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Outcome improvement over time in reduced intensity conditioning hematopoietic transplantation: a 20-year experience

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Abstract

The current study includes all consecutive patients (N = 484) who received a reduced-intensity conditioning regimen (RIC) allogeneic hematopoietic stem cell transplantation in our center from 1999 to 2020. Conditioning regimens were based on fludarabine with melphalan or busulfan, with low-dose thiotepa and pharmacological GVHD prophylaxis consisted of cyclosporine A (CsA)-methotrexate (MTX)/mofetil (MMF) (n = 271), tacrolimus-sirolimus (n = 145), and post-transplantation cyclophosphamide (PTCy)-tacrolimus (n = 68). The median time of overall follow-up in survivors was 8 years (1–22 years) and was at least 3 years in all three GVHD prophylaxis groups. Thirty-three percent had a high or very high disease risk index, 56% ≥ 4 European bone marrow transplantation risk, and 65% ≥ 3 hematopoietic stem cell transplantation comorbidity index score-age score. Neutrophil and platelet engraftment was longer for PTCy-tacro (p 0.0001). Cumulative incidence of grade III–IV aGVHD was 17% at 200 days, and that of moderate-severe cGvHD was 36% at 8 years. GVHD prophylaxis was the only prognostic factor in the multivariable analyses for the development of aGVHD and moderate-severe cGVHD (p 0.0001). NRM and relapse incidences were 29% and 30% at 8 years, while OS and PFS rates were 43% and 39% at 8 years. At 3 years, OS was highest in the PTCy-tacro group (68%) than in the tacro-siro (61%) and CsA-MTX/MMF (49%) cohorts (p < 0.01). In the three groups, respectively, the 200-day incidence of grade III–IV aGvHD (6% vs. 12% vs. 23%) and 3-year moderate-severe cGVHD (8% vs. 40% vs. 38%) were lower in the PTCy cohort. These better outcomes were confirmed in multivariable analyses. Based on our recent results, the PTCy could be considered as a real GvHD prophylaxis in the RIC setting due to improve best 3-year GvHD and survival outcomes.

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Funding

This project was funded by “La Marató de TV3” Foundation 2019 41–30, AGAUR 2017 SGR 1395, and 2021 SGR 01139 from the Catalan Government and a grant from “Obra Social La Caixa,” Barcelona, Spain. PERIS SLT002/16/0043 from the Catalan Government and FIS PI17/01246, PI20/01621, and RD16/0011/0028 from the Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Spain.

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Authors and Affiliations

  1. Hematology Department, Hospital de La Santa Creu I Sant Pau, IIB-Sant Pau and Jose Carreras Leukemia Research Institutes, Universitat Autonoma of Barcelona, Mas Casanovas, 90, 08041, Barcelona, Spain

    Albert Esquirol, Irene Garcia Cadenas, Silvana Novelli, Ana Garrido, Ana Carolina Caballero, Guadalupe Oñate, Jordi Lopez, Sara Redondo, Miguel Argüello, Silvana Saavedra, Carolina Moreno, Javier Briones, Jorge Sierra & Rodrigo Martino

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  1. Albert Esquirol
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  2. Irene Garcia Cadenas
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Contributions

A.E. designed the study, performed research, analyzed data, and wrote the manuscript; R.M. and J.S. designed the study and performed research; I.G.C., S.N, A.G, A.C.C., G.O., J.L., S.R., M.A., S.S., C.M., and J.B. contributed essential data; and all authors approved the final version of the manuscript. R.M. and J.S. contributed equally to this work as senior consultant.

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Correspondence to Albert Esquirol.

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Declarations

No human were directly involved in the study; we analyzed the final long-term outcomes in the standard procedure (RIC-alloSCT), without testing a different strategy than clinical practices. Even so, all transplants were performed according to the approved institutional protocols, and all patients signed the informed consent.

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The authors declare no competing interests.

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Jorge Sierra and Rodrigo Martino equally contributed as senior authors.

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Esquirol, A., Cadenas, I.G., Novelli, S. et al. Outcome improvement over time in reduced intensity conditioning hematopoietic transplantation: a 20-year experience. Ann Hematol 103, 321–334 (2024). https://doi.org/10.1007/s00277-023-05530-w

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