The association between acute lymphoblastic leukemia (ALL) and hemophagocytic lymphohistiocytosis (HLH) is less frequently reported than other malignancyassociated HLH.1 We describe the rapidly fatal course of a 2yearold boy who developed HLH while in remission from T cell acute lymphoblastic leukemia (TALL). He developed high fevers, severe pancytopenia, herpes simplex virusassociated gingivitis, stomatitis, and viremia during the delayed intensification chemotherapy phase. Despite resolution of viremia, high fevers persisted, with a lack of hematologic recovery and the development of massive hepatomegaly. Bone marrow examination showed extensive histiocytic hemophagocytosis without lymphoblasts and liver biopsy exhibited extensive histiocytosis (Figure 1). Serum ferritin and soluble IL2 receptor levels were markedly elevated. No HLHassociated pathogenic mutation was identified. Despite prompt initiation of etoposide and dexamethasone, he rapidly deteriorated and his family declined further HLHdirected therapy, electing supportive care. Few reports are available describing the clinical severity and fatal outcome of pediatric TALLassociated HLH. Only two survivors are reported by Moritake et al, and the rest died of complications of HLH, except one who died of leukemia progression. The two survivors were in maintenance when they developed HLH. An infectious association was present in about half of the cases reported, including cytomegalovirus, EpsteinBarr virus, or varicellazoster virus. However, unlike other HLHassociated disorders, in immunosuppression and malignancyassociated HLH, treatment of the inciting trigger alone may not be effective. HLHspecific therapy was also ineffective in the majority of TALLassociated HLH.1 Because of the limited data available, the benefit of HLHspecific immunosuppression therapy, including corticosteroids and etoposide, remains uncertain. Malignancyassociated HLH has a high mortality rate, with an overall survival rate of about 67%, in contrast to “on therapy” malignancyassociated HLH, which is often refractory to any treatment.1,2