Can multiple myeloma cause low albumin and elevated alkaline phosphatase (ALP)?

Multiple Myeloma Can Cause Low Albumin and Elevated Alkaline Phosphatase

Yes, multiple myeloma can cause both low serum albumin and elevated alkaline phosphatase (ALP) levels through several disease mechanisms. These laboratory abnormalities are important in both the diagnosis and prognostic assessment of multiple myeloma patients.

Low Albumin in Multiple Myeloma

• Low serum albumin is a well-established finding in multiple myeloma and is incorporated into the International Staging System (ISS) for prognostication 1
• Serum albumin < 3.5 g/dL is used as a key criterion in the ISS staging system, with lower albumin levels associated with more advanced disease 1
• The pathophysiology of hypoalbuminemia in multiple myeloma involves:
  • Decreased synthesis of albumin in the liver due to the underlying plasma cell proliferative disorder 2
  • Increased catabolism related to the inflammatory state associated with the malignancy 1
  • Potential renal losses of protein in patients with myeloma kidney disease 1

Elevated Alkaline Phosphatase in Multiple Myeloma

• Elevated ALP occurs in approximately 35% of multiple myeloma patients 3
• The most common cause of elevated ALP in multiple myeloma is bone involvement:
  • Pathological fractures can significantly increase serum ALP levels 2
  • Extensive bone lesions (one of the CRAB criteria) stimulate osteoblastic activity, leading to increased ALP 1
• Other potential causes of elevated ALP in multiple myeloma include:
  • Liver involvement from the disease process 3
  • Medication-related hepatotoxicity (e.g., lenalidomide) 4
  • Infiltration of the liver by plasma cells in advanced disease 1

Clinical Significance and Prognostic Value

• Low albumin is a poor prognostic indicator in multiple myeloma:

  • ISS stage II includes patients with serum albumin < 3.5 g/dL and β2-microglobulin < 3.5 mg/L 1
  • Patients with low albumin generally have worse outcomes compared to those with normal albumin levels 1

• ALP levels may have prognostic significance:

  • Moderate elevation of ALP (70-120 U/L) has been associated with better survival compared to very low (<70 U/L) or high (≥120 U/L) levels 5
  • ALP elevation during bortezomib treatment may predict better treatment response 6

Diagnostic Considerations

• When evaluating a patient with suspected multiple myeloma who has low albumin and elevated ALP:
  • Consider the full spectrum of CRAB criteria (hypercalcemia, renal insufficiency, anemia, bone lesions) 1
  • Assess for other biomarkers of malignancy (≥60% clonal bone marrow plasma cells, involved/uninvolved serum free light chain ratio >100, >1 focal lesion on MRI) 1
  • Perform a complete laboratory workup including serum protein electrophoresis, immunofixation, and serum free light chain assay 1
  • Conduct imaging studies to evaluate for bone disease, which may explain the elevated ALP 1

Important Caveats

• Not all cases of elevated ALP in multiple myeloma patients are directly caused by the disease:
  • Rule out other common causes of elevated ALP, such as biliary obstruction, primary liver disease, or medication effects 1
  • Consider measuring GGT to confirm hepatic origin of elevated ALP 1
• Low albumin may have multiple contributing factors in myeloma patients:
  • Malnutrition can exacerbate hypoalbuminemia 1
  • Renal dysfunction, common in myeloma, can contribute to albumin losses 1
  • Concurrent liver disease may further decrease albumin production 2

By understanding these laboratory abnormalities in the context of multiple myeloma, clinicians can better assess disease severity, prognosis, and treatment response in affected patients.