Carlos Salgado, MD

View details for Web of Science ID 000784584900071

View details for Web of Science ID 000778999300512

Abstract

Primary immunodeficiency may present with treatment-refractory enteropathy. We present two patients with celiac/celiac-like disease diagnosed in early childhood and refractory to the gluten-free diet. One patient had features of multi-system autoimmunity, whereas the other had celiac-like disease as an isolated clinical finding. Both patients underwent genetic testing given disease refractoriness and were ultimately diagnosed with cytotoxic T lymphocyte antigen 4 (CTLA4) haploinsufficiency. They are both now in complete clinical and endoscopic remission on abatacept. CTLA4 haploinsufficiency has incomplete penetrance and significant phenotypic heterogeneity but should be considered in the differential diagnosis of refractory celiac/celiac-like disease, as treatment implications are significant.

View details for DOI 10.3389/fimmu.2022.894648

View details for PubMedID 35935971

Abstract

We evaluated the efficacy of combination enzastaurin (LY317615) and bevacizumab for recurrent malignant gliomas and explored serologic correlates. We enrolled 81 patients with glioblastomas (GBM, n=40) and anaplastic gliomas (AG, n=41). Patients received enzastaurin as a loading dose of 1125mg, followed by 500 or 875mg daily for patients on non-enzyme-inducing or enzyme-inducing antiepileptics, respectively. Patients received bevacizumab 10mg/kg intravenously biweekly. Clinical evaluations were repeated every 4weeks. Magnetic resonance imaging was obtained at baseline and every 8weeks from treatment onset. Phosphorylated glycogen synthase kinase (GSK)-3 levels from peripheral blood mononuclear cells (PBMCs) were checked with each MRI. Median overall survival was 7.5 and 12.4months for glioblastomas and anaplastic glioma cohorts, with median progression-free survivals of 2.0 and 4.4months, respectively. Of GBM patients, 3/40 (7.5%) were not evaluable, while 8/37 (22%) had partial or complete response and 20/37 (54%) had stable disease for 2+ months. Of the 39 evaluable AG patients, 18 (46%) had an objective response, and 16 (41%) had stable disease for 2+ months. The most common grade 3+ toxicities were lymphopenia (15%), hypophosphatemia (8.8%) and thrombotic events (7.5%). Two (2.5%) GBM patients died suddenly; another death (1.3%) occurred from intractable seizures. Phosphorylated GSK-3 levels from PBMCs did not correlate with treatment response. A minimally important improvement in health-related quality of life was self-reported in 7-9/24 (29.2-37.5%). Early response based on Levin criteria was significantly associated with significantly longer progression free survival for glioblastomas. Enzastaurin (LY317615) in combination with bevacizumab for recurrent malignant gliomas is well-tolerated, with response and progression-free survival similar to bevacizumab monotherapy.

View details for DOI 10.1007/s11060-015-2020-x

View details for PubMedID 26643807

Abstract

Bevacizumab ((BEV) has become a mainstay of treating recurrent glioblastoma, but eventual tumor resistance is expected. Targeting multiple growth-associated signaling pathways may result in more effective treatment than targeting VEGF alone. Patients with recurrent glioblastoma were stratified by prior BEV exposure and treated with sunitinib 37.5mg daily in this phase II study. Response evaluations were performed at baseline and at the end of every 4week cycle. Six-month progression-free survival (PFS6) was the primary endpoint for both arms of the study. Secondary endpoints included health related quality of life measures and FDG-PET correlatives with patient outcomes. Sixty-three patients were accrued to this study; thirty-two were BEV-nave, 31 were BEV-resistant. PFS6 was 10.4% [95% CI 3.2-33.8] in the BEV-nave cohort and 0% in the BEV-resistant cohort. Median overall survival was 9.4months [95% CI 6.15-21.90] in the BEV-nave cohort and 4.37months [95% CI 3.02-6.21] in the BEV-resistant cohort. 3/29 patients (10%) of the BEV-nave, and 0/27 BEV-resistant patients achieved radiographic response. Thrombocytopenia, leukopenia, and neutropenia were the most common drug-associated adverse events and occurred with higher frequency than expected. Sunitinib treatment in BEV-nave patients did not appear to affect outcomes with subsequent BEV therapy. Continuous daily sunitinib did not prolong progression-free survival in BEV-nave nor BEV-resistant patients with recurrent glioblastoma.

View details for DOI 10.1007/s11060-012-0988-z

View details for PubMedID 23086433