Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2025 Apr 22;9(8):1966-1975.
doi: 10.1182/bloodadvances.2024015173.

Posttransplant cyclophosphamide as GVHD prophylaxis in patients receiving mismatched unrelated HCT: the PHYLOS trial

Anna Maria Raiola  1 , Benedetto Bruno  2 , Antonio Maria Risitano  3 , Federico Mosna  4 , Irene Maria Cavattoni  4 , Francesco Onida  5   6 , Giorgia Saporiti  6 , Francesca Patriarca  7 , Marta Lisa Battista  7 , Vincenzo Pavone  8 , Anna Mele  8 , Patrizia Chiusolo  9   10 , Simona Sica  9   10 , Barbara Loteta  11 , Carmen di Grazia  1 , Angelo Michele Carella  12 , Dalila Salvatore  12 , Enrico Morello  13   14 , Alessandro Leoni  13   14 , Luisa Giaccone  2 , Paolo Bernasconi  15 , Elisabetta Terruzzi  16 , Nicola Mordini  17 , Carlo Borghero  18 , Francesco Zallio  19 , Mario Luppi  20 , Anna Grassi  21 , Attilio Olivieri  22 , Eugenia Piras  23 , Nicoletta Sacchi  24 , Giovannino Ciccone  25 , Anna Castiglione  25 , Eliana Degrandi  26 , Emanuele Angelucci  1 , Massimo Martino  11 , Francesca Bonifazi  27
Affiliations
Clinical Trial

Posttransplant cyclophosphamide as GVHD prophylaxis in patients receiving mismatched unrelated HCT: the PHYLOS trial

Anna Maria Raiola et al. Blood Adv. .

Abstract

Posttransplant high-dose cyclophosphamide (PTCy) is effective in overcoming the negative impact of HLA disparity in the haploidentical setting. In light of these results, we investigated the efficacy of PTCy, in improving clinical outcomes of hematopoietic stem cell transplantation (HSCT) from a mismatched unrelated donor (MMUD) in patients with acute myeloid malignancies by reducing the incidence and severity of acute graft-versus-host disease (aGVHD). A prospective, single-arm, phase 2 study (PHYLOS) was conducted by the Gruppo Italiano Trapianto di Midollo Osseo. The ethical committees of the participating centers approved the study (EURODRACT 2017-003530-85). A total of 77 consecutive patients (acute myeloid leukemia: 64; myelodysplastic syndrome: 13) were enrolled at 26 Italian transplant centers (January 2020-November 2022). Median age of the patients was 53 (range, 19-65) years. The 100-day cumulative incidence of grades 2 to 4 aGVHD was 18.2% (95% CI, 10.6-27.6) and of grades 3 to 4 was 6.5% (95% CI, 3.1-15.1). Seventy-one patients (92%) had full-donor chimerism with complete neutrophil engraftment by day +30. One-year cumulative incidence of chronic GVHD was 13.4% (95% CI, 6.9-22.1). One-year cumulative incidence of nonrelapse mortality was 9.1% (95% CI, 4.0-16.9), and the relapse rate was 23.8% (95% CI, 14.9-33.9). One-year overall survival and graft relapse-free survival were 78.6% (95% CI, 67.4-86.3) and 55.3% (95% CI, 43.4-65.7), respectively. Our study in a homogeneous patient cohort suggests that PTCy leads to a low rate of aGVHD and improves clinical outcomes of HSCT from MMUD. This trial was registered at www.clinicaltrials.gov as #NCT03270748.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Overall outcomes. (A) Cumulative incidence of aGVHD grades 2 to 4 at 100 days. (B) Cumulative incidence of aGVHD grades 3 to 4 at 100 days. (C) Cumulative incidence of cGVHD moderate/severe at 12 months. (D) Cumulative incidence of relapse at 12 months. (E) Cumulative incidence of NRM at 12 months. (F) GRFS at 12 months. (G) OS at 12 months.
Figure 2.
Figure 2.
Count recovery. (A) Cumulative incidence of neutrophil recovery. (B) Cumulative incidence of platelet recovery.
See this image and copyright information in PMC

References

    1. Lee SJ, Klein J, Haagenson M, et al. High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood. 2007;110(13):4576–4583. - PubMed
    1. Anasetti C, Beatty PG, Storb R, et al. Effect of HLA incompatibility on graft-versus-host disease, relapse, and survival after marrow transplantation for patients with leukemia or lymphoma. Hum Immunol. 1990;29(2):79–91. - PubMed
    1. Flomenberg N, Baxter-Lowe LA, Confer D, et al. Impact of HLA class I and class II high-resolution matching on outcomes of unrelated donor bone marrow transplantation: HLA-C mismatching is associated with a strong adverse effect on transplantation outcome. Blood. 2004;104(7):1923–1930. - PubMed
    1. Woolfrey A, Klein JP, Haagenson M, et al. HLA-C antigen mismatch is associated with worse outcome in unrelated donor peripheral blood stem cell transplantation. Biol Blood Marrow Transplant. 2011;17(6):885–892. - PMC - PubMed
    1. Michallet M, Sobh M, Serrier C, et al. Allogeneic hematopoietic stem cell transplant for hematological malignancies from mismatched 9/10 human leukocyte antigen unrelated donors: comparison with transplants from 10/10 unrelated donors and human leukocyte antigen identical siblings. Leuk Lymphoma. 2015;56(4):999–1003. - PubMed

Publication types

Associated data