Unlocking the potential of anti-CD33 therapy in adult and childhood acute myeloid leukaemia

Acute Myeloid Leukaemia (AML) develops when there is a block in differentiation and uncontrolled proliferation of myeloid precursors, resulting in bone marrow failure. AML is a heterogeneous disease clinically, morphologically, and genetically, and biological differences between adult and childhood AML have been identified. AML comprises 15-20% of all children less than fifteen years diagnosed with acute leukaemia. Relapse occurs in up to 40% of children with AML and is the commonest cause of death.1,2 Relapse arises from leukaemic stem cells (LSCs) that persist after conventional chemotherapy. The treatment of AML is challenging and new strategies to target LSCs are required. The cell surface marker CD33 has been identified as a therapeutic target, and novel anti-CD33 immunotherapies are promising new agents in the treatment of AML. This review will summarise recent developments emphasising the genetic differences in adult and childhood AML, while highlighting the rationale for CD33 as a target for therapy, in all age groups

Harnessing the potential of epigenetic therapies for childhood acute myeloid leukemia

There is a desperate need for new and effective therapeutic approaches for AML in both children and adults. Epigenetic aberrations are common in adult AML, and many novel epigenetic compounds are in clinical development that may improve patient outcomes. Mutations in epigenetic regulators occur less frequently in AML in children compared to adults. However, investigating the potential benefits of epigenetic therapy in paediatric AML is an important issue that will be discussed in this review

Nonimmune neonatal anemias

No abstract available

Prevalence of protein-energy malnutrition at diagnosis in children with acute lymphoblastic leukemia

Background: The purpose of the present study was to test the hypothesis that protein-energy undernutrition is common in patients with acute lymphoblastic leukemia at diagnosis. Previous studies have failed to establish whether undernutrition is a common feature at diagnosis. Methods: Body mass index (BMI, weight/height2), expressed as a standard deviation score (SDS) relative to contemporary United Kingdom reference data, was used as the index of nutritional status. The index was calculated in a national cohort of standard-risk patients (n = 1019) treated in the same protocol in the United Kingdom. Results: Prevalence of undernutrition (defined as BMI SDS <-2.0) exceeded expected frequencies in boys (7.6%) and girls (6.7%). These differences were statistically significant (p < 0.001), with a 95% confidence interval for the prevalence of undernutrition of 5.8% to 9.0%. Conclusions: Undernutrition is relatively common in patients with newly diagnosed acute lymphoblastic leukemia, with a threefold excess of patients below the cutoff used to define undernutrition. Screening for undernutrition at diagnosis of acute lymphoblastic leukemia is indicated, and the BMI SDS is a simple index of nutritional status that could be readily calculated using measurements routinely made at diagnosis. The same simple screening technique could also be used clinically to detect and manage or prevent overnutrition (obesity), which is common in these patients after diagnosis

No evidence for an effect of nutritional status at diagnosis on prognosis in children with acute lymphoblastic leukemia.

Purpose: To test the hypothesis that nutritional status at diagnosis, defined as body mass index standard deviation score (SDS). is related to the prognosis in childhood acute lymphoblastic leukemia (ALL). Patients and Methods: The sample consisted of 1.025 patients with standard risk ALL who had been randomized to different intensification therapies. Outcome measures were relapse/no relapse and time to first relapse. The influence of body mass index SDS was tested by survival analysis. Results: There was no evidence that body mass index SDS was related to clinical outcome (proportional hazards model, p = 0.72). Conclusions: The study results suggest that nutritional status at diagnosis, defined on the basis of the body mass index, at least in developed countries, has no effect on the prognosis in ALL, and it should not be considered as a prognostic factor

One-parametric bottleneck transportation problems

SIGLETIB: RO 3475 (88) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Prevalence of protein-energy malnutrition at diagnosis in children with acute lymphoblastic leukemia

Background: The purpose of the present study was to test the hypothesis that protein-energy undernutrition is common in patients with acute lymphoblastic leukemia at diagnosis. Previous studies have failed to establish whether undernutrition is a common feature at diagnosis. Methods: Body mass index (BMI, weight/height2), expressed as a standard deviation score (SDS) relative to contemporary United Kingdom reference data, was used as the index of nutritional status. The index was calculated in a national cohort of standard-risk patients (n = 1019) treated in the same protocol in the United Kingdom. Results: Prevalence of undernutrition (defined as BMI SDS <-2.0) exceeded expected frequencies in boys (7.6%) and girls (6.7%). These differences were statistically significant (p < 0.001), with a 95% confidence interval for the prevalence of undernutrition of 5.8% to 9.0%. Conclusions: Undernutrition is relatively common in patients with newly diagnosed acute lymphoblastic leukemia, with a threefold excess of patients below the cutoff used to define undernutrition. Screening for undernutrition at diagnosis of acute lymphoblastic leukemia is indicated, and the BMI SDS is a simple index of nutritional status that could be readily calculated using measurements routinely made at diagnosis. The same simple screening technique could also be used clinically to detect and manage or prevent overnutrition (obesity), which is common in these patients after diagnosis

A diminutive chromosome 21 centromere in acute lymphoblastic leukemia

A chance observation of a tiny constitutional variant for the centromere of chromosome 21 in two patients with acute lymphoblastic leukemia (ALL), suggested a possible correlation with the cytogenetic findings in their leukemic cells. Interphase FISH revealed three 13/21 centromeric signals and a single MLL signal in the blast cells of each patient. Metaphase FISH with dual-color application of whole-chromosome paint (wcp) and centromeric probes for chromosome 21 showed two copies of chromosome 21, one with a tiny centromeric signal which corresponded to the invisible centromere in the interphase cells. Patient 2700 had a normal karyotype in his bone marrow at diagnosis. All metaphases from his stimulated peripheral blood also had the tiny chromosome 21 centromere, proving it to be a constitutional variant. Patient 3314 showed the abnormal karyotype 46,XY,inv(1)(p?q?),det(11)(q?),del(12)(p?),inc in his bone marrow. Interphase FISH revealed only one copy each of the ABL and ETV6 genes, in addition to the loss of the MLL signal. The question arises, is there an association between the diminutive centromeric signals for chromosome 21 and the chromosomal instability demonstrated by the deletions of key genes from the leukemic blasts of these two patients