Successful management of SARS-CoV-2 acute respiratory distress syndrome and newly diagnosed acute lymphoblastic leukemia.
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ABSTRACT:
SUBMITTER: Phillips L
PROVIDER: S-EPMC7509888 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
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Successful management of SARS-CoV-2 acute respiratory distress syndrome and newly diagnosed acute lymphoblastic leukemia.
Phillips Lia L Pavisic Jovana J Kaur Dominder D Dorrello N Valerio NV Broglie Larisa L Hijiya Nobuko N
Blood advances 20200901 18
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Project description:Polyethylene glycol (PEG)-asparaginase (pegaspargase) is a key agent in chemotherapy for acute lymphoblastic leukemia (ALL), but recipients frequently experience allergic reactions. We hypothesized that by decreasing antibody-producing CD20-positive B cells, rituximab may reduce these reactions. Children and adolescents (aged 1-18 years) with newly diagnosed B-ALL treated on the St. Jude Total XVII study were randomized to induction therapy with or without rituximab on day 3 (cohort 1) or on days 6 and 24 (cohort 2). Patient clinical demographics, CD20 expression, minimal residual disease (MRD), rituximab reactions, pegaspargase allergy, anti-pegaspargase antibodies, and pancreatitis were evaluated. Thirty-five patients received rituximab and 37 did not. Among the 35 recipients, 16 (45.7%) experienced a grade 2 or higher reaction to rituximab. There were no differences between recipients and non-recipients in the incidence of pegaspargase reactions (P > 0.999), anti-pegaspargase antibodies (P = 0.327), or pancreatitis (P = 0.480). CD20 expression on day 8 was significantly lower in rituximab recipients (P < 0.001), but there were no differences in MRD levels on day 8, 15, or at the end of induction. Rituximab administration during induction in pediatric patients with B-ALL was associated with a high incidence of infusion reactions with no significant decrease in pegaspargase allergies, anti-pegaspargase antibodies, or MRD.
| S-EPMC10666913 | biostudies-literature
Project description:ObjectiveTo evaluate the diagnostic yield of baseline chest radiographs (CXRs) of children with acute lymphoblastic leukemia (ALL).Study designWe reviewed the CXR findings at diagnosis for 990 patients aged 1-18 years with ALL treated during the Total XV and XVI studies at St. Jude Children's Research Hospital and evaluated the associations of these findings with clinical characteristics and initial management.ResultsCommon findings were peribronchial/perihilar thickening (n = 187 [19.0%]), pulmonary opacity/infiltrate (n = 159 [16.1%]), pleural effusion/thickening (n = 109 [11.1%]), mediastinal mass (n = 107 [10.9%]), and cardiomegaly (n = 68 [6.9%]). Portable CXRs provided results comparable with those obtained with 2-view films. Forty of 107 patients with a mediastinal mass (37.4%) had tracheal deviation/compression. Mediastinal mass, pleural effusion/thickening, and tracheal deviation/compression were more often associated with T-cell ALL than with B-cell ALL (P < .001 for all). Pulmonary opacity/infiltrate was associated with younger age (P = .003) and was more common in T-cell ALL than in B-cell ALL (P = .001). Peribronchial/perihilar thickening was associated with younger age (P < .001) and with positive central nervous system disease (P = .012). Patients with cardiomegaly were younger (P = .031), more often black than white (P = .007), and more often categorized as low risk than standard/high risk (P = .017). Patients with a mediastinal mass, pleural effusion/thickening, tracheal deviation/compression, or pulmonary opacity/infiltrate were more likely to receive less invasive sedation and more intensive care unit admissions and respiratory support (P ≤ .001 for all). Cardiomegaly was associated with intensive care unit admission (P = .008). No patients died of cardiorespiratory events during the initial 7 days of management.ConclusionsThe CXR can detect various intrathoracic lesions and is helpful in planning initial management.
| S-EPMC7388067 | biostudies-literature
Project description:This study describes skeletal, neuromuscular and fitness impairments among 109 children (median age 10 [range 4-18] years, 65.1% male, 63.3% white) with acute lymphoblastic leukemia (ALL). Outcomes were measured 7-10 days after diagnosis and compared to age- and sex-specific expected values. Associations between function and health-related quality of life (HRQL) were evaluated with logistic regression. Children with ALL had sub-optimal bone mineral density (BMD) Z-score/height (mean ± standard error: - 0.53 ± 0.16 vs. 0.00 ± 0.14, p < 0.01), body mass index percentile (57.6 ± 3.15 vs. 50.0 ± 3.27%, p = 0.02), quadriceps strength (201.9 ± 8.3 vs. 236.1 ± 5.4 N, p < 0.01), 6 min walk distance (385.0 ± 13.1 vs. 628.2 ± 7.1 m, p < 0.001) and Bruininks-Oseretsky Test of Motor Proficiency scores (23 ± 2.5 vs. 50 ± 3.4%, p < 0.01). Quadriceps weakness was associated with a 20.9-fold (95% confidence interval 2.5-173.3) increase in poor physical HRQL. Children with newly diagnosed ALL have weakness and poor endurance and may benefit from early rehabilitation that includes strengthening and aerobic conditioning.
| S-EPMC4336225 | biostudies-literature
Project description:Patients with acute lymphoblastic leukemia (ALL) are at increased risk of thrombotic and/or bleeding events during early chemotherapy, especially when receiving asparaginase. D-dimer is a marker of fibrinolysis that has been associated with thrombotic risk in solid cancers and acute myeloid leukemia; however, to date, no ALL-based study has assessed D-dimer level and risk for thrombosis. We sought to examine D-dimer as a biomarker for risk of thrombosis or bleeding during ALL treatment in a retrospective cohort study at The University of Chicago. We identified 61 consecutive adult patients with ALL, gathering demographic characteristics, treatment regimens, initial biomarkers including D-dimer, and assessing occurrence of venous or arterial thrombosis and bleeding in the first 100 days after diagnosis (index). The 100-day cumulative incidence (95% confidence interval [CI]) of venous or arterial thrombosis in patients with high D-dimer (≥4 µg/mL) was 52.9% (95% CI, 26.4-73.8) compared with 13.8% (95% CI, 5.5-25.7) in patients with low to moderate D-dimer (<4 µg/mL), corresponding with a hazard ratio of 5.04 (95% CI, 1.79-14.22). When testing for potential confounders in a series of bivariate logistic regression models, the association between D-dimer and thrombosis remained after adjusting for body mass index, age, sex, asparaginase treatment, disseminated intravascular coagulation score, initial platelet level, and ALL phenotype. In conclusion, D-dimer levels at ALL diagnosis are associated with venous or arterial thrombosis at 100 days. Future studies should include D-dimer collated with other known risk factors to build a risk assessment model for thrombosis in patients with newly diagnosed ALL.
| S-EPMC9631615 | biostudies-literature
Project description:Over the past several decades, L-asparaginase, an important component of therapy for acute lymphoblastic leukemia (ALL), has typically been administered intramuscularly rather than intravenously in North America because of concerns regarding anaphylaxis. We evaluated the feasibility of giving polyethylene glycosylated (PEG)-asparaginase, the polyethylene glycol conjugate of Escherichia coli L-asparaginase, by intravenous infusion in children with ALL. Between 2005 and 2007, 197 patients (age, 1-17 years) were enrolled on Dana-Farber Cancer Institute ALL Consortium Protocol 05-01 and received a single dose of intravenous PEG-asparaginase (2500 IU/m(2)) over 1 hour during remission induction. Serum asparaginase activity more than 0.1 IU/mL was detected in 95%, 88%, and 7% of patients at 11, 18, and 25 days after dosing, respectively. Toxicities included allergy (1.5%), venous thrombosis (2%), and pancreatitis (4.6%). We conclude that intravenous administration of PEG-asparaginase is tolerable in children with ALL, and potentially therapeutic enzyme activity is maintained for at least 2 weeks after a single dose in most patients. This trial was registered at www.clinicaltrials.gov as #NCT00400946.
| S-EPMC2826760 | biostudies-literature
Project description:The primary aim of the present retrospective study was to investigate lipid profiles and kinetics in acute promyelocytic leukemia (APL) patients. We analyzed 402 newly diagnosed APL patients and 201 non-APL patients with acute myeloid leukemia (as control). Incidence of hypertriglyceridemia in APL patients and non-APL patients was 55.82% and 28.4% (p = 0.0003). The initial levels of triglycerides, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were higher in APL patients than in control (all p < 0.0001). In APL patients, triglyceride levels were significantly increased during induction treatment with all-trans retinoic acid and arsenic. Multivariable analysis showed that age, being overweight (body mass index ≥25) and APL were independent risk factors for hypertriglyceridemia in all patients before treatment. High triglyceride levels were not significantly associated with disease-free survival or overall survival in the APL patients. In summary, in the current study triglyceride levels were significantly elevated in APL patients before treatment, and they increased during induction treatment, but there were no significant corresponding effects on survival.
| S-EPMC7724081 | biostudies-literature
Project description:Background/aimsWe performed a prospective study to determine the efficacy and safety of rituximab including chemotherapy in CD20-positive acute lymphoblastic leukemia (ALL).MethodsPatients with newly diagnosed ALL, aged ≥ 15 years, were eligible for the study if their leukemic blast cells in bone marrow expressed CD20 ≥ 20% at the time of diagnosis. Patients received multiagent chemotherapy with rituximab. After achieving complete remission (CR), patients received five cycles of consolidation with concomitant rituximab. Rituximab was administered monthly from day 90 of transplantation for patients who received allogeneic hematopoietic cell transplantation.ResultsIn patients with Philadelphia (Ph)-negative ALL, 39 of 41 achieved CR (95.1%), the 2- and 4-year relapse-free survival (RFS) rates were 50.4% and 35.7%, and the 2- and 4-year overall survival (OS) rates were 51.5% and 43.2%, respectively. In the group with Ph-positive ALL, all 32 patients achieved CR, the 2- and 4-year RFS rates were 60.7% and 52.1%, and the 2- and 4-year OS rates were 73.3% and 52.3%, respectively. In the Ph-negative ALL group, patients with higher CD20 positivity experienced more favorable RFS (p < 0.001) and OS (p = 0.06) than those with lower CD20 positivity. Patients who received ≥ 2 cycles of rituximab after transplantation had significantly improved RFS (hazard ratio [HR], 0.31; p = 0.049) and OS (HR, 0.29; p = 0.021) compared with those who received < 2 cycles.ConclusionThe addition of rituximab to conventional chemotherapy for CD20-positive ALL is effective and tolerable (Clinicaltrials. gov NCT01429610).
| S-EPMC10493456 | biostudies-literature
Project description:BackgroundBlinatumomab early-line treatment in B-cell precursor acute lymphoblastic leukemia (B-ALL) might improve clinical outcomes.MethodsWe conducted a retrospective real-world cohort analysis in 20 newly diagnosed B-ALL patients who received reduced-dose chemotherapy (idarubicin, vindesine, and dexamethasone) for 1-3 weeks, followed by blinatumomab for 1-4 weeks as an induction therapy.ResultsAt the end of the induction therapy, a complete remission rate of 100% was achieved; 17 (85%) patients were minimal residual disease (MRD) negative (<1 × 10-4 ). Adverse events (AEs) were reported in 12 (60%) patients-43.8% were grade 1-2 and 56.2% were grade 3-4. No incidence of neurotoxicity or grade ≥3 cytokine release syndrome was reported.ConclusionsBlinatumomab demonstrated a significant improvement in clinical outcomes in patients with newly diagnosed B-ALL irrespective of their poor-risk factor status and the pretreatment blast burden.
| S-EPMC10943272 | biostudies-literature
Project description:Holt-Oram syndrome (HOS) (OMIM#142900) is a rare condition with upper extremity malformations as well as structural and conduction cardiac anomalies. There are sparse reports in the literature documenting malignancy in association with HOS. We report a pediatric patient clinically diagnosed with HOS (missing thumbs bilaterally, atrial septal defect, ventricular septal defect, and first-degree heart block), who also developed B precursor acute lymphoblastic leukemia. During induction of chemotherapy with steroids, she developed profound bradycardia without clinical symptoms. The bradycardia resolved without intervention, but this case highlights the challenges of managing chemotherapy side effects in a patient with congenital heart disease. A literature review pertinent to the associated findings in the case is also presented.
| S-EPMC7437613 | biostudies-literature
Project description:PurposeThe Children's Oncology Group (COG) protocol AALL0434 evaluated the safety and efficacy of multi-agent chemotherapy with Capizzi-based methotrexate/pegaspargase (C-MTX) in patients with newly diagnosed pediatric T-cell lymphoblastic lymphoma (T-LL) and gained preliminary data using nelarabine in high-risk patients.Patients and methodsThe trial enrolled 299 patients, age 1-31 years. High-risk (HR) patients had ≥ 1% minimal detectable disease (MDD) in the bone marrow at diagnosis or received prior steroid treatment. Induction failure was defined as failure to achieve a partial response (PR) by the end of the 4-week induction. All patients received the augmented Berlin-Frankfurt-Muenster (ABFM) C-MTX regimen. HR patients were randomly assigned to receive or not receive 6 5-day courses of nelarabine incorporated into ABFM. Patients with induction failure were nonrandomly assigned to ABFM C-MTX plus nelarabine. No patients received prophylactic cranial radiation; however, patients with CNS3 disease (CSF WBC ≥ 5/μL with blasts or cranial nerve palsies, brain/eye involvement, or hypothalamic syndrome) were ineligible.ResultsAt end-induction, 98.8% of evaluable participants had at least a PR. The 4-year event-free survival (EFS) and overall survival (OS) were 84.7% ± 2.3% and 89.0% ± 2.0%. The 4-year disease-free survival (DFS) from end-induction was 85.9% ± 2.6%. There was no difference in DFS observed between the HR and standard-risk groups (P = .29) or by treatment regimen (P = .55). Disease stage, tumor response, and MDD at diagnosis did not demonstrate thresholds that resulted in differences in EFS. Nelarabine did not show an advantage for HR patients. CNS relapse occurred in only 4 patients.ConclusionCOG AALL0434 produced excellent outcomes in one of the largest trials ever conducted for patients with newly diagnosed T-LL. The COG ABFM regimen with C-MTX provided excellent EFS and OS without cranial radiation.
| S-EPMC7479761 | biostudies-literature