Post-transplant cyclophosphamide and early mixed donor Chimerism in myeloid malignancies; a single-center experience |
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| Institution: | 1. Department of General, Visceral, and Transplant Surgery, LMU University Hospitals, Ludwig-Maximilians-Universität Munich, Marchioninistraße 15, 81377 Munich, Germany;2. Walter-Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität Munich, Marchioninistraße 15, 81377 Munich, Germany;3. Institute of Laboratory Medicine, LMU University Hospitals, Ludwig-Maximilians-Universität Munich, Marchioninistraße 15, 81377 Munich, Germany;1. Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;2. Department of Anatomical Sciences, Sarab Faculty of Medical Sciences, Sarab, Iran;3. Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran;4. Medical and molecular genetics, Ataturk University, Erzurum, Turkey;5. Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran;6. Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;1. Division of Allergy, Pulmonary and Critical Care Medicine, Department of Internal Medicine, School of Medicine, Pusan National University, Busan, Republic of Korea; Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea;2. Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Busan, Republic of Korea; Department of Anesthesia and Pain Medicine, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea;3. Department of Anesthesia and Pain Medicine, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea;4. Department of Thoracic and Cardiovascular Surgery, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea;5. Department of Laboratory Medicine, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea;1. Department of Respiratory Medicine, Tokyo Women''s Medical University, Tokyo, Japan;2. Department of Infectious Diseases, Tokyo Women''s Medical University, Tokyo, Japan;3. Department of Infection Prevention and Control, Tokyo Women''s Medical University, Tokyo, Japan;4. Department of Pharmacy, Tokyo Women''s Medical University, Tokyo, Japan;5. Department of Urology, Tokyo Women''s Medical University, Tokyo, Japan;6. Department of General Medicine, Tokyo Women''s Medical University, Tokyo, Japan;7. Department of Surgery, Institute of Gastroenterology, Tokyo Women''s Medical University, Tokyo, Japan;8. Department of Hematology, Tokyo Women''s Medical University, Tokyo, Japan;1. Department of Neurology, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai City, Shandong Province, China;2. Department of Urology, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai City, Shandong Province, China |
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| Abstract: | BackgroundAllogeneic 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.ObjectiveWe investigated the impact of PT-Cy on early MC (EMC) and disease relapse in patients with a myeloid malignancy post allo-HSCT.Study designThis 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.ResultsA 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.ConclusionOur 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. |
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