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Open AccessArticle
Reduced Dose of Post-Transplant Cyclophosphamide with Tacrolimus for the Prevention of Graft-versus-Host Disease in HLA-Matched Donor Peripheral Blood Stem Cell Transplants: A Prospective Pilot Study
by
Alex Juárez
Alex Juárez 1,
María Queralt Salas
María Queralt Salas 1
,
Alexandra Pedraza
Alexandra Pedraza 2,
María Suárez-Lledó
María Suárez-Lledó 1,3,
Luís Gerardo Rodríguez-Lobato
Luís Gerardo Rodríguez-Lobato 1,3,
María Teresa Solano
María Teresa Solano 1,
Anna Serrahima
Anna Serrahima 1
,
Meritxell Nomdedeu
Meritxell Nomdedeu 2,
Joan Cid
Joan Cid 3,4
,
Miquel Lozano
Miquel Lozano 3,4
,
Paola Charry
Paola Charry 3,4
,
Jordi Arcarons
Jordi Arcarons 1,
Noemí Llobet
Noemí Llobet 1
,
Laura Rosiñol
Laura Rosiñol 1,3,5
,
Francesc Fernández-Avilés
Francesc Fernández-Avilés 1,3,5,
Montserrat Rovira
Montserrat Rovira 1,3,5 and
Carmen Martínez
Carmen Martínez 1,3,5,*
1
Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Cancer and Blood Disease (ICAMS), Hospital Clínic de Barcelona, 08036 Barcelona, Spain
2
Hemotherapy and Hemostasis Department, Institute of Cancer and Blood Disease (ICAMS), Hospital Clínic de Barcelona, 08036 Barcelona, Spain
3
August Pi i Sunyer Biomedical Research Institute—IDIBAPS, 08036 Barcelona, Spain
4
Apheresis and Cellular Therapy Unit, Hemotherapy and Hemostasis Department, Institute of Cancer and Blood Disease (ICAMS), Hospital Clínic de Barcelona, 08036 Barcelona, Spain
5
Institute Josep Carreras, Hospital Clínic de Barcelona, 08036 Barcelona, Spain
*
Author to whom correspondence should be addressed.
Cancers 2024, 16(14), 2567; https://doi.org/10.3390/cancers16142567 (registering DOI)
Submission received: 4 June 2024
/
Revised: 3 July 2024
/
Accepted: 16 July 2024
/
Published: 17 July 2024
Simple Summary
High-dose post-transplant cyclophosphamide is effective in preventing graft-versus-host disease (GVHD) but is associated with adverse outcomes such as delayed engraftment, infections, and cardiac issues. This pilot study evaluated the efficacy and toxicity of reduced-dose PTCY (40 mg/kg/day) in patients undergoing HLA-matched allogeneic hematopoietic stem cell transplantation (alloHSCT). Neutrophil and platelet engraftment occurred at medians of 15 and 16 days, respectively. At day 100, the incidences of grade II–IV and III–IV acute GVHD were 18.2% and 4.5%, respectively, with no cases of grade IV acute GVHD or steroid-refractory disease. One-year incidence of moderate-severe chronic GVHD was 6.4%. Both incidences, acute GVHD and chronic GVHD, are similar to our previous experience with higher doses of PTCY. Two-year overall survival and relapse-free survival were 77.1% and 58.3%. There were low incidences of infections and only one early cardiac event. These results suggest that reduced-dose PTCY provides adequate immunosuppression with a low toxicity profile.
Abstract
PTCY 50 mg/kg/day on days +3/+4 is an excellent strategy to prevent GVHD. However, its use is associated with adverse outcomes such as delayed engraftment, increased risk of infection, and cardiac complications. This pilot study evaluates the efficacy and toxicity of a reduced dose of PTCY (40 mg/kg/day) combined with tacrolimus in 22 peripheral blood HLA-matched alloHSCT patients. At day +100, the cumulative incidences of grade II–IV and III–IV acute GVHD were 18.2% and 4.5%, respectively. No grade IV acute GVHD or steroid-refractory disease was observed. The cumulative incidences of all-grade and moderate-severe chronic GVHD at 1-year were 11.4% and 6.4%, respectively. No patient died from transplant-related complications. Two-year OS and RFS were 77.1% and 58.3%, respectively. All patients engrafted, with neutrophil and platelet recovery occurring at a median of 15 (IQR 14–16) and 16 days (IQR 12–23), respectively. The cumulative incidences of bloodstream bacterial infections, polyomavirus BK hemorrhagic cystitis, HHV6 reactivation, CMV reactivation, and fungal infections were 13.6%, 9.1%, 9.1%, 4.6%, and 6%, respectively. Only one early cardiac event was observed. These results suggest that PTCY 40 mg/kg/day on a +3/+4 schedule provides adequate immunosuppression to allow for engraftment and prevent clinically significant GVHD with a low toxicity profile.
Share and Cite
MDPI and ACS Style
Juárez, A.; Salas, M.Q.; Pedraza, A.; Suárez-Lledó, M.; Rodríguez-Lobato, L.G.; Solano, M.T.; Serrahima, A.; Nomdedeu, M.; Cid, J.; Lozano, M.;
et al. Reduced Dose of Post-Transplant Cyclophosphamide with Tacrolimus for the Prevention of Graft-versus-Host Disease in HLA-Matched Donor Peripheral Blood Stem Cell Transplants: A Prospective Pilot Study. Cancers 2024, 16, 2567.
https://doi.org/10.3390/cancers16142567
AMA Style
Juárez A, Salas MQ, Pedraza A, Suárez-Lledó M, Rodríguez-Lobato LG, Solano MT, Serrahima A, Nomdedeu M, Cid J, Lozano M,
et al. Reduced Dose of Post-Transplant Cyclophosphamide with Tacrolimus for the Prevention of Graft-versus-Host Disease in HLA-Matched Donor Peripheral Blood Stem Cell Transplants: A Prospective Pilot Study. Cancers. 2024; 16(14):2567.
https://doi.org/10.3390/cancers16142567
Chicago/Turabian Style
Juárez, Alex, María Queralt Salas, Alexandra Pedraza, María Suárez-Lledó, Luís Gerardo Rodríguez-Lobato, María Teresa Solano, Anna Serrahima, Meritxell Nomdedeu, Joan Cid, Miquel Lozano,
and et al. 2024. "Reduced Dose of Post-Transplant Cyclophosphamide with Tacrolimus for the Prevention of Graft-versus-Host Disease in HLA-Matched Donor Peripheral Blood Stem Cell Transplants: A Prospective Pilot Study" Cancers 16, no. 14: 2567.
https://doi.org/10.3390/cancers16142567
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