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Article

Acute Leukemia in Children with Down Syndrome: A Report from the Hellenic HESPHO Group

by
Evgenia Papakonstantinou
1,*,
Athanasios Tragiannidis
2,
Mirella Ampatzidou
3,
Nikolaos Katzilakis
4,
Maria Nikita
5,
Georgios Totikidis
1,
Kleoniki I. Athanasiadou
1,
Vasiliki Antari
2,
Charikleia Kelaidi
3,
Iordanis Pelagiadis
4,
Dimitrios Doganis
5,
Margarita Mpaka
5,
Helen Kosmidis
6,
Antonis Kattamis
7,
Eftychia Stiakaki
4,
Vassilios Papadakis
3,
Emmanouel Hatzipantelis
2 and
Sophia Polychronopoulou
3
1
Department of Pediatric Hematology and Oncology, “Ippokratio” Hospital, 54642 Thessaloniki, Greece
2
Children & Adolescent Hematology-Oncology Unit, Second Department of Paediatrics, Aristotle University of Thessaloniki, AHEPA Hospital, 54636 Thessaloniki, Greece
3
Department of Pediatric Hematology-Oncology, “Aghia Sophia” Children’s Hospital, 11527 Athens, Greece
4
Pediatric Hematology Oncology Department, University Hospital of Heraklion, Medical School, University of Crete, 71003 Heraklion, Greece
5
Oncology Department, “P. and A. Kyriakou” Children’s Hospital, 11527 Athens, Greece
6
Department of Pediatric Oncology and Hematology, MITERA Children’s Hospital, 15123 Athens, Greece
7
Pediatric Hematology-Oncology Unit, 1st Pediatric Department, “Aghia Sophia” Children’s Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece
*
Author to whom correspondence should be addressed.
Hemato 2025, 6(2), 8; https://doi.org/10.3390/hemato6020008
Submission received: 20 December 2024 / Revised: 30 March 2025 / Accepted: 1 April 2025 / Published: 5 April 2025
Browse Figure
Versions Notes

Abstract

:
Background/Objectives: Down syndrome (DS), affecting 1 in 1000 births, has been linked to an increased risk of acute leukemia (AL). Patients with DS–acute lymphoblastic leukemia (DS-ALL) have historically had inferior outcomes when they have received risk-adapted therapy. Transient abnormal myelopoiesis (TAM) constitutes a transient leukemia with spontaneous remission in the neonatal period or represents a preleukemic state, preceding DS–acute myeloid leukemia (DS-AML). DS-AML has a better prognosis than that of AML without DS (NDS-AML) due to genetic and biological underlying features, a better response to chemotherapeutic agents, and a lower frequency of relapses. Methods: This retrospective cohort study presents the DS-AL outcomes from a nationwide survey in pediatric oncology centers. A total of 20 patients were studied, 10 with DS-ALL, 4 with DS-AML, 5 with TAM, and 1 with DS-AML after TAM, at median follow-ups of 9.25 (0.6–17.42) years and 7.25 (0.25–18.25) years for DS-ALL and DS-AML, respectively. Results: The median age at diagnosis was 4.7 (1.16–13.83) and 1.92 (1.25–3) years for ALL and AML, respectively. All DS-ALL patients had B-cell precursor ALL and achieved complete remission (CR). One patient relapsed and succumbed due to a severe infection. Three DS-AML patients had AMKL. All DS-AML patients achieved CR. One patient with TAM demanded treatment, all achieved CR, and one progressed to DS-AML. The overall survival (OS) was 70% and 80% for DS-ALL and DS-AML. Conclusions: The improved survival rates of our patients have been due to new protocols with less toxic therapies and better supportive care.

1. Introduction

Down syndrome (DS), or trisomy 21, is the most common congenital chromosomal abnormality, with a prevalence of 8.5–10 cases/10,000 live births. An association between DS and leukemia was initially reported in 1930 [1]. Children with DS have a 10–20-fold higher risk of developing acute lymphoblastic leukemia (ALL) and a 150-fold higher risk of acute myeloid leukemia (AML) than the general population, possibly implying that DS is a predisposing syndrome for acute leukemia [2,3,4]. Although an exact mechanism has not yet been elucidated, it appears to be related to the extra chromosome 21 [4].
Children with DS–acute lymphoblastic leukemia (DS-ALL) have historically had poorer outcomes than those in children with ALL without DS (NDS-ALL) at a similar risk level. Contributing factors include the less frequent detection of favorable cytogenetic characteristics and increased treatment-related toxicity, resulting in increased relapses and mortality [5]. Transient abnormal myelopoiesis (TAM) is a preleukemic state in neonates with spontaneous remission [6]. About 10% of patients with TAM will transition to AML during the first 4 years of their lives, while a small percentage may pass away [7]. DS-AML has a better prognosis than that of AML without DS (NDS-AML) due to genetic and biological underlying features, a better response to chemotherapeutic agents, and a lower frequency of relapses [8].
The aim of the present study is to present the data on pediatric patients with DS-AL treated in Greece between 2001 and 2021, as the optimal management of these patients still poses unique challenges.

2. Materials and Methods

A retrospective cohort study on DS-AL was conducted by the Hellenic Society of Pediatric Hematology–Oncology (HESPHO) including the pediatric patients with DS-ALL, AML, and TAM treated in all of the pediatric hematology–oncology centers in Greece between 2001 and 2021. Their demographic characteristics are shown in Table 1 and Table 2. A diagnosis was based on morphology, immunohistochemical data, flow cytometry, G-banding karyotype, RT-PCR, and FISH and made at local centers. For flow cytometry, a panel with 6 colors was used, with combinations of 4 to 6 markers, both surface and intracellular for complete typing of acute leukemia. Karyotype G-banding used the proteolytic enzyme trypsin, followed by staining with Leishman stain.
BCR/ABL translocation, MLL rearrangement, and TEL-AML1 fusion gene translocation were examined using FISH and RT-PCR. The FISH probe for the BCR/ABL LSI was a dual-color fusion probe. For MLL rearrangement (KMT2A), a MetaSystems Break Apart XL MLL plus probe was used. BCR/ABL, TEL-AML1, and GATA1 mutations were estimated using RT-PCR according to BIOMED-1’s protocol. An NGS analysis for GATA1 was conducted in two patients, but NGS-based molecular diagnostics was not performed for any patients with DS AL.
This study assessed the 5-year overall survival (OS) and relapse outcomes. The median follow-up was 9.25 (0.6–17.42) years for DS-ALL, 7.25 (0.25–18.25) years for DS-AML, and 3.1 (2.1–4.0) years for TAM.
The parents and/or guardians of the patients provided written informed consent for them to participate in this study. Equally, this study was approved by the Institutional Review Board of Ippokratio General Hospital, Thessaloniki, Greece (approval number: 146/04-07-2023).

3. The Statistical Analysis

The data were analyzed using the RStudio 3.5.3 statistical package. Categorical variables were presented as absolute numbers and percentages, normally distributed quantitative variables were presented as means ± standard deviations, and non-normally distributed were presented as medians (25th–75th percentiles). OS was defined as the time from diagnosis to death from any cause or the last follow-up, and the data were illustrated using Kaplan–Meier curves.

4. Results

A total of 20 patients were studied, 9 male (45%) and 11 female (55%). Ten children had DS-ALL (five male), five had DS-AML (two male), and six had TAM (three male), including one patient who progressed to DS-AML. The clinical and laboratory characteristics of the DS-AL patients are summarized in Table 1 and Table 2.

4.1. DS-ALL

Ten patients had DS-ALL, with a median age at diagnosis of 4.7 years. All presented with B-cell precursor ALL and achieved first complete remission (CR1). None had central nervous system (CNS) involvement. According to karyotype, two had hyper-diploidy with over 50 chromosomes, and two had a complex karyotype (with more than three abnormal chromosomes). None had translocations associated with an adverse outcome (Table 3). The treatment protocols used [UKALL-XI (3 pts), ALL BFM 95 (2 pts), and ALLIC BFM 2009 (5 pts)] did not include distinct treatment arms or recommendations for DS patients. According to the protocol classification, one patient was considered standard-risk (SR), eight were considered intermediate-risk (IR), and two were considered high-risk (HR). To reduce methotrexate (MTX) toxicity, two patients received treatment modifications after an expert opinion. One received lower but gradually increasing doses of MTX (500 mg/m2, 1 g/m2, 2 g/m2, 2 g/m2) during consolidation and a lower dose of PEG-asparaginase (1000 IU/m2 instead of 2500 IU/m2) at induction and late intensification and, although they were a poor prednisone-responder (PPR), was assigned into the IR group, as on D33, their fMRD (flow cytometry minimal residual disease) was under 0.01. The other received lower doses of MTX in the HD MTX blocks (1 g/m2, 500 mg/m2 for the other three blocks) and one out of two doses of doxorubicin and VCR at late intensification. Both children were alive at CR1. Two patients received prophylactic antifungal treatments during periods of neutropenia.
Some patients presented with comorbidities commonly seen in DS: four patients had heart problems; one with tetralogy of Fallot was operated on at 50 days of age and at 1.5 years of age, and one with a complete atrioventricular block was treated with a defibrillator. Regarding relapses, one patient experienced a bone marrow relapse at 18 months from diagnosis. Despite responding to the relapse protocol, he succumbed to E. coli sepsis. Two additional patients passed away, one from pulmonary aspergillosis and another after cardiac surgery. The treatment-related mortality (TRM) was 20%. Seven patients (70%) were alive at CR1, with a median follow-up of 9.25 (0.6–17.42) years. The OS was 62.5% (Figure 1a).

4.2. DS-AML

Five patients were diagnosed with DS-AML, with a median age at diagnosis of 1.92 years. One had TAM as a neonate. Three patients (60%) were diagnosed within the first two years of their lives, and all had been diagnosed by the age of three years. None had CNS disease. Regarding their karyotypes, one had tetrasomy 21, and one had trisomy 7, while none had a complex karyotype (Table 4). All achieved CR1 after treatment with the following protocols: AML NOPHO 84 (1 pt), AML BFM 98 (1 pt), AML BFM 2004 (1 pt), and ML DS 2006 (2 pts). Three (60%) had AMKL, M7, including two who received the ML-DS 2006 protocol and were alive at CR1. The third patient with AMKL received the NOPHO 84 protocol and, although they achieved remission, passed away due to aspergillosis 11 months after their diagnosis. This patient, who did not receive prophylactic antifungal therapy, was diagnosed in 2001, before supportive measures were instituted. Three patients (60%) received prophylactic antifungal treatment during periods of neutropenia according to the common clinical practice of the treating center. Regarding death, no other patient passed away. Four patients (80%) were alive at CR1 with a median follow-up of 7.25 years (0.25–18.25), including the one with TAM. The TRM was 20%. The OS was 75% (Figure 1b).

4.3. TAM

Six patients were diagnosed with TAM, with a median age at diagnosis of 9 days. One patient required treatment due to liver dysfunction, with one cycle of Ara-C (1.5 mg/kg for 8 days), resulting in normal liver function at two months. Two patients had leukocytosis and one had thrombocytopenia at diagnosis. The time required for a full recovery for patients in watch-and-wait management was two months. GATA1 mutant clones were detected through targeted next-generation resequencing (NGS) in two patients with TAM. NGS was carried out using MiSeq (Illumina, San Diego, CA, USA) and showed the pathogenic CDS-MUTATIONS c.90_91del and c.-19-17_10delinsAGA. Their variant IDs were NM_002049 4864905 and NM_002049 48649481. The children with TAM were placed under close monitoring, but only one progressed to AMKL 14 months later. The patient who received chemotherapy did not progress to AML. One patient with an intraventricular septal defect passed away 13 months later from pulmonary hypertension and a CMV infection.

5. Discussion

The findings of this study contribute to the growing understanding of the treatment outcomes for DS-AL and reinforce the need for tailored therapeutic strategies. Given the distinct biological behavior of leukemia in DS patients, optimizing the treatment protocols and risk stratification are crucial. This study’s real-world data offer valuable insights that can inform international clinical guidelines and patient management strategies. This study has several limitations, including the small sample size, which may limit its statistical power and the generalizability of its findings. Its retrospective design relies on past data, potentially introducing selection bias and limiting causal inferences. Additionally, the heterogeneity of the treatment protocols among patients affects the comparability of the outcomes, potentially confounding the results. Another limitation of this study is the absence of an NGS-based molecular diagnosis for any of the patients with DS AL, while there is a need for a cutting-edge diagnostic approach to AL, with details on the mutation status of various genes to aid in the classification, prognosis, and therapeutic decisions.
Despite its limitations, this study has several strengths. First, its nationwide scope ensured the inclusion of data from a broad patient population, enhancing its relevance to real-world clinical practice. Second, its contribution to the real-world data provides practical insights that may be directly applicable to healthcare providers managing DS-AL patients. Third, this study highlights the improved survival outcomes due to the refinement of risk-adapted protocols and treatment modifications with reduced intensification in selected patients. It also suggests that dosage modifications and downstaging in these patients do not negatively impact survival.

5.1. ALL

According to the clinical features, gender and WBC at diagnosis are similar between DS-ALL and NDS-ALL [9,10]. The age range is also similar, except for infants. DS-ALL in infants is very rare, while for NDS-ALL, it occurs in 2–6% of cases. In our cohort, no patient was <1 year old at diagnosis. Regarding the biological characteristics, T-ALL and Ph+ t(9;22), as well as favorable cytogenetic characteristics, are very rare in DS [11]. In a recent study, only 5 of 653 patients with DS-ALL had T-ALL (expected: 10–15%), and 15% had high hyper-diploidy (expected 40%), while 40% had a normal karyotype (expected: 7%) [12]. Similarly, a COG study reported lower rates of the favorable cytogenetic lesions ETV6-RUNX1 (2.5% vs. 24%) and trisomy 4 and 10 (7.7% vs. 24%) and a lower 5-year event-free survival (EFS) and OS in DS-ALL [9]. In our cohort, no patient presented with T-ALL, and most patients (60%) had a normal karyotype, while 20% had hyper-diploidy (>50 chromosomes), 20% had a complex karyotype, and 10% had trisomy 10. Despite these differences, recent studies have shown a similar response to treatment between DS-ALL and NDS-ALL when equivalent induction therapy is used, with remission rates between 96 and 99% [4,9]. This is in accordance with our results, as all patients achieved CR.
Early trials with reduced-intensity treatment or insufficient supportive care showed a reduced EFS and OS for DS-ALL [10]. On the contrary, recent studies have reported excellent results, with 10-year EFS rates of 94.4% [13]. Consequently, we must consider that DS-ALL represents a unique subtype of ALL with special biological characteristics, requiring an adequate intensity of chemotherapy and the appropriate supportive care.
The main cause of a reduced chemotherapy intensity leading to treatment failure in the past has been drug toxicity. Methotrexate (MTX) toxicity or hypersensitivity to MTX is attributed to the increased intracellular concentration of MTX in cells with trisomy 21, resulting in mucositis and gastrointestinal and hematological toxicity [14,15]. The BFM-AIEOP protocol recommends a reduction in MTX to 500 mg/m2 in the first block of high-dose (HD) MTX, with a gradual increase in subsequent courses to reduce MTX’s toxicity [16]. In our cohort, the patients who received reduced doses of HD MTX suffered only from grade 1 mucositis. A COG study with SR DS-ALL patients showed that the escalation of MTX in interim maintenance had excellent results, with 10-year EFS rates of 81.5–94.4% [13].
DS-ALL patients have increased TRM due to infections, with 40% TRM reported during maintenance [10,14]. A recent meta-analysis including 1303 children with DS-ALL showed significantly higher rates of TRM in the DS group [17]. Another study reported TRM rates of 13.2% between 54 patients with DS-ALL [18]. Patients with DS have impaired immunity, characterized by a reduced B-cell count, a low specific antibody response, and NK cells with a reduced function [19,20]. The current interventions include chemotherapeutic modifications, intravenous immunoglobulin (IVIG) treatment, prophylactic antibiotics/antifungals, and hospitalization during mild neutropenia.
Chemotherapeutic modifications include reduced doses of anthracycline, PEG-asparaginase, and MTX [16]. Protocols with amendments for DS-ALL patients are DCOG ALL10, DCOG ALL11, UKALL2003, and NOPHO 2002. In the first two Dutch protocols, patients fulfilling the criteria for HR stratification are assigned into an intermediate-risk (MR) group. In UKALL2003, all patients with DS-ALL were treated as an SR group. In NOPHO 2002, no patient with DS-ALL was assigned into the SR group, and no patient proceeded to hematopoietic stem cell transplantation (HSCT) [21]. The AIEOP-BFM ALL 2017 treatment protocol (NCT03643276) recommends treating HR patients in the consolidation phase with the standard-of-care therapy. In our study, although all patients suffered from severe infectious complications, they achieved CR1. One patient succumbed to E-coli septicemia after a relapse and treatment according to the Rez ALL BFM 96 protocol. Our results are comparable to those of the aforementioned groups.
All modifications should consider the risk of recurrence. Emerging guidelines suggest maintaining a balance between the optimal treatment and the prevention of treatment toxicity. A NOPHO study concluded that physicians’ reluctance to increase the maintenance dose of MTX/6MP, resulting in a cumulatively lower maintenance dose, may contribute to relapses [15]. DS-ALL patients have an estimated higher possibility of relapse in 8 years, at 26% vs. 15% in NDS-ALL [12]. Although relapses in DS-ALL are considered low-risk, they are related to a lower EFS and OS compared to that in NDS-ALL (17% vs. 41%, and 17% vs. 51%, respectively), especially due to fatal infections [22].
HSCT for resistant or relapsed disease is limited to patients in second remission due to the low 3-year disease-free survival (DFS) post-HSCT, at 24% [23]. Furthermore, targeted therapies can cover the need for less toxic treatments or replace the most intensive blocks [24,25]. Blinatumomab was successfully administered to adults with relapsed DS-ALL [26] and has already been incorporated into two phase III studies: the COG NCT03914625 trial and the AIEOP ALL 2017 protocol for HR ALL, including patients with DS. Our patients did not receive HSCT or targeted therapies. The challenges complicating these treatments are a high risk of complications, unique immune systems, and a limited population. Further research should explore the role of targeted therapies in DS-AL management. Additionally, integrating these advanced therapies into healthcare systems presents challenges related to their accessibility, cost, and regulatory approval, which warrant further discussion.

5.2. TAM and AML

In DS-AML, three separable stages of disease development are distinguished: abnormal fetal hematopoiesis due to trisomy 21, a mutation in the key hematopoietic transcription factor GATA1 during fetal life resulting in TAM during perinatal life, and additional somatic mutations during the first years of life transforming preleukemic TAM into DS-AML [27,28,29,30,31]. About 10% of neonates with DS will develop TAM. The incidence of TAM may be higher according to the use of NGS for the GATA1 mutation, adding in an additional 20% [30,32]. Early identification of the GATA1 mutation through regular screening is very important, as it can lead to an early diagnosis of DS-AML [33].
TAM is defined as the presence of more than 10% blasts in a peripheral blood smear from neonates with DS, which is associated with the GATA1 mutation and/or the clinical criteria [34]. Most TAM cases will resolve spontaneously with supportive care only, although about 20–30% of patients will subsequently develop acute megakaryoblastic leukemia (AMKL). Patients with TAM are at an intermediate risk of death if they have hepatomegaly, liver dysfunction, or high levels of leucocytes [17,35]. A multicenter clinical trial recommended using a low dose of cytarabine in symptomatic patients with TAM to reduce mortality [36]. Our patient with liver dysfunction was treated successfully with cytarabine according to this recommendation. There is currently no way to predict which patients will later develop AML. There is no evidence that the severity of symptoms is related to the development of DS-AML, nor that the application of treatment for TAM can prevent the development of AMKL [36].
Compared with NDS-AML, patients with DS-AML are diagnosed earlier, with 95% being diagnosed before the age of 4 years and a median age of diagnosis of 1.8 years vs. that of 7.5 years for NDS-AML [37]. In our cohort, three patients (60%) with DS-AML were diagnosed within the first two years of their life, while all diagnoses occurred within the first three years of life. The age at diagnosis of DS-AML in the patient with prior TAM was lower (1.2 years) than the median age at diagnosis in patients without a clinical history of TAM [38].
DS-AML comprises approximately 15% of all pediatric AML cases, with 50% of cases being AMKL [39,40]. In the fifth WHO review of myeloid neoplasms, immunophenotyping and the detection of markers of megakaryocytic differentiation have been deemed required to diagnose AMKL and detect the newly described “RAM immunophenotype” [6]. According to the FAB classification, AMKL is classified as AML M7. AMKL in patients with TAM results from leukemic transformation, which requires additional mutations in cohesin, epigenetic regulators, and signaling proteins [4]. In our cohort, three patients (60%) had AMKL, M7 AML. Our patients expressed the megakaryocytic markers CD36, CD41, CD42, and CD61 on the surface of their blast cells according to flow cytometry, in agreement with the literature [39]. Common cytogenetic abnormalities in DS AMKL include trisomy and structural abnormalities [41]. Two of our patients with AMKL had a normal karyotype, and one had tetrasomy 21. The classic cytogenetic abnormalities usually detected in pediatric AML cases are extremely rare in DS-AML.
Patients with DS-AML have a significantly good prognosis, with their long-term OS exceeding 80% due to their sensitivity to chemotherapy agents, particularly cytarabine (Ara-C) [42]. Most studies have used a backbone with high-dose Ara-C, resulting in high cure rates for DS-AML. Their Ara-C sensitivity is attributed to the increased expression of the cystathionine-beta-synthase gene, resulting in increased levels of intracellular Ara-C triphosphate and cell apoptosis [40,43]. In a Japanese study, a repeated cycle of low-dose Ara-C with anthracycline resulted in an EFS of approximately 80% [44]. Large pediatric oncology groups have similarly reported improved survival rates for DS-AML, exceeding 90% in the COG study group [45].
The current recommendations of the AML-BFM study group, based on the results of the ML-DS 2006 study, include a lower dose of etoposide, fewer prophylactic intrathecal injections, and the omission of maintenance therapy while maintaining a high dose of cytarabine [46]. The COG group, announcing the results of AAML0431, suggested the earlier use of HD-Ara-C, a reduction in the cumulative daunorubicin dose, and MRD recognized on day 28 as new prognostic factors [47].
Patients with refractory or relapsed disease have a very poor prognosis, with an OS of 12% in the POG9421 and CCG2891 trials. A Japanese study reported an OS of 25.9%, mainly due to treatment failure and disease progression [48]. Recent recommendations include AZA ± Panobinostat for cases with a low blast count or FLA ± GO for cases with a high blast count, followed by HSCT [49]. Relapses after HSCT and transplant-related complications remain the leading causes of death for patients with DS-AML, with a 3-year OS of 19% [50]. Relapses are often due to resistance to Ara-C [49]. In our study, all patients with DS-AML achieved CR, and none relapsed. Participation in clinical trials with novel agents is a future direction for DS-AML [51].

6. Conclusions

This study underscores the importance of specialized approaches to DS-AL treatment and highlights the need for continued research and international collaboration. The therapeutic outcomes of pediatric DS-AL patients in Greece are comparable to the results described by other research groups. The improved survival rates of our patients can be attributed to the refinement of risk-adapted protocols with less toxic therapies, treatment modifications with reduced intensification in selected patients, and the optimal supportive care. Participation in international protocols and targeted therapies seem to be future directions.

Author Contributions

Conceptualization: E.P. and S.P. Methodology: A.T., E.S., M.M. and E.P. Software: E.P. and A.T. Validation: M.N., G.T., I.P., E.P. and K.I.A. Formal analysis: E.P. Investigation: A.T., M.A., N.K., M.N., G.T., V.A. and C.K. Resources: N.K., I.P. and V.P. Data curation: V.A., C.K., E.S., M.M., E.P. and E.H. Writing—original draft preparation: E.P. and K.I.A. Writing—review and editing: S.P., M.A. and C.K. Visualization: M.A., C.K. and S.P. Supervision: H.K., A.K. and E.S. Project administration: D.D., E.S. and M.M. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

This study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Ippokratio General Hospital, Thessaloniki, Greece (approval number: 146/04-07-2023; date of approval: 4 July 2023).

Informed Consent Statement

Written informed consent has been obtained from the patient(s) to publish this paper.

Data Availability Statement

The data presented in this study are available on request from the corresponding author. The data are not publicly available due to privacy restrictions.

Conflicts of Interest

The authors declare no conflicts of interest.

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Hemato 06 00008 g001
Figure 1. Kaplan–Meier curves showing the probability of survival after diagnosis. (a) DS-ALL (n = 10); (b) DS-AML (n = 5).
Figure 1. Kaplan–Meier curves showing the probability of survival after diagnosis. (a) DS-ALL (n = 10); (b) DS-AML (n = 5).
Hemato 06 00008 g001
Table 1. Patient demographics.
Table 1. Patient demographics.
Clinical CharacteristicsALLAMLTAM
Gender, n (%)M: 5 (50)M: 2 (40)M: 3 (50)
F: 5 (50)F: 3 (60)F: 3 (50)
Median age at diagnosis (years)4.70 (1.16–13.83)1.92 (1.25–3)(days) 7 (3–16)
Leukemia type, n (%)Common-B: 7 (70)M7, AMKL: 3 (60)NA
Pre-B: 3 (30)M3: 1 (20)NA
M6: 1 (20)NA
Clinical presentation, n (%)Anemia: 6 (60)2 (40) 0
Hepatosplenomegaly: 4 (40)2 (40)1 (17)
Thrombopenia: 8 (80)4 (80) 1 (17)
Adenopathy: 4 (40)1 (20)0
M: male; F: female; AMKL: acute megakaryoblastic leukemia.
Table 2. Clinical and laboratory characteristics.
Table 2. Clinical and laboratory characteristics.
CharacteristicsALLAMLTAM
WBC (×103/μL)5.5 (1.6–394)3.3 (2.3–45.8)36 (31.3–70)
Hb (g/dL)7.9 (3.7–15.6)7.1 (2.8–10.2)15 (13.1–17)
PLTs (×103/μL)81 (8–103)21 (8–60)103 (20–248)
BMA blasts (%)80 (47–94)30 (21–50)NA
Heart disease (%)4 (40)2 (40)1 (17)
WBC: white blood count; Hb: hemoglobin; PLTs: platelets; BMA: bone marrow aspiration.
Table 3. Cytogenetics in DS-ALL.
Table 3. Cytogenetics in DS-ALL.
NKaryotype
1.55, XY, +X, +6, +9, +10, +14, +17, +18, +2, +21, +21c[19]/XY, +21c[1]
2.47 XY, +21c
3.47 XX, del (7) (p11), +21c[13]
4.47 XY, +21c
5.47 XY, +21c
6.47, XY, +21c/46, XY
7.47 XY, +21c
8.55, XY, +X, +3, +5, +6, del(9)(p21), +9, +10, +13, +17, +21c[6]/47,XY, +21c[7]
9.47 XY t(8;12)(p21;p13), +21c(4)/47 XY +21C(16)
10.47 ΧΧ, +21c, del 12
Table 4. Cytogenetics in DS-AML.
Table 4. Cytogenetics in DS-AML.
ΝFAB.Leukemic Karyotype
1.M747, XX, +21c
2.M347, XX, +21c
3.M748, XX, +21, +21c[13]/47XX, +21c
4.M747, XY, +21c
5.M647, XY, +7, p1;5, +21c
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Papakonstantinou, E.; Tragiannidis, A.; Ampatzidou, M.; Katzilakis, N.; Nikita, M.; Totikidis, G.; Athanasiadou, K.I.; Antari, V.; Kelaidi, C.; Pelagiadis, I.; et al. Acute Leukemia in Children with Down Syndrome: A Report from the Hellenic HESPHO Group. Hemato 2025, 6, 8. https://doi.org/10.3390/hemato6020008

AMA Style

Papakonstantinou E, Tragiannidis A, Ampatzidou M, Katzilakis N, Nikita M, Totikidis G, Athanasiadou KI, Antari V, Kelaidi C, Pelagiadis I, et al. Acute Leukemia in Children with Down Syndrome: A Report from the Hellenic HESPHO Group. Hemato. 2025; 6(2):8. https://doi.org/10.3390/hemato6020008

Chicago/Turabian Style

Papakonstantinou, Evgenia, Athanasios Tragiannidis, Mirella Ampatzidou, Nikolaos Katzilakis, Maria Nikita, Georgios Totikidis, Kleoniki I. Athanasiadou, Vasiliki Antari, Charikleia Kelaidi, Iordanis Pelagiadis, and et al. 2025. "Acute Leukemia in Children with Down Syndrome: A Report from the Hellenic HESPHO Group" Hemato 6, no. 2: 8. https://doi.org/10.3390/hemato6020008

APA Style

Papakonstantinou, E., Tragiannidis, A., Ampatzidou, M., Katzilakis, N., Nikita, M., Totikidis, G., Athanasiadou, K. I., Antari, V., Kelaidi, C., Pelagiadis, I., Doganis, D., Mpaka, M., Kosmidis, H., Kattamis, A., Stiakaki, E., Papadakis, V., Hatzipantelis, E., & Polychronopoulou, S. (2025). Acute Leukemia in Children with Down Syndrome: A Report from the Hellenic HESPHO Group. Hemato, 6(2), 8. https://doi.org/10.3390/hemato6020008

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