Modified Topotecan Combination with Cyclophosphamide and Ara-C (CAT) for Patients with Refractory/Relapsed Leukemia.

Abstract The prognosis of patients with leukemia has improved significantly. With combination chemotherapy, 60%–80% of adult patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia(ALL) achieve complete remission(CR). But most patients eventually relapse and do not response to current induction regimens based on cytarabine and anthracyclines any more. This emphasize the need to discover new agents for the treatment of leukemia to improve long-term prognosis. Topotecan is a semisynthetic analogue of the alkaloid camptothecin which acts as a specific inhibitor of topoisomerase I,by stabilization of the topoisomerase I DNA complex which leads to cell death.It also appears to be active against leukemias which have acquired the multi-drug resistant phenotype.[ Ulukan et al. Drug, 2000; Weihrauch et al. Leuk Lymphoma, 2004].It also could go through blood brain barrier[Kollmannsberger et al. Oncology, 1999].Here we observe the effect and side-effects of cyclophosphamide, cytanthetic analogue of rabine and topotecan (Modified CAT) combination regimen for treatment of refractory or relapsed leukemia. The study population comprise 26 patients with relapsed/refractory leukemia,including 12 with AML, 9 with ALL, 2 with myeloid blast phase of CML, 3 with lymphoma. Median age was 35 years.Patients received cyclophosphamide 300mg/m2 every 12 hours for 6 doses on day1 to 3.On day 2, topotecan was given at a dose of 1.5mg/m2/day for 5 days on days 2 to 6, and cytarabine 1.0 g/m2 /day for 5 days on days 2 to 6.The regimen (cytarabine reduced to 0.5g/m2 /day) could be repeated one or two cycles after remission. The total response rate of one course was 57%, eleven patients (42%) achived complete remission(CR). Responses occurred in 7of 12 AML (57%), including 5 CR(41%); in 6 of 9 patients with ALL (67%), including 5 CR(56%); and in 1 of 2 myeloid blast phase of CML(CR 50%). The median overall survival time after treatment was 2+ months, and the median overall survival time after CR was 4+ months. Severe myelosuppression was universal (100% Grade 4 neutropenia and thrombocytopenia), the median time to recovery of neutrophils to ≥0.5×109/L was 18 days,and the median time to platelet recovery to ≥ 20×109/L was 26 days.Infection developed in 96% cases, the most frequent events were oral mucositis(77%, 20/26), sepedogenesis(46%, 12/26),anusitis(38%,10/26),pneumonia(31%, 8/26), two patients died of infection complications(8%). Non-hematologic toxicity was seen frequently in gastrointestinal but it was mild. Nausea and/or vomiting occurred in 13 patients(50%)with gradeI-II in all of them.Two patients(8%) had diarrhea and grade 1–2 in them. In summary, Modified CAT regimen is well tolerated and has significant anti-leukemia activity as salvage therapy for relapsed/refractory leukemia.

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Caspase 3 Expression in Mantle Cell Lymphoma: An Immunohistochemical Study of 84 Patients.

Blood ◽

10.1182/blood.v106.11.4676.4676 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4676-4676

Author(s):

Carsten Schrader ◽

Wolfram Klapper ◽

Paul Riis ◽

Peter Meusers ◽

Guenter Brittinger ◽

...

Keyword(s):

Overall Survival ◽

Mantle Cell Lymphoma ◽

Survival Time ◽

Median Overall Survival ◽

Caspase 3 ◽

Clinical Course ◽

Cell Lymphoma ◽

Overall Survival Time ◽

Mantle Cell ◽

Median Overall Survival Time

Abstract Mantle cell lymphoma (MCL) is a malignant lymphoma associated with a relatively aggressive clinical course and a median overall survival time of 3–4 years. We investigated immunohistochemically the expression of the apoptotic marker caspase 3 in relation to the clinical course. Biopsy specimen from 84 untreated patients enrolled in two multicenter prospective trials were investigated immunohistochemically with monoclonal antibodies against CD20, CD5, CD3, CD23, cyclin D1, Caspase3. The Caspase3 expression was analyzed in three groups: less than 1 positive cell per high power field (HPF), more than 1 positive cell per HPF and more than 2 positive cells per HPF. The expression was compared with the overall survival data analysed according to Kaplan and Meier. In 75 cases the caspase 3 staining could be analyzed. The caspase 3 expression had a range of 0.1–4.7 positive cells per HPF (median value:1.1, mean:1.3). Patients with mantle cell lymphoma that had less than 1 caspase 3 positive cell per HPF (33 cases) had a median overall survival time of 48 months compared to 27 months for patients with more than 1 positive cell per HPF (24 cases) and 15 months for more than 2 positive cells per HPF (18). The Kaplan-Meier analysis showed a significant difference in the overall survival time between these groups (p<0.0001). The immunohistochemical detection of caspase 3 in mantle cell lymphoma is a predictor for survival in MCL.

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Apoptosis Regulating Proteins bax and p53 in Mantle Cell Lymphoma.

Blood ◽

10.1182/blood.v106.11.4710.4710 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4710-4710

Author(s):

Carsten Schrader ◽

Wolfram Klapper ◽

Dirk Janssen ◽

Paul Riis ◽

Peter Meusers ◽

...

Keyword(s):

Overall Survival ◽

Clinical Outcome ◽

Mantle Cell Lymphoma ◽

Survival Time ◽

Median Overall Survival ◽

Cell Lymphoma ◽

P53 Expression ◽

Overall Survival Time ◽

Mantle Cell ◽

Median Overall Survival Time

Abstract In malignant tumors beside cell proliferation also cell death plays role for cell survival. Apoptosis regulating genes can be divided into two groups: death antagonists and death agonists such as bax. The ratio of death agonists and antagonists determines if a cell goes into apoptosis. We investigated in a large collective the immunohistochemical expression of the apoptotic marker p53 and bax in relation to the clinical course. Biopsies were stained immunohistochemically with monoclonal antibodies against bax and p53 and the expression was subdivided in three groups: negative, weak positive and strong positive. The expression profiles were analyzed with the overall survival data according to Kaplan and Meier. Patients with mantle cell lymphoma that had negative p53 expression had a median overall survival time of 38.1 months compared to 22.3 months for patients with a weak and 11.3 months for a strong p53 expression (0<0.0001). The bax expression was in the majority of cases positive. Only one case showed a negative staining. Patients with weak and strong bax expression showed no differences in clinical outcome (median overall survival time: 23 vs 33 months, p=0.6051). The immunohistochemical detection of p53 in mantle cell lymphoma is a good predictor for the clinical outcome.

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Efficacy and Safety of Gemtuzumab-Based Regimens in Patients with CD33-Positive Refractory Leukemia.

Blood ◽

10.1182/blood.v110.11.4358.4358 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4358-4358

Author(s):

Suijing Wu ◽

Xin Du ◽

Wei Lin ◽

Jianyu Weng ◽

Jianjun Zhang ◽

...

Keyword(s):

Stem Cells ◽

Overall Survival ◽

Survival Time ◽

Myeloid Leukemia ◽

Median Overall Survival ◽

Response Rate ◽

Single Agent ◽

Efficacy And Safety ◽

Blast Phase ◽

Median Overall Survival Time

Abstract Patients with relapsed or refractory leukemia have less chances of obtaining remission than patients with newly diagnosed.It is reported that more than 80% of acute myeloid leukemia(AML) patients have myeloid blast cells that express the CD33 surface antigen. This antigen also is present on the leukemic stem cells at least some patients with chronic myeloid leukemia(CML)and acute lymphoblastic leukemia(ALL). It is absent from normal hematopoietic stem cells and nonhematopoietic cells and tissues. Gemtuzumab is a humanized anti-CD33 antibody conjugated to calicheamicin, a potent anti tumor antibiotic derived from a bacterium. It is conditionally approved in the US for treatment of CD33+ AML in first relapse in patients over 60 years[Sievers et al.Journal of Clinical Oncology,2001]. Here we evaluate the efficacy and safety of Gemtuzumab -based regimens. The study population comprise 11 patients with CD33-positive refractory leukemia (determined as CD33-antigen expression in over 50% of leukemic blasts by bone marrow aspirates and immunophenotyping), including two with myeloid blast phase of CML, one with refractory ALL, two relapsed after Auto-stem cell transplantation(Auto-SCT). The median age was 47 years. Four cases who were over 60 years or after Auto-SCT treated with single agent. The other seven cases treated with mylotarg and cytotoxic agents, including mylotarg plus idarubine (MI); Gemtuzumab plus fludarabine, cytarabine, CsA(MFAC); or plus mitoxantrone, Ara-C (MMA).The overall response rate was 54% (6/11), with 36%(4/11) patients obtaining complete remission (CR) and 18% (2/11) achieving CRp.The median overall survival time after treatment was 4.8 months, and the median overall survival time after CR was 8.2 months.Two patients with myeloid blast phase of CML achieved CR with BCR/ABL(−), the survival time after CR was 5+months and 20+months respectively, but failed in second relapse. One patient received Allo-SCT after CR with refractory ALL is still alive at present (21months) with disease free. The median time to ANC recovery of 0.5×109/L was 15 days.The common adverse events was myelosuppression (100% Grade 4 neutropenia and thrombocytopenia).Significant non-hematologic toxicitics included infection(96%), infusion-related chills and fever (55%).Although hepatic dysfunction and mucositis were observed,they were generally infrequent and not severe(Grade 1–2).Six patients (55%) developed Hepatic veno-occlusive disease(VOD), four of them were either over 60 years old or received Auto-SCT before although they received only single agent mylotarg therapy, but it was transient and no one died from it. In conclusion, patients with CD33-positive refractory leukemia, Gemtuzumab -based regimens have a comparable response rate and offer a more favorable toxicity profile, expecially for the patients with myeloid blast phase of CML. It is also effective for the patient with refractory ALL. In the treatment, we should pay attention to the hepatic condition of ones who are over 60 years old or after stem cell transplantation, attemps to avoid and treat VOD are warranted. Above all, When patients with refractory leukemia got remission, allogenic-SCT should be done as soon as possible

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Subcutaneous Alemtuzumab (MabCampath) in Fludarabine-Refractory CLL (CLL2H Trial of the GCLLSG).

Blood ◽

10.1182/blood.v110.11.3120.3120 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3120-3120 ◽

Cited By ~ 9

Author(s):

Stephan Stilgenbauer ◽

Dirk Winkler ◽

Andreas Bühler ◽

Thorsten Zenz ◽

Silja Groner ◽

...

Keyword(s):

Overall Survival ◽

High Risk ◽

Survival Time ◽

Median Overall Survival ◽

Progression Free Survival ◽

Outpatient Basis ◽

Free Survival ◽

Overall Survival Time ◽

Median Overall Survival Time ◽

Grade Iii

Abstract Fludarabine-refractory CLL has a poor prognosis with a median overall survival time of less than 12 months despite salvage chemotherapy and intravenous alemtuzumab (Campath-1H) is the approved treatment based on a remission rate of 33% and a median survival time of 16 months (Keating et al., Blood 2002). The CLL2H trial of the GCLLSG was initiated to evaluate the subcutaneous application of 3 × 30 mg alemtuzumab weekly in fludarabine refractory CLL. The current analysis is based on 109 consecutive patients enrolled until completion of the trial in April 2006. Median age was 63 (36–81) years, 71% were male. A median number of 3 (1–9) prior lines of therapy had been given. Subcutaneous treatment was performed on an outpatient basis in all cases and had to be temporarily interrupted in 68 patients due to neutropenia (43%), anemia (6%), thrombocytopenia (3%), infections (40%, CMV reactivations 30%), and was stopped early in 63 cases due to insufficient response (44%), hematotoxicity (16%), infection (17%), and CMV reactivation (13%). The median alemtuzumab dose given was 722 (3–2203) mg. Toxicity was mostly grade I/II apart from hematotoxicity (grade III/IV anemia: 42%, thrombocytopenia: 52%, neutropenia: 54%) and grade III/IV infections (25%). After a median follow up time of 21.4 months, 56 deaths have occurred (due to progression 52%, infections 39%, not CLL related 9%). The overall response rate was 33% (CR 4%, PR 27%), the median progression free survival time was 7.7 months, and median overall survival time was 19.1 months. Genetic high-risk factors were present in the vast majority of cases (unmutated VH 66%, 17p–29%, 11q–19%, TP53 mutation 39%). Responses (CR or PR) were observed in 22% of VH unmutated, 24% of 11q-, 39% of 17p-, and 33% of TP53 mutated cases. Progression free survival and overall survival were not significantly different when comparing the genetic subgroups, particularly TP53 mutated, 11q-, and 17p- (see figure). In conclusion, subcutaneous alemtuzumab is feasible in an outpatient setting in a high-risk population of fludarabine-refractory CLL and appears to be of similar efficacy as by intravenous administration. Most importantly, genetic high risk subgroups with unmutated VH, 11q- or 17p- appear to respond to alemtuzumab. Figure Figure

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Contribution of intraoperative stimulation mapping to glioblastoma surgery within or adjacent to descending motor pathways: survival analysis and functional outcome comparison between two series in a single institution

10.21203/rs.3.rs-302485/v1 ◽

2021 ◽

Author(s):

Jimmy Ming-Jung Chuang ◽

Li-Han Lin ◽

Meng-Hsiang Chen ◽

Wei-Che Lin ◽

Cheng-Hsien Lu ◽

...

Keyword(s):

Overall Survival ◽

Survival Time ◽

Neurological Outcome ◽

Median Overall Survival ◽

Extent Of Resection ◽

Rank Test ◽

Positive Effects ◽

Overall Survival Time ◽

Significant Difference ◽

Median Overall Survival Time

Abstract Purpose Extensive resection probably confers a modest survival advantage in patients with glioblastoma. Studies have revealed the positive effects of intraoperative stimulation mapping (ISM) on the extent of resection, but no consensus for contribution of intraoperative stimulation mapping is reached. Methods This retrospective study enrolled two groups of patients who underwent surgery for motor-eloquent glioblastoma: the non-ISM group of 57 patients (surgery in 2008–2013) and ISM group of 13 patients (surgery in 2014–2015). The two groups and subgroups based on resection extent and postoperative additional neurological deficit were compared using Kaplan–Meier analysis and the log-rank test. Results Gross or near total resection (≥ 90% resection quality) was significantly more common in the ISM group than the non-ISM group (76.9% versus 24.6%; p = 0.001). The extent of resection was also significantly greater (90.5% ± 15.6% versus 64.6% ± 29.2%; p = 0.002). The neurological outcome in the ISM group was thus superior, but the two differences were not significant. The median progression-free survival time was significantly longer in the ISM group (22.0 ± 5.1 months vs 8.0 ± 1.0 months; p = 0.037) but a significant difference was not indicated in median overall survival time (22.0 ± 8.4 months vs 16.0 ± 2.2 months; p = 0.167). Conclusion ISM was discovered to lead to higher quality of resection and delayed recurrence. The neurological outcome and median overall survival time in the ISM group was thus superior, but the two differences were not significant. Trial registration number (for clinical trials) Nil

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High Efficacy and Good Tolerability with Rituximab In Vivo Purging Followed by High Dose Chemotheraphy and Autologous Peripheral Blood Stem Cell Transplantation (APBSCT) in Non-Hodgkin’s Lymphoma (NHL).

Blood ◽

10.1182/blood.v104.11.4626.4626 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4626-4626

Author(s):

Yuankai Shi ◽

Sheng Yang ◽

Xiaohong Han ◽

Peng Liu ◽

Xiaohui He ◽

...

Keyword(s):

Bone Marrow ◽

Overall Survival ◽

Complete Remission ◽

Minimal Residual Disease ◽

Median Time ◽

Residual Disease ◽

High Dose ◽

Platelet Recovery ◽

Minimal Residual

Abstract Purpose: High-dose chemotherapy (HDC) supported by APBSCT has been shown to be superior to standard therapy in NHL. However, many patients relapse due to minimal residual disease (MRD) in vivo or in the graft. Rituximab has the potential to clear both blood and bone marrow of malignant CD20+ cells, prompting this multicenter trial of in vivo purging with rituximab and HDC with APBSCT in China. Methods: Cyclophosphamide 4g/m2 was used as the mobilization regimen, CY/TBI, BEAM or CBV could be used as HDC at the discretion of the institution. Four infusions of rituximab (375 mg/m2) were given: one day before mobilization, one day before harvesting, one day before transplantation and on day 8 after transplantation. BCL-2/Ig-H translocation was measured as a marker of minimal residual disease in blood or bone marrow before mobilization and during transplantation using real-time quantitative PCR. Results: Thirty-one patients from 12 centers with histologically proven CD20+ NHL (28 aggressive, 3 indolent NHL) were enrolled. Twenty-four patients were previously untreated, and 7 patients had relapsed disease. Median yields of CD34+ cells and mononuclear cells were 5.9×106/kg and 4.4×108 /kg respectively. Median time to recovery of WBC >1.5×109/L, ANC >0.5×109/L and platelets >20×109/L after APBSCT was 10 days in each case. Median time to platelet recovery >50×109/L was 13 days. Generally, this therapeutic strategy was well tolerated with few side effects attribute to rituximab. All patients achieved a complete remission after APBSCT. At a median-follow-up of 12 months, overall survival and progression-free survival (PFS) are 87% and 73% respectively for all patients. In patients with aggressive NHL, overall survival and PFS are 85% and 73% respectively and in indolent NHL are 100% and 67% respectively. PFS and overall survival were slightly higher in previously untreated compared with relapsed patients (88% vs. 83% for PFS, 73% vs. 69% for overall survival). One of five 5 patients who were initially found to be PCR-positive and achieved PCR-negative status subsequently experienced progression accompanied by a return to PCR positivity. The remaining four patients are still in complete remission and are PCR negative. Conclusion: These results suggest that the regimen of rituximab combined with HDCT and APBSCT is effective and well tolerated for the treatment of patients with NHL.

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Maintenance treatment in relapsed canine lymphoma after a short L-CHOP protocol

Tierärztliche Praxis Ausgabe K Kleintiere / Heimtiere ◽

10.1055/a-1481-7066 ◽

2021 ◽

Vol 49 (03) ◽

pp. 185-194

Author(s):

Karin Troedson ◽

Nataliia Ignatenko ◽

Csilla Fejos ◽

Yury Zablotski ◽

Johannes Hirschberger

Keyword(s):

Overall Survival ◽

Complete Remission ◽

Adverse Events ◽

Survival Time ◽

Maintenance Treatment ◽

Canine Lymphoma ◽

Disease Free Interval ◽

Overall Survival Time ◽

Free Interval ◽

Disease Free

Abstract Objective A number of different rescue protocols for relapsed canine multicentric large-cell lymphoma have been described. The aim of this pilot study was to evaluate the efficacy of a maintenance treatment in dogs that experienced a second complete remission after a short L-CHOP-rescue protocol. Material and methods Included in the study were dogs experiencing the first lymphoma relapse during a treatment-free period which were treated with a short L-CHOP protocol, achieved a complete remission and were afterwards treated with a continuous maintenance phase (MP) protocol. The L-CHOP protocol consisted of weekly treatments, with at least 3 additional treatments following complete remission. Thereafter the MP protocol with 2-week treatment intervals was conducted. It consisted of alternating oral home administration of different alkylating agents and one intravenously administered cytotoxic agent of a different mechanism of action. The dogs were presented either every 4 or 6 weeks for intravenous treatment and at this time a complete blood count was performed. The durations of the first remission, disease-free interval and overall survival time were evaluated. Results A total of 20 dogs were included in the study. A median of 7 weekly applications were given before the treatment was switched to the MP protocol. During MP, 14 dogs were treated intravenously every 6 weeks and 6 dogs every 4 weeks. Haematological adverse events were mainly mild. During the L-CHOP-protocol, one septic event occurred, and 2 dogs were hospitalized due to gastrointestinal adverse events. No patient required hospitalization during the MP. Fifteen dogs completed at least one cycle in the MP and a median of 8.5 chemotherapeutic treatments were administered. The median disease-free interval was 264 days and the median overall survival time was 737 days. Conclusion and clinical relevance The protocol was generally well tolerated. Since 5 patients showed disease progression during the first cycle of the MP, dogs should ideally be evaluated for minimal residual disease before being switched to the MP. The case number in the presented study was low and the treatment relatively heterogeneous. Therefore, more dogs have to be treated with the proposed protocol before general recommendations can be made.

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Is Intermediate-Dose Cytarabine a Good Control for Patients with Relapsed or Refractory Acute Myeloid Leukemia?

Blood ◽

10.1182/blood.v128.22.3991.3991 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3991-3991 ◽

Cited By ~ 1

Author(s):

Sarah Bertoli ◽

Noemie Gadaud ◽

Suzanne Tavitian ◽

Audrey Sarry ◽

Emilie Bérard ◽

...

Keyword(s):

Overall Survival ◽

Complete Remission ◽

Board Of Directors ◽

Median Overall Survival ◽

Daily Practice ◽

Advisory Committees ◽

Salvage Regimen ◽

Platelet Recovery ◽

Refractory Acute Myeloid Leukemia ◽

Refractory Diseases

Abstract Intermediate dose cytarabine (IDAC) defined by daily intravenous bolus of 1g/m² during 5 days has been recently defined as the standard control arm in phase 3 placebo-controlled randomized trials for patients with relapsed or refractory acute myeloid leukemia (R/R AML). In these trials assessing clofarabine/IDAC (CLASSIC-1 study, Faderl S et al., JCO 2012) or vosaroxin/IDAC (VALOR study, Ravandi F. et al., Lancet Oncol 2015) vs placebo/IDAC, complete remission rates and median overall survival with placebo/IDAC were 17.8%/18.9% and 6.3/6.1 months in the CLASSIC-1 and VALOR studies, respectively. However, the dose-intensity of this IDAC regimen remains questioned in routine practice since many centers still use higher doses of cytarabine often in combination with an anthracycline and a third drug including fludarabine, etoposide or gemtuzumab ozogamycin (FLAG-ida, MEC or MIDAM regimen for example) although these regimen have proved little efficacy and higher toxicity. We assessed the outcome of R/R AML patients that fulfilled main VALOR inclusion criteria consecutively treated in our center with intensive salvage regimen. All patients with a diagnosis of AML in first relapse or with refractory disease were eligible for this study. Acute promyelocytic leukemia were excluded. Relapse was defined as re-emergence of at least 5% leukemia blasts in bone marrow or at least 1% blasts in peripheral blood 90 days to 24 months after first complete remission or complete remission with incomplete platelet recovery. Refractory AML was defined as persistent disease at least 28 days after initiation of induction therapy, or relapse less than 90 days after first complete remission (CR) or CR with incomplete platelet recovery (CRi). All patients have received previous induction therapy with an anthracycline. Salvage regimen used were mainly cytarabine 3 g/m²/12h, d1-4 plus idarubicine 12 mg/m²/d, d1-3 or dauno 60 mg/m²/d, d1-2 or amsacrine 200 mg/m²/d, d1-3; less frequently MiDAM (mitoxantrone 12mg/m² d1-3, cytarabine1 g/m²/12h d1-5, GO 4-6mg/m², d4) or FLAG-Ida. Cytarabine dose for patients >60 was reduced to 1g/m²/12h, d1-5. We found, in our database, 151 R/R AML according to VALOR criteria treated between 2000 and 2013: 72 patients (48%) had refractory diseases (primary refractory: n=60, 40% and relapse less than 90 days after CR: n=12, 8.0%) and 79 (52%) had relapsed (early relapse more than 90 days after CR and less than one year: n=52, 66%; late relapse between one and two years: n=27, 34%). Patients characteristics were as follows: 85 (56%) were male, median age was 48 years (interquartile range [IQR], 36-60.5; 38 (27%) were 60 years or older). Cytogenetics at diagnosis was favorable in 18 (12%); intermediate in 93 (62%); adverse in 38 (25%) or unknown in 2 (1%) patients, respectively. They were treated as first line therapy with one (42%) or two cycles (58%). Early death rates at day 30 and day 60 were 7% and 17% in the whole cohort; 6% and 12% in younger patients and 12% and 29% in patients 60 years or older. Combined CR rate (defined as CR and CRi) was 53% for the whole cohort, and 57%/42%/56%/52%/63%/50% for <60 years/≥60 years/relapses/early relapses/late relapses/refractory diseases respectively. Allogeneic-SCT was performed in 25 out of 80 patients (31%) having achieved CR after salvage treatment. Median overall survival (OS) was 8 months for the whole cohort and 9.2/5.0/7.7/7.5/13.6/9.2 months for <60 years/≥60 years/relapses/early relapses/late relapses/refractory diseases respectively. Using VALOR inclusion criteria, age is the main factor that discriminate R/R AML patients selected for clinical trials using IDAC as control arm compared to patients of daily practice. Thus, those patient populations remain hardly comparable. However, as far as CR is concerned, IDAC seems suboptimal as compared to higher-intensity regimen used in daily practice. Yet, this higher CR rates do not translate into a significant gain in survival since median OS remains close to that of IDAC with the possible exception of refractory patients who seem to benefit from higher-intensity regimen. Thus, although unsatisfactory, IDAC could be considered as a fair control arm for overall survival endpoint especially in patients older than 60 year of age. Table Table. Disclosures Tavitian: Novartis: Membership on an entity's Board of Directors or advisory committees. Huguet:Pfizer, Novartis, BMS, Ariad, Jazz, Amgen: Membership on an entity's Board of Directors or advisory committees. Recher:Celgene, Sunesis, Amgen, Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene, Sunesis, Amgen, Novartis, Chugai: Research Funding.

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ATIM-46. A MULTICENTER, PHASE I, TRIAL OF RADIATION, TEMOZOLOMIDE AND RRx-001 FOLLOWED BY MAINTENANCE TEMOZOLOMIDE WITH OR WITHOUT RRx-001 IN NEWLY DIAGNOSED GLIOBLASTOMA PATIENTS

Neuro-Oncology ◽

10.1093/neuonc/noz175.044 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi11-vi12

Author(s):

Robert Aiken ◽

Howard Fine ◽

Nicholas Butowski

Keyword(s):

Overall Survival ◽

Confidence Interval ◽

Survival Time ◽

Median Time ◽

Lower Limit ◽

Dose Range ◽

Newly Diagnosed ◽

Overall Survival Time ◽

Newly Diagnosed Glioblastoma

Abstract BACKGROUND RRx-001 is an aerospace-derived radiochemosensitizer with minimal toxicity. The purpose of this trial was to establish the safety of RRx-001 plus radiotherapy and temozolomide and to look for signals of enhanced anti-tumor activity in patients with newly diagnosed glioblastoma. METHODS In this non-randomized trial called G-FORCE-1 (NCT02871843), 18 newly diagnosed, histologically verified glioblastoma patients were enrolled. The treatment plan included 6 weeks of temozolomide and radiotherapy with RRx-001 followed by maintenance temozolomide with or without RRx-001. Four cohorts of 3 patients received intravenous RRx-001 at doses of 0.5,1,2, or 4 mg/week during radiotherapy only. An additional two cohorts of 3 patients received 4 mg/week of RRx-001 during radiotherapy and 0.5 mg/week of RRx-001 during temozolomide maintenance. RESULTS There were no grade 3 or 4 dose-limiting toxicity events (DLT) that appeared related to RRx-001 for the dose range of 0.5 to 4 mg/week. A maximum tolerated dose was not defined. The main adverse event related to RRx-001 was injection-site reaction. The overall response rate was 16.7% (3 PR out of 18) pending confirmation since pseudoprogression was prevalent, and the disease control rate was 61.1% (3 PR, 8 SD out of 18). The median time to tumor progression (95% confidence interval lower limit of 9.2 months to NR) and the median overall survival time (95% confidence interval lower limit of 12.9 months to NR) have not been reached after a median follow-up time of 10.3 months (range: 2.7 to 25 months.). CONCLUSION RRx-001 was well tolerated with concurrent temozolomide and radiotherapy and with temozolomide maintenance in 18 newly diagnosed glioblastoma patients. The primary objective to determine the MTD of RRx-001 was not met, since no DLTs occurred. The median time to progression and overall survival time have not been met after a median follow up time of 10.3 months.

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Immunohistochemical Detection of CD95L (Fas Ligand) in Mantle Cell Lymphoma: A Prognostic Factor for Clinical Outcome.

Blood ◽

10.1182/blood.v104.11.4566.4566 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4566-4566

Author(s):

Carsten Schrader ◽

Peter Meusers ◽

Guenter Brittinger ◽

Dirk Janssen ◽

Reza Parwaresch ◽

...

Keyword(s):

Overall Survival ◽

Mantle Cell Lymphoma ◽

Survival Time ◽

Median Overall Survival ◽

Fas Ligand ◽

Clinical Course ◽

Cell Lymphoma ◽

Immunohistochemical Detection ◽

Overall Survival Time ◽

Mantle Cell

Abstract Mantle cell lymphoma is a malignant lymphoma associated with a relatively aggressive clinical course and a median overall survival time of 3–4 years. Proliferation indices are important prognostic factors in the clinical outcome. We investigated immunohistochemically the expression of the apoptotic marker CD95L (Fas Ligand) in relation to the clinical course. Biopsy specimen from 69 untreated patients enrolled in two multicenter prospective trials were investigated immunohistochemically with monoclonal antibodies against CD20, CD5, CD3, CD23, cyclin D1, CD95L. The CD95L expression was analyzed into three groups: negative, weak positive and strong positive. The expression was compared with the overall survival data analysed according to Kaplan and Meier. Patients with mantle cell lymphoma that had negative and weak positive CD95L expression had a median overall survival time of 32.0 months compared to 18.3 months for patients with a strong CD95L expression. The Kaplan-Meier analysis showed a significant difference in the overall survival time between the patients with strong CD95L expression and the group of patients with negative or weak positive tumor cells (p<0.0038). Based on these findings, the immunohistochemical detection of CD95L in mantle cell lymphoma is a prognostic factor.

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