Retrospective Analysis of the Treatment Outcome in Myeloid Leukemia of Down Syndrome in Polish Pediatric Leukemia and Lymphoma Study Group From 2005 to 2019

Czogała, Małgorzata; Pawińska-Wa̧sikowska, Katarzyna; Książek, Teofila; Sikorska-Fic, Barbara; Matysiak, Michał; Skalska‐Sadowska, Jolanta; Wachowiak, Jacek; Rodziewicz-Konarska, Anna; Chybicka, Alicja; Myszynska-Roslan, Katarzyna; Krawczuk‐Rybak, Maryna; Grabowski, Dominik; Kowalczyk, Jerzy; Maciejka-Kemblowska, Lucyna; Adamkiewicz-Drożyńska, Elżbieta; Bobeff, Katarzyna; Młynarski, Wojciech; Tomaszewska, Renata; Szczepański, Tomasz; J, Pohorecka; Chodała-Grzywacz, Agnieszka; Karolczyk, Grażyna; Mizia‐Malarz, Agnieszka; Mycko, Katarzyna; Badowska, Wanda; Zielezińska, Karolina; Urasiński, Tomasz; Nykiel, Magdalena; Woszczyk, Mariola; Ciebiera, Małgorzata; Chaber, Radosław; Skoczeń, Szymon; Balwierz, Walentyna

doi:10.3389/fped.2020.00277

Cited by 5 publications

(8 citation statements)

References 23 publications

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“…The incidence of DS in our AML population was 5.7%. As expected, 95% were younger than four years of age [6,8,9,14,19,24,27,29,30,32,33,35,37,42,[57][58][59], almost none (4.8%) had CNS involvement at diagnosis [29,30,33,34,37,58,59], only 6 (14.6%) presented with immunophenotype other than Fab M7 (sporadic AML-DS) [15,27,30,[33][34][35]37,57,59] and GATA-1 was mutated in 93.8% of ML-DS cases [42]. Also, only one patient of sporadic DS-AML aged 11 years old presented a favorable cytogenetic rearrangement [6,33,37,58,60].…”

Section: Discussionsupporting

confidence: 74%

“…All deaths-during induction and deaths in CR were due to sepsis complications, being infection-related mortality 24.4%. Although considerably higher than previously reported [24,27,[29][30][31][32][33][34]37,39,57,59,62], a significant reduction was observed over time, probably associated with treatment modifications (2 HDARA-C intensification blocks in 1-AML90-BFM/HPG and 1-AML95-BFM/HPG vs. 1 HDARA-C re-induction and 1 HDARA-C consolidation block in 4-AML99-BFM/HPG , and 12-AML07-BFM/HPG), as well as improvements on clinical support. When relapsed, DS-AML has a dismal prognosis [10,63,64].…”

Section: Discussioncontrasting

confidence: 67%

“…When relapsed, DS-AML has a dismal prognosis [10,63,64]. According to the literature, the five-year CIR is 3-12.0% [24,29,31,34,57,58,62] and the 3-year OS rate is 8.5-34.3% [33,63,64]. In our report, the relapse rate was 13.9% and no patient achieved a second CR.…”

Section: Discussionsupporting

confidence: 47%

“…Also, only one patient of sporadic DS-AML aged 11 years old presented a favorable cytogenetic rearrangement [6,33,37,58,60]. As previously described, the incidence of chromosomal abnormalities was higher in AML than in TAM patients [22,61], being +8 the most frequent chromosome alteration = [30,[33][34][35]37,41,57,59,60].…”

Section: Discussionmentioning

confidence: 91%

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Clonal Myeloproliferative Disorders in Patients with Down Syndrome—Treatment and Outcome Results from an Institution in Argentina

Pennella

Cassina

Rossi

et al. 2022

Cancers

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Children with Down syndrome (DS) are at an increased risk of developing clonal myeloproliferative disorders. The balance between treatment intensity and treatment-related toxicity has not yet been defined. We analyzed this population to identify risk factors and optimal treatment. This single-center retrospective study included 78 DS patients <16 years-old with Transient Abnormal Myelopoiesis (TAM, n = 25), Acute Myeloblastic Leukemia (DS-AML, n = 41) of which 35 had classical Myeloid Leukemia associated with DS (ML-DS) with megakaryoblastic immunophenotype (AMKL) and 6 sporadic DS-AML (non-AMKL). Patients with DS-AML were treated according to four BFM-based protocols. Classical ML-DS vs. non-DS-AMKL were compared and the outcome of ML-DS was analyzed according to treatment intensity. Only four patients with TAM required cytoreduction with a 5-year Event-Free Survival probability (EFSp) of 74.4 (±9.1)%. DS-AML treatment-related deaths were due to infections, with a 5-year EFSp of 60.6 (±8.2)%. Megakaryoblastic immunophenotype was the strongest good-prognostic factor in univariate and multivariate analysis (p = 0.000). When compared ML-DS with non-DS-AMKL, a better outcome was associated with a lower relapse rate (p = 0.0002). Analysis of administered treatment was done on 32/33 ML-DS patients who achieved CR according to receiving or not high-dose ARA-C block (HDARA-C), and no difference in 5-year EFSp was observed (p = 0.172). TAM rarely required treatment and when severe manifestations occurred, early intervention was effective. DS-AML good outcome was associated with AMKL with a low relapse-rate. Even if treatment-related mortality is still high, our data do not support the omission of HDARA-C in ML-DS since we observed a trend to detect a higher relapse rate in the arm without HDARA-C.

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Section: Discussionsupporting

confidence: 74%

Section: Discussioncontrasting

confidence: 67%

Section: Discussionsupporting

confidence: 47%

Section: Discussionmentioning

confidence: 91%

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Clonal Myeloproliferative Disorders in Patients with Down Syndrome—Treatment and Outcome Results from an Institution in Argentina

Pennella

Cassina

Rossi

et al. 2022

Cancers

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“…This study highlights the high incidence of life-threatening treatment-related toxicities in DS-acute leukaemia patients [ 4 , 20 ]. The peak age of DS-ALL was also found to be the same [ 24 ], but the peak age at diagnosis of DS-AML in this study differed from the published literature [ 25 , 26 ].…”

Section: Discussionmentioning

confidence: 47%

Acute leukaemia in children with Down syndrome in a low middle-income country

Al-Ain¹,

Faizan²,

Anwar³

et al. 2022

ecancer

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Down syndrome (DS) is the commonest chromosomal disorder and is considered to be the most common syndrome associated with acute leukaemia. The objective of this study was to determine the characteristics of acute leukaemia in children with DS in Pakistan. It was a retrospective, cohort study conducted over a 2-year period, and the data was analysed in SPSS 20.0 in terms of descriptive statistics. Nineteen DS patients with acute leukaemia were enrolled. The proportion of DS-acute leukaemia was found to be 1.84% among all cases of paediatric acute leukaemia. The mean age of presentation was 5.5 years ± 4.3 SD with a male to female ratio of 1.1:1. The precursor B-cell ALL was found in 13 (68.4%) and acute myeloid leukaemia was found in 6 (31.6%) patients of DS. Thirteen patients (68.4%) completed treatment, while 6 (31.6%) expired due to treatment-related toxicity. Mean overall survival was 38 months ± 5.34 SD. The status of diagnosis of DS before presentation with acute leukaemia was the only statistically significant factor associated with the outcome. Few distinct characteristics of DS-acute leukaemia have been found in our population. Treatment toxicity was the sole cause of treatment failure.

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Management of Down Syndrome–Associated Leukemias

et al. 2023

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ImportanceDown syndrome (DS), caused by an extra copy of material from chromosome 21, is one of the most common genetic conditions. The increased risk of acute leukemia in DS (DS-AL) has been recognized for decades, consisting of an approximately 150-fold higher risk of acute myeloid leukemia (AML) before age 4 years, and a 10- to 20-fold higher risk of acute lymphoblastic leukemia (ALL), compared with children without DS.ObservationsA recent National Institutes of Health-sponsored conference, ImpacT21, reviewed research and clinical trials in children, adolescents, and young adults (AYAs) with DS-AL and are presented herein, including presentation and treatment, clinical trial design, and ethical considerations for this unique population. Between 10% to 30% of infants with DS are diagnosed with transient abnormal myelopoiesis (TAM), which spontaneously regresses. After a latency period of up to 4 years, 20% to 30% develop myeloid leukemia associated with DS (ML-DS). Recent studies have characterized somatic mutations associated with progression from TAM to ML-DS, but predicting which patients will progress to ML-DS remains elusive. Clinical trials for DS-AL have aimed to reduce treatment-related mortality (TRM) and improve survival. Children with ML-DS have better outcomes compared with non-DS AML, but outcomes remain dismal in relapse. In contrast, patients with DS-ALL have inferior outcomes compared with those without DS, due to both higher TRM and relapse. Management of relapsed leukemia poses unique challenges owing to disease biology and increased vulnerability to toxic effects. Late effects in survivors of DS-AL are an important area in need of further study because they may demonstrate unique patterns in the setting of chronic medical conditions associated with DS.Conclusions and RelevanceOptimal management of DS-AL requires specific molecular testing, meticulous supportive care, and tailored therapy to reduce TRM while optimizing survival. There is no standard approach to treatment of relapsed disease. Future work should include identification of biomarkers predictive of toxic effects; enhanced clinical and scientific collaborations; promotion of access to novel agents through innovative clinical trial design; and dedicated studies of late effects of treatment.

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Retrospective Analysis of the Treatment Outcome in Myeloid Leukemia of Down Syndrome in Polish Pediatric Leukemia and Lymphoma Study Group From 2005 to 2019

Abstract: Conclusions:The study confirms that the reduced intensity protocols are very effective in ML-DS patients. The only cause of deaths was toxicities; however, systematic decrease of the treatment-related mortality was noticed.

Cited by 5 publications

References 23 publications

Clonal Myeloproliferative Disorders in Patients with Down Syndrome—Treatment and Outcome Results from an Institution in Argentina

Clonal Myeloproliferative Disorders in Patients with Down Syndrome—Treatment and Outcome Results from an Institution in Argentina

Acute leukaemia in children with Down syndrome in a low middle-income country

Management of Down Syndrome–Associated Leukemias

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