A5013974745- Chronic Lymphocytic Leukemia Research
- Lymphoma Diagnosis and Treatment
- Immunodeficiency and Autoimmune Disorders
- Chronic Myeloid Leukemia Treatments
- Monoclonal and Polyclonal Antibodies Research
- Acute Lymphoblastic Leukemia research
- Advanced Breast Cancer Therapies
- CAR-T cell therapy research
- PI3K/AKT/mTOR signaling in cancer
- Viral-associated cancers and disorders
- Multiple Myeloma Research and Treatments
- Galectins and Cancer Biology
- Biochemical and Molecular Research
- Acute Myeloid Leukemia Research
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Gastrointestinal Tumor Research and Treatment
- Cutaneous lymphoproliferative disorders research
- Lung Cancer Treatments and Mutations
- Radiopharmaceutical Chemistry and Applications
- CNS Lymphoma Diagnosis and Treatment
- Immune Cell Function and Interaction
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- T-cell and Retrovirus Studies
Cornell University
2016-2025
Weill Cornell Medicine
2016-2024
Presbyterian Hospital
2014-2023
New York Hospital Queens
2014-2023
NewYork–Presbyterian Hospital
2014-2023
Universitat Politècnica de Catalunya
2019
Barcelona Supercomputing Center
2019
University of Rochester
2015
Fox Chase Cancer Center
2006-2013
University of Arkansas for Medical Sciences
2010-2013
The treatment of relapsed chronic lymphocytic leukemia (CLL) has resulted in few durable remissions. Bruton's tyrosine kinase (BTK), an essential component B-cell-receptor signaling, mediates interactions with the tumor microenvironment and promotes survival proliferation CLL cells.We conducted a phase 1b-2 multicenter study to assess safety, efficacy, pharmacokinetics, pharmacodynamics ibrutinib (PCI-32765), first-in-class, oral covalent inhibitor BTK designed for B-cell cancers, patients...
Patients with relapsed chronic lymphocytic leukemia (CLL) who have clinically significant coexisting medical conditions are less able to undergo standard chemotherapy. Effective therapies acceptable side-effect profiles needed for this patient population. In multicenter, randomized, double-blind, placebo-controlled, phase 3 study, we assessed the efficacy and safety of idelalisib, an oral inhibitor delta isoform phosphatidylinositol 3-kinase, in combination rituximab versus plus placebo. We...
In patients with chronic lymphoid leukemia (CLL) or small lymphocytic lymphoma (SLL), a short duration of response to therapy adverse cytogenetic abnormalities are associated poor outcome. We evaluated the efficacy ibrutinib, covalent inhibitor Bruton's tyrosine kinase, in at risk for
Atypical hemolytic–uremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal levels hematologic measures but does not treat the underlying systemic disease.
Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (BTK) and effective in chronic lymphocytic leukemia (CLL). Resistance to inhibitors resistance associated with BTK inhibition have not been characterized. Although only a small proportion patients had relapse during ibrutinib therapy, understanding mechanisms important. We evaluated relapsed disease identify mutations that may mediate resistance.
Purpose Survival and progression of mature B-cell malignancies depend on signals from the antigen receptor, Bruton tyrosine kinase (BTK) is a critical signaling in this pathway. We evaluated ibrutinib (PCI-32765), small-molecule irreversible inhibitor BTK, patients with malignancies. Patients Methods relapsed or refractory lymphoma chronic lymphocytic leukemia received escalating oral doses ibrutinib. Two schedules were evaluated: one, 28 days on, 7 off; two, once-daily continuous dosing....
Irreversible inhibition of Bruton's tyrosine kinase (BTK) by ibrutinib represents an important therapeutic advance for the treatment chronic lymphocytic leukemia (CLL). However, also irreversibly inhibits alternative targets, which potentially compromises its index. Acalabrutinib (ACP-196) is a more selective, irreversible BTK inhibitor that specifically designed to improve on safety and efficacy first-generation inhibitors.In this uncontrolled, phase 1-2, multicenter study, we administered...
Peripheral T-cell lymphoma (PTCL) is a poor prognosis subtype of non-Hodgkin's with no accepted standard care. This study evaluated the efficacy and tolerability pralatrexate, novel antifolate promising activity.Patients independently confirmed PTCL who progressed following ≥ 1 line prior therapy received pralatrexate intravenously at 30 mg/m(2)/wk for 6 weeks in 7-week cycles. Primary assessment response was made by independent central review using International Workshop Criteria. The...
New treatments are needed for patients with fludarabine- and alemtuzumab-refractory (FA-ref) chronic lymphocytic leukemia (CLL) or fludarabine-refractory CLL bulky (> 5 cm) lymphadenopathy (BF-ref) who less suitable alemtuzumab treatment; these groups have poor outcomes available salvage regimens. Ofatumumab (HuMax-CD20) is a human monoclonal antibody targeting distinct small-loop epitope on the CD20 molecule. We conducted an international clinical study to evaluate efficacy safety of...
Among Bruton's tyrosine kinase inhibitors, acalabrutinib has greater selectivity than ibrutinib, which we hypothesized would improve continuous therapy tolerability. We conducted an open-label, randomized, noninferiority, phase III trial comparing and ibrutinib in patients with chronic lymphocytic leukemia (CLL).
Recurrent mutations in the spliceosome are observed several human cancers, but their functional and therapeutic significance remains elusive. SF3B1, most frequently mutated component of cancer, is involved recognition branch point sequence (BPS) during selection 3' splice site (ss) RNA splicing. Here, we report that common tumor-specific splicing aberrations induced by SF3B1 establish aberrant ss as frequent defect. Strikingly, mutant utilizes a BPS differs from used wild-type requires...
Atypical hemolytic uremic syndrome (aHUS) is a rare, possibly life-threatening disease characterized by platelet activation, hemolysis and thrombotic microangiopathy (TMA) leading to renal other end-organ damage. We originally conducted two phase 2 studies (26 weeks 1 year) evaluating eculizumab, terminal complement inhibitor, in patients with progressing TMA (trial 1) those long duration of aHUS chronic kidney 2). The current analysis assessed outcomes after years (median eculizumab...
Treatment of mantle-cell lymphoma (MCL) is nonstandardized, though patients are commonly treated immediately at diagnosis. Because data on observation, or "watch and wait," have not been previously reported, we analyzed the outcome deferred initial therapy.Inclusion criteria in this retrospective analysis were a diagnosis MCL between 1997 2007 known date first treatment. Hospital research charts reviewed for prognostic treatment-related information. Date death was derived from hospital...
Human babesiosis is a tickborne malaria-like illness that generally resolves without complication after administration of atovaquone and azithromycin or clindamycin quinine. Although patients experiencing unresponsive to standard antimicrobial therapy have been described, the pathogenesis, clinical course, optimal treatment regimen such cases remain uncertain.We compared immunologic status, 14 case who experienced morbidity death persistence Babesia microti infection, despite repeated...
The proteasome inhibitor bortezomib may enhance activity of chemoimmunotherapy in lymphoma. We evaluated dose-escalated plus standard cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) rituximab (R) patients with diffuse large B-cell lymphoma (DLBCL) mantle cell (MCL).Seventy-six subjects untreated DLBCL (n = 40) MCL 36) received CHOP every 21 days (CHOP-21) R at 0.7 mg/m(2) 4), 1.0 9), or 1.3 63) on 1 4 for six cycles.Median age was 63 years (range, 20 to 87), International...