Relapsed B-lineage acute lymphoblastic leukemia (ALL) in children is associated with poor prognosis. Therefore, it seems essential to stratify patients according to prognostic factors in order to adapt therapies. The evaluation of minimal/measurable residual disease (MRD) during chemotherapy constitutes the most powerful prognostic factor in all age groups, indeed, patients with early low MRD having better outcomes. New immunotherapies based on monoclonal antibodies have recently been developed and are giving promising results in chemoresistant forms with limited toxicities. Indeed, CD20, CD38, CD22 and, less developed, HER2/neu constitute therapeutic targets. However, few studies have reported on the expression level of these markers and compared it to the normal counterpart, precursor B-cells or hematogones. Such investigations would be useful to appreciate the potential efficacy of immunotherapies targeting these markers. Moreover, it could help for the detection of minimal/measurable residual disease during follow-up. A cohort of 125 B-ALL patients (1-25 years old) was retrospectively enrolled in this study, treated between January 2011 and February 2020. Samples collected from bone marrow or peripheral blood were studied in multiparameter flow cytometry (MFC). Cells were analyzed with a Canto II flow cytometer (BD Biosciences), and Diva (BD Biosciences) software was used to assess the expression of the antigenic markers. The same MFC assay had been performed over the whole period, allowing for fluorescence intensities comparison. Additionally, results from 36 normal bone marrow samples were examined, to compare the level of antigen expression by hematogones. CD20, CD38 and CD22 were expressed in respectively 53.6%, 99.2% 98.4% of the cases, rather homogeneously and at intermediate levels. The mean fluorescence intensity of CD38 was much higher on hematogones than blasts, which made it a leukemia-associated immunophenotype (LAIP) for 101 patients (81.4%). HER2/neu, a marker of breast cancer also expressed in a subset of ALL, was present in 16 samples (13.4%), but not detectable on hematogones, and can thus always be considered a LAIP. Interestingly, in this subgroup, patients had a significantly lower 5-year EFS compared to patients without expression of HER2/neu (63% versus 80.5%, p=0.02) (Figure 1). No significant difference in the expression of tested potential therapeutic markers was found between age groups. In conclusion, these 4 antigens have sufficient expression intensities to make them potential therapeutic targets, which could be an interesting alternative for the treatment of refractory/relapsed childhood B-ALL. For example, trastuzumab could be a potential immunotherapy in the HER2/neu expressing group, especially regarding their poorer prognosis. Moreover, CD38 and HER2/neu are good candidates for monitoring MRD. These results are of interest as it has been shown that monitoring MRD early was prognostic on patients' outcome. Figure Disclosures Chevallier: Incyte Corporation: Honoraria.
Acute lymphoblastic leukemia (ALL), the most common cancer in childhood, 1 has nowadays a 5-year overall survival (OS) exceeding 90%. 2 Unfortunately, relapse occurs in about 20% of the cases and even after a second cytological remission (CR), 5-year OS does not exceed 30%-40%. 3 Some antigens expressed by malignant leukemic cells can serve as therapeutic targets in refractory ALL for unconjugated monoclonal antibodies (MoAbs), alone or associated to chemotherapy, MoAbs conjugated to toxins or radionuclides or bispecific antibodies engaging T-cells. 4 Here, we evaluated the expression level of CD19, CD20, CD38, CD22, and HER2/neu on childhood B-ALL blasts, as potential therapeutic targets in case of treatment failure or relapse.Between January 2011 and February 2020, 125 young patients were diagnosed with B-ALL (n ¼ 115) or relapsed (n ¼ 10) in Nantes University Hospital. Their median age was 5.5 years old (range 1 year 3 months-24 years 9 months). There were 102 children (median age 4 years 9 months) and 23 adolescent-young adults (AYA; median age 19 years 5 months). Patients, or their parents, signed a written
AimThis study aimed to evaluate the incidence of self‐reported taste and smell alterations (TSA) in cancer paediatric patients and evaluate the impact of TSA on nutritional status in this population. We also developed and validated a composite score to detect TSA in children undergoing chemotherapy.MethodsPaediatric patients who were undergoing chemotherapy in a paediatric oncology unit were included. TSA were assessed from the Gustonco questionnaire from which a composite score was developed and internally validated, eating behaviour was assessed using Child Eating Behaviour Questionnaire, and major weight loss was defined from nutritional status. All data were calculated at 1, 3 and 6 months after chemotherapy start. Associations between nutritional status and scores were studied by using logistic models.ResultsAmong 49 patients included, TSA occurred in 71.7% of patients at 1 month after chemotherapy start and persisted at 3 and 6 months. TSA led to altered appetite since 1 month after chemotherapy start. The occurrence of a major weight loss at 6 months seemed to be associated with a high Gustonco score.ConclusionTaste and smell alterations often occurred in paediatric cancer patients after chemotherapy start and seemed to be associated with impaired nutrition at 6 months after chemotherapy.
BackgroundThanks to an improved therapeutic regimen in childhood B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL), 5 year‐overall survival now exceeds 90%. Unfortunately, the 25% of children who relapse have an initial poor prognosis, potentially driven by pre‐existing or emerging molecular anomalies. The latter are initially and essentially identified by cytogenetics. However, some subtle alterations are not visible through karyotyping.MethodsSingle nucleotide polymorphisms (SNP) array is an alternative way of chromosomal analysis allowing for a more in‐depth evaluation of chromosomal modifications such as the assessment of copy number alterations (CNA) and loss of heterozygosity (LOH). This method was applied here in retrospective diagnosis/relapse paired samples from seven children with BCP‐ALL and in a prospective cohort of 38 newly diagnosed childhood cases.ResultsIn the matched study, compared to the initial karyotype, SNP array analysis reclassified two patients as poor prognosis cases. Modulation during relapse was seen for 4 CNA and 0.9 LOH. In the prospective study, SNP reclassified the 10 patients with intermediate karyotype as 7 good prognosis and 3 poor prognosis. Ultimately, in all the children tested, SNP array allowed to identify additional anomalies compared to conventional karyotype, refine its prognostic value and identify some druggable anomalies that could be used for precision medicine. Overall, the anomalies detected could be segregated in four groups respectively involved in B‐cell development, cell proliferation, transcription and molecular pathways.ConclusionSNP therefore appears to be a method of choice in the integrated diagnosis of BCP ALL, especially for patients initially classified as intermediate prognosis. This complementary method of both cytogenetics and high throughput sequencing allows to obtain further classified information and can be useful in case of failure of these techniques.
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