Page 17 - 2019_07 resto del Mondo-web

Editorials
Table 1. Staging systems for AL amyloidosis.
Models
Mayo2004
Mayo2004
European Mayo2012
Variables and cutoffs
• NT-proBNP, 332 ng/L (or BNP, 81 ng/L) • cTnT, 0.035 ng/mL (or cTnI, 0.1 ng/mL)
Mayo 2004 stage III is divided into two groups according to
• NT-proBNP, 8500 ng/L (or BNP, 700 ng/L)
• NT-proBNP, 1800 ng/L
• cTnT, 0.025 ng/mL (or cTnI 0.1 ng/mL, or hs-cTnT 40 ng/L) • dFLC, 180 mg/L
Stages
Stage I: both variables below the cutoffs Stage II: one variable above the cutoff Stage III: both variables above the cutoffs
Stage IIIa: Mayo2004 stage III and NT-proBNP (or BNP) below the cutoff
Stage IIIb: Mayo2004 stage III and NT-proBNP (or BNP) above the cutoff
Stage I: all markers below the cutoffs Stage II: one marker above the cutoffs Stage III: two markers above the cutoffs Stage IV: all markers above the cutoffs
NT-proBNP, amino-terminal portion of pro-brain natriuretic peptide type B; BNP, natriuretic peptide type-B; cTnT, cardiac troponin T; cTnI, cardiac troponin I; hs-cTnT, high sensitivity cardiac troponin T; dFLC, difference between involved and uninvolved free light chain concentration.
Figure 1. Odds ratio for very early death (within 6 months of diagnosis) of patients classified as being at highest risk by the three staging systems. Data from 1,065 patients with AL amyloidosis diagnosed between 2004 and 2015 at the Pavia Amyloidosis Research and Treatment Center. Mayo 2004 stage III. Odds ratio 5.68 (95% confidence interval: 4.03- 8.00). Mayo 2012 stage IV. Odds ratio 5.82 (95% confidence interval: 4.22- 8.05). Mayo 2004/European stage IIIb. Odds ratio 7.42 (95% confidence interval: 5.24- 10.51).
find a significant advantage in discriminating ability of one model over the others. However, the Mayo2004/European staging system had the greatest ability to identify patients who died within the first year after diagnosis. In a landmark analysis including patients who survived at least 1 year, there was no difference in discriminating ability between the Mayo2004/European and the Mayo2012 staging sys- tems. Interestingly, however, in a 3-year landmark analysis, the Mayo 2012 model performed better than the Mayo2004/European staging system.
How do these studies help in selecting the best way to stratify patients with AL amyloidosis? Clearly, four-stage models perform better than the Mayo2004 staging system. Not surprisingly, the Mayo2004/European model, which was designed to detect very high-risk subjects, has the best performance in identifying patients who die early. In a series of 1,065 patients diagnosed with AL amyloidosis at the Pavia Amyloidosis Research and Treatment Center, subjects classified as stage IIIb with the Mayo2004/European model had the highest odds ratio for death within 6 months of diagnosis (Figure 1). Moreover, the Mayo2004/European staging system performs better in patients with atrial arrhythmia and low eGFR. Thus, the
Mayo2004/European model, which is powerful, simple (based on only 2 markers), and less influenced by confound- ing factors, appears to be generally preferable, and particu- larly useful in assessing eligibility for clinical trials. Stage IIIb patients identified by the Mayo2004/European staging sys- tem are at the highest risk of early death and should only be enrolled in clinical trials specifically designed for these extremely fragile subjects. However, while early deaths are mainly caused by severe cardiac dysfunction at presenta- tion, long-term survival is probably influenced by the ten- dency of the amyloid plasma cell clone to relapse. Indeed, the Mayo2012 model, which includes a marker of clonal disease burden, has better discriminating ability 3 years after diagnosis. Nevertheless, when relapse occurs, restag- ing with either the Mayo2004/European or the Mayo2012 staging system can reliably stratify patients with different survival.20
The fact that patients’ survival can be very effectively pre- dicted by staging systems entirely or mainly based on car- diac biomarkers emphasizes the peculiarity of AL amyloi- dosis: a hematologic disease causing multiorgan dysfunc- tion in which death most often occurs as a consequence of cardiac involvement. Thus, the workup of patients with AL
haematologica | 2019; 104(7)
1295