Second Course Of Chemotherapy Research Articles

Specific Myocardial Lesion in a Patient with Diffuse Large B-Cell Lymphoma (a Case Report)

Introduction. Myocardial lymphoma is one of the rarest lesion localizations among all the lymphoproliferative diseases. Regardless of the current lack of generally accepted specific recommendations for the treatment of primary and secondary myocardial lymphomas the chemotherapy is carried out in accordance with clinical guidelines for the treatment of lymphoproliferative diseases, which in some cases results in a successful outcome. Materials and methods . The article presents a clinical example of the diagnostic procedure and treatment of a 65-year-old female with the following diagnosis: non-Hodgkin’s lymphoma st. II BE gr. II with the involvement of myocardium, cervical and mediastinal lymph nodes, and the right palatine tonsil. The patient received six courses of R-CEOP chemotherapy. Results and discussion . An echo-positive structure 28mm by 20 mm in size attached to the interatrial septum was found inside the right atrium following the second course of chemotherapy. Ejection fraction: 61%. Effect: regression exceeding 50%. Four months following the completion of treatment the ejection fraction was 63%, regression – exceeding 80%, thus implying a partial response. Conclusion. The diagnosis of lymphoma with a lesion in the myocardium has been positively verified by histology and IHC. Currently less invasive techniques are normally preferred, transesophageal cardiac echo guided biopsy being one. Similar to any other lymphoproliferative disease, myocardial lymphoma is a chemosensitive tumour that responds well to treatment. In each individual case, the treatment strategy must be patient-specific and take into account the somatic status of the patient, the tumour size and the degree of its spread, the tumour morphological type, and whether it would be possible to arrange adequate specialized support needed.

Study of clinical outcome and prognosis in pediatric core binding factor-acute myeloid leukemia

目的分析儿童核心结合因子相关性急性髓系白血病（CBF-AML）的疗效及预后因素。方法对2005年8月至2017年9月收治住院的初诊CBF-AML患儿共121例进行回顾性研究。采用Kaplan-Meier曲线评估患儿的累积复发率（CIR）、无事件生存（EFS）率和总生存（OS）率，Cox回归模型评估预后因素。结果121例患儿中，120例有化疗后骨髓缓解情况评估结果，1个疗程后完全缓解（CR）100例（83.3%），2个疗程后CR 119例（99.2%）。121例患儿中复发13例（10.7%），中位复发时间13.8（3.7~58.8）个月，死亡17例（14.0%）。全部患儿3年CIR、EFS、OS率分别为12.7%、77.5%、82.8%。对发病时年龄、性别、初诊时WBC、是否有髓外白血病、是否伴C-KIT突变、是否有附加染色体异常、第1个疗程是否达CR等进行Cox多因素回归分析，只有伴附加染色体异常是影响患儿OS的独立危险因素（HR=4.289，95%CI 1.070~17.183，P=0.040）。结论儿童CBF-AML是一组独特的预后亚型，化疗疗效较好，伴附加染色体异常是影响患儿OS的独立危险因素。

Association of Persistent Minimal Residual Disease with Poor Outcomes of Patients with Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.

Background:Several studies have shown that detection of minimal residual disease (MRD) in acute myeloid leukemia (AML) is an independent prognostic factor. This study aimed to evaluate the significance of dynamic MRD pretransplantation on outcome of AML patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:We retrospectively analyzed 145 consecutive AML patients undergoing allo-HSCT in complete remission status between June 2013 and June 2016. MRD was determined with multiparameter flow cytometry after the first and second courses of chemotherapy and pre-HSCT.Results:In matched sibling donor transplantation (MSDT) settings, patients with positive MRD had higher cumulative incidence of relapse (CIR) than those without MRD after the first (32.3 ± 9.7% vs. 7.7 ± 3.1%, χ2 = 3.661, P = 0.055) or second course of chemotherapy (57.1 ± 3.6% vs. 12.5 ± 2.7%, χ2 = 8.759, P = 0.003) or pre-HSCT (50.0 ± 9.7% vs. 23.0 ± 3.2%, χ2 = 5.547, P = 0.019). In haploidentical SCT (haplo-SCT) settings, the MRD status at those timepoints had no significant impact on clinical outcomes. However, patients with persistent positive MRD from chemotherapy to pre-HSCT had higher CIR than those without persistent positive MRD both in MSDT and haplo-SCT settings. Patients with persistent positive MRD underwent MSDT had the highest relapse incidence, followed by those with persistent positive MRD underwent haplo-SCT, those without persistent MRD underwent haplo-SCT, and those without persistent MRD underwent MSDT (66.7 ± 9.2% vs. 38.5 ± 6.0% vs. 18.8 ± 8.7% vs. 12.0 ± 1.0%, χ2 = 20.763, P < 0.001). Multivariate analysis showed that persistent positive MRD before transplantation was associated with higher CIR (hazard ratio [HR] = 1.69, 95% confidence interval [CI]: 1.200–2.382, P = 0.003), worse leukemia-free survival (HR = 1.812, 95% CI: 1.168–2.812, P = 0.008), and overall survival (HR = 2.354, 95% CI: 1.528–3.627, P < 0.001).Conclusion:Our results suggest that persistent positive MRD before transplantation, rather than positive MRD at single timepoint, could predict poor outcome both in MSDT and haplo-SCT settings.

PC02.03 BID Radiation - CON

PC02.03 BID Radiation - CON

Olanzapine as antiemetic drug in oncology: a retrospective study in non-responders to standard antiemetic therapy

Background The role of olanzapine in the treatment of chemotherapy-induced nausea and vomiting (CINV) in addition to the antiemetic therapeutic combination with aprepitant, setrons, and corticosteroids has not been well defined. Objective To investigate the effectiveness of the addition of olanzapine to a standard triplet therapy for the prevention of CINV in patients who experienced CINV during their first chemotherapy course, despite receiving a well-managed prevention protocol. Setting One comprehensive cancer centre in France. Method In a retrospective study with comparator, patients with a high risk of emesis were assigned to two groups during two different 6-month periods, before and after the introduction of olanzapine in clinical practice, respectively. In the olanzapine group, the antiemetic protocol for the second course of chemotherapy was reinforced by the addition of olanzapine at 5mg/day from day 1 to 5 in contrast with the control group. Main outcome measure The proportion of patients who experienced neither nausea nor emesis during the delayed phase (24-120h). Results The 25 patients in each group exhibited comparable characteristics and emetic chemotherapy level. During the first course, no significant difference was observed. During the second course, nausea and vomiting were ameliorated in 12 patients in the olanzapine group and 4 patients in the control group (p < 0.05). Nausea (12 vs. 4, p < 0.05) and vomiting (18 vs. 11, p < 0.05) also significantly improved. In the OLZ group, no adverse event was linked to olanzapine use. Conclusion The addition of olanzapine was observed to effectively restore CINV prevention in patients who did not respond to standard antiemetic therapy.

Long-term outcomes of alternating chemoradiotherapy in patients with advanced nasopharyngeal cancer: a single-centre experience over the last decade.

We assessed the long-term outcomes of alternating chemoradiotherapy (ACRT) using 5-fluorouracil and cisplatin (FP) in 25 patients with stage II or advanced nasopharyngeal cancer treated at our institution between April 1999 and April 2010. Median follow-up duration was 87 months (range 2-189). According to the 2009 TNM classification (UICC), six patients were in stage II, nine in stage III, and 10 in stage IV. Treatment completion, response and five-year survival rates were retrospectively assessed. ACRT was performed with a first course of chemotherapy administered followed by the initial round of radiotherapy (36 Gy). Then, a second course of chemotherapy with additional radiotherapy (20-30 Gy) was administered, followed by a final third course of chemotherapy. For chemotherapy, 5-fluorouracil (5-FU, 800 mg/m2/24 h) was intravenously administered for five days, and cisplatin (CDDP, 50 mg/m2/24 h) was administered on the last two days. Treatment completion rate was 96% (24 of 25 cases), and the response rate was 100% (CR: 24 cases and PR: 1 case). Additionally, the five-year overall survival rate was 89.3%. We have demonstrated that ACRT is an effective regimen to treat nasopharyngeal cancer, revealing higher treatment completion, response, and five-year overall survival rates compared with other combinatorial radiotherapy and chemotherapy treatment regimens.

Lentinula edodes mycelia extract plus adjuvant chemotherapy for breast cancer patients: Results of a randomized study on host quality of life and immune function improvement.

Anthracycline-based chemotherapies for breast cancer are known to adversely affect patients' quality of life (QOL) and immune function. For that reason, adjuvants that improve those impairments are required. A randomized double-blind study was conducted to evaluate the effectiveness of Lentinula edodes mycelia extract (LEM), which is an oral biological response modifier (BRM) medicine for cancer patients as such an adjuvant. A total of 47 breast cancer patients who were scheduled to receive postoperative adjuvant anthracycline-based chemotherapy, i.e., 5-fluorouracil (5-FU) + cyclophosphamide + epirubicin (FEC regimen), 5-FU + cyclophosphamide + doxorubicin/pirarubicin (FAC regimen), cyclophosphamide + doxorubicin/pirarubicin (AC regimen) and cyclophosphamide + epirubicin (EC regimen), were entered in the study. The patients were randomly divided into either an LEM or a placebo tablet group; the tablets were orally ingested daily over 2 courses of each therapy. In the placebo group, the total scores for QOL were lower on day 8 of the second course of chemotherapy compared with the baseline scores, whereas in the LEM group the scores had not decreased. In the placebo group, the QOL functional well-being score was lower on day 8 after both the first and second courses of chemotherapy compared with the baseline score, but it had not decreased in the LEM group. Evaluation of immunological parameters indicated that an increase in the proportion of regulatory T cells to peripheral blood CD4+ cells tended to be inhibited in the LEM group compared with the placebo group. Oral LEM that was coadministered with anthracycline-based chemotherapies was useful for maintaining patients' QOL and immune function. Thus, LEM appears to be a useful oral adjuvant for patients receiving anthracycline-based chemotherapy.

Efficacy of the oral neurokinin-1 receptor antagonist aprepitant for nausea and vomiting induced by cisplatin and carboplatin in Japanese patients with gynecological cancer.

This study was conducted to evaluate the efficacy and the difference in effects of the oral neurokinin-1(NK-1) receptor antagonist aprepitant for chemotherapy-induced nausea/vomiting (CINV) in Japanese patients with gynecological cancer receiving highly emetogenic (cisplatin) and moderately emetogenic (carboplatin) chemotherapy. Aprepitant was added during the second course of chemotherapy in Japanese patients with grade≥2 (Common Terminology Criteria for Adverse Events, version 3.0) nausea and vomiting during the first course despite receiving antiemetic therapy (a first-generation 5-hydroxytryptamine 3 receptor antagonist + dexamethasone), and in patients who requested stronger antiemetic therapy despite only having grade 1 nausea and vomiting. The incidence of nausea and vomiting was compared between the first and second courses in each group. Ninety-six (55.5%) out of 173 patients received add-on therapy with aprepitant. There was a significant increase in the complete response (CR: no vomiting or salvage therapy) rate in the patients receiving aprepitant, with marked improvement being confirmed for delayed CINV. Stratified analysis showed that patients with delayed CINV treated with carboplatin had a significantly higher CR rate, while patients with both acute and delayed CINV treated with cisplatin had significantly higher CR rates. There was a positive correlation between the incidence of nausea and the incidence of vomiting in the patients treated with aprepitant. The oral NK-1 receptor antagonist aprepitant could be effective for both acute and delayed CINV with cisplatin and for delayed CINV with carboplatin in Japanese gynecological cancer patients.

Early response rates and Curie scores at end of induction: An update from a phase II study of an anti-GD2 monoclonal antibody (mAb) with chemotherapy (CT) in newly diagnosed patients (pts) with high-risk (HR) neuroblastoma (NB).

10534 Background: We are conducting a Phase II trial of the anti-GD2 mAb hu14.18K322A given concomitantly with CT in newly diagnosed pts with HR NB. Our primary objective is to compare the response rate (RR; defined as ≥ PR) after two courses of CT with cyclophosphamide (CTX)/topotecan (TPT) and hu14.18K322A with GM-CSF and IL-2 to the RR reported by Park et al. (JCO 29:4351, 2011), using identical CT with GCSF only, in a two-stage group sequential design. Semiquantitative MIBG scoring (Curie; CS) has been shown to be a prognostic indicator of outcome in pts with HR NB (Yanik et al, J Nucl Med, 2013), particularly, those with CS &gt; 2 at end of induction (EoI) CT have inferior outcomes. Here we update the RR and report the CS at EoI CT. Methods: Pts received induction CT (6 cycles) as described by Park et al, with the addition of hu14.18K332A (on d 2-5; 40mg/m2/d x 4d), daily sc GM-CSF and sc IL-2 (1 x 106 IU/m2/dose) qod x 6. 123I-MIBG scans and scoring (CS) were obtained on all pts at diagnosis, after second course of CT and at EoI. Results: 42 evaluable pts completed the first two courses of CT (24 male, median age 2.9 yrs (range 6 m -15.2 yrs), 36 INSS 4, 19 MYCNamplified); 40/42 evaluable pts had measurable reductions in primary tumor volume after two courses of CT (median 79%, average 69%, range +5 – 100%). Responses (≥ PR) after two courses were seen in 32/42 (76.2%; 95% CI 61.3 – 87.9%); No mAb dose-reductions were made but 20/43 (47%) pts had infusion times extended. The development of human anti-human antibody reactivity (HAHA) to hu14.18K322A in the first 22 pts is minimal. Of the 36 INSS 4 pts, 1 withdrew prior to EoI and 2 are too early. The median CS at diagnosis for the 33 stage 4 pts who have completed induction CT was 18 (range 1 – 28). At EoI the median CS was 0 (range 0 -23); 29/33 INSS 4 pts had EoI CS ≤ 2. Conclusions: The addition of hu14.18K322A to two courses of CTX/TPT significantly improves the RR compared to two courses of CTX/TPT alone (32/42 vs 12/30 as reported by Park et al,; P = 0.000004). The improved median CS of the stage 4 patients from 18 at diagnosis to 0 at EoI suggest the improvement in early RR may translate into improved EFS as well. Clinical trial information: NCT01857934.

Abstract PD3-03: Determining the prognostic role of early and end-of-neoadjuvant chemotherapy 18F-FDG PET/CT in patients with locally advanced breast cancer

Abstract Aim: To investigate the use of 18F-FDG PET/CT at diagnosis and after end-of-treatment in the prediction of response to neoadjuvant chemotherapy (NAC) and its role in the prognosis of patients with locally advanced breast cancer (LABC). Materials and Methods: One hundred thirty-two patients underwent a baseline FDG PET/ CT (PET-1) after the second course of chemotherapy (PET-2) and after the last course (PET-3). Breast tumors were classified into molecular phenotypes and grouped into risk categories according to the biological prognostic factors obtained by immunohistochemistry. PET/CT scans were semiquantitatively evaluated, obtaining the Δ% SUV1-2 and SUV1-3 in primary tumor and axillary lymph nodes to establish response groups attending to EORTC criteria. Moreover, a binary assessment was obtained classifying the studies as positive or negative. Pathological response was determined both in breast and axillary lymph node specimens. Overall survival (OS) and disease-free survival (DFS) were obtained during the follow-up. ROC analysis was performed to determine a cutoff value of Δ% SUV1-2 and SUV1-3 for the prediction of response and prognosis. Relations between molecular phenotypes, metabolic behavior, final pathological response, OS, and DFS were evaluated. This prospective and multicenter study was approved by the local ethics committee of our institution and included 7 hospitals of our region. Results: In binary analysis, only PET-3 was able to predict pathological response in lymph nodes. The cutoff values of %Δ SUV1-2 and %Δ SUV1-3 with the best sensitivity and specificity in the prediction of response in breast tumor were 62% (Se: 70% and Sp: 69%) and 84% (Se: 70%and Sp: 88%). A%ΔSUV1-3 of 74% in breast tumor was a predictor of DFS (AUC = 0.647; P = 0.037, Se: 52% and Sp: 66%). Kaplan- Meier analysis revealed significant relations between the binary lymph node assessment of PET-3 with OS (P = 0.016, χ2 = 5.78) and DFS (P = 0.003, χ2 = 9.10). Conclusions: Among the multiple metabolic response variables in breast tumor and lymph nodes, end-of-treatment 18F-FDG PET/CT was a significant predictor of breast and lymph node response and patient prognosis. The molecular phenotypes and pathological lymph node response rate were independent predictors of OS and DFS. This stresses the potential of the biological influence over metabolic variables in the prognosis of patients. Metabolic response variables work better in their predictive and prognostic value in high-risk tumors. Citation Format: Muñoz-Sánchez MdM, Molina-Garrido MJ, García Vicente AM, Soriano Rodríguez MdC, Amo Salas M, Olaverri Hernández A, Chacón Muñiz JI, Álvarez Cabellos R, Espinosa Aunión R, Ortega Ruipérez C, Martín Ordóñez F, Pena Pardo FJ, Jiménez Londoño GA, Val Pérez E, Santiago Crespo JA, Soriano Castrejón A. Determining the prognostic role of early and end-of-neoadjuvant chemotherapy 18F-FDG PET/CT in patients with locally advanced breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr PD3-03.

ED14.02 Thoracic Radiotherapy of SCLC

ED14.02 Thoracic Radiotherapy of SCLC

P1.03-013 Diagnosis, Assessment and Prediction of Early Response to Chemotherapy by Using Diffusion-Weighted MRI in Lung Cancer

Radiographic screening, diagnosing, staging, and assessing procedures with ironizing radiation-based tests are currently most widely used for lung cancer. However, one of the major harms of these imaging tests is the potential for radiation-induced carcinogenesis. Whether radiographic screening, diagnosing, staging, and assessing procedures increase cancer incidence and death in patients exposed to radiation of medical sources is ignored in the context of indefinite answer. We aimed to evaluate the ability of radiation-free diffusion-weighted magnetic resonance imaging (DW-MRI) to diagnose, assess and detect early response to chemotherapy in lung cancer patients. This study was approved by the institutional review board, and written informed consent was obtained from all subjects. Ninety patients with lung cancer as confirmed by pathologic examination (25 women, 65 men; mean age, 57 years) who underwent chemotherapy were enrolled between November 2014 and October 2015. All patients underwent MRI and computed tomography (CT), as the reference test, at baseline and after the second course of chemotherapy. The apparent diffusion coefficient (ADC) of each lung carcinoma was calculated from images. Ki-67 scores and tumor markers in the serum, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE) and squamous cell carcinoma antigen (SCC), were determined. ADC values were compared among different histopathologic types and between pretreatment and posttreatment. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance of ADC and its combination with tumor markers. The relationship between the baseline ADC values with Ki-67 scores and final tumor size reduction were analyzed by using the Pearson correlation coefficient. This study is registered with Clinical Trials.gov (NCT02320617). Before treatment, there were significant differences between NSCLC and SCLC (P=0.000), adenocarcinoma and SCLC (P=0.000), and squamous cell carcinoma and SCLC (P=0.002). ADC values and Ki-67 score showed negative correlation (r=−0.408, P=0.000). In ROC analysis, area under curve (AUC) of ADC in combination with CEA, SCC and NSE was 0.772, 0.821 and 0.761, respectively. ADC values were significantly different between pretreatment and posttreatment (P=0.001), and partial response (PR) and stable disease (SD) groups. ADC at baseline was negatively correlated with tumor size reduction (r=−0.434, P=0.017). As well, AUC of ADC after treatment to discriminate PR and SD groups was 0.804. Our findings extended the previous findings by that ADC in DW-MRI could: (1) discriminate different histopathologic types; (2) evaluate the malignancy; (3) predict and monitor the early response to chemotherapy. Radiation-free DW-MRI seems to be a promising tool for management of lung cancer.

Disseminated intravascular coagulation at diagnosis is a strong predictor for thrombosis in acute myeloid leukemia

AbstractVenous thromboembolism is a common complication in patients with cancer, but only limited data are available in acute myeloid leukemia (AML). In a prospective study in a cohort of 272 adult patients (aged 18-65) and an independent validation cohort of 132 elderly adults (aged >60) with newly diagnosed AML, we assessed markers of disseminated intravascular coagulation (DIC) (fibrinogen, D-dimer, α-2-antiplasmin, antitrombin, prothrombin time, and platelet count) and the DIC score according the International Society of Thrombosis and Haemostasis and their associations with the occurrence of venous and arterial thrombosis during follow-up. The prevalence of thrombosis was 8.7% (4.7% venous, 4.0% arterial) in the younger adults over a median follow-up of 478 days and 10.4% (4.4% venous, 5.9% arterial) in elderly patients. Most thrombotic events (66%) occurred before the start of the second course of chemotherapy. The calculated DIC score significantly predicted venous and arterial thrombosis with a hazard ratio (HR) for a high DIC score (≥5) of 4.79 (1.71-13.45). These results were confirmed in the validation cohort of elderly patients with AML (HR 11.08 [3.23-38.06]). Among all DIC parameters, D-dimer levels are most predictive for thrombosis with an HR of 12.3 (3.39-42.64) in the first cohort and an HR of 7.82 (1.95-31.38) in validation cohort for a D-dimer >4 mg/L vs ≤4 mg/L. It is concluded that venous and arterial thrombosis may develop in ∼10% of AML patients treated with intensive chemotherapy, which to a large extent can be predicted by the presence of DIC at time of AML diagnosis.

Prognostic Role of Early and End-of-Neoadjuvant Treatment 18F-FDG PET/CT in Patients With Breast Cancer.

To determine the use of early and final treatment F-FDG PET/CT in the prediction of response to neoadjuvant chemotherapy (NAC) and its role in the prognosis of patients with locally advanced breast cancer (LABC). One hundred thirty-two patients underwent a baseline FDG PET/CT (PET-1) after the second course of chemotherapy (PET-2) and after the last course (PET-3). Breast tumors were categorized into molecular phenotypes and risk categories according to the biological prognostic factors obtained by immunohistochemistry. PET/CT scans were semiquantitatively evaluated, obtaining the Δ% SUV1-2 and SUV1-3 in primary tumor and axillary lymph nodes to establish response groups attending to EORTC criteria. Moreover, a binary assessment was obtained classifying the studies as positive or negative. Histopathological response was obtained in breast and lymph node specimens. Overall survival (OS) and disease-free survival (DFS) were obtained after the follow-up. ROC analysis was performed to determine a cutoff value of Δ% SUV1-2 and SUV1-3 for the prediction of response and prognosis. Relations between phenotypes, metabolic behavior, final histopathological response, OS, and DFS were evaluated. In binary analysis, only PET-3 was able to predict histopathological response in lymph nodes. The cutoff values of %Δ SUV1-2 and %Δ SUV1-3 with the best sensitivity and specificity in the prediction of response in breast tumor were 62% (Se: 70% and Sp: 69%) and 84% (Se: 70% and Sp: 88%). A %ΔSUV1-3 of 74% in breast tumor was a predictor of DFS (AUC = 0.647; P = 0.037, Se: 52% and Sp: 66%). Kaplan-Meier analysis revealed significant relations between the binary lymph node assessment of PET-3 with OS (P = 0.016, χ = 5.78) and DFS (P = 0.003, χ = 9.10). End-of-treatment F-FDG PET/CT was a predictor of lymph node response and prognosis. Most of metabolic response variables related to histopathological response showed association with the prognosis.

Successful Therapy Reduction and Intensification for Childhood Acute Lymphoblastic Leukemia Based on Minimal Residual Disease Monitoring: Study ALL10 From the Dutch Childhood Oncology Group.

Outcome of childhood acute lymphoblastic leukemia (ALL) improved greatly by intensifying chemotherapy for all patients. Minimal residual disease (MRD) levels during the first months predict outcome and may select patients for therapy reduction or intensification. Patients 1 to 18 years old with ALL were stratified on the basis of MRD levels after the first and second course of chemotherapy. Thereafter, therapy was substantially reduced in patients with undetectable MRD (standard risk) and intensified in patients with intermediate (medium risk) and high (high risk) levels of MRD. Seven hundred seventy-eight consecutive patients were enrolled. The method of analysis was intention-to-treat. Outcome was compared with historical controls. In MRD-based standard-risk patients, the 5-year event-free survival (EFS) rate was 93% (SE 2%), the 5-year survival rate was 99% (SE 1%), and the 5-year cumulative incidence of relapse rate was 6% (SE 2%). The safety upper limit of number of observation years was reached and therapy reduction was declared safe.MRD-based medium-risk patients had a significantly higher 5-year EFS rate (88%, SE 2%) with therapy intensification (including 30 weeks of asparaginase exposure and dexamethasone/vincristine pulses) compared with historical controls (76%, SE 6%). Intensive chemotherapy and stem cell transplantation in MRD-based high-risk patients resulted in a significantly better 5-year EFS rate (78%, SE 8% v 16%, SE 8% in controls). Overall outcome improved significantly (5-year EFS rate 87%, 5-year survival rate 92%, and 5-year cumulative incidence of relapse rate 8%) compared with preceding Dutch Childhood Oncology Group protocols. Chemotherapy was substantially reduced safely in one-quarter of children with ALL who were selected on the basis of undetectable MRD levels, without jeopardizing the survival rate. Outcomes of patients with intermediate and high levels of MRD improved with therapy intensification.

OC-10 - Disseminated intravascular coagulation at diagnosis strongly predicts both arterial and venous thrombosis in acute myeloid leukemia patients

Acute myeloid leukemia (AML) is associated with a slightly increased risk of VTE with an incidence of 1.7-8.9%, but only limited data are available. The mechanism of the occurrence of thrombosis in hematological disorders is still unresolved. Disseminated intravascular coagulation (DIC) is associated with VTE and bleeding in acute promyelocytic leukemia and acute lymphoblastic leukemia. Although DIC has also been reported in AML, no data exist on the relationship between DIC and VTE in AML patients. We hypothesized that the presence of DIC at diagnosis of AML may contribute to the risk of both venous and arterial thrombosis in AML. Therefore we studied a large cohort of adult patients with newly diagnosed AML aged <65 years by measuring DIC parameters at diagnosis prior to treatment and assessing the occurrence of both venous and arterial thrombosis during follow up. The findings of this study were validated in a second large cohort of patient with newly diagnosed AML aged >60 years. In a prospective study we analysed markers of DIC and their association with the occurrence of thrombosis during follow up in a cohort of 272 young AML patients (aged 18-65) and a validation cohort of 132 elderly AML patients (aged >60) patients that were all treated with intensive chemotherapy. DIC parameters (fibrinogen, D-dimer, alpha-2-antiplasmin, antitrombin, prothrombin time and platelets) were measured at presentation with AML before start of induction chemotherapy. The DIC score according to the International Society of Thrombosis and Haemostasis DIC scoring systemwas calculated of all patients. The prevalence of thrombosis was 8.7% (4.7% venous, 4.0% arterial) in young patients over a median follow up of 478 days and 10.4% (4.4% venous, 5.9% arterial) in elderly patients. Most thrombotic events (66%) occurred before start of the second course of chemotherapy. The calculated DIC score significantly predicted venous and arterial thrombosis with a Hazard Ratio (HR) for a high DIC score (=>5) of 4.79 (1.71-13.45) in the cohort of young AML patients. These results were confirmed in our validation cohort of elderly AML patients. (HR 11.08 (3.23-38.06)). Of all DIC parameters D-dimer levels are most predictive for thrombosis with a HR of 12.3 (3.39-42.64) in the cohort of young AML patients and a HR of 7.82 (1.95-31.38) in the elderly cohort for a D-dimer >4.0 mg/L. It is concluded that both venous and arterial thrombosis occurs in around 10% of AML patients treated with intensive chemotherapy, which can be predicted by the presence of DIC, or individual DIC parameters at time of AML diagnosis.

Routine interim disease assessment in patients undergoing induction chemotherapy for acute myeloid leukemia: Can we do better?

The presence of >5% blasts at "day 14" (D14), in patients undergoing induction chemotherapy for acute myeloid leukemia (AML) is problematic. It is unclear if a second course of chemotherapy for early persistent disease will alter outcome in these patients. We conducted a retrospective study of AML patients undergoing induction chemotherapy where diagnostic, interim (around day 14), and recovery (days 21-42) bone marrow (BM) evaluations were available for review. Of the 113 patients included in the final analysis, 99 (87.6%) achieved CR at hematologic recovery. At D14, 90 patients (79.6%) had <5% blasts and of these, 87 (96.7%) ultimately achieved CR. At D14, Twenty-three (20.4%) patients had residual leukemia (>5% blasts). Of these, 11 (47.8%) received a second course of chemotherapy (double induction [DI]) and 12 (52.2%) were observed until count recovery (single induction [SI]). No significant difference in CR rates was observed between these two groups (58.3% DI group vs. 45.5% SI group, P value = 0.684). In our analysis, D14 BM evaluation did not uniformly identify patients with primary induction failure. To unequivocally determine the value of a D14 marrow assessment in AML, prospective studies in the context of large cooperative group trials are required. Considering our findings and similar reports from others, we propose that D14 marrow assessment should be individualized, and that other factors, such as cytogenetics and early peripheral blood blast clearance should be considered, to identify patients most likely to benefit from interim disease assessment during AML induction therapy.

Analysis of serum carcinoembryonic antigen for advanced non-small cell lung cancer chemotherapy curative effect

Objective To explore clinical value of serum carcinoembryonic antigen (CEA) rate in early evaluation of imaging tumor efficacy and prognosis of disease control for advanced non-small cell lung cancer (NSCLC) before and after the second course of chemotherapy, and provide the basis for clinical adjustment chemotherapy regimens. Methods Patients in the Third Affiliated Hospital of Sun Yat-sen University were randomly collected in January 2007- September 2014 during the pathological diagnosis of 130 cases for advanced NSCLC, who had an elevated serum CEA level, including pre-chemotherapy and pro-chemotherapy, were collected. Receiver operating characteristic (ROC) was used to evaluate efficacy of CEA change in evaluation of early disease control (DC). SPSS 18.0 was used to analyze the relationship between CEA change and prognosis. Results After two chemotherapy cycles, the area under the ROC curve was 70.6%. When the cut-point of the change rates of CEA levels was 2.05%, the Youden index reaches the maximum. Adenocarcinoma group and squamous cell carcinoma patients after 2 courses of CEA change rate evaluation, which area under the ROC curve was 72.0%(95% CI: 61.4%~82.5%), and 70.1%(95% CI: 45.8%~94.5%). Survival was analyzed with the Kaplan-Meier method, which showed the change rates of CEA levels were all the influencing factors of progression-free survival (PFS) in patients with advanced NSCLC(P<0.05). While the change rates of CEA levels were not predictive overall survival (OS) (P=0.715). Conclusions It prompts effective chemotherapy, and patients have the extended PFS, when CEA levels before and after chemotherapy dropped to a certain degree. Key words: Carcinoembryonic antigen/ME; Carcinoma, non-small-cell lung/ME/DT; Prognosis

A Painful Perianal Lesion

Gastroent Question: A 54-yearold white man with a history of infection with human immunodeficiency virus complicated with disseminated bartonellosis infection was recently diagnosed with multicentric Castleman disease. He was treated with 4 weekly doses of rituximab 375 mg/m and methylprednisone 4 mg/d. His further treatment consisted of ritonavir boosted daranuvir, emtricitabin, and tenofovir. His CD4 count was 100/ mL, and his viral load 151 copies/mL. During his second course of chemotherapy, he developed complaints of anal pain and rectal bleeding. On physical examination, he had a deep, solitary, punched-out perianal ulcer with granulating base and raised indurated edges (Figure A). His leukocyte count was 3400/mL, with 59% neutrophils and 34% lymphocytes. Serological testing was negative for Bartonella henselae immunoglobulin M enzyme-linked immunosorbent assay and Treponema pallidum rapid plasma reagent. Tissue cultures of the ulcer were negative for fungi, mycobacteria and pathogenic bacteria, as was the polymerase chain reaction (PCR) for Chlamydia trachomatis and Neisseria gonorrhoeae and the direct immunofluorescence assay for Herpes simplex types 1 and 2. Biopsies from the border of the ulcer showed a mixed inflammatory infiltrate (mainly consisting of neutrophils, without granuloma formation) in the basal layer of the stratified squamous epithelium (Figure B, arrow). Specific staining could not demonstrate any acid-fast bacilli, fungi, or herpesvirus antigens. What are major differential diagnoses, and how may you proceed? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.

Detection of Rearrangements of Mixed Lineage Leukemia Gene and Its clinical relevance

Background: The mixed lineage leukemia (MLL) gene located on chromosome 11 band q23 normally functions as a transcription regulator of the HOX genes and is essential for normal mammalian development and hematopoiesis. Chromosomal translocations involving MLL gene represent frequent cytogenetic abnormalities found in aggressive acute leukemia, both lymphoblastic and myeloid. AL MLL rearrangements have the unique clinical, hematological and prognostic features. We aimed to study the incidence and the types of fusion genes and the clinical relevance.Results: Study samples were from 60 acute leukemia (AL) patients from Sep. 2003 to Dec. 2005. There were 28 males and 32 females. The ages were from 3 months to 54 years old. 17 patients were less than 15 years old and 43 patients were more than 15 years old. All patients were diagnosed based on FAB diagnostic criteria. The patients included 30 with ALL (10 of ALL-L1 patients, 15 of ALL-L2, 5 of ALL-L3), 28 with AML (2 of AML-M1 patients, 5 of AML-M2, 5 of AML-M4, 13 of AML-M5, 1 of AML-M6, 2 of AML-M7), 1 with mixed cell leukemia (AMLL), and 1 with NK cell leukemia. 59 patients were newly diagnosed and 1 patient was refractory. The rearrangements of MLL gene were detected by fluorescence in situ hybridization (FISH) and 6 types of common fusion genes (MLL / AF4, MLL / ENL, MLL / AF9, MLL / ELL MLL / AF6, MLL / AF10) resulting from the rearrangements of MLL gene were detected by nested RT-PCR. There arrangements of MLL gene was found in 7 out of 60 AL patients, (11.67%). Among these 7 patients, 2 were diagnosed with AML- M5 and 5 patients were diagnosed with B-ALL. The fusion genes of the 2 AML-M5 patients who had the rearrangements of MLL gene were MLL/AF9. Among 5 B-ALL patients, 2 patients were confirmed to express MLL/ENL, 1 patient was confirmed to express MLL/AF4, and the other 2 patients did not express the fusion genes. 1 of 2 AML-M5 MLL fusion gene positive patients had invasion of leukemia cell in the left leg and CR was achieved after the first course of chemotherapy. The central nervous system leukemia was got after 1 year and died. The other achieved CR with the third of chemotherapy. 1 of 5 patients died from DIC and the cerebral hemorrhage on the second day after diagnosis B-ALL of MLL fusion gene positive. 2 of 5 patients were not in remission and died from multi-organ failures and infection 3 weeks after diagnosis with positive MLL fusion gene. 1 of 5 patients B-ALL of MLL fusion gene positive got invasion of leukemia cell in thoracic and achieved CR after the second course of chemotherapy. 1 of 5 patients of B-ALL of MLL fusion gene positive achieved CR after the first course of chemotherapy and was relapse 1 year after the bone marrow transplant and then died.Conclusions: We conclude that nested RT-PCR is convenient and feasible method to detect the types of fusion genes resulting from the rearrangements of MLL gene. The clinical features of AL with MLL fusion gene include high white blood cell, invasion of multiple organs, resistant to conventional chemotherapy, easy to relapse after remission, and poor prognosis. The detection of MLL gene rearrangement is of great importance in predicting prognosis and guiding therapy in AL. DisclosuresNo relevant conflicts of interest to declare.