Vol 7, No 4 (2016)
Case report
Published online: 2017-04-07
Hematopoietic stem cell transplantation in secondary relapsed hemophagocytic lymphohistiocytosis
Hematologia 2016;7(4):327-338.
Abstract
Hemophagocytic lymphohistiocytosis (HLH) is a rare condition having a severe clinical course and 50% mortality. Two subgroups of HLH may be distinguished: familial HLH or HLH due to genetic defects and secondary HLH linked to neoplasms, autoimmunological diseases and infections. The case presented is of secondary HLH apparently resulting from bacterial infection. Diagnosing HLH is a clinical challenge due to unclear clinical presentation and diagnostic difficulties in histopathogical evaluation. Patients with HLH have non-specific symptoms that may overlap with symptoms of an underlying condition like infections or lymphoma. In the presented case, diagnosis of HLH was delayed due to suspected lymphoma, that was subsequently ruled out. The Histiocyte Society HLH-1994 protocol of treatment was initiated based on dexamethasone, etoposide and cyclosporine A (CsA). A normalization of laboratory markers for HLH was achieved and cytopenia was resolved. Maintenance treatment with CsA was administered, but a recurrence of HLH was noted. The patient was referred to allogeneic hematopoietic stem cells transplantation (allo-HSCT) from the bone marrow of an unrelated donor. The follow up at the +100 day and then subsequently every 3 months after allo-HSCT showed a full hematological recovery and 100% donor chimerism. At present, 20 months after transplantation, total remission of HLH is noted. The patient does not present any adverse events linked to transplantation and is pursuing his professional career.
Keywords: hemophagocytic lymphohistiocytosishemophagocytic syndromeHLH-1994 protocolallogeneic hematopoietic stem cells transplantation
References
- Janka GE. Familial and acquired hemophagocytic lymphohistiocytosis. Annu Rev Med. 2012; 63: 233–246.
- Verbsky JW, Grossman WJ. Hemophagocytic lymphohistiocytosis: diagnosis, pathophysiology, treatment, and future perspectives. Ann Med. 2006; 38(1): 20–31.
- Zhang Z, Wang J, Ji B, et al. Incidence in Sweden and clinical features of familial hemophagocytic lymphohistiocytosis. Acta Paediatr Scand. 1991; 80(4): 428–435.
- Niece JA, Rogers ZR, Ahmad N, et al. Hemophagocytic lymphohistiocytosis in Texas: observations on ethnicity and race. Pediatr Blood Cancer. 2010; 54(3): 424–428.
- Janka GE. Hemophagocytic lymphohistiocytosis. Hematology. 2005; 10(sup1): 104–107.
- Parikh SA, Kapoor P, Letendre L, et al. Prognostic factors and outcomes of adults with hemophagocytic lymphohistiocytosis. Mayo Clin Proc. 2014; 89(4): 484–492.
- Ramos-Casals M, Brito-Zerón P, López-Guillermo A, et al. Adult haemophagocytic syndrome. The Lancet. 2014; 383(9927): 1503–1516.
- Atteritano M, David A, Bagnato G, et al. Haemophagocytic syndrome in rheumatic patients. A systematic review. Eur Rev Med Pharmacol Sci. 2012; 16(10): 1414–1424.
- Stabile A, Bertoni B, Ansuini V, et al. The clinical spectrum and treatment options of macrophage activation syndrome in the pediatric age. Eur Rev Med Pharmacol Sci. 2006; 10(2): 53–59.
- Janka G, Imashuku S, Elinder G, et al. Infection- and malignancy-associated hemophagocytic syndromes. Secondary hemophagocytic lymphohistiocytosis. Hematol Oncol Clin North Am. 1998; 12(2): 435–444.
- Henter JI, Samuelsson-Horne A, Aricò M, et al. Histocyte Society. Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation. Blood. 2002; 100(7): 2367–2373.
- Aricò M, Janka G, Fischer A, et al. Hemophagocytic lymphohistiocytosis. Report of 122 children from the International Registry. FHL Study Group of the Histiocyte Society. Leukemia. 1996; 10(2): 197–203.
- Buyse S, Teixeira L, Galicier L, et al. Critical care management of patients with hemophagocytic lymphohistiocytosis. Intensive Care Med. 2010; 36(10): 1695–1702.
- Rosado FGN, Kim AS. Hemophagocytic lymphohistiocytosis: an update on diagnosis and pathogenesis. Am J Clin Pathol. 2013; 139(6): 713–727.
- Henter JI, Horne A, Aricó M, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007; 48(2): 124–131.
- Lehmberg K, Nichols KE, Henter JI, et al. Study Group on Hemophagocytic Lymphohistiocytosis Subtypes of the Histiocyte Society. Consensus recommendations for the diagnosis and management of hemophagocytic lymphohistiocytosis associated with malignancies. Haematologica. 2015; 100(8): 997–1004.
- Rouphael NG, Talati NJ, Vaughan C, et al. Infections associated with haemophagocytic syndrome. Lancet Infect Dis. 2007; 7(12): 814–822.
- Rivière S, Galicier L, Coppo P, et al. Reactive hemophagocytic syndrome in adults: a retrospective analysis of 162 patients. Am J Med. 2014; 127(11): 1118–1125.
- Magro CM, Crowson AN, Kovatich AJ, et al. Lupus profundus, indeterminate lymphocytic lobular panniculitis and subcutaneous T-cell lymphoma: a spectrum of subcuticular T-cell lymphoid dyscrasia. J Cutan Pathol. 2001; 28(5): 235–247.
- Willemze R, Jansen PM, Cerroni L, et al. EORTC Cutaneous Lymphoma Group. Subcutaneous panniculitis-like T-cell lymphoma: definition, classification, and prognostic factors: an EORTC Cutaneous Lymphoma Group Study of 83 cases. Blood. 2008; 111(2): 838–845.
- Bosisio F, Boi S, Caputo V, et al. Lobular panniculitic infiltrates with overlapping histopathologic features of lupus panniculitis (lupus profundus) and subcutaneous T-cell lymphoma: a conceptual and practical dilemma. Am J Surg Pathol. 2015; 39(2): 206–211.
- George MR. Hemophagocytic lymphohistiocytosis: review of etiologies and management. J Blood Med. 2014; 5: 69–86.
- Allen CE, Yu X, Kozinetz CA, et al. Highly elevated ferritin levels and the diagnosis of hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2008; 50(6): 1227–1235.
- Grangé S, Buchonnet G, Besnier E, et al. The Use of Ferritin to Identify Critically Ill Patients With Secondary Hemophagocytic Lymphohistiocytosis. Crit Care Med. 2016; 44(11): e1045–e1053.
- Nikiforow S, Berliner N. The unique aspects of presentation and diagnosis of hemophagocytic lymphohistiocytosis in adults. Hematology Am Soc Hematol Educ Program. 2015; 2015: 183–189.
- Gupta A, Weitzman S, Abdelhaleem M. The role of hemophagocytosis in bone marrow aspirates in the diagnosis of hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2008; 50(2): 192–194.
- Strauss R, Neureiter D, Westenburger B, et al. Multifactorial risk analysis of bone marrow histiocytic hyperplasia with hemophagocytosis in critically ill medical patients--a postmortem clinicopathologic analysis. Crit Care Med. 2004; 32(6): 1316–1321.
- Schram AM, Berliner N. How I treat hemophagocytic lymphohistiocytosis in the adult patient. Blood. 2015; 125(19): 2908–2914.
- Fisman DN. Hemophagocytic syndromes and infection. Emerg Infect Dis. 2000; 6(6): 601–608.
- Wang Sa, Degar BA, Zieske A, et al. Hemophagocytosis exacerbated by G-CSF/GM-CSF treatment in a patient with myelodysplasia. Am J Hematol. 2004; 77(4): 391–396.
- Stéphan JL, Donadieu J, Ledeist F, et al. Treatment of familial hemophagocytic lymphohistiocytosis with antithymocyte globulins, steroids, and cyclosporin A. Blood. 1993; 82(8): 2319–2323.
- Johnson TS, Terrell CE, Millen SH, et al. Etoposide selectively ablates activated T cells to control the immunoregulatory disorder hemophagocytic lymphohistiocytosis. J Immunol. 2014; 192(1): 84–91.
- Imashuku S, Kuriyama K, Teramura T, et al. Requirement for etoposide in the treatment of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. J Clin Oncol. 2001; 19(10): 2665–2673.
- Thompson PA, Allen CE, Horton T, et al. Severe neurologic side effects in patients being treated for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2009; 52(5): 621–625.
- La Rosée P. Treatment of hemophagocytic lymphohistiocytosis in adults. Hematology Am Soc Hematol Educ Program. 2015; 2015: 190–196.
- Fischer A, Cerf-Bensussan N, Blanche S, et al. Allogeneic bone marrow transplantation for erythrophagocytic lymphohistiocytosis. J Pediatr. 1986; 108(2): 267–270.
- Ouachée-Chardin M, Elie C, de Saint Basile G, et al. Hematopoietic stem cell transplantation in hemophagocytic lymphohistiocytosis: a single-center report of 48 patients. Pediatrics. 2006; 117(4): e743–e750.
- Marsh RA, Allen CE, McClain KL, et al. How I treat hemophagocytic lymphohistiocytosis. Blood. 2011; 118(15): 4041–4052.
- Marsh RA, Vaughn G, Kim MO, et al. Reduced-intensity conditioning significantly improves survival of patients with hemophagocytic lymphohistiocytosis undergoing allogeneic hematopoietic cell transplantation. Blood. 2010; 116(26): 5824–5831.
- Abdelkefi A, Ben Jamil W, Torjman L, et al. Hemophagocytic syndrome after hematopoietic stem cell transplantation: a prospective observational study. Int J Hematol. 2009; 89(3): 368–373.
- Jordan MB, Filipovich AH. Hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis: a journey of a thousand miles begins with a single (big) step. Bone Marrow Transplant. 2008; 42(7): 433–437.
