Patient 1
A 23-month-old female with CD33+ AML was initially treated with the AML-BFM 2012 intermediate risk group protocol. Prior to receiving AML therapy, she was noted to have a mildly dilated LV with mitral regurgitation (MR) for which enalapril and furosemide were used during induction. Six months into maintenance therapy she developed an isolated medullary relapse and was re-induced (Table 1). A bone marrow biopsy and aspirate (BMBA) on day 15 of re-induction chemotherapy showed aplastic marrow with 88% blasts, prompting a decision to start GO for presumed chemorefractory disease.
Her pre-GO cumulative anthracycline exposure was 400mg/m2 and an echocardiogram (ECHO) showed low-normal left ventricular ejection fraction (LVEF) of 52% and low-normal LVSF of 26% with no MR (Figure 1). She received 3 mg/m2 GO on days 1, 4, and 7, and then underwent repeat BMBA that was hypoplastic and minimal residual disease (MRD)-negative. She then received an additional three GO doses (3mg/m2/dose) on days 15, 18, and 21 and subsequently developed prolonged pancytopenia but exhibited no symptoms of heart failure. At day 62 after GO, she initiated azacytidine and venetoclax as bridging therapy to planned bone marrow transplant (BMT).
At day 82 after GO, a routine ECHO revealed a decrease of LVEF to 40% and LVSF to 16%, a moderately dilated LV (4.41cm, from 3.5cm pre-GO), mild MR, and a brain natriuretic peptide (BNP) of 1592 pg/mL.  She was started on furosemide and enalapril, followed by carvedilol. Two weeks later, she developed pallor and fatigue requiring admission. An ECHO showed a severely dilated LV, LVEF of 32%, and LVSF of 16%. Her carvedilol dose was decreased, and digoxin was started. She completed 4 cycles of azacytidine and venetoclax during which time her LVEF improved to 54% and LVSF improved to 30% with mild LV dilation.
Seven months post-GO, she remained in an MRD-negative remission and underwent unrelated donor BMT, after which she had stable cardiac function and did not develop SOS. Her AML is in remission 9 months post-BMT and she is maintained on a regimen of carvedilol, digoxin, spironolactone, and enalapril with stable cardiac function.