Browsing by Subject "Precursor Cell Lymphoblastic Leukemia-Lymphoma"
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Item Open Access Dose intensification of methotrexate and cytarabine during intensified continuation chemotherapy for high-risk B-precursor acute lymphoblastic leukemia: POG 9406: a report from the Children's Oncology Group.(Journal of pediatric hematology/oncology, 2014-07) Tower, Richard L; Jones, Tamekia L; Camitta, Bruce M; Asselin, Barbara L; Bell, Beverly A; Chauvenet, Allen; Devidas, Meenakshi; Halperin, Edward C; Pullen, Jeanette; Shuster, Jonathan J; Winick, Naomi; Kurtzberg, JoannePurpose
To determine the efficacy and toxicity of higher dose versus standard dose intravenous methotrexate (MTX) and pulses of high-dose cytosine arabinoside with asparaginase versus standard dose cytosine arabinoside and teniposide during intensified continuation therapy for higher risk pediatric B-precursor acute lymphoblastic leukemia (ALL).Patients and methods
From 1994 to 1999, the Pediatric Oncology Group conducted a randomized phase III clinical trial in higher risk pediatric B-precursor ALL. A total of 784 patients were randomized in a 2×2 factorial design to receive MTX 1 g/m versus 2.5 g/m and to cytosine arabinoside/teniposide versus high-dose cytosine arabinoside/asparaginase during intensified continuation therapy.Results
Patients receiving standard dose MTX had a 5-year disease-free survival (DFS) of 71.8±2.4%; patients receiving higher dose MTX had a 5-year DFS of 71.7±2.4% (P=0.55). Outcomes on cytosine arabinoside/teniposide (DFS of 70.4±2.4) were similar to higher dose cytosine arabinoside/asparaginase (DFS of 73.1±2.3%) (P=0.41). Overall survival rates were not different between MTX doses or cytosine arabinoside/teniposide versus cytosine arabinoside/asparaginase.Conclusions
Increasing MTX dosing to 2.5 g/m did not improve outcomes in higher risk pediatric B-precursor ALL. Giving high-dose cytarabine and asparaginase pulses instead of standard dose cytarabine and teniposide produced nonsignificant differences in outcomes, allowing for teniposide to be removed from ALL therapy.Item Open Access Factors Associated with Long-Term Risk of Relapse after Unrelated Cord Blood Transplantation in Children with Acute Lymphoblastic Leukemia in Remission.(Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2017-08) Page, Kristin M; Labopin, Myriam; Ruggeri, Annalisa; Michel, Gerard; Diaz de Heredia, Cristina; O'Brien, Tracey; Picardi, Alessandra; Ayas, Mouhab; Bittencourt, Henrique; Vora, Ajay J; Troy, Jesse; Bonfim, Carmen; Volt, Fernanda; Gluckman, Eliane; Bader, Peter; Kurtzberg, Joanne; Rocha, VandersonFor pediatric patients with acute lymphoblastic leukemia (ALL), relapse is an important cause of treatment failure after unrelated cord blood transplant (UCBT). Compared with other donor sources, relapse is similar or even reduced after UCBT despite less graft-versus-host disease (GVHD). We performed a retrospective analysis to identify risk factors associated with the 5-year cumulative incidence of relapse after UCBT. In this retrospective, registry-based study, we examined the outcomes of 640 children (<18 years) with ALL in first complete remission (CR1; n = 257, 40%) or second complete remission (CR2; n = 383, 60%) who received myeloablative conditioning followed by a single-unit UCBT from 2000 to 2012. Most received antithymocyte globulin (88%) or total body irradiation (TBI; 69%), and cord blood grafts were primarily mismatched at 1 (50%) or 2+ (34%) HLA loci. Considering patients in CR1, the rates of 5-year overall survival (OS), leukemia-free survival (LFS), and relapse were 59%, 52%, and 23%, respectively. In multivariate analysis (MVA), acute GVHD (grades II to IV) and TBI protected against relapse. In patients in CR2, rates of 5-year OS, LFS, and the cumulative incidence of relapse were 46%, 44%, and 28%, respectively. In MVA, longer duration from diagnosis to UCBT (≥30 months) and TBI were associated with decreased relapse risk. Importantly, receiving a fully HLA matched graft was a strong risk factor for increased relapse in MVA. An exploratory analysis of all 640 patients supported the important association between the presence of acute GVHD and less relapse but also demonstrated an increased risk of nonrelapse mortality. In conclusion, the impact of GVHD as a graft-versus-leukemia marker is evident in pediatric ALL after UCBT. Strategies that promote graft-versus-leukemia while harnessing GVHD should be further investigated.Item Open Access Invasive Curvularia Infection in Pediatric Patients With Hematologic Malignancy Identified by Fungal Sequencing.(Journal of the Pediatric Infectious Diseases Society, 2019-03) Chang, Yeh-Chung; Graf, Erin; Green, Abby MCurvularia is a saprophytic dematiaceous mold and a rare human pathogen. Here, we report three severely immunocompromised pediatric patients who developed invasive Curvularia infection. Diagnosis was achieved or confirmed in all cases by fungal ribosome sequencing, which hastened species identification and targeted treatment for the patients reported. There are no treatment guidelines for invasive Curvularia infection, though we report three patients who were cured of their infection through a combination of surgical resection and various anti-fungal therapies, indicating a relatively low virulence and good prognosis in comparison to other angioinvasive molds.Item Open Access Outcome of transplantation for acute lymphoblastic leukemia in children with Down syndrome.(Pediatric blood & cancer, 2014-06) Hitzler, Johann K; He, Wensheng; Doyle, John; Cairo, Mitchell; Camitta, Bruce M; Chan, Ka Wah; Diaz Perez, Miguel A; Fraser, Christopher; Gross, Thomas G; Horan, John T; Kennedy-Nasser, Alana A; Kitko, Carrie; Kurtzberg, Joanne; Lehmann, Leslie; O'Brien, Tracey; Pulsipher, Michael A; Smith, Franklin O; Zhang, Mei-Jie; Eapen, Mary; Carpenter, Paul A; CIBMTR Pediatric Cancer Working CommitteeWe report on 27 patients with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) who received allogeneic hematopoietic cell transplantation (HCT) between 2000 and 2009. Seventy-eight percent of patients received myeloablative conditioning and 52% underwent transplantation in second remission. Disease-free survival (DFS) was 24% at a median of 3 years. Post-transplant leukemic relapse was more frequent than expected for children with DS-ALL (54%) than for non-DS ALL. These data suggest leukemic relapse rather than transplant toxicity is the most important cause of treatment failure. Advancements in leukemia control are especially needed for improvement in HCT outcomes for DS-ALL.Item Open Access Polyethylene Glycol-conjugated L-asparaginase versus native L-asparaginase in combination with standard agents for children with acute lymphoblastic leukemia in second bone marrow relapse: a Children's Oncology Group Study (POG 8866).(Journal of pediatric hematology/oncology, 2011-12) Kurtzberg, Joanne; Asselin, Barbara; Bernstein, Mark; Buchanan, George R; Pollock, Brad H; Camitta, Bruce MBackground
Administration of L-asparaginase is limited by hypersensitivity reactions mediated by anti-asparaginase antibodies. To overcome this problem, native Escherichia coli L-asparaginase was conjugated to polyethylene glycol (PEG) to formulate PEG-L-asparaginase, a preparation with decreased immunogenicity and increased circulating half-life. In early trials, PEG-L-asparaginase was tolerated by patients known to be hypersensitive to the native E. coli product.Methods
The Pediatric Oncology Group conducted a phase II, randomized trial to compare the efficacy and toxicity of PEG-L-asparaginase compared with native E. coli asparaginase in children with acute lymphoblastic leukemia in second bone marrow relapse. All patients (n=76) received standard doses of vincristine and prednisone. Nonhypersensitive patients (n=34) were randomized to receive either PEG-L-asparaginase of 2500 IU/m/dose intramuscularly on days 1 and 15 (treatment I) or native E. coli asparaginase of 10,000 IU/m/dose intramuscularly on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 (treatment II). Patients with a clinical history of an allergic reaction to unmodified asparaginase were directly assigned to treatment with PEG-L-asparaginase (n=42). Asparaginase levels and anti-asparaginase antibody titers were monitored in all patients. Response and toxicity were scored using conventional criteria.Results
The complete response rate for the total study population was 41%. There was no difference in complete response between patients randomized to PEG (47%) and native asparaginase (41%). PEG was well tolerated even in patients with prior allergic reactions to native asparaginase. PEG half-life was shorter in patients with prior allergy.Conclusions
PEG asparaginase is a useful agent in patients with allergic reactions to native asparaginase.Item Open Access Presentation and outcomes for children with bone marrow necrosis and acute lymphoblastic leukemia: a literature review.(Journal of pediatric hematology/oncology, 2011-10) Shah, Nirmish R; Landi, Daniel B; Kreissman, Susan G; Kulbachi, Evan; Moran, CassandraBone marrow necrosis is a rare histopathology finding with the majority of cases occurring in the setting of a hematologic malignancy. This article reports a case of diffuse marrow necrosis in a child secondary to acute lymphoblastic leukemia and summarizes the clinical features and outcomes for children with bone marrow necrosis secondary to leukemia from 20 published reports. This review demonstrated that the most common presenting features were bone pain, fever, pancytopenia, and that outcomes were less favorable when compared with those without necrosis. However, contemporary literature suggests that outcomes are similar for children who have bone marrow necrosis secondary to leukemia when compared with overall survival rates for pediatric leukemia.