Post-Transplant Myelodysplastic Syndromes In Pediatric Liver Transplantation Recipients: a Report of Two Cases

Organ transplantation recipients are generally considered to be at higher risk to develop a malignancy mainly due to prolonged inmunosuppression. The most common haematologic malignancies observed in the post-transplantation setting are B-cell lymphoproliferative disorders. Myeloid neoplasms are rare and most of them have been reported in patients undergoing heart, lung or kidney transplant. Only fifteen acute myeloid leukaemia (AML) and two myelodysplasic syndromes (MDS) cases have been described so far. We report the diagnosis of two MDS in two of the 160 paediatric recipients who underwent liver transplantation (LT) in our center.

Patient 1: A 6-year-old child received a liver graft for idiopatic fulminant hepatic failure in December 2006. Inmunosuppressive medication was consisted of Basiliximab induction plus Tacrolimus and prednisone. On the eighth postoperative day a histologically proven rejection grade I occurred, successfully treated with methylprednisolone bolus therapy. Subsequently the patient did well until Abril 2010, when a peripheral blood smear showed 18% blast cells, 31% neutrophils, 46%lymphocytes. The white blood cell count was 4.2 × 1000/μL, the haemoglobin 10.6 g/dL and the platelets 34 × 1000/μL. Bone marrow aspiration showed dysplastic changes in the myelopoietic cells and 12% of blast cells. Myelodysplastic syndrome type refractory anemia with exess blasts (RAEB-2) was diagnosed. The blast cells inmunophenotype was CD34+, CD117+, CD13++, and CD33+. Kariotype analysis revealed a normal 46XX kariotype.

Patient 2: In May 2007 a 15-year-old female patient underwent LT for idiopathic acute liver failure. Inmunosuppression consisted of tacrolimus and steroids for the first 3 months. No induction therapy was added. The patient remained in good health with good liver function for 31 months. In a routine follow-up in December 2009 pancytopenia was detected. The white blood cell count was 3.1 × 1000/μL with 31% neutrophils, 66% lymphocytes and 2% monocytes. The haemoglobin was 7.7 g/dL, and platelets were 29 × 1000/μL. Subsequent bone marrow aspiration showed multilineage dysplasia and 15% myeloid blast cells, classified as MDS type RAEB-2. No HLA related donor was found. Two months later the bone marrow showed leukemic infiltration with 38% myeloid blast cells. The inmunophenotype was CD34+, CD117+, CD13+, CD33+, CD133+, and MPO+. Cytogenetic analysis revealed a normal 46XX kariotype. AML with myelodysplasia-related changes was diagnosed.

No molecular changes typical of therapy-related MDS were found in any of the cases.

Donor and recipient genotypes were identified by real-time PCR to quantify donor chimerism (DC) after LT. In the first case, there was no difference between the donor and recipient genotype and chimerism study could not be done. In the second case DC after LT was not found neither at the moment of the MDS diagnose nor in the next 3 months.

MDS/AML has rarely been reported after liver transplantation, and MDS isn't frequently found in the paediatric population. In contrast to previous reports rapid progression to AML was observed in our patients. The present cases support the need for further investigation of the mechanism leading to post-transplant myelodysplastic syndromes and the acute leukaemia in the setting of solid organ transplantation.

No relevant conflicts of interest to declare.