In contrast to adult medicine, specific scoring systems predicting the treatment response for an individual pediatric patient (pt) with chronic myeloid leukemia (CML) have not yet been defined. We evaluated to what extend prognostic scores as described for adults (e.g., Sokal, Hasford, EUTOS score) resulted in comparable risk group categorizations in a pediatric cohort. Parameters for score calculation were extracted from a data set of 90 patients enrolled into trial CML-PAED-II and treated by a standard dose of imatinib. At month 3 and at month 6, treatment response was analyzed based on the transcript ratio BCR-ABL1/ABL1. By the EUTOS, Hasford, and Sokal scores 81, 59, and 62 % of the patients were categorized as low risk, respectively; 19, 14, and 16 % of the patients as high risk, respectively; and by Hasford and Sokal scores 27 and 22 % of the patients, respectively, as intermediate risk. Twenty-seven out of 72 patients analyzable (38 %) exhibited a transcript ratio >10 % at month 3. We show that only the EUTOS score, but not the Sokal and Hasford score, correlates with this early outcome (p = 0.008). Analyzing the EUTOS score separately, we can demonstrate that lowering the cutoff from 87 to 48 points for categorization in low- and high-risk individuals increases the odds ratio from 2.4 (95 % CI 0.6 to 10.4) to 3.6 (95 % CI 1.3 to 10.9). Data are provided on the distribution of risk categories and resulting discrepancies when adult scores are applied on children and adolescents with CML at diagnosis. A larger number of patients and longer follow-up are still needed to develop a prognostic score specifically adapted to the pediatric and adolescent age cohorts.
Introduction Imatinib (IM) front-line treatment impressively improved survival of children with chronic myeloid leukemia (CML). In contrast to adult CML, specific scoring systems predicting the treatment response in individual pediatric patients (pts) are still lacking. Here we analyzed a cohort of pediatric pts with CML applying the established prognostic scores for adults in a comparative fashion. We question the value of four scoring systems (Sokal-, Sokal young-, Hasford-, Eutos-Score) especially with regard to grouping individual children differently or homogeneously into a defined risk category. In addition, we analyzed which scoring system would classify most specifically the prognosis of pediatric CML with regard to early molecular response (MR) on IM. Methods A total of 90 pts (male/female: 57/33; median age: 11.6 yrs, range: 1-18) with CML-CP enrolled in the prospective trial CML-PAED-II were included in this analysis. Registry data were collected on standardized forms filled in by the treating physicians. On this basis the Eutos-, Sokal- and Hasford-Scores were calculated using internet resources of the ELN (www.leukemia-net.org/content/leukemias/cml/cml_score), whereas the Sokal young Score (Sy) – a score described specifically for adolescents and younger adults (Sokal JE, Blood 1985;66:1352) – was manually calculated. Pts were grouped using the original three risk categories (low=LR, intermediate=IR, high=HR) or two categories, respectively, for the Eutos-Score (LR or HR). Evaluation of therapeutic response was performed by assessing the MR by measurement of the transcript ratio BCR-ABL1/ABL1 in blood specimen sent to the central reference laboratory at month 3 after start of IM treatment. Measurements were expressed according to the International Scale. Results By Sokal-Score 59/90 pts were classified as LR, 20/90 pts as IR and 11/90 pts as HR. By Hasford Score 57/90 pts were classified as LR, 25/90 pts as IR, and 8/90 pts as HR. By Eutos Score 73/90 pts were classified as LR and 17/90 pts as HR. As the hematocrit value was not collected systematically at diagnosis, this necessary parameter for calculating the Sy-Score was applicable only in 46/90 pts and thus 44/46 pts were classified as LR, 2/46 as IR, and 0/46 as HR. Comparing results of individual pts only 25/46 pts (54%) were categorized homogeneously as LR by applying all 4 scoring systems, while 54/90 pts (60%) were classified as LR if Sy-Score was excluded. Thus, the remaining 21/46 pts (46%) were grouped heterogeneously by applying each of the 4 prognostic scores, and correspondingly 33/90 pts (37%) were classified heterogeneously within different risk categories by the Eutos, Hasford and Sokal Score. Only 3 pts were categorized homogenously as HR by each of the Sokal, Hasford, and Eutos Score and by applying all 4 scoring systems no patient was concordantly classified as HR. When comparing only the Sokal-Score to the Sy-Score, discordant results were obtained in 19/46 (41%) pts. BCR-ABL1/ABL1 transcript ratio could be analyzed quantitatively in 72/90 pts at month 3 after treatment initiation. In this cohort we identified 46/72 good responders (ratio BCR-ABL1/ABL1 <10%) and 26/72 poor responders (ratio >10%). Although the Eutos-score performed best in in a logistic regression analysis with an Odds Ratio OR=3.02 to predict an unfavorable course of IM-treated CML in the HR group, the discrimination did not reach statistical significance (p=0.08). However, by reducing the cut-off point for the Eutos Score from 87 to 64 an OR=4.8 with p=0.004 was achieved, thus indicating that a refined risk categorization appears beneficial. Conclusion Comparing risk categorization by all four scores in individual pediatric pts, results may vary considerably. Keeping in mind that the number of pts analyzed is still small, especially applying the Sy-Score seems not to provide benefit in this cohort with a median age of only 11 years. Contrasting results in adults, in this pediatric cohort the Sokal- and Hasford-Scores did not predict a poor IM treatment response at month 3 while the Eutos Score achieved borderline significance. Thus, there is an urgent need for the development of a more specific pediatric risk score. Disclosures: No relevant conflicts of interest to declare.
The European Psychiatric Association (EPA) Summer School is an intensive program which has been organised for 10 years now by the EPA Committee on Education and allows selected psychiatric trainees and early career psychiatrists (ECPs) from all over Europe to meet, network, and learn together. After the 2020 edition being cancelled due to COVID-19 pandemic, the 2021 edition was held online and continued the EPA educational mission in an innovative and up-to-date approach.Twenty one participants from 16 different countries were selected to attend by the EPA Committee on Education. During the two full days of training, participants were engaged in fundamental educational activities by renowned faculty members such as Dr.
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