Publications by authors named "Paul S Gaynon"

Children with relapse of T-cell acute lymphoblastic leukemia (T-ALL) or lymphoblastic lymphoma (T-LBL) have a dismal prognosis, largely due to difficulty attaining second remission. We hypothesized that adding etoposide and cyclophosphamide to the nucleoside analog nelarabine could improve response rates over single-agent nelarabine for relapsed T-ALL and T-LBL. This phase I dose-escalation trial's primary objective was to evaluate the dose and safety of nelarabine given in combination with etoposide at 100 mg/m /day and cyclophosphamide at 330-400 mg/m /day, each for 5 consecutive days in children with either T-ALL (13 patients) or T-LBL (10 patients).

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Background: Adriamycin, bleomycin, vinblastine, dacarbazine (ABVD), the de facto standard of care in adult-onset Hodgkin lymphoma (HL), has not been directly compared to doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC), a pediatric-aimed regimen designed to reduce late effects. We aimed to describe the single-institution experience of using both regimens in patients with pediatric HL.

Methods: This retrospective cohort study evaluated a total of 224 patients diagnosed with HL between 1999 and 2018 at Children's Hospital Los Angeles (CHLA), of which 93 patients were eligible having received ABVD (n = 46) or ABVE-PC (n = 47) chemotherapy as their initial treatment.

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Phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling is commonly dysregulated in acute lymphoblastic leukemia (ALL). The TACL2014-001 phase I trial of the mTOR inhibitor temsirolimus in combination with cyclophosphamide and etoposide was performed in children and adolescents with relapsed/refractory ALL. Temsirolimus was administered intravenously (IV) on days 1 and 8 with cyclophosphamide 440 mg/m2 and etoposide 100 mg/m2 IV daily on days 1-5.

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Pediatric acute myeloid leukemia (AML) is genetically heterogenous (Olsson et al., 2016). t(X;6)(p11;q23) is a rare but recurrent chromosomal translocation in infant AML thought to be associated with male sex and basophilic differentiation (Dastugue et al.

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The Children's Cancer Group 1991 study was a clinical trial for children with National Cancer Institute standard-risk acute lymphoblastic leukemia (ALL). This trial demonstrated that 5 doses of vincristine and escalating IV methotrexate (MTX) without leucovorin rescue in the interim maintenance (IM) phases resulted in superior event-free survival (EFS) when compared with 2 doses of vincristine, oral (PO) MTX, PO mercaptopurine, and dexamethasone. This report describes a favorable outcome of this regimen in patients with Down syndrome (DS).

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Children's Cancer Group CCG-1882 improved outcome for 1-21-year old with high risk acute lymphoblastic leukemia and Induction Day 8 marrow blasts ≥25% (slow early responders, SER) with longer and stronger post induction intensification (PII). This CCG-1961 explored alternative PII strategies. We report 10-year follow-up for patients with rapid early response (RER) and for the first time details our experience for SER patients.

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Purpose: Early intensification with methotrexate (MTX) is a key component of acute lymphoblastic leukemia (ALL) therapy. Two different approaches to MTX intensification exist but had not been compared in T-cell ALL (T-ALL): the Children's Oncology Group (COG) escalating dose intravenous MTX without leucovorin rescue plus pegaspargase escalating dose, Capizzi-style, intravenous MTX (C-MTX) regimen and the Berlin-Frankfurt-Muenster (BFM) high-dose intravenous MTX (HDMTX) plus leucovorin rescue regimen.

Patients And Methods: COG AALL0434 included a 2 × 2 randomization that compared the COG-augmented BFM (ABFM) regimen with either C-MTX or HDMTX during the 8-week interim maintenance phase.

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A pediatric patient diagnosed initially with B-lymphoblastic leukemia (B-ALL) relapsed with lineage switch to acute myeloid leukemia (AML) after chimeric antigen receptor T-cell (CAR-T) therapy and hematopoietic stem cell transplant. A TCF3-ZNF384 fusion was identified at diagnosis, persisted through B-ALL relapse, and was also present in the AML relapse cell population. ZNF384-rearrangements define a molecular subtype of B-ALL characterized by a pro-B-cell immunophenotype; furthermore, ZNF384-rearrangements are prevalent in mixed-phenotype acute leukemias.

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Background: Children with relapsed acute lymphoblastic leukemia (ALL) typically receive vincristine-prednisone-L-asparaginase-doxorubicin reinduction chemotherapy similar to contemporary induction regimens. However, up to 20% of patients are unable to receive vincristine-prednisone-L-asparaginase-doxorubicin secondary to asparaginase intolerance. We report our experience with a promising reinduction regimen for children with relapsed ALL who are unable to receive asparaginase.

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New agent development rests on the fundamental assumption that candidate agents or drug combinations that induce objective responses after relapse will prevent relapse, if applied prior to relapse. However, cumulative experience now includes at least 5 examples of interventions with post-relapse objective response rates greater than 50% that failed to improve outcomes when applied prior to relapse. Emerging insights into oligoclonality provide some explanation.

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Background: Children with T-lineage acute lymphoblastic leukemia ALL (T-ALL) historically have had inferior outcomes compared with the children with precursor-B ALL (B-ALL). After 1995, the Children's Cancer Group (CCG) treated patients with B- and T-ALL according to the National Cancer Institute (NCI) risk criteria, basing risk stratification on age and white blood cell (WBC) count regardless of immunophenotype. The Pediatric Oncology Group (POG) treated all the patients with T-ALL on separate, generally more intensive protocols than those used to treat the patients with B-ALL.

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In this issue of Blood, Karol et al establish a link between glutamate receptor polymorphisms and osteonecrosis, using a large discovery cohort and 2 validation cohorts. One validation cohort included patients under treatment of acute lymphoblastic leukemia (ALL) and the second is patients receiving glucocorticoid treatment of various other indications.

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Background: The objectives of this study were to assess the incidence of clinical allergy and end-induction antiasparaginase (anti-ASNase) antibodies in children with high-risk acute lymphoblastic leukemia treated with pegylated (PEG) Escherichia coli ASNase and to determine whether they carry any prognostic significance.

Methods: Of 2057 eligible patients, 1155 were allocated to augmented arms in which PEG ASNase replaced native ASNase postinduction. Erwinia chrysanthemi (Erwinia) ASNase could be used to replace native ASNase after allergy, if available.

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The role of end of induction minimal residual disease (MRD) as determined by flow cytometry for treatment assignment in pediatric T-cell acute lymphoblastic leukemia (T-ALL) is not well defined. We studied 33 children with newly diagnosed T-ALL. Thirty-two of 33 patients remain in continuous complete remission at a median of 4 years.

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Leukemia is the most common pediatric cancer. Despite great progress in the development of curative therapy, leukemia remains a leading cause of death from disease in childhood, and survivors are at life-long risk of complications of treatment. New agents are needed to further increase cure rates and decrease treatment-associated toxicities.

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Children and adolescents presenting with a markedly elevated white blood cell (ME WBC) count (WBC ≥200 × 10(9) /l) comprise a unique subset of high-risk patients with acute lymphoblastic leukaemia (ALL). We evaluated the outcomes of the 251 patients (12% of the study population) with ME WBC treated on the Children's Cancer Group-1961 protocol. Patients were evaluated for early response to treatment by bone marrow morphology; those with a rapid early response were randomized to treatment regimens testing longer and stronger post-induction therapy.

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