Hemofagocytair syndroom (HLH)

Inleiding

Hemofagocytaire lymfohistiocytose (HLH), ook wel het hemofagocytair syndroom genoemd, is een potentieel levensbedreigende aandoening die gekenmerkt wordt door ongecontroleerde immuun activatie en weefselschade. Gezien de hoge mortaliteit, moet er bij verdenking HLH snel gehandeld worden. Er wordt gestreefd om de diagnostiek binnen 24 uur in te zetten en indien een patiënt voldoet aan de criteria voor HLH moet behandeling gestart worden, soms zelfs voor afronding van de diagnostiek naar de onderliggende oorzaak. Ook bij een sterke verdenking op HLH, waarbij er nog niet aan 5 van de 8 criteria wordt voldaan, wordt gestart met therapie. De HLH-probability calculator (H-score), ontwikkeld op basis van retrospectieve data van volwassenen, kan hierbij behulpzaam zijn (http://saintantoine.aphp.fr/score/) (sensitiviteit 93% en specificiteit 89%).

Link: Blood 2019: Recommendations for the management of hemophagocytic lymphohistiocytosis in adults

Diagnostiek HLH

HLH T-cel phenotype

T-cel populatie (HLADR+/CD38bright/CD8+) pleit voor HLH versus sepsis.

Zie ook : https://pubmed.ncbi.nlm.nih.gov/33512385/

Behandeling HLH

Allogene SCT

Adults with primary HLH may need allogeneic hematopoietic SCT (alloSCT), which has dramatically improved outcomes in children. Transplant-related mortality in children using reduced-intensity conditioning (RIC) has been reported to compare favorably to myeloablative conditioning (MAC). A retrospective European Society of Blood and Marrow Transplantation study did not show superiority of RIC over MAC in adults. Decisions regarding transplantation should be made on clinical grounds and in consultation with experts in HLH and alloSCT. Inactive HLH before transplantation is strongly associated with better survival. Patients with primary HLH and nonmalignant sHLH may be candidates for RIC, as well as MAC. The pretransplant conditioning regimen in malignancy-associated HLH (Mal-HLH) may be guided by disease-specific protocols, as provided by local standards, which includes MAC to optimally control the underlying disease. In patients in whom HLH-causing mutations are detected, HLA typing of close relatives should also integrate screening for the same gene mutations, to avoid a stem cell source with the same pathogenic biallelic mutation(s).

For those requiring alloSCT because of underlying genetic mutations, HLH-94 maintenance therapy is often recommended after the initial 8 weeks of therapy. CSA may be replaced by tacrolimus, but both need careful drug level monitoring and toxicity assessment.

Link: Front Immunol 2020. Diagnosis and Management of Secondary HLH/MAS Following HSCT and CAR-T Cell Therapy in Adults

Link: Sandler RD BMT 2019. Haemophagocytic lymphohistiocytosis (HLH) following allogeneic haematopoietic stem cell transplantation (HSCT)-time to reappraise with modern diagnostic and treatment strategies?

Link: Alblooshi RM BMT 2019. My jamais vu in post allogeneic hematopoietic cell transplant: a review on secondary hemophagocytosis in adults.

Post HCT-HLH

Secondary hemophagocytic lymphohistiocytosis (HLH) post allogeneic hematopoietic stem cell transplant (HCT) in adults has various clinical context and aetiologies. It is characterized by hyperinflammatory process and cytokine release triggered by various stimuli, with a poorly understood pathophysiology and unknown etiology. It is an aggressive disease with dismal outcome despite prompt treatment.

Prevalentie: The prevalence of post allogeneic HCT HLH in 15 EBMT centers between 2005 and 2009 was 0.3% (5/1423) in patients who fulfilled the HLH criteria