Successful nivolumab therapy in an allogeneic stem cell transplant child with post-transplant lymphoproliferative disorder

Pediatr Transplant. 2018 Dec;22(8):e13302. doi: 10.1111/petr.13302. Epub 2018 Oct 21.

Abstract

Primary CNS PTLD is an extremely rare complication after allogeneic HSCT. At our centre, an 11-year-old patient developed nausea, vomiting, and diplopy on day +82 following HSCT. On brain MRI, multiple white matter lesions were seen. Histology showed a diffuse large B-cell lymphoma with high load of EBV in tissue. Despite stopping immunosuppression, treatment with EBV-specific cytotoxic T cells, systemic rituximab, HD-MTX, and intrathecal chemotherapy, progression was observed. With a combination of HD-MTX and cytarabine, only a partial response could be achieved. Having all conventional modalities not only failed but resulted in significant toxicity, a salvage monotherapy with biweekly nivolumab has been instituted. The starting dose was 1.1 mg/kg, later escalated to 2.2 mg/kg. After 8 months of nivolumab therapy, PET-CT showed complete metabolic remission. Subsequently, the patient has been switched to a maintenance dosage of 1.1 mg/kg. No cytopenias, graft failure, GvHD, or any other alloimmune complications were seen during nivolumab therapy. In conclusion, nivolumab may be considered as an effective and safe option for CNS PTLD therapy when all other modalities have failed.

Keywords: central nervous system; diffuse large B-cell lymphoma; hematopoietic stem cell transplantation; nivolumab; post-transplant lymphoproliferative disorder.

Publication types

  • Case Reports

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Child
  • Cytarabine / therapeutic use
  • Epstein-Barr Virus Infections / complications
  • Female
  • Fusion Proteins, bcr-abl / genetics
  • Humans
  • Immunosuppression Therapy
  • Injections, Spinal
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy*
  • Lymphoma, B-Cell / immunology
  • Lymphoproliferative Disorders / therapy*
  • Magnetic Resonance Imaging
  • Nivolumab / therapeutic use*
  • Positron Emission Tomography Computed Tomography
  • Postoperative Period
  • Remission Induction
  • Rituximab / therapeutic use
  • Stem Cell Transplantation*
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Antineoplastic Agents, Immunological
  • BCR-ABL1 fusion protein, human
  • Cytarabine
  • Nivolumab
  • Rituximab
  • Fusion Proteins, bcr-abl