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Successful salvage treatment with antithymocyte globulin for patients with early-onset hemophagocytic lymphohistiocytosis refractory to steroid and etoposide therapy following allogeneic hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 55, pages 1479–1482 (2020)Cite this article

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Early-onset hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome (HPS), after allogeneic hematopoietic stem cell transplantation (allo-SCT) is a relatively rare but crucial transplant-related complication, sometimes leading to fatal engraftment failure [1,2,3,4]. Because the event develops before or around the timing of engraftment after allo-SCT, it is often difficult to make an accurate diagnosis and an appropriate treatment. Although the mechanisms of early-onset HLH after allo-SCT are complicated and not fully understood, hyper-immune reaction for alloreactivity in which several cytokines are highly elevated in the serum is likely to cause HLH in bone marrow, liver, and spleen. The cytokine stormy circumstances could create the optimal platform for T cell and monocytes/macrophages activations [4,5,6,7]. In the context of this pathophysiology, early-onset HLH after allo-SCT is mainly due to the hyper-reactivation of monocytes/macrophages triggered by several inflammatory cytokines, including interleukin-1, tumor necrosis factor-α, and interferon γ released by activated donor T cells [8, 9].

Therapeutic strategies have been developed based on these pathophysiology of early-onset HLH after allo-SCT, though an optimal treatment has not yet been established. The administration of etoposide (ETP) or dexamethasone palmitate is reportedly successful to soothe the activated monocytes/macrophages, leading to avoid looming graft failure [10,11,12]. On the other hand, Fukunaga et al. reported that ETP was insufficient, but additional vincristine (VCR) and steroid did overcome the unsatisfactoriness for two adult patients with early-onset HLH after unrelated cord blood transplantation (UCBT) [13]. Takagi et al. reported that in 78% of patients who developed early-onset HLH after UCBT, several regimens including steroid, intravenous immunoglobulin (IVIG), cyclosporine, and ETP failed to avoid engraftment failure [14].

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Acknowledgements

The authors thank all physicians, nurses, pharmacists, medical social workers, and support personnel for their care of patients.

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Authors and Affiliations

  1. Department of Hematology, Aasahikawa City Hospital, Aasahikawa, Japan

    Yasutaka Kakinoki, Naoki Miyashita, Takahiro Sekine & Kohei Kasahara

  2. Department of Hematology, Hokkaido University Faculty of Medicine, Graduate School of Medicine, Sapporo, Japan

    Takashi Ishio & Joji Shimono

  3. Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan

    Hiroyuki Kimura

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  1. Yasutaka Kakinoki
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YK managed the care for patients and wrote the paper. TI, YK, and JS primarily took care of these patients. NM, TS, and KK actively participated in reviewing patient’s data.

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Correspondence to Yasutaka Kakinoki.

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Kakinoki, Y., Ishio, T., Kimura, H. et al. Successful salvage treatment with antithymocyte globulin for patients with early-onset hemophagocytic lymphohistiocytosis refractory to steroid and etoposide therapy following allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 55, 1479–1482 (2020). https://doi.org/10.1038/s41409-020-0802-z

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