The prognostic significance of early treatment response in pediatric relapsed acute myeloid leukemia: results of the international study Relapsed AML 2001/01

Creutzig, Ursula; Zimmermann, Martin; Dworzak, Michael; Gibson, Brenda; Tamminga, R. Y. J.; Abrahamsson, Jonas; Ha, Shau Yin; Hasle, Henrik; Maschan, Alexey; Bertrand, Yves; Leverger, Guy; Neuhoff, Christine von; Razzouk, Bassem I.; Rizzari, Carmelo; Smíšek, Petr; Smith, Owen; Stark, Batia; Reinhardt, Dirk; Kaspers, Gertjan J. L.

doi:10.3324/haematol.2014.104182

Cited by 48 publications

(56 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Acute myeloid leukemia (AML) is a genetically heterogeneous disease that arises from mutations in hematopoietic stem and progenitor cells (HSPC) [1]. The characteristic, and often disproportionate, suppression of native hematopoiesis that develops in the bone marrow (BM) during disease progression and post-treatment relapse accounts for significant morbidity and mortality [2][3][4][5][6]. Substantial experimental evidence supports the malignant transition of BM function during AML invasion, and its role in disrupting hematopoiesis and sustaining AML [7][8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Extracellular vesicles impose quiescence on residual hematopoietic stem cells in the leukemic niche

et al. 2019

View full text Add to dashboard Cite

Progressive remodeling of the bone marrow microenvironment is recognized as an integral aspect of leukemogenesis. Expanding acute myeloid leukemia (AML) clones not only alter stroma composition, but also actively constrain hematopoiesis, representing a significant source of patient morbidity and mortality. Recent studies revealed the surprising resistance of long‐term hematopoietic stem cells (LT‐HSC) to elimination from the leukemic niche. Here, we examine the fate and function of residual LT‐HSC in the BM of murine xenografts with emphasis on the role of AML‐derived extracellular vesicles (EV). AML‐EV rapidly enter HSC, and their trafficking elicits protein synthesis suppression and LT‐HSC quiescence. Mechanistically, AML‐EV transfer a panel of miRNA, including miR‐1246, that target the mTOR subunit Raptor, causing ribosomal protein S6 hypo‐phosphorylation, which in turn impairs protein synthesis in LT‐HSC. While HSC functionally recover from quiescence upon transplantation to an AML‐naive environment, they maintain relative gains in repopulation capacity. These phenotypic changes are accompanied by DNA double‐strand breaks and evidence of a sustained DNA‐damage response. In sum, AML‐EV contribute to niche‐dependent, reversible quiescence and elicit persisting DNA damage in LT‐HSC.

show abstract

Section: Introductionmentioning

confidence: 99%

Extracellular vesicles impose quiescence on residual hematopoietic stem cells in the leukemic niche

et al. 2019

View full text Add to dashboard Cite

show abstract

“…The poor prognostic impact of the short first remission duration has been demonstrated in many previous studies. An OS rate of 28% at 4 years was reported in the relapsed AML 2001/01 study by the I‐BFM study group, in contrast to an OS rate of 48% in cases of late relapse . Our previous study on the outcome of children with AML who had relapsed after the AML99 study, showed a larger impact of the duration of first CR on overall mortality compared to that of the AML cytogenetics: a significantly higher hazard ratio of 3.06 in cases of early relapse than late relapse, while that of non‐CBF was 1.28 relative to CBF, which was not significant …”

Section: Discussionmentioning

confidence: 89%

Fludarabine, cytarabine, granulocyte colony‐stimulating factor and idarubicin for relapsed childhood acute myeloid leukemia

Nakayama

Tomizawa

Tanaka

et al. 2017

Pediatrics International

View full text Add to dashboard Cite

show abstract

“…Oko 5 % djece s AML-om ima refraktornu bolest i 30 % doživi relaps 29 . Internacionalna studija o relapsnom AML-u (Relapsed AML 2001/01) potvrdila je da je rani odgovor na terapiju najvažniji prognostički čimbe-nik 34 . Alogeni TKMS je općenito indiciran u drugoj remisiji 35 .…”

Section: Rezultatiunclassified

Acute myeloid leukemia in children: the study of clinical and biological features and results of the treatment at the Department of pediatrics, Clinical Hospital Centre Rijeka

et al. 2016

View full text Add to dashboard Cite

Sažetak. Cilj: Ispitati kliničke i biološke (citomorfologija, imunofenotipizacija, citogenetika) značajke te stopu preživljenja pedijatrijskih pacijenata s akutnom mijeloičnom leukemijom (AML) liječenih u tercijarnom centru. Ispitanici i metode: Epidemiološko, retrospektivno, deskriptivno istraživanje u koje su uključeni pacijenti s novodijagnosticiranim AML-om mlađi od 18 godina, u razdoblju od 1. 1. 2002. do 31. 12. 2013. godine. Rezultati: U dvanaestogodišnjem razdoblju hospitalizirano je devetero djece s AML-om, 5 (55,6 %) djevojčica i 4 (44,4 %) dječaka. Prosječna dob bila je 11 (± 3,8 SD) godina. Najčešći simptomi i znaci bili su astenija (66,7 %), perzistentna vrućica (55,6 %), bljedoća (44,4 %) i krvarenje (44,4 %). Limfadenopatija i hepatomegalija su bile prisutne u 3 (33,3 %), a splenomegalija u jednog (11,1 %) pacijenta. Jedan (11,1 %) pacijent imao je inicijalno zahvaćen središnji živčani sustav. Trombocitopenija je bila prisutna u 8 (88,9 %) pacijenata, anemija u 7 (77,8 %) pacijenata, leukocitoza u 4 (44,5 %) pacijenta, a leukopenija u 3 (33,3 %) pacijenta. Svi su pacijenti imali blaste u razmazu periferne krvi. Utvrđeno je 7 citomorfoloških podtipova s karakterističnim imunofenotipskim značajkama. Sedam (77,8 %) pacijenata imalo je numeričke i strukturne aberacije kromosoma. Tri (33,3 %) pacijenta svrstana su u skupinu standardnog rizika, a 6 (66,7 %) u skupinu visokog rizika. Remisija je postignuta petnaestog dana kemoterapije u 6 (66,7 %) pacijenata. Alogena transplantacija krvotvornih matičnih stanica učinjena je u 3 (33,3 %) pacijenta. Osam (88,9 %) pacijenata je u kompletnoj remisiji s medijanom praćenja od 10,1 godina. Smrtni ishod je nastupio u jednog pacijenta (11,1 %) zbog septičkog šoka. Zaključci: Pedijatrijski AML je heterogena hematološka neoplazma. Agresivna kemoterapija i transplantacija krvotvornih matičnih stanica omogućuju visoku stopu izlječenja.Ključne riječi: akutna mijeloična leukemija; dijete; liječenje Abstract. Objective: To investigate clinical and biological (cytomorphology, immunophenotyping, cytogenetics) features and the survival rate of pediatric patients with acute myeloid leukemia (AML) in a tertiary centre. Material and Methods: Epidemiological, retrospective, descriptive study involving patients with newly diagnosed AML younger than 18 years, from January 1st 2002 to December 31 st 2013. Results: In a 12-year period, 9 children with AML were hospitalized, 5 (55.6 %) girls and 4 (44.4 %) boys. The median age was 11 (± 3.8 SD) years. The most common symptoms were asthenia (66.7 %), persistent fever (55.6 %), pallor (44.4 %) and bleeding (44.4 %). Lymphadenopathy and hepatomegaly were present in 3 patients (33.3 %), and splenomegaly in one (11.1 %) patient. One (11.1 %) patient had initial central nervous system involvement. Thrombocytopenia was present in 8 (88.9 %) patients, anemia in 7 (77.8 %) * Dopisni autor: Prof. dr. sc. Jelena Roganović, prim., dr. med. Odjel za hematologiju i onkologiju Klinika za pedijatriju,

show abstract

The prognostic significance of early treatment response in pediatric relapsed acute myeloid leukemia: results of the international study Relapsed AML 2001/01

Cited by 48 publications

References 18 publications

Extracellular vesicles impose quiescence on residual hematopoietic stem cells in the leukemic niche

Extracellular vesicles impose quiescence on residual hematopoietic stem cells in the leukemic niche

Fludarabine, cytarabine, granulocyte colony‐stimulating factor and idarubicin for relapsed childhood acute myeloid leukemia

Acute myeloid leukemia in children: the study of clinical and biological features and results of the treatment at the Department of pediatrics, Clinical Hospital Centre Rijeka

Contact Info

Product

Resources

About