Hemophagocytic Syndrome in a Patient with ALL: Morphology Still Matters

We report a case of a young patient suffering from very-high risk B-acute lymphoblastic leukemia (ALL) refractory to first-line therapy with early central nervous system relapse, sequentially treated with inotuzumab. At this timepoint, the patient showed persistent transfusion-refractory thrombocytopenia (platelets < 5000/uL), fever and cytomegalovirus infection. A bone marrow revaluation showed complete remission of ALL, but hemophagocytic elements and activated macrophages were present. At physical examination, the spleen was palpable. Blood chemistry showed hyperferritinemia (1419 ng/mL, normal range 24–336), NK cells suppression (11 cells/microL, minimum value 90) and IL-6 increase (119.1 pg/dL, normal values < 1.8). Triglycerides and fibrinogen were normal. A diagnosis of hemophagocytic lymphohistiocytosis (HLH) was made according to HLH-2004 criteria. The patient was treated with the IL-1 inhibitor anakinra at escalating dosage. After an initial improvement in altered HLH parameters, a clinical worsening occurred with progressing thrombocytopenia and anemia and a remarkable increase in ferritin (4066 ng/mL). The patient then underwent rituximab-based salvage treatment but died due to HLH and B-ALL progression. HLH could be a rare complication in ALL patients. Despite increasing biological knowledge, prognosis remains poor, and more efforts are needed in order to improve survival in these patients.