This study reports on 382 COVID-19 patients having undergone allogeneic (n = 236) or autologous (n = 146) hematopoietic cell transplantation (HCT) reported to the European Society for Blood and Marrow Transplantation (EBMT) or to the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH). The median age was 54.1 years (1.0–80.3) for allogeneic, and 60.6 years (7.7–81.6) for autologous HCT patients. The median time from HCT to COVID-19 was 15.8 months (0.2–292.7) in allogeneic and 24.6 months (−0.9 to 350.3) in autologous recipients. 83.5% developed lower respiratory tract disease and 22.5% were admitted to an ICU. Overall survival at 6 weeks from diagnosis was 77.9% and 72.1% in allogeneic and autologous recipients, respectively. Children had a survival of 93.4%. In multivariate analysis, older age (p = 0.02), need for ICU (p < 0.0001) and moderate/high immunodeficiency index (p = 0.04) increased the risk while better performance status (p = 0.001) decreased the risk for mortality. Other factors such as underlying diagnosis, time from HCT, GVHD, or ongoing immunosuppression did not significantly impact overall survival. We conclude that HCT patients are at high risk of developing LRTD, require admission to ICU, and have increased mortality in COVID-19.

Background Patients with cancer have been shown to have a higher risk of clinical severity and mortality compared to non-cancer patients with COVID-19. Patients with hematologic malignancies typically are known to have higher levels of immunosuppression and may develop more severe respiratory viral infections than patients with solid tumors. Data on COVID-19 in patients with hematologic malignancies are limited. Here we characterize disease severity and mortality and evaluate potential prognostic factors for mortality. Methods In this population-based registry study, we collected de-identified data on clinical characteristics, treatment and outcomes in adult patients with hematologic malignancies and confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection within the Madrid region of Spain. Our case series included all patients admitted to 22 regional health service hospitals and 5 private healthcare centers between February 28 and May 25, 2020. The primary study outcome was all-cause mortality. We assessed the association between mortality and potential prognostic factors using Cox regression analyses adjusted for age, sex, comorbidities, hematologic malignancy and recent active cancer therapy. Results Of 833 patients reported, 697 were included in the analyses. Median age was 72 years (IQR 60–79), 413 (60%) patients were male and 479 (69%) and 218 (31%) had lymphoid and myeloid malignancies, respectively. Clinical severity of COVID-19 was severe/critical in 429 (62%) patients. At data cutoff, 230 (33%) patients had died. Age ≥ 60 years (hazard ratios 3.17–10.1 vs < 50 years), > 2 comorbidities (1.41 vs ≤ 2), acute myeloid leukemia (2.22 vs non-Hodgkin lymphoma) and active antineoplastic treatment with monoclonal antibodies (2·02) were associated with increased mortality; conventional chemotherapy showed borderline significance (1.50 vs no active therapy). Conversely, Ph-negative myeloproliferative neoplasms (0.33) and active treatment with hypomethylating agents (0.47) were associated with lower mortality. Overall, 574 (82%) patients received antiviral therapy. Mortality with severe/critical COVID-19 was higher with no therapy vs any antiviral combination therapy (2.20). Conclusions In this series of patients with hematologic malignancies and COVID-19, mortality was associated with higher age, more comorbidities, type of hematological malignancy and type of antineoplastic therapy. Further studies and long-term follow-up are required to validate these criteria for risk stratification.

Chimeric antigen receptor (CAR) T-cell therapy is one of the most promising emerging treatments for B-cell malignancies. Recently, two CAR T-cell products (axicabtagene ciloleucel and tisagenlecleucel) have been approved for patients with aggressive B-cell lymphoma and acute lymphoblastic leukemia; many other CART constructs are in research for both hematological and non-hematological diseases. Most of the patients receiving CART therapy will develop fever at some point after infusion, mainly due to cytokine release syndrome (CRS). The onset of CRS is often indistinguishable from an infection, which makes management of these patients challenging. In addition to the lymphodepleting chemotherapy and CAR T cells, the treatment of complications with corticosteroids and/or tocilizumab increases the risk of infection in these patients. Data regarding incidence, risk factors and prevention of infections in patients receiving CART cell therapy are scarce. To assist in patient care, a multidisciplinary team from hospitals designated by the Spanish Ministry of Health to perform CART therapy prepared these recommendations. We reviewed the literature on the incidence, risk factors, and management of infections in adult and pediatric patients receiving CART cell treatment. Recommendations cover different areas: monitoring and treatment of hypogammaglobulinemia, prevention, prophylaxis, and management of bacterial, viral, and fungal infections as well as vaccination prior and after CART cell therapy.

In our osteosarcoma patient population, (18)F-FDG PET/CT indices (either combined metabolic/volumetric or metabolic indices) determined after neoadjuvant chemotherapy were useful in predicting tumour responses. This held true after only one chemotherapy course.

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Tisagenlecleucel (tisa‐cel) is a second‐generation autologous CD19‐targeted chimeric antigen receptor (CAR) T‐cell therapy approved for relapsed/refractory (R/R) large B‐cell lymphoma (LBCL). The approval was based on the results of phase II JULIET trial, with a best overall response rate (ORR) and complete response (CR) rate in infused patients of 52% and 40%, respectively. We report outcomes with tisa‐cel in the standard‐of‐care (SOC) setting for R/R LBCL. Data from all patients with R/R LBCL who underwent leukapheresis from December 2018 until June 2020 with the intent to receive SOC tisa‐cel were retrospectively collected at 10 Spanish institutions. Toxicities were graded according to ASTCT criteria and responses were assessed as per Lugano 2014 classification. Of 91 patients who underwent leukapheresis, 75 (82%) received tisa‐cel therapy. Grade 3 or higher cytokine release syndrome and neurotoxicity occurred in 5% and 1%, respectively; non‐relapse mortality was 4%. Among the infused patients, best ORR and CR were 60% and 32%, respectively, with a median duration of response of 8.9 months. With a median follow‐up of 14.1 months from CAR T‐cell infusion, median progression‐free survival and overall survival were 3 months and 10.7 months, respectively. At 12 months, patients in CR at first disease evaluation had a PFS of 87% and OS of 93%. Patients with an elevated lactate dehydrogenase showed a shorter PFS and OS on multivariate analysis. Treatment with tisa‐cel for patients with relapsed/refractory LBCL in a European SOC setting showed a manageable safety profile and durable complete responses.

Relapse remains the main cause of treatment failure in patients with acute myelogenous leukemia (AML) after allogeneic hemopoietic stem cell transplantation (SCT). The Wilms' tumor 1 gene (WT1) is reportedly overexpressed in >90% of patients with AML and thus can be useful for minimal residual disease (MRD) monitoring. The aim of this study was to evaluate the usefulness of WT1 expression as a relapse predictor marker in patients with AML after SCT and compare it with flow cytometry (FC) and chimerism studies. WT1 expression was assessed retrospectively using quantitative RT-PCR in bone marrow and peripheral blood from 21 patients. Patients were classified according to WT1 dynamics posttransplantation. Eleven of the 21 patients had low and stable WT1 levels. All of these 11 patients showed complete chimerism and negative MRD by FC and remained in complete remission with a median follow-up of 27 months (range, 18-98 months). In contrast, 10 of 21 patients showed WT1 overexpression after SCT, and 9 of these 10 patients relapsed. The incidence of relapse differed significantly between the 2 groups of patients according to WT1 expression post-SCT (P = .00003). Relapse in the 9 patients occurred at a median of 314 days (range, 50-560 days). Interestingly, in these patients, relapse was first predicted by WT1 (with negative FC and complete chimerism) in 7 patients. WT1 overexpression was correlated with disease burden in patients with AML before and after allogeneic SCT. In patients who relapsed, both medullary and extramedullary relapse were better anticipated by WT1 overexpression compared with FC and chimerism.