Humoral and Cellular Immune Response to Covid-19 Vaccination in Patients with Chronic Graft-versus-Host Disease on Immunosuppression.

Chronic graft-versus-host disease (cGVHD) and its management with immunosuppressive therapies increase the susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as well as progression to severe Coronavirus 19 disease (COVID-19). Vaccination against COVID-19 is strongly recommended, but efficacy data are limited in this patient population. In this study, responses to COVID-19 vaccination were measured at 3 time points-after the initial vaccine series, before the third dose, and after the third dose-in adults with cGVHD receiving immunosuppressive therapy. Humoral response was measured by quantitative anti-spike antibody and neutralizing antibody levels. Anti-nucleocapsid antibody levels were measured to detect natural infection. T cell response was evaluated by a novel immunosequencing technique combined with immune repertoire profiling from cryopreserved peripheral blood mononuclear cell samples. Present or absent T cell responses were determined by the relative proportion of unique SARS-CoV-2-associated T cell receptor sequences ("breadth") plus clonal expansion of the response ("depth") compared with those in a reference population. Based on both neutralizing antibody and T cell responses, patients were categorized as vaccine responders (both detected), nonresponders (neither detected), or mixed (one but not both detected). Thirty-two patients were enrolled for the initial series, including 17 (53%) positive responders, 7 (22%) mixed responders, and 8 (25%) nonresponders. All but one patient categorized as mixed responders had humoral responses while lacking T cell responses. No statistical differences were observed in patient characteristics among the 3 groups of patients categorized by immune response, although sample sizes were limited. Significant positive correlations were observed between the robustness of cellular and humoral responses after the initial series. Among the 20 patients with paired samples (pre- and post-third dose), a third vaccination resulted in increased neutralizing antibody titers. cGVHD worsened in 10 patients (26%; 6 after the initial series and 4 after the third dose), necessitating escalation of immunosuppressive doses in 5 patients, although 4 had been tapering immunosuppression and 5 had already worsening cGVHD at the time of vaccination, and a clear association between COVID-19 vaccination and cGVHD could not be drawn. Among the patients with cGVHD on immunosuppressive therapy, 72% demonstrated a neutralizing antibody response after a 2-dose primary COVID-19 vaccination, two-thirds of whom also developed a T cell response; 25% had neither a humoral nor a T cell response. A third dose further amplified the antibody response.

Distress in a Pandemic: Association of the Coronavirus Disease-2019 Pandemic with Distress and Quality of Life in Hematopoietic Stem Cell Transplantation.

The global coronavirus disease 2019 (COVID-19) pandemic has drastically disrupted cancer care, potentially exacerbating patients' distress levels. Patients undergoing hematopoietic stem cell transplantation (HSCT) may be especially vulnerable to this pandemic stress. However, the associations of the COVID-19 pandemic with distress, fatigue, and quality of life (QoL) are not well understood in this population. In a cross-sectional analysis of data from 205 patients undergoing HSCT enrolled in a supportive care trial, we compared baseline pre-HSCT distress symptoms (depression, anxiety, and posttraumatic stress disorder [PTSD]), fatigue, and QoL between enrollees before (ie, March 2019-January 2020) and during (ie, March 2020-January 2021) the COVID-19 pandemic. We used linear regression models adjusting for sociodemographics and cancer diagnosis to examine the associations between enrollment period and patient-reported outcomes. We used semistructured qualitative interviews in 20 allogeneic HSCT recipients who were ≥3-months post-HSCT to understand the impact of the COVID-19 pandemic on their recovery post-HSCT. One hundred twenty-four participants enrolled before COVID-19, and 81 participants enrolled during the pandemic. The 2 cohorts had similar baseline demographics and disease risk factors. In multivariate regression models, enrollment during COVID-19 was not associated with pre-HSCT symptoms of depression, anxiety, PTSD, fatigue, or QoL impairment. COVID-19-era participants reported themes of negative (eg, increased isolation) and positive (eg, engagement with meaningful activities) implications of the pandemic on HSCT recovery. We found no differences in pre-HSCT distress, fatigue, or QoL in patients undergoing HSCT before or during the COVID-19 pandemic; however, patients in early recovery post-HSCT report both negative and positive implications of the COVID-19 pandemic in their lives.

Blood and marrow transplantation during the emerging COVID-19 pandemic: the Seattle approach.

On January 20, 2020, the first patient with coronavirus disease 2019 (COVID-19) in the United States of America was diagnosed in Washington state, which subsequently experienced rapidly increasing numbers of COVID-19 cases, hospitalizations, and deaths. This placed the Seattle Blood and Marrow Transplant Program at Fred Hutchinson Cancer Research Center (Fred Hutch) in the national epicenter of this pandemic. Here, we summarize the experience gained during our rapid response to the COVID-19 pandemic. Our efforts were aimed at safely performing urgent and potentially life-saving stem cell transplants in the setting of pandemic-related stresses on healthcare resources and shelter-in-place public health measures. We describe the unique circumstances and challenges encountered, the current state of the program amidst evolving COVID-19 cases in our community, and the guiding principles for recovery. We also estimate the collateral impact of directing clinical resources toward COVID-19-related care on cancer patients in need of stem cell transplantation. Although our experience was influenced by specific regional and institutional factors, it may help inform how transplant programs respond to COVID-19 and future pandemics.

Hematopoietic Cell Transplantation with Cryopreserved Grafts for Severe Aplastic Anemia.

With the COVID-19 pandemic and the ensuing barriers to the collection and transport of donor cells, it is often necessary to collect and cryopreserve grafts before initiation of transplantation conditioning. The effect on transplantation outcomes in nonmalignant disease is unknown. This analysis examined the effect of cryopreservation of related and unrelated donor grafts for transplantation for severe aplastic anemia in the United States during 2013 to 2019. Included are 52 recipients of cryopreserved grafts who were matched for age, donor type, and graft type to 194 recipients who received noncryopreserved grafts. Marginal Cox regression models were built to study the effect of cryopreservation and other risk factors associated with outcomes. We recorded higher 1-year rates of graft failure (hazard ratio [HR], 2.26; 95% confidence interval, 1.17 to 4.35; P = .01) and of 1-year overall mortality (HR, 3.13; 95% CI, 1.60 to 6.11; P = .0008) after transplantation of cryopreserved compared with noncryopreserved grafts, with adjustment for sex, performance score, comorbidity, cytomegalovirus serostatus, and ABO blood group match. The incidence of acute and chronic graft-versus-host disease did not differ between the 2 groups. Adjusted probabilities of 1-year survival were 73% (95% CI, 60% to 84%) in the cryopreserved graft group and 91% (95% CI, 86% to 94%) in the noncryopreserved graft group. These data support the use of noncryopreserved grafts whenever possible in patients with severe aplastic anemia.