Complete Remission Rate In Patients Research Articles

Assessment of Complete Remission Rate in Patients with Acute Myeloid Leukemia Undergoing 7+3 Induction Chemotherapy

Acute leukemia is a fast-growing, overpopulated clone of immature proliferating cells that largely predominate in the bone marrow and have the capacity to prolong life indefinitely. Upon inspection and cytologic assessment of bone marrow or peripheral blood, the cells demonstrate quantified uncertainties. Objective: To determine the frequency of complete remission after induction 7+3 chemotherapy in patients with acute myeloid leukemia. Methods: The nature of this study was cross sectional study at Department of Oncology, Pakistan Institute of Medical Sciences, and Islamabad from 26 November, 2022 to 26 May, 2023. The hospital’s laboratory fulfilled the complete blood count and provided the confirmed baseline bone marrow biopsy reports. All patients who were admitted received treatment with a 7+3 regime, a standard treatment protocol for all the adolescents and adults admitted. Every patient was prescribed for 7+3 induction therapy regimen which consists of 200 mg/m2 cytarabine for seven days and idarubicin for three days, 12 mg/m2 on the 1st, 3rd and 5th day. Results: The complete remission estimated turns out to be 61.1% and rest need further treatment. The average age of the patients was 48.56 ± 6.91 years. The mean BMI stood at 24.46 ± 1.49 kg/m2. gender wise, 74 were male and 21 were female. Our mean CR was 61.1% that is 58 participants all the complete demographic is available. Conclusions: This study revealed a Complete Remission (CR) rate of 61.1% in patients with AML undergoing 7+3 induction chemotherapy. However, our findings suggest that older age is associated with lower CR rates, highlighting the need for tailored treatment strategies that balance efficacy with the potential risks of intensive therapies in this population.

Assessment of Complete Remission Rate in Patients with Acute Myeloid Leukemia Undergoing 7+3 Induction Chemotherapy

Acute leukemia is a fast-growing, overpopulated clone of immature proliferating cells that largely predominate in the bone marrow and have the capacity to prolong life indefinitely. Upon inspection and cytologic assessment of bone marrow or peripheral blood, the cells demonstrate quantified uncertainties. Objective: To determine the frequency of complete remission after induction 7+3 chemotherapy in patients with acute myeloid leukemia. Methods: The nature of this study was cross sectional study at Department of Oncology, Pakistan Institute of Medical Sciences, and Islamabad from 26 November, 2022 to 26 May, 2023. The hospital’s laboratory fulfilled the complete blood count and provided the confirmed baseline bone marrow biopsy reports. All patients who were admitted received treatment with a 7+3 regime, a standard treatment protocol for all the adolescents and adults admitted. Every patient was prescribed for 7+3 induction therapy regimen which consists of 200 mg/m2 cytarabine for seven days and idarubicin for three days, 12 mg/m2 on the 1st, 3rd and 5th day. Results: The complete remission estimated turns out to be 61.1% and rest need further treatment. The average age of the patients was 48.56 ± 6.91 years. The mean BMI stood at 24.46 ± 1.49 kg/m2. gender wise, 74 were male and 21 were female. Our mean CR was 61.1% that is 58 participants all the complete demographic is available. Conclusions: This study revealed a Complete Remission (CR) rate of 61.1% in patients with AML undergoing 7+3 induction chemotherapy. However, our findings suggest that older age is associated with lower CR rates, highlighting the need for tailored treatment strategies that balance efficacy with the potential risks of intensive therapies in this population.

Prognosis and complete remission rate of diffuse large B-cell lymphoma patients in standard R-CHOP with reduction of vincristine: A retrospective study.

The effect of stopping or reducing the dose of vincristine in diffuse large B-cell lymphoma (DLBCL) on the outcome and prognosis of the disease is still in doubt. The present study aimed to investigate and compare the prognosis and complete remission of two R-CHOP treatment regimens with and without vincristine reduction in DLBCL patients. This retrospective study was conducted on newly diagnosed DLBCL patients during 2018-2021. The patients were over 18 years of age, had been histologically confirmed by a pathologist, and were under treatment with R-CHOP regimen. The clinical information of the subjects as well as the number of treatment courses were extracted from their medical records and then compared. Overall, 269 patients with DLBCL were included in this study, 15.99% of whom (n = 43) had vincristine reduction. There was no significant difference between the studied factors regarding the reduction of vincristine and the complete R-CHOP regimen (p > 0.05). Besides, no difference was observed in the 1-year overall survival (OS) and progression-free survival (PFS) of the patients in the two groups treated with R-CHOP regimen with and without vincristine reduction (p > 0.05). The complete remission rates of the patients treated with R-CHOP regimen with and without vincristine (p > 0.05) were not different either. The results of the Cox multivariate regression showed that reducing the dose of vincristine from the R-CHOP treatment regimen had no relationship with the 1-year OS and PFS of the DLBCL patients (hazard ratio [HR]OS = 1.59, 95% confidence interval [CI]: 3.67-0.690, HRPFS = 1.67, 95% CI: 0.798-3.82). The results of this study showed that the reduction of vincristine from the R-CHOP regimen in the DLBCL patients was not likely to make a difference in the 1-year OS and PFS of the patients. However, further studies are needed on the issue.

Early T-Cell Precursor Leukemia: A High-Risk Subtype of Acute Lymphoblastic Leukemia, Single Center Experience in Jordan

Background and ObjectivesEarly T-cell precursor (ETP) acute lymphoblastic leukemia/lymphoma (ALL/LBL) is a newly recognized entity of T-lymphoblastic leukemia/lymphoma. The optimal therapeutic approaches to adult patients are poorly studied. Patients and MethodsWe compared the outcomes of adult's patents with ETP-ALL/LBL who received frontline chemotherapy regimens with other T-ALL/LBL immunophenotypic subtypes. Patients with ETP-ALL/LBL were identified based on CD1a (-), CD8 (-), CD5 (-) (dim), and positivity for 1 or more stem cell or myeloid antigens. ResultsSixty-nine patients were included between the years 2010 and 2021 (19 ETP-T-ALL/LBL; 50 non ETP- T-cell ALL/LBL). The median age was 26 year (IQR: 21, 33). Fifty-six patients presented as ALL, while 16 with lymphoblastic lymphoma. Forty-seven patients achieved complete remission, and 43 were alive at last encounter. The complete remission rate in patients with ETP-ALL/LBL was lower than that of non-ETP-ALL/LBL patients (32% vs. 68%; P = .2), and the MRD at end of induction was significantly higher (26% vs. 6.2%, P < .001), and more likely to receive allo-SCT consolidation in CR1 (95% vs. 40%, P < .001). After a median follow-up of survivors of 48 months (range: 32-74 months), the median overall survival for patients with ETP-ALL/LBL was not reached versus 11.5 months for the non-ETP-ALL/LBL patients (P = .014)). Twenty-six patients receive allo-SCT in CR1. There was no significant difference in overall survival (79% vs. 70%; P = .49) between both transplant-cohorts in both groups. ConclusionETP-ALL/LBL represents a high-risk disease subtype of adult ALL. Novel treatment strategies are needed to improve treatment outcomes in this patient's population

Genome Editing for Engineering the Next Generation of Advanced Immune Cell Therapies.

Our current genetic engineering capacity through synthetic biology and genome editing is the foundation of a revolution in biomedical science: the use of genetically programmed cells as therapeutics. The prime example of this paradigm is the adoptive transfer of genetically engineered T cells to express tumor-specific receptors, such as chimeric antigen receptors (CARs) or engineered T-cell receptors (TCR). This approach has led to unprecedented complete remission rates in patients with otherwise incurable hematological malignancies. However, this approach is still largely ineffective against solid tumors, which comprise the vast majority of neoplasms. Also, limitations associated with the autologous nature of this therapy and shared markers between cancer cells and T cells further restrict the access to these therapies. Here, we described how cutting-edge genome editing approaches have been applied to unlock the full potential of these revolutionary therapies, thereby increasing therapeutic efficacy and patient accessibility.

TRICIN: A Phase II Trial on the Efficacy of Topical TRIchloroacetic Acid in Patients with Cervical Intraepithelial Neoplasia

Data on non-surgical treatment approaching persistent cervical intraepithelial neoplasia (CIN) are scarce. Retrospective analysis suggest high efficacy of topical treatment with trichloroacetic acid (TCA). This prospective phase II study set out to investigate the efficacy of a single application of 85% TCA in the treatment of CIN I/II. Patients with CIN I/II were treated a single time with 85% TCA. After three and six months colposcopic, histologic, and HPV evaluation was performed. The primary endpoint was treatment efficacy defined as complete histologic remission six months after treatment. The secondary endpoint was HPV clearance six months after treatment. A total of 102 patients with CIN I/II were included into this trial. Complete histologic remission rates were 75.5% and 78.4% three and six months after TCA treatment, respectively. Clearance rates of HPV 16, 18 and other high risk types were 76.5%, 91.7%, 68.7% after six months, respectively. Side effects of TCA were mild and lasted usually less than 30 min. This is the first prospective trial reporting high histologic complete remission rates in patients with CIN I/II after a single 85% TCA treatment. In the future, TCA may represent an effective and feasible non-surgical treatment approach for CIN.

Expression of TCF3 in Burkitt's Lymphoma and Its Proliferative Effect and Prognostic Significance

To observe the mutation and expression of TCF3 gene in Burkitt's lymphoma (BL), and explore its effect on the proliferation of BL cells and clinical efficacy and prognosis. The mutation and expression of TCF3 in tumor tissues from BL patients were observed by the second-generation sequencing and real-time quantitative PCR. The proliferation and apoptosis of lymphoma cells after TCF3 knocked down were observed by siRNA interference technique and CCK-8 method. Survival analysis was used to observe the relationship between TCF3 mutation and the treatment efficacy and prognosis of BL patients. There were high frequency mutation rate (mutation rate was 23.7%) and high expression of TCF3 in BL patients. After TCF3 knocked down, cell proliferation was inhibited and apoptosis was promoted. In TCF3-siRNA group and control group, the cell proliferation rate at 48 h was (50.2±5.9)% and (96.6±11.4)%, and apoptosis rate was 30.1% and 1.5%, respectively, which showed significantly different between the two groups (P<0.001, P=0.005). The complete remission rate of patients with TCF3 mutation was low. The complete remission rate of mutant group and wild-type group was 44.4% and 82.8%, respectively (P=0.023). The 2-year progression-free survival rate and overall survival rate of the patients with TCF3 mutation was 55.6% and 61.0%, respectively, which was lower than 83.2% and 85.2% of the patients without mutation, but the differences were not statistically significant. There are mutation and abnormal expression of TCF3 in patients with BL. Patients with TCF3 mutations have low remission rate and poor prognosis.

AML-302 Impact of Body Mass Index on Complete Remission Rates in Patients With Acute Myeloid Leukemia

The impact of body mass index (BMI) on the outcomes of patients with acute myeloid leukemia (AML) has been assessed in different studies. However, the results remain controversial. The aim of our study was to assess the impact of BMI on the response to induction chemotherapy in adult patients with newly diagnosed AML. Our study enrolled 140 patients with AML. The data were collected from electronic medical records at the Oncology Center of Mansoura University. The patients were further classified according to BMI into those with normal BMI (40 patients), overweight (42 patients), and obese patients (58 patients). All patients received induction chemotherapy with 3+7 protocol (3 days of anthracycline and 7 days of cytarabine). Among the 40 patients with normal BMI, 25 patients (62.5%) achieved complete remission (CR), 7 patients (17.5%) died, and 8 patients (20%) were refractory to induction chemotherapy. Among those 8 patients, 7 received salvage chemotherapy with 4 patients achieving CR and 3 deaths. Regarding the 42 overweight patients, 14 patients (33.3%) attained CR, 22 patients (52.4%) died, and 6 patients (14.3%) remained refractory. After salvage chemotherapy, 3 patients achieved CR and 3 patients died. When it comes to the 58 obese patients, 27 patients (46.6%) achieved CR, 26 patients (44.8%) died, and 5 patients were refractory. Four of those refractory patients received salvage chemotherapy, and all died. Regarding CR rates after induction chemotherapy, our study concluded that CR rates are higher in patients with normal BMI compared to overweight and obese patients (95% CI, P=0.004). A larger, prospective randomized trial would be required to confirm these results.

Bone-Related Extramedullary Disease in Newly Diagnosed Myeloma Patients is an Independent Poor Prognostic Predictor

Background:Bone-related extramedullary disease (EMD-B) is mass of clonal plasma cells derived from adjacent bone lesions and has obvious heterogeneities in clinical outcomes. This retrospective study aims to evaluate the treatment outcomes and long-term prognosis of newly diagnosed myeloma patients with EMD-B.Methods:This was a retrospective study conducted in Beijing Chaoyang Hospital from January 1, 2010 to December 31, 2019. Seventy-seven newly diagnosed multiple myeloma patients with EMD-B were selected. Propensity score matching (1:2) was used to match patients with and without EMD-B. After matching, 132 patients without extramedullary disease (non-EMD) were included in the study. All patients received bortezomib-based regimens as induction therapy.Results:After matching, baseline data of the 2 groups were comparable. The Cox regression analysis of patients with EMD-B showed that age, paravertebral lesions, and immunoglobulin D (IgD) type may have adverse effects on survival. Bone-related extramedullary disease at new diagnosis was a risk predictor of survival (hazard ration [HR] = 1.80, 95% confidence interval [CI]: 1.09-2.98, P = .022). The median survival time of the EMD-B group was significantly shorter than that of the non-EMD group (52 months vs 96 months, P = .043). Induction therapy did not show any significant differences in effectiveness between the 2 groups. Autologous stem cell transplantation (ASCT) significantly increased complete remission rate of patients with EMD-B (EMD-B vs non-EMD: no ASCT 15.7% vs 31.9%, P = .035; ASCT 42.3% vs 48.8%, P = .626) and improved their median overall survival rate (EMD-B vs non-EMD: no ASCT 49 months vs 75 months, P = .003; ASCT not reached vs 96 months, P = .505).Conclusions:This study demonstrated that newly diagnosed myeloma patients with EMD-B had poor outcomes, which could be improved by ASCT.

The effect of laparoscopic sleeve gastrectomy on type 2 diabetes remission outcomes in patients with body mass index between 25 kg/m 2 and 32.5 kg/m 2

BackgroundThe effect of laparoscopic sleeve gastrectomy (LSG) in the treatment of type 2 diabetes (T2D) patients with body mass index (BMI is calculated by dividing weight in kilograms by height in meters squared) higher than 25 kg/m2 but lower than 32.5 kg/m2, especially in East Asian population characterized by abdominal obesity, are still unclear. This study aims to explore the effect of LSG in T2D patients with BMI higher than 25 kg/m2 but lower than 32.5 kg/m2. MethodsA total of 49 T2D patients with BMI(25–32.5 kg/m2) treated successfully with LSG were included in our study. The effect of LSG on T2D remission outcomes at 12 and 24 months after operation was analyzed. ResultsAll patients were treated successfully with LSG without conversion. The mean preoperative body weight,BMI, fasting plasma glucose, glycosylated hemoglobin (A1c) and fasting C-peptide were 81.7 ± 10.0 kg, 29.1 ± 2.4 kg/m2, 10.4 ± 3.9 mmol/L,8.2 ± 1.5%, and 2.3 ± 1.1 nmol/L,respectively.The age, duration of diabetes and ABCD score were 48.6 ± 9.6 years,6.6 ± 5.1 years, and 2.9 ± 1.5. The mean fasting plasma glucose,A1c, and C-peptide levels were significantly decreased at 12 and 24 months after operation. At postoperative 24 months, 18 out of 49 patients (36.7%) reached diabetes complete remission (A1c levels≤6.0%).14 out of 49 patients (28.6%) reached partial remission (6.0% < A1c levels<6.5%). 8 out of 49 patients (16.3%) reached notable improvement (6.5% < A1c levels<7%). At 24 months after LSG, the complete remission rate of T2D patients with a BMI of 25–27.5 kg/m2 was 35.3%, the complete remission rate of patients with a BMI of 27.5–30 kg/m2 was 11.1%, and the complete remission rate of patients with a BMI of 30–32.5 kg/m2 was 47.8%.At postoperative 24 months, the complete remission rate of T2D patients with ABCD score≤2 was 5.0%, the complete remission rate of patients with ABCD score 3 to 4 was 52.4%, and the complete remission rate of patients with ABCD score≥5 was 75.0%. ConclusionOur study demonstrates that LSG could result in a significant effect on T2D in patients with BMI 30–32.5 kg/m2. In addition, our study indicates that higher ABCD score can predict a better diabetes remission outcome in diabetes patients with BMI ≤32.5 kg/m2.

Newer biological agents: CAR T cells, PARP inhibitors, and ALK inhibitors

The oncology world is awash with a steady flow of new and exciting biologic agents and targeted immune therapies. Chimeric antigen receptor T cells are a new class of “living drugs” that are designed to reprogram T cells to target and kill tumor cells upon contact. Chimeric antigen receptor T cell treatment has yielded impressive results with respect to overall response rates and complete remission rates in patients with multiply relapsed and resistant leukemia and lymphoma. Drugs that target and inhibit the anaplastic lymphoma kinase inhibitor and poly-ADP ribose polymerase inhibitor pathways are extending progression-free survival in subsets of patients with non-small cell lung cancer and ovarian tumors who harbor these mutations, respectively.

Outcome of Primary Central Nervous System Lymphoma Treated with Combined Surgical Resection and High- Dose Methotrexate Chemotherapy: A Single-Institution Retrospective Study.

To evaluate the feasibility and long-term clinical results of combined surgical resection and high-dose methotrexate (HD-MTX) chemotherapy for primary central nervous system lymphoma (PCNSL) of the brain. Fifty-eight patients were diagnosed with PCNSL by histopathological examination of brain biopsy specimens at the Second Affiliated Hospital of Bengbu Medical College from March 2013 to December 2017. All patients received MTX at adose of 3.5 g/m2 every 2 weeks for 6 cycles. Clinical information, including ages, number of lesions, and tumor locations, were retrospectively collected from the medical records. The complete remission rates in patients treated with MTX plus craniotomy for surgical resection and those treated with MTX alone were 70.0% and 32.1%, respectively (p=0.021). Adding craniotomy to MTX chemotherapy did not increase the complication rate. The most common adverse events were hematological toxicity, liver toxicity, and gastrointestinal reaction were similar between groups. Multivariate analysis showed that surgical resection was associated with longer progression-free survival (PFS) (OR: p=0.002). Combining craniotomy for surgical resection and MTX-based chemotherapy may be safe and effective for treating PCNSL.

Critical Considerations in Anticancer Drug Development and Dosing Strategies: The Past, Present, and Future.

Critical Considerations in Anticancer Drug Development and Dosing Strategies: The Past, Present, and Future.

Lenalidomide combined with intensive chemotherapy in acute myeloid leukemia and higher-risk myelodysplastic syndrome with 5q deletion. Results of a phase II study by the Groupe Francophone Des Myélodysplasies.

Patients with acute myeloblastic leukemia or higher risk myelodysplastic syndromes with 5q deletion (generally within a complex karyotype) respond poorly to intensive chemotherapy and have very poor survival. In this population, we evaluated escalating doses of lenalidomide combined with intensive chemotherapy in a phase II study. Treatment consisted of daunorubicin (45 mg/m2/day, days 1–3 in cohort 1, escalated to 60 mg/m2/day, days 1–3 in cohorts 2 and 3) combined with cytosine arabinoside (200 mg/m2/day, days 1–7) and lenalidomide (10 mg/day, days 1–21 in cohorts 1 and 2, escalated to 25 mg/day, days 1–21 in cohort 3). Eighty-two patients with 5q deletion were enrolled, including 62 with acute myeloblastic leukemia, 62/79 (78%) of whom had a complex karyotype (median 7 cytogenetic abnormalities, all but 2 of them monosomal) and three had unknown karyotypes. Thirty-eight patients (46%) achieved complete remission and the overall response rate was 58.5%. Among the 62 patients with a complex karyotype, 27 achieved complete remission (44%) and 21 had cytogenetic responses. A lower response rate was observed in patients with acute myeloblastic leukemia but other pretreatment factors, including cytogenetic complexity and treatment cohort, did not significantly influence response. Fifteen patients underwent allogeneic stem cell transplantation, including 11 patients in first remission. The 1-year cumulative incidence of relapse was 64.6% and the median overall survival was 8.2 months. By comparison with conventional intensive chemotherapy, the treatment protocol we used appeared to produce higher hematologic and cytogenetic complete remission rates in patients with very poor cytogenetics, but response duration was short in this very poor risk population, highlighting the need for better post-induction strategies. Clinical trial registry number: NCT00885508

Serum concentrations of l-kynurenine predict clinical outcomes of patients with peripheral T-cell lymphoma, not otherwise specified.

Indoleamine 2,3-dioxygenase exerts intense immunomodulatory effects due to enzymatic activities that catalyze the breakdown of the essential amino acid l-tryptophan. The activity of indoleamine 2,3-dioxygenase can be estimated by measuring serum l-kynurenine concentrations. Here, we aimed to determine the role of l-kynurenine as a prognostic factor for peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) in a retrospective analysis of data derived from 31 consecutive patients between June 2000 and March 2013 who were histologically diagnosed with PTCL-NOS according to the World Health Organization classification and treated with 6-8 cycles of cyclophosphamide, doxorubicin or pirarubicin, vincristine, and prednisolone. l-kynurenine concentrations in serum samples collected at admission were measured using high-performance liquid chromatography. The median serum concentration of l-kynurenine was 3.28 (range 0.92-8.16) μM. The l-kynurenine cutoff was set at 3.07 μM using receiver operating characteristics curves. The complete remission rates of patients with l-kynurenine <3.07 and ≥3.07 μM were 69% and 51%, respectively. The 5-year overall survival (OS) rates for patients with l-kynurenine <3.07 and ≥3.07 μM were 80.2% and 23.4%, respectively (p < 0.001). More advanced age, poor performance status, elevated lactate dehydrogenase, an unfavorable International Prognostic Index, and a poor prognostic index for T-cell lymphoma were significantly worse factors for OS. Multivariate analyses revealed only l-kynurenine as an independent prognostic factor for OS. In conclusion, serum concentrations of l-kynurenine might comprise a novel prognostic factor with which to determine the outcomes of treatment for PTCL-NOS. Copyright © 2016 John Wiley & Sons, Ltd.

Expression of CD131 Gene in Acute Myeloid Leukemic Cells

To detect the expression level and the mutantion of CD131 in acute myeloid leukemic (AML) cells, and to analyze the relationship of CD131 expression level with clinical features. The peripheral blood mononuclear cells (PBMNC) from 44 AML patients and 25 healthy donors were collected, and the expression level of CD131 mRNA was detected by RT-PCR. The full length coding sequence of CD131 from 15 patients and 5 healthy donors was amplified by RT-PCR, and linked to pGEM-T vector to clone TA, 10 positive recombinant clones of each sample were analyzed by DNA sequencing. The AML patients were divided into CD131 negative and CD131 positive groups according the expression level of CD131, and white blood cell counts, CD34(+) cells percentage, complete remission rate of patients were compared. CD131 was expressed at a lower level in AML than that in healthy donor. Five kinds of CD131 mutantions could be detected in both AML and healthy donor groups, but the mutation rate in AML (75.33%) was higher than that in healthy donors (18.0%). CD131 negative group showed a higher CD34(+) cells percentage (69.1% ± 20.8%), and lower complete remission rate (33.3%) than that in CD131 positive group (69.1% ± 20.8%, 33.3%). No statistically significant difference of WBC counts was found between 2 groups. CD131 is expressed at a low level and shows high frequency of mutation in acute myeloid leukemic cells. CD131 negative AML correlats with high proportion of CD34(+) cells, and showed insensitive to chemotherapy.

Clinical effect of laparoscopic gastric bypass for the treatment of type 2 diabetes mellitus patients with low body mass index

Objective To evaluate the clinical effect of laparoscopic Roux-en-Y gastric bypass (LRYGB) for the treatment of type 2 diabetes mellitus patients with low body mass indexes (BMI). Methods The clinical data of 70 patients with type 2 diabetes mellitus who underwent LRYGB at Daping Hospital of Third Military Medical University from April 2010 to February 2015 were retrospectively analyzed. Thirty patients with BMI>30 kg/m2 were allocated to the high BMI group, and 40 patients with BMI<30 kg/m2 were allocated to the low BMI group. The postoperative prognosis of diabetes mellitus in patients was evaluated according to Guidelines for surgical treatment of obesity and type 2 diabetes mellitus in China (2014). The patients were followed up by inpatient, outpatient examination and telephone interview till February 2015. Body weight, abdominal perimeter, fasting blood glucose, glycosylated hemoglobin (HbAlc), blood pressure, total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were regularly detected at postoperative month 1, 3, 6, 12, 24. Measurement data with normal distribution were presented as ±s and were analyzed by the t test. Repeated measures data were analyzed by the repeated measures ANOVA. The comparison of rate was analyzed using the chi-square test. Results All the 70 patients underwent successfully LRYGB without death, hemorrhage or intestinal obstruction in the perioperative period and received follow-up with a median time of 6 months (range, 1-24 months). Five patients had postoperative complications, including 1 case of stomal leakage, 1 of gastric-jejunal stoma stenosis, 2 of stomal ulcer and 1 of anemia, and had remission of symptoms after symptomatic treatment. The BMI, abdominal perimeter, HbAlc, blood pressure, TC, TG, HDL-C, LDL-C before and after operation between the high BMI and low BMI group were (35.4±4.5)kg/m2-(24.9±1.5)kg/m2 and (26.8±2.3)kg/m2-(21.9±2.0)kg/m2, (110±15)cm-(81±8)cm and (92±8)cm-(79±8)cm, 6.4%±1.4%-6.0%±0.5% and 6.3%±2.1%-6.2%±0.8%, (133±15)mmHg-(132±10)mmHg/(75±9)mmHg-(73±4)mmHg (1 mmHg=0.133 kPa) and (133±11)mmHg-(132±14)mmHg/(74±8)mmHg-(72±7)mmHg, (6.0±2.3)mmol/L-(5.0±1.8)mmol/L and (4.9±1.2)mmol/L-(4.0±0.5)mmol/L, (3.2±1.7)mmol/L-(1.0±0.2)mmol/L and (3.6±2.6)mmol/L-(1.0±0.4)mmol/L, (1.0±0.2)mmol/L-(1.6±0.3)mmol/L and (1.2±0.8)mmol/L-(1.3±0.2)mmol/L, (3.0±0.7)mmol/L-(2.9±1.2)mmol/L and (2.5±0.7)mmol/L-(2.5±0.9)mmol/L, respectively, with no significant differences in the changing trends (F=1.65, 1.72, 0.75, 1.04, 0.98, 1.53, 1.70, 1.05, 0.84, P>0.05). The fasting blood glucose before and after operation in the high BMI group and low BMI group were (8.6±3.5)mmol/L-(5.6±0.9)mmol/L and (8.6±3.3)mmol/L-(6.5±1.7)mmol/L, respectively, with a significant difference in the changing trends (F=2.21, P<0.05). The fasting blood glucose in the high BMI group at postoperative 3, 6, 12, 24 month were lower than those in the low BMI group (t=2.87, 3.88, 3.10, 2.80, P<0.05). Twenty-six patients had complete remission and 4 patients had partial remission in the high BMI group, among 40 patients in the low BMI group, 28 patients had complete remission, 8 patients had partial remission, 3 patients had significant improvement and 1 patient had non-remission, with a significant difference (χ2=4.69, P<0.05). Conclusion LRYGB is safe and feasible for the treatment of type 2 diabetes mellitus with a good comprehensive therapeutic effect, although complete remission rate of patients with BMI 30 kg/m2. Key words: Diabetes mellitus, type 2; Obesity; Gastric bypass; Body mass index; Laparoscopy

The pharmacology of second-generation chimeric antigen receptors

Second-generation chimeric antigen receptors (CARs) retarget and reprogramme T cells to augment their antitumour efficacy. The combined activating and co-stimulatory domains incorporated in these CARs critically determine the function, differentiation, metabolism and persistence of engineered T cells. CD19-targeted CARs that incorporate CD28 or 4-1BB signalling domains are the best known to date. Both have shown remarkable complete remission rates in patients with refractory B cell malignancies. Recent data indicate that CD28-based CARs direct a brisk proliferative response and boost effector functions, whereas 4-1BB-based CARs induce a more progressive T cell accumulation that may compensate for less immediate potency. These distinct kinetic features can be exploited to further develop CAR-based T cell therapies for a variety of cancers. A new field of immunopharmacology is emerging.

Randomized Phase II Trial of Pentostatin, Cyclophosphamide, and Rituximab with or without Concurrent Avastin for Previously Untreated B-Chronic Lymphocytic Leukemia (CLL)

BACKGROUND: Although chemoimmunotherapy (CIT) has improved response rates, treatment free survival, and overall survival in patients with chronic lymphocytic leukemia (CLL), only 40-50% of patients achieve a complete remission and the majority have residual disease when evaluated using sensitive assays. Interactions with nurturing environments can enhance CLL B-cell resistance to apoptosis. These interactions include cytokine mediated prosurvival signals by angiogenic molecules, such as VEGF and bFGF that nurture CLL B-cells in an autocrine fashion and promote CLL cell survival partly through up regulation of anti-apoptotic proteins. These findings provide a strong rationale for testing anti-VEGF therapy in combination with a purine nucleoside analogue CIT regimen for upfront treatment. We conducted a randomized phase 2 CIT trial using pentostatin, cyclophosphamide, and rituximab with (PCR-B) or without (PCR) bevacizumab (B), an anti-VEGF monoclonal anti-body.METHODS: Eligible patients were previously untreated and had CLL in need of treatment by NCI-WG criteria (Blood 111:5446). Patients were randomized using a dynamic allocation procedure stratifying for stage (0-II vs. III-IV) and FISH (17p or 11q deletion vs. other) to receive either 6 cycles of rituximab (100 mg on day 1 of cycle 1; 375 mg/m2on day 2 of cycle 1 and day 1 of cycles 2-6) followed by pentostatin (2 mg/m2) and cyclophosphamide (600 mg/m2) (PCR) administered every 21 days. Patients in the PCR-B cohort also received bevacizumab 15mg/kg on day 1 of cycles 1-5 and days 1, 22, & 43 of cycle 6. All patients underwent complete response evaluation 3 months after day 1 of cycle 6 (or last cycle of treatment for those completing < 6 cycles). MRD was assessed using 6-color flow cytometry (Leukemia 21:956) at the completion of treatment.RESULTS: 68 patients were enrolled through the Mayo Clinic Cancer Research Consortium between 1/2009 and 1/2013. Three patients were excluded from analysis: 1 patient canceled prior to treatment, 1 was dosed incorrectly, and 1 was ineligible due to immunophenotyping inconsistent with CLL. Median age of eligible patients was 63 years (range 43-81) and 43 (66%) were men. With respect to disease stage, 3 (5%), 38 (58%), and 24 (37%) had low, intermediate and high Rai stage disease. Eleven (17%) patients had deletion 17p or 11q & 29 (45%) had unmutated IGHV. No statistically significant differences were observed in these variables by treatment arm.All 65 evaluable patients have completed active treatment, with 54 (83.1%) completing the intended 6 cycles (PCR group 27/32 [84.4%] and PCR-B 27/33 [81.8%]). Hematologic grade 3+ adverse events deemed at least possibly related to treatment were observed in 10 (31.3%) patients on PCR and 12 (36.4%) on PCR-B (p=0.79).Non-hematologic grade 3+ adverse events deemed at least possibly related to treatment were observed in 9 (28.1%) patients on PCR and 18 (54.4%) on PCR-B (p=0.04). The most common such events were hypertension (PCR: 3.1% vs. PCR-B: 21.2%), proteinuria (0% vs. 6.1%) and creatinine increase (3.1% vs. 6.1%).Across both arms, 64/65 (98.5%) patients achieved a response including 31/32 (96.9%) treated with PCR and 33/33 (100%) treated with PCR-B (p=0.49). CR/CRi was achieved in 10/32 (31.3%) patients treated with PCR & 18/33 (54.5%) treated with PCR-B (p=0.08). Of the 28 who achieved a CR/CRi, MRD analysis was completed on 26, of whom 12 (46%) were MRD negative. With respect to treatment arm, 5/32 (16%) patients on PCR and 7/33 (21%) on PCR-B achieved an MRD negative CR.Median time to retreatment for all 65 patients was 44.8 (95% CI: 34.6 – NA) months. Median overall survival has not yet been reached. With current follow-up no differences between treatment-free survival (p=0.38), progression-free survival (p=0.23), or overall survival (p=0.45) are observed by treatment arm.Plasma levels of angiogenic cytokines VEGF, bFGF, thrombospondin (TSP) and the chemokines CCL3 and CCL4 were measured prior to treatment and at the time of the post treatment response evaluation. Correlations of these cytokines with clinical outcome will be presented.CONCLUSION: The addition of bevacizumab to purine analogue-based CIT was generally well-tolerated and may increase complete remission rates in patients with CLL. No clear improvement in treatment free survival has been observed to date. DisclosuresShanafelt:Hospiria: Research Funding; Pharmacyclics/Jannsen: Research Funding; Cephalon: Research Funding; Celgene: Research Funding; glaxoSmithKline: Research Funding; Genetech: Research Funding; Polyphenon E Int’l: Research Funding. Off Label Use: Off label use of pentostatin for treatment of CLL. Off label use of bevacizumab for treatment of CLL. . Kay:Genetech: Research Funding; Pharmacyclics: Research Funding; Hospira: Research Funding; Celgene: Membership on an entity’s Board of Directors or advisory committees; Gilead: Membership on an entity’s Board of Directors or advisory committees.

Vosaroxin in Combination With Cytarabine Provides a New Salvage Option for AML

The addition of vosaroxin to cytarabine improves overall survival and complete remission rates in patients with relapsed, refractory acute myeloid leukemia. This combination is not associated with increased early mortality. Patients at least age 60 years seemed to benefit more than younger patients.