Discussion
Recently, we described a novel human Pol ε defect associated with
hematopoietic failure.3 The patients in our current
report are the same siblings reported there and thus may represent the
first HCT report of Pol ε defect associated hematopoietic failure. Both
cases presented with trilineage dysplasia with fluctuations in the
proportion of blasts in bone marrow, which meets the diagnostic criteria
of MDS-EB-1.4 Along with persistent transfusion
dependency, HCT was performed according to protocol for MDS
patients.5,6 MAC was selected in Case 1 because her
bone marrow showed hypercellularity and, without precedent, MAC was
considered ideal to obtain definite engraftment. As expected, Case 1
achieved stable full donor chimerism. Based on this experience, we
decided to reduce the conditioning intensity of Case 2 to avoid cardiac
toxicity7 and late complications, including impaired
fertility.8 HCT certainly resolved their bone marrow
failure, and they became transfusion independent. In Case 1, IBD also
resolved after HCT. The association of IBD and POLE gene variant
is uncertain; however, reconstitution of the immune system may be
beneficial, as in other monogenic forms of IBD.9 On
the other hand, as with variants in the exonuclease domain of thePOLE ,10 there may be outcome factors other than
bone marrow failure in these cases, and continued careful follow-up is
essential.