Post-transplant cyclophosphamide and early mixed donor Chimerism in myeloid malignancies; a single-center experience

Fieke W. Hoff; Stephen S. Chung; Prapti A Patel; Naveen Premnath; Jude Khatib; Mirjana Tadic-Ovcina; Abeer AhmedRabie; Debra Helton; Selamawit Yohannes; Jaime Shahan; Hetalkumari Patel; Praveen Ramakrishnan Geethakumari; Madhuri Vusirikala; Robert H. Collins; Yazan F. Madanat

doi:10.1016/j.trim.2023.101808

Post-transplant cyclophosphamide and early mixed donor Chimerism in myeloid malignancies; a single-center experience

Fieke W. Hoff, Stephen S. Chung, Prapti A Patel, Naveen Premnath, Jude Khatib, Mirjana Tadic-Ovcina, Abeer AhmedRabie, Debra Helton, Selamawit Yohannes, Jaime Shahan, Hetalkumari Patel, Praveen Ramakrishnan Geethakumari, Madhuri Vusirikala, Robert H. Collins, Yazan F. Madanat

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative option for high-risk myeloid malignancies. Post-transplant cyclophosphamide (PT-Cy) has proven to be effective for graft versus host disease (GVHD) prophylaxis. Given that graft-versus-tumor (GVT) effect plays a major role in reducing the risk of disease relapse, the application of PT-Cy must balance the risk of relapse. Mixed chimerism (MC) refers to a state of concurrent presence of recipient and donor cells post allo-HSCT which may precede relapse disease. Objective: We investigated the impact of PT-Cy on early MC (EMC) and disease relapse in patients with a myeloid malignancy post allo-HSCT. Study design: This retrospective single-center study included patients that underwent allo-HSCT between 2015 and 2021. Patient and disease characteristics were collected from the electronic health records. EMC was defined as <95% donor cells at day 90–120 post allo-HSCT. Results: A total of 144 patient that received an allo-HSCT were included in the study. One hundred and eight (75%) patients received PT-Cy as part of the GVHD prophylaxis regimen. The majority underwent allo-HSCT for acute myeloid leukemia (62%) or myelodysplastic syndrome (31%). Sixty-five percent received allo-HSCT from a matched unrelated donor transplant and 65% received a myeloablative conditioning regimen. A lower rate of chronic GVHD (p = 0.03) and a higher rate of EMC (p = 0.04) were observed in patients that received PT-Cy. PT-Cy was not associated with overall survival (OS) and relapse-free survival (RFS). Multivariable analysis identified measurable residual disease status (p = 0.003), hematopoietic cell transplantation-specific comorbidity index (p = 0.012) and chronic GVHD (p = 0.006) as independent prognostic variables for OS. AML-adverse risk (p = 0.004) and EMC (p = 0.018) were independently prognostic for RFS. While EMC overall was not significantly associated with higher risk of relapse, EMC was associated with shorter RFS within adverse-risk AML patients. Conclusion: Our study shows that PT-Cy was associated with an increased risk of EMC. The predictive value of EMC for relapse remains unclear and may depend on the underlying disease, which should be validated in a larger cohort.

Original language	English (US)
Article number	101808
Journal	Transplant Immunology
Volume	77
DOIs	https://doi.org/10.1016/j.trim.2023.101808
State	Published - Apr 2023

Keywords

Cyclophosphamide
Early mixed Chimerism
GVHD prophylaxis
Hematopoietic stem cell transplantation
Myeloid malignancy

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Transplantation

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10.1016/j.trim.2023.101808

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Hoff, F. W., Chung, S. S., Patel, P. A., Premnath, N., Khatib, J., Tadic-Ovcina, M., AhmedRabie, A., Helton, D., Yohannes, S., Shahan, J., Patel, H., Geethakumari, P. R., Vusirikala, M., Collins, R. H., & Madanat, Y. F. (2023). Post-transplant cyclophosphamide and early mixed donor Chimerism in myeloid malignancies; a single-center experience. Transplant Immunology, 77, Article 101808. https://doi.org/10.1016/j.trim.2023.101808

Hoff, FW, Chung, SS, Patel, PA, Premnath, N, Khatib, J, Tadic-Ovcina, M, AhmedRabie, A, Helton, D, Yohannes, S, Shahan, J, Patel, H, Geethakumari, PR, Vusirikala, M, Collins, RH & Madanat, YF 2023, 'Post-transplant cyclophosphamide and early mixed donor Chimerism in myeloid malignancies; a single-center experience', Transplant Immunology, vol. 77, 101808. https://doi.org/10.1016/j.trim.2023.101808

@article{dc64db91e11f47c989f562e2ee35a9fc,

title = "Post-transplant cyclophosphamide and early mixed donor Chimerism in myeloid malignancies; a single-center experience",

abstract = "Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative option for high-risk myeloid malignancies. Post-transplant cyclophosphamide (PT-Cy) has proven to be effective for graft versus host disease (GVHD) prophylaxis. Given that graft-versus-tumor (GVT) effect plays a major role in reducing the risk of disease relapse, the application of PT-Cy must balance the risk of relapse. Mixed chimerism (MC) refers to a state of concurrent presence of recipient and donor cells post allo-HSCT which may precede relapse disease. Objective: We investigated the impact of PT-Cy on early MC (EMC) and disease relapse in patients with a myeloid malignancy post allo-HSCT. Study design: This retrospective single-center study included patients that underwent allo-HSCT between 2015 and 2021. Patient and disease characteristics were collected from the electronic health records. EMC was defined as <95% donor cells at day 90–120 post allo-HSCT. Results: A total of 144 patient that received an allo-HSCT were included in the study. One hundred and eight (75%) patients received PT-Cy as part of the GVHD prophylaxis regimen. The majority underwent allo-HSCT for acute myeloid leukemia (62%) or myelodysplastic syndrome (31%). Sixty-five percent received allo-HSCT from a matched unrelated donor transplant and 65% received a myeloablative conditioning regimen. A lower rate of chronic GVHD (p = 0.03) and a higher rate of EMC (p = 0.04) were observed in patients that received PT-Cy. PT-Cy was not associated with overall survival (OS) and relapse-free survival (RFS). Multivariable analysis identified measurable residual disease status (p = 0.003), hematopoietic cell transplantation-specific comorbidity index (p = 0.012) and chronic GVHD (p = 0.006) as independent prognostic variables for OS. AML-adverse risk (p = 0.004) and EMC (p = 0.018) were independently prognostic for RFS. While EMC overall was not significantly associated with higher risk of relapse, EMC was associated with shorter RFS within adverse-risk AML patients. Conclusion: Our study shows that PT-Cy was associated with an increased risk of EMC. The predictive value of EMC for relapse remains unclear and may depend on the underlying disease, which should be validated in a larger cohort.",

keywords = "Cyclophosphamide, Early mixed Chimerism, GVHD prophylaxis, Hematopoietic stem cell transplantation, Myeloid malignancy",

author = "Hoff, {Fieke W.} and Chung, {Stephen S.} and Patel, {Prapti A} and Naveen Premnath and Jude Khatib and Mirjana Tadic-Ovcina and Abeer AhmedRabie and Debra Helton and Selamawit Yohannes and Jaime Shahan and Hetalkumari Patel and Geethakumari, {Praveen Ramakrishnan} and Madhuri Vusirikala and Collins, {Robert H.} and Madanat, {Yazan F.}",

note = "Publisher Copyright: {\textcopyright} 2023",

year = "2023",

month = apr,

doi = "10.1016/j.trim.2023.101808",

language = "English (US)",

volume = "77",

journal = "Transplant Immunology",

issn = "0966-3274",

publisher = "Elsevier",

}

TY - JOUR

T1 - Post-transplant cyclophosphamide and early mixed donor Chimerism in myeloid malignancies; a single-center experience

AU - Hoff, Fieke W.

AU - Chung, Stephen S.

AU - Patel, Prapti A

AU - Premnath, Naveen

AU - Khatib, Jude

AU - Tadic-Ovcina, Mirjana

AU - AhmedRabie, Abeer

AU - Helton, Debra

AU - Yohannes, Selamawit

AU - Shahan, Jaime

AU - Patel, Hetalkumari

AU - Geethakumari, Praveen Ramakrishnan

AU - Vusirikala, Madhuri

AU - Collins, Robert H.

AU - Madanat, Yazan F.

PY - 2023/4

Y1 - 2023/4

N2 - Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative option for high-risk myeloid malignancies. Post-transplant cyclophosphamide (PT-Cy) has proven to be effective for graft versus host disease (GVHD) prophylaxis. Given that graft-versus-tumor (GVT) effect plays a major role in reducing the risk of disease relapse, the application of PT-Cy must balance the risk of relapse. Mixed chimerism (MC) refers to a state of concurrent presence of recipient and donor cells post allo-HSCT which may precede relapse disease. Objective: We investigated the impact of PT-Cy on early MC (EMC) and disease relapse in patients with a myeloid malignancy post allo-HSCT. Study design: This retrospective single-center study included patients that underwent allo-HSCT between 2015 and 2021. Patient and disease characteristics were collected from the electronic health records. EMC was defined as <95% donor cells at day 90–120 post allo-HSCT. Results: A total of 144 patient that received an allo-HSCT were included in the study. One hundred and eight (75%) patients received PT-Cy as part of the GVHD prophylaxis regimen. The majority underwent allo-HSCT for acute myeloid leukemia (62%) or myelodysplastic syndrome (31%). Sixty-five percent received allo-HSCT from a matched unrelated donor transplant and 65% received a myeloablative conditioning regimen. A lower rate of chronic GVHD (p = 0.03) and a higher rate of EMC (p = 0.04) were observed in patients that received PT-Cy. PT-Cy was not associated with overall survival (OS) and relapse-free survival (RFS). Multivariable analysis identified measurable residual disease status (p = 0.003), hematopoietic cell transplantation-specific comorbidity index (p = 0.012) and chronic GVHD (p = 0.006) as independent prognostic variables for OS. AML-adverse risk (p = 0.004) and EMC (p = 0.018) were independently prognostic for RFS. While EMC overall was not significantly associated with higher risk of relapse, EMC was associated with shorter RFS within adverse-risk AML patients. Conclusion: Our study shows that PT-Cy was associated with an increased risk of EMC. The predictive value of EMC for relapse remains unclear and may depend on the underlying disease, which should be validated in a larger cohort.

AB - Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative option for high-risk myeloid malignancies. Post-transplant cyclophosphamide (PT-Cy) has proven to be effective for graft versus host disease (GVHD) prophylaxis. Given that graft-versus-tumor (GVT) effect plays a major role in reducing the risk of disease relapse, the application of PT-Cy must balance the risk of relapse. Mixed chimerism (MC) refers to a state of concurrent presence of recipient and donor cells post allo-HSCT which may precede relapse disease. Objective: We investigated the impact of PT-Cy on early MC (EMC) and disease relapse in patients with a myeloid malignancy post allo-HSCT. Study design: This retrospective single-center study included patients that underwent allo-HSCT between 2015 and 2021. Patient and disease characteristics were collected from the electronic health records. EMC was defined as <95% donor cells at day 90–120 post allo-HSCT. Results: A total of 144 patient that received an allo-HSCT were included in the study. One hundred and eight (75%) patients received PT-Cy as part of the GVHD prophylaxis regimen. The majority underwent allo-HSCT for acute myeloid leukemia (62%) or myelodysplastic syndrome (31%). Sixty-five percent received allo-HSCT from a matched unrelated donor transplant and 65% received a myeloablative conditioning regimen. A lower rate of chronic GVHD (p = 0.03) and a higher rate of EMC (p = 0.04) were observed in patients that received PT-Cy. PT-Cy was not associated with overall survival (OS) and relapse-free survival (RFS). Multivariable analysis identified measurable residual disease status (p = 0.003), hematopoietic cell transplantation-specific comorbidity index (p = 0.012) and chronic GVHD (p = 0.006) as independent prognostic variables for OS. AML-adverse risk (p = 0.004) and EMC (p = 0.018) were independently prognostic for RFS. While EMC overall was not significantly associated with higher risk of relapse, EMC was associated with shorter RFS within adverse-risk AML patients. Conclusion: Our study shows that PT-Cy was associated with an increased risk of EMC. The predictive value of EMC for relapse remains unclear and may depend on the underlying disease, which should be validated in a larger cohort.

KW - Cyclophosphamide

KW - Early mixed Chimerism

KW - GVHD prophylaxis

KW - Hematopoietic stem cell transplantation

KW - Myeloid malignancy

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U2 - 10.1016/j.trim.2023.101808

DO - 10.1016/j.trim.2023.101808

M3 - Article

C2 - 36842566

AN - SCOPUS:85149254144

SN - 0966-3274

VL - 77

JO - Transplant Immunology

JF - Transplant Immunology

M1 - 101808

ER -

Post-transplant cyclophosphamide and early mixed donor Chimerism in myeloid malignancies; a single-center experience

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