Table 4.

Supportive Care Considerations in Patients Who Develop IEC-HS.

Monitoring: Daily monitoring of complete blood cell count with differential, coagulation parameters (PT/PTT) and fibrinogen. Frequent (e.g., daily) evaluation for renal and hepatic dysfunction Assessment for bacterial, viral reactivation or new infection, and fungal disease, in blood, urine, and sputum cultures, +/− sampling of other possible infectious sources (e.g., bronchoscopy, cerebrospinal fluid), Consider testing for HLH diagnostic parameters including soluble CD25, NK-cell function, triglycerides, IFNγ, CXCL9 ratio, CXCL10, IL-10, IL-18
4a. Cytopenias and coagulopathy
Cytopenias	Maintain hemoglobin ≥ 7g/dL148,149 Platelet count ≥ 50 cells × 109/L is recommended in those with active bleeding or coagulopathy Use of romiplostim or eltrombopag is unknown Use of G-CSF to maintain an absolute neutrophil count (ANC) ≥ 500 cells/mm3 remains controversial during periods of active inflammation.133–136 Consult gynecology in female patients with menorrhagia
Coagulopathy	Aggressive management with cryoprecipitate or fibrinogen concentrate is recommended to keep fibrinogen level >100 if no bleeding and >150 if bleeding is present.141 If INR is > 1.5, then vitamin K supplementation should be considered. If INR is > 2, then administration of fresh frozen plasma in addition to cryoprecipitate should be considered. Use of agents for prevention of venous thromboembolism should be used with caution with preference of agents that are easily reversed (i.e., heparin). Consult hematology for patients with refractory or difficult to manage coagulopathy
4b. Infections
Infectious Disease^ Considerations	Immunosuppressive therapy	Associated infection risk	Prophylaxis/preemptive therapy*129,150 and monitoring
	Steroids (e.g., dexamethasone, methylprednisolone)	Fungal infection, viral reactivation, PJP	Mold active antifungal HSV prophylaxis (if seropositive) CMV pre-emptive therapy Consider weekly monitoring for viral reactivation (e.g., CMV)
	IL-1 Receptor Antagonist (anakinra)	No specific infections described with single-agent use. In combination with other agents (e.g., tocilizumab, corticosteroids), risk of infection may be high.105,151,152	Recommend infectious disease consultation to guide optimal management Consider: Mold active antifungal HSV prophylaxis (if seropositive) CMV pre-emptive therapy Consider weekly monitoring for viral reactivation (e.g., CMV) Recommendations will depend upon the adjunctive agents used in combination with anakinra
	IL-6 Receptor Antagonist (tocilizumab)	Tuberculosis, invasive fungal, bacterial, viral, protozoal	Mold active antifungal HSV prophylaxis (if seropositive) CMV pre-emptive therapy153 Consider bacterial prophylaxis during neutropenia
	JAK 1 / 2 Inhibitors (ruxolitinib)	Tuberculosis, herpes zoster, esophageal candidiasis, PJP, CMV, cryptococcal infections	Fungal prophylaxis154 PJP prophylaxis VZV prophylaxis (if seropositive) CMV pre-emptive therapy
	Chemotherapy (etoposide)	Bacterial infections with neutropenia	Consider bacterial prophylaxis during neutropenia

HSV: herpes simplex virus, CMV: cytomegalovirus, VZV: varicella zoster virus PJP: pneumocystis jiroveci pneumonia

^*Agents used for anti-infective prophylaxis: mold active antifungals include voriconazole, posaconazole, isavuconazole; antivirals for HSV and VZV prophylaxis include acyclovir and valacyclovir; antivirals for CMV pre-emptive therapy include ganciclovir, valganciclovir and foscarnet; agents for PJP prophylaxis include TMP-SMX, atovaquone, pentamidine; antibacterial prophylaxis with levofloxacin is recommended.

^{^}This is not intended to be an exhaustive list, and management decisions should be made in consultation with an Infectious Diseases specialist.