Elevated cytokines and chemokines in peripheral blood of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma.

The global SARS-CoV-2 coronavirus pandemic continues to be devastating in many areas. Treatment options have been limited and convalescent donor plasma has been used by many centers to transfer passive neutralizing antibodies to patients with respiratory involvement. The results often vary by institution and are complicated by the nature and quality of the donor plasma itself, the timing of administration and the clinical aspects of the recipients. SARS-CoV-2 infection is known to be associated with an increase in the blood concentrations of several inflammatory cytokines/chemokines, as part of the overall immune response to the virus and consequential to mediated lung pathology. Some of these correlates contribute to the cytokine storm syndrome and acute respiratory distress syndrome, often resulting in fatality. A Phase IIa clinical trial at our institution using high neutralizing titer convalescent plasma transfer gave us the unique opportunity to study the elevations of correlates in the first 10 days after infusion. Plasma recipients were divided into hospitalized COVID-19 pneumonia patients who did not (Track 2) or did (Track 3) require mechanical ventilation. Several cytokines were elevated in the patients of each Track and some continued to rise through Day 10, while others initially increased and then subsided. Furthermore, elevations in MIP-1α, MIP-1ß and CRP correlated with disease progression of Track 2 recipients. Overall, our observations serve as a foundation for further study of these correlates and the identification of potential biomarkers to improve upon convalescent plasma therapy and to drive more successful patient outcomes.

Clinical and laboratory evaluation of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma.

Here, we report on a phase IIa study to determine the intubation rate, survival, viral clearance, and development of endogenous Abs in patients with COVID-19 pneumonia treated with convalescent plasma (CCP) containing high levels of neutralizing anti-SARS-CoV-2 Abs. Radiographic and laboratory evaluation confirmed all 51 treated patients had COVID-19 pneumonia. Fresh or frozen CCP from donors with high titers of neutralizing Abs was administered. The nonmechanically ventilated patients (n = 36) had an intubation rate of 13.9% and a 30-day survival rate of 88.9%, and the overall survival rate for a comparative group based on network data was 72.5% (1625/2241). Patients had negative nasopharyngeal swab rates of 43.8% and 73.0% on days 10 and 30, respectively. Patients mechanically ventilated had a day-30 mortality rate of 46.7%; the mortality rate for a comparative group based on network data was 71.0% (369/520). All evaluable patients were found to have neutralizing Abs on day 3 (n = 47), and all but 1 patient had Abs on days 30 and 60. The only adverse event was a mild rash. In this study on patients with COVID-19 disease, we show therapeutic use of CCP was safe and conferred transfer of Abs, while preserving endogenous immune response.

Optimizing Communication and Adherence to Iron Chelation Therapy From Diagnosis to Treatment in Patients With Myelodysplastic Syndromes.

Myelodysplastic syndromes (MDS), a heterogeneous group of blood diseases, are usually diagnosed in older individuals, with a median age at diagnosis of more than 70 years. Anemia is a common symptom in patients with MDS and may require frequent red blood cell transfusions, which can lead to iron overload. Iron chelation therapy is recommended to decrease iron concentrations in tissue and minimize organ dysfunction. However, the currently available iron chelation therapies are associated with side effects, financial constraints, and dosing issues, which may affect patient adherence. Moreover, many patients with MDS lack an understanding of the disease and their prognosis and treatments. This review can be used in the advanced practice setting to discuss the importance of communicating with patients about MDS from the time of diagnosis and will explore strategies to enhance adherence to iron chelation therapy. An individualized approach that weighs the risks and benefits of treatment for older patients with MDS will allow advanced practitioners to set expectations while developing adherence strategies to optimize outcomes. This approach provides a platform for advanced practitioners to communicate with patients to ensure they understand the natural history of MDS, their individual prognoses, and the goals of both active treatment and supportive care.

The graft-versus-myeloma effect: chronic graft-versus-host disease but not acute graft-versus-host disease prolongs survival in patients with multiple myeloma receiving allogeneic transplantation.

We conducted a study of patients with multiple myeloma (MM) undergoing allogeneic transplantation to evaluate outcome parameters. Fifty-seven consecutive patients with MM received an allogeneic transplantation between 2004 and 2011 at our institution. Patients who had received at least 1 prior autologous transplantation were included. Twenty-six patients underwent allogeneic transplantation for consolidation after a response to their first autograft, and 30 patients received an allogeneic transplantation as salvage therapy. Donor source was evenly distributed between related and unrelated. The median follow-up was 52 months. Thirty-two (57.1%) patients achieved a complete response (CR). At 5 years, 49.2% of all patients were in CR. Sixteen patients received either donor lymphocyte infusions or immune suppression withdrawal for disease progression, with a 62.5% response rate. The 5-year overall survival (OS) for all patients was 59%. The 5-year OS for the 30 patients in the consolidation group was 82% compared with 38% for those in the salvage group. In multivariate analysis, 3 factors remained significantly associated with OS. These include being in the salvage group (hazard ratio [HR], 4.05; P = .0196), acute graft-versus-host disease (aGVHD) (HR, 2.99; P = .034), and chronic graft-versus-host disease (cGVHD), which was highly protective, with a 5-year OS of 78.8% for patients with cGVHD versus 42.6% for patients without cGVHD (HR .17, P = .008). Our data show that allogeneic transplantation for MM can lead to sustained remissions. aGVHD is significantly deleterious to OS and progression-free survival, whereas cGVHD is strongly favorable, supporting an important role for the graft-versus-myeloma effect.

Management of chronic graft-versus-host disease.

Chronic graft-versus-host disease (GVHD) is an immune-mediated disorder that adversely affects quality of life and clinical outcomes in patients following hematopoietic stem cell transplantation. Conventional treatment of GVHD includes prolonged and high-dose corticosteroids; however, those drugs are associated with multiple side effects. This article describes the ability of extracorporeal photopheresis therapy to exhibit a steroid-sparing effect, which can reduce long-term complications as a consequence of steroid treatment.

Unrelated donor hematopoietic stem cell transplantation for patients with hematologic malignancies using a nonmyeloablative conditioning regimen of fludarabine, low-dose total body irradiation, and rabbit antithymocyte globulin.

Hematopoietic stem cell chimerism can be established after low-dose conditioning regimens, although the risk of donor cell rejection increases for unrelated donor transplantations. We added pretransplantation rabbit antithymocyte globulin (6 mg/kg) to an established conditioning regimen of fludarabine (90 mg/m2) and single-fraction total body irradiation (200 cGy) followed by postgrafting immunosuppression with cyclosporine A and mycophenolate mofetil for 22 patients with hematologic malignancies. One patient rejected the graft and successfully underwent transplantation with cells from a second donor by using the same conditioning regimen. The actuarial probability of developing acute graft-versus-host disease grade II to IV before day 100 was 40%, although 9 of 14 patients who survived beyond 100 days developed chronic graft-versus-host disease. These data support a hypothesis that the addition of antithymocyte globulin decreases the risk of graft-versus-host and host-versus-graft reactions when combined with a nonmyeloablative conditioning regimen of fludarabine and total body irradiation.