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- Hagleitner, M M, et al.
(author)
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Clinical spectrum of immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome).
- 2008
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In: Journal of medical genetics. - : BMJ. - 1468-6244. ; 45:2, s. 93-9
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Journal article (peer-reviewed)abstract
- BACKGROUND: Immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome) is a rare autosomal recessive disease characterised by facial dysmorphism, immunoglobulin deficiency and branching of chromosomes 1, 9 and 16 after PHA stimulation of lymphocytes. Hypomethylation of DNA of a small fraction of the genome is an unusual feature of ICF patients which is explained by mutations in the DNA methyltransferase gene DNMT3B in some, but not all, ICF patients. OBJECTIVE: To obtain a comprehensive description of the clinical features of this syndrome as well as genotype-phenotype correlations in ICF patients. METHODS: Data on ICF patients were obtained by literature search and additional information by means of questionnaires to corresponding authors. Results and CONCLUSIONS: 45 patients all with proven centromeric instability were included in this study. Facial dysmorphism was found to be a common characteristic (n = 41/42), especially epicanthic folds, hypertelorism, flat nasal bridge and low set ears. Hypo- or agammaglobulinaemia was demonstrated in nearly all patients (n = 39/44). Opportunistic infections were seen in several patients, pointing to a T cell dysfunction. Haematological malignancy was documented in two patients. Life expectancy of ICF patients is poor, especially those with severe infections in infancy or chronic gastrointestinal problems and failure to thrive. Early diagnosis of ICF is important since early introduction of immunoglobulin supplementation can improve the course of the disease. Allogeneic stem cell transplantation should be considered as a therapeutic option in patients with severe infections or failure to thrive. Only 19 of 34 patients showed mutations in DNMT3B, suggesting genetic heterogeneity. No genotype-phenotype correlation was found between patients with and without DNMT3B mutations.
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| 2. |
- Kroeze, E., et al.
(author)
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Pediatric Precursor B-Cell Lymphoblastic Malignancies: From Extramedullary to Medullary Involvement
- 2022
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In: Cancers. - : MDPI AG. - 2072-6694. ; 14:16
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Journal article (peer-reviewed)abstract
- Simple Summary B-cell lymphoblastic lymphoma (BCP-LBL) and B-cell acute lymphoblastic leukemia (BCP-ALL) are both malignancies of immature B-cells. However, BCP-ALL has been extensively studied and treatment protocols have changed over the last decades, whereas BCP-LBL is quite rare, and treatment has stayed roughly the same. In this retrospective study, we compare the clinical characteristics of a cohort of BCP-LBL patients to a cohort BCP-ALL patients. With the comparison of this unique large cohort of immature B-cell malignancies, we aim to contribute to elucidating whether BCP-LBL and BCP-ALL represent two diseases, or different representations of the same disease. Increasing the understanding of BCP-LBL in comparison to BCP-ALL is crucial for improving treatment and prognosis for BCP-LBL. B-cell lymphoblastic lymphoma (BCP-LBL) and B-cell acute lymphoblastic leukemia (BCP-ALL) are the malignant counterparts of immature B-cells. BCP-ALL is the most common hematological malignancy in childhood, while BCP-LBL accounts for only 1% of all hematological malignancies in children. Therefore, BCP-ALL has been well studied and treatment protocols have changed over the last decades, whereas treatment for BCP-LBL has stayed roughly the same. Clinical characteristics of 364 pediatric patients with precursor B-cell malignancies were studied, consisting of BCP-LBL (n = 210) and BCP-ALL (n = 154) patients. Our results indicate that based on the clinical presentation of disease, B-cell malignancies probably represent a spectrum ranging from complete isolated medullary disease to apparent complete extramedullary disease. Hepatosplenomegaly and peripheral blood involvement are the most important discriminators, as both seen in 80% and 95% of the BCP-ALL patients and in 2% of the BCP-LBL patients, respectively. In addition, we show that the overall survival rates in this cohort differ significantly between BCP-LBL and BCP-ALL patients aged 1-18 years (p = 0.0080), and that the outcome for infants (0-1 years) with BCP-LBL is significantly decreased compared to BCP-LBL patients of all other pediatric ages (p < 0.0001).
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| 3. |
- Andrés-Jensen, Liv, et al.
(author)
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Severe toxicity free survival : physician-derived definitions of unacceptable long-term toxicities following acute lymphocytic leukaemia
- 2021
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In: The Lancet Haematology. - : Elsevier. - 2352-3026. ; 8:7, s. E513-E523
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Research review (peer-reviewed)abstract
- 5-year overall survival rates have surpassed 90% for childhood acute lymphocytic leukaemia, but survivors are at risk for permanent health sequelae. Although event-free survival appropriately represents the outcome for cancers with poor overall survival, this metric is inadequate when cure rates are high but challenged by serious, persistent complications. Accordingly, a group of experts in paediatric haematology-oncology, representative of 17 international acute lymphocytic leukaemia study groups, launched an initiative to construct a measure, designated severe toxicity-free survival (STFS), to quantify the occurrence of physician-prioritised toxicities to be integrated with standard cancer outcome reporting. Five generic inclusion criteria (not present before cancer diagnosis, symptomatic, objectifiable, of unacceptable severity, permanent, or requiring unacceptable treatments) were used to assess 855 health conditions, which resulted in inclusion of 21 severe toxicities. Consensus definitions were reached through a modified Delphi process supplemented by two additional plenary meetings. The 21 severe toxicities include severe adverse health conditions that substantially affect activities of daily living and are refractory to therapy (eg, refractory seizures), are without therapeutic options (eg, blindness), or require substantially invasive treatment (eg, cardiac transplantation). Incorporation of STFS assessment into clinical trials has the potential to improve and diversify treatment strategies, focusing not only on traditional outcome events and overall survival but also the frequencies of the most severe toxicities. The two major aims of this Review were to: prioritise and define unacceptable long-term toxicity for patients with childhood acute lymphocytic leukaemia, and define how these toxicities should be combined into a composite quantity to be integrated with other reported outcomes. Although STFS quantifies the clinically unacceptable health tradeoff for cure using childhood acute lymphocytic leukaemia as a model disease, the prioritised severe toxicities are based on generic considerations of relevance to any other cancer diagnosis and age group.
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