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

Abstract

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, n = 187), AML-PPGLBC 94 (1994–1997, n = 74), AML-PPGLBC 98 (1998–2004, n = 151), AML-BFM 2004 Interim (2004–2015, n = 356), and AML-BFM 2012 (2015–2019, n = 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.

Blinatumomab as a Bridge Therapy for Hematopoietic Stem Cell Transplantation in Pediatric Refractory/Relapsed Acute Lymphoblastic Leukemia

“…Despite enormous progress being made in recent decades in the treatment of pediatric acute leukemias, e.g., converting ALL from a fatal to highly curable disease, relapsed/refractory patients still have a dismal prognosis [ 2 , 19 ]. Increasing the intensity of chemotherapy significantly increases the number of adverse events, rather than improving treatment outcomes.…”

Concentrations of Insulin-like Growth Factors and Insulin-like Growth Factor-Binding Proteins and Respective Gene Expressions in Children before and after Hematopoietic Stem Cell Transplantation

“…Hematopoietic stem cell transplantation (HSCT) is an important, life-saving treatment modality in children with cancer and selected non-neoplastic diseases [1][2][3]. Late complications of HSCT include various metabolic abnormalities, including obesity, dyslipidemia, and metabolic syndrome, which not only may affect the health status of long-term HSCT survivors but also can be important risk factors of cardiovascular disease in patients after HSCT [4][5][6].…”

Analysis of Peripheral Blood Mononuclear Cells Gene Expression Highlights the Role of Extracellular Vesicles in the Immune Response following Hematopoietic Stem Cell Transplantation in Children

“…Hematopoietic Stem Cell Transplantation (HSCT) is a procedure applied in patients with dysfunctional or depleted bone marrow that involves the administration of healthy hematopoietic stem cells, which leads to the improvement of bone marrow function and allows to destroy cancer cells or generate fully functional blood cells, thus restoring the efficiency of the hematopoietic or immune systems [ 1 ]. HSCT is used to treat both neoplastic and non-neoplastic diseases [ 2 , 3 , 4 , 5 ]. Depending on the indications, various therapeutic protocols are used, and the stem cell donor may be the patient himself (autologous transplantation) or an HLA-matched donor (allogeneic transplantation).…”