Hemophagocytic Syndrome (HPS) after Autologous Peripheral Stem Cell Tansplantation (APSCT) for Multiple Myeloma (MM)- Successful Treatment with High Dosages of Intravenous Immunoglobulin (IVIG).

HPS is characterized by activation of histiocytes with prominent hemophagocytosis in bone marrow and reticulo-endothelial system, resulting in cytopenias. Reactive HPS (R-HPS) is known to be associated with infection, malignancies and autoimmune disorders. We report a case of R-HPS with massive life-threatening gastro-intestinal (GI) tract bleeding after APSCT for MM which responded to high dosages of IVIG. In May 2005, a 54-year old female diagnosed with MM stage III A, achieved CR after 4 cycles of VAD. APSCT conditioning consisted of L-PAM 140mg/m². 2x10⁶ CD34+ cells/kg were infused. G-CSF 10μg/kg was started on D0. Pt was placed on cefepime and vancomycin (D+4) and amphotericin B (D+7) for FUO and discontinued after neutrophil recovered (D+10). During aplasia, she received 2 packed RBC and 4 PLT transfusions (irradiated and filtrated). On D+12 G-CSF was discontinued. Four days after thrombocytopenia aggravated (PLT 3000/mm³) and she presented with fever (39°C) and disseminated petechiae. Other coagulation tests were normal. A complete search for infection was negative- cultures (urine and blood) and thoracic, abdominal and sinus CT scan. Pt was again placed on cefepime, vancomycin and amphotericin B without defervescence. In the following 3 days, hypovolemic shock due to profuse GI tract bleeding occurred. Upper endoscopy showed diffuse petechiae and bleeding. Bone marrow (BM) aspirate was performed and revealed 3% histiocytes with hemophagocytic activity. R-HPS was diagnosed. Massive RBC and PLT transfusions were started (4x/day) without response. Search for HSV, EBV, HIV, CMV, auto-immune disease and malignancy were negative. She was on prophylactic acyclovir. On D+21 pt received IVIG 1g/kg/day for 2 days and dexamethasone 40mg for 4 days. Hemorrhage resolved and PLT counts improved. However, on D+30 PLT counts dropped again (PLT 24000/mm³) and BM aspirate showed persistent hemophagocytosis with 4% of histiocytes. A new course of IVIG was given and repeated once a week for 2 weeks when it was no longer needed. BM aspirate on D+39 was normal, with no evidence of hemophagocytosis and there was no recurrence of R-HPS. In this case platelet was the more affected cell lineage resulting in severe and life-threatening hemorrhagic syndrome. The immune mechanism of HPS is not clear, but a defect in immune regulation has been hypothesized. R-HPS after auto-BMT is rare event and appears to be associated with hematological and immunological recovery. We believe that IVIG was effective and its known mechanism of action is compatible with current knowledge of HPS pathophysiology. IVIG might be an effective treatment for R-HPS secondary to auto-BMT.