A review of current induction strategies and emerging prognostic factors in the management of children and adolescents with acute lymphoblastic leukemia

Introduction: Acute lymphoblastic leukemia is the most frequent hematologic malignancy in children. Almost 95% of children potentially achieve a complete remission after the induction treatment, but over the last years, new insights in the genomic disease profile and in minimal residual disease detection techniques have led to an improvement in the prognostic stratification, identifying selected patients’ subgroups with peculiar therapeutic needs. Areas covered: According to a comprehensive search of peer-review literature performed in Pubmed, in this review we summarize the recent evidences on the induction treatment strategies comprised in the children acute lymphoblastic leukemia scenario, focusing on the role of key drugs such as corticosteroids and asparaginase and discussing the crucial significance of the genomic characterization at baseline which may drive the proper induction treatment choice. Expert opinion: Current induction strategies already produce durable remissions in a significant proportion of standard-risk children with acute lymphoblastic leukemia. A broader knowledge of the biologic features related to acute lymphoblastic leukemia subtypes with worse prognosis, and an optimization of targeted drugs now available, might lead to the achievement of long-term molecular remissions in this setting

Evaluation of a New, Rapid, Fully Automated Assay for the Measurement of ADAMTS13 Activity

Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy (TMA) characterized by the severe deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity (< 10%). Rapid ADAMTS13 testing is crucial for an early diagnosis and optimal management of acute TTP. We evaluated the performance of the HemosIL AcuStar ADAMTS13 activity assay (Instrumentation Laboratory, Bedford, Massachusetts, United States), a fully automated chemiluminescent immunoassay with an analytical time of 33 minutes. A method comparison study was performed on 176 samples from 49 healthy donors and 127 TMA patients (109 TTP, 7 atypical hemolytic uremic syndrome, 11 other TMAs), comparing this new assay with an in-house FRETS-VWF73 assay and a commercial enzyme-linked immunosorbent assay (ELISA) (TECHNOZYM ADAMTS-13 Activity, Technoclone GmbH, Vienna, Austria). Agreement between methods was assessed with focus on ADAMTS13 activity less than 10%, the medical decision level relevant for TTP diagnosis. The HemosIL AcuStar ADAMTS13 Activity showed good correlation with both the FRETS-VWF73 (r = 0.96) and ELISA (r = 0.96) methods. Slope of the Passing-Bablok regression was 1.05 for FRETS-VWF73 and 1.02 for ELISA, and absolute bias at the medical decision level was +0.1 and +0.3%, respectively. The study also revealed high agreement with FRETS-VWF73 (kappa 0.97) and ELISA (kappa 0.98) methods in classifying TTP patients with a severe deficiency of ADAMTS13 activity. Because of its short turnaround time and full automation, the HemosIL AcuStar ADAMTS13 activity assay might become the assay of choice to rapidly test ADAMTS13 activity in plasma and thus establish the diagnosis of acute TTP in emergency settings

Fatigue in newly diagnosed acute myeloid leukaemia: General population comparison and predictive factors

Objectives: This study compared the burden of fatigue between treatment-naïve patients with newly diagnosed acute myeloid leukaemia (AML) and the general population and investigated patient factors associated with fatigue severity. Methods: Pretreatment patient-reported fatigue was assessed with the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire in a sample of 463 newly diagnosed patients with AML who were enrolled in a clinical trial. Multivariable linear regression models were used to estimate the adjusted mean differences in fatigue between patients with AML and adults from the general population (n=847) by AML disease risk categories. A clinically meaningful difference in fatigue was defined as ≥3 points. Univariable and multivariable linear regression models were used to identify sociodemographic, clinical and molecular correlates of worse fatigue in patients with AML. Results: Patients with AML reported adjusted mean fatigue scores that were 7.5 points worse than the general population (95% CI -8.6 to -6.4, p<0.001). Across AML disease risk categories, adjusted mean differences in fatigue compared with the general population ranged from 6.7 points worse (patients with favourable risk: 95% CI -8.6 to -4.8, p<0.001) to 8.9 points worse (patients with poor risk, 95% CI -10.5 to -7.2, p<0.001). Overall, 91% of patients with AML reported fatigue that was equal to or worse than the general population's median fatigue score. Higher pretreatment fatigue was independently associated with female sex, WHO performance status ≥1 and lower platelet levels. Conclusions: Patients with newly diagnosed AML reported worse fatigue than the general population, and mean differences exceeded twice the threshold for clinical significance. Our findings may help to identify patients with AML most likely to benefit from supportive care interventions to reduce fatigue

Fatigue in newly diagnosed acute myeloid leukaemia: General population comparison and predictive factors

Objectives: This study compared the burden of fatigue between treatment-naïve patients with newly diagnosed acute myeloid leukaemia (AML) and the general population and investigated patient factors associated with fatigue severity. Methods: Pretreatment patient-reported fatigue was assessed with the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire in a sample of 463 newly diagnosed patients with AML who were enrolled in a clinical trial. Multivariable linear regression models were used to estimate the adjusted mean differences in fatigue between patients with AML and adults from the general population (n=847) by AML disease risk categories. A clinically meaningful difference in fatigue was defined as ≥3 points. Univariable and multivariable linear regression models were used to identify sociodemographic, clinical and molecular correlates of worse fatigue in patients with AML. Results: Patients with AML reported adjusted mean fatigue scores that were 7.5 points worse than the general population (95% CI -8.6 to -6.4, p<0.001). Across AML disease risk categories, adjusted mean differences in fatigue compared with the general population ranged from 6.7 points worse (patients with favourable risk: 95% CI -8.6 to -4.8, p<0.001) to 8.9 points worse (patients with poor risk, 95% CI -10.5 to -7.2, p<0.001). Overall, 91% of patients with AML reported fatigue that was equal to or worse than the general population's median fatigue score. Higher pretreatment fatigue was independently associated with female sex, WHO performance status ≥1 and lower platelet levels. Conclusions: Patients with newly diagnosed AML reported worse fatigue than the general population, and mean differences exceeded twice the threshold for clinical significance. Our findings may help to identify patients with AML most likely to benefit from supportive care interventions to reduce fatigue

Hypersensitivity reactions related to oxaliplatin (OHP)

Patients treated with platinum compounds are subject to hypersensitivity reactions. Our study has highlighted the reactions related to oxaliplatin (OHP) infusion. One hundred and twenty-four patients affected by advanced colorectal cancer were treated with different schedules containing OHP, at the Institute of Haematology and Medical Oncology 'L. and A. Seragnoli' of Bologna and at the Medical Oncology Division of Livorno Hospital. Seventeen patients (13%) showed hypersensitivity reactions after a few minutes from the start of the OHP infusion. Usually, these reactions were seen after 2-17 exposures to OHP (Mean\ub1s.e.: 9.4\ub11.07). No patient experienced allergic reactions at his/her first OHP infusion. Eight patients developed a mild reaction consisting of flushing and swelling of the face and hands, itching, sweating and lachrymation. The remaining nine patients showed a moderate-severe reaction with dyspnoea, wheezing, laryngospasm, psycho-motor agitation, tachycardia, precordial pain, diffuse erythema, itching and sweating. Six patients out of 17 were re-exposed to the drug with premedication of steroids and all except one developed the hypersensitivity reaction again. The cumulative dose, the time of exposure to OHP and the clinical features are variable and unpredictable. The risk of developing hypersensitivity reactions in patients treated with a short infusion of OHP cannot be underestimated. \ua9 2003 Cancer Research UK