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Amandeep Salhotra

Publications and source records attributed to Amandeep Salhotra.

4 recordsLinked to original sources

CAR T-cell therapy as a definitive consolidation for older adults with B-ALL in first complete remission.

We report a phase 1 study assessing the safety and efficacy of CD19 chimeric antigen receptor (CAR) T cells as definitive consolidation in older adults (aged ≥55 years) with B-cell acute lymphoblastic leukemia (B-ALL) in first complete remission (CR1). Eighteen patients received lymphodepletion followed by infusion of memory-enriched CD19 CAR T cells. The median age was 64 years, and all patients were measurable residual disease (MRD)-negative before lymphodepletion. There were no dose-limiting toxicities, grade ≥2 cytokine release syndrome, or any grade immune effector cell-associated neurotoxicity syndrome. Estimated 18-month event-free and overall survival were 84% and 100%, respectively. CAR T cells expanded in the blood and cerebrospinal fluid despite patients' MRD-negative status. Comparing clinical samples from patients with relapsed/refractory (R/R) B-ALL from our historical trial (ClinicalTrials.gov identifier: NCT02146924) and patients in CR1, we found that the blood and CAR T-cell products from patients with R/R B-ALL were hyperinflammatory and hyperimmunometabolic, respectively. First-line CAR T-cell therapy was safe and well tolerated and potentially extended remission in patients in MRD-negative CR1. These findings support further investigation of the early use of CAR T-cell therapy for B-ALL. This trial was registered at www.clinicaltrials.gov as NCT05707273.

Humans↗

Venous thromboembolism occurs infrequently in meningioma patients receiving combined modality prophylaxis.

BACKGROUND: Individuals with brain tumors have an increased risk of venous thromboembolism (VTE). Within this population, patients with meningiomas have been reported to have the highest incidence, exceeding rates associated with gliomas and brain metastases. However, earlier studies did not employ VTE prophylaxis, and VTE were detected with radionuclide scans, the reliability of which has since been questioned. Therefore, we conducted a retrospective review of postoperative meningioma patients receiving contemporary VTE prophylaxis and diagnostic methods to define the current incidence of and risk factors for symptomatic VTE in this population. METHODS: Medical records were reviewed from all patients undergoing craniotomy for meningioma at Johns Hopkins Hospital in 2004 and 2005. The association between clinical characteristics and VTE was assessed using parametric and nonparametric statistical tests and survival analysis. RESULTS: A total of 224 individuals met criteria for the review. The mean age was 52 years (standard deviation [SD] 14 years), and 167 patients (75%) were women. Median follow-up time was 230 days (interquartile range [IQR], 89-428 days). VTE was diagnosed in 11 patients (4.9%; 95% confidence interval, 2.5%-8.6%) at a median of 16 days (IQR, 7-33 days) postoperatively. The development of VTE was associated with older age (mean, 68 years vs 52 years; P = .0001), male gender (P = .007), and nonambulatory status postoperatively (P < .0001). CONCLUSIONS: VTE occurs infrequently in postoperative meningioma patients who receive combined modality VTE prophylaxis. VTE risk factors in these patients include advanced age, male gender, and nonambulatory status postoperatively.

Adult↗

Systemic anti-hepatocyte growth factor monoclonal antibody therapy induces the regression of intracranial glioma xenografts.

PURPOSE: Hepatocyte growth factor (HGF) and its receptor Met are involved in the initiation, progression, and metastasis of numerous systemic and central nervous system tumors. Thus, an anti-HGF monoclonal antibody (mAb) capable of blocking the HGF-Met interaction could have broad applicability in cancer therapy. EXPERIMENTAL DESIGN: An anti-HGF mAb L2G7 that blocks binding of HGF to Met was generated by hybridoma technology, and its ability to inhibit the various biological activities of HGF was measured by in vitro assays. The ability of L2G7 to inhibit the growth of tumors was determined by establishing s.c. and intracranial xenografts of human U87 and U118 glioma cell lines in nude mice, and treatment with 100 microg of L2G7 or control given i.p. twice per week. RESULTS: MAb L2G7 strongly inhibited all biological activities of HGF measured in vitro, including cell proliferation, cell scattering, and endothelial tubule formation. Treatment with L2G7 completely inhibited the growth of established s.c. xenografts in nude mice. Moreover, systemic administration of L2G7 from day 5 induced the regression of intracranial U87 xenografts and dramatically prolonged the survival of tumor-bearing mice from a median of 39 to >90 days. L2G7 treatment of large intracranial tumors (average tumor size, 26.7 mm(3)) from day 18 induced substantial tumor regression (control group, 134.3 mm(3); L2G7 treated group, 11.7 mm(3)) by day 29 and again prolonged animal survival. CONCLUSIONS: These findings show that blocking the HGF-Met interaction with systemically given anti-HGF mAb can have profound antitumor effects even within the central nervous system, a site previously believed to be resistant to systemic antibody-based therapeutics.

Animals↗

Central core disease.

Central core disease is a congenital myopathy characterized by generalized hypotonia, muscle weakness and presence of central cores on muscle biopsy. It generally presents during infancy. It is familial with autosomal dominant inheritance [Chromosome 19q13.1; Gene Locus RyR1 (Ryanodine receptor gene)]. We report here two cases of central core disease in a 3-year-old male child and 8 year old female child.

Activities of Daily Living↗