Central Nervous System Disease and Outcome in Pediatric Acute Myeloid Leukemia: Results from NOPHO-DBH AML2012 Trial

Nira Arad-Cohen; Daniel Cheuk; Barbara De Moerloose; Jose Mavarro; Henrik Hasle; Kirsi Jahnukainen; Kristian Juul-Dam; Gertjan Kaspers; Zhanna Kovalova; Olafur Jonsson; Birgitte Lausen; Monica Cheng Munthe-Kaas; Ulrika Norén-Nyström; Josefine Palle; Ramunė Pasaulienė; Cornelis Pronk; Kadri Saks; Anne Tierens; Bernward Zeller; Jonas Abrahamsson

doi:10.21203/rs.3.rs-5449535/v1

Central Nervous System Disease and Outcome in Pediatric Acute Myeloid Leukemia: Results from NOPHO-DBH AML2012 Trial

Nira Arad-Cohen (Corresponding Author), Daniel Cheuk, Barbara De Moerloose, Jose Mavarro, Henrik Hasle, Kirsi Jahnukainen, Kristian Juul-Dam, Gertjan Kaspers, Zhanna Kovalova, Olafur Jonsson, Birgitte Lausen, Monica Cheng Munthe-Kaas, Ulrika Norén-Nyström, Josefine Palle, Ramunė Pasaulienė, Cornelis Pronk, Kadri Saks, Anne Tierens, Bernward Zeller, Jonas Abrahamsson

Research output: Working paper › Preprint

Abstract

Background: Central nervous system disease (CNS3) in pediatric acute myeloid leukemia (pAML) is reported in 6% to 29% of cases. However, its impact on event-free survival (EFS) and overall survival (OS) remains uncertain. This study evaluates the effect of CNS involvement at diagnosis on relapse and survival in patients treated on the NOPHO-DBH AML2012 protocol.

Methods:

Data from 931 pediatric AML patients in the NOPHO-DBH AML2012 protocol were analyzed, comparing outcomes, relapse rates, and survival between those with and without CNS disease. CNS-directed therapy included intensified intrathecal chemotherapy without irradiation.

Results: Of 922 patients with available CNS status, 10.9% had CNS3 at diagnosis. CNS3 patients were younger (median age 3.5 vs. 8 years,P=0.001) with higher white blood cell counts (56.1x109/L vs 18.7x109/L,P<0.001) and higher frequency of other extramedullary disease (30.4% vs 11.3%,P<0.001) and inv(16)(P<0.001).

EFS5y was 71.5% for CNS-positive patients vs. 62.7% for CNS-negative (p=0.14), and OS5y was 81.4% vs. 79.3% (p=0.54). Patients with CNS disease had a lower cumulative incidence of relapse (15.6% vs 26.5%,P=0.023), and CNS relapse occurred in 0.9% and 0.7% of patients with and without CNS disease.

Conclusion: CNS disease at diagnosis in pAML does not adversely affect survival or treatment response.

Original language	English
Publisher	Research Square
Pages	1-15
DOIs	https://doi.org/10.21203/rs.3.rs-5449535/v1
Publication status	Published - 18 Dec 2024
Externally published	Yes

Field of Science*

3.2 Clinical medicine

Publication Type*

1.4. Reviewed scientific article published in Latvia or abroad in a scientific journal with an editorial board (including university editions)

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10.21203/rs.3.rs-5449535/v1Licence: CC BY

Central Nervous SystemSubmitted manuscript, 565 KBLicence: CC BY

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Arad-Cohen, N., Cheuk, D., De Moerloose, B., Mavarro, J., Hasle, H., Jahnukainen, K., Juul-Dam, K., Kaspers, G., Kovalova, Z., Jonsson, O., Lausen, B., Munthe-Kaas, M. C., Norén-Nyström, U., Palle, J., Pasaulienė, R., Pronk, C., Saks, K., Tierens, A., Zeller, B., & Abrahamsson, J. (2024). Central Nervous System Disease and Outcome in Pediatric Acute Myeloid Leukemia: Results from NOPHO-DBH AML2012 Trial. (pp. 1-15). Research Square. https://doi.org/10.21203/rs.3.rs-5449535/v1

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title = "Central Nervous System Disease and Outcome in Pediatric Acute Myeloid Leukemia: Results from NOPHO-DBH AML2012 Trial",

abstract = "Background: Central nervous system disease (CNS3) in pediatric acute myeloid leukemia (pAML) is reported in 6% to 29% of cases. However, its impact on event-free survival (EFS) and overall survival (OS) remains uncertain. This study evaluates the effect of CNS involvement at diagnosis on relapse and survival in patients treated on the NOPHO-DBH AML2012 protocol.Methods:Data from 931 pediatric AML patients in the NOPHO-DBH AML2012 protocol were analyzed, comparing outcomes, relapse rates, and survival between those with and without CNS disease. CNS-directed therapy included intensified intrathecal chemotherapy without irradiation.Results: Of 922 patients with available CNS status, 10.9% had CNS3 at diagnosis. CNS3 patients were younger (median age 3.5 vs. 8 years,P=0.001) with higher white blood cell counts (56.1x109/L vs 18.7x109/L,P<0.001) and higher frequency of other extramedullary disease (30.4% vs 11.3%,P<0.001) and inv(16)(P<0.001).EFS5y was 71.5% for CNS-positive patients vs. 62.7% for CNS-negative (p=0.14), and OS5y was 81.4% vs. 79.3% (p=0.54). Patients with CNS disease had a lower cumulative incidence of relapse (15.6% vs 26.5%,P=0.023), and CNS relapse occurred in 0.9% and 0.7% of patients with and without CNS disease.Conclusion: CNS disease at diagnosis in pAML does not adversely affect survival or treatment response.",

author = "Nira Arad-Cohen and Daniel Cheuk and {De Moerloose}, Barbara and Jose Mavarro and Henrik Hasle and Kirsi Jahnukainen and Kristian Juul-Dam and Gertjan Kaspers and Zhanna Kovalova and Olafur Jonsson and Birgitte Lausen and Munthe-Kaas, {Monica Cheng} and Ulrika Nor{\'e}n-Nystr{\"o}m and Josefine Palle and Ramunė Pasaulienė and Cornelis Pronk and Kadri Saks and Anne Tierens and Bernward Zeller and Jonas Abrahamsson",

year = "2024",

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day = "18",

doi = "10.21203/rs.3.rs-5449535/v1",

language = "English",

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Arad-Cohen, N, Cheuk, D, De Moerloose, B, Mavarro, J, Hasle, H, Jahnukainen, K, Juul-Dam, K, Kaspers, G, Kovalova, Z, Jonsson, O, Lausen, B, Munthe-Kaas, MC, Norén-Nyström, U, Palle, J, Pasaulienė, R, Pronk, C, Saks, K, Tierens, A, Zeller, B & Abrahamsson, J 2024 'Central Nervous System Disease and Outcome in Pediatric Acute Myeloid Leukemia: Results from NOPHO-DBH AML2012 Trial' Research Square, pp. 1-15. https://doi.org/10.21203/rs.3.rs-5449535/v1

TY - UNPB

T1 - Central Nervous System Disease and Outcome in Pediatric Acute Myeloid Leukemia

T2 - Results from NOPHO-DBH AML2012 Trial

AU - Arad-Cohen, Nira

AU - Cheuk, Daniel

AU - De Moerloose, Barbara

AU - Mavarro, Jose

AU - Hasle, Henrik

AU - Jahnukainen, Kirsi

AU - Juul-Dam, Kristian

AU - Kaspers, Gertjan

AU - Kovalova, Zhanna

AU - Jonsson, Olafur

AU - Lausen, Birgitte

AU - Munthe-Kaas, Monica Cheng

AU - Norén-Nyström, Ulrika

AU - Palle, Josefine

AU - Pasaulienė, Ramunė

AU - Pronk, Cornelis

AU - Saks, Kadri

AU - Tierens, Anne

AU - Zeller, Bernward

AU - Abrahamsson, Jonas

PY - 2024/12/18

Y1 - 2024/12/18

N2 - Background: Central nervous system disease (CNS3) in pediatric acute myeloid leukemia (pAML) is reported in 6% to 29% of cases. However, its impact on event-free survival (EFS) and overall survival (OS) remains uncertain. This study evaluates the effect of CNS involvement at diagnosis on relapse and survival in patients treated on the NOPHO-DBH AML2012 protocol.Methods:Data from 931 pediatric AML patients in the NOPHO-DBH AML2012 protocol were analyzed, comparing outcomes, relapse rates, and survival between those with and without CNS disease. CNS-directed therapy included intensified intrathecal chemotherapy without irradiation.Results: Of 922 patients with available CNS status, 10.9% had CNS3 at diagnosis. CNS3 patients were younger (median age 3.5 vs. 8 years,P=0.001) with higher white blood cell counts (56.1x109/L vs 18.7x109/L,P<0.001) and higher frequency of other extramedullary disease (30.4% vs 11.3%,P<0.001) and inv(16)(P<0.001).EFS5y was 71.5% for CNS-positive patients vs. 62.7% for CNS-negative (p=0.14), and OS5y was 81.4% vs. 79.3% (p=0.54). Patients with CNS disease had a lower cumulative incidence of relapse (15.6% vs 26.5%,P=0.023), and CNS relapse occurred in 0.9% and 0.7% of patients with and without CNS disease.Conclusion: CNS disease at diagnosis in pAML does not adversely affect survival or treatment response.

AB - Background: Central nervous system disease (CNS3) in pediatric acute myeloid leukemia (pAML) is reported in 6% to 29% of cases. However, its impact on event-free survival (EFS) and overall survival (OS) remains uncertain. This study evaluates the effect of CNS involvement at diagnosis on relapse and survival in patients treated on the NOPHO-DBH AML2012 protocol.Methods:Data from 931 pediatric AML patients in the NOPHO-DBH AML2012 protocol were analyzed, comparing outcomes, relapse rates, and survival between those with and without CNS disease. CNS-directed therapy included intensified intrathecal chemotherapy without irradiation.Results: Of 922 patients with available CNS status, 10.9% had CNS3 at diagnosis. CNS3 patients were younger (median age 3.5 vs. 8 years,P=0.001) with higher white blood cell counts (56.1x109/L vs 18.7x109/L,P<0.001) and higher frequency of other extramedullary disease (30.4% vs 11.3%,P<0.001) and inv(16)(P<0.001).EFS5y was 71.5% for CNS-positive patients vs. 62.7% for CNS-negative (p=0.14), and OS5y was 81.4% vs. 79.3% (p=0.54). Patients with CNS disease had a lower cumulative incidence of relapse (15.6% vs 26.5%,P=0.023), and CNS relapse occurred in 0.9% and 0.7% of patients with and without CNS disease.Conclusion: CNS disease at diagnosis in pAML does not adversely affect survival or treatment response.

U2 - 10.21203/rs.3.rs-5449535/v1

DO - 10.21203/rs.3.rs-5449535/v1

M3 - Preprint

SP - 1

EP - 15

BT - Central Nervous System Disease and Outcome in Pediatric Acute Myeloid Leukemia

PB - Research Square

ER -

Central Nervous System Disease and Outcome in Pediatric Acute Myeloid Leukemia: Results from NOPHO-DBH AML2012 Trial

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