Incidence and Risk Factors for Acute and Chronic Kidney Injury after Adult Cord Blood Transplantation

Gutgarts, Victoria; Sathick, Insara Jaffer; Zheng, Junting; Politikos, Ioannis; Devlin, Sean M.; Maloy, Molly; Giralt, Sergío; Scordo, Michael; Bhatt, Valkal; Glezerman, Ilya G.; Muthukumar, Thangamani; Jaimes, Edgar A.; Barker, Juliet N.

doi:10.1016/j.bbmt.2019.12.768

Cited by 14 publications

(17 citation statements)

References 62 publications

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“…As for adverse events by cyclosporine in stem cell transplantation, our post-marketing data revealed that the signal scores for toxic nephropathy, nephrotic syndrome, and membranous glomerulonephritis were noteworthy. It is consistent with a clinical study in adult patients receiving cord blood transplantation at significant acute kidney injury (AKI) risk, and AKI is associated with an increased risk of chronic kidney disease [24]. The mechanism of cyclosporine-induced nephrotoxicity is partly due to total cyclosporine exposure [25].…”

Section: Discussionsupporting

confidence: 84%

Current Status of Adverse Event Profile of Cyclosporine in Kidney, Stem Cell, and Heart Transplantations Using the Japanese Pharmacovigilance Database

Niinomi¹,

Oyama²,

Inada³

et al. 2022

Cureus

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Background: Cyclosporine is widely used to prevent allograft rejection after transplantation. The purpose of this study was to clarify the adverse events profiles associated with cyclosporine in transplant patients using a spontaneous reporting system database.Methods: Retrospective pharmacovigilance disproportionality analysis was conducted using the Japanese Adverse Drug Event Report (JADER) database, with the reporting odds ratio (ROR) and 95% confidence interval (CI) for each adverse event.Results: The database comprised 3,327, 958, and 956 reports associated with cyclosporine in the kidney, stem cell, and heart transplant patients, respectively. Infectious and renal disorders were commonly detected in these transplant patients. The signal scores of cyclosporine for toxic nephropathy were noteworthy in the kidney (ROR: 15.1, 95% CI: 11-20.8) and stem cell (ROR, 216; 95% CI, 29.3-1593) transplantation. Cyclosporine in heart transplantation was strongly associated with gastric cancer (ROR, 39.4; 95% CI, 16.7-93.2), but not kidney or stem cell transplantation.Conclusion: It was suggested that there is a diversity in the strength of the association between cyclosporine and adverse events in the kidney, stem cell, and heart transplantation. Our results may provide useful information for treatment with cyclosporine, although further research with more data is needed.

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Section: Discussionsupporting

confidence: 84%

Current Status of Adverse Event Profile of Cyclosporine in Kidney, Stem Cell, and Heart Transplantations Using the Japanese Pharmacovigilance Database

Niinomi¹,

Oyama²,

Inada³

et al. 2022

Cureus

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“…Increasing CSA trough target early after transplant may be an option in selected patients but can risk nephrotoxicity. 20,43 We are now investigating adding a single dose of tocilizumab to CSA/mycophenolate mofetil as an approach to reduce severe aGVHD risk. 44 Other strategies of augmented, but nonlymphodepleting, prophylaxis, risk-adapted aGVHD therapy, or new agents warrant investigation.…”

Section: Discussionmentioning

confidence: 99%

High progression-free survival after intermediate intensity double unit cord blood transplantation in adults

et al. 2020

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Cord blood transplantation (CBT) after high intensity or nonmyeloablative conditioning has limitations. We investigated cyclosporine-A/mycophenolate mofetil–based intermediate intensity (cyclophosphamide 50 mg/kg, fludarabine 150 mg/m2, thiotepa 10 mg/kg, total body irradiation 400 cGy) unmanipulated double-unit CBT (dCBT) with prioritization of unit quality and CD34+ cell dose in graft selection. Ninety adults (median age, 47 years [range, 21-63]; median hematopoietic cell transplantation comorbidity index, 2 [range, 0-8]; 61 [68%] acute leukemia) received double-unit grafts (median CD34+ cell dose, 1.3 × 105/kg per unit [range, 0.2-8.3]; median donor-recipient human leukocyte antigen (HLA) match, 5/8 [range 3-7/8]). The cumulative incidences of sustained CB engraftment, day 180 grade III-IV acute, and 3-year chronic graft-versus-host disease were 99%, 24%, and 7%, respectively. Three-year transplant-related mortality (TRM) and relapse incidences were 15% and 9%, respectively. Three-year overall survival (OS) is 82%, and progression-free survival (PFS) is 76%. Younger age and higher engrafting unit CD34+ cell dose both improved TRM and OS, although neither impacted PFS. Engrafting unit-recipient HLA match was not associated with any outcome with a 3-year PFS of 79% in 39 patients engrafting with 3-4/8 HLA-matched units. In 52 remission acute leukemia patients, there was no association between minimal residual disease (MRD) and 3-year PFS: MRD negative of 88% vs MRD positive of 77% (P = .375). Intermediate intensity dCBT is associated with high PFS. Use of highly HLA mismatched and unmanipulated grafts permits wide application of this therapy, and the low relapse rates support robust graft-versus-leukemia effects even in patients with MRD.

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“…Overall, the greatest risk of AKI is with myeloablative allo-HCT (21-73%), followed by nonmyeloablative allo-HCT (29-56%), and then autologous transplantation (10.4-19%) (36,41,42). Reports vary on whether the incidence of AKI is higher with cord blood or HLA mismatched donor transplantation (28,(43)(44)(45)(46)(47).…”

Section: Kidney Disease After Hctmentioning

confidence: 99%

Recent Advances of Acute Kidney Injury in Hematopoietic Cell Transplantation

et al. 2022

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Acute kidney injury (AKI) is a common complication of allogeneic hematopoietic cell transplantation (allo-HCT) and is associated with non-relapse mortality (NRM) and quality of life (QOL). Multiple factors may contribute to AKI during allo-HCT and are often present at the same time making it difficult to determine the cause of AKI in each patient. Nephrotoxic drugs, infections, thrombotic microangiopathy (TMA), and sinusoidal obstruction syndrome (SOS) are well described causes of AKI during allo-HCT. Acute graft-versus-host disease (aGVHD) is a major complication of allo-HCT that mainly targets the intestines, liver, and skin. However, recent studies suggest aGVHD may also attack the kidney and contribute to AKI following allo-HCT. For example, severe aGVHD is associated with AKI, suggesting a link between the two. In addition, animal models have shown donor immune cell infiltration and increased expression of inflammatory cytokines in recipient kidneys after allo-HCT. Therefore, aGVHD may also target the kidney and contribute to AKI following allo-HCT. Herein, we describe the etiology, diagnosis, risk factors, pathophysiology, prevention, and treatment of renal injury after allo-HCT. In addition, we highlight emerging evidence that aGVHD may contribute to the development of AKI after allo-HCT.

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Incidence and Risk Factors for Acute and Chronic Kidney Injury after Adult Cord Blood Transplantation

Cited by 14 publications

References 62 publications

Current Status of Adverse Event Profile of Cyclosporine in Kidney, Stem Cell, and Heart Transplantations Using the Japanese Pharmacovigilance Database

Current Status of Adverse Event Profile of Cyclosporine in Kidney, Stem Cell, and Heart Transplantations Using the Japanese Pharmacovigilance Database

High progression-free survival after intermediate intensity double unit cord blood transplantation in adults

Recent Advances of Acute Kidney Injury in Hematopoietic Cell Transplantation

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