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. 2023 Feb 22;9(3):e1451.
doi: 10.1097/TXD.0000000000001451. eCollection 2023 Mar.

Busulfan or Treosulfan Conditioning Platform for Allogeneic Stem Cell Transplantation in Patients Aged >60 Y With Acute Myeloid Leukemia/Myelodysplastic Syndrome: A Subanalysis of the GITMO AlloEld Study

Michele Malagola  1 , Nicola Polverelli  1 , Massimo Martino  2 , Francesca Patriarca  3 , Benedetto Bruno  4   5 , Luisa Giaccone  4   5 , Giovanni Grillo  6 , Stefania Bramanti  7 , Paolo Bernasconi  8 , Marco De Gobbi  9   10 , Annalisa Natale  11 , Elisabetta Terruzzi  12 , Attilio Olivieri  13 , Patrizia Chiusolo  14   15 , Angelo Michele Carella  16 , Marco Casini  17 , Enrico Maffini  18 , Chiara Nozzoli  19 , Patrizio Mazza  20 , Simona Bassi  21 , Francesco Onida  22 , Adriana Vacca  23 , Sadia Falcioni  24 , Mario Luppi  25 , Anna Paola Iori  26 , Vincenzo Pavone  27 , Cristina Skert  28 , Paola Carluccio  29 , Carlo Borghero  30 , Anna Proia  31 , Carmine Selleri  32 , Vicky Rubini  33 , Nicoletta Sacchi  34 , Elena Oldani  35 , Francesca Bonifazi  18 , Fabio Ciceri  36 , Domenico Russo  1
Affiliations

Busulfan or Treosulfan Conditioning Platform for Allogeneic Stem Cell Transplantation in Patients Aged >60 Y With Acute Myeloid Leukemia/Myelodysplastic Syndrome: A Subanalysis of the GITMO AlloEld Study

Michele Malagola et al. Transplant Direct. .

Abstract

The conditioning regimens with different alkylators at different doses can influence the outcome of allogeneic stem cell transplantation (SCT), but conclusive data are missing.

Methods: With the aim to analyze real-life allogeneic SCTs performed in Italy between 2006 and 2017 in elderly patients (aged >60 y) with acute myeloid leukemia or myelodysplastic syndrome, we collected 780 first transplants data. For analysis purposes, patients were grouped according to the type of alkylator included in the conditioning (busulfan [BU]-based; n = 618; 79%; treosulfan [TREO]-based; n=162; 21%).

Results: No significant differences were observed in nonrelapse mortality, cumulative incidence of relapse, and overall survival, although in the TREO-based group, we observed a greater proportion of elderly patients (P < 0.001); more active diseases at the time of SCT (P < 0.001); a higher prevalence of patients with either hematopoietic cell transplantation-comorbidity index ≥3 (P < 0.001) or a good Karnofsky performance status (P = 0.025); increased use of peripheral blood stem cells as graft sources (P < 0.001); and greater use of reduced intensity conditioning regimens (P = 0.013) and of haploidentical donors (P < 0.001). Moreover, the 2-y cumulative incidence of relapse with myeloablative doses of BU was significantly lower than that registered with reduced intensity conditioning (21% versus 31%; P = 0.0003). This was not observed in the TREO-based group.

Conclusions: Despite a higher number of risk factors in the TREO group, no significant differences were observed in nonrelapse mortality, cumulative incidence of relapse, and overall survival according to the type of alkylator, suggesting that TREO has no advantage over BU in terms of efficacy and toxicity in acute myeloid leukemia and myelodysplastic syndrome.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1.
FIGURE 1.
Long-term outcomes of the 780 transplants included in this analysis. (A) Cumulative incidence of NRM (BU vs TREO at 2 y 31.4% vs 28.8%); (B) cumulative incidence of relapse (BU vs TREO at 2 y 25.7% vs 26.8%); (C) overall survival (BU vs TREO at 2 y 45.6% vs 53.2%). BU, busulfan; NRM, nonrelapse mortality; TREO, treosulfan.
FIGURE 2.
FIGURE 2.
Cumulative incidence of relapse according to alkylator and conditioning intensity. (A) MAC regimens (BU vs TREO at 2 y 21% vs 26%; P = 0.127). (B) RIC regimens (BU vs TREO at 2 y 31% vs 27%; P = 0.37). BU, busulfan; MAC, myeloablative conditioning; RIC, reduced-intensity conditioning; TREO, treosulfan.
FIGURE 3.
FIGURE 3.
Cumulative incidence of relapse according to alkylator and conditioning intensity. (A) BU-based (MAC vs RIC at 2 y 21% vs 31%; P = 0.0003). (B) TREO-based) (MAC vs RIC at 2 y 26% vs 28%; P = 0.773). BU, busulfan; MAC, myeloablative conditioning; RIC, reduced-intensity conditioning; TREO, treosulfan.
FIGURE 4.
FIGURE 4.
Cumulative incidence of aGVHD grade ≥2: (A) BU vs TREO at 100 d 20% vs 22%; cumulative incidence of extensive cGVHD. (B) BU vs TREO at 2 y 11% vs 14%. BU, busulfan; aGVDH, acute graft versus host disease; cGVDH, chronic graft versus host disease; TREO, treosulfan.
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References

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