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.