Induction Therapy Group Research Articles

Comparative Quantitative Lymph Node Assessment in Localized Esophageal Cancer Patients After R0 Resection With and Without Neoadjuvant Chemoradiation Therapy

IntroductionThe effects of neoadjuvant chemoradiation therapy on lymph node retrieval during esophagectomy for patients with esophageal cancer are unclear. The aim of this study was to quantify lymph node retrieval after R0 esophagectomy and to assess its impact on overall survival in induction therapy patients. MethodsOne hundred seventy-four consecutive patients underwent esophagectomy with or without induction therapy from 2008 to 2015 for esophageal cancer. Total lymph nodes, positive lymph nodes, and lymph node ratios were compared between two groups of patients: those treated with either upfront surgery or those treated with neoadjuvant chemoradiation therapy followed by surgery. Comparisons were made using Student’s t test. Overall survival was obtained and compared using Kaplan Meier survival curves. ResultsTotal lymph node counts were less in the induction therapy group (p = 0.027), while positive lymph node counts and lymph node ratios did not differ between groups (p = 0.262 and p = 0.310, respectively). In the neoadjuvant chemoradiation followed by surgery group, overall survival was significantly shorter for patients who had any positive lymph nodes in the pathologic specimen (p = 0.0065). ConclusionsTotal lymph node counts were significantly lower in the induction therapy group, while positive lymph node counts and lymph node ratios did not differ from the upfront surgery group. Although overall survival was not different between groups, it was decreased within the induction therapy cohort among those who had any positive lymph nodes retrieved at surgery. This study confirms that unstratified gross lymph node counts do not substantially relate to prognosis in the heterogeneous population of locally advanced esophageal cancer patients who may or may not have had neoadjuvant chemoradiation.

The ratio of cancer cells to stroma after induction therapy in the treatment of non-small cell lung cancer.

Induction therapy induces degenerative changes of various degrees in both cancerous and non-cancerous cells of non-small cell lung cancer (NSCLC). The effect of induction therapy on histological characteristics, in particular the ratio of residual cancer cells to non-cancerous components, is unknown. Seventy-four NSCLC patients treated with induction therapy followed by surgery were enrolled. Residual cancer cells were identified using anti-pan-cytokeratin antibody (AE1/AE3). We analyzed and quantified the following three factors via digital image analysis; (1) the tumor area containing cancer cells and non-cancerous components (TA), (2) the total area of AE1/AE3 positive cancer cells (TACC), (3) the percentage of TACC to TA (%TACC). These factors were also analyzed in a matched control group (surgery alone, n=80). The median TACC of the induction therapy group was significantly lower than that of the control group (p<0.01). In addition, the median %TACC of the induction therapy group (5.9%) was significantly lower than that of the control group (58.6%) (p<0.01). TACC had a strong positive correlation with TA in the control group (r=0.93), but not in the induction therapy group. Conversely, TACC had a strong positive correlation with %TACC in the induction therapy group (r=0.95), but not in the control group. Unlike the control group, the smaller the total area of residual cancer cells, the higher residual tumor contained non-cancerous components in the induction group, which may be the characteristic histological feature of NSCLC after induction therapy.

Safety and efficacy of preoperative induction therapy using a single high dose ATG-F in renal transplantation: a meta-analysis of randomized controlled trials

This study aimed to evaluate the safety and efficacy of preoperative induction therapy using a single high dose (9 mg/kg) of antithymocyte globulin-Fresenius S (ATG-F) for patients undergoing renal transplantation. Randomized controlled clinical trials (RCTs) on the safety and efficacy of preoperative induction therapy using a single high dose of ATG-F for patients undergoing renal transplantation were searched in Cochrane Library, PubMed, EMBASE covering a period from the beginning of databases to July 2015. The meta-analysis was conducted using RevMan 5.2. Five RCTs with 346 patients were included in this study. The meta-analysis showed that the incidences of acute rejection for the patients with renal transplantation were 20.6% (37/180) in the induction therapy group using a single high dose of ATG and 42.8% (71/166) in the control group, with a combined relative risk (RR) of 0.49 and 95% confidence interval (CI) of[0.36, 0.69](P<0.000 1). The patient survival rate (1 year: RR=1.02, 95% CI[0.98, 1.06], P=0.43; 5 years: RR=1.01, 95% CI[0.94, 1.08], P=0.83) and the graft survival rate (RR=1.04, 95% CI[0.97, 1.12], P=0.24) of the two groups were similar. The incidences of CMV infection, urinary tract infection, and malignant tumor were also similar in the two groups. The induction therapy using a single high dose of ATG-F significantly reduced the incidence of acute rejection after transplantation and showed no increased incidence of urinary tract infection, CMV infection, or malignant tumor. The results of our meta-analysis suggest that the application of a high dose of ATG-F may be a safe and effective induction therapy.

The 3-Hole Minimally Invasive Esophagectomy: A Safe Procedure Following Neoadjuvant Chemotherapy and Radiation

Induction therapy followed by esophagectomy has become standard for treatment of intermediate-stage esophageal cancer in many centers. Herein we evaluate the feasibility and safety of the 3-hole minimally invasive esophagectomy (3HMIE) approach in patients who received induction radiation and chemotherapy. Between 2003 and 2012, the records of 119 consecutive patients with esophageal cancer who underwent 3HMIE were reviewed for perioperative complications and long-term outcomes. Comparison was made between procedures performed for patients receiving neoadjuvant chemoradiation and patients who were treated with only surgery. Of them, 78 patients received neoadjuvant chemoradiation and 41 patients were treated with only surgery. Tumor locations were upper (2), middle (16), distal (64), and gastroesophageal junction (37). In all, 76 patients were at clinical stage IIA or above at presentation. Increased requirement for blood replacement in the induction therapy group was significant compared with the surgery-only group. Operative time, estimated blood loss, proximal and distal margin lengths, and length of stay were not significantly different between the cohorts. There was a 30-day perioperative death (0.8%), and this patient was from the surgery-only group. No conduit necrosis or need for diversion was recorded. Overall, 5-year survival was 62% among the 107 patients with early-stage esophageal cancer. 3HMIE is feasible with low mortality and acceptable morbidity even in patients with locally advanced esophageal cancer who received neoadjuvant radiochemotherapy. Overall perioperative and survival outcomes are similar to or better than those reported in the published literature on esophagectomy after induction therapy.

Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma: Evolution and Outcomes over More Than Two Decades within EBMT Centers

Background:Autologous stem cell transplantation and the development of new agents with potent anti-tumor activity have considerably improved the survival of multiple myeloma (MM) patients. However, there is still a high risk of relapse mainly due to the inability of these agents to cure and eliminate definitively the MM cells. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment particularly for patients with high risk factors but its use is still controversial. We recently demonstrated in a prospective study that long-term outcome in MM patients was better with auto/RIC-allo as compared with auto-HSCT alone (Gahrton et al. , Blood 2013). The debate is still ongoing concerning the best time to propose allogeneic transplantation for MM patients; while there is agreement in the scientific community to perform it preferentially within a clinical trial, the majority of patients in Europe are still treated outside of a clinical trial.The objective of this study is to describe the context of use of allo-HSCT for MM in Europe within EBMT centers over more than two decades with the evaluation of different outcomes.Material and methods:We included in this study a total of 7333 patients who received allo-HSCT between January 1990 and December 2012, 4539 (62%) males and 2794 (38%) females with a median age at allo-HSCT of 51 years (range: 18-78), of which 4726 (64%) have been transplanted after year 2004. We identified 6 groups in this population, patients who received allo-HSCT upfront after induction therapy (Group 1, N=1934), patients who received allo-HSCT maximum 8 months after single auto-HSCT (Group 2, N=1997), patients who received allo-HSCT later than 8 months after single auto-HSCT (Group 3, N=1588), patients who received allo-HSCT maximum 8 months after double auto-HSCT (Group 4, N=588), patients who received allo-HSCT later than 8 months after double auto-HSCT (Group 5, N=930), and finally patients who received allo-HSCT after having received at least 3 different HSCT (Group 6, N=296). The different patient, disease and transplantation characteristics according to each group are detailed in the table.Results:The upfront use of allo-HSCT was seen to decrease after year 2000 to represent 12% of allo-HSCT performed in 2012 while the peak of allo-HSCT use directly after 1 auto-HSCT (within 8 months) was around year 2004 to attend 19% of usage in 2012. Remarkably, allo-HSCT was moreover used at the highest rate during the last years later than 8 months after single auto-HSCT which could be translated in a context of relapse post- first auto-HSCT to reach 33% of usage in 2012. The usage according to groups 4, 5 and 6 was 14%, 17% and 5% in 2012 respectively (Figure).The median overall survival (OS) for groups 1, 2, 3, 4, 5 and 6 was 33, 69, 25, 25, 23 and 15 months respectively with a 5 years OS probability of 39%, 53%, 33%, 31%, 29% and 23% respectively; the median progression-free survival (PFS) was 45, 39, 21, 22, 21 and 13 months respectively with a 5 years PFS probability of 43%, 42%, 26%, 28%, 24%, and 15% respectively. The cumulative incidence of transplant-related mortality for the 6 groups at 3 years was 36%, 20%, 32%, 33%, 36% and 35% respectively. The use of reduced intensity conditioning was associated with a significantly better OS only in group 2 compared to myeloablative conditioning with a median OS of 76 months versus 45 months (p=0.002) respectively. Year of transplantation before or after 2004 did not influence on outcomes.Conclusion:This large retrospective study shows different ways of using allo-HSCT for MM in Europe over a defined time period, it describes the different expected outcomes in each case. Allo-HSCT has not found its place yet in the treatment course of MM patients and the debate should continue based on advantages and disadvantages showed for each group of patients. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Cost Analysis of Immunotherapy Using Dendritic Cells for Acute Myeloid Leukemia Patients

INTRODUCTIONTreatment for acute myeloid leukemia (AML) presents a significant economic burden to patients, health care insurers and society, and is expected to remain so in the near future. There are few studies describing the costs of AML in the literature. However, the high cost of treating AML and the demographic evolution of the world population, indicate that such studies are needed to support ongoing efforts to allocate resources efficiently in health care. OBJECTIVETo describe and compare the costs of AML therapies daily used at the Antwerp University Hospital in adult patients receiving chemotherapy with/without stem cell transplantation and in patients receiving immunotherapy using dendritic cell vaccination. DESIGN AND METHODSThis monocentric study compares direct hospital medical costs of treatment for AML between 2005 and 2010, allocated and charged according to the hospital analytic accounting system. Information on use of medical resources was collected from electronic medical records. Professional and facility charges associated with inpatient and outpatient management were collected using electronic billing information. Drug costs and drug administration costs were based on list prices published by the Belgian reimbursement authority (RIZIV/INAMI). The cost analysis distinguished between group 1, patients treated with induction and consolidation therapy alone; group 2, patients treated with induction and consolidation therapy plus allogeneic hematopoietic stem cell transplantation (HSCT) and group 3, patients treated with induction and consolidation therapy plus immunotherapy using dendritic cells engineered to express the Wilms’ tumor protein (Van Tendeloo et al. Proc Natl Acad Sci USA. 2010;107(31):13824-9). RESULTS AND DISCUSSION51 adult patients who were treated for newly diagnosed AML were included. Costs on medical and nursing care at the hematology ward, pharmaceutical prescriptions, transfer episodes to the intensive care ward, laboratory tests and medical imaging were analyzed. The cost of dendritic cell vaccine preparation was € 20 450 per patient. The median cost in group 1 (15 patients) was € 32,648 (range: € 4,759 - € 140,383). Only 1 patient in group 1 went into remission after induction therapy and received consolidation therapy. All patients in group 1 died within 5 year after diagnosis, 13 patients died within 1 year and 5 died within 1 month. The median cost in group 2 (26 patients) was € 184,554 (range: € 87,932 - € 449,155). The median post-consolidation treatment cost in group 2 was € 110,430 (range: € 31,364 - € 255,948). Five-year survival in group 2 was 19%. Seventeen patients in group 2 died within 1 year after HSCT. The median cost in group 3 (10 patients) was € 88,635 (range: € 23,392 - € 215,119). The median post-consolidation treatment cost in group 3 was € 40,748 (range: € 26,907- € 156,870). Five-year survival in group 3 was 30%. Four patients in group 3 died within 1 year after vaccination. CONCLUSIONThis study comparing different post-consolidation therapies confirmes the high cost of treating AML and suggests that savings to the healthcare system could be achieved by sustaining complete remission status for longer periods. Dendritic cell vaccination is one of the new therapeutic options to attain a long remission status. DisclosuresNo relevant conflicts of interest to declare.

Impact of induced therapy before allogeneic hematopoietic stem-cell transplantation for higher-risk myelodysplastic syndrome: experience of single centre

To explore the impact of prior-to-transplantation induction therapy (IT) on patient outcome after allogeneic hematopoietic stem-cell transplantation (Allo-HSCT) for higher-risk myelodysplastic syndromes (MDS). A total of 49 consecutive patients underwent Allo-HSCT for MDS between November 2002 and December 2012. Twenty-six lower-risk MDS cases received supportive therapy (ST). And 17/23 cases of higher-risk MDS received IT prior to transplantation while another 6 only with ST. Their survival, relapse rate and incidence of transplantation-related mortality (TRM) were retrospectively analyzed according to International Prognostic Scoring System (IPSS) scores and marrow blast count. The 5-year cumulative overall survival (OS), disease-free survival (DFS), relapse rate and incidence of transplantation related mortality (TRM) were 59.9%, 59.2%, 10.5% and 31.8% during a median follow-up period of 24.4 (6.2-72.0) months. The OS and DFS of higher-risk group with IT, ST and lower-risk group were different (72.1% vs 16.7% vs 68.1%, P = 0.028; 72.1% vs 16.7% vs 67.9%, P = 0.030). And the OS and DFS of higher-risk group with IT were similar to those of lower-risk group (P = 0.526,0.504) . For the higher-risk group, the patients on IT had improved survival than those on ST in terms of OS and DFS (both P = 0.020). Moreover, the OS and DFS of remission group were higher than non-remission group in patients on IT (both 100% vs 46.7%, P = 0.049). The number of marrow blasts significantly decreased after IT (P = 0.010) without increased TRM (28.9% vs 33.6%, P = 0.612). Induction therapy prior to Allo-HSCT for MDS may reduce clone burden and improve the outcomes of higher-risk MDS without increased TRM.

Comparison of Diagnostic Performance of Preoperative PET-CT for Patients with and without Neoadjuvant Therapy in Non-Small Cell Lung Cancer: Does Induction Therapy Affect the Preoperative PET-CT Results?.

PET-CT has been widely used for restaging after induction therapy in patients with non-small cell lung carcinoma. We aimed to as- sess the role of preoperative PET-CT in patients receiving induction therapy and compare with those without induction therapy. Pa- tients treated with surgery for non-small cell lung carcinoma were included. There were two subgroups according to the presence of preoperative induction therapy. The results of preoperative PET-CT in these two groups were compared. There were 217 pati- ents, 58 in neoadjuvant group and 159 in control (without preoperative induction therapy) group. In N2 lymph nodes, the positive predictive value (PPV) was significantly higher in the neoadjuvant group than in the control group (p=0.01), where the negative pre- dictive value (NPV) (p=0.0001) and accuracy (p=0.03) were significantly lower. In aorticopulmonary lymph nodes, the NPV was sig- nificantly higher in the control group (p=0.002). In lower N2 lymph nodes, the PPV was higher (p=0.007) and the NPV was lower (p=0.003) in the neoadjuvant group. In N1 lymph nodes, the specificity was found to be lower in the neoadjuvant group (p=0.01). The sensitivity, PPV and accuracy for mass was lower in the neoadjuvant group (p=0.002, p=0.0003, and p=0.001, respectively). The negative predictive value and accuracy of PET-CT were slightly decreased in patients with non-small cell lung carcinoma rece- ived induction therapy before surgical resection. PET-CT appears to be beneficial for the assessment of patients those are planned to be treated surgically for lung cancer whether they have received induction therapy or not.

Innovative method using circulating tumor cells for prediction of the effects of induction therapy on locally advanced non-small cell lung cancer

BackgroundThe existence of circulating tumor cells (CTCs) in patients with lung cancer has been reported. The purpose of this study was to assess whether CTCs are predictive of the pathological effects of induction chemoradiotherapy for patients with non-small cell lung cancer.MethodsPatients who underwent induction chemoradiotherapy followed by surgery were compared with those who underwent surgery alone. Peripheral and pulmonary venous blood samples from the involved lobe were collected intraoperatively, and the number of CTCs was counted using the CellSearch™ system, an epithelial cell adhesion molecule-based immunomagnetic technique.ResultsOf the 9 patients who underwent induction therapy, 4 achieved pathological CR, 4 achieved major response, and 1 achieved minor response. All patients who underwent induction therapy and surgery alone were negative for CTCs in peripheral blood. In the induction therapy group, 4 patients showing pathological CR were negative for CTCs in pulmonary venous blood (pvCTCs) and 5 showing major/minor response were positive (mean, 57.8 cells). The numbers of CTCs in patients showing major/minor response were significantly higher than those in patients showing pathological CR (p = 0.012, Mann–Whitney U test). All 6 patients undergoing surgery alone were positive for pvCTCs (mean, 207.5 cells), showing a significant difference from those undergoing induction therapy (p = 0.038).ConclusionsThe existence of CTCs in pulmonary venous blood reflects pathological non-CR, and therapeutic pathological response may be predicted by pvCTC measurement.

Evaluation of the Reliability of Clinical Staging of T2 N0 Esophageal Cancer: A Review of The Society of Thoracic Surgeons Database

Clinical staging of esophageal cancer has improved with positron-emission tomography/computed tomography and endoscopic ultrasound imaging. Despite such progress, small single-center studies have questioned the reliability of clinical staging of T2 N0 esophageal cancer. This study broadly examines the adequacy of clinical staging of T2 N0 disease using The Society of Thoracic Surgeons database. We retrospectively studied 810 clinical stage T2 N0 patients from 2002 to 2011, with 58 excluded because of incomplete pathologic staging data. Clinical stage, pathologic stage, and preoperative characteristics were recorded. Logistic regression analysis was used to identify factors associated with upstaging at the time of surgical intervention. Among 752 clinical stage T2 N0 patients, 270 (35.9%) received induction therapy before the operation. Of 482 patients who went directly to surgical intervention, 132 (27.4%) were confirmed as pathologic T2 N0, 125 (25.9%) were downstaged (ie, T0-1 N0), and 225 (46.7%) were upstaged at the operation (T3-4 N0 or Tany N1-3). Exclusive tumor upstaging (ie, pathologic T3-4 N0) accounted for 41 patients (18.2%), whereas exclusive nodal upstaging (ie, pathological T1-2 N1-3) accounted for 100 (44.5%). Combined tumor and nodal upstaging (ie, pathological T3-4 N1-3) accounted for 84 patients (37.3%). Among patients who received induction therapy, 103 (38.1%) were upstaged vs 225 (46.7%) without induction therapy (p = 0.026). Comparing the induction therapy group and the primary surgical group, postoperative 30-day mortality (3.7% vs 3.7%, p > 0.99) and morbidity (46.3% vs 45%, p = 0.76) were similar. Despite advances in staging techniques, clinical staging of T2 N0 esophageal cancer remains unreliable. Recognizing T2 N0 as a threshold for induction therapy in esophageal cancer, many surgeons have opted to treat T2 N0 disease with induction therapy, even though one-quarter of these patients will be pathologic T1 N0. Although this study demonstrated similar perioperative morbidity and mortality with and without induction therapy, further study is needed to examine the effect of upstaging on long-term survival.

Impact of Induction Therapy on Airway Complications After Sleeve Lobectomy for Lung Cancer

Sleeve lobectomy is a valid alternative to pneumonectomy for the treatment of centrally located operable non-small cell lung cancer (NSCLC), but concern has been evoked regarding a potentially increased risk of bronchial anastomosis complications after induction therapy. This study examined the impact of induction therapy on airway healing after sleeve lobectomy for NSCLC. Bronchial anastomosis complications were recorded with respect to the induction regimen applied (neoadjuvant chemotherapy vs chemoradiotherapy) in a consecutive series of patients with sleeve lobectomy for NSCLC. Ninety-nine patients underwent sleeve resection, 28 of them after induction therapy. Twelve patients received chemotherapy alone, and 16 patients had radiochemotherapy. There were no significant differences in postoperative 90-day mortality (3.6% vs 2.8%) and morbidity (54% vs 49%) for patients with and without induction therapy. Bronchial anastomosis complications occurred in 3 patients (10.8%) with neoadjuvant therapy and in 2 (2.8%) without (p = 0.3). In the induction therapy group, two bronchial stenoses occurred after radiochemotherapy and one bronchopleural fistula after chemotherapy alone. In patients without induction therapy, one bronchial stenosis and one bronchopleural fistula were observed. All bronchial stenoses were successfully treated by dilatation, and both bronchopleural fistulas occurring after right lower lobectomy were successfully treated by reoperation and completion sleeve bilobectomy with preservation of the upper lobe. Sleeve lobectomy for NSCLC can be safely performed after induction chemotherapy and radiochemotherapy with mortality and incidence of airway complications similar to that observed in nonpretreated patients. The treatment of airway complications does not differ for patients with and without induction therapy.

Basiliximab induction in renal transplantation: Long-term outcome

Anti-IL-2 receptor has been proven to be effective in reducing the rate of acute rejection in kidney transplantation and also in improving the graft and patient survival rates. In this study, we retrospectively reviewed the role of the anti-IL-2 receptor, basiliximab, as an induction immunosuppression. Fifty-seven kidney transplant recipients from living donors who received the IL-2 blocker basiliximab (Group 1) as induction therapy in combination with cyclosporine (CsA), steroids and mycophenolate mofetil (MMF) or azathioprine (AZA) were compared with similarly matched renal transplant recipients (N = 312) who did not receive induction therapy (Group 2). Survival analysis was performed using the Kaplan-Meir method. Chi-square test was used to compare the outcome difference of various parameters between the two groups. Both the groups were similar in terms of demographic characteristcs and maintenance immunosuppression used. The total number of rejections was significantly less in Group 1, 14% vs 25% in Group 2 (P = 0.04, Odds ratio = 0.44). A higher number of patients in Group 2 had steroid-resistant rejections, although the difference was not statistically significant (9.9% in Group 2 vs 5.3% in Group 1). Death-censored graft survival was not significantly better in Group 1 at five years as compared with Group 2 (79.4% vs 47.2%, P = 0.09). On multivariate analysis for association with graft survival, only late acute rejections and steroid-resistant rejections were independently associated with poor graft survival, while the type of maintenance immuno-suppression (MMF vs AZA), use of basiliximab induction therapy and total number of acute rejection episodes had no association. Our study suggests that the use of anti-IL-2 receptor antibody basiliximab as induction immuno-suppression results in significantly better prevention of acute rejection, but it does not result in a significantly improved graft survival at five years. It also results in reduced severity of acute rejection.

Impact of Biologics for Induction in Kidney Transplant Patients with a Positive Serology for Hepatitis C

Introduction: Kidney transplantation is the best therapeutic option for HCV-positive patient with terminal chronic renal failure. However, there is limited and contradictory information on the impact that induction therapy with biological agents may have in this risk group. Aim of the study: Analyze the mid-term efficacy and safety of the induction with biologics (lymphocyte-depleting antibodies or anti-CD25 antibodies) in kidney transplant patients with anti-HCV antibodies positive, in terms of patient survival, graft survival and outcome of liver disease. Patients and methods: Retrospective observational study, based on the analysis of the clinical charts of HCV positive kidney recipients (EIA 1,2,3) at the moment of transplantation (TX) receiving a kidney graft in two Spanish units from March 1990 to March 2007, with follow-up until May 2007. 465 patients who met the inclusion criteria (anti-HCV antibodies positive at the moment of transplantation), and none of the exclusion criteria (HBsAg (+), IFN before Tx, previous or simultaneous transplant of a non-kidney graft), 301 did not receive induction therapy (Group I), 117 were treated with ATG, OKT3 or Timoglobuline ® (Group II), and 47 were treated with anti-CD25 antibodies (Group III). Induction therapy is only applied in patients with a high-immunological risk. Results: The induction with biological agents were not identified as an independent risk factor for the death of the patient (OR = 0, 869, 95% CI 0, 552-1, 369, p = 0, 545) being the 3-years patient survival of 91%, 92% and 93% in the three groups respectively (p = 0. 597). No patient died due to liver disease in groups II and III, and only five did so in group I. The death-censored graft survival to 3 years was similar between groups: 83% group I; 76% Group II; 81% Group III respectively (p = 0. 565). In addition, in the multivariate analysis, induction therapy was not an independent risk factor for graft loss among HCV-positive patients (O = 0. 877, CI 95% 0.646-1.192, p = 0. 403). Also, there were no significant differences in the evolution of ALT post-transplant levels, or in the incidence of postransplant severe clinical liver disease. Conclusion: Our data suggest that induction with biologics in HCV-positive kidney transplant patients with high-immunological risk, is related to a favorable mid-term results with regard to the graft survival, patient survival and without a negative impact on the clinical course of liver disease.

Clinical T2-T3N0M0 Esophageal Cancer: The Risk of Node Positive Disease

No consensus exists on the optimal treatment strategy for clinical T2-T3N0M0 esophageal cancer. This study was conducted to determine rates of nodal positivity (N+) and to evaluate results of treatment strategies in this cohort. Surgically treated patients with cT2-T3N0M0 esophageal cancer were reviewed. Adequacy of lymph node dissection was assessed by guidelines applied to clinical stage. Survival was determined by Kaplan-Meier analysis. Univariate and multivariate analyses were done for predictors of N+ and survival. We identified 102 patients, 51 cT2N0 and 51 cT3N0, 39 (38%) of whom had induction therapy. Despite being clinically node negative, 61 patients (60%) had nodal metastases. Applied to cT classification, adequate nodal dissection was achieved in 64 patients (63%). Transthoracic esophagectomy was more likely than transhiatal esophagectomy to achieve adequate nodal dissection (69% versus 31%, p=0.005). Adequate nodal dissection was more likely to document pN+ disease in both the surgery alone group (70% versus 50%, p=0.13) and induction therapy group (71% versus 33%, p=0.02). Five-year overall survival was 44% with surgery alone and 55% with induction therapy. On multivariate analysis, pN+ was the strongest predictor of overall survival (relative risk 2.73, confidence interval: 1.29 to 5.78). Most cT2-T3N0M0 patients have pN+ disease. Despite induction therapy, more than 50% have persistent nodal disease. Transthoracic esophagectomy is more likely to detect pN+ disease and more likely to meet criteria of adequate nodal dissection than is transhiatal esophagectomy. Therefore, the majority of patients with cT2-T3N0M0 should be considered for neoadjuvant protocols and should be treated by transthoracic resection whenever possible.

Treatment of Molecular and Clinical Relapse of Acute Promyelocytic Leukemia (APL) with Arsenic Trioxide: Results of the European Registry of Relapsed APL

AbstractAbstract 15Arsenic trioxide (ATO) is presently regarded as the best treatment option in relapsed PML-RARA+ acute promyelocytic leukemia (rAPL). However, given the relative rarity of relapses following standard front-line APL therapy, the optimal management of this group of patients remains to be firmly established. For this reason, and in order to ensure homogeneity in patient data collection and gain insights into the epidemiology and clinical aspects of rAPL, a European registry of rAPL was established in 2008 under the auspices of the European LeukemiaNet (ELN). Patients with a genetically confirmed (PML-RARA+) molecular or clinical relapse of APL occurring from January 2003 onwards were eligible for registration using uniform CRFs. Management of relapse was at the discretion of the treating physician, but could be based on the treatment recommendations developed by an expert panel provided on the ELN website (www.leukemia-net.org/content/). By 15 July 2010, 122 cases of rAPL had been registered by participants of 7 European countries (Spain, Italy, UK, France, Germany, Greece, Poland) representing the starting group of this ongoing initiative open for participation. In 80 pts (69 in first, 11 in 2nd and later relapse), information was available on ATO salvage therapy. At time of first diagnosis median age was 43 years (14-77); all pts had received all-trans retinoic acid (ATRA) and anthracyclines ± ara-C as first-line therapy. No patients received ATO as part of front-line therapy. According to Sanz Score, 26% were low risk, 45% intermediate and 29% high risk. 39% of pts had the bcr1/2 and 61% the bcr3 isoform of PML-RARA. Median duration of first remission was 493 days (93d to 5.7 years). The usual dosage of ATO was 0,15mg/kg/day, or regimens with the same cumulative dose were used. ATO induction therapy was combined with ATRA (45 mg/m2/day) in 40% of pts and during the consolidation cycle in 50% of pts, respectively. The median duration of ATO (± ATRA) for induction was 30 days and for consolidation 25 days. CNS relapses were treated with intrathecal application of methotrexate ± ara-C ± hydrocortisone and ATO. Among the 69 pts with first relapse, there were (Group A) 25 molecular and (Group B) 42 hematological relapses (bone marrow), in three pts combined with CNS involvement. Two pts had isolated CNS or extramedullary relapse. Main characteristics of pts at start of induction therapy in Group A vs. B were: median WBC count (x109/L) 4.4 (1.9-6.2) vs. 2.3 (0.5-102) (p=0.015); median platelet count (x109/L) 178 (40-392) vs. 87 (9-273) (p=0.0007); median Hb (g/L) 14 (10.6-15.7) vs. 12 (7.6-14.8) (p=0.0008). In Group A, none of the pts had coagulopathy compared to 8 of 25 (32%) pts with coagulopathy in Group B (p=0.004). In Group A, ATO therapy was not complicated by hyperleukocytosis and no episodes of differentiation syndrome were observed. In Group B, 9 (21%) pts had suspected or manifest differentiation syndrome (p=0.02), and additional chemotherapy was administered in 14 (33%) pts to control hyperleukocytosis. Other toxicities were rare and had no significant influence on therapy. In Group A, the rate of 2nd molecular remission after induction was 52% (13 of 25 pts) and after consolidation therapy 64%. No pt died. In Group B, 39 (88%) pts achieved 2nd CR, 2 (5%) pts were resistant and 3 (7%) pts died early from cerebral bleeding. Second molecular remission was reached in 12 of 32 (38%) pts after induction and in 62% after consolidation. Information on postconsolidation therapy was available in 45 pts of Group A and B. Of these, 14 pts underwent allogeneic, 18 pts autologous transplantation and 13 pts further therapy with ATO ± gemtuzumab ozogamicin. 11 of the 45 (24%) pts relapsed (median 2nd remission duration 10 months, 4 to 26), and 9 deaths were reported between 9 and 14 months after the end of consolidation therapy. In pts with 2nd and later relapse, despite previous exposure to ATO, further responses with this agent were observed. Conclusions:ATO is an effective therapy for all stages of relapsed APL. The results argue in favor of serial PML-RARA monitoring in front-line therapy of APL to allow early treatment of emergent relapses, avoiding hyperleukocytosis and risk of death due to bleeding and differentiation syndrome. Furthermore, the favorable toxicity profile of ATO seems to benefit the feasibility of subsequent transplantation. Disclosures:Lengfelder:Cephalon: Research Funding. Fenaux: CELGENE, JANSSEN CILAG, AMGEN, ROCHE, GSK, NOVARTIS, MERCK, CEPHALON: Honoraria, Research Funding.

Long-Term Efficacy of Induction Therapy With Anti–Interleukin-2 Receptor Antibodies or Thymoglobulin Compared With No Induction Therapy in Renal Transplantation

Background Although the utility of antibody induction therapy has been demonstrated in clinical trials, the ideal regimen to use based on patient risk factors has not been fully elucidated. The objectives of this study were to determine the impact of either anti–interleukin-2 receptor antibodies (IL-2RA) or thymoglobulin induction therapies versus no induction therapy on acute rejection rates and on 3-year graft survival rates. Methods This retrospective analysis compared 3 patient groups—those who did not receive induction, those who received IL-2RA induction, and those who received thymoglobulin induction. Results Three hundred eleven patients were included in this study. Patients were well matched for demographic and immunologic characteristics in the noninduced and IL-2RA induction therapy groups; the thymoglobulin induction group included significantly higher risk patients. The acute rejection rates were significantly lower in the IL-2RA and thymoglobulin groups when compared with the no induction therapy group (28% vs 15% vs 41%, respectively; P = .001), which was confirmed with multivariate analysis. The 3-year graft loss rates (no induction 21% vs IL2-RA induction 19% vs thymoglobulin induction 25%; P > .50) and creatinine concentrations (no induction 1.8 ± 0.7, IL-2RA induction 2.0 ± 1.0, and thymoglobulin induction 1.9 ± 1.2; P = .47) were similar between all groups. Conclusion The use of induction therapy significantly reduces the incidence of acute rejection. The use of thymoglobulin induction equalizes 3-year graft survival rates in high-risk patients to those seen in low-risk patients receiving either no induction or IL-2RA induction.

Persistent N2 Disease After Induction Therapy Does Not Jeopardize Early and Medium Term Outcomes of Pneumonectomy

Operative management of patients with persistent N2 disease after induction therapy is still debated. One hundred fifty-three consecutive patients underwent pneumonectomy from January 1999 until July 2005; 28 patients (18.3%) had persistent N2 disease after induction therapy (group 1), 32 patients (20.9%) had pathologic stage N0 or N1 after induction therapy (group 2), and 93 patients (60.8%) with pathologic N2 disease underwent immediate surgery (group 3). Short-term end points were operative mortality at 30 and 90 days and major complications. Long-term end points were 5-year survival and disease-free survival rates. Demographics of the three groups were similar (age, sex, side of operation, type of chemotherapy, smoking status, and comorbidity such as coronary artery disease, diabetes, and chronic obstructive pulmonary disease). Thirty-day postoperative mortality was 10.7% in group 1, 3.1% in group 2 (p = 0.257), and 4.3% in group 3 (p = 0.201); 90-day postoperative mortality was 10.7% in group 1, 12.5% in group 2 (p = 0.577), and 9.7% in group 3 (p = 0.558). Incidence of major postoperative complications was similar. Five-year survival rate was 32.2% (median, 28 months; 95% confidence interval, 7 to 43) in group 1, 34.8% (median, 27 months; 95% confidence interval, 7 to 47) in group 2 (p = 0.685), and 12.4% (median, 15 months; 95% confidence interval, 11 to 19) in group 3 (p = 0.127). No statistical difference was found in terms of 5-year event-free survival, or regarding the side of pneumonectomy. Our results suggest that pneumonectomy is justified in patients with persistent N2 disease after induction chemotherapy.

P2-182: Feasibility of sleeve lobectomy with induction chemoradiotherapy: Analysis of morbidity and recurrence pattern compared with sleeve lobectomy without induction therapy

The purpose of this study was to evaluate the feasibility of sleeve lobectomy after induction chemoradiotherapy. We reviewed seven patients who underwent sleeve lobectomy after inductin chemoradiotherapy(Group A) for locally advanced non-small cell lung cancer, and 19 patients who underwent sleeve lobectomy without induction therapy(Group B). The complication of group A was in 3 (33%) of 7 cases, 1 necrosis of apex of lower lobe, 1 atelectasis and 1 arrhythmia. Of group B was in 9(47%) of 19 cases, 2 failure of anastomosis, 3 air leakage>7day, 3 wound infection, 2 arrhythmia, 2 recurrent nerve palsy, and 1 pneumonia. The recurrence of group A was in 2(29%) of 7 cases. One case was brain on the 220th and pulmonary on the 430th. Another one case was kidney on the 365th and duodenum on the 700th. The recurrence of group B was in 3(16%) of 19 cases, which were observed in 1 pulmonary, 1 skin, and 1 plural, respectively. The complication of bronchial anastomosis and local recurrence was not permitted in group A. Although it is a small number of study, sleeve lobectomy with induction chemoradiotherapy is considered to be feasible technique from safety and oncologically.

A Single-dose Daclizumab Induction Protocol in Renal Allograft Recipients: A Chinese Single Center Experience

This study prospectively compared immunoprophylaxis with a single dose of daclizumab versus no induction in kidney transplant recipients treated with a cyclosporine, mycophenolate mofetil, and prednisone-based immunosuppression regimen seeking to observe the impact of a single-dose regimen for prevention of acute rejection among Chinese renal allograft recipients. A total of 118 renal transplant recipients were randomized into a daclizumab induction therapy group (daclizumab group, n = 58) and a no induction group (control group, n = 60). The daclizumab group received a single-dose (1 mg/kg of ideal body weight by intravenous infusion) 2 hours before the operation. There was no induction therapy in the control group. There was no significant difference in the baseline parameters at randomization between the two groups. The mean time to the first episode of acute rejection was 41.2 ± 3.2 days for the daclizumab group versus 11.2 ± 4.6 days for the control group. The number of first biopsy-confirmed acute rejection episodes during the 6-months after transplantation was significantly different in the daclizumab (7,12.1%) versus the control group (14,23.3%; P < .001). At the end of 12 months, patient and graft survivals were 100% in the groups with or without daclizumab. We noted that the incidence of infection, including serious infection was similar, in the daclizumab group to that in the control group, 17.2% and 20.0%, respectively. This study showed that a single-dose of daclizumab effectively prevented acute rejection in Chinese renal allograft recipients.

Therapy-Related Acute Lymphoblastic Leukemia (t-ALL).

Introduction: Myelodysplasia and Acute Myeloid Leukemia are recognized and well characterized complications of cancer therapy. Much less is known about t-ALL, but an increasing number of cases are being reported.Materials and Methods: We conducted a MEDLINE search to identify patients with ALL diagnosed after exposure to chemotherapy and/or radiotherapy. Data extracted included: latency period, radiation and type of chemotherapy drug exposure, phenotype, cytogenetics and survival.Results: 74 patients were identified with a median age at the time of t-ALL of 33 years, (range 2 to 90; 16 cases age ≤ 10 and 9 cases age ≥60). History of a prior malignancy, including solid tumors in 45 (sarcomas 12, breast cancer 11, others 22) and hematological malignancies in 25 (Hodgkin's lymphoma 17, others 8), was documeted in all patients with the exception of 4, who received chemotherapy or radiation for a non-malignant disorder. Exposure to radiotherapy was documented in 65% of patients (4 cases had exposure only to radiotherapy), 64% had recieved topoisomerase II inhibitors and 84% other chemotherapy drugs. Median time to t-ALL was 38 months. Follow up data was available in 56/74 (75.6%), 20 were reported alive (27%), 3 to 132 months from t-ALL diagnosis. Twelve patients received stem cell transplants, 7 of them were survivors (8 to 79 months). Based on phenotype and/or cytogenetics, 5 subsets of patients were identified. Group A: 32 patients (43%) with 11q23 translocations and/or MLL rearrangements: 23 of these patients (72%) presented with pro-B cell phenotype (CD19+, CD10−)(2 pre-B cell, 2 T cell, 5 unknown); 90% had history of exposure to topoisomerase II inhibitors; median time to t-ALL was 21 months in Group A, significanlty shorter (p<.0001) when compared to all other patients (median 60 months). Median overall survival was 8 months, 5 year survival 27%. Group B: 11 patients (14.8%), with L3/Burkitt's leukemia; all with t(8;14), t(8;22) or t(2;8) abnormalities. None of them are long term survivors. Group C: 4 patients with t(9;22) (5.4%). Group D: 4 patients with T cell phenotype (5.4%). Group E: the remaining 23 patients (31%) with primarily a pre-B cell phenotype (CD19+, CD10+) with normal (21.7%), complex (21.7%) or unknown cytogenetics (56%). Of the 18 patients who received induction therapy in Group E, 9 (50%) are survivors (median 60 months from diagnosis).Conclusions: Various subsets of t-ALL can be recognized, resembling the pattern seen in patients with de novo ALL. However, high-risk subtypes such as 11q23/MLL + cases are overrepresented. Patients with t-ALL not identified by 11q23 or t(9;22) abnormalities, L3/Burkitt's or T cell phenotype (Group E) appear to have a better prognosis: survival at 5 years 45% compared to 24% for all other patients.