The majority of intensivists surveyed recognize stress-related mucosal bleeding as a relatively infrequent event; however, implementation of a stress ulcer prophylaxis risk stratification scheme for ICU patients is necessary. Histamine-2 receptor antagonists are consistently perceived as appropriate initial agents, although proton pump inhibitors have become first-line therapy in an increasing percentage of critical care patients, despite limited data regarding their use in this population.
Blinatumomab is a novel BiTE therapeutic monoclonal antibody that has shown promising results in patients with relapsed or refractory ALL or those achieving a CR with persistent MRD. Phase III clinical trials should define the optimal place in therapy of blinatumomab.
Background:
Various studies have demonstrated that interleukin-6 (IL-6) activates the central magnocellular arginine vasopressin (AVP)-secreting neurons in the brain to produce non-osmotic, non-volume-mediated increases in AVP. The most common toxicity of CD19+ chimeric antigen receptor (CAR) T-cells is cytokine release syndrome, which is related to increased levels of IL-6. This study will evaluate the correlation of IL-6 levels with hyponatremia in patients receiving CD19+ CAR T-cells.
Materials and methods:
This is a single-center retrospective analysis of adult patients who received CD19+ CAR T-cells for the treatment of relapsed/refractory acute lymphoblastic leukemia (ALL).
Results:
Hyponatremia, defined as a serum sodium (Na) ≤ 135 mEq/L, occurred in 31 (61%) patients. A change in Na > 7 mEq occurred in 32 (63%) patients, and the median lowest Na was 133 mEq/L (interquartile range (IQR): 131 – 136)). There was an inverse linear relationship between IL-6 levels and lowest Na (p = 0.001). Overall, per 10-fold increase in IL-6, Na decreased by an average of 2.68 mEq/L.
Conclusion:
Hyponatremia is common in patients who received CD19+ CAR T-cells. There is an inverse linear relationship between IL-6 levels and nadir Na (p = 0.001). Further studies will be needed to confirm a causative relationship between IL-6 levels and hyponatremia following CD19+ CAR T-cell infusion.
Asparaginase administration has become a crucial component of front-line pediatric and pediatric inspired multi-agent regimens for the treatment of acute lymphoblastic leukemia (ALL). The aim of this study was to retrospectively assess the safety and feasibility of switching to Erwinia asparaginase after pegaspargase intolerance in adult ALL patients treated at Memorial Sloan Kettering Cancer Center. Our analysis included 10 patients, with a median age of 39 years (range 20–72), 90% males, 70% with B-cell ALL, and 30% with T-cell ALL. Nine patients were switched to Erwinia asparaginase after pegaspargase hypersensitivity and one patient after grade 4 hyperbilirubinemia secondary to pegaspargase. With Erwinia asparaginase, no hypersensitivity reactions occurred and no patient developed other known clinical asparaginase-related toxicities. Laboratory adverse effects consisted of mostly mild elevation in liver enzymes. No morphologic relapses have occurred in any patient switched to Erwinia asparaginase in first remission at a follow up of 0.4–34.6 months. These findings are unique in that all of our patients received Erwinia asparaginase after hypersensitivity or intolerance to pegaspargase and 50% of them were older than 40 years of age, a population with very limited data. Our observations provide preliminary information that treatment with Erwinia asparaginase can proceed as scheduled in adult patients, despite pegaspargase hypersensitivity and possibly liver intolerance.
Outcomes of patients with relapsed disease are improving thanks to new therapies such as blinatumomab, inotuzumab, and CAR T-cells. Although the efficacy of these therapies is impressive, they are not without toxicity, both physical and financial. The optimal sequencing of these therapies still remains a question.
Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly spike protein messenger RNA (mRNA) vaccines, to date have yielded a high degree of efficacy against symptomatic infection and severe 2]. However, outcomes of patients with active hematologic malignancies are not well described, and remain a significant concern given data demonstrating poorer outcomes in sub-groups of these patients who become infected [3]; for example, a recent study of patients with chronic lymphocytic leukemia (CLL) demonstrated reduced antibody seroprevalence after vaccination in patients on active therapy with Burton Tyrosine Kinase (BTK) inhibitors [4]. These observations prompted us to evaluate post-vaccination antibody response in patients with Philadelphia-chromosome positive and negative Myeloproliferative Neoplasms (MPNs), including untreated patients and patients on active therapy.We evaluated antibody response in 74 consecutive patients with MPNs subsequent to two doses of the mRNA BNT162b2 (Pfizer) or mRNA-1273 (Moderna) vaccines, as per the U.S. Food and Drug Administration Emergency Use Authorization (EUA). We included patients with chronic myeloid leukemia (CML), essential thrombocythemia (ET), polycythemia vera (PV), myelofibrosis (MF), or blastphase MPN (MPN-BP). Serology testing was performed as part of routine clinical practice using the AdviseDx SARS-CoV-2 IgG II reagent assay (Abbott Diagnostics). A result was considered positive with ≥50 AU/mL. The study was approved by the Institutional Review Board of Memorial Sloan Kettering Cancer Center.Data were collected from a period spanning from April 2021 to September 2021, from 74 patients in total. The cohort consisted of 22 patients with CML, 14 patients with ET, 14 patients with PV, 22 patients with MF, and 2 patients with MPN-BP (both transformed from prior post-ET Myelofibrosis). The median age of included subjects was 68.2 years. Eighteen CML patients were receiving active treatment with ABL kinase inhibitors, including dasatinib
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