A Cohort Study of Free Light Chain Ratio in Combination with Serum Protein Electrophoresis as a First-Line Test in General Practice
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Laboratory Methods
2.3. Statistics
3. Results
3.1. Patients
3.2. sFLC Ratio Test Results
3.3. Diagnostic Value of Individual and Combined Tests
3.4. Clinical Cut-Offs
3.5. Comorbidity
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Patients Characteristics | Total | Patients without MCD | Patients with MCD |
---|---|---|---|
Total, n | 13,210 | 12,916 | 294 |
Age | |||
Years, Median (range) | 64 (1–106) | 64 (1–106) | 70 (39–97) |
Sex | |||
Female, n (%) | 7961 (60) | 7841 (61) | 120 (41) |
Male, n (%) | 5249 (40) | 5075 (39) | 174 (59) |
Creatinine, µmol/L, Median (range) | 71 (40–280) | 71 (41–189) | 76 (40–280) |
Number of patients for each analysis, n (%) | |||
sFLC κ:λ | 3742 (28) | 3595 (28) | 144 (49) |
SPE | 12,950 (98) | 12,658 (98) | 292 (99) |
UPE | 3373 (26) | 3237 (25) | 136 (46) |
Combinations of analyses, n (%) | |||
SPE | 6717 (51) | 6619 (51) | 98 (33) |
SPE and UPE | 2649 (20) | 2598 (20) | 51 (17) |
UPE | 102 (<1) | 101 (1) | 1(<1) |
SPE and FLC ratio | 2964 (22) | 2905 (22) | 59 (20) |
UPE and FLC ratio | 2 (<1) | 2 (<1) | 0 |
FLC ratio | 156 (<1) | 155 (1) | 1 (<1) |
SPE, UPE and FLC ratio | 620 (5) | 536 (4) | 84 (29) |
Diagnostic Tests | Total (N) | MCD (N) | Sensitivity | Specificity | PPV | NPV | False Positive N (%) | False Negative N (%) |
---|---|---|---|---|---|---|---|---|
Individual tests | ||||||||
SPE | 12,950 | 292 | 89.7 (85.7–93.0) | 95.9 (95.6–96.3) | 33.7 (30.4–37.2) | 99.8 (99.6–99.8) | 515 (4) | 30 (<1) |
UPE | 3373 | 136 | 50.7 (42.0–59.4) | 92.3 (91.3–93.2) | 21.6 (17.2–26.6) | 97.8 (97.2–98.3) | 250 (7) | 67 (2) |
sFLC κ:λ (0.26–1.65) | 3742 | 144 | 71.5 (63.4–78.7) | 83.7 (82.5–84.9) | 14.9 (12.4–17.8) | 98.7 (98.2–99.0) | 586 (16) | 41 (1) |
sFLC κ:λ (0.26–4.32) | 3742 | 144 | 51.4 (42.9–59.8) | 97.8 (97.3–98.3) | 48.4 (40.2–56.6) | 98.0 (97.5–98.5) | 79 (2) | 70 (2) |
sFLC κ:λ (0.26–7.0) | 3742 | 144 | 43.8 (35.5–52.3) | 98.4 (98.0–98.8) | 52.9 (43.6–62.2) | 97.8 (97.2–98.2) | 56 (1) | 81 (2) |
sFLC κ:λ (0.1–10.0) | 3742 | 144 | 34.7 (27.0–43.1) | 99.4 (99.0–99.6) | 68.5 (56.6–78.9) | 97.4 (96.9–97.9) | 23 (1) | 93 (2) |
Combination of test * SPE and UPE a | 3269 | 135 | 95.6 (90.6–98.4) | 88.4 (87.2–89.5) | 26.2 (22.3–30.3) | 99.8 (99.5–99.9) | 364 (11) | 6 (<1) |
SPE and sFLC κ:λ (0.26–1.65) b | 3584 | 143 | 95.1 (90.2–98.0) | 80.3 (79.0–81.6) | 16.7 (14.2–19.5) | 99.7 (99.5–99.9) | 677 (19) | 7 (<1) |
SPE a | 3269 | 135 | 87.4 (80.6–92.5) | 95.0 (94.2–95.7) | 42.9 (37.0–49.0) | 99.4 (99.1–99.7) | 157 (5) | 17 (3) |
SPE b | 3584 | 143 | 86.0 (79.2–91.2) | 95.1 (94.3–95.8) | 42.1 (36.4–48.0) | 99.4 (99.1–99.6) | 169 (5) | 20 (1) |
UPE a | 3269 | 135 | 50.4 (41.6–59.1) | 92.2 (91.2–93.1) | 21.8 (17.3–26.8) | 97.7 (97.1–98.2) | 244 (7) | 67 (2) |
sFLC κ:λ (0.26–1.65) b | 3584 | 143 | 71.3 (63.2–78.6) | 83.3 (82.1–84.6) | 15.1 (12.5–18.0) | 98.6 (98.1–99.0) | 573 (16) | 41 (7) |
Alternative reference ranges for sFLC κ:λ SPE + sFLC κ:λ (0.26–4.32) b | 3584 | 143 | 93.0 (87.5–96.6) | 93.6 (92.7–94.4) | 37.7 (32.6–43.0) | 99.7 (99.4–99.9) | 229 (6) | 10 (<1) |
FLC- κ:λ b | 3584 | 143 | 51.0 (42.6–59.5) | 97.8 (97.2–98.2) | 48.7 (40.4–57.0) | 98.0 (97.4–98.4) | 77 (2) | 70 (2) |
SPE + sFLC κ:λ (0.26–7.00) b | 3584 | 143 | 92.3 (86.7–96.1) | 94.0 (93.2–94.8) | 39.2 (33.9–44.6) | 99.7 (99.4–99.8) | 205 (6) | 11 (<1) |
sFLC κ:λ b | 3584 | 143 | 43.4 (35.1–51.9) | 98.4 (98.0–98.8) | 53.4 (44.0–62.8) | 97.7 (97.1–98.1) | 54 (2) | 81 (2) |
SPE + sFLC κ:λ (0.1–10) b | 3584 | 143 | 92.3 (86.7–96.1) | 94.8 (94.0–95.5) | 42.3 (36.8–48.0) | 99.7 (99.4–99.8) | 180 (5) | 11 (<1) |
sFLC κ:λ b | 3584 | 143 | 34.3 (26.5–47.7) | 99.3 (99.0–99.6) | 68.1 (56.0–78.6) | 97.3 (96.7–97.8) | 23 (<1) | 94 (3) |
Patient | Diagnosis | κ | λ | sFLC κ:λ | UPE | Days from Sample until Diagnosis |
---|---|---|---|---|---|---|
1 | MM | 1728 | 1 | 1728 | N/A | 2 |
2 | MM | 13 | 386 | 0.03 | pos | 150 |
3 | Amyloidosis | 681 | 11 | 61.9 | N/A | 35 |
4 | Amyloidosis * | 64 | 859 | 0.07 | pos | 47 |
5 | WM * | 33 | 6 | 5.48 | pos | 65 |
6 | MGUS | 27 | 15 | 1.8 ** | neg | 34 |
7 | MGUS | 1350 | 6 | 225 | pos | 351 |
8 | MGUS | 559 | 18 | 31.1 | pos | 9 |
9 | MGUS* | 155 | 36 | 4.31 ** | pos | 890 |
10 | MGUS | 490 | 39 | 12.6 | pos | 17 |
11 | MGUS | 187 | 7 | 26.7 | pos | 12 |
12 | MGUS* | 22 | 13 | 1.69 ** | pos | 20 |
13 | MGUS | 13 | 287 | 0.05 | pos | 2 |
Comorbidity | Comorbidity Prior to Blood Test | Comorbidity 3 Months after Blood Test | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
n = 3742 | MCD | Non-MCD | MCD | Non-MCD | ||||||||||
Total | sFLC Abnomal | sFLC Normal | p-Value * | sFLC Abnormal | sFLC Normal | p-Value * | Total | sFLC Abnormal | sFLC Normal | p-Value * | sFLC Abnormal | sFLC Normal | p-Value * | |
Myocardial infarction | 152 | 4 | 0 | NA | 24 | 124 | 0.98 | 166 | 4 | 0 | NA | 25 | 137 | 0.76 |
Congestive heart failure | 398 | 9 | 2 | NA | 62 | 325 | 0.88 | 438 | 10 | 3 | NA | 72 | 353 | 0.70 |
Peripheral vascular | 386 | 5 | 4 | NA | 56 | 321 | 0.43 | 437 | 7 | 5 | 0.32 | 63 | 362 | 0.38 |
Cerebrovascular | 205 | 5 | 0 | NA | 34 | 166 | 0.78 | 232 | 5 | 0 | NA | 38 | 189 | 0.85 |
CPD | 290 | 7 | 2 | NA | 45 | 236 | 0.90 | 344 | 7 | 2 | NA | 49 | 286 | 0.39 |
Diabetes | 210 | 5 | 0 | NA | 42 | 163 | 0.09 | 251 | 5 | 0 | NA | 50 | 196 | 0.08 |
Diabetes with end-organ damage | 68 | 2 | 0 | NA | 12 | 54 | 0.84 | 79 | 2 | 0 | NA | 14 | 63 | 0.65 |
Renal disease | 82 | 0 | 2 | NA | 25 | 55 | <0.001 | 118 | 2 | 2 | NA | 32 | 82 | 0.001 |
Mild liver disease | 15 | 1 | 0 | NA | 2 | 12 | NA | 24 | 1 | 0 | NA | 2 | 21 | NA |
Ulcer disease | 51 | 2 | 1 | NA | 7 | 41 | 1.00 | 76 | 3 | 1 | NA | 8 | 64 | 0.26 |
Connective tissue disease | 50 | 1 | 0 | NA | 11 | 48 | 0.24 | 67 | 8 | 1 | NA | 14 | 52 | 0.27 |
Any tumour | 204 | 5 | 1 | NA | 53 | 145 | <0.001 | 396 | 8 | 1 | NA | 77 | 310 | 0.04 |
Leukaemia | 2 | 0 | 0 | 1 | 1 | NA | 10 | 0 | 0 | 4 | 6 | NA | ||
Lymphoma | 0 | 4 | 1 | 0 | NA | 0 | 3 | NA | ||||||
Metastatic solid tumor | 57 | 2 | 1 | NA | 14 | 40 | 0.05 | 907 | 17 | 8 | 0.64 | 138 | 744 | 0.55 |
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Sandfeld-Paulsen, B.; Aggerholm-Pedersen, N.; Samson, M.H.; Møller, H.J. A Cohort Study of Free Light Chain Ratio in Combination with Serum Protein Electrophoresis as a First-Line Test in General Practice. Cancers 2022, 14, 2930. https://doi.org/10.3390/cancers14122930
Sandfeld-Paulsen B, Aggerholm-Pedersen N, Samson MH, Møller HJ. A Cohort Study of Free Light Chain Ratio in Combination with Serum Protein Electrophoresis as a First-Line Test in General Practice. Cancers. 2022; 14(12):2930. https://doi.org/10.3390/cancers14122930
Chicago/Turabian StyleSandfeld-Paulsen, Birgitte, Ninna Aggerholm-Pedersen, Mie Hessellund Samson, and Holger Jon Møller. 2022. "A Cohort Study of Free Light Chain Ratio in Combination with Serum Protein Electrophoresis as a First-Line Test in General Practice" Cancers 14, no. 12: 2930. https://doi.org/10.3390/cancers14122930