Abstract
Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages that secrete high amounts of inflammatory cytokines. HLH occurring after SCT is difficult to diagnose. It is characterized by severe clinical manifestations and high mortality. Despite current therapeutic approaches, outcomes remain poor. We analyzed the incidence and risk factors of HLH after SCT and the response to treatment and prognosis of 554 patients with HLH after SCT. The cumulative incidence of HLH after SCT was 4.3% (24/554). Use of etoposide in the conditioning regimen was only factor that reduced HLH after SCT (P=0.027). All patients who received autologous transplantation were successfully treated. Patients with liver dysfunction (for example, high total bilirubin level, prolonged prothrombin time and high level of fibrinogen degradation products) had a poor response to treatment for HLH. Physicians should be cautious of HLH, while not using etoposide for conditioning regimen.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Janka GE . Hemophagocytic syndromes. Blood Rev 2007; 21: 245–253.
Arico M, Janka G, Fischer A, Henter JI, Blanche S, Elinder G et al. Hemophagocytic lymphohistiocytosis. Report of 122 children from the International Registry. FHL Study Group of the Histiocyte Society. Leukemia 1996; 10: 197–203.
Bode SF, Lehmberg K, Maul-Pavicic A, Vraetz T, Janka G, Stadt UZ et al. Recent advances in the diagnosis and treatment of hemophagocytic lymphohistiocytosis. Arthritis Res Ther 2012; 14: 213.
Ishii E, Ohga S, Imashuku S, Yasukawa M, Tsuda H, Miura I et al. Nationwide survey of hemophagocytic lymphohistiocytosis in Japan. Int J Hematol 2007; 86: 58–65.
Rigaud S, Fondanèche MC, Lambert N, Pasquier B, Mateo V, Soulas P et al. XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome. Nature 2006; 444: 110–114.
Abdelkefi A, Ben Jamil W, Torjman L, Ladeb S, Ksouri H, Lakhal A et al. Hemophagocytic syndrome after hematopoietic stem cell transplantation: a prospective observational study. Int J Hematol 2009; 89: 368–373.
Takagi S, Masuoka K, Uchida N, Ishiwata K, Araoka H, Tsuji M et al. High incidence of haemophagocytic syndrome following umbilical cord blood transplantation for adults. Br J Haematol 2009; 147: 543–553.
Koyama M, Sawada A, Yasui M, Inoue M, Kawa K . Encouraging results of low-dose etoposide in the treatment of early-onset hemophagocytic syndrome following allogeneic hematopoietic stem cell transplantation. Int J Hematol 2007; 86: 466–467.
Fukunaga A, Nakamura F, Yoshinaga N, Inano S, Maruyama W, Hirata H et al. Successful treatment with combined chemotherapy of two adult cases of hemophagocytic lymphohistiocytosis in recipients of umbilical cord blood cell transplantation. Int J Hematol 2011; 93: 551–554.
Ishida H, Yoshida H, Yoshihara T, Ito M, Morimoto A . Origin of macrophages involved in the development of allogeneic hematopoietic stem cell transplantation-associated hemophagocytic syndrome: observations on a patient with juvenile myelomonocytic leukemia. Bone Marrow Transplant 2007; 40: 701–703.
Levy J, Wodell RA, August CS, Bayever E . Adenovirus-related hemophagocytic syndrome after bone marrow transplantation. Bone Marrow Transplant 1990; 6: 349–352.
Nagafuji K, Eto T, Hayashi S, Tokunaga Y, Gondo H, Niho Y . Fatal cytomegalovirus interstitial pneumonia following autologous peripheral blood stem cell transplantation. Fukuoka Bone Marrow Transplantation Group. Bone Marrow Transplant 1998; 21: 301–303.
Takahashi T, Kanda Y, Mori M, Saito T, Chiba S, Mitani K et al. B cell lymphoma-associated hemophagocytic syndrome after PBSCT. Bone Marrow Transplant 1998; 21: 623–625.
Fukuno K, Tsurumi H, Yamada T, Oyama M, Moriwaki H . Graft failure due to hemophagocytic syndrome after autologous peripheral blood stem cell transplantation. Int J Hematol 2001; 73: 262–265.
Ostronoff M, Ostronoff F, Coutinho M, Calixto R, Souto Maior AP, Sucupira A et al. Hemophagocytic syndrome after autologous peripheral blood stem cell transplantation for multiple myeloma; successful treatment with high-dose intravenous immunoglobulin. Bone Marrow Transplant 2006; 37: 797–798.
Sokal E, Michel M, Ninane J, Latinne D, de Bruyere M, Cornu G . Bone marrow transplantation from an unrelated donor for Fanconi's anaemia: two unusual complications. Bone Marrow Transplant 1987; 2: 99–102.
Reardon DA, Roskos R, Hanson CA, Castle V . Virus-associated hemophagocytic syndrome following bone marrow transplantation. Am J Pediatr Hematol Oncol 1991; 13: 305–309.
Sato M, Matsushima T, Takada S, Hatsumi N, Kim K, Sakuraya M et al. Fulminant, CMV-associated, haemophagocytic syndrome following unrelated bone marrow transplantation. Bone Marrow Transplant 1998; 22: 1219–1222.
Ishikawa J, Maeda T, Miyazaki T, Manabe N, Honda S, Nishiura T et al. Early onset of hemophagocytic syndrome following allogeneic bone marrow transplantation. Int J Hematol 2000; 72: 243–246.
Abe Y, Choi I, Hara K, Matsushima T, Nishimura J, Inaba S et al. Hemophagocytic syndrome: a rare complication of allogeneic nonmyeloablative hematopoietic stem cell transplantation. Bone Marrow Transplant 2002; 29: 799–801.
Tanaka T, Matsubara H, Adachi S, Chang H, Fujino H, Higashi Y et al. Second transplantation from HLA 2-loci-mismatched mother for graft failure due to hemophagocytic syndrome after cord blood transplantation. Int J Hematol 2004; 80: 467–469.
Kishi Y, Kami M, Murashige N, Tanaka Y, Haraguchi K, Fujisaki G et al. Hyperacute GVHD and emergence of peripheral CD3+CD56+ T cells and activated natural killer cells are useful markers for early diagnosis of post-transplant hemophagocytic syndrome. Bone Marrow Transplant 2005; 35: 415–417.
Boelens JJ, Lazo G, Gaiser JF, Wulffraat NM . Epstein-Barr virus-associated haemophagocytic lympho-histiocytosis after stem cell transplantation. Bone Marrow Transplant 2006; 38: 709–710.
Tanaka H, Ohwada C, Sakaida E, Takeda Y, Abe D, Oda K et al. Successful engraftment by second cord blood transplantation with reduced-intensity conditioning after graft rejection due to hemophagocytic syndrome following initial CBT. Bone Marrow Transplant 2007; 40: 995–996.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
Kobayashi, R., Tanaka, J., Hashino, S. et al. Etoposide-containing conditioning regimen reduces the occurrence of hemophagocytic lymphohistiocytosis after SCT. Bone Marrow Transplant 49, 254–257 (2014). https://doi.org/10.1038/bmt.2013.145
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/bmt.2013.145
Keywords
This article is cited by
-
Congenital sideroblastic anemia model due to ALAS2 mutation is susceptible to ferroptosis
Scientific Reports (2022)
-
Radiation-sparing reduced-intensity unrelated umbilical cord blood transplantation for rare hematological disorders in children
International Journal of Hematology (2022)
-
Hematopoietic Cell Transplantation with Reduced Intensity Conditioning Using Fludarabine/Busulfan or Fludarabine/Melphalan for Primary Immunodeficiency Diseases
Journal of Clinical Immunology (2021)
-
Haemophagocytic lymphohistiocytosis (HLH) following allogeneic haematopoietic stem cell transplantation (HSCT)—time to reappraise with modern diagnostic and treatment strategies?
Bone Marrow Transplantation (2020)
-
My jamais vu in post allogeneic hematopoietic cell transplant: a review on secondary hemophagocytosis in adults
Bone Marrow Transplantation (2020)