Ruxolitinib for hematopoietic cell transplantation-associated hemophagocytic lymphohistiocytosis

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a severe complication after allogeneic hematopoietic cell transplantation (HCT) and can cause graft failure or multi-organ failure. Here, we report two children with refractory HCT-associated HLH treated with ruxolitinib. In the first patient, ruxolitinib resolved fever, cytopenia and hyperferritinemia. In another patient, although severe hepatic failure, which developed and worsened before the administration of ruxolitinib, was irreversible, rapid improvement in fever, leukopenia and hyperferritinemia was observed. Of note, multiplex cytokine profiling showed amelioration of cytokine storm in both patients. Ruxolitinib may be an encouraging option for HCT-associated HLH.

Successful ruxolitinib administration for a patient with steroid‐refractory idiopathic pneumonia syndrome following hematopoietic stem cell transplantation: A case report and literature review

“…4 In the clinical setting, ruxolitinib potentially inhibited JAK/STAT pathway-derived cytokines, including IL-6, IFN-gamma, and several others associated with refractory GVHD, primary or secondary HLH, IPF, and COVID-19-related acute respiratory distress syndrome. 4,12,[19][20][21][22][23] Remarkable reductions in ferritin and sIL-2R were observed in our patient, resembling the reported response pattern for secondary HLH. 21,23 KL-6 and SP-D were useful markers for tracking the patient's disease status.…”

“…4,12,[19][20][21][22][23] Remarkable reductions in ferritin and sIL-2R were observed in our patient, resembling the reported response pattern for secondary HLH. 21,23 KL-6 and SP-D were useful markers for tracking the patient's disease status.…”

Ruxolitinib as Adjunctive Therapy for Hemophagocytic LymPhohistiocytosis after Liver Transplantation: A Case Report and Literature Review

“…The patient’s fever subsided within 24 h of initiating ruxolitinib, and recovery was achieved without other treatments [ 14 ]. Ono successfully used ruxolitinib in a pediatric patient who developed HLH after hematopoietic cell transplantation [ 15 ].…”

“…Hence, we considered that the patient was unresponsive to the HLH-2004 treatment protocol. In addition, a pilot study reported ruxolitinib as a first-line treatment for adult secondary HLH [ 6 ], and case reports described the use of ruxolitinib as a first-line therapy to treat Hematopoietic Cell Transplantation-associated HLH [ 10 , 11 , 15 ]. Moreover, some clinicians argued that ruxolitinib may exert a synergistic effect with HLH-2004 treatment [ 55 ].…”

“…It is mainly used in the hematological field and also in COVID-19 patients [ 5 ]. There are case reports and pilot studies using ruxolitinib as a salvage therapy or first-line treatment for HLH patients showing good efficacy and safety [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. However, it has never been used for post-transplant patients with HLH.…”