INTRODUCTION:

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for high-risk acute myeloid leukemia (AML).The preparative regimen consisting of busulfan and cyclophosphamide (BuCy) is considered as one of the classical myeloablative conditioning regimens (MAC); however, it is associated with significant early and long-term toxicities, leading to a high rate of transplant-related mortality (TRM).

Purpose: To compare toxicities and outcomes of BuCy and FluBu12 conditioning in the pediatric population.

Methods:

We retrospectively analyzed 71 pediatric high-risk AML patients in CR1/2 (n=51, 71,8%) and R/R disease (n=20, 28,2%) received allo-HSCT from MSD (n=16, 22,5%), MUD (n=43, 60,6%) and Haplo donor (n=12, 16,9%). BuCy and FluBu conditioning regimens were used in 47 (66,2%) and 24 (33,8%) patients respectively. Median age was 6 years (0-17). GVHD prophylaxis was PTCy±CNI±m-TOR inhibitor in 32 (45%) or ATG±CNI in 39 (55%) patients. The primary end points were TRM, relapse-free survival (RFS), graft-versus-host disease (GVHD) free, relapse free survival (GRFS) and overall survival (OS). Secondary end points included neutrophil engraftment, sinusoidal obstruction syndrome (SOS), acute and chronic GVHD. Patient were censored at the time of death or last follow-up. Probabilities of OS, RFS and GRFS were estimated using Kaplan-Meier curves. TRM was defined as any death that occurred in the absence of disease relapse; relapse was a competing risk for this event.

Results:

Engraftment rate was 91% and 87,5% in patients received BuCy and FluBu, respectively (p=0,4). There was a trend to lower day 100 TRM after FluBu (4,1% vs 14,9% after BuCy, p=0,07). Overall survival at 2 years did not differ as well (BuCy 48,9%, FluBu 56%, p=0,5). BuCy showed borderline higher RFS at 2 years (70,2% vs 52%, p=0,06). The composite endpoint GRFS did not differ between two study cohorts being 31,8% and 29,2% at 2 years for BuCy and FluBu (p=0,7). We observed a tendency towards a higher incidence of III0-IV0 aGVHD and cGVHD following BuCy when compared with FluBu: 57,1% vs 41% (p=0,06) and 46,5% vs 28,5% respectively (p=0,2). No significant differences were found between the BuCy and FluBu groups in risk of SOS (6% and 8%, respectively).

Conclusions:

The optimal conditioning regimen for children with AML is still a matter of debate. Our results suggest that FluBu represents a valid myeloablative regimen, able to provide lower TRM, aGVHD and cGVHD. This conditioning might become an alternative approach in patients with a high risk of severe post-transplant complications.

Disclosures

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.

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