Advances in the First Line Treatment of Pediatric Acute Myeloid Leukemia in the Polish Pediatric Leukemia and Lymphoma Study Group from 1983 to 2019

Background: From 1983, standardized therapeutic protocols for pediatric acute myeloid leukemia (AML) based on the BFM group experience were introduced in Poland. We retrospectively analyzed the results of pediatric AML treatment in Poland from 1983 to 2019 (excluding promyelocytic, therapy-related, biphenotypic, and Down syndrome AML).

Methods: The study included 899 children suffering from AML treated with the following: AML-PPPLBC 83 (1983-1993, = 187), AML-PPGLBC 94 (1994-1997, = 74), AML-PPGLBC 98 (1998-2004, = 151), AML-BFM 2004 Interim (2004-2015, = 356), and AML-BFM 2012 (2015-2019, = 131).

Results: The probability of three-year overall survival was 0.34 ± 0.03, 0.37 ± 0.05, 0.54 ± 0.04, 0.67 ± 0.03, and 0.75 ± 0.05; event-free survival was 0.31 ± 0.03, 0.34 ± 0.05, 0.44 ± 0.04, 0.53 ± 0.03, and 0.67 ± 0.05; and relapse-free survival was 0.52 ± 0.03, 0.65 ± 0.05, 0.58 ± 0.04, 0.66 ± 0.03, and 0.78 ± 0.05, respectively, in the subsequent periods. A systematic reduction of early deaths and deaths in remission was achieved, while the percentage of relapses decreased only in the last therapeutic period. Surprisingly good results were obtained in the group of patients treated with AML-BFM 2012 with unfavorable genetic abnormalities like KMT2A-MLLT10/t(10;11)(p12;q23) and DEK-NUP214/t(6;9)(p23;q24), while unsatisfactory outcomes were found in the patients with FLT3-ITD.

Conclusions: The use of standardized, systematically modified therapeutic protocols, with the successive consideration of genetic prognostic factors, and advances in supportive care led to a significant improvement in AML treatment outcomes over the last 40 years.

Citing Articles

Analysis of early and treatment related deaths among children and adolescents with acute myeloid leukemia in Poland: 2005-2023.

Pawinska-Wasikowska K, Czogala M, Bukowska-Strakova K, Surman M, Rygielska M, Ksiazek T Front Pediatr. 2024; 12:1482720.

PMID: 39483533 PMC: 11524810. DOI: 10.3389/fped.2024.1482720.

Treatment Outcomes of Adolescents Compared to Younger Pediatric Patients with Acute Myeloid Leukemia: Do They Need a Special Approach?.

Pawinska-Wasikowska K, Czogala M, Bukowska-Strakova K, Surman M, Rygielska M, Ksiazek T Cancers (Basel). 2024; 16(6).

PMID: 38539480 PMC: 10969545. DOI: 10.3390/cancers16061145.

Gemtuzumab ozogamicin for relapsed or primary refractory acute myeloid leukemia in children-the Polish Pediatric Leukemia and Lymphoma Study Group experience.

Pawinska-Wasikowska K, Czogala M, Skoczen S, Surman M, Rygielska M, Ksiazek T Front Immunol. 2024; 14:1268993.

PMID: 38187390 PMC: 10766767. DOI: 10.3389/fimmu.2023.1268993.

Characteristics and Outcome of FLT3-ITD-Positive Pediatric Acute Myeloid Leukemia-Experience of Polish Pediatric Leukemia and Lymphoma Study Group from 2005 to 2022.

Czogala M, Czogala W, Pawinska-Wasikowska K, Ksiazek T, Bukowska-Strakova K, Sikorska-Fic B Cancers (Basel). 2023; 15(18).

PMID: 37760526 PMC: 10526903. DOI: 10.3390/cancers15184557.

Pediatric Acute Myeloid Leukemia Post Cytotoxic Therapy-Retrospective Analysis of the Patients Treated in Poland from 2005 to 2022.

Czogala M, Czogala W, Pawinska-Wasikowska K, Ksiazek T, Bukowska-Strakova K, Sikorska-Fic B Cancers (Basel). 2023; 15(3).

PMID: 36765692 PMC: 9913333. DOI: 10.3390/cancers15030734.

References

Dluzniewska A, Balwierz W, Armata J, Balcerska A, Chybicka A, Kowalczyk J . Twenty years of Polish experience with three consecutive protocols for treatment of childhood acute myelogenous leukemia. Leukemia. 2005; 19(12):2117-24. DOI: 10.1038/sj.leu.2403892. View

Jastaniah W, Abrar M, Khattab T . Improved outcome in pediatric AML due to augmented supportive care. Pediatr Blood Cancer. 2012; 59(5):919-21. DOI: 10.1002/pbc.24195. View

Zwaan C, Soderhall S, Brethon B, Luciani M, Rizzari C, Stam R . A phase 1/2, open-label, dose-escalation study of midostaurin in children with relapsed or refractory acute leukaemia. Br J Haematol. 2018; 185(3):623-627. DOI: 10.1111/bjh.15593. View

Quessada J, Cuccuini W, Saultier P, Loosveld M, Harrison C, Lafage-Pochitaloff M . Cytogenetics of Pediatric Acute Myeloid Leukemia: A Review of the Current Knowledge. Genes (Basel). 2021; 12(6). PMC: 8233729. DOI: 10.3390/genes12060924. View

Harrison C, Hills R, Moorman A, Grimwade D, Hann I, Webb D . Cytogenetics of childhood acute myeloid leukemia: United Kingdom Medical Research Council Treatment trials AML 10 and 12. J Clin Oncol. 2010; 28(16):2674-81. DOI: 10.1200/JCO.2009.24.8997. View

Creutzig U, Ritter J, Schellong G . Identification of two risk groups in childhood acute myelogenous leukemia after therapy intensification in study AML-BFM-83 as compared with study AML-BFM-78. AML-BFM Study Group. Blood. 1990; 75(10):1932-40. View

Lehrnbecher T, Varwig D, Kaiser J, Reinhardt D, Klingebiel T, Creutzig U . Infectious complications in pediatric acute myeloid leukemia: analysis of the prospective multi-institutional clinical trial AML-BFM 93. Leukemia. 2003; 18(1):72-7. DOI: 10.1038/sj.leu.2403188. View

Creutzig U, Ritter J, Zimmermann M, Hermann J, Gadner H, Sawatzki D . Idarubicin improves blast cell clearance during induction therapy in children with AML: results of study AML-BFM 93. AML-BFM Study Group. Leukemia. 2001; 15(3):348-54. DOI: 10.1038/sj.leu.2402046. View

Balgobind B, Raimondi S, Harbott J, Zimmermann M, Alonzo T, Auvrignon A . Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study. Blood. 2009; 114(12):2489-96. PMC: 2927031. DOI: 10.1182/blood-2009-04-215152. View

10.

Niktoreh N, Walter C, Zimmermann M, von Neuhoff C, von Neuhoff N, Rasche M . Mutated , and Fusion in Various Combinations Define a Poor Prognostic Group in Pediatric Acute Myeloid Leukemia. J Oncol. 2019; 2019:1609128. PMC: 6699323. DOI: 10.1155/2019/1609128. View

11.

Locatelli F, Masetti R, Rondelli R, Zecca M, Fagioli F, Rovelli A . Outcome of children with high-risk acute myeloid leukemia given autologous or allogeneic hematopoietic cell transplantation in the aieop AML-2002/01 study. Bone Marrow Transplant. 2014; 50(2):181-8. DOI: 10.1038/bmt.2014.246. View

12.

Betts D, Ammann R, Hirt A, Hengartner H, Beck-Popovic M, Kuhne T . The prognostic significance of cytogenetic aberrations in childhood acute myeloid leukaemia. A study of the Swiss Paediatric Oncology Group (SPOG). Eur J Haematol. 2007; 78(6):468-76. DOI: 10.1111/j.1600-0609.2007.00854.x. View

13.

Zwaan C, Kolb E, Reinhardt D, Abrahamsson J, Adachi S, Aplenc R . Collaborative Efforts Driving Progress in Pediatric Acute Myeloid Leukemia. J Clin Oncol. 2015; 33(27):2949-62. PMC: 4567700. DOI: 10.1200/JCO.2015.62.8289. View

14.

Ksiazek T, Czogala M, Kaczowka P, Sadowska B, Pawinska-Wasikowska K, Bik-Multanowski M . High Frequency of Fusion Gene Transcript Resulting From t(10;11)(p12;q23) Translocation in Pediatric Acute Myeloid Leukemia in Poland. Front Pediatr. 2020; 8:278. PMC: 7366384. DOI: 10.3389/fped.2020.00278. View

15.

Creutzig U, Zimmermann M, Bourquin J, Dworzak M, von Neuhoff C, Sander A . Second induction with high-dose cytarabine and mitoxantrone: different impact on pediatric AML patients with t(8;21) and with inv(16). Blood. 2011; 118(20):5409-15. DOI: 10.1182/blood-2011-07-364661. View

16.

Rubnitz J, Raimondi S, Halbert A, Tong X, Srivastava D, Razzouk B . Characteristics and outcome of t(8;21)-positive childhood acute myeloid leukemia: a single institution's experience. Leukemia. 2002; 16(10):2072-7. DOI: 10.1038/sj.leu.2402633. View

17.

Meshinchi S, Alonzo T, Stirewalt D, Zwaan M, Zimmerman M, Reinhardt D . Clinical implications of FLT3 mutations in pediatric AML. Blood. 2006; 108(12):3654-61. PMC: 1895470. DOI: 10.1182/blood-2006-03-009233. View

18.

Creutzig U, Zimmermann M, Bourquin J, Dworzak M, Fleischhack G, Graf N . Randomized trial comparing liposomal daunorubicin with idarubicin as induction for pediatric acute myeloid leukemia: results from Study AML-BFM 2004. Blood. 2013; 122(1):37-43. DOI: 10.1182/blood-2013-02-484097. View

19.

Creutzig U, van den Heuvel-Eibrink M, Gibson B, Dworzak M, Adachi S, De Bont E . Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel. Blood. 2012; 120(16):3187-205. DOI: 10.1182/blood-2012-03-362608. View

20.

Creutzig U, Zimmermann M, Reinhardt D, Dworzak M, Stary J, Lehrnbecher T . Early deaths and treatment-related mortality in children undergoing therapy for acute myeloid leukemia: analysis of the multicenter clinical trials AML-BFM 93 and AML-BFM 98. J Clin Oncol. 2004; 22(21):4384-93. DOI: 10.1200/JCO.2004.01.191. View