Pf350 Construction of a Prognostic Model for HLH in Adults – Analysis From the Palg HLH in Adults Database

Abstract

Background: Congenital neutropenia (CN) is a heterogeneous group of rare inborn genetic defects with different gene mutations and different patterns of inheritance. Mutations in the HCLS1 associated Protein X-1 (HAX1) make up the largest cohort of autosomal recessive CN in Europe. There are two HAX1 splice isoforms. Mutations affecting one isoform (p.W44X) only can be found in consanguineous families of Turkic or Arabic origin while mutations affecting both isoforms were found in the original pedigree from Sweden (p.Q190X) and in Japanese pts (p.R86X). Independent of the mutation, HAX1 pts benefit from G-CSF treatment, which improved the life expectancy and quality of life significantly. However, a significant risk of secondary leukemia has been unmasked for pts with HAX1 mutations (comparable to pts with ELANE mutations).Aims: Here we report on the genotype -phenotype correlation and outcome of pts revealing different HAX1 mutations. Methods: We identified 57 pts with HAX1 mutations within the CN cohort documented by the European Branch of the SCNIR since 1994. Results: HAX1 mutations have been identified in 57 (25 female; 32 male) of 501 pts with CN. The median age is 9.49 years (range 0.28-38.69 years), with 664.83 pt years under observation. 45 of 57 pts reveal homozygous mutations in one transcript variant (p.W44X), in 1pt with an additional heterozygous ELANE mutation. In 2 of 57 pts, both isoforms are affected (p.Q190X). 5 of 57 pts have mutations at other sites of the HAX1 gene and in 5 pts the position was not reported. At diagnosis, all HAX1 pts presented with severe neutropenia and a maturation arrest at the promyelocyte/myelocyte stage in the bone marrow. All pts received long-term G-CSF treatment with a median dose of 4.25 µg/kg/day compared to 4.61 µg/kg/day for the total CN cohort of the SCNIR Europe. Median ANC increased from 160 to 1775/µL during G-CSF treatment. Additional clinical features included cardiac defects in 4 pts, hypogonadism in 5 female pts and growth retardation in 6 pts,

Hemophagocytic Lymphohistiocytosis for the Internist and Other Primary Care Providers

“…Although reliable data pertaining to HLH’s prevalence in American adult outpatient practice were not readily available at the time of this writing, a retrospective study of 86 patients with HLH in the Polish Adult Leukemia Group demonstrated a median survival of 144 days; 29 patients (33.7%) survived at least 1 year, with only 2 of these 29 ultimately dying, both of HLH relapse. 8 Thus, it can be concluded that a significant percentage of HLH patients does survive to the point of requiring outpatient surveillance, and that ongoing surveillance is necessary to detect deadly HLH relapse.…”