Childhood Acute Lymphoblastic Leukaemia and Aplastic Anaemia

Abstract

Aplastic anaemia (AA) can be associated with disorders that are known to exhibit clonal haematopoiesis, like paroxysmal nocturnal haemoglobinuria (PNH), myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). It appears that the long term survivors of severe AA treated with immunosuppressive agents such as ATG have a continuing, late mortality caused by the evolution of clonal disorders which are not usually seen when bone marrow transplant is used.

In children, typical AA may precede the onset of acute lymphoblastic leukemia (ALL). The aplastic phase is often transient and remission may be spontaneous or rapidly induced by steroid, and followed a few months later by acute leukaemia. This modality of presentation may be observed in up to 2-3% of all cases of paediatric ALL.

A 13-year old girl who presented with two spontaneously reversible episodes of marrow aplasia has been reported recently. She developed ALL 8 months later. Southern analysis snowed identical clonal immunoglobulin heavy chain gene rearrangement bands in her leu-kaemic cells as well as the marrow cells obtained at the two aplastic episodes. Hypoxanthine phosphoribosy transferase polymorphism studies showed that all the ALL blast cells, bone marrow and peripheral cells during the two aplastic episodes all exhibited clonal haematopoiesis with the same X-chromosome inactivated. This case provides strong evidence that A A and ALL can represent evolution of the same abnormal clone.

Key Words:

• Acute lymphoblastic leukaemia
• aplastic anaemia
• clonal haematopoiesis