Courses Of Standard Chemotherapy Research Articles

Combination of Interleukin-6, C-Reactive Protein and Procalcitonin Values as Predictive Index of Sepsis in Course of Fever Episode in Adult Haematological Patients: Observational and Statistical Study.

Haematological patients represent a vulnerable population to opportunistic infections, mainly due to the disease itself and chemotherapy-induced neutropenia. The level of immune suppression strongly increases the importance of timely antibiotic treatment in order to prevent sepsis-related mortality. During the initial fever episode, serum biomarkers are usually used to estimate the probability of blood stream infection prior to the results of microbial diagnosis. A new serum biomarker combination study on a febrile haematological population, including C-reactive protein (CRP), interleukin-6 (IL-6) and procalcitonin (PCT), is proposed in order to improve their predictive accuracy. In our prospective study, CRP, IL-6 and PCT were evaluated in 34 immunosuppressed haematological patients immediately after the onset of 51 fever episodes, either during the course of standard chemotherapy or high-dose chemotherapy and autologous stem cell transplant. The fever episodes were divided into documented infections and fever alone. Receiver operating characteristic analysis (ROC) was performed for each biomarker and a combination of all three biomarkers (multiROC) to define a new predictive index. Significant differences were evidenced between the two groups (documented infection and no infection) for both PCT and IL-6 (p = 0.03 and p = 0.035, respectively), but none for CRP (p = 0.1). The composite parameter is more reliable than any single biomarker alone, with an area under the curve (AUC) of 79% and with high sensitivity and specificity. IL-6 gave the closest response compared to the composite index. Composite parameters of serum biomarkers could be used for an early diagnosis of infection at fever onset in haematological patients.

Expression level and prognostic potential of beta-catenin-interacting protein in acute myeloid leukemia.

Inhibitor of beta-catenin and TCF (ICAT) is a key protein in the Wnt-β-catenin signaling pathway. However, its role in acute myeloid leukemia (AML) remains unknown. In this study, we evaluated its expression level as well as its prognostic value in AML patients. A total of 72 patients with AML and 30 control subjects were enrolled in this study during the period of January 2017 and December 2019 at Zhongshan Hospital of SunYat-sen University. ICAT and β-catenin expression levels in peripheral blood were determined via enzyme-linked immunosorbent assays. ICAT levels in AML patients were significantly lower and β-catenin levels were higher than those of the control group. After the first course of standard chemotherapy, the concentration of ICAT in the partial remission group (93.79 ng/mL) was significantly higher than that in the initial diagnosis group (49.38 ng/mL) and the no response group (39.94 ng/mL). AML subtypes had lower ICAT expression levels than controls, and ICAT levels were significantly correlated with body mass index, bone marrow/peripheral blood blast cell proportions, and white blood cell and red blood cell counts at initial diagnosis. Furthermore, low ICAT expression was found to be associated with poor disease-free survival and overall survival in AML. ICAT is closely associated with AML progression and can be used as an indicator to monitor AML treatment efficacy.

CLINICAL EXPRESSION OF TH17 RELATED CYTOKINESIN ACUTE MYELOID LEUKEMIA PATIENTS: A PROSPECTIVE DESCRIPTIVE STUDY

Background: Acute myeloid leukemia (AML) is a hematological neoplasm that affects adults of all ages and accounts for 1-2% of malignancies worldwide. T- cell function is significantly impaired in AML patients. Increasing evidence states that a recently identified subtype of CD4 + T cells called T helper 17(Th17) is associated with the pathogenesis of AML. Aim: This study aims to estimate the concentration of Th 17 related cytokines IL-23 and IL-17 in the plasma samples diagnosed with AML and to assess their clinical value in the prognosis of AML. Methods: This study includes 31 patients who were newly diagnosed with AML. Similarly, 21 healthy subjects were selected for normal control group. After two courses of induction chemotherapy 22 patients achieved complete remission (CR), whereas 9 patients failed to achieve CR. IL-23 and IL-17 plasma levels were measured using ELISA kits. Results: The IL-23 and IL-17 plasma levels in the newly diagnosed group were significantly higher than the CR and control group. Similarly, after two courses of standard chemotherapy, the IL-23 and IL-17 expression levels in the non-remission (NR) group were also much higher than in the CR and control group. No significant differences in the expression of IL-23 and IL-17 between CR and control groups were found. In AML patients, a significant positive correlation was found between IL-23 and IL-17. Conclusion: The IL-23 and IL-17 plasma levels correlate with the progression of AML, which may express clinical significance in the prognosis and therapeutic evaluation of AML.

Дослідження глікобіому поверхні лімфоцитів хворих на В-клітинний хронічний лімфолейкоз

The purpose of the study was to investigate the intensity of exposure of peripheral blood lymphocyte surface glycans in patients with B-cell chronic lymphocytic leukemia by measuring the density of lectin- or antigen-positive epitopes under antitumor therapy in order to evaluate it for a more reasonable selection of qualitative and quantitative composition of therapy. Materials and methods. The objects of the study were blood lymphocytes of patients with chronic lymphocytic leukemia (n=15) aged 58-66 years before and after a course of standard chemotherapy according to the COP scheme. The control group consisted of healthy volunteers (n=15) aged 55 to 65 years. Isolation of lymphocytes was performed by a modified method of A. Boyum. Polyclonal antibodies to α1-acid glycoprotein and fibronectin were used. Exposure to Tn antigen and CD43 on blood lymphocytes was determined with secondary antibodies to mouse immunoglobulins conjugated to FITC (Millipore, USA). To study the exposure of glycans on the surface of lymphocytes, we used a set of seven lectins labeled with FITC. Data recording was performed on a Beckman Flower EPICS flow cytometer. Processing of the results was done using the program FCS3 Express. Results and discussion. Compared with the group of hematologically healthy donors on the surface of lymphocytes in patients with chronic lymphocytic leukemia, a 20-fold increase in the density of exposure to ConA epitopes, 10 times – UEAI- and SNA-positive epitopes were shown; MAA II epitope, Tn, and CD43 antigen densities were increased 100-fold (p <0.01). Exposure densities of MAA II-, Tn-, and CD43-positive epitopes on the plasma membrane of lymphocytes in patients with chronic lymphocytic leukemia receiving alkylation therapy decreased 10-fold relative to treatment data, but remained 10-fold higher than in the group of healthy hematologists. Conclusion. On the plasma membranes of lymphocytes in patients with chronic lymphocytic leukemia, the density of exposure of mannose and neuraminic acid residues was significantly increased. COP therapy reduced the density of these epitopes to control values. A significant increase in the density of carcinogenesis markers – Tn- and CD43-antigens on the plasma membranes of lymphocytes in patients with chronic lymphocytic leukemia has been shown. COP therapy provided only a partial decrease in their density, which indicates the insufficient effectiveness of COP therapy, its inability to completely stop the oncological process in patients with chronic lymphocytic leukemia

Stratification of Intermediate-Risk Acute Myeloid Leukemia According to the Expression Level of WT1 mRNA at Diagnosis

IntroductionDespite advances in the genetic analysis of acute myeloid leukemia (AML), Wilms' tumor oncogene 1 (WT1) mRNA remains an important pan-marker of AML. A log reduction in WT1 mRNA expression after chemotherapy is a predictor of prognosis, and WT1 mRNA can be used as a marker of minimal residual disease or relapse. In the 1990s, a high expression level of WT1 mRNA at diagnosis was considered a poor prognostic factor. However, recent analyses have found that WT1 mRNA expression varies with AML type. Since the prognosis is affected by cytogenetic abnormalities and therapeutic intensity, we re-evaluated the clinical significance of WT1 mRNA expression at diagnosis in the context of the European Leukemia Net (ELN) risk classification and treatment.MethodWe retrospectively analyzed 216 patients at five institutions between 2011 and 2020. The expression level of WT1 mRNA was measured for all patients at diagnosis using bone marrow (BM) samples from 191 patients and peripheral blood (PB) samples from 25. WT-1 mRNA expression was measured using real-time quantitative polymerase chain reaction and the measured values were converted in normal logarithm. The median age at diagnosis was 62 (range: 23-93) years. The cytogenetic risk of ELN was classified as favorable (n = 41), intermediate (n = 123), and adverse risk (n = 41). Selected therapeutics were standard chemotherapy (n = 182, 84.3%, including CAG regimen; cytarabine, aclarubicin and G-CSF), hypomethylating agents or low-dose cytarabine (n = 19, 8.8%), and best supportive care (n = 15, 6.9%). Also, 143 patients (66.2%) received one or more courses of standard consolidation chemotherapy and 61 (28.3%) underwent allogeneic hematopoietic stem cell transplantation (allo-HCT). The median observation period was 518 [1-3418] days (Table 1). The overall survival (OS) and event-free survival (EFS) rates were assessed. Relapse or death was defined as an event, and OS was evaluated on the date of death.ResultThe median expression level of WT1 mRNA was 4.68 (range: 1.0-5.72) [log copies/µg RNA, units are omitted thereafter] in BM and 3.66 (range: 1.34-5.20) in PB (Table 1). Favorable-risk AML had the highest WT1 mRNA expression level in BM (4.95, p = 0.0054), whereas there was no difference between the expression levels in intermediate- and adverse-risk AML in BM (4.63 and 4.47, p = 0.711, Fig. 1A). WT1 mRNA expression in PB were 4.04, 3.84, and 3.05 for favorable-, intermediate-, and adverse-risk AML, respectively, and were higher for those with a favorable-risk AML (vs. adverse risk, p = 0.048, Fig. 1B). When WT1 mRNA expression level in BM was compared between the two groups, i.e., <4.0 (BM-WT1 low) vs. ≥4.0 (BM-WT1 high), 2-year EFS rates were 26.8% and 49.7% (p = 0.0035) and 2-year OS rates were 44.9% and 61.5% (p = 0.00053), respectively. When WT1 mRNA expression level in PB was compared between the two groups, i.e., <3.0 (PB-WT1 low) vs. ≥3.0 (PB-WT1 high), 2-year EFS rates were 0% and 51.5% (p = 0.023) and 2-year OS rates were 0% and 73.1% (p = 0.01), respectively. PB- or BM-WT1 low showed a worse prognosis at diagnosis.Since AML prognosis is affected by ELN risk and selected therapeutics, we evaluated 109 intermediate-risk patients who had received at least one course of standard chemotherapy. Fifty of them (45.9%) underwent subsequent allo-HCT. The 2-year EFS rates of PB or BM-WT1 low (n = 25, PB = 2 and BM = 23) vs. PB or BM-WT1 high (n = 84, PB = 23 and BM = 61) were 23.9% and 50.4%, respectively (p = 0.023, Fig. 2A) and the 2-year OS rates were 51.2% and 64.6%, respectively (p = 0.03, Fig. 2B). PB or BM-WT1 low of intermediate-risk AML had a poor prognosis even with standard chemotherapy. Multivariate analysis adjusted for ages, the reduction rate of WT1 mRNA after induction chemotherapy, duration of receiving consolidation chemotherapy, allo-HCT, and PB or BM-WT1 low at diagnosis were independent poor prognosis factors for EFS in intermediate-risk AML (HR: 3.32, 95%CI: 1.29-8.53, p = 0.013). The OS rate of PB or BM-WT1 low also worsened (HR: 2.33, 95%CI: 0.88-6.18, p = 0.089) (Table 2). Whereas, the outcome of adverse-risk AML was not affected by PB or BM-WT1 low/high.ConclusionThe expression level of WT1 mRNA at diagnosis was negatively correlated with prognosis. Favorable-risk AML had higher expressions of WT1 mRNA. PB or BM-WT1 low in intermediate-risk AML was associated with a poor prognosis. In standard-risk AML, WT1 mRNA may be a useful pan-marker to predict prognosis at diagnosis. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Evolution of Mechanical Stress (In-vitro) on Properties of Granulocytes in Acute Lymphoblastic Leukemia.

Acute lymphoid leukemia (ALL) affects the lymph cells or lymphocytes that make up the lymph tissue and prevents the proper maturation of the bone marrow cells. The processes through which cells convert mechanical stimuli into biochemical signals are called mechanical transitions and result in the sensation of specific cellular responses. In the present study, the functional properties of granulocytes of the patients with ALL were investigated using the in vitro mechanical stress model. The experimental part of the work was executed using blood from patients with ALL (n=30) being treated in the Hematological Department of Belgorod Region Hospital, Belgorod, Russia. The patients were in the age range of 18-45 years. Sample blood was obtained from all the patients who underwent a standard course of chemotherapy. Blood sampling was performed using a venepuncture and collected into the vacuum tubes Vacuette K3E. Blood samples from each experimental group were divided into two groups of control and experiment. The injection model of mechanical stress was used for the experiment groupin vitro. Subsequently, the adenosine triphosphate (ATP) concentration increased by 1.8 times in this group, compared with the controls. Young's module, which numerically characterizes the rigidity of the granulocytes' plasmalemma, decreased by 54.4% (P<0.05) under the influence of mechanical stress. The surface potential of plasmalemma was not significantly different between samples in the group of control and experiment in patients with ALL. However, the adhesive force between erythrocyte and granulocyte increased by 30.7% (P<0.05). The osmotic load test showed an increase in the cell's volume during incubation. The use of membrane reserve by granulocytes increased by 47% (P<0.05) at the initial seconds of incubation. The obtained results pointed to the regulatory role of ATP molecules in intercellular signaling and add to the present literature regarding the mechanisms of intercellular interaction in the microvasculature on the development of leukemia. Moreover, the obtained results can be taken into account for the development of new pharmacological immune correctors.

БИОФИЗИЧЕСКИЕ СВОЙСТВА КЛЕТОЧНОЙ ПОВЕРХНОСТИ И ФУНКЦИОНАЛЬНАЯ АКТИВНОСТЬ ГРАНУЛОЦИТОВ БОЛЬНЫХ ОСТРЫМ ЛИМФОБЛАСТНЫМ ЛЕЙКОЗОМ ПРИ МОДЕЛИРОВАНИИ НАГРУЗКИ С АТФ IN VITRO

The current study is devoted to the investigation of the biophysical properties of the cell surface and the functional activity of granulocytes in patients with acute lymphoblastic leukemia when simulating the ATP load in vitro. The experiment was performed on the peripheral blood of patients with acute lymphoblastic leukemia (ALL) who underwent a standard course of chemotherapy. In experimental tests, exogenous loading with ATP was simulated in vitro by adding 100.0 μM adenosine-5-triphosphate disodium salt trihydrate to the granulocyte suspension. Incubation with the drug was carried out for 15 min at 370 C. As a control, a suspension of granulocytes in RPMI 1640 medium from the same patient, but without the addition of the drug, was used, this was incubated for 15 min at a temperature of 370 C. After the incubation time, the biophysical properties (rigidity, charge of the cell surface, the strength of intercellular adhesion) of granulocytes in experimental and control samples were studied using atomic force microscopy, and the migration activity of cells was also assessed in a direct capillary test under agarose. A model with exogenous ATP in ALL patients showed a decrease in the rigidity and potential of the plasma membrane surface, an increase in the adhesive properties and migration activity of granulocytes. The revealed effects point to the key role of the ATP molecule in the mechanisms of intercellular signaling in the microvasculature.

This Is a Title: Cytarabine Combined with PD-1 Inhibitor in the Treatment of R/R-AML: A Report of 3 Cases and Literature Review

Objectives: To explore the efficacy and safety of high-dose cytarabine combined with PD-1 inhibitors and demethylation drugs in relapsed and refractory acute myeloid leukemia (R/R-AML) in Chinaand to investigatethe dynamic changes of Treg cells, CD4+ T cells, CD8+ T cells, TNF-α, INF-γ, and IL-6 in the prognosis of the disease. Methods:A total of three patients with R/R-AML treated in our department were included in the study. None of the three patients had received at least two courses of standard chemotherapy before and did not obtain remission.The cellular immunity and cytokines were evaluated on the 1st, 8th, 15th, and 22nd day of the treatment.In the study,eligible R/ R-AML patients (n=3) were treated with azacytidine 75mg/m2 d1-d7, cytarabine 2g/m2 d1-d5, PD-1 inhibitor 200mg d1、d14.The efficacy were evaluated by CR, PR, ORR, PFS, OS, and ED. The safety were evaluated by hematological and non-hematological toxicity. Results: Among the three patients, one patient achieved CR, and one patient achieved PR. The patient who achieved CR successfully underwent allo-HSCT. One patient did not achieve remission and died of disease progression. Three patients were well tolerated to chemotherapy, and non-hematological toxicity was mainly respiratory tract infection, gastrointestinal reaction, and liver function damage.At present, no immune-related tissue injury was observed. Grade III-IV hematologic toxicity was the major adverse reaction, and the longest duration of agranulocytosis was 22 days.The proportion of Treg cells decreased, and the proportion of CD4+ T cells and CD8+ T lymphocytes increased in 2 patients after treatment. One patient received CR and underwent allo-HSCT. One patient showed an increase in the proportion of Treg cells, but there was no significant dynamic change in CD4+ T lymphocytes and CD8+ T lymphocytes. INF-γ increased in 1 patient. Dynamic changes in IL-10, IL-6, and TNF-α were not observed. Conclusions: PD-1 inhibitor combined with high dose cytarabine based chemotherapy may be a salvage treatment for R/R-AML. The dynamic changes of CD4+ T lymphocyte, CD8+ T lymphocyte, Treg cell, and INF-α may reflect the therapeutic effect in advance. Disclosures No relevant conflicts of interest to declare.

A multicentric randomized phase II clinical trial evaluating high-dose thiotepa as adjuvant treatment to standard chemotherapy in patients with resectable relapsed osteosarcoma

BackgroundThe role of high-dose chemotherapy in relapsing osteosarcomas has not been established. We evaluated the efficacy and tolerance of high-dose thiotepa (HDTp) after standard chemotherapy (SCT) in patients with relapsed osteosarcoma. Patients and methodsThis randomised open-label phase II study enrolled patients 1–50 years, with local or metastatic relapse of a high-grade osteosarcoma, not progressive after two cycles of SCT, for whom a complete surgery can be achievable following treatment. The trial assigned enrolled patients in a 1:1 ratio to receive two additional courses of SCT + HDTp and autologous transplantation (Arm A), or SCT alone (Arm B). Surgery for complete resection was scheduled as soon as feasible. Primary endpoint was overall survival (OS). Secondary objectives included progression-free survival (PFS) and safety. ResultsFrom September 2009 to November 2016, 44 patients were randomised (A:22; B:22). In total, 54.5% were males, and the median age was 16 years (9-32years). The two-year OS rate was 66.7% (95% CI 42.5–82.5) (SCT + HDTp, Arm A) versus 50.0% (95% CI 28.2–68.4) for SCT alone (Arm B). Median OS was 27.4 and 24.8 months, respectively (hazard ratio [HR] 0.826, 95% CI 0.393–1.734; p = 0.6123). Median PFS was 15.6 (8.9–24.9) months in Arm A versus 7.2 (4.8–33.3) months in Arm B, p = 0.3845. Among the 22 patients treated with SCT + HDTp, 16 (72.7%) experienced at least one grade ≥3 adverse events versus 18/22 (81.8%) patients treated with SCT. No toxic death occurred. ConclusionAdjuvant HDTp failed to significantly improve OS and PFS in resectable relapsed osteosarcomas. Despite a trend of prolonged survival and an acceptable toxicity, thiotepa cannot be recommended. Key messageHDTp and autologous transplantation added to SCT did not improve OS and PFS in patients with resectable relapsed osteosarcomas. Despite a trend of prolonged survival, thiotepa cannot be recommended.

Impact of FLT3-ITD Remission Depth in Acute Myeloid Leukemia Patients Prognosis Prediction before Allogeneic Hematopoietic Cell Transplantation

Introduction: Activating internal tandem duplication of FMS-like tyrosine kinase 3 (FLT3-ITD) is one of the most frequently mutations in acute myeloid leukemia (AML) patients with a frequency of 20-30%. Although AML with FLT3-ITD mutation is not recognized as a distinct entity in the World Health Organization classification system, AML patients with FLT3-ITD usually have high white blood cell count, high risk in poor prognostic outcome and are benefited from FLT3 inhibitors. However, the outcome prediction of AML with FLT3-ITD is still not very clear in patients undergoing allogeneic hematopoietic cell transplantation (alloHCT). Recent studies showed that the depth of remission, mostly accessed by flow cytometry (FCM) based measurable residual disease (MRD) and next generation sequencing based molecular MRD, was highly predictive for relapse in AML before alloHCT. The depth of remission is considered an important criterion for evaluating AML relapse before alloHCT. Hence, FLT3-ITD remission depth showed a potential application in evaluating FLT3-ITD subtype's prognosis. Therefore, in this retrospective study we tried to evaluate prognostic impact of FLT3-ITD remission depth in AML before alloHCT. Methods: A total of 117 FLT3-ITD positive patients were obtained in our study if they were 18 years or older, had a diagnosis of AML excluding acute promyelocytic leukemia, received standard induction chemotherapy comprising anthracycline and cytoarabine, at first affiliated hospital of Soochow University between September 2011 to January 2018 . All patients were examined a panel of 51 genes mutation by next generation sequencing and FLT3-ITD allelic ratio (AR) in newly diagnosed bone marrow samples (Fig1 A). 57 patients received two courses of standard chemotherapy and immediate alloHSCT in four months. The median time from first chemotherapy to alloHSCT was 99 days. FLT3-ITD was also examined direct after secondary chemotherapy with the sensitivity level of 0.005. Distribution of OS and RFS were estimated by Kaplan-Meier method. Difference of FLT3-ITD positive ratio in FLT3-ITD subtypes was analyzed by Chi-squared test. The two-sided level of significance was set at p&amp;lt;0.05. The deadline for follow-up was May 31, 2019, with a median follow-up time of 24 (5-83) months. Results: In our cohort, the median FLT3-ITD AR of 117 patients was 0.53 (range 0.02-7.72) in newly diagnosis. Interestingly, patients with DNMT3A mutation (0.615, range 0.04-7.72) had a higher FLT3-ITD AR than those of patients with CEBPA double mutation (0.19, range 0.02-0.74), with statistical difference (p=0.007). Patients with DNMT3A mutation also had lower complete remission rate than those of patients with NPM1 mutation and DNMT3A wildtype after first chemotherapy (x2=5.987, P=0.018). In 57 patients undergoing alloHSCT, we found there were no differences in OS and RFS among patients classified by FLT3-ITD AR or concomitant NPM1 mutation. However, patients with FLT3-ITD positive had a poorer OS (p&amp;lt;0.001) and RFS (p&amp;lt;0.001) than those of patients with FLT3-ITD negative accoding to the FLT3-ITD states after secondary chemotherapy. In addition, patients with FLT3-ITD AR&amp;gt;0.01 had a poorer OS and EFS than those of patients with FLT3-ITD AR&amp;lt;0.01, indicating FLT3-ITD remission depth is helpful in prognosis prediction for patients undergoing alloHCT (Fig1 B,C). Moreover, we found patients with DNMT3A mutation had a higher FLT3-ITD positive ratio than those of patients with NPM1 mutation after secondary chemotherapy. This result was also found in patients with normal chromosome karyotype (NK). There was no FLT3-ITD positive in patients with CEBPA double mutation or t(8;21) after secondary chemotherapy in our cohort, while 4 of 8 patients with chromosome karyotype abnormalities (no favorable) had FLT3-ITD positive after secondary chemotherapy. From these results above, we finally found patients with DNMT3A mutation had a poorer OS and EFS in NK patients undergoing alloHCT(Fig1 D,E). In conclusion, our results suggested FLT3-ITD remission depth is useful in prognosis prediction for AML patients with FLT3-ITD before alloHCT. Figure Disclosures No relevant conflicts of interest to declare.

Pediatric Bone Sarcomas: Outcome of Multimodality Treatment in a Single Institution in South India over a Decade

Abstract Context: Pediatric bone sarcoma is a rare entity with low incidence of around 2.5–6 per million population in India. Management of this condition is well standardized, and global survival data are available; however, there is a paucity of data in the Indian perspective. Aim of the Study: The aim of this study is to analyze various prognostic factors and survival outcome. The purpose of this study is to assess the role of surgery, multiagent chemotherapy, and radiation in the management of these tumors. Patients and Methods: Retrospective analysis of patients aged 18 and less, diagnosed as bone sarcomas and treated in our tertiary cancer center. All the patients received at least one form of therapy depending on stage and site of the primary lesion. Results: Twenty-one patients of Ewing sarcoma and 20 patients of osteosarcomas were eligible and were included in the study. In Ewing sarcoma, completing the full course of standard chemotherapy and radiotherapy to the local site was associated with improved survival. In osteosarcoma, limb salvage surgery (LSS) had a significant difference in overall survival compared to amputation. Induction chemotherapy was associated with better percentage of necrosis and showed improved survival. The percentage of necrosis correlated positively with survival which was statistically significant (P = 0.015). Conclusion: The median survival in both these bone sarcomas is inferior to global trends. Probable reasons for such discrepancy are lack of compliance to treatment protocols due to age factors and late presentation. Completion of multiagent chemotherapy in both the tumors add to better survival. Radiotherapy in Ewing sarcoma improves survival. In osteosarcoma, LSS is an oncologically safe alternative to amputation. The percentage of necrosis following chemotherapy in osteosarcoma is a reliable predictor of prognosis.

PF299 EARLY RESPONSE OBSERVATION OF PEDIATRIC PATIENTS WITH BURKITT'S LYMPHOMA TREATED WITH CHIMERIC ANTIGEN RECEPTOR (CAR) T‐CELLS

Background:Pediatric patients with relapsed or refractory Burkitt's lymphoma (BL) present as a major challenge due to their poor outcomes despite use of high‐intensity chemotherapy and rituximab. CAR‐T has shown efficacy in treating refractory or relapsed leukemia and non‐Hodgkin lymphoma (NHL) in adult patients.Aims:To assess the safety and efficacy of CAR‐T in the treatment of refractory or relapsed BL in pediatric patients.Methods:Our trial (ChiCTR18000144) enrolled and treated 5 patients with BL. The inclusion criteria includes: 1) The patient who didn’t get complete remission(CR)after at least 5 courses of standard chemotherapy plus CD20 mAb; and 2) The patient who didn’t get partial remission (PR) or showing progression after 2 courses of second‐line chemotherapy; and 3) High expression of at least one B cells markers (CD19/CD20/CD22) examined by immunohistochemistry. The highest expressed marker was chosen as first round CAR‐T target. The therapeutic doses of CAR‐T range from1∗10^6 to 3∗10^6 per kilogram of body weight each course. The effects and adverse events of CART cells after infusion were observed. The change of CAR‐T cells and cytokines were measured weekly. Tumor response was evaluated at day 30 and day 60 post infusion and every two months afterwards.Results:Five patients aged 6 to 10 years with a median age of 8 years, were enrolled, including 4 male (80%) and 1 female (20%). St Jude staging at the time of diagnosis: 3 cases (60%) in stage III, 2 cases (40%) in stage IV, 1 case of CNS invasion (20%), 1 case of bone marrow invasion (20%) and none in stage I or stage II.Five patients were treated with 1 to 3 rounds of CAR‐T. The overall response rate (OR) was 100%. Three cases (60%) achieved CR by one round of CD19 CAR‐T cell therapy, while two cases (40%) achieved PR with CD19 CAR‐T treatment and achieved CR after subsequent treatment with CD22 or CD22 and CD20 CAR‐T.During the treatment, fever, gastro‐intestine discomfort, rash, capillary leak syndrome, Immunopneumonia, tremor, hypotension, Immunocytopenia abnormal coagulation, liver dysfunction, and other toxic effects occurred. One patient (20%) was diagnosed of cytokine‐release syndrome(CRS) grading I and the other four grading III. All cases recoverd fully after active symptomatic and supportive treatment (including application of glucocorticoids in CRS grading III). There were no death events.The last follow‐up was January 30, 2019. The longest follow‐up duration was 382 days, the shortest 62 days, and the median was 249 days. Currently, all patients were in event‐free survival.Summary/Conclusion:CD19/CD20/CD22‐CAR‐T therapy shows robust efficacy in pediatric patients with refractory and relapsed BL and the toxic and adverse effects are moderate and can be well controlled.

Granulocyte colony stimulating factor priming chemotherapy is more effective than standard chemotherapy as salvage therapy in relapsed acute myeloid leukemia

Introduction and objectiveTo improve the complete remission (CR) rate of newly diagnosed acute myeloid leukemia (AML) patients and alleviate the severe side effects of double induction chemotherapy, we combined a standard regimen with granulocyte colony-stimulating factor (G-CSF) priming chemotherapy to compose a new double induction regimen for AML patients who failed to achieve CR after the first course. Patients and methodsNinety-seven patients with AML who did not achieve CR after the first course of standard chemotherapy were enrolled. Among them, 45 patients received G-CSF priming combined with low-dose chemotherapy during days 20–22 of the first course of chemotherapy, serving as priming group, 52 patients were administered standard chemotherapy again, serving as control group. ResultsBetween the two groups there were no differences in the French–American–British (FAB) classification, risk status, the first course of chemotherapy, blood cell count or blasts percentage of bone marrow before the second course. But the CR rate was significantly higher and the adverse effect was much lower in the priming group than the control group. Cox multivariate regression analysis showed that WBC level before the second course and the selection of the second chemotherapy regimen were two independent factors for long survival of patients. DiscussionThese results elucidate that standard chemotherapy followed by G-CSF priming new double induction chemotherapy is an effective method for AML patients to improve CR rate and reduce adverse effects.

Granulocyte colony stimulating factor priming chemotherapy is more effective than standard chemotherapy as salvage therapy in relapsed acute myeloid leukemia

Introduction and objectiveTo improve the complete remission (CR) rate of newly diagnosed acute myeloid leukemia (AML) patients and alleviate the severe side effects of double induction chemotherapy, we combined a standard regimen with granulocyte colony-stimulating factor (G-CSF) priming chemotherapy to compose a new double induction regimen for AML patients who failed to achieve CR after the first course. Patients and methodsNinety-seven patients with AML who did not achieve CR after the first course of standard chemotherapy were enrolled. Among them, 45 patients received G-CSF priming combined with low-dose chemotherapy during days 20–22 of the first course of chemotherapy, serving as priming group, 52 patients were administered standard chemotherapy again, serving as control group. ResultsBetween the two groups there were no differences in the French–American–British (FAB) classification, risk status, the first course of chemotherapy, blood cell count or blasts percentage of bone marrow before the second course. But the CR rate was significantly higher and the adverse effect was much lower in the priming group than the control group. Cox multivariate regression analysis showed that WBC level before the second course and the selection of the second chemotherapy regimen were two independent factors for long survival of patients. DiscussionThese results elucidate that standard chemotherapy followed by G-CSF priming new double induction chemotherapy is an effective method for AML patients to improve CR rate and reduce adverse effects.

Prognostic value of PD-1 and TIM-3 on CD3+ T cells from diffuse large B-cell lymphoma.

To investigate the expression of PD-1 and TIM-3 in CD3+ T cells in patients with diffuse large B-cell lymphoma (DLBCL). A retrospective analysis was conducted on data from 46 patients with newly diagnosed DLBCL and 30 healthy people. Flow cytometry was used to detect the expression of PD-1 and TIM-3 before and after chemotherapy. Compared to healthy control, the expression of PD-1 and TIM-3 in patients with DLBCL was increased in CD3+ T cells. There is no significant change of PD-1 and TIM-3 in patients with stage I/II DLBCL, however, they were markedly increased in patients with stage III/IV DLBCL. The expression of PD-1 and TIM-3 elevated in DLBCL patients with B symptoms, IPI score >2 points and high level of LDH and Ki-67. After four courses of standard chemotherapy, PD-1 and TIM-3 expression level decreased. The treatment efficiency is higher in patients with low expression of PD-1 and TIM-3 than in patients with high PD-1 and TIM-3 expression. DLBCL patients have high expression level of PD-1 and TIM-3, which are related to DLBCL staging. PD-1 and TIM-3 expression levels are also related to the efficiency of chemotherapy. PD-1 and TIM-3 expression levels may be used as an indicator of chemotherapeutic efficacy in patients with DLBCL.

Maintenance treatment of advanced non-small cell lung cancer

Currently platinum-based double chemotherapy is the standard first-line treatment for advanced non-small cell lung cancer (NSCLC).When the disease is under control,the next step after a standard course of chemotherapy is controversial,and maintenance treatment is used in the treatment of advanced NSCLC increasingly.Maintenance treatment of advanced NSCLC includes continue maintenance treatment and medication changed maintenance therapy.currently used for maintenance therapy with pemetrexed and erlotinib are shown to improve overall survival,which are usually used for maintenance treatment. Key words: Carcinoma, non-small-cell lung; Maintenance treatment; Targeted therapy

Chemotherapy-related toxicity in patients with non-metastatic Ewing sarcoma: influence of sex and age

Influence of age and sex on chemotherapy-related toxicity was evaluated in children (3–9 years), adolescents (10–17 years), and adults (up to 40 years) with localized Ewing sarcoma (ES) enrolled in the ISG/SSG III protocol. Treatment was based on vincristine, doxorubicin, cyclophosphamide, ifosfamide, dactinomycin, and etoposide. High-dose chemotherapy with busulfan and melphalan was given in poor responder patients. The analysis was based on 2191 courses of standard chemotherapy and 230 patients. A lower risk of G4 leukopenia and thrombocytopenia, hospitalization, febrile neutropenia, and red blood cell (RBC) transfusions was observed in males. Use of granulocyte colony-stimulating factor (G-CSF) was more frequent in adults, while children more often received RBC transfusions. A significant correlation between sex and chemotherapy-related toxicity was observed in the study, whereas no significant differences in terms of bone marrow toxicity can be expected according to patient age. Further studies should analyse the role of pharmacokinetics, pharmacogenomics, and clinical characteristics.

Cognitive function in breast cancer and lymphoma patients receiving chemotherapy: An ongoing nationwide University of Rochester Cancer Center (URCC) Community Clinical Oncology Program (CCOP) observational study with 1,200 patients and controls.

TPS9647 Background: Chemotherapy-related cognitive impairment (CRCI) is a major concern for up to 75% of cancer patients that can negatively affect quality of life. Studies which have objectively assessed cognitive function (CF) in patients suggest that chemotherapy is associated with declines in multiple domains. A large, prospective longitudinal study with age- and gender- paired healthy controls is needed to confirm and expand these findings, to identify etiological mechanisms of CRCI, and to identify the best assessment methods for detecting CRCI. Methods: We are conducting a nationwide prospective observational study (N=1,200), conducted through the URCC CCOP Research Base and 23 CCOPs. The primary aim is to test the hypothesis that breast cancer and lymphoma patients receiving chemotherapy will have greater impairments in CRCI over time than a control comparison group. Breast cancer (stage I-IIIc) and lymphoma patients (intermediate/high grade disease) meet the following eligibility: 1) chemotherapy naïve, 2) ≥21 years of age, 3) no CNS disease, 4) scheduled to receive a standard course of chemotherapy, and 5) no concurrent radiation. Healthy control participants meet eligibility criteria 1-3 and are the same gender and age as paired patients. CF is assessed at pre-chemotherapy (Assess. 1), post-chemotherapy (Assess. 2), and 6 months post-chemotherapy in patients; their paired controls are assessed at the same time intervals. CF is measured via: 1) Computer-based CANTAB neuropsychological (NP) battery (assessing memory (primary aim), verbal memory, sustained attention, processing speed, and executive function (secondary aims)), 2) paper-based objective NP assessment (secondary aims), 3) phone-based objective NP assessment (tertiary aims), and 4) Single item, patient-reported CF (tertiary aims). Blood is collected at Assess. 1 and 2 to explore inflammatory and genetic mechanisms. 807 participants have been enrolled in 21 months. Funding: U10CA037420-26 Supp. MCJ; U10CA037420, GRM; &amp; URCC/RPCI Grant, MCJ &amp; CBA. Clinical trial information: NCT01382082.

Testicular tumors

Germ cell tumors of the testes represent a unique paradigm of diseases which can be cured even in extremely advanced phase. Unfortunately, this makes them unique among adult solid tumors. Seminoma and non seminoma are relatively rare with approximatively 25,000 patients in Europe per year, but numbers are increasing world wide. Different strategies are needed depending on stage and prognostic scores. Seminoma is extremely sensitive to radiation therapy and chemotherapy, while all germ cell tumors show a very good response to chemotherapy. Clinical stage I seminoma is currently treated with radiation, single course carboplatin or surveillance policy. Clinical stage I non seminoma can also be approached with different strategies such as retroperitoneal lymph node dissection, observation or one-two courses of standard chemotherapy. Stage II seminoma may be treated with either radiation or chemotherapy, while for all advanced stages chemotherapy is mandatory. Since the mid-eighties PEB (Cisplatin, Etoposide and Bleomycin) is the regimen of choice and no other schedule has proved superior in terms of efficacy. Surgery on the residual disease is crucial to the whole strategy and should be performed or attempted in all cases. Consequently, the correct treatment strategy for these tumors does not depend only on the ability of a single physician, but on a skilled team specialized in this particular tumor. Second line therapies (VeIP, PEI, TIP) can cure 25%–40% of patients, but improved strategies for resistant tumors are desperately needed. High-dose chemotherapy has shown very good results in some studies while being less impressive in others. In any case, it should remain an option for relapsing patients and could be used in some cases of upfront chemotherapy in patients with slow marker decline, but this should only be considered in referring centers.

Évaluation de la réponse au traitement du lymphome avec la TEP 18F-FDG : existe-t-il un consensus dans l’évaluation de la réponse ?

The concept of risk-adapted therapy in lymphoma is increasingly accepted as a way to achieve higher cure rates with a lower or equal risk of treatment-related morbidity and mortality. Tailoring and individualizing therapy according to the need of the patient is a therapeutic option which could maybe soon become the standard of care. However, it is still not proven that modifying therapy based on interim-PET can improve patient outcomes. Therefore, this issue must be analyzed in appropriately designed clinical trials. 18F-FDG PET enables evaluation of the early metabolic changes rather than the morphologic changes which occur later during therapy. In lymphoma these early metabolic changes are highly predictive of the final treatment response. PET performed after a few courses of standard chemotherapy is a reliable prognostic tool to identify poor responders to therapy. Interim-PET is a powerful prognostic tool when compared to other well-established clinical parameters in lymphoma. However, the major drawback in the literature appeared to be related to the lack of uniform and reliable criteria for interim-PET scan interpretation. Therefore, in April 2009 an international meeting took place in Deauville (France), where uniform criteria were established for interim-PET scan interpretation. On the other hand, when PET is used to assess treatment response after completion of therapy, the criteria established in the International Harmonization Project in 2007 must be applied. These recommendations were designed to standardize the interpretation of interim PET and PET at the conclusion of therapy of patients with lymphoma both in clinical practice and clinical trials.