Seema Naik1, Marcie Riches2, Parameswaran Hari3, Soyoung Kim3,4, Min Chen3, Carlos Bachier5, Paul Shaughnessy6, Joshua Hill7, Per Ljungman8, Minoo Battiwalla5, Saurabh Chhabra9, Andrew Daly10, Jan Storek11, Celalettin Ustun12, Miguel Angel Diaz13, Jan Cerny14, Amer Beitinjaneh15, Jean Yared16, Valerie Brown17, Kristin Page18, Parastoo B Dahi19, Siddhartha Ganguly20, Sachiko Seo21, Nelson Chao22, Cesar O Freytes6, Ayman Saad23, Bipin N Savani24, Kwang Woo Ahn3,4, Michael Boeckh25, Helen E Heslop26, Hillard M Lazarus27, Jeffery J Auletta28, Rammurti T Kamble26. 1. Penn State Cancer Institute, Hershey, Pennsylvania. 2. Division of Hematology/Oncology, The University of North Carolina, Chapel Hill, North California. 3. Department of Medicine, Medical College of Wisconsin, Center for International Blood and Marrow Transplant Research (CIBMTR), Milwaukee, Wisconsin. 4. Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, Wisconsin. 5. Sarah Cannon Center for Blood Cancer, Nashville, Tennessee. 6. Texas Transplant Institute, Sarah Cannon Blood Cancer Network, San Antonio, Texas. 7. Fred Hutchinson Cancer Research Center, Seattle, Washington. 8. Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Stockholm, Sweden. 9. Department of Medicine, Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, Wisconsin. 10. Tom Baker Cancer Centre, Calgary, AB, Canada. 11. Department of Medicine, University of Calgary, Calgary, AB, Canada. 12. Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota Medical Center, Minneapolis, Minnesota. 13. Department of Hematology/Oncology, Hospital Infantil Universitario Nino Jesus, Madrid, Spain. 14. UMass Memorial Medical Center, Worcester, Massachusetts. 15. University of Miami, Miami, Florida. 16. Blood & Marrow Transplantation Program, Division of Hematology/Oncology, Department of Medicine, Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland. 17. Division of Pediatric Oncology/Hematology, Department of Pediatrics, Penn State Hershey Children's Hospital and College of Medicine, Hershey, Pennsylvania. 18. Division of Pediatric Blood and Marrow Transplantation, Duke University Medical Center, Durham, North Carolina. 19. Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, New York. 20. Division of Hematological Malignancy and Cellular Therapeutics, University of Kansas Health System, Kansas City, Kansas. 21. Department of Hematology, Oncology, Dokkyo Medical University, Tochigi, Japan. 22. Division of Cell Therapy and Hematologica, Department of Medicine, Duke University Medical Center, Durham, North Carolina. 23. Division of Hematology/Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama. 24. Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. 25. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. 26. Division of Hematology and Oncology, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas. 27. Seidman Cancer Center, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio. 28. Blood and Marrow Transplant Program and Host Defense Program, Divisions of Hematology/Oncology/Bone Marrow Transplant and Infectious Diseases, Nationwide Children's Hospital, Columbus, Ohio.
Abstract
BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are associated with significant morbidity and mortality following allogeneic hematopoietic cell transplant (alloHCT). Although most PTLD is EBV-positive (EBVpos ), EBV-negative (EBVneg ) PTLD is reported, yet its incidence and clinical impact remain largely undefined. Furthermore, factors at the time of transplant impacting survival following PTLD are not well described. METHODS: Between 2002 and 2014, 432 cases of PTLD following alloHCT were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). After exclusions, 267 cases (EBVpos = 222, 83%; EBVneg = 45, 17%) were analyzed. RESULTS: Two hundred and eight patients (78%) received in vivo T-cell depletion (TCD) with either anti-thymocyte globulin (ATG) or alemtuzumab. Incidence of PTLD was highest using umbilical cord donors (UCB, 1.60%) and lowest using matched related donors (MRD, 0.40%). Clinical features and histology did not significantly differ among EBVpos or EBVneg PTLD cases except that absolute lymphocyte count recovery was slower, and CMV reactivation was later in EBVneg PTLD [EBVpos 32 (5-95) days versus EBVneg 47 (10-70) days, P = .016]. There was no impact on survival by EBV status in multivariable analysis [EBVneg RR 1.42, 95% CI 0.94-2.15, P = .097]. CONCLUSIONS: There is no difference in survival outcomes for patients with EBVpos or EBVneg PTLD occurring following alloHCT and 1-year survival is poor. Features of conditioning and use of serotherapy remain important.
BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are associated with significant morbidity and mortality following allogeneic hematopoietic cell transplant (alloHCT). Although most PTLD is EBV-positive (EBVpos ), EBV-negative (EBVneg ) PTLD is reported, yet its incidence and clinical impact remain largely undefined. Furthermore, factors at the time of transplant impacting survival following PTLD are not well described. METHODS: Between 2002 and 2014, 432 cases of PTLD following alloHCT were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). After exclusions, 267 cases (EBVpos = 222, 83%; EBVneg = 45, 17%) were analyzed. RESULTS: Two hundred and eight patients (78%) received in vivo T-cell depletion (TCD) with either anti-thymocyte globulin (ATG) or alemtuzumab. Incidence of PTLD was highest using umbilical cord donors (UCB, 1.60%) and lowest using matched related donors (MRD, 0.40%). Clinical features and histology did not significantly differ among EBVpos or EBVneg PTLD cases except that absolute lymphocyte count recovery was slower, and CMV reactivation was later in EBVneg PTLD [EBVpos 32 (5-95) days versus EBVneg 47 (10-70) days, P = .016]. There was no impact on survival by EBV status in multivariable analysis [EBVneg RR 1.42, 95% CI 0.94-2.15, P = .097]. CONCLUSIONS: There is no difference in survival outcomes for patients with EBVpos or EBVneg PTLD occurring following alloHCT and 1-year survival is poor. Features of conditioning and use of serotherapy remain important.
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