Allogeneic hematopoietic stem cell transplantation is associated with cure and durable remission of late‐onset primary isolated central nervous system hemophagocytic lymphohistiocytosis

Abstract

Primary isolated CNS presentation of HLH is exceedingly rare and typically associated with significant morbidity and mortality. We describe an adolescent patient with late-onset, primary isolated CNS HLH and a compound heterozygous PRF1 mutation (c50delT (p.L17 fs); c.1229G>C (p.R410P)), not previously reported with this phenotype. He was successfully treated with allogeneic HSCT following a reduced-intensity conditioning regimen, despite a high pre-HSCT comorbidity index. Two years after transplant, he is alive and in disease remission. While patients with systemic HLH and active CNS disease have relatively poorer outcomes, a high index of suspicion may aid with early diagnosis of primary isolated CNS HLH; prompt treatment with HSCT may be associated with improved cure and durable remission of this rare disease.

Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis

“…A number of case reports have pointed out that FHL can also present as a highly variable and non-specific neuroinflammatory disease [10][11][12][13][14][15][16][17][18][19][20][21][22] in the absence of any systemic features of HLH. This different clinical manifestation leads to initial presentation to the neurologist who is less familiar with this rare disease than the hemato-oncologist or immunologist who are usually confronted with FHL patients due to their systemic inflammatory and hematologic manifestations.…”

“…Notably, there are also case reports of isolated CNS disease in FHL patients, occurring in the absence of any systemic disease features, mostly in older patients with hypomorphic mutations [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Reported cases are rare and therefore the spectrum of clinical manifestations, response to therapy and prognosis remain poorly defined.…”

Pediatric CNS-isolated hemophagocytic lymphohistiocytosis

“…8 Patients with PRF1 mutations have been reported with isolated CNS inflammation for weeks to months before therapy initiation 1,9–12 ; 2 such patients underwent HCT. 9,11 These reports raise, but do not answer, the question as to whether isolated chronic CNS inflammation can occur in the absence of systemic HLH findings.…”

The Spectrum of Clinical, Immunological, and Molecular Findings in Familial Hemophagocytic Lymphohistiocytosis: Experience From India

“…In our cohort, we identified four FHL patients with atypical initial presentations, namely, two FHL2 patients with malignancy (P6 and P7), one FHL5 patient with ALPS (P93), and one FHL2 patient with isolated neurological relapse (P14). Particularly, isolated CNS manifestations in FHL can be challenging to diagnose (17,40,41). These findings highlight some of the atypical manifestations in FHL which may delay diagnosis in selected cases.…”