A5086994519- Acute Myeloid Leukemia Research
- Hematopoietic Stem Cell Transplantation
- Neuroblastoma Research and Treatments
- Acute Lymphoblastic Leukemia research
- Cancer therapeutics and mechanisms
- Glioma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- Blood disorders and treatments
- Chronic Lymphocytic Leukemia Research
- Multiple Myeloma Research and Treatments
- Pharmaceutical studies and practices
- Childhood Cancer Survivors' Quality of Life
- Immunodeficiency and Autoimmune Disorders
- Neutropenia and Cancer Infections
- Polyomavirus and related diseases
- Chronic Myeloid Leukemia Treatments
- Chemotherapy-induced organ toxicity mitigation
- Telomeres, Telomerase, and Senescence
- Microtubule and mitosis dynamics
- Lung Cancer Research Studies
- PI3K/AKT/mTOR signaling in cancer
- Parvovirus B19 Infection Studies
Phoenix Children's Hospital
2012-2024
Center for Cancer and Blood Disorders
2006-2024
University of Arizona
2024
Children's Center
2019
Seattle University
2017
Harvard University
2014
Dana-Farber Cancer Institute
2014
Children's Healthcare of Atlanta
2009-2013
Memorial Sloan Kettering Cancer Center
2001-2013
University of Colorado Denver
2013
Familial myelodysplastic syndromes arise from haploinsufficiency of genes involved in hematopoiesis and are primarily associated with early-onset disease. Here we describe a familial syndrome seven patients four unrelated pedigrees presenting loss chromosome 7/7q. Their median age at diagnosis was 2.1 years (range, 1–42). All presented thrombocytopenia or without additional cytopenias hypocellular marrow an increase blasts. Genomic studies identified constitutional mutations (p.H880Q,...
Abstract Background Plerixafor, a reversible CXCR4 antagonist, inhibits interactions between leukemic blasts and the bone marrow stromal microenvironment may enhance chemosensitivity. A phase 1 trial of plerixafor in combination with intensive chemotherapy children young adults relapsed or refractory acute lymphoblastic leukemia (ALL), myeloid (AML), myelodysplastic syndrome (MDS) was performed to determine tolerable biologically active dose. Procedure Plerixafor administered daily for 5...
Quality of response to immunosuppressive therapy and long-term outcomes for pediatric severe aplastic anemia remain incompletely characterized. Contemporary evidence inform treatment relapsed or refractory patients is also limited. The clinical features 314 children treated from 2002 2014 with acquired were analyzed retrospectively 25 institutions in the North American Pediatric Aplastic Anemia Consortium. majority subjects (n=264) received horse anti-thymocyte globulin (hATG) plus...
Abstract Purpose: Heat shock protein 90 (Hsp90) is essential for the posttranslational control of many regulators cell growth, differentiation, and apoptosis. 17-N-Allylamino-17-demethoxygeldanamycin (17-AAG) binds to Hsp90 alters levels proteins regulated by Hsp90. We conducted a phase I trial 17-AAG in pediatric patients with recurrent or refractory neuroblastoma, Ewing's sarcoma, osteosarcoma, desmoplastic small round tumor determine maximum tolerated dose, define toxicity pharmacokinetic...
Germline mutations in SAMD9 and SAMD9L genes cause MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, enteropathy) (OMIM: *610456) ataxia-pancytopenia *611170) syndromes, respectively, are associated with chromosome 7 deletions, myelodysplastic syndrome (MDS), bone marrow failure. In this retrospective series, we report outcomes allogeneic hematopoietic cell transplantation (HCT) patients hematologic disorders SAMD9/SAMD9L mutations. Twelve...
Abstract Background To evaluate efficacy, pharmacokinetics (PK) and pharmacodynamics of single‐agent everolimus in pediatric patients with radiographically progressive low‐grade glioma (LGG). Methods Everolimus was administered at 5 mg/m 2 once daily as a tablet or liquid for planned 48‐week duration until unacceptable toxicity disease progression. Patients neurofibromatosis type 1 were excluded. PK pharmacodynamic endpoints assessed consenting patients. Results Twenty‐three eligible (median...
Abstract Severe aplastic anemia (SAA) is a rare potentially fatal hematologic disorder. Although overall outcomes with treatment are excellent, there variations in management approach, including differences between adult and pediatric patients. Certain aspects of under active investigation clinical trials. Because the rarity disease, some hematologists may have relatively limited experience complex SAA. The following recommendations reflect an up‐to‐date evidence‐based approach to children...
Decitabine is a deoxycytidine nucleoside derivative inhibitor of DNA-methyltransferases, which has been studied extensively and approved for myelodysplastic syndrome in adults but with less focus children. Accordingly, we conducted phase 1 multicenter, randomized, open-label study to evaluate decitabine pre-treatment before standard induction therapy children newly diagnosed AML assess safety tolerability explore number biologic endpoints.Twenty-four patients were fully assessable all...
The North American Pediatric Aplastic Anemia Consortium (NAPAAC) is a group of pediatric hematologist-oncologists, hematopathologists, and bone marrow transplant physicians from 46 institutions in America with interest expertise aplastic anemia, inherited failure syndromes, myelodysplastic syndromes. NAPAAC Bone Marrow Failure Diagnosis Care Guidelines Working Group was established the charge harmonizing approach to diagnostic workup anemia an effort standardize best practices field. This...
Purpose To determine the dose of cetuximab that can be safely combined with irinotecan for treatment pediatric and adolescent patients refractory solid tumors. Patients Methods This open-label, phase I study enrolled ages 1 to 18 years advanced tumors, including tumors CNS. Patient cohorts by age group (children, 12 years; adolescents, 13 years) received escalating weekly doses (75, 150, 250 mg/m 2 ) in a 3 + design, plus (16 or 20 /d) 5 days consecutive weeks every 21 days. The primary end...
BACKGROUND: Purpose: The ras/raf signaling pathway is crucial in the development of pediatric low-grade gliomas (LGGs). Aberrant involved tumorigenesis through promotion cell proliferation, survival, and differentiation sporadic LGG. Everolimus (RAD001) a potent selective inhibitor mTOR, downstream element pathway. activity, safety pharmacokinetics everolimus patients with radiographic recurrent/progressive LGG are presented. METHODS: Pediatric progressive or recurrent LGGs without...
Abstract Purpose: Ridaforolimus (MK-8669, AP23573) is a potent and selective mammalian target of rapamycin (mTOR) inhibitor. Preclinically, ridaforolimus displays antiproliferative activity against variety human tumors in vitro tumor xenograft models vivo, with additive or synergistic when combined other anticancer agents. Antitumor has been confirmed adults. This phase I study determined the safety, pharmacological, biologic, toxicity profiles pediatric patients refractory malignancies....
Abstract Background In a multicenter phase 1 study of children with relapsed/refractory acute lymphoblastic leukemia (ALL), moxetumomab pasudotox, an anti‐CD22 immunotoxin, demonstrated manageable safety profile and preliminary evidence clinical activity. A 2 further evaluated efficacy. Procedure This international, multicenter, enrolled B‐cell precursor ALL who received pasudotox 40 µg/kg intravenously every other day, for six doses per 21‐day cycle. The primary objective was to evaluate...
Background. Chronic lung disease and pulmonary failure are complications that can occur after bone marrow transplantation (BMT) associated with severe morbidity mortality. Methods. We report on four patients who developed chronic, progressive, irreversible 1 to 3 years allogeneic BMT in childhood. These had chronic graft-versus-host (n=3) or radiation-related fibrosis (n=1). Three underwent double transplants one patient a single transplant 2 14 BMT. Results. All tolerated the procedure well...
Relapsed/refractory acute myeloid leukemia (AML) has an extremely poor prognosis. We describe 17 children and adolescents with relapsed/refractory AML who received clofarabine, cyclophosphamide, etoposide. Seven patients (41%) responded: 4 a complete response (CR); 1 CR incomplete platelet recovery; 2 partial response. Additionally, developed hypocellular marrow without evidence of leukemia; 5 had resistant disease; suffered early toxic death. After further therapy including transplantation,...
Abstract Severe aplastic anemia (SAA) is a rare potentially fatal hematologic disorder. Although overall outcomes with treatment are excellent, there variations in management approach, including differences between adult and pediatric patients. Certain aspects of under active investigation clinical trials. Because the rarity disease, some hematologists may have relatively limited experience complex SAA. The following recommendations reflect an up‐to‐date evidence‐based approach to children...
Abstract Background By inhibiting DNA repair, clofarabine (CLO) may augment cyclophosphamide (CY)‐induced damage and apoptosis. We performed a Phase I study for refractory and/or relapsed (R/R) leukemia in children to determine maximum‐tolerated dose (MTD) of time‐sequential CLO followed by CY. Procedure Thirteen patients with ALL (n = 8) AML (N 5), median age 9 years (range: 2–12 years), were treated escalating doses on days 1, 2, 3 8, 9, 10 CY 200 mg/m 2 /day 0 1 then 400 3, 10. Ten at...
Abstract Background Platinum agents have been used for a variety of cancers, including pivotal use in pediatric tumors many years. Oxaliplatin, third generation platinum, has different side effect profile and may provide improved activity cancers. Procedure Patients 21 years or younger with progressive refractory malignant solid tumors, the central nervous system were enrolled on this multi‐center open label, non‐randomized Phase 1 dose escalation study. The study standard 3 + design 2...
This phase 1/2 study (NCT01751308) evaluated cabazitaxel in pediatric patients. Phase 1 determined the maximum tolerated dose (MTD) patients with recurrent/refractory solid tumors, including central nervous system (CNS) tumors. 2 activity recurrent high-grade glioma (HGG) or diffuse intrinsic pontine (DIPG).In 1, a 3 + dose-escalation design was followed. Cabazitaxel administered at starting of 20 mg/m2 . Dose-limiting toxicities (DLTs) during cycle were assessed to determine MTD. Tumor...