Successful Hematopoietic Stem Cell Transplantation In a Child With Paroxysmal Nocturnal Hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disorder characterized by complement-mediated hemolysis, thrombosis, and bone marrow failure. The clinical manifestations of PNH are usually seen in adulthood and are very rarely reported in children. The experience with transplantation in the management of children with PNH is also very limited. Here in this paper, we report a child with PNHpresenting with an episode of hemolytic anemia who was treated successfully with hematopoietic stem cell transplantation (HSCT).

An eleven-year-old patient presented with a history of fatigue. On physical examination, there was no lymphadenopathy, and liver and spleen were not palpable. Laboratory analysis revealed a hemoglobin of 5.7 g/dL, platelets of 124.000/mL, and white blood cells were 1420/ml. She had increased lactate dehydrogenase and reticulocyte count and decreased haptoglobulin level. Bone marrow biopsy showed erythroid hyperplasia and relative hypocellularity in myeloid cell lines. Chromosomal karyotyping of bone marrow cells was normal. To look for PNH, immunophenotyping was performed. Flow cytometric analysis showed a PNH clone within the RBCs, granulocytes and monocytes. These findings were consistent with a diagnosis of PNH and she was started on anti-complement therapy with eculizumab. Since matched sibling donor was available, she was referred to our center for transplantation. The conditioning regimen of HSCT consisted of fludarabine (40 mg/m²day -9 to -6) and busulphan (4 mg/kg, day -5 to -2) combined with anti-thymocyte globulin (ATG) (Fresenius, Munich, Germany) (5 mg/kg, day -2 to 0). GVHD prophylaxis consisted of metotrexate plus cyclosporin. The infusion of bone marrow stem cells contained 11.8x10⁶ CD34⁺ cells/kg and 7.9 x10⁸total nucleated cells/kg. The patient had no significant complications in the post-transplant period. Neutrophil and platelet engraftment occurred on posttransplant day 11 and day 18, respectively. She is alive and is doing well over 14 months following BMT. Recovery is complete with full donor chimerism and the eradication of PNH clone.

PNH can occur in children but is often misdiagnosed and mismanaged. Although with the advent of anti-complement therapy, pure hemolytic anemia is no longer a clear indication for HSCT in adult patient, it is not licensed for use in pediatrics. HSCT is the only curative option for patients with PNH and if suitable matched sibling donor is available, transplant should be considered. However, the experience with tranplantation is also very limited. This case is worth mentioning as it shows that busulphan, fludarabine and ATG can be safely and effectively used for conditioning in PNH in children.

No relevant conflicts of interest to declare.