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Incidence, Predictors, and Outcomes of Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation.
Biol Blood Marrow Transplant. 2020 Mar; 26(3):529-539.BB

Abstract

fludarabine with intravenous busulfan at doses of 3.2 mg/kg (Flu/Bu1) or 6.4 mg/kg (Flu/Bu2). Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a serious complication of hematopoietic stem cell transplantation (HCT) that is felt to be triggered, at least in part, by damage to the liver sinusoidal endothelium from cytotoxic conditioning regimens. Accordingly, the incidence of VOD/SOS after reduced-intensity conditioning (RIC) HCT is low compared with myeloablative transplantation, and the natural history, risk factors, and outcomes of VOD/SOS after RIC have not been well characterized. We retrospectively reviewed 1583 consecutive patients receiving RIC HCT at the Dana-Farber Cancer Institute between 2007 and 2017 and ascertained 26 cases of VOD/SOS. The median day of VOD/SOS onset was 26 days (range, 5 to 48) and the cumulative incidence at day 50 was 1.6% (95% confidence interval [CI], 1.1% to 2.4%). Day 100 nonrelapse mortality rate was 23% in the VOD/SOS cohort compared with 6.4% in patients without VOD/SOS (P = .006). Cumulative incidence of VOD/SOS at day 50 was 3.1% after RIC regimen with Flu/Bu2 ± ATG (fludarabine with two doses of busulfan, total dose 6.4 mg/kg, with or without anti-thymocyte globulin), compared with 0.15% after Flu/Bu1 ± ATG (fludarabine with single busulfan dose 3.2 mg/kg, with or without anti-thymocyte globulin) (P = .0002); the incidence rate was 2.1% after RIC HCT with sirolimus-containing graft-versus-host disease prophylaxis, compared with 0.8% for RIC without sirolimus (P = .06). Significant risk factors identified in multivariable analysis for the development of VOD/SOS were sirolimus use (hazard ratio [HR], 5.1; 95% CI, 1.8 to 14.2; P = .002) and RIC regimen with Flu/Bu2 ± ATG (HR, 34; 95% CI, 4.5 to 252; P < .001) or other (HR, 32; 95% CI, 3.9 to 257; P = .001) compared with Flu/Bu1 ± ATG. Rising serum tacrolimus or sirolimus levels, new acute kidney injury, and increasing platelet transfusion requirements were significant early predictors of onset in the week preceding prior VOD/SOS diagnosis. When compared with a previously published cohort of 76 patients with VOD/SOS who developed VOD/SOS after myeloablative HCT in the same time period, VOD/SOS after RIC occurred later and was associated with a lower peak bilirubin level and better overall survival. The variability in presenting features for RIC VOD/SOS highlights the importance of maintaining a high index of suspicion for this entity in RIC HCT.

Authors+Show Affiliations

Department of Haematology, Auckland City Hospital, Auckland, New Zealand.Department of Data Sciences, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health, Boston, Massachusetts.Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.Department of Medical Oncology, Division of Hematologic Malignancies, Dana-Farber Cancer, Institute, Harvard Medical School, Boston, Massachusetts.Department of Medical Oncology, Division of Hematologic Malignancies, Dana-Farber Cancer, Institute, Harvard Medical School, Boston, Massachusetts.Department of Medical Oncology, Division of Hematologic Malignancies, Dana-Farber Cancer, Institute, Harvard Medical School, Boston, Massachusetts.Department of Medical Oncology, Division of Hematologic Malignancies, Dana-Farber Cancer, Institute, Harvard Medical School, Boston, Massachusetts.Department of Medical Oncology, Division of Hematologic Malignancies, Dana-Farber Cancer, Institute, Harvard Medical School, Boston, Massachusetts.Department of Medical Oncology, Division of Hematologic Malignancies, Dana-Farber Cancer, Institute, Harvard Medical School, Boston, Massachusetts.Department of Medical Oncology, Division of Hematologic Malignancies, Dana-Farber Cancer, Institute, Harvard Medical School, Boston, Massachusetts.Department of Medical Oncology, Division of Hematologic Malignancies, Dana-Farber Cancer, Institute, Harvard Medical School, Boston, Massachusetts.Department of Medical Oncology, Division of Hematologic Malignancies, Dana-Farber Cancer, Institute, Harvard Medical School, Boston, Massachusetts.Department of Medical Oncology, Division of Hematologic Malignancies, Dana-Farber Cancer, Institute, Harvard Medical School, Boston, Massachusetts.Department of Medical Oncology, Division of Hematologic Malignancies, Dana-Farber Cancer, Institute, Harvard Medical School, Boston, Massachusetts.Department of Medical Oncology, Division of Hematologic Malignancies, Dana-Farber Cancer, Institute, Harvard Medical School, Boston, Massachusetts.Department of Medical Oncology, Division of Hematologic Malignancies, Dana-Farber Cancer, Institute, Harvard Medical School, Boston, Massachusetts. Electronic address: Vincent_Ho@DFCI.Harvard.Edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31678537

Citation

Lewis, Clinton, et al. "Incidence, Predictors, and Outcomes of Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome After Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 26, no. 3, 2020, pp. 529-539.
Lewis C, Kim HT, Roeker LE, et al. Incidence, Predictors, and Outcomes of Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2020;26(3):529-539.
Lewis, C., Kim, H. T., Roeker, L. E., Cutler, C., Koreth, J., Nikiforow, S., Armand, P., Gootpu, M., Romee, R., Glotzbecker, B., Nageshwar, P., Antin, J. H., Alyea, E. P., Richardson, P., Soiffer, R. J., & Ho, V. T. (2020). Incidence, Predictors, and Outcomes of Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 26(3), 529-539. https://doi.org/10.1016/j.bbmt.2019.10.024
Lewis C, et al. Incidence, Predictors, and Outcomes of Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome After Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2020;26(3):529-539. PubMed PMID: 31678537.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Incidence, Predictors, and Outcomes of Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation. AU - Lewis,Clinton, AU - Kim,Haesook T, AU - Roeker,Lindsey E, AU - Cutler,Corey, AU - Koreth,John, AU - Nikiforow,Sarah, AU - Armand,Philippe, AU - Gootpu,Mahasweta, AU - Romee,Rizwan, AU - Glotzbecker,Brett, AU - Nageshwar,Prashant, AU - Antin,Joseph H, AU - Alyea,Edwin P, AU - Richardson,Paul, AU - Soiffer,Robert J, AU - Ho,Vincent T, Y1 - 2019/10/31/ PY - 2019/07/16/received PY - 2019/10/22/revised PY - 2019/10/25/accepted PY - 2019/11/5/pubmed PY - 2019/11/5/medline PY - 2019/11/4/entrez KW - Allogeneic KW - HCT KW - RIC KW - SOS KW - Transplant KW - VOD SP - 529 EP - 539 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol. Blood Marrow Transplant. VL - 26 IS - 3 N2 - fludarabine with intravenous busulfan at doses of 3.2 mg/kg (Flu/Bu1) or 6.4 mg/kg (Flu/Bu2). Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a serious complication of hematopoietic stem cell transplantation (HCT) that is felt to be triggered, at least in part, by damage to the liver sinusoidal endothelium from cytotoxic conditioning regimens. Accordingly, the incidence of VOD/SOS after reduced-intensity conditioning (RIC) HCT is low compared with myeloablative transplantation, and the natural history, risk factors, and outcomes of VOD/SOS after RIC have not been well characterized. We retrospectively reviewed 1583 consecutive patients receiving RIC HCT at the Dana-Farber Cancer Institute between 2007 and 2017 and ascertained 26 cases of VOD/SOS. The median day of VOD/SOS onset was 26 days (range, 5 to 48) and the cumulative incidence at day 50 was 1.6% (95% confidence interval [CI], 1.1% to 2.4%). Day 100 nonrelapse mortality rate was 23% in the VOD/SOS cohort compared with 6.4% in patients without VOD/SOS (P = .006). Cumulative incidence of VOD/SOS at day 50 was 3.1% after RIC regimen with Flu/Bu2 ± ATG (fludarabine with two doses of busulfan, total dose 6.4 mg/kg, with or without anti-thymocyte globulin), compared with 0.15% after Flu/Bu1 ± ATG (fludarabine with single busulfan dose 3.2 mg/kg, with or without anti-thymocyte globulin) (P = .0002); the incidence rate was 2.1% after RIC HCT with sirolimus-containing graft-versus-host disease prophylaxis, compared with 0.8% for RIC without sirolimus (P = .06). Significant risk factors identified in multivariable analysis for the development of VOD/SOS were sirolimus use (hazard ratio [HR], 5.1; 95% CI, 1.8 to 14.2; P = .002) and RIC regimen with Flu/Bu2 ± ATG (HR, 34; 95% CI, 4.5 to 252; P < .001) or other (HR, 32; 95% CI, 3.9 to 257; P = .001) compared with Flu/Bu1 ± ATG. Rising serum tacrolimus or sirolimus levels, new acute kidney injury, and increasing platelet transfusion requirements were significant early predictors of onset in the week preceding prior VOD/SOS diagnosis. When compared with a previously published cohort of 76 patients with VOD/SOS who developed VOD/SOS after myeloablative HCT in the same time period, VOD/SOS after RIC occurred later and was associated with a lower peak bilirubin level and better overall survival. The variability in presenting features for RIC VOD/SOS highlights the importance of maintaining a high index of suspicion for this entity in RIC HCT. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/31678537/Incidence_Predictors_and_Outcomes_of_Veno_Occlusive_Disease/Sinusoidal_Obstruction_Syndrome_after_Reduced_Intensity_Allogeneic_Hematopoietic_Cell_Transplantation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(19)30706-2 DB - PRIME DP - Unbound Medicine ER -
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