Donor-Cell Acute Leukemia after Sibling Marrow Grafting for Aplastic Anemia: Another Type of Familial Monosomy 7?.

We report here the case of a bone marrow transplant (BMT) patient who received a graft from her 1-year-old HLA-identical brother for severe aplastic anemia (AA) with severe thrombopenia at the age of 4, followed by myelodysplasia at the age of 6 that transformed to AREBt/AML type M6 at the age of 7. She died at the age of 8.

Two years after the BMT, the brother developed hypoplasia that rapidly transformed to AML-M2 and he died rapidly during chemotherapy induction.

Cytogenetic results showed that the brother initially developed an AML-M2 with a t(16;21) translocation and, 3 years later, the patient developed an AREBt/AML-M6 with a monosomy 7 and a donor profile (45,XY,−7). Retrospective examinations did not allow the detection of the t(16;21) in any samples of the patient nor monosomy 7 in any available sample from her brother.

This observation shows that the same cells (the donor cells) in another microenvironment, even HLA-identical, can transform to different acute leukemia types with different chromosomal abnormalities. In both, the chromosomal abnormalities seem to appear at a late stage of the disease and can be considered a secondary event. Familial MDS/AML with monosomy 7 are well described: heterozygous deletion and nonpreferential deletion of parental chromosome suggest that the inherited gene(s) might not be located on chromosome 7. Other familial hematological disorders such as familial platelet disorders present a AML1 translocation or mutation. In our case, on one hand, two hematological disorders in siblings (one AA and one AML at diagnosis) can be considered a familial case even if the past medical history of the other members of the family is unremarkable. On the other hand, the same cells (the brother’s cells) have provided a translocation involving AML1 in the donor and a monosomy 7 in the recipient, the two genetic abnormalities being involved in familial hematological disorders. We could hypothesize that those two events might have been induced by the same inherited gene(s) that could be responsible at the same time for familial monosomy 7 and for other familial hematological disorders.