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Single centre results of targeted busulphan, fludarabine and serotherapy conditioning in haematopoietic stem cell transplantation for haemophagocytic lymphohistiocytosis

Bone Marrow Transplantation volume 53, pages 784–786 (2018)Cite this article

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Haemophagocytic lymphohistiocytosis (HLH) is a multisystem clinical syndrome characterised by an excessive immune response to various stimuli, with subsequent development of a hyperinflammatory state [1]. The clinical features of HLH reflect this pattern of excessive inflammation, and typically include manifestations, such as prolonged fever, splenomegaly and cytopenias [2]. HLH can be the result of primary defects in natural killer (NK) cell or cytotoxic T-cell function, or secondary to infection, autoimmune disease or malignancy, and often a combination of these predisposing factors [1]. There are well-described molecular defects that can predispose patients to the development of HLH, including familial HLH and primary immunodeficiencies [3]. Untreated HLH has high rates of mortality, but primary HLH can be corrected by haematopoietic stem cell transplantation (HSCT) [4].

Early attempts at HSCT for HLH with myeloablative conditioning had poor outcomes, with high rates of transplant related mortality (TRM) and poor long-term survival [5]. More recently reduced intensity conditioning (RIC) regimens containing Fludarabine and Melphalan have been demonstrated to be safe and effective [5,6,7,8]. However, these reduced intensity transplants have high levels of mixed donor chimerism, which if very low, may contribute to primary disease relapse [9]. With this knowledge, the use of targeted, non-myeloablative Busulphan dosing, with measurement of area-under-the-curve (AUC) and dose adjustment accordingly has been considered an attractive option for conditions where full myeloablative conditioning is not required or potentially harmful. Here we describe the use of targeted, non-myeloablative Busulphan dosing, alongside Fludarabine and serotherapy, including alemtuzumab in the majority of these patients, in a cohort of patients with HLH and disorders predisposing to HLH in a single centre.

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Authors and Affiliations

  1. Department of Allergy and Immunology, The Royal Children’s Hospital, Melbourne, VIC, Australia

    Stephanie Richards, Sharon Choo & Theresa Cole

  2. Laboratory Services, Immunology Laboratory, The Royal Children’s Hospital, Melbourne, VIC, Australia

    Stephanie Richards & Sharon Choo

  3. Children’s Cancer Centre, The Royal Children’s Hospital, Melbourne, VIC, Australia

    Francoise Mechinaud

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  1. Stephanie Richards
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  2. Sharon Choo
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Correspondence to Stephanie Richards.

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Richards, S., Choo, S., Mechinaud, F. et al. Single centre results of targeted busulphan, fludarabine and serotherapy conditioning in haematopoietic stem cell transplantation for haemophagocytic lymphohistiocytosis. Bone Marrow Transplant 53, 784–786 (2018). https://doi.org/10.1038/s41409-018-0125-5

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