Conditioning, GVHD prophylaxis, and supportive care

The RIC regimen was fludarabine (25 mg/m² per day intravenously [IV] × 5 days) and melphalan (140 mg/m²) on day −2. For patients ≥ 60 of age, melphalan was at 100 mg/m². The MAC regimen was fludarabine (30 mg/m² IV) and total body irradiation at 150 cGy twice a day in 8 fractions (Figure 1). PBSC was the graft source. PTCy (50 mg/kg/day) was administered on days +3 and +4. Tacrolimus (1 mg continuous IV) was started on day +5 with dose adjustment to maintain a level of 5 to 15 ng/mL and then changed to the equivalent oral dose. A tacrolimus taper was started on day +90 in patients without active GVHD. MMF was administered at a 15-mg/kg dose 3 times per day beginning on day +5 (maximum dose, 1 g orally, 3 times per day) and stopped on day +35 if there was no severe GVHD. Granulocyte colony-stimulating factor (5 µg/kg per day) was given from day +5 until there was an absolute neutrophil count > 1500/mm³ for 3 consecutive days. Additional supportive care was provided according to institutional guidelines, including prophylactic antibiotics and sinusoidal obstruction syndrome prophylaxis. Letermovir for cytomegalovirus (CMV) prophylaxis was initiated as part of institutional guidelines for CMV-seropositive recipients on 1 March 2018.

Study schema and HCT outcomes. (A) RIC regimen. Fludarabine was administered at the daily dose of 25 mg/m² from days −7 to −3 before HCT. Melphalan was given on day −2 at 140 mg/m² for patients who were younger than 60 years old. Melphalan dose for patients ≥60 years old was 100 mg/m². (B) MAC regimen consisted of daily fludarabine at 30 mg/m², from days −7 to −5 before HCT. Total body irradiation was administered in 8 fractions of 150 cGy, 2 times a day, from days −4 to −1, for a total of 1200 cGy. Graft source was PBSCs for both strata, and GVHD prophylaxis was PTCy at 50-mg/kg daily dose on days +3 and +4. Granulocyte colony-stimulating factor administration (5 µg/kg per day) was started on day +5 and continued until absolute neutrophil count >1500/mm³ for 3 consecutive days. Tacrolimus (1 mg continuous IV) administration started on day +5 with dose adjustment to maintain a level of 5 to 15 ng/mL and then changed to equivalent oral dose once stable. Tacrolimus taper was started on day +90 if patient did not have active GVHD. MMF was administered at 15 mg/kg dose 3 times per day beginning on day +5 (maximum dose, 1 g orally, 3 times per day). MMF administration was stopped on day +35 if there was no severe GVHD. (C) Kalan-Meier curve showing survival outcomes and (D) relapse and nonrelapse mortality outcomes.