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Haemophagocytic lymphohistiocytosis following allogeneic hematopoietic cell transplantation from mismatched unrelated donors associated with low CD34 and CD3 cell counts in the graft

Bone Marrow Transplantation volume 57, pages 658–660 (2022)Cite this article

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Haemophagocytic lymphohistiocytosis (HLH) is an immune dysregulation characterized by hypercytokinemia and hyperinflammatory condition. HLH is primarily caused by abnormal survival and activation of macrophages and cytotoxic T-lymphocytes (CTL) [1]. It has been observed as occurring without infectious trigger after allogeneic hematopoietic cell transplantation (allo-HCT) and was initially considered a form of graft-versus-host disease (GVHD) for which proliferation and activation of donor T-cells are crucial [2,3,4]. Post allo-HCT HLH is an aggressive and devastating complication with a poor prognosis (60–90% mortality) and little known risk factors due to the rarity of this syndrome [5]. A relatively high incidence of HLH has been described in allo-HCT from umbilical cord blood (16.8%) and from haplo-identical related donor (12.2%) graft sources but not from mismatched unrelated donor (MMUD) grafts [6, 7]. Compared to a matched unrelated donor, transplantation from MMUD has been associated with lower survival and higher treatment-related mortality [8]. This is mainly due to a higher incidence of GVHD without clear association with HLH.

Patient 1 suddenly presented with a > 39 °C fever before engraftment at D + 22 and patient 2 and 3 presented > 39 °C fever at D + 15 and D + 21 at the time of engraftment. No bacterial, fungal, or viral (CMV, EBV, HHV6, adenovirus, parvovirus B19) trigger were found. The diagnosis of HLH was made between D + 20 and D + 23 in the three patients with a H-Score between 256 and 337 resulting in a probability > 99% of having an HLH [9]. First line treatment consisted of high dose methylprednisolone 2 mg/kg/day, assuming a GVHD-like phenomenon. Patient 1 experienced a complete response, but relapse of HLH (major cytopenia, neurological signs, ferritin level: 36377 ng/mL, H-score: 217, HLH probability 96%) was diagnosed at D + 56. He received etoposide 150 mg/m² for 3 days but died of E. Coli sepsis at D + 67. Methylprednisolone was ineffective in patients 2 and 3. Patient 2 quickly evolved into mixed chimerism (78.7% donor) and persistent aplasia, preventing any further treatment, and dying at D + 43. For patient 3, etoposide 150 mg/m2 for 2 days was used and a spectacular remission was observed, but the patient later died from infectious complications (HHV6 encephalitis, Pseudomonas Aeruginosa bacteriemia, pulmonary aspergillosis).

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Fig. 1: Description of HLH-patients and the log10 [CD34*CD3] variable.

Data availability

The data that support the findings of this study are available on request from the corresponding author.

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Acknowledgements

The authors would like to thank Rachel Tipton for proofreading the paper for English. This study was not endorsed by a research grant.

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Authors and Affiliations

  1. Department of Hematology, CHU Lille, Lille, France

    Nicolas Gower, Valérie Coiteux, Micha Srour, Léonardo Magro, Paul Chauvet, Ibrahim Yakoub-Agha & David Beauvais

  2. Department of internist medicine and clinical immunology, CHU Lille, Lille, France

    Louis Terriou

  3. Immunology Institut, CHU Lille, Lille, France

    Pauline Varlet

  4. Univ. Lille, Inserm, CHU Lille, U1286-Infinite-Institute for Translational Research in Inflammation, Lille, France

    Pauline Varlet, Ibrahim Yakoub-Agha & David Beauvais

  5. Établissement Français du Sang Hauts-de-France-Normandie, Unité de Thérapie Cellulaire et Banque de Sang Placentaire site de LILLE, 59 000, Lille, France

    Caroline Ballot

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Contributions

NG and DB designed the study. VC, LT, and IYA supervised the study. NG, MS, LM, PC collected clinical data. PV and CB collected biological data. NG and DB performed data analysis and wrote the initial paper. All authors read and approved the final paper.

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Correspondence to David Beauvais.

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Gower, N., Coiteux, V., Srour, M. et al. Haemophagocytic lymphohistiocytosis following allogeneic hematopoietic cell transplantation from mismatched unrelated donors associated with low CD34 and CD3 cell counts in the graft. Bone Marrow Transplant 57, 658–660 (2022). https://doi.org/10.1038/s41409-022-01585-x

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