Reference: Uptodate).

3. Patient’s normocytic anemia was led to be bone marrow infiltrative disease after excluding iron deficiency, Folate deficiency, nor vitamin B12 deficiency. Then bone marrow examination is indicated.
4. Another hint for suspicion of plasma cell myeloma is A/G reverse. Patient’s albumin level is 2.8 g/dL, total protein level is 13.0 g/L, then the estimated globulin level will be 10.2 g/dL. It’s reasonable to suspect plasma cell myeloma for this high level of globulin.

What are the next steps in management of this patient? 
In addition to therapy directed at the malignant clone, the management of most patients with plasma cell myeloma (MM) includes preventative measures to reduce the incidence of skeletal events, renal damage, infections, and thrombosis.
1. Skeletal lesions and bone health: Prevention — Osteoclast inhibitors (eg, bisphosphonate therapy) are administered to prevent skeletal events in patients with one or more lesions on skeletal imaging and those with osteopenia
2. Kidney impairment — All patients with myeloma should take measures to minimize kidney damage (e.g., avoid nephrotoxins such as aminoglycosides and NSAIDs and maintain adequate hydration). Many medications used for myeloma require dose adjustment for kidney impairment (e.g., lenalidomide, zoledronic). Treatment of kidney impairment is directed at the underlying cause. 
3. Infection — Prophylactic measures that may minimize infection in patients with MM include yearly influenza vaccines, pneumococcal vaccine at the time of diagnosis, prophylactic antibiotics during the first months of induction chemotherapy, and intravenous immune globulin for selected patients who have recurrent, serious infections.
4. Thromboembolism — Patients with MM are at increased risk of having comorbidities known to be risk factors for the development of venous thromboembolism (VTE) in the general population. In addition, treatment with immunomodulatory drugs (e.g., lenalidomide, pomalidomide, thalidomide) has been associated with high rates of VTE. All patients with MM should have an assessment of their VTE risk so that appropriate prophylaxis may be employed.
Multiple myeloma: Overview of management - UpToDate

Patient Care (Case Correlation to ACGME Core Competency Requirements)
1.Understand the most important test for diagnosis of plasma cell myeloma.
2.Recognize the clinical manifestations of plasma cell myeloma.
3.Obtain an appropriate history to determine if a patient presented with symptoms of “CRAB”.
4.Determinewhat is the initial step encountering similar patient and when to refer to hematology.

Medical Knowledge (Case Correlation to ACGME Core Competency Requirements)
1.Understand the evaluation of anemia.
2.Understand the imaging abnormality of metastatic bone lesion in CT scan.
2.Interpret the results of immunofixation electrophoresis.
3.Determine how to treat patient with plasma cell myeloma.

Practice-Based Learning and Improvement (Case Correlation to ACGME Core Competency Requirements)
1.Set goals for studying about plasma cell myeloma epidemiology, risk factor, clinical manifestations, diagnosis and treatment options.
2.Demonstrate the ability to perform bone marrow biopsy.

Interpersonal and Communication Skills (Case Correlation to ACGME Core Competency Requirements)
1.Discuss the results of lab and radiographic finding with a patient.
2.Discuss the diagnosis of plasma cell myeloma with a patient.
3.Discuss the need for appropriate follow up and monitoring with a patient
4.Comprehensively explain different treatment options based on disease manifestations.

Professionalism (Case Correlation to ACGME Core Competency Requirements)
1.Encourage patients and family to ask questions regarding their disease and empower them to be active participants in their care.
2.Provide adequate time and accessibility to address patient and family’s concerns.
3.Demonstrate an understanding of informed consent with regard to invasive procedure like bone marrow biopsy. (如網頁下方附件：骨髓抽取及切片檢查說明暨同意書.pdf)

System-Based Practice (Case Correlation to ACGME Core Competency Requirements)
1.Create a team approach to manage patients with anemia and A/G reverse, engaging physicians from multiple disciplines.
2.Identify barriers to access and delivery of care for patients with recurrent , refractory diseases.
3.Learn about resources available to improve delivery of care and patient support.



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