In a recent article in Haematologica, Zhang and colleagues highlighted
the efficacy and safety of ruxolitinib and the possibility of
ruxolitinib-based front-line therapy in pediatric patients with
secondary hemophagocytic lymphohistiocytosis (HLH)1.
The rapid recovery of clinical manifestations and normalization of
clinical laboratory indexes demonstrated that ruxolitinib could serve as
a potential front-line treatment option for secondary HLH in children,
consequently reducing the toxicity compared to intense chemotherapy.
Although HLH-1994/2004 regimen has been recommended to the treatment of
HLH in recent decades, there are still some patients who do not respond
well or have intolerable side effects from conventional
chemotherapies2, 3. To date, there are many case
reports about the experiences of utilizing Janus kinase (JAK) 1/2
inhibitor, ruxolitinib, in the treatment of HLH4, 5.
However, most of these cases involved adults, and few cases have been
reported about the use of ruxolitinib in pediatric patients with HLH.
The study firstly enrolled 12 children with HLH, and evaluated the
safety and efficacy of ruxolitinib in pediatric patients. They found
that the overall response rate of ruxolitinib was 83.3%, with 66.7% in
complete response (CR). More importantly, no serious adverse effects
were observed in this study, except for some grade 1-2 gastrointestinal
adverse events (gastritis, nausea, and loss of appetite) in two
patients. They also brought up a new idea that clinicians could attempt
to utilize ruxolitinib first for approximately 3 days to determine the
treatment response and sort applicable patients to avoid chemotherapy as
possible. And they found that those patients who poorly responded to
ruxolitinib after 3-7 days of treatment all responded well to the
subsequent HLH-1994 protocol. HLH-1994/2004 regimen and ruxolitinib can
be two complementary front-line therapy strategies, and further studies
are warranted to testify this idea and sort the specific HLH group
sensitive to ruxolitinib to guide effective treatment in the future.
Epstein-Barr virus (EBV)-associated HLH accounts for approximately 60%
of all pediatric HLH patients in China, and most of those patients have
a poor response to the standard treatment of HLH-1994/2004 and have a
poor prognosis6. Moreover, current ongoing clinical
trials studying the use of ruxolitinib in HLH patients have not yet
enrolled the patients with (EBV)-associated HLH. The study enrolled 8
pediatric patients with HLH and found that the response rate of
EBV-associated HLH patients was 100% and the CR rate was 75%, and EBV
DNA load in plasma of all EBV-associated HLH patients decreased
dramatically within one week. All of above suggested the great
possibility of ruxolitinib for treating EBV-associated HLH, though the
sample size was too small.
To truly improve the clinical treatment outcome for HLH in children,
further trials will require a large cohort size, coherent eligibility
criteria and dosing schedules to evaluate the safety and efficacy of
ruxolitinib in treating HLH in children patients, especially
EBV-associated HLH. Nonetheless, this reported pilot study made a major
progress in managing HLH in children patients without traditional
chemotherapy.
Conflict of Interest
statement: The authors declared that they have no conflicts of interest
to this work.
Acknowledgements: This work
is supported by the National Natural Science Foundation of China (No.
31701207).
References:
1. Zhang Q, Wei A, Ma HH, Zhang L, Lian HY, Wang D, et al. A pilot study
of ruxolitinib as a front-line therapy for 12 children with secondary
hemophagocytic lymphohistiocytosis. Haematologica. 2020 Jul 30. doi:
10.3324/haematol.2020.253781. [Epub ahead of print]
2. Trottestam H, Horne A, Aricò M, Egeler RM, Filipovich AH, Gadner H,
et al. Chemoimmunotherapy for hemophagocytic lymphohistiocytosis:
long-term results of the HLH-94 treatment protocol. Blood.
2011;118(17):4577-84.
3. Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, et
al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic
lymphohistiocytosis. Pediatric blood & cancer. 2007;48(2):124-31.
4. Ahmed A, Merrill SA, Alsawah F, Bockenstedt P, Campagnaro E, Devata
S, et al. Ruxolitinib in adult patients with secondary haemophagocytic
lymphohistiocytosis: an open-label, single-centre, pilot trial. The
Lancet Haematology. 2019;6(12):e630-e7.
5. Wang J, Wang Y, Wu L, Wang X, Jin Z, Gao Z, et al. Ruxolitinib for
refractory/relapsed hemophagocytic lymphohistiocytosis. Haematologica.
2020;105(5):e210-e2.
6. Wang J, Wang Y, Wu L, Zhang J, Lai W, Wang Z. PEG-aspargase and DEP
regimen combination therapy for refractory Epstein-Barr virus-associated
hemophagocytic lymphohistiocytosis. Journal of hematology & oncology.
2016;9(1):84.