Non-Hodgkin Lymphoma after kidney transplantation in a Cobalamin B deficiency patient: an incidental finding or increased risk of cancer?

Background: Renal transplant is a successful therapeutic approach in methylmalonic aciduria due to either methylmalonil-CoA or cobalamin A (cblA) or B (cblB) deficiency. However, little is known about the possible long-term complications of transplanted MMA patients. Herein, we present a cblB patient who developed a malignant neoplasm twenty years after kidney transplantation.

Case report

Patient V.G. with cblB deficiency (homozygous p.R186W, MMAB gene, courtesy of M. Baumagartner, Zurich) was diagnosed at 6 months of age and underwent a kidney transplant at 18 years old due to severe kidney insufficiency. After induction with basiliximab, he was treated with corticosteroids, tacrolimus and mycophenolate. After transplantation, he had no metabolic decompensations or neurological complications and graduated with a degree in biology. However, 20 years after the transplant, the patient suddenly developed grade IV diffuse large cell non-Hodgkin lymphoma (NHL), centrogerminative type, located in the colon, and was EBV and HHV8 negative. During chemotherapy, he presented with severe pneumonia, followed by pulmonary embolism and a basal ganglia haemorrhage. He died three months after the diagnosis, at 39 years of age.

Discussion: Data from international databases show an increased incidence of NHL in recipients of solid organ transplants. The incidence has a biphasic pattern, occurring either less than 12 months after transplantation or after 7-10 years. Recognised risk factors are seronegative EBV status, donor/recipient EBV mismatch, high dose depleting polyclonal antibody induction, long maintenance immunosuppression and older age. The role of MMA as a risk factor for post-transplant NHL has not yet been reported, although histone deacetylation by propionyl-CoA, mitochondrial dysfunction, and increased oxidative stress may play a role in the increased tumour risk.