Discussion
No reported cases of TAM have required such lengthy treatment to achieve
disease control. In treating this patient with repeated short courses of
LDAC, we sought to achieve a safe level of disease without introducing
unacceptable toxicity, allowing time for growth and maturation before
any need for treatment escalation. Recent outcome studies confirm LDAC
is well tolerated1 and improves mortality outcomes
when compared to no-treatment4 or higher doses of
cytarabine.5 More intensive chemotherapy was
considered, however, given the fragile respiratory and cardiac status of
our patient, and the development of necrotizing enterocolitis during the
second course of LDAC, it was unlikely he would have tolerated this. A
similar approach using repeated doses of LDAC courses (but in
conjunction with vincristine and vitamin A) has been reported in the
treatment of MLDS, but not TAM.6
It is not clear why disease in this patient was unusually aggressive and
recalcitrant to treatment. Cyto- and molecular genetic analysis (Table
2) initially revealed two pathogenic variants in GATA-1. Consecutive
samples have been sequenced to high sensitivity using targeted high
throughput sequencing, but have shown no additional variants to indicate
to mutational profile of transformation to MLDS.7Interestingly though one of the GATA-1 variants became dominant, and the
other was lost, a phenomenon previously described in
TAM.7
Our instructive case demonstrates that in TAM that requires treatment
and is resistant, recurrent courses of LDAC is a practical treatment
option that can achieve disease control in fragile neonates, who are
unlikely to tolerate more intensive approaches.