Abnormalities of the lymphocyte subsets and their immunophenotype, and their prognostic significance in adult patients with hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a final common pathway resulting from diverse immune processes. Most of the current understanding of HLH is based on studies involving pediatric patients (pHLH). Adult HLH (aHLH) is distinct from pHLH, with less frequent genetic basis, higher frequency of chemo-resistance and a higher mortality. Immunological processes underlying aHLH are poorly understood. So far, no immunophenotypic abnormalities associated with aHLH have been described, and their etiopathologic and prognostic significance has not been explored. We reviewed all adult patients with bone marrow hemophagocytosis and identified 21 who fulfilled the criteria for HLH. We then analyzed abnormalities in their lymphocyte subsets and immunophenotype and tested association of these abnormalities with survival. Twenty of 21 patients showed abnormalities in either lymphocyte subsets and/or immunophenotype: 10 showed increased CD8+ cells and decreased CD4:CD8 ratio, 8 had decreased CD3+ cells, 3 each had increased CD56+ cells, increased CD7-/CD4+ cells, and increased CD3+/CD4-/CD8- (DN) cells, and one had increased CD3-/CD4+ cells. Six of 10 patients with increased numbers of CD8+ cells and decreased CD4:CD8 ratio are alive, compared to 2/11 with normal values (p = 0.0385). On the other hand, all 8 patients with decreased CD3+ cells are dead, compared to 8/13 with normal numbers (p = 0.0417). Those who survived were younger than those who did not (median, range: 29 years, 19-88, vs 62 years, 24-81; p = 0.0272). In conclusion, most aHLH patients show diverse abnormalities in either lymphocytes and/or immunophenotype. Young age, increased numbers of CD8+ cells or decreased CD4:CD8 ratio are favorably associated with survival, while a decreased number of CD3+ cells is adversely associated with survival in aHLH patients.