No abstract

We conducted a 45 patient prospective study of reduced-intensity conditioning (RIC) and transplantation of unrelated umbilical cord blood (UCB) and CD34 ؉ stem cells from a haploidentical family member. Median age was 50 years; weight was 80 kg. Fifty-eight percent had active disease. Neutrophil engraftment occurred at 11 days (interquartile range [IQR], 9-15) and platelet engraftment at 19 days (IQR, 15-33). In the majority of patients, early haploidentical engraftment was replaced by durable engraftment of UCB by 100 days, with regular persistence of minor host and/or haplo-hematopoiesis. Percentage of haplochimerism at day 100 correlated with the haplo-CD34 dose (P ‫؍‬ .003). Cumulative incidence of acute GVHD (aGVHD) was 25% and chronic GVHD (cGVHD) was 5%. Actuarial survival at 1 year was 55%, progression-free survival (PFS) was 42%, nonrelapse mortality (NRM) was 28%, and relapse was 30%. RIC and haplo-cord transplantation results in fast engraftment of neutrophils and platelets, low incidences of aGVHD and cGVHD, low frequency of delayed opportunistic infections, reduced transfusion requirements, shortened length of hospital stay, and promising long-term outcomes. UCB cell dose had no impact on time to hematopoietic recovery. Therefore, UCB selection can prioritize matching, and better matched donors can be identified rapidly for most patients. This study is registered at http://clinicaltrials.gov as NCI clinical trial no. NCT00943800. (Blood. 2011;118(24):6438-6445)

Comorbidity measurements have recently been used to improve estimation of tolerance to allogeneic hematopoietic cell transplantation (HCT). We sought to determine the independent effect of comorbidity and performance status on HCT outcome and to devise a simple risk classification system for transplant-related mortality. We analyzed 105 consecutively enrolled patients who underwent HCT and received reduced intensity conditioning with fludarabine, melphalan, and alemtuzumab. Comorbid conditions were tabulated using 2 scales, the Charlson Comorbidity Index (CCI) and the Kaplan-Feinstein Scale (KFS). Comorbid conditions were found in 47% of patients by the KFS and in 27% by the CCI (P < .001). Using the Eastern Cooperative Oncology Group Performance Status (PS) scale, 34% had a PS score >0 (range, 0-2). A simple scale combining the KFS and PS enabled separation of high- from low-risk patients, with 6-month cumulative incidences 50% and 15%, respectively for transplant-related mortality (P = .001) and enhanced prognostic power over the CCI alone (P = .018). Prospective studies evaluating more comprehensive functional and comorbidity measurements are warranted.

BK virus (BKV) is an important pathogen and cause of nephropathy in renal transplant recipients, but its significance following hematopoetic stem cell transplantation (HSCT) is less well described. We measured blood and urine BKV in 124 allogeneic HSCT patients (67 had undergone prior HSCT [surveillance cohort]; 57 were monitored from transplant day 0 [prospective cohort]). BK viruria was manifest in 64.8% of the patients; 16.9% developed viremia. In the prospective cohort, the median time from transplantation to BK viremia development (128 days) was longer than for viruria (24 days; P < 0.0001). Among clinical factors (gender, disease, transplant type, alemtuzumab use, CMV viremia, GVHD, donor HLA C7 allele), only CMV viremia was more common in patients with BKV infection (P ≤ 0.04). There was a direct relationship between blood and urine BKV levels and the occurrence, and degree, of hematuria (P ≤ 0.03). Finally, BKV infection was analyzed along with other clinical factors in relation to the development of post-HSCT renal impairment. On multivariate analysis, only BK viremia (P = 0.000002) and alternative-donor transplantation (P = 0.002) were independent predictors of development of post-HSCT renal impairment, with BK viremia associated with a median 1.62 mg/dL rise in creatinine from the pre-transplant baseline. Among eight patients in the surveillance cohort with BK viremia, two developed biopsy-proven BKV nephropathy requiring hemodialysis. Investigation of whether prophylaxis against, or treatment of, BKV in the post-HSCT setting mitigates the associated morbidities, especially kidney injury, warrants prospective evaluation.

We tested the independent prognostic impact of two commonly used biomarkers, C-reactive protein (CRP) and interleukin-6 (IL-6), on allogeneic hematopoietic cell transplantation (HCT) outcomes. Consecutive patients who underwent a uniform reduced intensity regimen of fludarabine, melphalan and alemtuzumab were evaluated. Cryopreserved sera drawn before conditioning was available to measure CRP and IL-6 levels from 81 and 79 patients, respectively. Patients having CRP values above the median of 18.5 mg/L had significantly more grade 3 to 4 hepatic toxicity (P = 0.08), longer HCT hospital stay (P = 0.005), more aGVHD (P = 0.003), greater non-relapse mortality (NRM) (P =0.01) and inferior overall survival (P =0.02). Higher baseline CRP also correlated with more grade 3 to 4 infectious toxicity (P = 0.09). In contrast, pre-HCT IL-6 levels above the median of 78.3 pg/mL, did not confer a statistically significant increased risk of toxicities or mortality. Elevated hematopoietic cell transplantation-comorbidity index (HCT-CI) did not predict for any measure of HCT morbidity. After adjustment for disease status, comorbidity, performance status and age, elevated CRP concentration remained predictive of NRM. CRP holds promise as a readily available serum biomarker that can be measured prior to HCT conditioning to enhance estimates of transplantation tolerance.