Early administration of cyclosporine may reduce the incidence of cytokine release syndrome after HLA-haploidentical hematopoietic stem-cell transplantation with post-transplant cyclophosphamide

2021 ◽  
Vol 100 (5) ◽  
pp. 1295-1301
Author(s):  
Naoki Kurita ◽  
Tatsuhiro Sakamoto ◽  
Takayasu Kato ◽  
Manabu Kusakabe ◽  
Yasuhisa Yokoyama ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Early Administration ◽  
Hematopoietic Stem ◽  
Post Transplant

scholarly journals Common points of therapeutic intervention in COVID-19 and in allogeneic hematopoietic stem cell transplantation associated severe cytokine release syndrome

2021 ◽  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Consolidation Therapy ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct

AbstractAllogeneic 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.

scholarly journals 574. De-escalation of Broad Spectrum Antibiotics during Cytokine Release Syndrome with Haploidentical Hematopoietic Stem Cell Transplantation

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S352-S352
Author(s):  
Molly Schiffer ◽  
Sarah Perreault ◽  
Dayna McManus ◽  
Francine Foss ◽  
Lohith Gowda ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Broad Spectrum ◽  
Antibacterial Prophylaxis ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Hematopoietic Stem

Abstract Background Fever is a common component of cytokine release syndrome (CRS) occurring in 90% of patients undergoing haploidentical hematopoietic stem cell transplantation (Haplo-HSCT). Fevers typically occur between the stem cell infusion (Day 0) and initiation of post-transplant cyclophosphamide and are often confused with febrile neutropenia (FN). Due to longer time to engraftment in Haplo-HSCT, CRS/FN exposes patients to prolonged courses of empiric broad spectrum antibiotic (BSA) therapy increasing the risk for multi-drug resistant organisms. Recently, at Yale New Haven Health, our practice has changed to now recommend antibiotic de-escalation to prophylaxis after 7 days of BSA if no infection is identified. The objective of this study was to assess the incidence of breakthrough infections with the de-escalation of BSA in CRS/FN. Secondary endpoints include rate of FN, rate of de-escalation, rate of recurrent fevers, duration of BSA, and positive blood culture data. Methods The patient population included those undergoing Haplo-HSCT between July 2016 and February 2020 and who developed CRS/FN between Day 0 and Day +5. Patients were excluded if they had prolonged hospitalization due to non-infectious complications or engraftment failure. Bacteremia was defined using NHSN definitions. Results Of the 53 Haplo-HSCTs assessed, 43 experienced CRS/FN. Thirty-five Haplo-HSCT (81%) with CRS/FN had negative cultures and 23 (66%) of these were de-escalated back to antibacterial prophylaxis. The median duration of BSA in the de-escalated group was 7 days (range 5–13) compared to 16.5 days range (13–21) in the non-de-escalated group (p< 0.001). Among those de-escalated, 7 (30%) had recurrent fever occurring at a median of 4 days (range 2–14) and were placed back on BSA. Two Haplo-HSCT (9%) that had fever after de-escalation developed a breakthrough bacteremia. No Haplo-HSCT after de-escalation had fever or re-admission for bacteremia 30 days after engraftment. Four Haplo-HSCT (9%) with CRS/FN had positive blood cultures; however, three (7%) were still able to be de-escalated from BSA to narrower agents based on susceptibilities. Conclusion De-escalation of BSA in FN/CRS in Haplo-HSCT patients reduced unnecessary, prolonged antibiotic exposure with a low incidence of breakthrough infections. Disclosures All Authors: No reported disclosures

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