Introduction: 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. Case Presentation: 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. Conclusion: To our knowledge, this represents the first case demonstrating the efficacy of DLI for relapsed primary HLH.

Janka GE. Familial and acquired hemophagocytic lymphohistiocytosis. Annu Rev Med. 2012;63:233–46.
Memon F, Ahmed J, Malik F, Ahmad J, Memon DA. Adult-onset primary hemophagocytic lymphohistiocytosis: reporting a rare case with review of literature. Cureus. 2020;12(1):e6723.
Schram AM, Comstock P, Campo M, Gorovets D, Mullally A, Bodio K, et al. Haemophagocytic lymphohistiocytosis in adults: a multicentre case series over 7 years. Br J Haematol. 2016;172(3):412–9.
Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124–31.
Ouachée-Chardin M, Elie C, de Saint Basile G, Le Deist F, Mahlaoui N, Picard C, et al. Hematopoietic stem cell transplantation in hemophagocytic lymphohistiocytosis: a single-center report of 48 patients. Pediatrics. 2006;117(4):e743–50.
Horne A, Janka G, Maarten Egeler R, Gadner H, Imashuku S, Ladisch S, et al. Haematopoietic stem cell transplantation in haemophagocytic lymphohistiocytosis. Br J Haematol. 2005;129(5):622–30.
Cesaro S, Locatelli F, Lanino E, Porta F, Di Maio L, Messina C, et al. Hematopoietic stem cell transplantation for hemophagocytic lymphohistiocytosis: a retrospective analysis of data from the Italian Association of Pediatric Hematology Oncology (AIEOP). Haematologica. 2008;93(11):1694–701.
Henter JI, Aricò M, Egeler RM, Elinder G, Favara BE, Filipovich AH, et al. HLH-94: a treatment protocol for hemophagocytic lymphohistiocytosis. HLH study Group of the Histiocyte Society. Med Pediatr Oncol. 1997;28(5):342–7.
Marsh RA, Vaughn G, Kim MO, Li D, Jodele S, Joshi S, et al. Reduced-intensity conditioning significantly improves survival of patients with hemophagocytic lymphohistiocytosis undergoing allogeneic hematopoietic cell transplantation. Blood. 2010;116(26):5824–31.
Marsh RA, Kim MO, Liu C, Bellman D, Hart L, Grimley M, et al. An intermediate alemtuzumab schedule reduces the incidence of mixed chimerism following reduced-intensity conditioning hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis. Biol Blood Marrow Transplant. 2013;19(11):1625–31.
Marsh RA, Jordan MB, Filipovich AH. Reduced-intensity conditioning haematopoietic cell transplantation for haemophagocytic lymphohistiocytosis: an important step forward. Br J Haematol. 2011;154(5):556–63.
Khanolkar RA, Tripathi G, Dharmani-Khan P, Dabas R, Kinzel M, Kalra A, et al. Incomplete chimerism following myeloablative and anti-thymocyte globulin-conditioned hematopoietic cell transplantation is a risk factor for relapse and chronic graft-versus-host disease. Cytotherapy. 2022;24(12):1225–31.
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995;15(6):825–8.
Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, et al. National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 diagnosis and staging working group report. Biol Blood Marrow Transplant. 2015;21(3):389–401.e1.
Huang W, Wang Y, Wang J, Zhang J, Wu L, Li S, et al. Clinical characteristics of 192 adult hemophagocytic lymphohistiocytosis. Zhonghua Xue Ye Xue Za Zhi. 2014;35(9):796–801.
Wang Y, Huang W, Hu L, Cen X, Li L, Wang J, et al. Multicenter study of combination DEP regimen as a salvage therapy for adult refractory hemophagocytic lymphohistiocytosis. Blood. 2015;126(19):2186–92.
Locatelli F, Jordan MB, Allen C, Cesaro S, Rizzari C, Rao A, et al. Emapalumab in children with primary hemophagocytic lymphohistiocytosis. N Engl J Med. 2020;382(19):1811–22.
Boonstra PS, Ahmed A, Merrill SA, Wilcox RA. Ruxolitinib in adult patients with secondary hemophagocytic lymphohistiocytosis. Am J Hematol. 2021;96(4):E103–5.
Wang J, Wang Z. Multicenter study of ruxolitinibcombined DEP regimen as a salvage therapy for refractory/relapsed hemophagocytic lymphohistiocytosis. Blood. 2019;134(Supplement_1):1042.
Marsh RA, Allen CE, McClain KL, Weinstein JL, Kanter J, Skiles J, et al. Salvage therapy of refractory hemophagocytic lymphohistiocytosis with alemtuzumab. Pediatr Blood Cancer. 2013;60(1):101–9.
Chang YJ, Huang XJ. Donor lymphocyte infusions for relapse after allogeneic transplantation: when, if and for whom?Blood Rev. 2013;27(1):55–62.
Deol A, Lum LG. Role of donor lymphocyte infusions in relapsed hematological malignancies after stem cell transplantation revisited. Cancer Treat Rev. 2010;36(7):528–38.
Ye Y, Yang L, Yuan X, Huang H, Luo Y. Optimization of donor lymphocyte infusion for AML relapse after allo-HCT in the era of new drugs and cell engineering. Front Oncol. 2021;11:790299.
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