RESUMO
Allogeneic hematopoietic stem cell transplantation (HSCT) and coronavirus disease 2019 (COVID-19) infection can both lead to severe cytokine release syndrome (sCRS) resulting in critical illness and death. In this single institution, preliminary comparative case-series study we compared clinical and laboratory co-variates as well as response to tocilizumab (TCZ)-based therapy of 15 allogeneic-HSCT- and 17 COVID-19-associated sCRS patients. Reaction to a TCZ plus posttransplant cyclophosphamide (PTCY) consolidation therapy in the allogeneic-HSCT-associated sCRS group yielded significantly inferior long-term outcome as compared to TCZ-based therapy in the COVID-19-associated group (P = 0.003). We report that a TCZ followed by consolidation therapy with a Janus kinase/signal transducer and activator of transcription (JAK/STAT) inhibitor given to 4 out of 8 critically ill COVID-19 patients resulted in their complete recovery. Non-selective JAK/STAT inhibitors influencing the action of several cytokines exhibit a broader effect than TCZ alone in calming down sCRS. Serum levels of cytokines and chemokines show similar changes in allogeneic-HSCT- and COVID-19-associated sCRS with marked elevation of interleukin-6 (IL-6), regulated upon activation normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein-1 (MCP-1) and interferon γ-induced protein 10 kDa (IP-10) levels. In addition, levels of IL-5, IL-10, IL-15 were also elevated in allogeneic-HSCT-associated sCRS. Our multi-cytokine expression data indicate that the pathophysiology of allogeneic-HSCT and COVID-19-associated sCRS are similar therefore the same clinical grading system and TCZ-based treatment approaches can be applied. TCZ with JAK/STAT inhibitor consolidation therapy might be highly effective in COVID-19 sCRS patients.
RESUMO
Introduction: Autologous hemopoietic stem cell transplantation remains a promising therapy in certain malignant and non-malignant conditions. The procedure, however, will increase the risk of complications, most notably early and late infections. Aim: To analyze the frequency and spectrum of pathogens in early (<+100 days) post-transplant infections and to evaluate risk factors for mortality. Method: Prospectively collected data from 699 patients undergoing autologous hemopoietic stem cell transplantation between 2007 and 2014 at our center were retrospectively reviewed and analyzed. Results: The median age of 699 patients was 56 (interquartile range: 43-62) years, 54% (376) were male. 25 patients have been transferred to other centers and 19 patients were lost to follow up. Neutropenic fever occurred in 69.8% (488) of patients. In addition, 102 infectious episodes in 96 patients were identified. Most commonly bacteremia occurred (49 episodes) with a median onset of 7 (5-11) days. The majority (33/49) of bacteremias have been observed during the pre-engraftment period. Their incidence proved to be higher in patients with malignant lymphoma compared to individuals with plasma cell disorders (p = 0.0005, OR: 2.41, 95% CI: 1.49-3.99). 12 episodes of viral infections and 8 cases of proven or probable invasive mycoses have been identified. Among the 655 patients with complete follow up, 16 in-hospital deaths (2.4%) occurred, 8 of them were associated with infections. Survival was adversely affected by early infections (p = 0.0001). Conclusion: In autologous stem cell transplantation, microbiologically unconfirmed neutropenic fever is common. Documented early bacteremia, however, is infrequent. Lymphoma patients have a significantly higher chance to develop bloodstream infections compared to individuals with plasma cell disorders. Early infections decrease the chance of survival; thus, an effective prophylaxis and therapy remains of paramount importance. Orv Hetil. 2020; 161(3): 103-109.
