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Early Clinical Predictors of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Myeloablative Stem Cell Transplantation.
Biol Blood Marrow Transplant. 2019 01; 25(1):137-144.BB

Abstract

Hepatic veno-occlusive disease (VOD), or sinusoidal obstruction syndrome (SOS), is a serious complication of hematopoietic stem cell transplantation (HSCT) with mortality in its severe form exceeding 80%. Although the incidence of VOD/SOS has fallen with contemporary transplantation practices, the increasing use of inotuzumab, the return of gemtuzumab, and the popularity of pharmacokinetic-guided high-dose busulfan may impact incidence. Early intervention with defibrotide improves survival, but prompt diagnosis can be difficult. We aimed to identify clinical parameters that could aid in early detection of VOD/SOS in a large, retrospective, cohort study. Of the 1823 adult patients who underwent myeloablative HSCT between 1996 and 2015 in our center, 205 (11%) developed VOD/SOS, with a median onset of day +14. We compared parameters in the 7 days preceding VOD/SOS onset for cases to 447 randomly selected control subjects in an analogous time frame to determine those with predictive value. Between 7 days before and the day of diagnosis, VOD/SOS patients had higher serum creatinine levels and were more likely to develop acute kidney injury (61% versus 33%, P < .0001), more commonly experienced refractoriness to platelet transfusion (48% versus 24%, P < .0001), and had higher trough serum tacrolimus levels (7 days before VOD/SOS onset: median 8.8 versus 7.3, P = .0002; day of onset: median 9.3 versus 7.2, P < .0001) compared with control subjects. Acute renal dysfunction, platelet refractoriness, and elevated or abnormal tacrolimus levels are dynamic clinical markers that should alert clinicians to the development of VOD/SOS before the presence of classical diagnostic criteria. Using these clinical features to recognize VOD/SOS earlier in its clinical course could promote earlier treatment and lead to improved outcomes of this potentially serious complication.

Authors+Show Affiliations

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.Department of Biostatistics and Computation Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: vtho@partners.org.

Pub Type(s)

Comparative Study
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

30081073

Citation

Roeker, Lindsey E., et al. "Early Clinical Predictors of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome After Myeloablative Stem Cell Transplantation." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 25, no. 1, 2019, pp. 137-144.
Roeker LE, Kim HT, Glotzbecker B, et al. Early Clinical Predictors of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Myeloablative Stem Cell Transplantation. Biol Blood Marrow Transplant. 2019;25(1):137-144.
Roeker, L. E., Kim, H. T., Glotzbecker, B., Nageshwar, P., Nikiforow, S., Koreth, J., Armand, P., Cutler, C., Alyea, E. P., Antin, J. H., Richardson, P. G., Soiffer, R. J., & Ho, V. T. (2019). Early Clinical Predictors of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Myeloablative Stem Cell Transplantation. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 25(1), 137-144. https://doi.org/10.1016/j.bbmt.2018.07.039
Roeker LE, et al. Early Clinical Predictors of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome After Myeloablative Stem Cell Transplantation. Biol Blood Marrow Transplant. 2019;25(1):137-144. PubMed PMID: 30081073.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Early Clinical Predictors of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Myeloablative Stem Cell Transplantation. AU - Roeker,Lindsey E, AU - Kim,Haesook T, AU - Glotzbecker,Brett, AU - Nageshwar,Prashant, AU - Nikiforow,Sarah, AU - Koreth,John, AU - Armand,Philippe, AU - Cutler,Corey, AU - Alyea,Edwin P, AU - Antin,Joseph H, AU - Richardson,Paul G, AU - Soiffer,Robert J, AU - Ho,Vincent T, Y1 - 2018/08/03/ PY - 2018/03/22/received PY - 2018/07/25/accepted PY - 2018/8/7/pubmed PY - 2019/12/24/medline PY - 2018/8/7/entrez KW - Defibrotide KW - SOS KW - Sinusoidal obstruction syndrome KW - Tacrolimus KW - VOD KW - Veno-occlusive disease SP - 137 EP - 144 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol. Blood Marrow Transplant. VL - 25 IS - 1 N2 - Hepatic veno-occlusive disease (VOD), or sinusoidal obstruction syndrome (SOS), is a serious complication of hematopoietic stem cell transplantation (HSCT) with mortality in its severe form exceeding 80%. Although the incidence of VOD/SOS has fallen with contemporary transplantation practices, the increasing use of inotuzumab, the return of gemtuzumab, and the popularity of pharmacokinetic-guided high-dose busulfan may impact incidence. Early intervention with defibrotide improves survival, but prompt diagnosis can be difficult. We aimed to identify clinical parameters that could aid in early detection of VOD/SOS in a large, retrospective, cohort study. Of the 1823 adult patients who underwent myeloablative HSCT between 1996 and 2015 in our center, 205 (11%) developed VOD/SOS, with a median onset of day +14. We compared parameters in the 7 days preceding VOD/SOS onset for cases to 447 randomly selected control subjects in an analogous time frame to determine those with predictive value. Between 7 days before and the day of diagnosis, VOD/SOS patients had higher serum creatinine levels and were more likely to develop acute kidney injury (61% versus 33%, P < .0001), more commonly experienced refractoriness to platelet transfusion (48% versus 24%, P < .0001), and had higher trough serum tacrolimus levels (7 days before VOD/SOS onset: median 8.8 versus 7.3, P = .0002; day of onset: median 9.3 versus 7.2, P < .0001) compared with control subjects. Acute renal dysfunction, platelet refractoriness, and elevated or abnormal tacrolimus levels are dynamic clinical markers that should alert clinicians to the development of VOD/SOS before the presence of classical diagnostic criteria. Using these clinical features to recognize VOD/SOS earlier in its clinical course could promote earlier treatment and lead to improved outcomes of this potentially serious complication. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/30081073/Early_Clinical_Predictors_of_Hepatic_Veno_Occlusive_Disease/Sinusoidal_Obstruction_Syndrome_after_Myeloablative_Stem_Cell_Transplantation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(18)30428-2 DB - PRIME DP - Unbound Medicine ER -