A5025991750- Lymphoma Diagnosis and Treatment
- Chronic Lymphocytic Leukemia Research
- Viral-associated cancers and disorders
- Polyomavirus and related diseases
- Chronic Myeloid Leukemia Treatments
- Acute Myeloid Leukemia Research
- CNS Lymphoma Diagnosis and Treatment
- Hematopoietic Stem Cell Transplantation
- Multiple Myeloma Research and Treatments
- Retinoids in leukemia and cellular processes
- Transplantation: Methods and Outcomes
- Cytomegalovirus and herpesvirus research
- Advanced Breast Cancer Therapies
- Neutropenia and Cancer Infections
- Cutaneous lymphoproliferative disorders research
- PI3K/AKT/mTOR signaling in cancer
- Acute Lymphoblastic Leukemia research
- Cancer Treatment and Pharmacology
- Monoclonal and Polyclonal Antibodies Research
- Eosinophilic Disorders and Syndromes
- Histone Deacetylase Inhibitors Research
- Parvovirus B19 Infection Studies
- RNA and protein synthesis mechanisms
- Platelet Disorders and Treatments
- Autoimmune Bullous Skin Diseases
University of Pennsylvania
2014-2024
National Tsing Hua University
2024
Loxo Oncology at Lilly (United States)
2019-2024
Hospital of the University of Pennsylvania
2005-2024
Eli Lilly (United States)
2021-2024
Abramson Cancer Center
2004-2023
Mansoura University
2023
National Institutes of Health
2022
Southern University College
2020
Sidney Kimmel Cancer Center
2017-2019
Covalent (irreversible) Bruton's tyrosine kinase (BTK) inhibitors have transformed the treatment of multiple B-cell cancers, especially chronic lymphocytic leukemia (CLL). However, resistance can arise through mechanisms, including acquired mutations in BTK at residue C481, binding site covalent inhibitors. Noncovalent (reversible) overcome this mechanism and other sources resistance, but mechanisms to these therapies are currently not well understood.
Patients with chronic lymphocytic leukemia (CLL) or small lymphoma (SLL) have poor outcomes after the failure of covalent Bruton's tyrosine kinase (BTK) inhibitor treatment, and new therapeutic options are needed. Pirtobrutinib, a highly selective, noncovalent (reversible) BTK inhibitor, was designed to reestablish inhibition. We conducted phase 1–2 trial in which patients relapsed refractory B-cell cancers received pirtobrutinib. Here, we report efficacy results among CLL SLL who had...
Pirtobrutinib is a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor (BTKi). We report the safety and efficacy of pirtobrutinib in patients with covalent (cBTKi) pretreated mantle-cell lymphoma (MCL), population poor prognosis.Patients cBTKi relapsed/refractory (R/R) MCL received monotherapy multicenter phase I/II trial (BRUIN; ClinicalTrials.gov identifier: NCT03740529). Efficacy was assessed first 90 consecutively enrolled who met criteria for inclusion primary...
Background. Posttransplant lymphoproliferative disorder (PTLD) is an Epstein-Barr virus–associated malignancy that occurs in the setting of pharmacologic immunosuppression after organ transplantation. With increased use transplantation and intensive immunosuppression, this disease becoming more common. We explore reduction as initial therapy for PTLD. Methods. analyzed our transplant patient database to identify patients with biopsy-proven PTLD who were initially treated their...
Information regarding treatment of post-transplant lymphoproliferative disease (PTLD) beyond reduction in immunosuppression (RI) is limited. We retrospectively evaluated patients receiving rituximab and/or chemotherapy for PTLD response, time to failure (TTF) and overall survival (OS). Thirty-five met inclusion criteria. Twenty-two underwent treatment, with response rate (ORR) 68%. Median TTF was not reached at 19 months estimated OS 31 months. In univariable analysis, Epstein-Barr virus...
While EBV PCR is used in the management of PTLD, optimal primer set, relative importance intracellular versus free plasma EBV, and baseline profile an organ transplant population remains unclear. We performed a prospective 2-arm trial utilizing panel measuring LMP-1, EBER-1 EBNA-1 both as well whole blood. Control Arm A consisted 31 lung patients B 35 being evaluated for possible PTLD. In A, 1/31 (3%) developed transient load. Thirteen (42%) had detectable EBV. B, 17 (49%) were diagnosed...
BACKGROUND Brentuximab vedotin (BV) is an anti‐CD30 monoclonal antibody‐drug conjugate that was approved in 2011 for the treatment of patients with anaplastic large cell and Hodgkin lymphomas. The product label indicates 3 who were treated BV developed progressive multifocal leukoencephalopathy (PML), a frequently fatal JC virus‐induced central nervous system infection. Prior immunosuppressive therapy compromised immune systems postulated risk factors. In current study, authors reported 5...
We conducted a retrospective study of patients with pemphigus vulgaris (n = 24) and foliaceus 7) treated adjuvant rituximab to determine efficacy adverse events. The end point for was complete remission disease taking no or minimal therapy.Eighteen (58%) achieved the point. Of these, 13 off systemic therapy. Patients achieving had median duration before therapy 19 months vs 86 in those not (P .01). For 18 point, (SD) (2) months. Eight these (44%) relapsed from 6 17 after treatment. Serious...
Patients with Epstein-Barr virus (EBV)-positive posttransplant lymphoproliferative disease (EBV+ PTLD) in whom initial treatment fails have few options and historically low median overall survival (OS) of 0.7 months after allogeneic hematopoietic cell transplant (HCT) 4.1 solid organ (SOT). Tabelecleucel is an off-the-shelf, EBV-specific cytotoxic T-lymphocyte immunotherapy for EBV+ PTLD. Previous single-center experience showed responses patients PTLD HCT or SOT. We now report outcomes from...
The UlsnRNP-A (U1-A) protein was used to select specific RNA sequences from a degenerate pool of transcripts using direct binding and polymerase chain reaction amplification (PCR). Sequences were randomized in loops 10 or 13 nucleotides as linear stretch 25 nucleotides. From all three structural contexts, an unpaired ten nucleotide consensus sequence obtained. A selected stemloop structure that resembled the natural U1-A site on loop II U1 demonstrated highest affinity comparison with other...
Abstract Purpose: PF-3512676 (formerly CpG 7909) is a novel Toll-like receptor 9–activating oligonucleotide with single-agent antitumor activity that augments preclinical rituximab efficacy. This Phase I trial was designed to investigate the safety, tolerability, and preliminary of in combination rituximab. Experimental Design: Patients relapsed/refractory CD20+ B cell non–Hodgkin's lymphoma received i.v. (375 mg/m2/week for 4 weeks) weekly weeks either (0.04, 0.16, 0.32, or 0.48 mg/kg) s.c....
Inhibiting mammalian target of rapamycin (mTOR) signaling in acute myelogenous leukemia (AML) blasts and leukemic stem cells may enhance their sensitivity to cytotoxic agents. We sought determine the safety describe toxicity this approach by adding mTOR inhibitor, sirolimus (rapamycin), intensive AML induction chemotherapy.We performed a phase I dose escalation study with chemotherapy regimen MEC (mitoxantrone, etoposide, cytarabine) patients relapsed, refractory, or untreated secondary...
IMPORTANCE B-cell depletion with the anti-CD20 antibody rituximab is highly effective for pemphigus vulgaris (PV) treatment. However,most patients experience relapse, and intravenous infusions are expensive. Therefore, cost-effective therapies desirable.OBSERVATIONS A compassionate-use investigational new drug protocol was approved to administer veltuzumab, a second-generation humanized antibody, patient refractory PV. Veltuzumab administered as two 320-mg (188mg/m2) subcutaneous doses 2...
Rituximab has emerged as a front-line therapy for pemphigus, but prognostic factors achieving complete remission off (CROT) with oral systemic agents remain unknown.To describe rates of CROT and relapse identify after rituximab pemphigus.A single-center, retrospective, cohort study was conducted at the University Pennsylvania including 112 patients pemphigus treated least 12 months' clinical follow-up start therapy. Multivariate regression analysis predictive Kaplan-Meier disease were...