Inconsistency in prognostic scores occurs where two different risk categories are applied to the same chronic myeloid leukemia (CML) patient. This study evaluated common scoring systems for identifying risk groups based on patients’ molecular responses to select the best prognostic score when conflict prognoses are obtained from patient profiles. We analyzed 104 patients diagnosed with CML and treated at King Abdulaziz Medical City, Saudi Arabia, who were monitored for major molecular response (achieving a
The Australian Institute of Health and Welfare (AIHW) classified myeloid cancers as the ninth most commonly diagnosed cancer in 2016, with more than 3,600 cases in Australia [
Prognostic scores in patients with CML are used to stratify CML patients according to risk profile to ensure appropriate treatment. Historically, the science of prognostication has evolved rapidly, and various scoring systems have been developed to optimize the use of clinical experience in CML treatment. These scores were developed using logistic regression with the selection of the patients’ clinical and hematological parameters at diagnosis. The common prognostic scores have shown variable correlation with complete cytogenetic response (CCyR) [
The European LeukemiaNet (ELN) current recommendations for the management of CML are basically addressed to the goal of achieving an at least MMR [
Our analysis evaluated the different scores outcomes with the long-term molecular response in patients treated with imatinib to determine which was the best prognostic score to apply where a conflict prognosis was generated by prognostic scores.
Participants in this study were members of the Saudi population diagnosed with CML and treated at King Abdulaziz Medical City, Jeddah [
Characteristics of 95 patients with CML at diagnosis.
Factor | Median | Range | SD |
---|---|---|---|
Age (yrs) | 40.21 | 18–74 | 15.13 |
Spleen size (cm, BCM) | 8.33 | 0–25 | 7.53 |
Platelet count (×109/L) | 510.97 | 4.42–2876 | 439.88 |
Basophils (%) | 1.32 | 0–7 | 1.10 |
Eosinophils (%) | 0.83 | 0–0.07 | 1.24 |
Peripheral blast (%) | 1.50 | 0–10 | 1.39 |
SD = standard deviation; BCM = below costal margin.
Four common prognostic scoring systems are available for CML patients prior to commencing therapy: (1) the Sokal score [
The current methods used to identify risk in CML.
Scoring systems | ||||||
---|---|---|---|---|---|---|
Study | Factors | Equation | Method | Risk categories | Target prediction | Data and results |
Sokal score, Sokal et al. [ | Age, spleen size (cm), blast (%), and platelets (109/L) | exp(0.0116 × (age [years] − 43.4)) + 0.0345 × (spleen size [cm] − 7.51) + (0.188 × ((platelets [109/L]/700)2 − 0.563)) + (0.0887 × (blasts [%] − 2.10)) | Multivariate analysis of survival | Low-risk score < 0.8, of patients, intermediate-risk in 0.8–1.2, and high-risk > 1.2 | Risk groups for chemotherapy | Six European and American sources ( |
| ||||||
Hasford score, Hasford et al. [ | Age, spleen size (cm), blasts (%), eosinophils (%), basophils (%), and platelets (109/L) | (0.6666 × age [0 when age < 50 years; 1 otherwise]) + (0.0420 × spleen size [cm]) + (0.0584 × blasts [%]) + (0.0413 × eosinophils [%]) + (0.2039 × basophils [0 when basophils < 3%; 1 otherwise]) + (1.0956 × platelet count [0 when platelets < 1500 × 109/L; 1 otherwise]) × 1000 | Multivariate analysis of survival | Low-risk score ≤ 780, intermediate-risk in 781–1480, and high-risk ≥ 1481 | Risk groups for interferon alpha alone | 14 studies ( |
| ||||||
EUTOS score, Hasford et al. [ | Basophils (%) and spleen size (cm) | (7 × basophil [%]) + (4 × spleen [cm]) | Multivariate analysis of response | Low-risk score < 87 and high-risk ≥ 87 | CCgR at 18 months to imatinib | Five national study groups ( |
| ||||||
ELTS score, Pfirrmann et al. [ | Age, spleen size (cm), blast (%), and platelets (109/L) | 0.0025 × (age in completed years/10)3 + 0.0615 × spleen size below costal margin + 0.1052 × blasts in peripheral blood + 0.4104 × (platelet count/1000)−0.5 | Multivariate analysis of response | Low-risk score ≤ 1.5680, intermediate-risk in 1.5680–2.2185, and high-risk > 2.2185 | Long-term survival | ( |
The analysis is conducted in two steps: (1) studying the prognostic index using combined groups and (2) consistency analysis between the risk categories obtained from the scoring systems. First, from Table
Secondly, in consistency analysis, the combined category is selected based on the higher-accuracy results from combined groups to study the inconsistency between scoring systems. We are dealing with two models advising on the same patient. Each score may provide an index that conflicts with the other. The patients were classified into a consistency group or an inconsistency group. The consistency group included patients who observed consistent risk categorization from scoring systems, while the inconsistency group included patients who observed inconsistent risk categorization from scoring systems. The possible combination of risk categories for
This study presents the analysis of each scoring system for distinguishing patients. We evaluated scoring systems in CML for identifying risk categories based on patients’ molecular responses to determine which was the best prognostic score to apply where a conflict prognosis was generated by prognostic scores.
Of the 104 CML patients included in this study, the data of 9 patients were removed due to incomplete MMR data, to improve overall data quality. Of the 95 patients with complete data, 33 (34%) did not achieve MMR, while 62 (65%) did achieve MMR. The number of CML patients per prognostic score included in the two different combined methods is shown in Table
The number of patients in different risk groups as per calculated scores.
| Not achieving MMR | Achieving MMR | Accuracy | |
---|---|---|---|---|
Combined groups (1) | ||||
| ||||
High | 25 | 11 | 14 | 62.10 |
Low and intermediate | 70 | 22 | 48 | |
| ||||
High | 6 | 4 | 2 | 67.37 |
Low and intermediate | 89 | 29 | 60 | |
| ||||
High | 10 | 4 | 6 | 63.15 |
Low | 85 | 29 | 56 | |
| ||||
High | 17 | 7 | 10 | 62.10 |
Low and intermediate | 78 | 26 | 52 | |
| ||||
Combined groups (2) | ||||
| ||||
Intermediate and high | 62 | 23 | 39 | 48.42 |
Low | 33 | 10 | 23 | |
| ||||
Intermediate and high | 46 | 20 | 26 | 58.94 |
Low | 49 | 13 | 36 | |
| ||||
High | 10 | 4 | 6 | 63.15 |
Low | 85 | 29 | 56 | |
| ||||
Intermediate and high | 42 | 19 | 23 | 61.05 |
Low | 53 | 14 | 39 |
It is clearly observed that the combined method of low and intermediate risk in Sokal, Hasford, and ELTS score as low risk achieved higher accuracy than the second combined method of intermediate and high risk in Sokal, Hasford, and ELTS score as high risk. Comparison of the accuracies in Sokal was 62.10% versus 48.42%, Hasford was 67.37% versus 58.94%, and ELTS was 62.10% versus 61.05%. Indeed, the ELN [
In Table
The consistency/inconsistency of prognostic scores for predicting major molecular response.
Analysis groups | Score prediction | MMR | Total | ||||
---|---|---|---|---|---|---|---|
Sokal | Hasford | EUTOS | ELTS | Achieving MMR, | Not achieving MMR, | ||
Conflict group | Low and intermediate | Low and intermediate | Low | High | 5 | 2 | 30 |
Low and intermediate | Low and intermediate | High | Low and intermediate | 0 | 0 | ||
Low and intermediate | Low and intermediate | High | High | 0 | 1 | ||
Low and intermediate | High | Low | Low and intermediate | 0 | 0 | ||
Low and intermediate | High | Low | High | 0 | 0 | ||
Low and intermediate | High | High | Low and intermediate | 0 | 0 | ||
Low and intermediate | High | High | High | 0 | 0 | ||
High | Low and intermediate | Low | Low and intermediate | 7 | 5 | ||
High | Low and intermediate | Low | High | 0 | 1 | ||
High | Low and intermediate | High | Low and intermediate | 1 | 1 | ||
High | Low and intermediate | High | High | 4 | 0 | ||
High | High | Low | Low and intermediate | 1 | 1 | ||
High | High | Low | High | 0 | 1 | ||
High | High | High | Low and intermediate | 0 | 0 | ||
| |||||||
Consensus group | Low and intermediate | Low and intermediate | Low | Low and intermediate | 43 | 19 | 65 |
High | High | High | High | 1 | 2 | ||
| |||||||
Single score in consensus group and conflict group | Low and intermediate | 48 | 22 | 95 | |||
High | 14 | 11 | |||||
Low and intermediate | 36 | 13 | |||||
High | 26 | 20 | |||||
Low | 56 | 29 | |||||
High | 6 | 4 | |||||
Low and intermediate | 52 | 26 | |||||
High | 10 | 7 | |||||
| |||||||
Single score in conflict group | Low and intermediate | 5 | 3 | 30 | |||
High | 13 | 9 | |||||
Low and intermediate | 17 | 10 | |||||
High | 1 | 2 | |||||
Low | 13 | 10 | |||||
High | 5 | 2 | |||||
Low and intermediate | 9 | 7 | |||||
High | 9 | 5 |
Although the results show that the Hasford performance in the consensus and conflict groups was not recommended, the Hasford score accuracy percentage (63%) shows that Hasford may be useful in identifying risk group in conflict CML patients. In the conflict group, the Hasford prognostic score identified more low-risk categories for CML patients and few high-risk patients, while the Sokal score identified more high-risk patients and few low-risk patients. Only one study [
There is no conflict of interests regarding the publication of this paper.
Haneen R. Banjar designed and performed the research, analyzed the data, and wrote the manuscript. Enaam Alsobhi is a principle investigator of the data. Both authors contributed substantially to drafts and revisions to the manuscript. They also approved the current revised version.