Effect of Graft-versus-Host Disease on Post-Transplantation Outcomes following Single Cord Blood Transplantation Compared with Haploidentical Transplantation with Post-Transplantation Cyclophosphamide for Adult Acute Myeloid Leukemia

Konuma, Takaaki; Matsuda, Kensuke; Shimomura, Yoshimitsu; Tanoue, Susumu; Sato, Junichi; Inamoto, Yoshihiro; Hirayama, Masahiro; Ara, Takahide; Nakamae, Hirohisa; Ota, Shuichi; Maruyama, Yumiko; Eto, Tetsuya; Uchida, Naoyuki; Tanaka, Masatsugu; Ishiwata, Kiichi; Koi, Satoshi; Takahashi, Satoshi; Ozawa, Yukiyasu; Onizuka, Makoto; Kanda, Yoshinobu; Kimura, Takafumi; Ichinohe, Tatsuo; Atsuta, Yoshiko; Kanda, Junya; Yanada, Masamitsu

doi:10.1016/j.jtct.2023.03.001

Cited by 7 publications

(3 citation statements)

References 62 publications

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“…The similar report in the HLA-matched setting suggests that it is the use of PTCy rather than the haploidentical donor source that is responsible for the separation of GVHD and GVL. Similar results following haploidentical SCT were reported by Japanese and Italian registries [27,28]. The Baltimore group reported different outcomes in a group of 340 patients with various hematological malignancies following haploidentical SCT with non-myeloablative conditioning and PTCy [29].…”

Section: Discussionsupporting

confidence: 74%

Post-transplant cyclophosphamide separates graft-versus host disease and graft versus leukemia effects after HLA- matched stem-cell transplantation for AML

Shimoni,

Peczynski,

Labopin

et al. 2024

Preprint

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The association of graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects after allogeneic stem-cell transplantation (SCT) is well-established but was not confirmed in modern era and following post-transplant cyclophosphamide (PTCy). We assessed GVHD/ GVL association in AML patients following HLA-matched SCT with standard calcineurin-based (n = 12,653) or PTCy-based (n = 508) GVHD prophylaxis. Following standard prophylaxis, the rates of acute GVHD grade II-IV and III-IV, chronic GVHD and extensive chronic GVHD were 23.8%, 7.5%, 37.0% and 16.3%, respectively. Acute GVHD grade II and III-IV were associated with lower relapse [hazard-ratio (HR) 0.85, P = 0.002; HR 0.76, P = 0.003, respectively)], higher non-relapse mortality (NRM) (HR 1.5, P < 0.001; HR 6.21, P < 0.001) and lower overall-survival (OS) (HR 1.49, P < 0.001; HR 6.1, P < 0.001). Extensive chronic GVHD was associated with lower relapse (HR 0.69, P < 0.001), higher NRM (HR 2.83, P < 0.001) and lower OS (HR 2.74, P < 0.001). Following PTCy, GVHD rates were 22.8%, 6.2%, 35.5% and 17.7%, respectively. Acute GVHD grade II-IV was not associated with relapse (HR 1.37, P = 0.15) but predicted higher NRM (HR 3.34, P < 0.001) and lower OS (HR 1.92, P = 0.001). Chronic GVHD was not prognostic for these outcomes. In conclusion, GVHD and GVL are strongly associated in contemporary SCT. However, following PTCy, GVHD is not associated with reduced relapse.

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Section: Discussionsupporting

confidence: 74%

Post-transplant cyclophosphamide separates graft-versus host disease and graft versus leukemia effects after HLA- matched stem-cell transplantation for AML

Shimoni,

Peczynski,

Labopin

et al. 2024

Preprint

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“…In fact, previous studies have demonstrated that grade I–II acute GVHD and limited chronic GVHD after CBT reduce the risk of relapse for patients with acute leukemia or myelodysplastic syndrome 24 , 26 , 41 . Furthermore, a recent study has shown that grade I–II acute GVHD was associated with better OS in CBT, but not with PTCy-haplo transplantation 42 . Third, information on the day when each grade of GVHD occurred was not fully available.…”

Section: Discussionmentioning

confidence: 99%

Mild Acute Graft-Versus-Host Disease Improves Outcomes After HLA-Haploidentical-Related Donor Transplantation Using Posttransplant Cyclophosphamide and Cord Blood Transplantation

Wada,

Kanda,

Kamijo

et al. 2023

Cell Transplant

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Haploidentical-related donor transplantation using posttransplant cyclophosphamide (PTCy-haplo) and cord blood transplantation (CBT) are valid alternatives for patients with hematological malignancies when HLA-matched donor transplantation (MDT) is unavailable. However, the effects of graft-versus-host disease (GVHD) on outcomes after these transplants have not been fully elucidated. Therefore, we evaluated the effects of acute and chronic GVHD on transplant outcomes after PTCy-haplo transplants and compared them with CBT and MDT. We included a total of 914 adult patients with hematological malignancies in the Kyoto Stem Cell Transplantation Group registry who received PTCy-haplo (N = 120), CBT (N = 402), and MDT (N = 392), and achieved neutrophil engraftment. A multivariate analysis revealed that grade I–II acute GVHD improved of overall survival (OS) after PTCy-haplo [hazard ratio (HR) = 0.39, P = 0.018] and CBT (HR = 0.48, P < 0.001), but not after MDT (HR = 0.80, P = 0.267) compared with patients without acute GVHD. Grade I–II acute GVHD had a trend toward reducing the risk of nonrelapse mortality (NRM) after PTCy-haplo (HR = 0.13, P = 0.060) and this positive effect was significant after CBT (HR = 0.39, P = 0.003). A negative impact of grade III–IV acute GVHD on NRM was observed after CBT and MDT, but not after PTCy-haplo. Limited chronic GVHD had a positive impact on OS after CBT and MDT, but not after PTCy-haplo. In conclusion, mild acute GVHD improved outcomes after PTCy-haplo and CBT, and limited chronic GVHD improved outcomes after CBT and MDT. These data indicated that the effects of GVHD on transplant outcomes depended on transplant platforms.

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“…The need for risk stratification for GVHD is high, due to problems associated with immunosuppression. It is either not aggressive enough leaving patients with a high GVHD risk vulnerable, or it is too aggressive leading to infections and other complications (3,8).…”

Section: Background On Graft-versushost-diseasementioning

confidence: 99%

Unlocking protein-based biomarker potential for graft-versus-host disease following allogenic hematopoietic stem cell transplants

Iacobescu,

Pop,

Uifălean

et al. 2024

Front. Immunol.

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Despite the numerous advantages of allogeneic hematopoietic stem cell transplants (allo-HSCT), there exists a notable association with risks, particularly during the preconditioning period and predominantly post-intervention, exemplified by the occurrence of graft-versus-host disease (GVHD). Risk stratification prior to symptom manifestation, along with precise diagnosis and prognosis, relies heavily on clinical features. A critical imperative is the development of tools capable of early identification and effective management of patients undergoing allo-HSCT. A promising avenue in this pursuit is the utilization of proteomics-based biomarkers obtained from non-invasive biospecimens. This review comprehensively outlines the application of proteomics and proteomics-based biomarkers in GVHD patients. It delves into both single protein markers and protein panels, offering insights into their relevance in acute and chronic GVHD. Furthermore, the review provides a detailed examination of the site-specific involvement of GVHD. In summary, this article explores the potential of proteomics as a tool for timely and accurate intervention in the context of GVHD following allo-HSCT.

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Effect of Graft-versus-Host Disease on Post-Transplantation Outcomes following Single Cord Blood Transplantation Compared with Haploidentical Transplantation with Post-Transplantation Cyclophosphamide for Adult Acute Myeloid Leukemia

Cited by 7 publications

References 62 publications

Post-transplant cyclophosphamide separates graft-versus host disease and graft versus leukemia effects after HLA- matched stem-cell transplantation for AML

Post-transplant cyclophosphamide separates graft-versus host disease and graft versus leukemia effects after HLA- matched stem-cell transplantation for AML

Mild Acute Graft-Versus-Host Disease Improves Outcomes After HLA-Haploidentical-Related Donor Transplantation Using Posttransplant Cyclophosphamide and Cord Blood Transplantation

Unlocking protein-based biomarker potential for graft-versus-host disease following allogenic hematopoietic stem cell transplants

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