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.