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448 Is the Eutos Long Term Survival (ELTS) Score a Useful Marker to Predict Outcome in Children with Newly Diagnosed Chronic Myeloid Leukemia (CML) in Chronic Phase (CP)? the Experience of the International Registry of Childhood CML

Program: Oral and Poster Abstracts
Type: Oral
Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Treatment-Free Remission and Prognostication
Sunday, December 10, 2023: 10:15 AM

Frederic Millot1*, Joe De Keizer2*, Markus Metzler, MD3*, Meinolf Suttorp4*, Petr Sedlacek, MD, PhD5*, Maaike Luesink6*, Frankie WT Cheng, MD7*, Krzysztof Kalwak8*, Birgitte Lausen9*, Gordana Jakovljevic10*, Barbara De Moerloose, MD11*, Michael Dworzak12*, Marina Borisevich13*, Julia Yajima14*, Mirella Ampatzidou15*, Roula Farah16*, Emilia Kaiserova17*, Adalet Meral Günes18* and Andre Baruchel19

1Inserm CIC 1402 - CHU Poitiers, Poitiers, France
2Inserm CIC 1402, Poitiers, France
3Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Erlangen, Germany
4Pediatric Hematology and Oncology, Medical Faculty, Technical University, Dresden, Germany
5Department of Pediatric Hematology–Oncology, University Hospital Motol, Charles University, Prague, Czech Republic
6Dutch Childhood Oncology Group, Princess Maxima Center for pediatric oncology, Princess Maxima Center for pediatric oncology, Utrecht, Netherlands
7Department of Pediatrics, Prince of Wales Hospital, Hong Kong, China
8Department of Pediatric Hematology Oncology and BMT, Wroclaw Medical University, Wroclaw, Poland
9Department of Pediatrics and Adolescent Medicine, Rigshospitalet, University of Copenhagen, Denmark, Copenhagen, Denmark
10Department of Pediatric Hematology Oncology, Children’s Hospital, Zagreb, Croatia
11Department of Pediatric Hematology-Oncology, Ghent University Hospital, Ghent, Belgium
12St. Anna Children's Cancer Research Institute, Vienna, Austria
13Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk, Belarus
14Centro Infantil Boldrini, Sao Paulo, Brazil
15Department of Pediatric Hematology Oncology, Aghia Sophia Children’s Hospital, Athens, Greece
16Department of Pediatrics, LAU Medical Center Rizk Hospital, Beirut, Lebanon
17Department of Pediatric Oncology of University Children's Hospital, Bratislava, Slovakia
18Pediatric Hematology and Oncology Hospital Görükle, Bursa, Turkey
19Department of Pediatric Hematology, Robert Debré Hospital, Paris, France

Aims. CML is a very rare disease in children. The present work aims to describe the characteristics of children with CML in chronic phase (CP) and to determine the outcome of this pediatric population.

Methods. We retrospectively analyzed children with CML in CP registered in The International Registry of Childhood Chronic Myeloid Leukemia (I-CML-Ped Study; www.clinicaltrials.gov NCT01281735) which represents the largest cohort of children with CML.

Results. Between January 2011 and March 2021, 576 CML patients less than 18 years of age at diagnosis were registered. We retrospectively selected 535 (92.8 %) children in CP according to the European leukemia net (ELN) criteria at diagnosis. Boys accounted for 58% of all patients with a boy to girl ratio of 1.25. The median age at diagnosis was 12.4 years (range, 8 months to 18 years). The most common symptoms at presentation were asthenia, weight loss and abdominal pain in 46%, 25% and 23% of the patients, respectively. CML in CP was diagnosed incidentally in 80 (16%) children when a blood assessment was performed for medical reasons. At diagnosis, thrombosis was observed in only one patient whilst 20% of the children presented with bleeding. Bleeding signs were associated with a higher frequency of palpable spleen (p=0.0007), higher leukocyte (p<0.0001) and platelets (p=0.02) counts, and a lower hemoglobin level (p=0.02). Clinical signs of leukostasis were observed in 88 (16.5%) patients. At diagnosis, spleen was palpable in 76% of the patients with a median of 9 cm (range, 1 to 32) below the costal margin. The median leukocyte count was 222 G/L (quartile 95-353). There is no statistical difference between boys and girls in terms of frequency of signs of leukostasis, frequency of splenomegaly, spleen size, median of the leucocyte count and hemoglobin level but the median of the platelet count was significantly higher in girls (p<0.0001). The majority (67%) of the children was allocated to the low-risk group according to the Eutos Long Term Survival (ELTS) score. First line therapy consisted of imatinib in 482 children with a median follow up of 4.6 years (IQR. 2.2-8.4). Among them, 208 (43%) children remained on imatinib with a median follow up of 2.9 years (IQR. 1.5-5.6). The main reason for switching (38.7% of the switches) was failure to achieve hematologic, cytogenetic or molecular response. Among the patients treated with imatinib first line, 15 (3.1%) children died and the probability of overall survival at 36 months was 97.4% (95% CI: 95-99%) (Figure 1). ELTS score was calculated for 406 of these patients: the 3-year survival rate was 98.1.% (95% CI: 96.3-100%), 94.4% (95% CI: 89.1-99.9%) and 95% (95% CI: 88.5-100%) in the low-, intermediate- and high-risk group, respectively (p logrank=0.009). Nineteen of these patients (3.9%) switched from imatinib to another treatment due to progression (accelerated or blastic phase). Progression free survival (PFS) rate at 3-years was 97.1% (95% CI: 94.9-99.2%), 91.7% (95% CI:84.5-98.3%) and 72.0% (95% CI: 59-87.9%) in the ELTS low-, intermediate- and high-risk group, respectively (p logrank<0.001) (Figure 2).

Conclusion. The analysis of clinical and biological parameters of the largest cohort of children with CML in CP demonstrated that pediatric CML is characterized by a bulky disease (large splenomegaly, high leucocyte counts). However, these characteristics did not translate in a low rate of response and the outcome was similar to adults. While the ELTS score can identify children with the poorest outcome, a refined prognostic score specific for the pediatric population needs to be established and validated.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH