Acute kidney injury and chronic kidney disease in umbilical cord blood transplant recipients.

Introduction: Acute kidney injury (AKI) is a frequent early complication post hematopoietic stem cell transplant (HSCT), associated with high morbidity and mortality. Cord blood transplant (CBT) recipients are potentially exposed to more nephrotoxic insults, compared to patients undergoing HSCT from other donor sources. We aimed to identify risk factors for AKI in patients undergoing CBT. We also aimed to identify the impact of AKI on chronic kidney disease (CKD) and survival outcomes by one-year post-CBT. Methods: Adults and children who underwent a first CBT at our Institution were retrospectively evaluated. AKI was staged according to Kidney Disease Improving Global Outcomes (KDIGO) definitions. Cox regression models were used to estimate the association of demographic factors and post-CBT parameters with the cause-specific hazard of AKI. Results: We identified 276 patients. Median age was 32 years, 28% (77/276) were children (<18 years) and 129 (47%) were white. A myeloablative conditioning regimen was administered to 243 patients (88%) and 248 (90%) received cyclosporine for GVHD prophylaxis. One-hundred and eighty-six patients (67%) developed AKI by day 60 post-transplant, with 72 (26%) developing severe AKI (stage 2 and 3). In a multivariable analysis, each increase in bilirubin level of 1 mg/dL was associated with a 23% increase in the risk of severe AKI (adjusted HR 1.23, 95% CI 1.13 - 1.34, p<.0001). Conversely, systemic steroid administration appeared to be protective of severe AKI (unadjusted HR 0.36, 95% CI 0.18 - 0.72, p=.004) in a univariate model . Two-hundred-forty-seven patients were evaluable at the one-year time point. Among those, 100 patients (40%) developed CKD one-year post-CBT. Severe AKI was associated with a higher hazard of non-relapse mortality (adjusted HR=3.26, 95% CI 1.65-6.45, p=.001) and overall mortality (adjusted HR=2.28, 95% CI 1.22-4.27, p=.01). Discussion: AKI is a frequent complication after CBT and is associated with worse outcomes. Questions remain as to the mechanism of the protective role of steroids on kidney function in the setting of CBT.

High Incidence of Herpes Zoster After Cord Blood Hematopoietic Cell Transplant Despite Longer Duration of Antiviral Prophylaxis.

BACKGROUND: Cord blood transplant (CBT) recipients have a high incidence of herpes zoster (HZ) in the context of short-term peritransplant antiviral prophylaxis. In 2009, international guidelines recommended HZ prophylaxis for at least 1 year after hematopoietic cell transplant. The impact of longer-term antiviral prophylaxis on HZ incidence after CBT is unknown. METHODS: We retrospectively analyzed varicella zoster virus (VZV)-seropositive CBT recipients who were transplanted between 2006 and 2016. We abstracted HZ events and other variables for up to 5 years post-CBT. We calculated the cumulative incidence of HZ and used Cox proportional hazards regression to identify variables associated with HZ. RESULTS: The study cohort consisted of 227 patients. Among 1-year survivors, 91% were still receiving prophylaxis, for a median duration of 20.6 months. HZ occurred in 44 patients (19%) at a median of 23.6 months. The cumulative incidence of HZ by 1 year after CBT was 1.8% (95% confidence interval [CI], .1%-4%), but increased to 26% (95% CI, 19%-33%) by 5 years. In a multivariable analysis, acute graft-vs-host disease was associated with increased risk, whereas antiviral prophylaxis was associated with reduced risk for HZ (adjusted hazard ratio, 0.19 [95% CI, .09-.4]). There was no association between CD4+ T-cell counts at 1 year post-CBT and subsequent risk for HZ. CONCLUSIONS: We found a high incidence of HZ after CBT despite antiviral prophylaxis for > 1 year. Based on these findings, we suggest longer duration of prophylaxis for HZ after CBT. Compliance with antiviral prophylaxis, VZV-specific immune monitoring, and vaccination to mitigate HZ after CBT also require further study.

Late effects in high-risk neuroblastoma survivors treated with high-dose chemotherapy and stem cell rescue.

BACKGROUND: Current treatment strategies have improved the outcome of high-risk neuroblastoma (HRNB) at the cost of increasing acute and late effects of treatment. Although high-dose chemotherapy with stem cell rescue (HDC-SCR) has replaced total body irradiation (TBI) based HRNB therapy, late effects of therapy remain a significant concern. OBJECTIVES: To describe late effects prevalence, severity, and risks after HDC-SCR. METHODS: Retrospective chart review of relapse-free HRNB survivors ≥1 year after single HDC-SCR between 2000 and 2015 at Fred Hutchinson Cancer Research Center. RESULTS: Sixty-one survivors (30 males) were eligible. Median age (years) at SCR was 3.5 years (range 0.7-27 years) and median posttransplant follow-up was 5.4 years (1.2-16.3 years) . Fifty-three (86.9%) survivors developed late effects that increased over time (P < 0.001) and varied in severity from grade 1 (35) to grade 5 (1). These were unrelated to gender or age. High-frequency hearing loss seen in 82% of survivors was the most common abnormality present and 43% of those required hearing aids. Seventeen (27.9%) survivors developed dental late effects and these were most common in children <2 years of age at transplant (P = 0.008). Other toxicities included endocrine (18%), orthopedic (14.8 %), renal (3.9%), melanotic nevi (8.2%), neuropsychological impairments (8.2%), subsequent malignancies (4.9%), pulmonary (4.9%), cardiac (4.9%), and focal nodular liver hyperplasia (3.3%). At 9 years posttransplant, the median height and weight Z-scores were significantly lower than Z-scores at the time of HDC-SCR (-0.01/-1.08, P < 0.001; -0.14/-0.78, P = 0.005). CONCLUSION: Avoidance of TBI does not mitigate the need to provide diligent, ongoing surveillance for late effects.