Short-term effectiveness of ruxolitinib in the treatment of recurrent or refractory hemophagocytic lymphohistiocytosis in children

Int J Hematol. 2020 Oct;112(4):568-576. doi: 10.1007/s12185-020-02936-4. Epub 2020 Jul 14.

Abstract

To investigate the efficacy and safety of the Janus kinase inhibitor ruxolitinib in the treatment of recurrent or refractory hemophagocytic lymphohistiocytosis (HLH) in children. We performed a retrospective analysis of ruxolitinib in children with recurrent or refractory HLH in Beijing Children's Hospital. All patients were treated firstly with HLH-94 protocol. Patients received oral ruxolitinib on a continuous 28-day cycle or until disease progression or unacceptable toxicity. The median age of enrolled patients was 1.7 years (range 9 months-5.0 years). The median time from the beginning of first-line treatment to the initiation of ruxolitinib was 3 (2-6) weeks. The median follow-up time was 14 months (1 week-24 months). Five children were diagnosed with EBV-related HLH, two with familial HLH, one with autoinflammatory disease-related HLH, and the other with unclear etiology. After the first-line treatment, seven patients had no remission (NR). The other two patients relapsed within 2-4 weeks after complete remission (CR). After oral administration of ruxolitinib, all patients' body temperatures decreased to the normal range within 48 h. At 1 week of receiving ruxolitinib, three patients (33.3%) achieved partial remission (PR). Five patients (55.6%) improved but did not achieve PR. One patient (11.1%) died. Compared with other causes of HLH, children with refractory or recurrent EBV-HLH had a poor response to ruxolitinib alone (Fisher's exact test, P = 0.048). Until the last follow-up, the three patients who achieved CR survived without recurrence. For children with recurrent or refractory HLH, ruxolitinib is a tolerable salvage therapy. Although some children could not achieve CR after one week of treatment, combination with chemotherapy could gain time for further treatment or bone marrow transplantation.

Keywords: Hemophagocytic lymphohistiocytosis; JAK-STAT pathway; Ruxolitinib; Treatment.

MeSH terms

  • Administration, Oral
  • Age Factors
  • Autoimmunity
  • Child
  • Child, Preschool
  • Epstein-Barr Virus Infections / complications
  • Female
  • Follow-Up Studies
  • Humans
  • Lymphohistiocytosis, Hemophagocytic / etiology
  • Lymphohistiocytosis, Hemophagocytic / genetics
  • Lymphohistiocytosis, Hemophagocytic / therapy*
  • Male
  • Nitriles
  • Pyrazoles / administration & dosage*
  • Pyrimidines
  • Recurrence
  • Remission Induction
  • Retrospective Studies
  • Salvage Therapy
  • Time Factors
  • Treatment Outcome

Substances

  • Nitriles
  • Pyrazoles
  • Pyrimidines
  • ruxolitinib