A comprehensive model to predict severe acute graft-versus-host disease in acute leukemia patients after haploidentical hematopoietic stem cell transplantation.

BACKGROUND: Acute graft-versus-host disease (aGVHD) remains the major cause of early mortality after haploidentical related donor (HID) hematopoietic stem cell transplantation (HSCT). We aimed to establish a comprehensive model which could predict severe aGVHD after HID HSCT. METHODS: Consecutive 470 acute leukemia patients receiving HID HSCT according to the protocol registered at https://clinicaltrials.gov (NCT03756675) were enrolled, 70% of them (n = 335) were randomly selected as training cohort and the remains 30% (n = 135) were used as validation cohort. RESULTS: The equation was as follows: Probability (grade III-IV aGVHD) = [Formula: see text], where Y = -0.0288 × (age) + 0.7965 × (gender) + 0.8371 × (CD3 + /CD14 + cells ratio in graft) + 0.5829 × (donor/recipient relation) - 0.0089 × (CD8 + cell counts in graft) - 2.9046. The threshold of probability was 0.057392 which helped separate patients into high- and low-risk groups. The 100-day cumulative incidence of grade III-IV aGVHD in the low- and high-risk groups was 4.1% (95% CI 1.9-6.3%) versus 12.8% (95% CI 7.4-18.2%) (P = 0.001), 3.2% (95% CI 1.2-5.1%) versus 10.6% (95% CI 4.7-16.5%) (P = 0.006), and 6.1% (95% CI 1.3-10.9%) versus 19.4% (95% CI 6.3-32.5%) (P = 0.017), respectively, in total, training, and validation cohort. The rates of grade III-IV skin and gut aGVHD in high-risk group were both significantly higher than those of low-risk group. This model could also predict grade II-IV and grade I-IV aGVHD. CONCLUSIONS: We established a model which could predict the development of severe aGVHD in HID HSCT recipients.

Pretreatment whole blood Epstein-Barr virus DNA predicts prognosis in Hodgkin lymphoma.

The study investigated pretreatment Epstein-Barr virus (EBV) DNA status and its prognostic values in 96 patients newly diagnosed Hodgkin lymphoma (HL). With 13.5 % patients in positive EBV DNA status before therapy, the positive group had inferior progression-free survival (PFS) (P = 0.023) as well as overall survival (OS) (P = 0.001). Pretreatment EBV DNA positivity was observed as an independent prognostic factor in OS (P = 0.036) while a trend to predict PFS (P = 0.064). By monitoring changes of EBV DNA copies in 13 patients with positive pretreatment EBV DNA status, 5 of 6 patients with complete response (CR) had their copies undetectable after 3 cycles of first-line treatment and 7 patients with progressive disease (PD) all had elevated EBV DNA copies during their relapsed period. Whole blood EBV DNA may be an adjunctive biomarker to reflect treatment response, risk of disease relapse as well as prognosis in HL patients.

25-Hydroxy vitamin D deficiency predicts inferior prognosis in Hodgkin lymphoma.

The study investigated serum 25-Hydroxy vitamin D (25-(OH)D) deficiency and its prognostic values of patients newly diagnosed Hodgkin lymphoma (HL). With seventy-seven patients enrolled, the median level of 25-(OH)D was 44.5 nmol/L (range, 15.5-100.9 nmol/L) and 16 (20.8 %) of them were considered as 25-(OH)D deficiency. With a median follow-up of 28 months (range, 4-56 months), the 2-year progression-free survival (PFS) and overall survival (OS) rate were 75.3 %±5.5 % and 94.7 %±3.0 %, respectively. Patients with deficient 25-(OH)D level had inferior PFS (P<0.001) as well as OS (P<0.001). In multivariate Cox analysis, 25-(OH)D deficiency was observed as an independent prognostic factor for both PFS (hazard ratio (HR) 3.323, 95 % CI 1.527-7.229, P = 0.002) and OS (HR 5.819, 95 % CI 1.322-25.622, P = 0.020). Receiver-operator characteristic (ROC) curve showed International Prognostic Score (IPS) plus 25-(OH)D deficiency (IPS-D) predicted more accurately than IPS in PFS (AUC: 0.735 (95 % CI 0.622-0.829) vs. 0.701 (95 % CI 0.586-0.800), P = 0.033) and OS (AUC: 0.864 (95 % CI 0.767-0.932) vs. 0.825 (95 % CI 0.722-0.902), P = 0.028). All these findings suggest that serum 25-(OH)D level may be an adjunctive indicator to predict prognosis in HL patient.

Low serum cholesterol levels predict inferior prognosis and improve prognostic index scoring for peripheral T-cell lymphoma, unspecified.

Peripheral T-cell lymphomas, unspecified (PTCL-U) is a heterogeneous group of non-Hodgkin lymphomas, arising from the transformation of mature, post-thymic T-cells. Prognostic index for PTCL-U (PIT) is based on Europeans and may not be applicable for Chinese PTCL-U patients. Besides, low circulating cholesterol concentration is associated with elevated cancer incidence and mortality. The purpose of our study was to assess the prognostic value of serum lipid levels in PTCL-U and improve PIT. We screened the prognostic factors associated with progression-free survival (PFS) and overall survival (OS) by multivariate Cox regression analysis in ninety-one enrolled patients. The results showed that low-level high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were associated with unfavorable OS. Furthermore, we developed a new risk model, PITC, based on low-level HDL-C, LDL-C and PIT. In Chinese PTCL-U, PITC was superior to PIT in PFS and OS. In conclusion, serum cholesterol levels may be good candidates for predicting prognosis in PTCL-U.

Low T3 syndrome as a predictor of poor prognosis in chronic lymphocytic leukemia.

Low triiodothyronine (T3) state is associated with poor prognosis in critical acute and prolonged illness. However, the information on thyroid dysfunction and cancer is limited. The aim of our study was to evaluate the prognostic value of low T3 syndrome in chronic lymphocytic leukemia (CLL). Two hundred and fifty-eight patients with detailed thyroid hormone profile at CLL diagnosis were enrolled. Low T3 syndrome was defined by low free T3 (FT3) level accompanied by normal-to-low free tetraiodothyronine (FT4) and thyroid-stimulating hormone (TSH) levels. A propensity score-matched method was performed to balance the baseline characteristics. Multivariate Cox regression analyses screened the independent prognostic factors related to time-to-first-treatment (TTFT) and cancer-specific survival (CSS). Area under the curve (AUC) assessed the predictive accuracy of CLL-International Prognostic Index (IPI) together with low T3 syndrome. The results showed that 37 (14.34%) patients had low T3 syndrome, which was significantly associated with unfavorable TTFT and CSS in the propensity-matched cohort, and it was an independent prognostic indicator for both TTFT and CSS. Serum FT3 level was positively related to protein metabolism and anemia, and inversely related to inflammatory state. Patients with only low FT3 demonstrated better survival than those with synchronously low FT3 and FT4, while those with synchronously low FT3, FT4 and TSH had the worst clinical outcome. Low T3 syndrome together with CLL-IPI had larger AUCs compared with CLL-IPI alone in TTFT and CSS prediction. In conclusion, low T3 syndrome may be a good candidate for predicting prognosis in future clinical practice of CLL.

Prognostic impact of Epstein-Barr virus (EBV)-DNA copy number at diagnosis in chronic lymphocytic leukemia.

Epstein-Barr virus (EBV)-DNA is detected in the blood of some persons with chronic lymphocytic leukemia (CLL) at diagnosis. Whether this is important in the development or progression of CLL is controversial. We interrogated associations between blood EBV-DNA copy number and biological and clinical variables in 243 new-diagnosed consecutive subjects with CLL. Quantification of EBV-DNA copies was done by real-time quantitative PCR (RQ-PCR). All subjects had serological evidence of prior EBV-infection. However, only 24 subjects (10%) had a EBV-DNA-positive test at diagnosis. EBV-DNA-positive subjects at diagnosis had lower hemoglobin concentrations and platelet levels, higher thymidine kinase-1 and serum ferritin levels, un-mutated IGHV genes and a greater risk of Richter transformation compared with EBV-DNA-negative subjects. Percent CD20-, CD148- and ZAP70-positive cells and mean fluorescence intensity (MFI) of each cluster designation were also increased in EBV-DNA-positive subjects at diagnosis. EBV-DNA test positivity was associated with a briefer time-to-treatment interval (HR 1.85; [95% confidence interval, 1.13, 3.03]; P=0.014) and worse survival (HR 2.77; [1.18, 6.49]; P=0.019). Reduction in EBV copies was significantly associated with therapy-response. A positive blood EBV-DNA test at diagnosis and sequential testing of EBV copies during therapy were significantly associated with biological and clinical variables, time-to-treatment, therapy-response and survival. If validated these data may be added to CLL prognostic scoring systems.