The impact on revised IMWG diagnostic criteria of new findings regarding BM aspiration and BM biopsy

In a letter to the editor of the Blood Cancer Journal, N. Lee and colleagues from the Seoul National University Hospital, Korea, described their findings regarding discrepancies between the percentage of plasma cells (PCs) as assessed by bone marrow (BM) aspiration (BMA) and BM biopsy (BMB). With new guidelines (issued by the International myeloma working group, IMWG) placing more emphasis on the PC percentage, and less emphasis on previously used CRAB symptoms (hypercalcemia, renal insufficiency, anemia, bone lesion), the need for accurate measurement of PC percentage is critical. Previous measurements of BMA did not take into account dilution of peripheral blood and there was no consensus regarding the volume taken, resulting in significant user error. In addition, routine methods to calculate PC percentage using BMB lacked objectivity.

Currently, the presence of clonal PC >10% is the main indicator for Multiple Myeloma (MM). The new guidelines indicate that BMB can be used in addition to BMA to assess PC percentage and that in cases of discrepancy, the higher value for either method should be considered. Therefore, this study set out to evaluate the percentage PC of BMB in patients with a low measured BMA PC (<10%), and to track the conversion rate from BMA PC (<10%) to BMB PC (≥10%), in order to assess user error and to compare PC estimates using the two different methods.

Key Highlights

• Pts enrolled with newly diagnosed MM (NDMM) = 389
• BMA PC<10% = 67 pts; 58 were available for analysis of BMB
• CD138 staining was used for image analysis of BM sections
• BMB PC count ≥ 10% = 55 pts and <10% = 3 pts
• Mean PC% in BMB = 52.9%; SD = 30.7
• Adequate BMA quality = 39.7%; mild to severe dilution = 60.3%
• Most pts with diluted BMA had increased PC% upon BMB
• Pts were divided into two groups on the basis of BMA PC ≥10% or <10%
• Pts with BMA PC<10% were further subdivided into two groups on the basis of BMB PC% ≥10% or <10%
• Median OS: high BMB PC% = 93.2 months vs. low BMB PC% = 67.9 months (p=0.010)
• Median OS: BMA PC% = no significant difference
• Conversion rate of BMA PC <10% to >10% in BMB = 75% (55/73 pts)
• Majority of pts with <10% PC in BMA had diluted BM aspiration and less diffuse PC in BMB
• BMB PC% moderately correlated with corresponding end organ disorders, quantitative FISH results, and OS in patients with low BMA PC%

Obtaining an accurate PC count has become increasingly important for the accurate diagnosis of MM. The authors established that the BMB PC count provides more diagnostic relevance than BMA, and better reflects the recently revised criteria, although combined evaluation (of both BMA and BMB) is more reliable for diagnosis. The use of CD138 staining and image analysis for PC% by BMB enables greater objectivity and decreased user error, and is practical enough for routine clinical use.