Allogeneic hematopoietic stem cell transplantation is curative in myelofibrosis, and current prognostic scoring systems aim to select patients for transplantation. Here, we aimed to develop a prognostic score to determine prognosis after transplantation itself, using clinical, molecular, and transplant-specific information from a total of 361 patients with myelofibrosis. Of these, 205 patients were used as a training cohort to create a clinical-molecular myelofibrosis transplant scoring system (MTSS), which was then externally validated in a cohort of 156 patients. Multivariable analysis on survival identified age at least 57 years, Karnofsky performance status lower than 90%, platelet count lower than 150 × 109/L, leukocyte count higher than 25 × 109/L before transplantation, HLA-mismatched unrelated donor, ASXL1 mutation, and non-CALR/MPL driver mutation genotype being independent predictors of outcome. The uncorrected concordance index for the final survival model was 0.723, and bias-corrected indices were similar. Risk factors were incorporated into a 4-level MTSS: low (score, 0-2), intermediate (score, 3-4), high (score, 5), and very high (score, >5). The 5-year survival according to risk groups in the validation cohort was 83% (95% confidence interval [CI], 71%-95%), 64% (95% CI, 53%-75%), 37% (95% CI, 17%-57%), and 22% (95% CI, 4%-39%), respectively (P < .001). Increasing score was predictive of nonrelapse mortality (P < .001) and remained applicable to primary (0.718) and post-essential thrombocythemia (ET)/polycythemia vera (PV) myelofibrosis (0.701) improving prognostic ability in comparison with all currently available disease-specific systems. In conclusion, this MTSS predicts outcome of patients with primary and post-ET/PV myelofibrosis undergoing allogeneic stem cell transplantation.

Background Previous studies reporting the causes of death in patients with severe COVID-19 have provided conflicting results. The objective of this study was to describe the causes and timing of death in patients with severe COVID-19 admitted to the intensive care unit (ICU). Methods We performed a retrospective study in eight ICUs across seven French hospitals. All consecutive adult patients (aged ≥ 18 years) admitted to the ICU with PCR-confirmed SARS-CoV-2 infection and acute respiratory failure were included in the analysis. The causes and timing of ICU deaths were reported based on medical records. Results From March 1, 2020, to April 28, 287 patients were admitted to the ICU for SARS-CoV-2 related acute respiratory failure. Among them, 93 patients died in the ICU (32%). COVID-19-related multiple organ dysfunction syndrome (MODS) was the leading cause of death (37%). Secondary infection-related MODS accounted for 26% of ICU deaths, with a majority of ventilator-associated pneumonia. Refractory hypoxemia/pulmonary fibrosis was responsible for death in 19% of the cases. Fatal ischemic events (venous or arterial) occurred in 13% of the cases. The median time from ICU admission to death was 15 days (25th–75th IQR, 7–27 days). COVID-19-related MODS had a median time from ICU admission to death of 14 days (25th–75th IQR: 7–19 days), while only one death had occurred during the first 3 days since ICU admission. Conclusions In our multicenter observational study, COVID-19-related MODS and secondary infections were the two leading causes of death, among severe COVID-19 patients admitted to the ICU.

Background The aim of this study is to determine whether severe COVID-19 patients harbour a higher risk of ICU-acquired pneumonia. Methods This retrospective multicentre cohort study comprised all consecutive patients admitted to seven ICUs for severe COVID-19 pneumonia during the first COVID-19 surge in France. Inclusion criteria were laboratory-confirmed SARS-CoV-2 infection and requirement for invasive mechanical ventilation for 48 h or more. Control groups were two historical cohorts of mechanically ventilated patients admitted to the ICU for bacterial or non-SARS-CoV-2 viral pneumonia. The outcome of interest was the development of ICU-acquired pneumonia. The determinants of ICU-acquired pneumonia were investigated in a multivariate competing risk analysis. Result One hundred and seventy-six patients with severe SARS-CoV-2 pneumonia admitted to the ICU between March 1st and 30th June of 2020 were included into the study. Historical control groups comprised 435 patients with bacterial pneumonia and 48 ones with viral pneumonia. ICU-acquired pneumonia occurred in 52% of COVID-19 patients, whereas in 26% and 23% of patients with bacterial or viral pneumonia, respectively (p < 0.001). Times from initiation of mechanical ventilation to ICU-acquired pneumonia were similar across the three groups. In multivariate analysis, the risk of ICU-acquired pneumonia remained independently associated with underlying COVID-19 (SHR = 2.18; 95 CI 1.2–3.98, p = 0.011). Conclusion COVID-19 appears an independent risk factor of ICU-acquired pneumonia in mechanically ventilated patients with pneumonia. Whether this is driven by immunomodulatory properties by the SARS-CoV-2 or this is related to particular processes of care remains to be investigated.

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Background CAR-T cell (chimeric antigen receptor T) therapy has emerged as an effective treatment of refractory hematological malignancies. Intensive care management is intrinsic to CAR-T cell therapy. We aim to describe and to assess outcomes in critically ill CAR-T cell recipients. Study design and methods Hospital-wide retrospective study. Consecutive CAR-T cell recipients requiring ICU admission from July 2017 and December 2020 were included. Results 71 patients (median age 60 years [37–68]) were admitted to the ICU 6 days [4–7] after CAR-T cell infusion. Underlying malignancies included diffuse large B cell lymphoma (n = 53, 75%), acute lymphoblastic leukemia (17 patients, 24%) and multiple myeloma (n = 1, 1.45%). Performance status (PS) was 1 [1–2]. Shock was the main reason for ICU admission (n = 40, 48%). Isolated cytokine release syndrome (CRS) was the most common complication (n = 33, 46%), while 21 patients (30%) had microbiologically documented bacterial infection (chiefly catheter-related infection). Immune effector cell-associated neurotoxicity syndrome was reported in 26 (37%) patients. At ICU admission, vasopressors were required in 18 patients (25%) and invasive mechanical ventilation in two. Overall, 49 (69%) and 40 patients (56%) received tocilizumab or steroids, respectively. Determinant of mortality were the reason for ICU admission (disease progression vs. sepsis or CRS (HR 4.02 [95%CI 1.10–14.65]), Performance status (HR 1.97/point [95%CI 1.14–3.41]) and SOFA score (HR 1.16/point [95%CI 1.01–1.33]). Conclusions Meaningful survival could be achieved in up to half the CAR-T cell recipients. The severity of organ dysfunction is a major determinant of death, especially in patients with altered performance status or disease progression.

Purpose of review Immunocompromised patients are notably vulnerable to severe coronavirus disease 2019. This review summarizes COVID-19 features and outcomes in autologous and allogeneic hematopoietic stem cell transplantation (HSCT) recipients. Recent findings Recent findings suggest that HSCT recipients exhibit a high burden of comorbidities and COVID-19 clinical features almost similar to the general COVID population. Furthermore, HSCT recipients exhibit a protracted SARS-CoV-2 shedding, prolonging duration of symptoms and promoting the generation of highly mutated viruses. Last, most of studies report a higher COVID-19 mortality in HSCT recipients, mainly driven by age, comorbidities, time from transplantation, and immunosuppression because of both treatments and underlying hematological malignancy. Summary Further studies are warranted to determine the proper impact of HSCT-related immune disorders on COVID-19 outcomes, and to evaluate specific treatments and vaccination strategy in this high-risk population. Taken together, those findings emphasize the need for more rigorous surveillance and preemptive measures for all HSCT recipients.

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Introduction: Although early identified as a deadly infectious disease, the precise mortality rate of the most severe forms of COVID-19 is a matter of debate. To the best of our knowledge, no study investigated so far, the causes that ultimately led to death as well as the relation between timing and causes of death.Material & Methods: We performed a retrospective study in eight ICU within eight French hospitals. All consecutive adult patients (aged≥ 18 years old) admitted in the ICU with a PCR-confirmed SARS-CoV-2 infection and acute respiratory failure were included in the analysis. Causes and timing of death were reported based on medical records. A binomial logistic regression statistical analysis was performed to identify the determinants associated with ICU-mortality.Results: From March 1st, 2020 to April 28th, 287 patients were admitted to ICU for SARS-CoV-2 related acute respiratory failure. COVID-19 related multiple organ dysfunction syndromes (MODS) was the leading cause of death (29%, n=27/93). End-of-life decisions occurred in 25% of patients (n=23/93). Secondary infections-related MODS accounted for 21% of ICU death, with a majority of ventilator-associated pneumonia. Fatal ischemic events (venous or arterial) occurred in 12% of patients. Refractory hypoxemia was a relatively uncommon cause of death and occurred only in 8 cases (9%). Regarding the timing of death, only one death occurred during the first three days of ICU admission. Determinants associated with ICU-mortality in logistic regression were age >65, requirement for vasopressors, renal replacement therapy and extracorporeal membrane oxygenation.Conclusion: Our data suggest the existence of a specific pattern of outcome in severe COVID-19 patients compared to severe bacterial and viral pneumonia, consisting in a high proportion of delayed COVID-19 related MODS.