Salvage Therapy and Allogeneic Hematopoietic Cell Transplantation for the Severe Cytokine Storm Syndrome of Hemophagocytic Lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) can be considered as a severe cytokine storm syndrome disorder. HLH typically manifests as a life-threatening inflammatory syndrome characterized by fevers, cytopenias, hepatosplenomegaly, and various other accompanying manifestations such as coagulopathy, hepatitis or liver failure, seizures or altered mental status, and even multi-organ failure. Standard up-front treatments do not always bring HLH into remission or maintain adequate response, and salvage or alternative therapies are often needed. For patients with genetic diseases that cause HLH, curative allogeneic hematopoietic cell transplantation is usually offered to prevent future episodes of life-threatening HLH. Here, we will discuss the options and approaches for salvage therapy and hematopoietic cell transplantation for patients with HLH.

Marsh RA 《Advances in Experimental Medicine and Biology》

Hemophagocytic lymphohistiocytosis: a review inspired by the COVID-19 pandemic.

Soy M ，Atagündüz P ，Atagündüz I ，Sucak GT ... -  《-》

Ruxolitinib for hematopoietic cell transplantation-associated hemophagocytic lymphohistiocytosis.

Ono R ，Ashiarai M ，Hirabayashi S ，Mizuki K ，Hosoya Y ，Yoshihara H ，Ohtake J ，Mori S ，Manabe A ，Hasegawa D ... -  《-》

Complete Response to Donor Lymphocyte Infusion for Primary Hemophagocytic Lymphohistiocytosis Relapse after Allogeneic Hematopoietic Cell Transplantation.

Primary hemophagocytic lymphohistiocytosis (HLH) is a hyper-inflammatory disorder characterized by dysregulation of inflammatory cells and cytokine signaling. Although first-line treatment consisting of immunosuppressive therapy and allogeneic hematopoietic cell transplantation (HCT) is often curative, it remains unknown whether any effective therapies exist for disease relapse/progression after HCT. Here we present a case of a 29-year-old male with primary HLH who failed HLH-94 protocol and subsequently underwent myeloablative HCT. Disease relapse occurred at 9 months following HCT, and donor lymphocyte infusion (DLI) was initiated as salvage therapy. The patient subsequently achieved durable long-term disease-free survival following a DLI, without significant treatment-related complications. To our knowledge, this represents the first case demonstrating the efficacy of DLI for relapsed primary HLH.

Khanolkar RA ，Kuehne N ，Storek J 《-》

An intermediate alemtuzumab schedule reduces the incidence of mixed chimerism following reduced-intensity conditioning hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis.

Reduced-intensity conditioning (RIC) improves the outcomes of hematopoietic cell transplantation (HCT) in patients with hemophagocytic lymphohistiocytosis (HLH). Proximal (ie, close to graft infusion) dosing of alemtuzumab is associated with a high incidence of mixed chimerism, whereas distal (ie, distant from graft infusion) dosing is associated with less mixed chimerism but more acute graft-versus-host disease (GVHD). The alemtuzumab dose per kilogram of body weight also influences these outcomes. We hypothesized that an intermediate alemtuzumab dosing schedule would reduce mixed chimerism and maintain a low incidence of acute GVHD. In this study, 24 consecutive HCTs were performed in patients with HLH or a related disorder using a novel intermediate alemtuzumab schedule of 1 mg/kg starting on day -14. The cumulative incidences (CIs) of mixed chimerism, upfront acute GVHD grades II-IV, and receipt of additional hematopoietic cell products after HCT were compared in patients treated with a distal alemtuzumab schedule (n = 15) and those treated with a proximal alemtuzumab schedule (n = 33). All patients received fludarabine and melphalan. The CI of mixed chimerism was 31% in the intermediate group, 72% in the proximal group (P < .01), and 75% in the distal group patients who received ≥2 mg/kg alemtuzumab (P = .03). The CI of acute GVHD grades II-IV before the development of mixed chimerism was 4% in the intermediate group, 0% in the proximal group, and 13% in the distal group (P = .04, proximal versus distal). The 1-year CI of administration of additional hematopoietic cell products for mixed chimerism (donor lymphocyte infusion ± hematopoietic stem cell boost ± repeat HCT) was 14% in the intermediate group, 53% in the proximal group (P = .01), and 38% in the distal ≥2 mg/kg alemtuzumab group (P = .02). Our findings indicate that intermediate RIC reduces the incidence of mixed chimerism, is associated with a low incidence of upfront acute GVHD, and decreases the need for additional hematopoietic cell products after HCT.

Marsh RA ，Kim MO ，Liu C ，Bellman D ，Hart L ，Grimley M ，Kumar A ，Jodele S ，Myers KC ，Chandra S ，Leemhuis T ，Mehta PA ，Bleesing JJ ，Davies SM ，Jordan MB ，Filipovich AH ... -  《-》