Daily C - Reactive Protein (CRP) Levels Allow Early Identification of Patients with Severe Complications after Melphalan (MEL) and Autologous Stem Cell Transplantation (ASCT) for Multiple Myeloma (MM).

Background: CRP is an acute-phase reactant that increases rapidly in response to inflammation (including infection).

Objective: to assess the value of daily CRP level as a predictor of severe complications [pneumonia, bacteremia or severe mucositis (Grades 3–4, NCI Common Toxicity Criteria)] after MEL-ASCT for MM.

Patients and Methods: 199 MM patients (pts) who received a MEL-ASCT and had daily CRP levels on days 0–21 after ASCT.

Results: Median age was 58 years (32 – 77) and 60% were males. Mucositis was present in 89% of pts and was severe in 20%; bacteremia and pneumonia developed in 23 % and 13 % of pts respectively.Daily CRP levels (days 0-21): All pts with severe complications had higher daily CRP levels vs. those with mild or no complications (p< 0.0001). Higher CRP levels were observed among pts with pneumonia (p< 0.0001 vs. no pneumonia), bacteremia (p< 0.0001 vs. no bacteremia) and severe mucositis (p=0.002 vs. mild (grades 1–2) and no mucositis). When present among pts with mild mucositis, infection was associated with a higher CRP level (p< 0.0001 vs. no infection). CRP peak levels: Comparable CRP peak levels were observed among pts with various complications: pneumonia (n=27), bacteremia (n=46) or severe mucositis (n=41) [Mean and range in mg/dl: 16.6 (3.63 – 35.3); 17.18 (1.29 – 36.9); 17.81 (4.8 – 36.01) respectively; p= 0.95]. The presence of infection among pts with mild mucositis significantly increased CRP peak [mean and range 15.73 (1.29 – 36.9) vs. 11.59 (1.31 – 35.06) respectively, p= 0.0028].Rate of CRP increase: A significantly faster rate of CRP increase was observed among pts with severe complication vs. those with mild or no complications: mean and range of increase: 2.39 mg/dl/day (0.30 – 9.86) vs. 1.9 mg/dl/day (0.15 – 7.83). A model predictive of severe complications based on rate of CRP increase per day was developed based on the following formula:

p = exp(−0.6630 + 0.1837 * CRP slope (mg /dl/day))

1+ exp (−0.6630 + 0.1873 * CRP slope (mg/dl/day))

This model will now be prospectively validated.

Conclusions: Daily CRP levels provide an early identification of MM pts with severe complications after MEL-ASCT. Higher CRP levels correlate with severe mucositis and/or infection. Among pts with mild mucositis, a rapidly increasing and/or a high CRP level suggest the presence of severe infection.