Background The confirmed cases of acute leukemia (AL) complicated with hemophagocytic syndrome (HLH) are increasing, especially in adolescents.

Objective To investigate the clinical characteristics and diagnostic and treatment options of youth patients with AL combined HLH.

Methods Clinical data about five patients with AL combined HLH who visited the hematology department of our hospital from September 2013 to December 2022 were retrospectively collected, and their diagnostic process, treatment options and treatment regression were analyzed.

Results Four of the five patients were male and one was female, aged 14-29 years, and three of them were diagnosed with AL and HLH at the same time. All patients had fever, splenomegaly, reduced peripheral blood two or three lines, abnormal coagulation function, increased serum ferritin and negative peripheral blood EBV at the time of HLH diagnosis. Three cases had positive or protein expression of familial phagocytosis-related genes, three cases with Soluble CD25 increased, three cases with natural killer cell activity decreased, one patient had bone marrow phagocytosis, one case with increased triacylglycerol, and one case with reduced fibrinogen. Three of our primary patients achieved remission with leukemia chemotherapy, HLH was effectively treated, and one case completed bone marrow transplantation. One case relapsed then the patient abandoned further treatment, one case did not undergo transplantation after remission and was complicated by other tumors. One case of AL failed induction chemotherapy and was complicated by HLH with unsatisfactory efficacy of standard treatment, one case of acute myeloid leukemia (AML) after induction remission with myelosuppressive phase and complicated by HLH, which improved with the addition of DEP regimen (doxorubicin + etoposide + hormone) + hormone therapy then obtained the opportunity of hematopoietic stem cell transplantation.

Conclusion The clinical diagnosis of AL combined with HLH is rare, and the treatment is difficult. Early identification and diagnosis and active treatment can improve the prognosis, and patients undergoing allogeneic hematopoietic stem cell transplantation can benefit from it.