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MRD response in a refractory paediatric T-ALL patient through anti-programmed cell death 1 (PD-1) Ab treatment associated with induction of fatal GvHD

Bone Marrow Transplantation volume 52, pages 1221–1224 (2017)Cite this article

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Children with acute lymphoblastic T-cell leukaemia (T-ALL) who relapse after allogeneic stem cell transplantation (SCT) have limited treatment options and a poor prognosis.1 Immune checkpoint inhibitors targeting the programmed death (PD-1) receptor pathway may enhance the GvL effect by blockade of inhibitory signals to T cells mediated by its ligand PD-L1.2 There has been limited experience with the use of checkpoint inhibitors in haematologic malignancies post allogeneic SCT, especially concerning the (re)activation of GvHD.3, 4, 5, 6, 7 Recently, Singh et al.5 reported a patient receiving anti-PD-1 treatment for refractory Hodgkin’s lymphoma after allogeneic SCT who developed fatal GvHD. Previous reports of anti-PD-1 treatment post SCT demonstrated no induction of GvHD post SCT. However, these patients had no previous acute or chronic GvHD.4, 7, 8

The presented case is the first one to our knowledge to report a remarkable and fast response to PD-1 inhibition followed by a severe lethal inflammatory disease and GvHD of the skin, liver, lung, CNS and eyes in the setting of a paediatric T-ALL patient post allogeneic SCT. This clinical course and intensity of acute GvHD was similar to the patient reported by Singh et al.5 Other reports of patients treated with immune checkpoint inhibitors (ipilimumab, pidilizumab and nivolumab) after allogeneic SCT, showed no exacerbation or reactivation of GvHD.3, 4, 12 In a recently published study of 28 patients with haematologic malignancies receiving ipilimumab after allogeneic SCT, three patients developed chronic GvHD of the liver and one patient developed acute GvHD of the gut.6 In contrast to our patient presented above, all of the symptoms resolved with glucocorticoids. It should be noted that all these SCTs reported were from matched-related or -unrelated donors and not from haploidentical donors. It is still unclear which factors trigger the GvHD reaction and which are preventive. The risk of GvHD re(activation) due to PD-1/PD-L1 inhibition might be more severe during the early phase post transplantation. Our patient received pembrolizumab 12 months after the SCT, which was earlier than in previously described cases.4, 7 In addition, the haploidentical donor type may have increased the risk for severe GvHD. Until now, there is no standardised treatment option for refractory T-ALL available, indicating an urgent need for new therapeutic approaches. Since the MRD response in the patient described here was very promising, it will be important to gain more information and experience regarding the efficient and safe treatment with PD-1 inhibitors post allogeneic SCT.

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Authors and Affiliations

  1. Department of Paediatric Hematology, Oncology and Stem Cell Transplantation, Dr von Hauner University Children’s Hospital, Ludwig Maximilian University, Munich, Germany

    A-M Boekstegers, F Blaeschke, I Schmid, V Wiebking, S Immler, F Hoffmann & T Feuchtinger

  2. Department of Clinical Radiology, Institute for Clinical Radiology, Ludwig Maximilian University, Munich, Germany

    K Bochmann

  3. Institute of Pathology, Ludwig Maximilian University, Munich, Germany

    S Müller

  4. Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Pathology, Ludwig Maximilians University, Munich, Germany

    T G P Grünewald

  5. Memorial Sloan Kettering Cancer Center, Center for Cell Engineering, New York, NY, USA

    J Feucht

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Correspondence to A-M Boekstegers.

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Boekstegers, AM., Blaeschke, F., Schmid, I. et al. MRD response in a refractory paediatric T-ALL patient through anti-programmed cell death 1 (PD-1) Ab treatment associated with induction of fatal GvHD. Bone Marrow Transplant 52, 1221–1224 (2017). https://doi.org/10.1038/bmt.2017.107

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