Introduction:
Hemophagocytic Histiocytosis (HLH), an acute immune activated state described as cytokine storm, diagnosed by both clinical and laboratory parameters in haematological diseases and as complications in cellular therapies and is uniformly related to inferior outcome in the early- as well as late-period. The incidence of HLH in patients of AML is not explored comprehensively in past. In countries with poor health care facilities, the AML-patients, present late and the overall outcome is poor despite younger age. We hypothesized HLH could be contributing to the inferior outcome. In this study, we prospectively looked for HLH in AML patients both clinically as well as by flow cytometry.
Methods:
We evaluated 34 AML patients prospectively in our institute, with the baseline symptoms (fever) with or without organomegaly, serum ferritin levels and flow cytometry (T-cell profiling) in AML patients (n=34). Clinical HLH in our study was defined as, high-grade unremitting fever with elevated ferritin (> 1000 ng/ml). We performed flow cytometry on peripheral blood for the enumeration of T-lymphocytes and their subtypes and correlated with the clinical HLH.
Results:
Median age 35.5 years (range 15-66) with 70% male population. 58% were newly diagnosed and the rest were relapsed/refractory AML patients. Average baseline blast count of 56%, Hb of 8.9 g/dl, TLC of 18,214 /microlitre and serum ferritin of 1301 ng/ml. More commonly seen with NPM1(23%), RUNX1-RUNX1T1(23%) and IDH2R140Q (20%) mutated were in the group. Out of 34 patients, 27 developed clinical HLH during induction chemotherapy. Induction therapy used were 2+5+Ven (two days of daunorubicin, 5 days of ARA-C and 5 days of venetoclax) under a clinical study. Out of 34 patients, 29 exhibited enhanced expression of CD38 along with HLA-DR (70.22%; range: 33.51%-91.46%) on cytotoxic T-cells. In contrast 5 patients did not show a significant proportion of CD38 with HLA-DR (10.26%; range: 5.43%-14.61%). These findings suggest a potential correlation with HLH, as elevated CD38 expression on cytotoxic T cells has been associated with the hyperactivation and proliferative responses seen in HLH, reflecting a state of heightened immune activation and dysregulation. Notably, 1 patient displayed a dim expression of CD38 (98.83%) without HLA-DR. Clinical data with serum ferritin and fever were correlated with the flow cytometric analysis (correlation co-efficient 0.59, p<0.01). In that out of 34 patients, 20 (58%) showed evidence of HLH by flow cytometry as well as clinical HLH.
Conclusion:
Flow cytometry could be useful in identifying HLH at baseline in patients of AML. Further data regarding early mortality, relapse, and survival will be presented in the conference
No relevant conflicts of interest to declare.
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