Skip to main content
Erschienen in: Journal of Medical Case Reports 1/2023

Open Access 01.12.2023 | Case report

Successful use of emapalumab in refractory hemophagocytic lymphohistiocytosis in a child with Chédiak–Higashi syndrome: a case report

verfasst von: Ali AlAhmari, Haitham Khogeer

Erschienen in: Journal of Medical Case Reports | Ausgabe 1/2023

Abstract

Background

Hemophagocytic lymphohistiocytosis is a life-threatening disease heralded by fever, cytopenia, hepatosplenomegaly, and multisystem organ failure. Its association with genetic mutations, infections, autoimmune disorders, and malignancies is widely reported.

Case presentation

A 3-year-old male Arab Saudi patient with insignificant past medical history and parental consanguinity presented with abdominal distension of moderate severity and persistent fever despite receiving antibiotics. This was accompanied by hepatosplenomegaly and silvery hair. The clinical and biochemical profiles were suggestive of Chédiak–Higashi syndrome with hemophagocytic lymphohistiocytosis. The patient received the hemophagocytic lymphohistiocytosis-2004 chemotherapy protocol and had multiple hospital admissions mainly due to infections and febrile neutropenia. After achieving the initial remission, the patient’s disease reactivated and did not respond to reinduction with the hemophagocytic lymphohistiocytosis-2004 protocol. Due to the disease reactivation and intolerance of conventional therapy, the patient commenced emapalumab. The patient was successfully salvaged and underwent an uneventful hematopoietic stem cell transplantation.

Conclusions

Novel agents such as emapalumab can be helpful for the management of refractory, recurrent, or progressive disease, while avoiding the toxicities of conventional therapy. Due to a paucity of available data on emapalumab, additional data are needed to establish its role in hemophagocytic lymphohistiocytosis treatment.
Hinweise

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Abkürzungen
Ab
Antibody
ALT
Alanine aminotransferase
AST
Aspartate transaminase
BM
Bone marrow
CHS
Chédiak–Higashi syndrome
CMV
Cytomegalovirus
CNS
Central nervous system
CSA
Cyclosporin A
D100
Day 100
EBV
Epstein–Barr virus
FK506
Tacrolimus
GCSF
Granulocyte colony-stimulating factor
GVHD
Graft-versus-host disease
Hb
Hemoglobin
HLA
Human leukocyte antigen
HLH
Hemophagocytic lymphohistiocytosis
HSC
Hematopoietic stem cell
HSCT
Hematopoietic stem cell transplantation
IVIG
Intravenous immune globulin
LDH
Lactate dehydrogenase
MTX
Methotrexate
PT
Prothrombin time
PTT
Partial thromboplastin time
TNC
Total nucleated cell
VOD
Veno-occlusive disease
VP16
Etoposide
WBC
White blood cell

Background

Chédiak–Higashi syndrome (CHS) is a rare autosomal recessive disorder associated with frequent infections and bleeding, oculocutaneous albinism, neurological disorders, and high risk of hemophagocytic lymphohistiocytosis (HLH) [1, 2]. HLH is a hyperinflammatory condition characterizing the “accelerated phase” of CHS and the primary cause of death in CHS patients [2]. The self-perpetuating loop of T cell, natural killer (NK) cell, and macrophage overactivation characteristic of HLH can lead to a cytokine storm, with high mortality if left untreated [3]. HLH can be familial with a clear genetic component (primary HLH), or can be an acquired disorder due to other conditions such as infections and malignancy (secondary HLH) [4]. HLH is primarily complicated by delays in diagnosis and treatment, predominately due to its nonspecific symptoms (fever, cytopenia, hepatosplenomegaly, and multisystem organ failure), and inadequate access to necessary specific laboratory and genetic testing [3, 5].
Allogeneic hematopoietic stem cell transplantation (HSCT) after disease remission is the only potentially curative treatment for both CHS and HLH [6, 7]. The mainstay of HLH treatment remains the combination of immunosuppression, chemotherapy, and biologics targeting the suppression of the cytokine storm and the elimination of overactivated immune cell populations. Coupling dexamethasone and etoposide is a commonly used approach to treat HLH based on the Histiocyte Society HLH-1994 and HLH-2004 recommendations [8]. However, more targeted treatment approaches are essential and are being considered in light of the poor tolerability of conventional therapy and the poor prognosis of relapsed/refractory HLH. Emapalumab is a monoclonal antibody targeted against interferon gamma, with proven efficacy for the treatment of HLH [9], approved for use in both adults and children with relapsed, refractory or progressive disease, or in cases where conventional therapy cannot be used [10]. That being said, experience with emapalumab remains limited and its use is mainly reserved for the second-line setting [11]. As additional data are needed to establish the role of emapalumab in front-line disease management, we present the case of CHS with relapsing HLH, treated with emapalumab prior to successful HSCT. This case could help guide physicians’ decision-making process while treating a challenging case of HLH.

Case presentation

A 3-year-old Arab Saudi boy was referred to our hospital with a history of recurrent fever which had persisted for ~ 3 months despite receiving antibiotics. The patient had abdominal distension of moderate severity, accompanied by hepatosplenomegaly and silvery hair. Past medical history was insignificant. The patient was born as a full term baby through a normal vaginal delivery without any complications in the neonatal period. Family history was significant for parental consanguinity as the parents are first cousins. Patient has one sibling who is alive and well, with no history of any inherited disorders from the family. There is no history of any allergy and vaccination history is appropriate for patient’s age. Developmentally, all age-appropriate milestones were achieved. Father earns a good income and socioeconomic status is fair.
On arrival to the hospital, the patient had a temperature of 36.2 °C. Other vital signs were normal with a peripheral pulse rate of 109 beats per minute, blood pressure of 107/73 mmHg, respiratory rate of 28 breaths per minute, and oxygen saturation of 100% at room air.
On examination, the patient had an average build with fair skin and silvery hair. Anthropometric measurements were normal with a height of 88 cm, weight of 12 kg, and a body mass index of 16.5 kg/m2. Respiratory system examination was normal with bilateral air entry and equal breath sounds. In the cardiovascular system, patient was found to have normal peripheral perfusion and S1 and S2, with no murmur or other abnormality. Patient was neurologically intact with a Glasgow Coma Scale of 15/15, with normal sensory and motor function. No focal defects were detected. In the gastrointestinal examination, abdomen was distended but nontender. There was a massive hepatosplenomegaly with liver 10 cm below the right costal margin and spleen 15 cm below the left costal margin when palpated. Bowel sounds were normal.
His initial laboratory tests at presentation revealed: white blood cells (WBC) 4.39 × 109/L, platelets 23 × 109/L, hemoglobin (Hb) 96 g/L, total bilirubin 21.9 µmol/L, alanine aminotransferase (ALT) 84 U/L, aspartate transaminase (AST) 277 U/L, lactate dehydrogenase (LDH) 459 U/L, prothrombin time (PT) 13.8 seconds, partial thromboplastin time (PTT) 56.3 seconds, triglyceride 6.48 mmol/L, ferritin 894 µg/L, and soluble CD25 5000 pg/mL (for full laboratory results, see Table 1).
Table 1
Laboratory findings on admission
Parameter
Status
CBC
White blood cells
4.39 × 109
Red blood cells
3.92 × 1012
Hemoglobin
96 g/L
Hematocrit
0.287 L/L
Platelet
23 × 109/L
Polymorph
7%
Lymphocytes
75%
Monocytes
15%
Liver function test
Total bilirubin
21.9 µmol/L
Direct bilirubin
4 µmol/L
Lactate dehydrogenase
459 U/L
Alanine aminotransferase
84 U/L
Aspartate aminotransferase
277 U/L
Renal function test
Blood urea nitrogen
3.3 mmol/L
Creatinine blood
20 µmol/L
Urinalysis
Glucose
Negative
Protein
Negative
Bilirubin
Negative
Urobilinogen
Negative
 pH
7.5
Ketone
Negative
Blood
Negative
Nitrite
Negative
Leukocytes
Negative
Specific gravity
1.005
Serology
Hepatitis A IgM antibody
Nonreactive
Hepatitis A total antibody
Reactive
Hepatitis B surface antigen
Nonreactive
CMV
Seropositive
EBV
500 IU/mL
Microbiology
Blood culture
Negative
Fungal culture
Negative
PCR
Negative
Chemistry
Ferritin
195 µg/L
Fibrinogen
113 mg/dL
Triglyceride
6.48 mmol/L
Prothrombin time
14.7 seconds
Partial thromboplastin time
44.8 seconds
Potassium
3.9 mmol/L
Sodium
137 mmol/L
Blood glucose random
5.6 mmol/L
Hemoglobin electrophoresis
Normal
Coagulation profile
Normal
CBC complete blood count, CMV cytomegalovirus, EBV Epstein–Barr virus, PCR polymerase chain reaction
Hair microscopy revealed hypopigmented hair shafts with pigment clumps, and magnetic resonance imaging findings showed diffuse brain parenchymal volume loss with cerebral white matter disease (Fig. 1). Peripheral blood smear showed giant granules in the cytoplasm neutrophils (Fig. 2). Bone marrow biopsy showed normocellular marrow with 100% cellularity, adequate megakaryocytes, and erythropoiesis. Granulopoieses was adequate with increased lymphocytes and histiocytes. Central nervous system (CNS) involvement, and silvery hair results, were also suggestive of CHS with HLH. Molecular study revealed bi-allelic mutation of the LYST gene consistent with CHS.
Treatment history is presented in Table 2. The patient was initially treated on 6 June 2019 with dexamethasone (10 mg/m2/day) and intravenous Ig only due to parent refusal of chemotherapy with good initial response resulting in tapering the dose of dexamethasone. However, the patient experienced a disease reactivation that necessitated starting the HLH-2004 on 1 November 2019. Thereafter, the patient experienced multiple disease reactivations associated with febrile neutropenia and infections, requiring several hospital admissions in less than 1 year. On 25 February 2020, the patient was treated with reinduction of HLH-2004 protocol. On 18 April 2020, the patient was admitted for disease reactivation and cytomegalovirus (CMV) infection. The patient was treated again with reinduction of the HLH-2004 chemotherapy protocol and ganciclovir. After achieving the initial remission, patient’s disease reactivated and did not respond to the reinduction with HLH-2004 protocol, with increasing risks of drug toxicities. As a result, the patient received emapalumab from 27 July until 13 August 2020 (six doses, one dose every 3 days) and achieved remission without any significant adverse effects. Reported side effects included erythematous rash over the right forearm, anterior, and posterior thigh after the first dose of emapalumab. There was no further history of rashes, fever, or diarrhea. Treatment with emapalumab was followed by a successful HSCT on 7 September 2020 from a human leukocyte antigen (HLA) identical male sibling. Graft-versus-host disease (GVHD) prophylaxis was given with methotrexate and tacrolimus. Patient received myeloablative conditioning in the form of fludarabine and treosulfan. Pentamidine was used for pneumocystis pneumonia (PCP) prophylaxis. Follow-up at day 100 after transplant showed that the patient recovered the absolute neutrophil count (ANC) on 28 September 2020 (21st day), and platelets were recovered on 1 October 2020 (24th day). Patient developed, hypertension and cytomegalovirus infection, bacterial infection, as well as the fungal infection, which were treated successfully. Granulocyte colony-stimulating factor (GCSF) was used to maintain the ANC > 1000. There was no GVHD, mucositis, veno-occlusive disease, hemorrhagic cystitis, or thrombotic microangiopathic anemia reported during the first 100 days, post-transplant. The patient got engrafted with a picture of mixed chimerism. The patient continued to be in remission and engrafted at 6 months follow-up. GCSF was continued due to persistent neutropenia. Adrenal insufficiency and renal impairment were treated successfully. CMV viremia resolved.
Table 2
Routes of administration, duration of treatment, and doses of all medications that were given during hospital stay and follow-up
Medication
Route
Dose
Duration
Dexamethasone
Intravenous
10 mg/m2/day
Started on 6 June 2019, stopped on 29 November 2019
Restarted on 9 January 2020, stopped on 4 October 2020
Immunoglobulin
Intravenous
7.5 g
Started on 6 June 2019, stopped on 8 November 2020
FK506 (tacrolimus)
Oral
0.5 mg daily
Started on 3 March 2020, stopped on 30 October 2020
Cyclosporine
Oral
30 mg BID
Started on 26 November 2019, stopped on 2 March 2020
Etoposide
Intravenous
90 mg
Started on 26 October 2019, stopped on 6 May 2020
Emapalumab
Intravenous
50 mg
Started on 27 July 2020, stopped on 13 August 2020
Filgrastim
Intravenous
80 µg
Started on 23 October 2019, stopped 15 December 2019
Ganciclovir
Intravenous
75 mg
Started on 17 March 2020, stopped on 2 June 2020
Conditioning medications
 Treosulfan
Intravenous
10 g daily
Started on day -5 (2 September 2020), stopped on day -3 (4 September 2020)
 Fludarabine
Intravenous
30 mg daily
Started on day 6- (1 September 2020), stopped on day -2 (5 September 2020)
Prophylaxis
GVHD prophylaxis
Methotrexate
Intravenous
7.5 mg on days 1, 3, and 6
Started on 8 September 2020, stopped on 13 September 2020
Leucovorin
Intravenous
7.5 mg days 2, 4, and 7
Started on 9 September 2020, stopped on 16 September 2020
FK506 (tacrolimus)
Oral/NGT
0.5 mg daily
Started on day 3 (4 September 2020), stopped on 4 January 2021
Antiviral prophylaxis
Acyclovir
Intravenous
315 mg TID daily
Started on day 3 (4 September 2020), stopped on 9 September 2020
Antifungal prophylaxis
Fluconazole
Oral
100 mg daily
Stared on 17 September 2020, stopped on 30 December 2020
PCP prophylaxis
 Pentamidine
Intravenous
70 mg (once every 4 weeks
Started on day 3 (4 September 2020), stopped on 5 July 2021
Others
Ursodiol
Oral
150 mg, BID
Started on 30 August 2020, stopped on 30 December 2020
BID twice daily, GVHD graft-versus-host-disease, PCP pneumocystis pneumonia, TID three times daily
The patient continued to have a mixed chimerism at 6 months. Evolution of lymphoid and myeloid donor cells chimerism was as follows (respectively): 82% and 76% on 2 November 2020, 82% and 47% on 30 November 2020, 88% and 40% on 4 January 2021, 86% and 27% on 1 February 2021.

Discussion and conclusions

The presented case is that of a 3-year-old Arab Saudi male patient presenting with clinical evidence suggestive of Chédiak–Higashi syndrome with HLH. The patient had refractory recurrent disease; disease reactivation occurred after the first remission, with failure to respond to reinduction with the HLH-2004 protocol. Due to disease reactivations and intolerance of conventional therapy, the patient commenced emapalumab. The patient was successfully salvaged and underwent uneventful hematopoietic stem cell transplant. This case illustrates that alternative treatment options, such as emapalumab can lead to remission in a challenging clinical scenario of frequently relapsing disease, with no major toxicity, thus allowing the conduction of the only potentially curative treatment for HLH and Chédiak–Higashi syndrome.
HLH is a very common clinical manifestation of primary immunodeficiencies, such as CHS, and a major driver of mortality rates in young patients [12, 13].
Genetic mutations are implicated in both CHS and HLH. Consanguinity rates remain high in Saudi Arabia, where familial history of HLH is also relatively common [14]. Establishing the genetic profile of HLH and the prevalent mutations in local populations is important to improve early diagnosis and treatment. STXBP2 and STX11 gene mutations were previously reported to be the two most predominant mutations in Saudi patients with HLH [15]. Our findings fit the spectrum of pathogenic variants reported for nonfamilial HLH in Saudi Arabia, where pathogenic variants of the LYST gene (some of which were novel mutations) were detected in 5.8% of all mutant patients [15]. These novel homozygous LYST gene mutations consequently confirmed the diagnosis of CHS [15].
In addition to CNS involvement, concurrent infections (viral or bacterial infections) seem to be intimately related to HLH [12, 13, 16]. Viral infections such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Epstein–Barr virus (EBV), and CMV have been reported to trigger HLH in infants and children, with or without primary immunodeficiencies [17, 18]. Several bacterial (Klebsiella), fungal (Candida), and viral (EBV, CMV) infections were observed over the course of the presented patient’s management. CMV infection was evident upon disease reactivation in the presented case, prompting the use of the HLH-2004 protocol along with ganciclovir. One study suggests that disease remission could be more likely in infection-associated HLH, while EBV-related disease leads to a higher risk of relapse [19]. Long-term outcomes of the HLH-2004 study showed improved 5-year survival rates compared with the HLH-94 protocol. The HLH-2004 protocol actually ensured up to 71% 5-year survival in children without family history or genetically verified disease [20].
That being said, the use of the HLH-2004 protocol does not always yield the desired clinical response, with patients experiencing partial response, disease recurrence, and death [19, 21, 22]. Our patient ultimately did not respond to reinduction with the HLH-2004 protocol. Alternative options were therefore needed to achieve disease remission and bridge to HSCT, particularly considering the increasing toxicity risk of previous therapy.
It is known that patients with HLH still experience major toxicities and unfavorable outcomes remain common despite major advances in treatment modalities. As previously mentioned, allogeneic HSCT after disease remission is the only potentially curative treatment for both CHS and HLH [6, 7]. However, access to HSCT could be limited in developing countries, with few patients undergoing transplantation [23]. Previous experience from King Faisal Specialist Hospital showed 40% survival after full match HSCT of Saudi CHS patients [24]. In a cohort of Saudi patients with HLH, HSCT greatly improved 5-year overall survival rates to reach at least 66.5% of patients [15]. Conditioning regimens could play an important role in preventing graft failure and improving clinical outcomes and survival after HSCT [25]. Early reports of the use of etoposide in local CHS patients undergoing HSCT at King Faisal Specialist Hospital were positive in terms of management of the accelerated phase, but not conditioning before HSCT [26].
Globally, emapalumab is increasingly being considered as bridge therapy to curative HSCT, and as a way to improve survival and clinical outcomes after transplantation [27]. This was reflected in our case, where treatment with emapalumab led to remission in a frequently relapsing disease with no major toxicity, thus allowing a successful HSCT. Available evidence supports the use of emapalumab for the treatment of severe refractory HLH, due to its efficacy, safety, and tolerability, and the absence of effect on control of concurrent viral and other infections [9, 28, 29]. The use of emapalumab has been suggested for EBV-related HLH to reduce the risk of secondary malignancy due to etoposide [18]. Regardless, clinicians should be aware of the potential drawbacks of inducing severe immunosuppression, and the consequent inhibition of the febrile response to infection, with the use of emapalumab in combination with other immunomodulatory agents such as dexamethasone and etoposide [30].
Despite our center being one of the biggest HLH centers in the world, various challenges are still faced in the treatment of HLH, particularly patients with refractory disease and disease reactivation. In this case, emapalumab proved to be effective in achieving disease remission, without any major complications, in less than a month. It also decreased the patient’s readmission requirements and hospital length of stay, all of which were of major concern in this case. That being said, one limitation of this case could be the absence of any substantial data to support the use of emapalumab at our center, which in turn emphasizes the need for more studies to endorse emapalumab use in local HLH populations.
Even with the advancements made in HLH treatment, significant unfavorable outcomes and toxicities remain common. Treatment-refractory and relapsing disease remains especially challenging. The presented case provides support to the notion that novel agents such as emapalumab can be helpful for the management of refractory, recurrent, or progressive disease, and clinical scenarios where treatment options become limited by the toxicities of conventional therapy. While emapalumab seems to be promising in the management of challenging HLH cases, more insights and robust studies are needed to explore its role in first-line disease treatment.

Acknowledgements

The author thanks the patient and their family for accepting the publication of the case. The authors would also like to thank Nancy Al Akkary, MSc, BSc from Phoenix Clinical Research for editorial and medical writing assistance for the preparation of this manuscript.

Declarations

Informed consent was obtained from the legal representative of the patient for the publication of the present case report.
Written informed consent was obtained from the patient's legal guardian for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare that they have no competing interests.
Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://​creativecommons.​org/​licenses/​by/​4.​0/​. The Creative Commons Public Domain Dedication waiver (http://​creativecommons.​org/​publicdomain/​zero/​1.​0/​) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Unsere Produktempfehlungen

e.Med Interdisziplinär

Kombi-Abonnement

Für Ihren Erfolg in Klinik und Praxis - Die beste Hilfe in Ihrem Arbeitsalltag

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf SpringerMedizin.de.

© Springer Medizin

Bis 11. April 2024 bestellen und im ersten Jahr 50 % sparen!

e.Med Allgemeinmedizin

Kombi-Abonnement

Mit e.Med Allgemeinmedizin erhalten Sie Zugang zu allen CME-Fortbildungen und Premium-Inhalten der allgemeinmedizinischen Zeitschriften, inklusive einer gedruckten Allgemeinmedizin-Zeitschrift Ihrer Wahl.

© Springer Medizin

Bis 11. April 2024 bestellen und im ersten Jahr 50 % sparen!

Literatur
1.
Zurück zum Zitat Maaloul I, Talmoudi J, Chabchoub I, Ayadi L, Kamoun TH, Boudawara T, et al. Chediak-Higashi syndrome presenting in accelerated phase: a case report and literature review. Hematol Oncol Stem Cell Ther. 2016;9(2):71–5.CrossRefPubMed Maaloul I, Talmoudi J, Chabchoub I, Ayadi L, Kamoun TH, Boudawara T, et al. Chediak-Higashi syndrome presenting in accelerated phase: a case report and literature review. Hematol Oncol Stem Cell Ther. 2016;9(2):71–5.CrossRefPubMed
2.
Zurück zum Zitat Sharma P, Nicoli E-R, Serra-Vinardell J, Morimoto M, Toro C, Malicdan MCV, et al. Chediak-Higashi syndrome: a review of the past, present, and future. Drug Discov Today Dis Models. 2020;31:31.CrossRefPubMed Sharma P, Nicoli E-R, Serra-Vinardell J, Morimoto M, Toro C, Malicdan MCV, et al. Chediak-Higashi syndrome: a review of the past, present, and future. Drug Discov Today Dis Models. 2020;31:31.CrossRefPubMed
4.
Zurück zum Zitat Allen CE, McClain KL. Pathophysiology and epidemiology of hemophagocytic lymphohistiocytosis. Hematology. 2015;2015(1):177–82.CrossRefPubMed Allen CE, McClain KL. Pathophysiology and epidemiology of hemophagocytic lymphohistiocytosis. Hematology. 2015;2015(1):177–82.CrossRefPubMed
6.
Zurück zum Zitat Lehmberg K, Moshous D, Booth C. Haematopoietic stem cell transplantation for primary haemophagocytic lymphohistiocytosis. Front Pediatr. 2019;7:435.CrossRefPubMedPubMedCentral Lehmberg K, Moshous D, Booth C. Haematopoietic stem cell transplantation for primary haemophagocytic lymphohistiocytosis. Front Pediatr. 2019;7:435.CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Eapen M, DeLaat CA, Baker KS, Cairo MS, Cowan MJ, Kurtzberg J, et al. Hematopoietic cell transplantation for Chediak-Higashi syndrome. Bone Marrow Transplant. 2007;39(7):411–5.CrossRefPubMed Eapen M, DeLaat CA, Baker KS, Cairo MS, Cowan MJ, Kurtzberg J, et al. Hematopoietic cell transplantation for Chediak-Higashi syndrome. Bone Marrow Transplant. 2007;39(7):411–5.CrossRefPubMed
8.
Zurück zum Zitat Henter J-I, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124–31.CrossRefPubMed Henter J-I, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124–31.CrossRefPubMed
9.
Zurück zum Zitat Locatelli F, Jordan MB, Allen CE, Cesaro S, Rizzari C, Rao A, et al. Safety and efficacy of emapalumab in pediatric patients with primary hemophagocytic lymphohistiocytosis. Blood. 2018;132(Supplement 1):LBA6.CrossRef Locatelli F, Jordan MB, Allen CE, Cesaro S, Rizzari C, Rao A, et al. Safety and efficacy of emapalumab in pediatric patients with primary hemophagocytic lymphohistiocytosis. Blood. 2018;132(Supplement 1):LBA6.CrossRef
11.
Zurück zum Zitat La Rosée P, Horne A, Hines M, von Bahr GT, Machowicz R, Berliner N, et al. Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood. 2019;133(23):2465–77.CrossRefPubMed La Rosée P, Horne A, Hines M, von Bahr GT, Machowicz R, Berliner N, et al. Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood. 2019;133(23):2465–77.CrossRefPubMed
13.
Zurück zum Zitat Nagai K, Ochi F, Terui K, Maeda M, Ohga S, Kanegane H, et al. Clinical characteristics and outcomes of Chédiak-Higashi syndrome: a nationwide survey of Japan. Pediatr Blood Cancer. 2013;60(10):1582–6.CrossRefPubMed Nagai K, Ochi F, Terui K, Maeda M, Ohga S, Kanegane H, et al. Clinical characteristics and outcomes of Chédiak-Higashi syndrome: a nationwide survey of Japan. Pediatr Blood Cancer. 2013;60(10):1582–6.CrossRefPubMed
14.
Zurück zum Zitat Elyamany G, Alzahrani A, Elfaraidi H, Alsuhaibani O, Othman N, Mussaed E Al, et al. Hemophagocytic lymphohistiocytosis: single-center series of 12 cases from Saudi Arabia. Clin Med Insights Pediatr. 2016;10. Elyamany G, Alzahrani A, Elfaraidi H, Alsuhaibani O, Othman N, Mussaed E Al, et al. Hemophagocytic lymphohistiocytosis: single-center series of 12 cases from Saudi Arabia. Clin Med Insights Pediatr. 2016;10.
15.
Zurück zum Zitat Ahmari Al A, Alsmadi O, Sheereen A, Elamin T, Jabr A, El-Baik L, et al. Genetic and clinical characteristics of pediatric patients with familial hemophagocytic lymphohistiocytosis. Blood Res. 2021;56(2):86–101.CrossRef Ahmari Al A, Alsmadi O, Sheereen A, Elamin T, Jabr A, El-Baik L, et al. Genetic and clinical characteristics of pediatric patients with familial hemophagocytic lymphohistiocytosis. Blood Res. 2021;56(2):86–101.CrossRef
16.
Zurück zum Zitat Nielsen C, Agergaard CN, Jakobsen MA, Møller MB, Fisker N, Barington T. Infantile hemophagocytic lymphohistiocytosis in a case of Chediak-Higashi syndrome caused by a mutation in the LYST/CHS1 gene presenting with delayed umbilical cord detachment and diarrhea. J Pediatr Hematol Oncol. 2015;37(2):e73–9.CrossRefPubMed Nielsen C, Agergaard CN, Jakobsen MA, Møller MB, Fisker N, Barington T. Infantile hemophagocytic lymphohistiocytosis in a case of Chediak-Higashi syndrome caused by a mutation in the LYST/CHS1 gene presenting with delayed umbilical cord detachment and diarrhea. J Pediatr Hematol Oncol. 2015;37(2):e73–9.CrossRefPubMed
17.
Zurück zum Zitat Lange M, Linden T, Müller HL, Flasskuehler MA, Koester H, Lehmberg K, et al. Primary haemophagocytic lymphohistiocytosis (Chédiak-Higashi Syndrome) triggered by acute SARS-CoV-2 infection in a six-week-old infant. Br J Haematol. 2021;195(2):198–200.CrossRefPubMedPubMedCentral Lange M, Linden T, Müller HL, Flasskuehler MA, Koester H, Lehmberg K, et al. Primary haemophagocytic lymphohistiocytosis (Chédiak-Higashi Syndrome) triggered by acute SARS-CoV-2 infection in a six-week-old infant. Br J Haematol. 2021;195(2):198–200.CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Imashuku S, Morimoto A, Ishii E. Virus-triggered secondary hemophagocytic lymphohistiocytosis. Acta Paediatr. 2021;110(10):2729–36.CrossRefPubMed Imashuku S, Morimoto A, Ishii E. Virus-triggered secondary hemophagocytic lymphohistiocytosis. Acta Paediatr. 2021;110(10):2729–36.CrossRefPubMed
19.
Zurück zum Zitat Zhang L-J, Qiu H-X, Li J-Y, Xu J, Wang L-L, Hu Y-X, et al. Clinical analysis of 10 cases of secondary hemophagocytic lymphohistiocytosis treated with HLH-2004 chemotherapy. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2010;18(6):1525–30.PubMed Zhang L-J, Qiu H-X, Li J-Y, Xu J, Wang L-L, Hu Y-X, et al. Clinical analysis of 10 cases of secondary hemophagocytic lymphohistiocytosis treated with HLH-2004 chemotherapy. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2010;18(6):1525–30.PubMed
20.
Zurück zum Zitat Bergsten E, Horne A, Aricó M, Astigarraga I, Egeler RM, Filipovich AH, et al. Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study. Blood. 2017;130(25):2728–38.CrossRefPubMedPubMedCentral Bergsten E, Horne A, Aricó M, Astigarraga I, Egeler RM, Filipovich AH, et al. Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study. Blood. 2017;130(25):2728–38.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Gopaal N, Sharma JN, Agrawal V, Lora SS, Jadoun LS. Chediak-Higashi Syndrome with Epstein-Barr virus triggered hemophagocytic lymphohistiocytosis: a case report. Cureus. 2020;12(11). Gopaal N, Sharma JN, Agrawal V, Lora SS, Jadoun LS. Chediak-Higashi Syndrome with Epstein-Barr virus triggered hemophagocytic lymphohistiocytosis: a case report. Cureus. 2020;12(11).
22.
Zurück zum Zitat Bubik RJ, Barth DM, Hook C, Wolf RC, Muth JM, Mara K, et al. Clinical outcomes of adults with hemophagocytic lymphohistiocytosis treated with the HLH-04 protocol: a retrospective analysis. Leuk Lymphoma. 2020;61(7):1592–600.CrossRefPubMed Bubik RJ, Barth DM, Hook C, Wolf RC, Muth JM, Mara K, et al. Clinical outcomes of adults with hemophagocytic lymphohistiocytosis treated with the HLH-04 protocol: a retrospective analysis. Leuk Lymphoma. 2020;61(7):1592–600.CrossRefPubMed
23.
Zurück zum Zitat Elsharkawy A, Assem H, Salama M, Mikhael N, Zeid MY, El Chazli Y. Clinical characteristics and outcomes of 101 children with hemophagocytic lymphohistiocytosis: a four-year single-center experience from Egypt. Pediatr Hematol Oncol. 2021;38(3):194–207.CrossRefPubMed Elsharkawy A, Assem H, Salama M, Mikhael N, Zeid MY, El Chazli Y. Clinical characteristics and outcomes of 101 children with hemophagocytic lymphohistiocytosis: a four-year single-center experience from Egypt. Pediatr Hematol Oncol. 2021;38(3):194–207.CrossRefPubMed
24.
Zurück zum Zitat Al-Ghonaium A. Stem cell transplantation for primary immunodeficiencies: King Faisal Specialist Hospital experience from 1993 to 2006. Available from: www.nature.com/bmt. Al-Ghonaium A. Stem cell transplantation for primary immunodeficiencies: King Faisal Specialist Hospital experience from 1993 to 2006. Available from: www.​nature.​com/​bmt.
25.
Zurück zum Zitat Amayiri N, Al-Zaben A, Ghatasheh L, Frangoul H, Hussein AA. Hematopoietic stem cell transplantation for children with primary immunodeficiency diseases: single center experience in Jordan. Pediatr Transpl. 2013;17(4):394–402.CrossRef Amayiri N, Al-Zaben A, Ghatasheh L, Frangoul H, Hussein AA. Hematopoietic stem cell transplantation for children with primary immunodeficiency diseases: single center experience in Jordan. Pediatr Transpl. 2013;17(4):394–402.CrossRef
26.
Zurück zum Zitat Ayas M, Al-Ghonaium A. In patients with Chediak-Higashi syndrome undergoing allogeneic SCT, does adding etoposide to the conditioning regimen improve the outcome? Bone Marrow Transplant. 2007;40(6):603–603.CrossRefPubMed Ayas M, Al-Ghonaium A. In patients with Chediak-Higashi syndrome undergoing allogeneic SCT, does adding etoposide to the conditioning regimen improve the outcome? Bone Marrow Transplant. 2007;40(6):603–603.CrossRefPubMed
27.
Zurück zum Zitat Garonzi C, Chinello M, Cesaro S. Emapalumab for adult and pediatric patients with hemophagocytic lymphohistiocytosis. Expert Rev Clin Pharmacol. 2021;14(5):527–34.CrossRefPubMed Garonzi C, Chinello M, Cesaro S. Emapalumab for adult and pediatric patients with hemophagocytic lymphohistiocytosis. Expert Rev Clin Pharmacol. 2021;14(5):527–34.CrossRefPubMed
28.
Zurück zum Zitat Lounder DT, Bin Q, de Min C, Jordan MB. Treatment of refractory hemophagocytic lymphohistiocytosis with emapalumab despite severe concurrent infections. Blood Adv. 2019;3(1):47–50.CrossRefPubMedPubMedCentral Lounder DT, Bin Q, de Min C, Jordan MB. Treatment of refractory hemophagocytic lymphohistiocytosis with emapalumab despite severe concurrent infections. Blood Adv. 2019;3(1):47–50.CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Merli P, Algeri M, Gaspari S, Locatelli F. Novel therapeutic approaches to familial HLH (emapalumab in FHL). Front Immunol. 2020;11. Merli P, Algeri M, Gaspari S, Locatelli F. Novel therapeutic approaches to familial HLH (emapalumab in FHL). Front Immunol. 2020;11.
30.
Zurück zum Zitat Singh JK, Terao MA, Sarangi S, Toth J, Toretsky JA. Afebrile S. aureus bacteremia in two patients with hemophagocytic lymphohistiocytosis receiving emapalumab/dexamethasone/etoposide. Pediatr Blood Cancer. 2021;68(8). https://doi.org/10.1002/pbc.29001. Singh JK, Terao MA, Sarangi S, Toth J, Toretsky JA. Afebrile S. aureus bacteremia in two patients with hemophagocytic lymphohistiocytosis receiving emapalumab/dexamethasone/etoposide. Pediatr Blood Cancer. 2021;68(8). https://​doi.​org/​10.​1002/​pbc.​29001.
Metadaten
Titel
Successful use of emapalumab in refractory hemophagocytic lymphohistiocytosis in a child with Chédiak–Higashi syndrome: a case report
verfasst von
Ali AlAhmari
Haitham Khogeer
Publikationsdatum
01.12.2023
Verlag
BioMed Central
Erschienen in
Journal of Medical Case Reports / Ausgabe 1/2023
Elektronische ISSN: 1752-1947
DOI
https://doi.org/10.1186/s13256-023-03808-1

Weitere Artikel der Ausgabe 1/2023

Journal of Medical Case Reports 1/2023 Zur Ausgabe