The outcomes of children with acute myeloid leukemia treated in accordance with the AML–MM-2006 protocol

Abstract

Over the past years, the outcomes of patients with acute myeloid leukemia (AML) have significantly improved due to the use of intensive chemotherapy, more effective supportive therapy, and the availability of allogeneic hematopoietic stem cell transplantation. This article presents the outcomes of children with AML treated in accordance with the AML-MM-2006 protocol. Our study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The study included 233 patients with a median age of 6.5 years (7 days – 18 years) who were stratified into the following risk groups: standard risk, intermediate risk, and high risk. The 5-year event-free survival (EFS) was 0.64 ± 0,14, 0.49 ± 0.05, and 0.43 ± 0.05 for standard-risk (n = 12), intermediate-risk (n = 106), and high-risk (n = 115) patients, respectively (p = 0.14), while the 5-year overall survival (OS) was 1.0 year, 0.7 ± 0.05 and 0.55 ± 0.05, respectively (p = 0.001). The OS in the entire cohort was 0.68 ± 0.032. Factors associated with poor prognosis included hyperleukocytosis, the presence of extramedullary lesions, and age < 1 year. The overall survival rates in these patient groups were 0.55 ± 0.08, 0.39 ± 0.09 and 0.49 ± 0.08, respectively. The worst prognosis was for patients with monosomy 7 and t(7;12) whose OS rates were 0.25 ± 0.2 and 0.4 ± 0.2, respectively. For non-responders and patients with relapsed AML, the OS was 0.33 ± 0.08 and 0.54 ± 0.06, respectively. Early death (before remission could be achieved) occurred in 4% of patients, and 3.8% of patients died in first remission. Sixtytwo percent of deceased patients died of disease progression. In the entire cohort of patients, the five-year EFS was 0.53 ± 0.047, the cumulative risk of relapse after 3 years of remission was 40%, the confidence interval was 23–89%.

Treatment results of children and adolescents with relapsed AML who were initially treated according to the AML-MM-2006 protocol

“…В настоящее исследование было включено 62 ребенка с рецидивом ОМЛ, что составило 33 % от всех больных, у которых была достигнута ПР1 при лечении согласно протоколу «ОМЛ-ММ-2006» и которые подлежали оценке с точки зрения риска развития рецидива [3], что соответствует частоте развития рецидивов ОМЛ у детей по данным литературы [1,[7][8][9][10][11].…”

“…Использование в терапии протоколов, основанных на применении стандартных доз цитарабина с антрациклинами в качестве индукционной терапии и курса цитарабином в высоких дозах c антрациклинами («вторая индукция»), позволило достигать первой полной ремиссии (ПР1) у 85-90 % детей с впервые диагностированным острым миелоидным лейкозом (ОМЛ) [1][2][3]. Несмотря на дальнейшую интенсивную постремиссионную терапию, основанную на цитарабине в высоких дозах, рецидив заболевания развивается у 30-40 % больных; при этом вероятность развития рецидива строго зависит от инициальных цитогенетических и молекулярно-генетических характеристик ОМЛ, варьируя в диапазоне от 10 до 90 % [2][3][4][5].…”

“…Результаты терапии по протоколу «ОМЛ-ММ-2006» описаны ранее[3]. ОВ в проведенном исследовании составила 68 %.…”