The effect of extracellular polymeric substances on MICP solidifying rare earth slags and stabilizing Th and U.

Microbially induced carbonate precipitation (MICP) has been used to cure rare earth slags (RES) containing radionuclides (e.g. Th and U) and heavy metals with favorable results. However, the role of microbial extracellular polymeric substances (EPS) in MICP curing RES remains unclear. In this study, the EPS of Lysinibacillus sphaericus K-1 was extracted for the experiments of adsorption, inducing calcium carbonate (CaCO3) precipitation and curing of RES. The role of EPS in in MICP curing RES and stabilizing radionuclides and heavy metals was analyzed by evaluating the concentration and morphological distribution of radionuclides and heavy metals, and the compressive strength of the cured body. The results indicate that the adsorption efficiencies of EPS for Th (IV), U (VI), Cu2+, Pb2+, Zn2+, and Cd2+ were 44.83%, 45.83%, 53.7%, 61.3%, 42.1%, and 77.85%, respectively. The addition of EPS solution resulted in the formation of nanoscale spherical particles on the microorganism surface, which could act as an accumulating skeleton to facilitate the formation of CaCO3. After adding 20 mL of EPS solution during the curing process (Treat group), the maximum unconfined compressive strength (UCS) of the cured body reached 1.922 MPa, which was 12.13% higher than the CK group. The contents of exchangeable Th (IV) and U (VI) in the cured bodies of the Treat group decreased by 3.35% and 4.93%, respectively, compared with the CK group. Therefore, EPS enhances the effect of MICP curing RES and reduces the potential environmental problems that may be caused by radionuclides and heavy metals during the long-term sequestration of RES.

Elevated BNP caused by recombinant human interleukin-11 treatment in patients with chemotherapy-induced thrombocytopenia.

Thrombocytopenia is a condition characterized by abnormally low levels of thrombocytes and often induced by chemotherapy. Recombinant human interleukin-11 (rhIL-11) is a cytokine that can stimulate thrombopoiesis and is commonly used to treat thrombocytopenia. We observed the side effects of rhIL-11 in 24 leukemia patients with chemotherapy-induced thrombocytopenia. To determine the cardiovascular effects of rhIL-11, we detected changes in the patients' serum brain natriuretic peptide (BNP), blood pressure fluctuations, weight change, and whether edema or heart failure occurred in leukemia patients after chemotherapy. The results showed that BNP was significantly elevated after using rhIL-11 (P < 0. 05) but regressed after 2-4 days. Furthermore, nine patients had edema and experienced weight gain, and four experienced acute left heart failure. In addition, the average blood pressure was 119/75 mmHg (range 139/86 mmHg to 99/64 mmHg) before rhIL-11 administration and 127/79 mmHg (range 146/89 mmHg to 108/69 mmHg) after rhIL-11 use. In conclusion, although rhIL-11 is useful for treating chemotherapy-induced thrombocytopenia, it is important to monitor the patients' clinical status and re-examine BNP levels frequently during the use of rhIL-11. Furthermore, senile patients should be given special attention. However, the appropriate timing to begin and discontinue rhIL-11 treatment needs further investigation.

ENO2 Promotes Cell Proliferation, Glycolysis, and Glucocorticoid-Resistance in Acute Lymphoblastic Leukemia.

BACKGROUND/AIMS: The metabolic features of cancer cells have long been acknowledged to be altered and to provide new therapeutic opportunities. The expression of glycolytic enzyme enolase 2 (ENO2) was found to be closely associated with the clinical features of acute lymphoblastic leukemia (ALL) patients, but its functions remain unclear in ALL. METHODS: We evaluated the association between ENO2 mRNA expression in bone marrow mononuclear cells (BM-MNCs) and the efficacy of chemotherapy, and further explored the function of ENO2 in ALL. The molecular mechanisms of ENO2 expression and its effects on cell growth, glycolysis and glucocorticoid resistance were explored by Cell Counting Kit-8, glucose-consumption assay, Quantitative RT-PCR, Western blotting and in vivo tumorigenesis in NOD/SCID mice. RESULTS: The results showed that ENO2 mRNA expression in BM-MNCs was significantly decreased when patients completed induction chemotherapy and reached complete remission (CR). ENO2 mRNA expression was increased when patients suffered relapse. Functional studies demonstrated that ENO2 promoted cell growth, glycolysis, and glucocorticoid resistance, all of which were effectively inhibited when ENO2 was silenced with shRNAs. Further studies revealed that ENO2 up-regulated various glycolysis-related genes and enhanced Akt activity with subsequent glycogen synthase kinase3ß (GSK-3ß) phosphorylation, inducing cell proliferation and glycolysis. The combination of silencing ENO2 and 2-deoxyglucose (2-DG) synergistically inhibited leukemia cell survival. CONCLUSIONS: These results indicate that ENO2 may be a biological marker for monitoring chemotherapeutic efficacy and relapse in ALL. ENO2 may provide a potential therapeutic strategy for ALL.

High level of soluble interleukin-2 receptor in serum predicts treatment resistance and poor progression-free survival in multiple myeloma.

The IL-2/IL-2 receptor (IL-2R) system plays a central role in maintaining normal T cell immunity, and its disturbance is associated with several hematologic disorders. Studies have found in several types of lymphoma that abnormal amounts of soluble IL-2R (sIL-2R) may result in imbalance of the IL-2/IL-2R system and hence of the T cell immunoregulation. Whether the level of sIL-2R in blood could predict treatment outcomes or not needs to be investigated in multiple myeloma (MM) patients. The level of sIL-2R in serum was measured using enzyme-linked immunosorbent assay (ELISA) in 81 patients with newly diagnosed MM. Twenty-six patients (32.1%) were treated with bortezomib-based regimens and 55patients (67.9%) received old drugs-based regimens. The mean concentration of sIL-2R for myeloma patients was 8.51 ng/ml, significantly higher than that of healthy controls (0.56 ng/ml, p < 0.0001). The best cutoff value for sIL-2R in predicting high risk for disease progression is 6.049 ng/ml with an area under curve (AUC) of 0.665 (p = 0.013). Thirty-six patients (44.4%) were classified as higher sIL-2R level group (> 6.049 ng/ml), and 45 patients (55.6%) as lower group (≤ 6.049 ng/ml). The overall response rate (ORR) was 60.0% in lower sIL-2R level group, and 41.7% in higher level group (p = 0.156). The median progression-free survival (PFS) and overall survival (OS) was 12 months (range, 2.0-65 months) and 20 months (range, 2.0-118 months), respectively. In a multivariate survival analysis, including Eastern Cooperative Oncology Group performance status score, treatment response, and sIL-2R level, it was found that all these three parameters were significantly independent prognostic factors for PFS (p = 0.032, 0.016, and 0.043, respectively), but none factors maintained their value in predicting OS. Subgroup analysis revealed that high level of sIL-2R is correlated with significantly inferior PFS in patients treated with bortezomib-based regimens (p = 0.004). Serum sIL-2R level is an independent prognostic factor for PFS, indicating novel drugs targeting the imbalance of IL-2/IL-2R system may be a promising strategy in MM.

High level of interleukin-10 in serum predicts poor prognosis in multiple myeloma.

BACKGROUND: Interleukin-10 (IL-10) is a inhibiting inflammatory cytokine that plays an important role in immune suppressive microenvironment in multiple myeloma (MM). Whether the level of serum IL-10 could predict treatment response and survival outcomes or not needs to be investigated in MM patients. METHODS: The level of IL-10 in serum was measured using enzyme-linked immunosorbent assay in 188 patients with newly diagnosed MM. RESULTS: The best cutoff value for IL-10 in predicting survival is 169.69 pg ml(-1) with an area under the curve (AUC) value of 0.747 (P<0.001). In all, 92 patients (48.9%) were classified as high-IL-10 group (>169.96 pg ml(-1)) and 96 patients (51.1%) as low-IL-10 group (⩽169.96 pg ml(-1)). The overall response rate (ORR) was 79.2% in low-IL-10 group, significantly higher than that in high-IL-10 group (53.3%, P<0.001). Patients in low-IL-10 group had significantly better survival compared with those in high-IL-10 group (3-year PFS rate: 69.3% vs 13.3%, P<0.001; 3-year OS rate: 93.6% vs 51.9%, P<0.001). Multivariate analysis revealed that serum IL-10 level >169.96 pg ml(-1) at diagnosis and certain cytogenetic abnormalities were two adverse factors for PFS and OS. CONCLUSIONS: Our data suggest that serum IL-10 at diagnosis is a novel, powerful predictor of prognosis for MM.

Properties and mechanisms of steel slag strengthening microbial cementation of cyanide tailings.

The advantages of microbial induced carbonate precipitation (MICP) as bio-cementation technology for tailings-solidification are under extensive investigation. In order to improve performance of bio-cementation, many strengthening materials were applied to the bio-cementation of tailings. Steel slag (SS) is a kind of industrial solid waste, its chemical composition and mineral composition are similar to cement, and it has a certain application prospect as an auxiliary cementing material. In this study, the properties and mechanism of SS strengthening MICP cementation of cyanide tailings (CT) were investigated. The results showed that Sporosarcina pasteurii growth is not inhibited by SS, and Sporosarcina pasteurii can promote the hydration reaction of SS, providing a suitable alkaline environment and Ca2+, promoting the production of more CaCO3 in the MICP process. When 200 mL of CT leachate was added 1.4 g SS (200-400 mesh), the adsorption of Cu, Pb, Zn, Cd, total cyanide (T-CN), and free cyanide (F-CN) reached 48.05%, 44.28%, 36.25%, 16.67%, 79.05%, and 67.20%, respectively. The maximum unconfined compressive strength（UCS） of the cemented body (with 5%, 150 mesh SS) was 1.97 MPa, which was 3.396 times as high as that without SS. The cemented body with the addition of SS (5%, 150 mesh) contained more carbonate bound Cu (2.75%), Pb (4.89%), Zn (5.37%), and Cd (5.75%), and less exchangeable Cu (3.65%), Pb (6.85%), Zn (2.27%), and Cd (4.42%) than that without SS. In summary, the addition of SS improved the UCS of cemented bodies and the stability of heavy metals and cyanide, reduced the environmental risks existing in the process of CT storage. Meanwhile, it also provides new ideas for resource utilization of industrial solid waste SS and improvement of mine filling materials.

Study on the performance of Anerinibacillus sp. in degrading cyanide wastewater and its metabolic mechanism.

Cyanide extraction dominates the gold smelting industry, which leads to the generation of large amounts of cyanide-containing wastewater. In this study, Aneurinibacillus tyrosinisolvens strain named JK-1 was used for cyanide wastewater biodegradation. First, we tested the performance of JK-1 in degrading cyanide under different conditions. Then, we screened metabolic compounds and pathways associated with cyanide degradation by JK-1. Finally, we explored the potential JK-1-mediated cyanide degradation pathway. Our results showed that the optimal pH and temperature for cyanide biodegradation were 7.0 and 30 °C, respectively; under these conditions, a degradation rate of >98% was achieved within 48 h. Untargeted metabolomics results showed that increased cyanide concentration decreased the abundance of metabolic compounds by 71.1% but upregulated 32 metabolic pathways. The Kyoto Encyclopedia of Genes and Genomes enrichment results revealed significant changes in amino acid metabolism pathways during cyanide degradation by JK-1, including cyanoamino acid metabolism, ß-alanine metabolism, and glutamate metabolism. Differential metabolic compounds included acetyl-CoA, l-asparagine, l-glutamic acid, l-phenylalanine, and l-glutamine. These results confirmed that cyanide degradation by JK-1 occurs through amino acid assimilation. This study provides new insights into the mechanism of cyanide biodegradation, which can be applied in the treatment of cyanide wastewater or tailings.

Chlorogenic Acid Induced Neuroblastoma Cells Differentiation via the ACAT1-TPK1-PDH Pathway.

BACKGROUND: Chlorogenic acid (CHA) has been shown to have substantial biological activities, including anti-inflammatory, antioxidant, and antitumor effects. However, the pharmacological role of CHA in neuroblastoma has not yet been assessed. Neuroblastoma is a type of cancer that develops in undifferentiated sympathetic ganglion cells. This study aims to assess the antitumor activity of CHA against neuroblastoma and reveal its mechanism of action in cell differentiation. METHODS: Be(2)-M17 and SH-SY5Y neuroblastoma cells were used to confirm the differentiation phenotype. Subcutaneous and orthotopic xenograft mouse models were also used to evaluate the antitumor activity of CHA. Seahorse assays and metabolomic analyses were further performed to investigate the roles of CHA and its target ACAT1 in mitochondrial metabolism. RESULTS: CHA induced the differentiation of Be(2)-M17 and SH-SY5Y neuroblastoma cells in vivo and in vitro. The knockdown of mitochondrial ACAT1, which was inhibited by CHA, also resulted in differentiation characteristics in vivo and in vitro. A metabolomic analysis revealed that thiamine metabolism was involved in the differentiation of neuroblastoma cells. CONCLUSIONS: These results provide evidence that CHA shows good antitumor activity against neuroblastoma via the induction of differentiation, by which the ACAT1-TPK1-PDH pathway is involved. CHA is a potential drug candidate for neuroblastoma therapy.

Thalassaemia in China.

Because of successful thalassaemia prevention programmes in resource-rich countries and it's huge population China now has the greatest number of new cases of thalassaemia globally as well as more people with thalassaemia than any other country. 30 million Chinese have thalassaemia-associated mutations and about 300,000 have thalassaemia major or intermedia requiring medical intervention. Over the past 2 decades there has been tremendous economic growth in China including per capita spending on health care. There is now nation-wide availability and partial or full insurance for prenatal genetic testing, RBC-transfusions, iron-chelating drugs and haematopoietic cell transplants. Prenatal screening and educational programmes have reduced the incidence of new cases. However, substantial challenges remain. For example, regional differences in access to medical care and unequal economic development require innovations to reduce the medical, financial and psychological burdens of Chinese with thalassaemia and their families. In this review we discuss success in preventing and treating thalassaemia in China highlighting remaining challenges. Our discussion has important implications for resource-poor geospaces challenged with preventing and treating thalassaemia.

[Effect of Aging on Stabilization of Cd2+ Through Biochar Use in Alkaline Soil of Bayan Obo Mining Area].

Although biochar has been widely used in the remediation of heavy metal pollution in acidic and neutral soils, less attention has been paid to whether biochar will alter its structural properties and the ability to retain heavy metals after different degrees of aging in alkaline soils. In this study, two artificial accelerated aging methods (freeze-thaw cycle and dry-wet cycle) and a short-term natural aging method were used to simulate the aging process of biochar prepared from corn stalk. We investigated the changes in the soil pH and bioavailability, total content, and transformation of Cd2+ before and after aging treatments. Biochar was separated from the soil for characterization to explore the effect of aging on the passivation of Cd2+ by biochar in the alkaline soil of the mining area. The results showed that adding biochar to alkaline soil in the Bayan Obo mining area had no significant liming effect, and pH decreased after the freeze-thaw and dry-wet accelerated aging treatments. Compared with that in the control, the CaCl2-extractable contents of Cd2+ decreased by 19.32%-30.67%, and the total contents of Cd2+ decreased by 5.02%-7.18%. Aging did not significantly change the transformation of Cd2+ but reduced the distribution of acid-soluble and reducible fractions, indicating that biochar could immobilize Cd2+ for a long time after aging, which was related to the increase in oxygen-containing functional groups and the pore structure of biochar. These results are important for evaluating its long-term application prospects in the mining environment.

A prognostic survival model based on metabolism-related gene expression in plasma cell myeloma.

Accurate survival prediction of persons with plasma cell myeloma (PCM) is challenging. We interrogated clinical and laboratory co-variates and RNA matrices of 1040 subjects with PCM from public datasets in the Gene Expression Omnibus database in training (N = 1) and validation (N = 2) datasets. Genes regulating plasma cell metabolism correlated with survival were identified and seven used to build a metabolic risk score using Lasso Cox regression analyses. The score had robust predictive performance with 5-year survival area under the curve (AUCs): 0.71 (95% confidence interval, 0.65, 0.76), 0.88 (0.67, 1.00) and 0.64 (0.57, 0.70). Subjects in the high-risk training cohort (score > median) had worse 5-year survival compared with those in the low-risk cohort (62% [55, 68%] vs. 85% [80, 90%]; p < 0.001). This was also so for the validation cohorts. A nomogram combining metabolic risk score with Revised International Staging System (R-ISS) score increased survival prediction from an AUC = 0.63 [0.58, 0.69] to an AUC = 0.73 [0.66, 0.78]; p = 0.015. Modelling predictions were confirmed in in vitro tests with PCM cell lines. Our metabolic risk score increases survival prediction accuracy in PCM.

Safety and efficacy of thalidomide in patients with transfusion-dependent ß-thalassemia: a randomized clinical trial.

Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent ß-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P < 0.001). Adverse events of drowsiness, dizziness, fatigue, pyrexia, sore throat, and rash were more common with thalidomide than placebo. In the extension phase, treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9 ± 19.0 g/L, without blood transfusion. Significant increase in Hb concentration and reduction in RBC transfusions were associated with non ß0/ß0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.

Comprehensive analysis of two potential novel SARS-CoV-2 entries, TMPRSS2 and IFITM3, in healthy individuals and cancer patients.

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, with acute respiratory failure as the most significant symptom, has led to a global pandemic. Angiotensin-converting enzyme 2 (ACE2) is considered as the most important receptor of SARS-CoV-2 and wildly expressed in human tissues. Whereas, the extremely low expression of ACE2 in lung could hardly interpret the severe symptom of pneumonia in COVID-19 patients. Here we profiled two SARS-CoV-2 infection related genes, the transmembrane serine protease 2 (TMPRSS2) and the interferon-inducible transmembrane protein 3 (IFITM3), in human tissues and organs. Consistent with the expression and distribution of ACE2, TMPRSS2 was also highly expressed in digestive, urinary and reproductive systems, but low expressed in lung. Notably, the anti-virus protein IFITM3 also expressed much lower in lung than other tissues, which might be related to the severe lung symptoms of COVID-19. In addition, the low expression of IFITM3 in immune cells suggested that SARS-CoV-2 might attack lymphocytes and induce the cytokine release syndrome (CRS). Furthermore, cancer patients were considered as more susceptible to SARS-CoV-2 infection. Our data supposed that fourteen types of tumors might have different susceptibility to the virus according to ACE2, TMPRSS2 and IFITM3 expression patterns. Interestingly the prognosis of six types of cancers including breast carcinoma (BRCA), lung adenocarcinoma (LUAD), uterine corpus endometrial carcinoma (UCEC), renal clear cell carcinoma (KIRC), prostate adenocarcinoma (PRAD), and hepatocellular carcinoma (LIHC) were closely related to these gene expressions. Our study explored the expression and distribution profiles of two potential novel molecules that might participate in SARS-CoV-2 infection and involved in immunity, which may provide a functional basis for preventing infection of SARS-CoV-2.

Identification of cancer stem cell characteristics in liver hepatocellular carcinoma by WGCNA analysis of transcriptome stemness index.

Cancer stem cells (CSCs) are characterized by self-renewal and -differential potential as compared to common cancer cells and play an important role in the development and therapeutic resistance of liver hepatocellular carcinoma (LIHC). However, the specific pathogenesis of LIHC stem cells is still unclear, and the genes involved in the stemness of LIHC stem cells are currently unknown. In this study, we investigated novel biomarkers associated with LIHC and explored the expression characteristics of stem cell-related genes in LIHC. We found that mRNA expression-based stemness index (mRNAsi) was significantly overexpressed in liver cancer tissues. Further, mRNAsi expression in LIHC increased with the tumor pathological grade, with grade 4 tumors harboring the greatest stem cell features. Upon establishing mRNAsi scores based on mRNA expression of every gene, we found an association with poor overall survival in LIHC. Moreover, modules of interest were determined based on weighted gene co-expression network analysis (WGCNA) inclusion criteria, and three significant modules (red, green, and brown) and 21 key genes (DCN, ECM1, HAND2, PTGIS, SFRP1, SRPX, COLEC10, GRP182, ADAMTS7, CD200, CDH11, COL8A1, FAP, LZTS1, MAP1B, NAV1, NOTCH3, OLFML2A, PRR16, TMEM119, and VCAN) were identified. Functional analysis of these 21 genes demonstrated their enrichment in pathways involved in angiogenesis, negative regulation of DNA-binding transcription factor activity, apoptosis, and autophagy. Causal relationship with proteins indicated that the Wnt, Notch, and Hypoxia pathways are closely related to LIHC tumorigenesis. To our knowledge, this is the first report of a novel CSC biomarker, mRNAsi, to predict the prognosis of LIHC. Further, we identified 21 key genes through mRNA expression network analysis, which could be potential therapeutic targets to inhibit the stemness of cancer cells in LIHC.

NSE from diffuse large B-cell lymphoma cells regulates macrophage polarization.

Background/aims: Diffuse large B-cell lymphoma (DLBCL) is a highly common type of malignant and heterogeneous non-Hodgkin's lymphoma. Tumor-associated macrophages, specially the M2-type, promote tumor progression and drug resistance. The clinical outcome of patients with high neuron-specific enolase (NSE) expression is worse than that with low NSE expression. The tumor-promoting mechanism of NSE, however, remains unclear. This study explored the role of NSE in macrophage polarization associated with the immune microenvironment of DLBCL. Results: Our results showed that NSE protein expression was higher in lymphoma cell lines than in the B lymphocytes. Functional studies demonstrated that upregulation of NSE in lymphoma cells could promote M2 polarization and migration ability of macrophage, thereby consequently promoting the progression of lymphoma in vitro and in vivo. Further mechanism studies revealed that lymphoma-derived exosomes could mediate NSE into macrophages, NSE enhanced nuclear p50 translocation with subsequent defective classical nuclear factor-κB activity in macrophages. Conclusions: These results indicate that NSE may be a potential target for lymphoma therapy and a prognosis marker for lymphoma.

Asparagine synthetase expression is associated with the sensitivity to asparaginase in extranodal natural killer/T-cell lymphoma in vivo and in vitro.

BACKGROUND: Although asparagine synthetase (AsnS) is associated with drug resistance in leukemia, its function in extranodal natural killer (NK)/T-cell lymphoma (ENKTL) remains unclear. METHODS: The present study investigated the relationship between baseline AsnS mRNA levels and response to asparaginase in ENKTL cell lines. It also determined whether upregulating or downregulating the AsnS mRNA level induces or reverses asparaginase-resistant phenotype. RESULTS: Interestingly, considerable differences were observed in the sensitivity to asparaginase of the five ENKTL cell lines. The AsnS expression levels were positively correlated with the IC50 values. In addition, the asparaginase resistance was induced or reversed by upregulating or downregulating the AsnS mRNA level in vivo and in vitro. Functional analyses indicated that AsnS did not affect the proliferation and apoptosis of ENKTL cells in the absence of asparaginase. CONCLUSION: Together, the data stress the importance of AsnS in the sensitivity to asparaginase in ENKTL and suggest a different therapeutic strategy for patients with a different level of AsnS expression.

Use of PEG-asparaginase in newly diagnosed adults with standard-risk acute lymphoblastic leukemia compared with E. coli-asparaginase: a retrospective single-center study.

Acute lymphoblastic leukemia (ALL) is a heterogeneous disease, and the long-term survival varies with different ages. We performed a retrospective analysis of 122 newly diagnosed adults with standard-risk ALL treated with Escherichia coli asparaginase (E. coli-asparaginase, n = 50) and polyethylene glycol-conjugated asparaginase (PEG-asparaginase, n = 72). No treatment-related mortality (TRM) occurred in the E. coli-asparaginase group, and 3 TRM events occurred in the PEG-asparaginase group without relation to asparaginase. In addition, 22 (44.0%) and 48 (66.7%) patients achieved a complete response (CR) on day 14 in the E. coli-asparaginase and PEG-asparaginase groups, respectively (P = 0.032). No different 5-year event-free survival (EFS) or overall survival (OS) rate (P = 0.632 and 0.769) was observed. Multivariate analysis revealed later CR (P = 0.008) and older age (P = 0.049) as adverse prognostic factors for both EFS and OS. In addition, we specifically monitored the known adverse effects of asparaginase, and no asparaginase-related death was observed. Allergy occurred in 9 patients using E. coli-asparaginase, and no patient in the PEG-asparaginase group suffered from allergies (P < 0.001). The incidence of other asparaginase-related toxicities was similar. We conclude that PEG-asparaginase can be safely and effectively used as asparaginase in adults with newly diagnosed standard-risk ALL.

A childhood chemotherapy protocol improves overall survival among adults with T-lymphoblastic lymphoma.

A broadly accepted standard treatment for adult T-lymphoblastic lymphoma (T-LBL) has not yet been defined. To address that issue, we retrospectively compared three chemotherapy regimens used to treat 110 adult patients with newly diagnosed T-LBL. These included two adult regimens (ECOG2993 and hyper-CVAD) and a childhood regimen (BFM-90). These intensive drug regimens are mainly used to treat childhood and adult acute lymphoblastic leukemia. They included induction, consolidation, and maintenance chemotherapy protocols and were administered over the course of 2 years. Seventy-five patients (80%) achieved a complete remission (CR). Within a median follow-up time of 31 months (range: 5-152 months), the 5-year overall survival (OS) and progression-free survival (PFS) rates were 47.7% (95% CI, 35.0-69.8%) and 45.7% (95% CI, 27.6-56.6%), respectively. Shorter survival was associated with age > 40 years, poor ECOG PS and bone marrow involvement. Elevated lactic dehydrogenase (LDH) level, Ann Arbor stage and International Prognostic Index (IPI) score had no prognostic value. The childhood chemotherapy regimen improved CR and the overall survival rate more than the adult regimen in patients aged < 40 years.