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Incremental donor lymphocyte infusion to treat mixed chimerism after allogeneic stem cell transplantation in children with non-malignant diseases

Bone Marrow Transplantation volume 58, pages 109–111 (2023)Cite this article

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Mixed chimerism (MC) post hematopoietic stem cell transplantation (HSCT) is observed in children with non-malignant diseases (NMD), especially after reduced intensity conditioning [1,2,3], and can increase the risk of graft loss and recurrence of disease [1, 4, 5]. Data from limited case series indicate that donor lymphocyte infusion (DLI) could revert low levels of donor chimerism to curative levels, averting the need for a second HSCT [6,7,8]. We conducted a retrospective study in two tertiary care pediatric centers. Thirty-two children with NMD, transplanted between 2010 and 2020, received DLI for MC. Written informed consent for data collection was obtained by parents or legal guardians. Chimerism was monitored monthly, as described [9]. If MC was detected, in the absence of graft versus host disease (GVHD), immune-suppression was tailed and stopped in 2–4 weeks. Decision to proceed to DLI was based on the rate of decline of donor chimerism, on the presence of complications possibly related to MC (e.g., autoimmunity) and, if available, on lineage-specific chimerism. Escalating DLI was administered at Great Ormond Street Hospital in a maximum of three doses (1 × 107, 5 × 107, and 1 × 108 CD3+ cells/kg) at a minimum interval of 6 weeks [10]. The majority of patients at Hadassah Medical Centre received 1 × 106, 5 × 106, and 1 × 107 CD3+ cells/kg, with some variability due to physicians’ preference. Main reasons to discontinue DLI were significant acute or any chronic GVHD (aGVHD or cGVHD), achievement of a response, or need for the second HSCT. Response was categorized as partial response (PR) if stable chimerism or an increase in donor chimerism >20% with no disease-related symptoms, and complete response (CR) if reversal to full donor chimerism occurred. Categorical and continuous variables were compared using two-tailed Fisher’s exact test and Student’s t-test, respectively. Survival comparison was performed with Log Rank test. Events included death, second transplant, or stem cell boost, whichever occurred first.

Characteristics of patients, transplants, and DLI are presented in Supplementary Table I.

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Fig. 1: Outcome after DLI.

Data availability

The datasets of the current study are available from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. Bone Marrow Transplantation, Great Ormond Street Hospital for Children, London, UK

    Maria Gabelli, Giorgio Ottaviano, Khushnuma Mullanfiroze, Arina Lazareva, Giovanna Lucchini, Robert Chiesa, Juliana Silva, Maria Finch, Annette Hill, Rachel Mead, Persis J. Amrolia & Kanchan Rao

  2. Pediatric Hematology, Oncology and Stem Cell Transplantation, Università degli studi di Padova, Padova, Italy

    Maria Gabelli

  3. Bone Marrow Transplantation, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel

    Polina Stepensky, Irina Zaidman, Ehud Even-Or, Yael Dinur Schejter & Adeeb Naser Eddin

  4. Specialist Integrated Hematology and Malignancy Diagnostic Service, Hematology, Great Ormond Street Hospital for Children, London, UK

    Stuart Adams & Susanne Kricke

  5. St John’s College, Cambridge, UK

    Delphine Veys

  6. Immunology, Great Ormond Street Hospital for Children, London, UK

    Austen Worth

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  1. Maria Gabelli
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Contributions

MG and KR designed the research study and wrote the manuscript. MG and PS collected patient data. MG and GO analyzed the data. MG, PS, KM, AL, IZ, EE-O, GL, JS, RC, MF, AH, RM, YDS, ANE, AW, PJA, and KR looked after patients and provided essential data. SA and SK performed chimerism analysis. All authors reviewed and approved the manuscript.

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Correspondence to Maria Gabelli.

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Gabelli, M., Stepensky, P., Ottaviano, G. et al. Incremental donor lymphocyte infusion to treat mixed chimerism after allogeneic stem cell transplantation in children with non-malignant diseases. Bone Marrow Transplant 58, 109–111 (2023). https://doi.org/10.1038/s41409-022-01844-x

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