Terms Of Complete Response Rate Research Articles

Decisional Role of Interim PET in Relapsed/Refractory Classical Hodgkin Lymphoma Treated with Begev Chemotherapy As First Salvage

Achievement of complete response (CR) before autologous stem cell transplantation (ASCT) is one of the main predictive factors of outcome in patients (pts) affected by relapsed/refractory (R/R) classical Hodgkin Lymphoma (cHL) eligible to high-dose chemotherapy. The predictive role of interim PET during salvage treatment is well established in pts treated with IGEV or ICE but has not been investigated in pts receiving BEGEV (Bendamustine, Gemcitabine and Vinorelbine) as first salvage treatment. With the aim to investigate the predictive value of PET after 2 cycles of BEGEV (PET2) in terms of CR rate and survival, we retrospectively collected data of consecutive R/R cHL pts eligible to ASCT treated from 2011 to 2021 in 3 Italian centres. PET scans were locally evaluated using Deauville Score (DS), considering a score 1-3 negative and consistent with CR. Early relapse was defined as a relapse occurring ≤12 months from the end of first-line therapy. Survival functions were calculated from the date of initiation of BEGEV chemotherapy. Ninety-four cHL R/R pts receiving BEGEV as first salvage therapy were included. Fifty-one (54.3%) pts were male. First-line therapy consisted in 2 to 6 ABVD chemotherapy cycles accordingly to clinical stage followed by consolidation radiotherapy (RT) in 24 (25.5%) pts. At relapse, median age was 37 years (range: 18-71 years), 51 (54.3%) pts were in stage III-IV, 16 (17%) pts had B symptoms and 34 (36.2%) pts had extranodal involvement (EI). Fifty-one (54.3%) pts were primary refractory, 23 (24.5%) pts had an early and 20 pts (21.3%) a late relapse. PET2 was performed in 86 (91.5%) pts, and resulted negative in 61 (70.9%) and positive in 25 (29.1%) pts (DS 4 in 17 and DS 5 in 8 pts). PET after 4 BEGEV cycles (PET4) was performed in 82 (87.2%) pts and resulted negative in 63 (67%) and positive in 19 (20.2%) pts (DS 4 in 10 and DS 5 in 9 pts). Complete response after 4 BEGEV was achieved in 55/61 (90.2%) PET2 negative pts and 7/25 (28%) PET2 positive pts. Considering pts evaluable for both PET2 and PET4, PET2 positive pts had a statistically lower probability to achieve CR at PET4 when compared to PET2 negative pts (Odds ratio: 0.07, CI 95%: 0.02-0.29; p<0.00001). Autologous SCT was performed in 81 (86.2%) pts, following BEGEV in 56 pts (69.1%) and after further salvage treatments in 25 (30.9%). A post-ASCT consolidation strategy was performed in 24 (29.6%) pts, and consisted in RT in 18 pts and brentuximab-vedotin in 6 pts. Ten pts received an allotransplant: in 3 cases allotransplant was planned in a tandem modality, while in 7 cases was performed after further salvage treatments for post-ASCT relapse or progression. With a median follow-up of 36.4 months (interquartile range: 20.1-50.0), 3-years overall survival (OS), progression-free survival (PFS) and event-free survival (EFS) for the whole study population were 91.7%, 61.6% and 53.9%, respectively. No significant differences in OS were detected according to PET2 result. Conversely, both 3-years PFS and EFS were significantly superior in PET2 negative vs PET2 positive pts: 3-years PFS was 61.6% (CI 95%: 52.1-72.9) in PET2 negative and 43.6% (CI 95%: 27.9-68.4) in PET2 positive pts (p=0.0004) (Figure 1), while 3-years EFS was 71% (CI 95%: 59.8-84.3) and 23.3% (CI 95%: 11.3-48.1), (p<0.001). Univariable analysis of PFS was performed using Cox regression model and evaluating adverse risk factors at relapse (primary refractory and early relapse vs late relapse, presence of EN involvement and B-symptoms) and demonstrated a significantly inferior PFS for pts with EI (HR 1.94, CI 95% 1.01-3.74, p=0.47) and primary refractory disease or early relapse (HR 2.02, CI 95%: 1.01-4.04, p=0.047), but not for pts with B symptoms (HR 1.05, CI 95%: 0.43-2.51, p=0.9). Multivariate Cox regression model of PFS evaluating presence of EI at relapse (HR 1.55 , CI 95%: 0.74-3.25, p=0.240), time to relapse (primary refractory and early relapse vs late relapse, HR 0.84 (CI 95%: 0.36-1.96, 0.683) and PET2 result, identified PET2 positivity as the only predictive factor for PFS (HR 3.24, CI 95%: 1.55-6.77, p=0.002). In conclusion, R/R cHL pts with PET2 positive during BEGEV salvage treatment had a lower probability to achieve CR after 2 additional BEGEV cycles and a significantly inferior PFS, and could benefit from early exposure to new therapeutic strategies before ASCT. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Lower Relapses Rate With Infliximab Versus Adalimumab in Sight-Threatening Uveitis: A Multicenter Study of 330 Patients

PURPOSETo compare the relapse rate of sight-threatening noninfectious uveitis (NIU) in patients treated with infliximab (IFX) or adalimumab (ADA). DESIGNObservational retrospective multicenter study. METHODSA total of 330 patients (median age, 36 years; interquartile range, 27-54), 45.2% men) with sight-threatening NIU (ie, retinal vasculitis and/or macular edema) treated with anti−tumor necrosis factor [TNF]−α agents (IFX intravenously at 5 mg/kg at weeks 0, 2, 6, and every 4 to 6 weeks or ADA subcutaneously at 80 mg, then 40 mg every 2 weeks). Data were obtained retrospectively from patients’ medical records. Main outcome measures were relapse rate, complete response of NIU, corticosteroid sparing effect, and safety. RESULTSMain etiologies of uveitis included Behçet disease (27%), idiopathic juvenile arthritis (5.8%), and sarcoidosis (5.5%). The estimated relapse rate at 6 months after introduction of biological agents was 13% (95% CI = 0.009-0.16). IFX was associated with less relapse risk than ADA (hazard ratio [HR] = 0.52, 95% CI = 0.36- 0.77, P = .001). ADA and IFX were comparable in terms of complete response rate of NIU as well as corticosteroid-sparing effect. Behçet disease was associated with higher odds of complete response (HR = 2.04, 95% CI = 1.16 -3.60, P = .01] and lower relapse rate (HR = 0.53, 95% CI = 0.33-0.85, P = .009) than other causes of NIU with anti−TNF-α agents. CONCLUSIONSIn sight-threatening NIU, IFX seems to be associated with a lower relapse rate than ADA.

The equivalency study of novel current standard 3-drugs combination regimen (ondansetron, dexamethasone and olanzapine) to netupitant containing regimen for preventing high dose cisplatin induce nausea and vomiting treatment, double blind placebo control trial.

12100 Background: Prevention of chemotherapy-induced nausea and vomiting (CINV) is vital in cancer treatment. Here, we compared the efficacy of netupitant-containing regimen; composed of NEPA, dexamethasone, and olanzapine (NEPAs), which is recommended for preventing CINV from high-emetogenic chemotherapy (HEC) to standard 3-drugs; ondansetron, dexamethasone, olanzapine for preventing CINV from high-dose cisplatin (≥75 mg/m2). Methods: This randomized, double-blind, placebo-control trial randomly assigned untreated patients who were received high-dose cisplatin in a 1:1 ratio to either NEPAs or standard 3-drugs combination regimen. Dose of dexamethasone in NEPAs regimen was modified after preplanned interim safety analysis to increase from 4 to 8 mg per day on days 2-4. The stratification factors were concurrent treatment with radiation and sex. The primary endpoint was the overall complete response (CR) rate defined as no vomiting and no use of rescue antiemetic drugs. The protocol allowed crossover to NEPAs for those who received standard 3-drugs and did not reach CR in the first cycle. We collected outcome in the first 2-cycle of treatment. Results: Between January 2019 and December 2020, hundred patients were randomly assigned to either NEPAs (n = 51) or in-house standard 3-drugs (n = 49). Demographic characteristics were well-balanced in both arms. Total events in both arms were 101 events for NEPAs and 78 events for standard 3-drug. Overall CR rate were 70% and 69% in NEPAs and standard 3-drugs, ( p-value 0.87) respectively. According to emesis phase, CR in acute (0- 24 hrs.) and delay phase (24-120 hrs.) were not different in both arms; 91% vs. 89% and 72% vs. 71% in NEPAs and standard 3-drugs respectively. However, mean nausea VAS score was significantly lower in NEPAs (1.63 vs. 2.02, p-value = 0.001). The ad hoc subgroup analysis shown similar efficacy between before and after protocol amendment of NEPAs regimen in term of delay emesis CR rate; 70.9% vs. 73.9% ( p-value 0.73). Conclusions: The NEPA-containing regimen did not show superiority compare to standard 3-drug in terms of complete response rate for CINV prevention among patients receiving high-dose cisplatin. Furthermore, the dexamethasone dosage of 4 vs. 8 mg per day might not affect the efficacy of delay emesis of the NEPAs regimen. Clinical trial information: TCTR20190508001. [Table: see text]

Time to review the role of intraluminal brachytherapy for dose escalation after concurrent chemoradiation in cancer esophagus: A retrospective audit.

e16054 Background: Intraluminal brachytherapy (ILBT) for dose escalation after concurrent chemoradiation (CRT) in cancer esophagus is not routinely practiced. This is particularly attributable to radiotherapy toxicity in terms of strictures and fistulas. Cancer esophagus has poor locoregional control and overall survival rates in comparison to head and neck cancers. Dose escalation may be an option to counteract the high failure rates. Methods: A retrospective analysis was conducted for esophageal cancer patients treated between 2008 to 2016 planned for radical CRT to a minimum dose of 59.4 Gy in 33 fractions along with concurrent cisplatin 35 mg/m2 and 5 FU 375 mg/m2 on weekly basis. Further, the patients who received dose escalation after external beam radiotherapy (EBRT) completion by ILBT to a dose of 6 Gy in a single fraction to the pre EBRT volume were also analysed. The patient, tumor, treatment characteristics along with response rates, survival outcomes, and toxicities were evaluated and compared between the two groups - the patients who received ILBT and those who did not. Statistical significance between variables was analysed with the Chi-Square or Fischer’s exact test and t-test. Survival analysis was done by Log-Rank test. The analysis was done on a worst-case scenario basis where the patients lost to follow-up were considered dead. Results: The total number of patients treated by CRT was 69, out of which 13 patients received ILBT for dose escalation. The median age was 60 years (Range - 40 to 80 years) and the male: female ratio was 1.09, mean tumor length was 6.4 ± 2.4 cms (Range-1.5-12 cms). The commonest tumor site was the middle third observed in 58% patients. The median EBRT dose was 59.4 Gy (Range- 9 to 63 Gy). The median concurrent chemotherapy cycles were 5. The median follow-up period was 15 months (range 1-100 months). In terms of complete response rates, there was a trend towards significant improvement in patients receiving ILBT compared to those receiving EBRT alone (84.61% versus 57.49%, p=0.07). Also, the overall survival (OS) was significantly higher in the ILBT group (45.31 months versus 19.20 months; p = 0.005). The other patient, tumor, and treatment characteristics analyzed showed no significant impact on OS. There was no significant difference in the incidence of strictures (p=0.206) and severity (p=0.764) of strictures amongst both the groups. Grade ≥3 late toxicity was reported in 10 patients (17.85%) receiving EBRT alone and in 3 patients (23.07%) receiving ILBT. None of the patients receiving ILBT developed a fistula. Conclusions: The present study reveals a dramatic increase in OS by dose escalation with ILBT. The limitations of the present study were a small sample size and a lesser number of patients in the ILBT group. Recapitulating the concept of ILBT to increase the local tumoricidal dose may improve the survival rates.

Pooled analysis of 115 patients from updated data of Epitopes-HPV01 and Epitopes-HPV02 studies in first-line advanced anal squamous cell carcinoma.

Aims:The addition of docetaxel to cisplatin and 5-fluorouracil (DCF) has shown promising efficacy in advanced squamous cell carcinoma of the anus (SCCA). Preliminary results of Epitopes-HPV01 study showed a high rate of long-lasting complete response to DCF. The prospective, multicenter, Epitopes-HPV02 trial then confirmed the high efficacy of the modified DCF (mDCF) regimen in terms of complete response rate and long-term survival in metastatic or non-resectable locally advanced recurrent SCCA. Here, we present updated results of the Epitopes-HPV01 and Epitopes-HPV02 studies.Patients & methods:Epitopes-HPV01 is a prospective study performed by the regional cancer network of Franche-Comté, France. Epitopes-HPV02 is a phase II study supported by two French collaborative oncological groups, performed in 25 centers. Both studies included patients with metastatic, or with unresectable local recurrent SCCA, treated with DCF regimen.Results:In Epitopes-HPV01, 51 patients were enrolled between September 2012 and January 2019, and 49 patients were included for analysis; while 69 patients were included between September 2014 and December 2016 in Epitopes-HPV02, and 66 patients for analysis. Pooled analysis of 115 patients showed a median progression-free survival of 12.2 months [95% confidence interval (CI) 10.6–16.1] [11.0 months (9.3–16.0) in -HPV02, and 15.6 months (11.2–34.5) in -HPV01, (p = 0.06)]. The median overall survival was 39.2 months (26.0–109.1) [36.3 in -HPV02 (25.2–NR), and 61.1 months (21.4–120.0) in -HPV01 (p = 0.62)]. Objective response rate was 87.7% (90.9% in -HPV02 and 83.3% in -HPV01) with 40.3% of complete response (45.5% in -HPV02 and 33.3% in -HPV01). No differences were observed between standard DCF (n = 54) and mDCF (n = 58) in terms of OS (p = 0.57) and PFS (p = 0.99). 5-years PFS and OS rates were 24.5% and 44.4%, respectively, in the whole population. No treatment-related death was observed.Conclusion:Updated results of Epitopes-HPV01 and 02 studies, as well as the pooled analysis, confirm mDCF as a standard treatment in patients with advanced SCCA.

AMAFRICA, a patient-navigator program for accompanying lymphoma patients during chemotherapy in Ivory Coast: a prospective randomized study

BackgroundPrevious studies have indicated that accompanying socially underserved cancer patients through Patient Navigator (PN) or PN-derived procedures improves therapy management and reassurance. At the Cancer Institute of Toulouse-Oncopole (France), we have implemented AMA (Ambulatory Medical Assistance), a PN-based procedure adapted for malignant lymphoma (ML) patients under therapy. We found that AMA improves adherence to chemotherapy and safety. In low-middle income countries (LMIC), refusal and abandonment were documented as major adverse factors for cancer therapy. We reasoned that AMA could improve clinical management of ML patients in LMIC.MethodsThis study was set up in the Abidjan University Medical Center (Ivory Coast) in collaboration with Toulouse. One hundred African patients were randomly assigned to either an AMA or control group. Main criteria of judgment were refusal and abandonment of CHOP or ABVD chemotherapy.ResultsWe found that AMA was feasible and had significant impact on refusal and abandonment. However, only one third of patients completed their therapy in both groups. No differences were noted in terms of complete response rate (CR) (16% based on intent-to-treat) and median overall survival (OS) (6 months). The main reason for refusal and abandonment was limitation of financial resources.ConclusionAltogether, this study showed that PN may reduce refusal and abandonment of treatment. However, due to insufficient health care coverage, its ultimate impact on OS remains limited.

Advanced Stage Hodgkin’s Lymphoma Has More Aggressive Characteristics but Similar Outcome in HIV-Infected Than in HIV-Negative Patients in the Combination Antiretroviral Therapy Era

Background: In the combination antiretroviral therapy (cART) era the prognosis of HIV-infected patients with Hodgkin’s lymphoma (HL) approaches to that of the HIV-negative population. Treatment of advanced stage HL with ABVD has been shown feasible and effective in HIV patients. However, there is scarce information about the impact of cART on clinical and biological characteristics of HIV-related HL as well as on its prognosis.Aim: To compare the clinical and biological characteristics and outcome of patients with advanced stage HL treated with ABVD according to HIV-status in the cART era.Methods: Two groups of patients with advanced stage HL treated with ABVD were studied. The first group consisted of 63 HIV-infected patients diagnosed with HL in the cART era in 15 Spanish hospitals, and the control group included 31 HIV-negative patients diagnosed in the same period in a single institution. Demographic, clinical and biological data were collected, and complete response rate (CRR), disease-free survival (DFS) and overall survival (OS) were calculated. Then, HIV-infected patients were stratified according to whether they started cART therapy before or concomitantly with chemotherapy. Survival analyses were performed using the Kaplan-Meier method and compared using the log-rank test. The Cox regression proportional hazards model was used for multivariate analyses. Significance level was established at p<0.05.Results: The HIV-infected group showed a higher percentage of males (p=0.001), a higher serum LDH level at diagnosis (p=0.002); and non-significantly, worse ECOG performance status (p=0.05) and more extranodal areas affected (p=0.066). However, the percentage of patients with low Hasenclever score (<3 points) was similar in both groups (p=0.794). The most common HL subtype in HIV-negative patients was nodular sclerosis HL (58%) followed by mixed cellularity (26%), while in HIV-infected population the most common subtype was mixed cellularity (40%), followed by nodular sclerosis (29%).There were no differences in CRR between the two groups (89% in HIV-infected vs. 87% in HIV-negative, p=1). Furthermore, with a median follow-up of 8.7 years, there were no differences in OS and DFS: 10-year OS 75% (95%CI, 64%-86%) in HIV-infected vs. 67% (50%-84%) in HIV-negative (p=0.674); 10-year DFS 74% (60%-88%) in HIV-infected vs. 64% (42%-86%) in HIV-negative (p=0.196). The only variable associated with a worse OS in the entire series was elevated serum LDH at diagnosis (p=0.047). Low Hasenclever score was not a prognostic factor for OS. No variable was associated with DFS.In the HIV-infected group, CD4+ cell count at diagnosis (<200/µL vs. >=200/µL) and undetectable viral load were not associated with different CRR (p=0.688 and 0.188, respectively). Furthermore, no lymphoma-related variables were associated with DFS or OS.Patients who started cART simultaneously (s-cART) with chemotherapy and those who started it previously (p-cART) were comparable in their baseline characteristics except for viral load (undetectable in 50% of patients in the p-cART group vs. 0% in the s-cART group, p=0.001), whereas there were no differences in CD4+ cell count at diagnosis. The prognosis of the 2 groups was similar in terms of CRR and DFS, but s-cART patients showed a trend towards a better OS: 10-year OS 70% (95%CI, 57-83%) in p-cART vs. 92% (77-100%) in s-cART, p=0.072).Conclusion: Advanced stage HL is still associated with more aggressive features in HIV-positive than HIV-negative patients in the cART era. However, HIV infection is no longer a negative prognostic factor in patients with HL treated with ABVD.This work was supported in part by grants EC11-041 and RD12/0036/0029 RTICC from “Instituto Carlos III” Spain and 2014 SGR225 (GRE) from Generalitat de Catalunya, and by Josep Carreras International Foundation. DisclosuresNo relevant conflicts of interest to declare.

P2-27-2 - Examination of 5Ht3 Receptor Antagonists for Cinv Induced by Tc Therapy in Patients with Gynecologic Cancers

Background: Chemotherapy-induced nausea and vomiting (CINV) often disturbs treatment completion, and various actions have been carried out in many facilities to prevent CINV. Our department of Gynecology uses 5HT3 receptor antagonists such as granisetron 3mg (GRA) i.v. or palonosetron 0.75mg (PALO) i.v. to prevent CINV of CBDCA + PTX (TC) therapy. In this analysis, we retrospectively investigated which drug was superior in CINV prevention by drug management instruction operations and reviewing of the medical records.Methods: Antiemetic effect of GRA and PALO in terms of Complete Response rate (CR rate: no emesis and no rescue medication) was evaluated. And Complete Control rate (CC rate: no emesis and no rescue medication and no more than mild nausea) and Total Control rate (TC rate: no emesis and no rescue medication and no nausea) were also evaluated. In addition, CR, CC and TC rate in each periods as overall phase (0-120 h), acute phase (0-24 h), delayed phase (24-120 h) after postchemotherapy were evaluated.Results: Thirty-two patients with gynecologic cancers who received TC therapy from January 2013 to December 2013 in our institution were included in the efficacy analysis: 16 patients in the GRA group and 16 patients in the PALO group. The median dose of CBDCA:PTX were 700:260 (mg/body) in the GRA group and 680:260 (mg/body) in the PALO group. The CR rates of GRA/PALO group were 69/81% in overall phase, 94/100% in acute phase, 69/81% in delayed phase. The CC rates were 56/81% in overall phase, 94/100% in acute phase, 56/81% in delayed phase. The TC rates were 50/81% in overall phase, 94/100% in acute phase, 50/81% in delayed phase.Conclusion: It was suggested that as 5HT3 antagonist, PALO was preferable to GRA in preventing CINV induced by TC therapy in this retrospective analysis. Using PALO is considered to be recommended especially for the TC therapy as a result of this analysis.

The combination of CO2 laser vaporation and photodynamic therapy in treatment of condylomata acuminata

The aim of this study was to investigate the effectiveness of CO2 laser vaporation and topical PDT combination on condylomata acuminate (CA) located in the perianal and external genital area. A total of 119 patients (perianal CA=52 cases and external genital CA=67 cases) with at least one CA lesion >2mm were treated with monopulse CO2 laser followed by topical ALA-PDT. PDT was repeated till complete response was achieved. Approximately half of the patients only needed one session of PDT treatment and another half needed multiple PDT treatments to achieve complete response. During the 6-month follow-up 7.1% of patients relapsed. In terms of complete response rate and recurrence rate there were no statistical differences between perianal and genital groups. No severe adverse effects were observed. CO2 laser vaporation plus ALA-PDT is a highly effective modality for treating CA.

Peripheral T-Cell Lymphomas (PTCL) Treated With Or Without Upfront Autologous Stem Cell Transplantation: Results Of a Retrospective Single Center Analysis

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of rare diseases, characterized by an aggressive behavior and a poor clinical outcome. High-dose therapy followed by autologous stem cell transplantation (ASCT) has been used as salvage and upfront treatment with conflicting results. However, no standard therapy has so far been established due to the lack of randomized studies.The records of 54 untreated patients with a confirmed diagnosis of PTCL managed at our Institute between 2001 and 2011 were reviewed. The histologic subtypes were: 37 (68%) peripheral T-cell lymphomas unspecified (PTCL-U), 13 (24%) anaplastic large cell lymphomas (ALCL), of which 4 (30%) ALK-positive, 2 (4%) angio-immunoblastic lymphomas (AITL) and 2 (4%) enteropathy-associated T-cell lymphomas (EATL). The clinical characteristics were: median age 56 years (range 18-79); 40 men and 14 women; 13 (24%) and 41 (76%) patients were, respectively, in Ann Arbor stages I-II and III-IV. An elevated serum LDH was present in 33% of patients, 48% had B symptoms and 24% had a bone marrow involvement. The ECOG performance status was 2-3 in 28% of patients. According to the International Prognostic Index (IPI) and the prognostic index for T-cell lymphomas (PIT), 11% and 22% were classified as low risk, 30% and 33% as low-intermediate risk, 12% and 33% as high-intermediate risk and 29% and 12% as high risk, respectively. CHOP-like regimens were given to 32 (59%) patients, 14 of whom received the CHOEP regimen. The remaining 22 (41%) patients were treated with more intensive third generation regimens (MACOP-B like). ASCT was planned as upfront consolidation therapy for 16/54 (30%) patients.A complete response (CR) was obtained in 30/54 (55.5%) patients, a partial response in 7 (13%), while 17 (31.5%) patients showed a lymphoma progression during induction therapy. No difference in terms of CR rate was observed between the CHOP-like and MACOP-B-like regimens. At a median follow-up of 19 months (range 3-138), the 5-years OS and 5-years PFS were 32% (95% CI 25.3-38.5) and 27% (95% CI 20.2-34.5), respectively. At univariate analysis, bone marrow involvement (p=0.003), PIT high risk group (p<0.001) and lymphocytopenia (p=0.06) predicted a shorter PFS. Five of 16 (31%) patients did not receive the planned ASCT consolidation due to early progression. Patients who received an ASCT as consolidation therapy presented a slightly better 5-year PFS than patients treated with chemotherapy alone (95% CI 37.7% vs 25%; p=0.08).The prognosis of PTCLs remains poor despite the use of intensive chemotherapy regimen including upfront ASCT. More active induction chemotherapy regimens, including novel agents, should be designed in an attempt to increase the quality of response before ASCT consolidation therapy. Disclosures:No relevant conflicts of interest to declare.

Therapeutic plasma exchange in patients with thrombotic thrombocytopenic purpura: A retrospective multicenter study

Thrombotic thrombocytopenic purpura (TTP) is a particular form of thrombotic microangiopathy typically characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological abnormalities, and renal dysfunction. TTP requires a rapid diagnosis and an adapted management in emergency. Daily sessions of therapeutic plasma exchange (TPE) remain the basis of management of TTP. Also, TTP is a rare disease that is fatal if it is not treated. TPE has resulted in excellent remission and survival rates in TTP patients. AimWe aimed to present our experience in 163 patients with TTP treated with TPE during the past 5years from 10 centers of Turkey. Patients and methodsOne hundered and sixty-three patients with TTP treated with TPE during the past 5years from 10 centers of Turkey were retrospectively evaluated. TPE was carried out 1–1.5times plasma volume. Fresh frozen plasma (FFP) was used as the replacement fluid. TPE was performed daily until normalization of serum lactate dehydrogenase (LDH) and recovery of the platelet count to >150×109/dL. TPE was then slowly tapered. Clinical data, the number of TPE, other given therapy modalities, treatment outcomes, and TPE complications were recorded. ResultsFifty-eight percent (95/163) of the patients were females. The median age of the patients was 42years (range; 16–82). The median age of male patients was significantly higher than female (53 vs. 34years; p<0.001). All patients had thrombocytopenia and microangiopathic hemolytic anemia. At the same time, 82.8% (135/163) of patients had neurological abnormalities, 78.5% (128/163) of patients had renal dysfunction, and 89% (145/163) of patients had fever. Also, 10.4% (17/163) of patients had three of the five criteria, 10.4% (17/163) of patients had four of the five criteria, and 6.1% (10/163) of patients had all of the five criteria. Primary TTP comprised of 85.9% (140/163) of the patients and secondary TTP comprised of 14.1% (23/163) of the patients. Malignancy was the most common cause in secondary TTP. The median number of TPE was 13 (range; 1–80). The number of TPE was significantly higher in complete response (CR) patients (median 15.0 vs. 3.5; p<0.001). CR was achieved in 85.3% (139/163) of the patients. Similar results were achieved with TPE in both primary and secondary TTP (85% vs. 87%, respectively; p=0.806). There was no advantage of TPE+prednisolone compared to TPE alone in terms of CR rates (82.1% vs. 76.7%; p=0.746). CR was not achieved in 14.7% (24/163) of the patients and these patients died of TTP related causes. There were no statistical differences in terms of mortality rate between patients with secondary and primary TTP [15% (21/140) vs. 13% (3/23); p=0.806]. But, we obtained significant statistical differences in terms of mortality rate between patients on TPE alone and TPE+prednisolone [14% (12/86) vs. 3% (2/67), p<0.001]. ConclusionsTPE is an effective treatment for TTP and is associated with high CR rate in both primary and secondary TTP. Thrombocytopenia together with microangiopathic hemolytic anemia is mandatory for the diagnosis of TTP and if these two criteria met in a patient, TPE should be performed immediately.

Combination of Cytarabine and Topotecan Improves Response Rate for Patients Treated for Acute Myeloid Leukemia with Persistent Disease After Frontline Induction

Abstract 2605 Background:Achievement of first complete response (CR) is the objective of frontline treatment for patients treated for acute myeloid leukemia (AML). After a first course of induction chemotherapy, 30 to 40% of the patients do not achieve CR. The association of anthracyclins and intermediate dose cytarabine (IDAC) allow 50 to 60% of patients with persistent AML to achieve CR when given as early as day 14 (Lioure ASH 2006). Previous studies have shown that topotecan had a significant activity in AML patients and could be safely combined with IDAC (Kantarjian cancer 2006). We hypothesize that switching from anthracyclins to another class of topo-isomerase inhibitor for patients with persistent AML at day 14 of induction may be useful to improve tolerance and efficacy of the salvage regimen. Design:This is a retrospective single center study. Patients had (1) a diagnosis of de novo or therapy related AML excluding APL, (2) received an initial 3+7 induction regimen with 60mg/m2/d of daunorubicin, (3) had a bone marrow aspirate at day 14 with ≥5% marrow blast. We evaluated the combination of IDAC (1000mg/m2/12h day14-17) and topotecan (TA, 1.25mg/m2/d CIV day 14–17) in 31 consecutive AML and compared its results in terms of CR rate and survival with a series of 54 patients treated with IDAC (1000mg/m2/12h day14-17) + anthracyclins (AA group, daunorubicin 35 mg/m2/d day 14–15 or idarubicin 8 mg/m2/d day 14–15). Results:Pretreatment patient’s characteristics were comparable between TA and AA groups including median age (48y vs 45y, p=0.34), cytogenetic risk stratification (with low/intermediate/high risk in 3/65/32% vs 2/52/46% of patients,p=0.44), median WBC count at diagnosis (11G/l vs 7 G/l), and median day 14 bone marrow blast count (21% vs 35%, p=0.23). Median follow-up was 51 months. Induction death rate (6%), neutropenia duration (38 days), thrombocytopenia duration (37 days), and frequency of microbiologically documented infections (47%) were comparable between the 2 groups. In univariate analysis, TA regimen was associated with a better CR rate (81% vs 59%, p=0.04), a better probability of overall survival (2-years estimate 66% vs 33%, p=0.03) and a better cumulative incidence of relapse (2-years estimate 38% vs 67%, p=0.002) as compared with AA. Our analysis also showed that high WBC count (more than 30G/L) and presence of adverse cytogenetics were associated with a lower frequency of CR. Adverse cytogenetics had also a negative impact on CIR and OS. The potential benefit of TA regimen was confirmed in the multivariate model for CR (HR=3.3, 95%CI [1.02–10.6], p=0.04), OS (HR=0.5, 95%CI [0.28–0.91], p=0.02), and CIR (HR=0.26, 95%CI [0.11–0.6], p=0.001). Patients in the TA group were more frequently allo-transplanted in CR1 as compared with AA (9/32 in AA group vs 17/25 in TA group, p=0.002) but survival results were confirmed if we censored patients at the time of allogeneic transplantation for CIR (p=0.002) whereas only a trend was shown for OS (p=0.057). Conclusion:This work shows that the substitution of anthracyclins by topotecan in combination with IDAC for second induction is safe and is associated with a better efficacy for AML patients with persistent leukemia after induction. The use of topotecan may be especially interesting in the context of high dose anthracyclins induction regimen in order to introduce an alternative drug in diseases selected with high resistance to chemotherapy and to limit the cumulative dose of anthracyclins administered. Disclosures:Off Label Use: RAD001.

A Phase III Study of Double Autotransplantation Incorporating Bortezomib-Thalidomide-Dexamethasone (VTD) or Thalidomide-Dexamethasone (TD) for Multiple Myeloma: Superior Clinical Outcomes with VTD Compared to TD.

Abstract 351▪▪This icon denotes an abstract that is clinically relevant. IntroductionA phase III study of melphalan (200 mg/m2)-based double autologous stem-cell transplantation (ASCT) incorporating thalidomide (T) and dexamethasone (D) with or without the addition of bortezomib (V) as first-line therapy for younger (≤65 years) patients (pts) with newly diagnosed multiple myeloma (MM) is currently being conducted by the Italian Myeloma Network GIMEMA. Patients and MethodsBy study design, pts were random assigned to receive three 21-d cycles of either bortezomib-thalidomide-dexamethasone (VTD) (V, 1.3 mg/m2 twice-weekly; T, 200 mg/d through d 1 to 63; D, 320 mg/cycle) or thalidomide-dexamethasone (TD) (both drugs at the same dose and schedule than in VTD) as induction therapy in preparation for ASCTs. Two 35-d cycles of either VTD or TD were given as consolidation therapy following ASCTs (V, 1.3 mg/m2 once-weekly; T, 100 mg/d through d 1 to 70; D, 320 mg/cycle). Primary study end point was the rate of high-quality responses [immunofixation negative complete response (CR) and ≥very good partial response (VGPR)] to induction therapy. Secondary study end points included response to, and toxicity of, subsequent treatment phases (including first and second ASCTs, and consolidation therapy), progression-free survival (PFS) and overall survival (OS). Analyses were intent to treat. All the 474 pts were evaluated for response to, and toxicity of, induction therapy. Responses reported by study investigators were centrally reassessed to confirm CR and VGPR; pts reported as complete responders but in whom bone marrow aspirate was not evaluable or not performed were reassessed as in VGPR. The VGPR category included the subcategories of near CR and VGPR. ResultsThe study was closed to pts accrual after a total of 480 pts were enrolled; of these, 6 failed inclusion criteria and the remaining 474 were randomized to the VTD (n=236) or TD (n=238) arm. The mean total dose of V received in induction therapy was 14.7 mg (or 94% of that planned). Grade 3 peripheral neuropathy (PN) and skin rash (SR) were reported more frequently with VTD induction therapy than with TD (PN: 9.7% vs 2.1%, respectively; P<0.001) (SR: 10% vs 1.7%, respectively; P<0.001). In the VTD arm, resolution or reduction to at least grade 2 of PN was observed within a median of 26 days. Remarkably, once-weekly standard dose administration of V and reduction of T dose in VTD as consolidation therapy resulted in a dramatic decrease in the frequency of grade ≥3 PN (2%) and SR (1%). Reported rates of herpes zoster infection with VTD as both induction and consolidation therapy were 0.4% and 1%, respectively. Overall, the CR (≥VGPR) rate with VTD induction therapy was 19% (62%) vs 5% (31%) with TD (P<0.001 for both CR and ≥VGPR comparisons); no pt had disease progression while on VTD, as compared to 5% of pts treated with TD (P<0.001) who discontinued therapy and went off study. Progression through the subsequent treatment phases was associated with an increase in the frequency of CR and ≥VGPR up to a final value of 44% and 80%, respectively, in the VTD arm; the corresponding rates in the TD arm were 32% (p=0.02) and 65% (p=0.001), respectively. On an intention to treat basis, best responses in the VTD vs TD arm were the following: CR, 55% vs 38%, respectively (P<0.001); ≥VGPR: 87% vs 69%, respectively (P<0.001). Superiority of the VTD vs TD arm in terms of CR rate was confirmed in pts with high-risk cytogenetics, as defined by the presence of t(4;14) and/or del(17p) (58% vs 33%, respectively; p=0.004). Two year-projected PFS was 85% in the VTD arm as compared to 75% in TD (p=0.008). Improved PFS with VTD vs TD, both added to double ASCT, was consistent across subgroup analyses of pts with poor prognosis, including those with high-risk cytogenetic profiles (p=0.03; HR=0.42, 95% CI: 0.18 to 0.96). PFS curves for pts in the VTD arm who carried or not high-risk cytogenetics were similar (p=0.19). No difference in OS was seen between the two treatment groups, but longer follow up is required. ConclusionsIncorporation of VTD into double ASCT for newly diagnosed MM resulted in a significant improvement in clinical outcomes (CR, ≥VGPR, PFS) in comparison with TD and double autotransplantation. Superior benefit with VTD and double ASCT in comparison with the control group was maintained in pts at high risk of progression or death, including those with t(4;14) and/or del(17p). Disclosures:Cavo:Celgene: Honoraria; Ortho Biotech, Janssen-Cilag: Honoraria, Research Funding, Speakers Bureau; Millennium Pharmaceuticals: Honoraria; Novartis: Honoraria.

Variations on the Fludarabine, Cyclophosphamide, and Rituximab Combination in Chronic Lymphocytic Leukemia Therapy: What Have We Learned?

Fludarabine, cyclophosphamide, and rituximab (FCR) each have single-agent efficacy in the treatment of chronic lymphocytic leukemia (CLL). In combination, these agents are synergistic as demonstrated by the results of the FCR regimen developed by Michael Keating et al at The University of Texas M. D. Anderson Cancer Center, Houston, TX. Clearly, with high complete remission rates and long remission durations, the FCR regimen is among the frontline regimens for treatment of CLL. Indeed, the question has been raised, “Should FCR be considered the new gold standard for CLL therapy?” Unfortunately, the extraordinary biologic and clinical heterogeneity of CLL make it difficult to compare the results of clinical trials, so the answer to this question will require additional randomized clinical trials developed with attention to critical prognostic factors for risk stratification of patients with CLL. However, despite this limitation, we can, nevertheless, still learn much from comparing phase II trials of the FCR combination. In this issue of the Journal of Clinical Oncology, two small phase II trials aimed at reducing toxicity while preserving efficacy examine modifications of the FCR combination. The report by Foon et al presents an FC dose-reduced, R dose-escalated version of the FCR regimen, termed “FCR-Lite,” whereas Lamanna et al introduce a sequential “F3C3R” regimen. To evaluate these trials, it is important to recapitulate the recently reported long-term results of the 300 patients with CLL receiving FCR as initial therapy at M. D. Anderson Cancer Center (Table 1). Impressive clinical activity was noted, with a complete response (CR) rate of 72% and an overall response rate of 95%. Six-year overall survival and failure-free survival were 77% and 51%, respectively; median time to progression was 80 months. Evaluation for minimal residual disease (MRD) by flow cytometry (FL-C) at the end of treatment and polymerase chain reaction (PCR) correlated with improved overall survival. FL-C negativity was associated with superior time to progression (median, 85 months v 49 months) and survival (84% v 65% at 6 years). PCR applied to patients already known to be FL-C negative had little additional impact. Although it is noteworthy that two thirds of patients had intermediate-risk disease by Rai criteria, these are the most robust single-institution data to date in terms of CR rate, remission duration, and survival. In addition, these data reconfirm and emphasize the importance of MRD negativity after completion of treatment. The efficacy of the combination of FCR, as well as the associated toxicities, led Foon et al to test a dose-reduced version of FCR, with the intent of maintaining efficacy. Fludarabine was dose reduced to 20 mg/m, and cyclophosphamide was reduced to 150 mg/m. Rituximab was increased to 500 mg/m on days 1 and 14 of a 28-day cycle, and rituximab maintenance was included after completion of six cycles of the combination. The authors report on 48 assessable patients, all of whom responded to treatment (100% overall response rate) with 38 CRs (79%). Of these 38 patients, 37 (97%) had a FL-C– negative CR. Although the authors state that none of the 38 patients achieving CR have relapsed at the time of report, the median duration of CR is 22.3 months with a range of 5.2 to 42.5 months, which is rather short follow-up at this point. Grade 3 to 4 toxicities were rare, with grade 3 or 4 neutropenia occurring in 13% of treatment cycles. The authors conclude that their results confirm the high response rate of the FCR regimen, albeit FCR-Lite, with a lower toxicity than reported for classic FCR. Moreover, they emphasize that 34 (68%) of 40 patients were treated by community oncologists. It should be noted that 84% of enrolled patients had intermediate-risk disease, and as such, the patient population was heavily skewed toward early-stage Table 1. Comparison of Three FCR Regimens

Comparison of tolerability and efficacy of concurrent chemoradiation (CRT) for anal squamous cell carcinoma (SCC) in HIV-positive (HIV+) and -negative (HIV-) patients (pts)

4606 Background: It is believed that the prognosis of anal SCC is poor in HIV+ pts, and their appropriate treatment is uncertain. We compared the tolerability and efficacy of concurrent CRT as definitive therapy for anal SCC in HIV+ and HIV-/unknown pts in the HAART- era. Methods: Pts serially diagnosed and treated in a single institution from Apr/2000 to May/2007. Definitive CRT consisted of 45- 59.4Gy, divided in 5 fractions/week, given with concurrent mitomycin-C (MMC) 15mg/m2D1 IV and 5-fluoruracil (5FU) 1g/m2/d IV, continuous infusion, D1-D4 and D29-D32. Baseline hematologic, hepatic and renal functions were normal in all pts, and the same treatment was delivered irrespective of HIV-status. HIV+ pts were under antiretroviral therapy according to standard recommendations. Results: 78 pts were included in the analysis, median age 56.5y (23–85y), 63 female (81%). Stage: Tis (3 pts), I (4), II (26), IIIA (15), IIIB (20), IV (1). Nine pts were identified as HIV+. HIV+ pts were younger (39.4 vs. 59.2 y, p<0.0001) and predominantly male (8/9 pts). No difference in tumor stage or grade was detected in HIV+ pts. For all pts, the median dose of RT was 45Gy, given over 42d. No difference in terms of treatment duration or administered CRT intensity between HIV+ or HIV- /unknown pts was observed and treatment was well tolerated. Complete response (CR) was achieved in 45 pts (58%), partial response in 7 pts (9%), stable disease in 6 pts (8%) and disease progression in 3 pts (4%). No difference was seen in HIV+ pts in terms of CR rate (6/9 CR (67%), p=0.664). With a mean follow-up of 25mo, 14 deaths have occurred. The median overall survival (OS) was not reached (NR). The 2-y OS rate was 78%. No difference in OS was seen between HIV+ or HIV-/unknown pts (NR in both groups, p=0.248), and a 2-y OS rate of 100% was observed in HIV+ pts. We also observed both longer median PFS (NR vs. 11.5 mo, p=0.0009, HR 0.254, 95%CI 0.034–0.417) and median OS (NR vs. 12.9 mo, p=0.0007, HR 0.180, 95%CI 0.013–0.309) among patients that needed no colostomy. Conclusions: In this group of anal SCC pts no differences in terms of prognosis, treatment tolerance or efficacy could be identified based on HIV status, and the standard 5FU/MMC-based CRT could be delivered successfully. No significant financial relationships to disclose.

FLAG-IDA Regimen (Fludarabine, Cytarabine, Idarubicin and G-CSF) in the Treatment of Patients with High-Risk Acute Myeloid Leukemia and Myelodysplastic Syndromes.

Background: Preliminary results with the combination of fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor (G-CSF) (FLAG-IDA), reported complete response (CR) rates of 47–95% in patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), with acceptable toxicity. These results lead to a generalized use of FLAG-IDA regimen in this set of patients. However, these studies have been made in small series and the long-term outcome of patients have not been described.Objectives: Analyze the results of FLAG-IDA regimen, in terms of CR rate and long-term outcome, in a large series of patients with high-risk AML and MDS treated in a single institution.Methods: From 1997 to 2007, 158 adult patients (median age 60 years, range 16–79) received FLAG-IDA regimen (Fludarabine, 30 mg/m2 intravenous (iv) for 4 days, cytarabine 2 g/m2 iv for 4 days, idarubicin 10 mg/m2 iv for 3 days and glycosylated G-CSF at a daily dose of 300 mcg/m2, from day -1 until day 5). Post-remission therapy consisted of allogeneic transplantation (Allo-HSCT) in eligible patients, or consolidation (idarubicin, 10 mg/m2 iv for 3 days and cytarabine, 200 mg/m2 iv for 5 days), followed by intensification with Auto-HSCT or one cycle of carboplatin (300 mg/m2 for 4 days, as a 24 h continuous infusion). Patients were diagnosed with high-risk MDS (11%), treatment related AML (10%), AML secondary to MDS (29%), primary refractory AML (17%), AML in first relapse (27%), and AML in second or subsequent relapse (6%). Median follow-up of the cohort was 40 months (range 2–104). We calculated the Kaplan-Meier estimates curves for overall survival (OS), disease-free (DFS) and relapse-free survival (RFS).Results: CR and partial remission (PR) was achieved in 84 patients (53%) and in 19 patients (12%), respectively. Twenty-three patients (15%) died during induction, mostly due to infection (19 patients). The CR rates according to the disease status were the following: high-risk MDS 61%, treatment related AML 73%, AML secondary to MDS 52%, primary refractory AML 54%, AML in first relapse 49%, and AML in second or subsequent relapse 30%. Post-remission therapy consisted of Allo-HSCT in 16 patients (8 related and 8 unrelated), Auto-HSCT in 15 patients, and chemotherapy alone in 53 patients. The 1 and 5 year OS, DFS and RFS of the entire cohort were 36% and 11%, 40% and 11%, and 51% and 23%, respectively. The 1 and 5 year OS in patients achieving CR, PR and resistance were 64% and 22%, 26% and 7%, and 4% and 0%, respectively (p<0.0001). The 5 year RFS of patients treated with chemotherapy alone, Auto-HSCT and Allo-HSCT were 13%, 16% and 64%, respectively (p=0.09). The 5 year RFS of patients aged >55 years and ≤55 years were 4% and 53%, respectively (p=0.0005). The 5 year DFS of patients treated with chemotherapy alone, Auto-HSCT and Allo-HSCT were 7%, 13% and 35%, respectively (p=0.22).Conclusion: Our results confirm the acceptable toxicity and high response rate observed with FLAG-IDA regimen in this very high-risk subgroup of patients. This regimen can be a bridge towards Allo-HSCT, that appear to be the most curative therapy in this setting.

The Impact of Relative Dose Intensity (RDI) of CHOP on Outcome of Diffuse Large B-Cell Lymphoma: Results of a Single Center Study.

Introduction: The achievement of a clinical response to the first induction chemotherapy has been considered for predicting survival in patients (pts) with aggressive non-Hodgkin lymphoma (NHL). Reduced dose intensity of chemotherapy has been likely to compromise long-term outcome of the patients with aggressive NHL treated with a standard chemotherapy of cyclophosphamide (CY), doxorubicin (ADR), vincristine and prednisone (CHOP). In particular, recent studies have revealed the relevance of relative dose intensity (RDI) to clinical outcomes, with reduced RDI leading to a poor survival, as well as the impact of RDI<85% for aggressive NHL with detailed analysis of risk factors influencing reduce RDI<85% (Gary H. Lyman, J. Clin Oncol 22: 4302, 2004). This study was conducted to investigate the impact of RDI<85% of CHOP on outcomes of the pts with diffuse large B-Cell lymphoma (DLCL).Methods: Data were retrospectively collected on 100 pts with DLCL who had been initially treated with more than 3 courses of CHOP (n=70) or CHOP plus rituximab (CHOP-R, n=30) at our institution between 1995 and 2006. We evaluated whether RDI might affect clinical outcomes, including complete response (CR) and event free survival (EFS). The average RDI derived from CY and ADR (referred to as RDI-CY/ADR) was determined for each patient, with classified into 2 populations according to the differences from the value of 85%, including RDI-CY/ADR<85% (n=60), and RDI-CY/ADR≥85% (n=40).Results: The median age of the study population was 54 years (range, 17 to 76), with 36 pts older than 60 years (yrs) of age. According to International Prognostic Index (IPI) score, pts were classified into 2 groups of low/ low-intermediate (n=46) and high/ high-intermediate (n=54). The overall CR rate reached 62%, and the probability of overall survival (OS) or EFS at 5 years estimated 77% or 43%, respectively with a median follow-up of 13.3 months. Multivariate analysis identified RDI-CY/ADR<85%, as well as IPI score to be associated with CR rate and EFS. Thus, RDI-CY/ADR<85% and IPI score of high/ high-intermediate were significant factors for lower CR rate (as RDI-CY/ADR≥85%, HR=0.3, 95% CI 0.1 to 0.7, p=0.009, and HR=5.5, 95% CI 2.2 to 14, p<0.001, respectively), and for reduced EFS (HR=1.9, 95% CI 1.0 to 3.7, p=0.048, and as IPI score of low/ low-intermediate HR=0.3, 95% CI 0.2 to 0.6, p<0.001, respectively). Furthermore, logrank analysis revealed that CY/ADR-RDI<85% was the significant factor for reduced EFS in non elderly pts (≤60 yrs of age), or in pts with IPI score of low/ low-intermediate (p=0.01, p=0.02, respectively).Conclusion: These data thus suggested the impact of RDI-CY/ADR<85% in influencing outcomes of the pts with DLCL, in terms of CR rate and EFS. Further investigation is currently planned to confirm this promising results with longer follow-up in larger numbers of pts with NHL.

Increased Sensitivity of Radiated Murine Cervical Cancer Tumors to E7 Subunit Vaccine–driven CTL-mediated Killing Induces Synergistic Anti-tumor Activity

The development of therapeutic vaccines has important implications for the treatment of cancer patients. Here we investigate whether human papillomavirus (HPV) E7 subunit vaccines can enhance tumor radioresponse using an established cervical cancer animal model. Radiation plus E7 subunit vaccines improved complete response, cure, and recurrence rates of tumors dramatically compared with single therapy alone. In particular, both components of the E7 subunit vaccines (E7 protein and CpG-oligodeoxynucleotide) were required for the induction of antigen (Ag)-specific cytotoxic T-lymphocyte (CTL) responses and for therapeutic synergy with radiotherapy. Moreover, with combined therapy the radiation dose could be reduced by 16 Gy to achieve an equivalent anti-tumor efficacy to radiation treatment alone. This therapeutic synergy was found to be mediated by CD8(+) CTLs and was concomitant with histological changes (presence of apoptotic bodies and multinucleated giant cells; heavy infiltration of lymphocytes), as determined by in vivo T-cell depletion and histological analysis. Finally, phenotypic changes of radiated tumors and their increased sensitivity to CTL-mediated killing appeared to be responsible for therapeutic synergy. These results show that E7 subunit vaccines act as a potent enhancer of tumor radioresponse and that this is mediated by increased sensitivity of radiated tumors to CTL-mediated killing. This study further suggests that E7-targeted therapeutic vaccines have the potential to improve radiotherapy in patients with cervical cancer.

Two Cycles of Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine Plus Extended-Field Radiotherapy Is Superior to Radiotherapy Alone in Early Favorable Hodgkin's Lymphoma: Final Results of the GHSG HD7 Trial

To investigate whether combined-modality treatment (CMT) with two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by extended-field radiotherapy (EF-RT) is superior to EF-RT alone in patients with early favorable Hodgkin's lymphoma (HL). Between 1993 and 1998, 650 patients with newly diagnosed, histology-proven HL in clinical stages IA to IIB without risk factors were enrolled onto this multicenter study and randomly assigned to receive 30 Gy EF-RT plus 10 Gy to the involved field (arm A) or two cycles of ABVD followed by the same radiotherapy (arm B). Results At a median observation time of 87 months, there was no difference between treatment arms in terms of complete response rate (arm A, 95%; arm B, 94%) and overall survival (at 7 years: arm A, 92%; arm B, 94%; P = .43). However, freedom from treatment failure was significantly different, with 7-year rates of 67% in arm A (95% CI, 61% to 73%) and 88% in arm B (95% CI, 84% to 92%; P <or= .0001). This was due mainly to significantly more relapses after EF-RT only (arm A, 22%; arm B, 3%). No patient treated with CMT experienced relapse before year 3. Relapses were treated mainly with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, or with the combination cyclophosphamide, vincristine, procarbazine, and prednisone/ABVD; treatment of relapse was significantly more successful in arm A than in arm B (P = .017). In total, there were 39 second malignancies, with 21 in arm A and 18 in arm B, respectively. The incidence was approximately 0.8% per year during years 2 to 9 and was highest in older patients (P < .0001) and those with "B" symptoms (P = .012). CMT consisting of two cycles of ABVD plus EF-RT is more effective than EF-RT alone.

Therapeutic plasma exchange for the treatment of thrombotic thrombocytopenic purpura: A retrospective multicenter study

Background Thrombotic thrombocytopenic purpura (TTP) is a rare disease that is fatal if it is not treated. Therapeutic plasma exchange (TPE) has resulted in excellent remission and survival rates in TTP patients. Material and methods We describe our experience with 52 TTP patients treated with TPE during the past eight years (65% of the patients were females; patient median age = 34 years, range: 17–73). TPE was carried out 1–1.5 times plasma volume. Fresh frozen plasma (FFP) or cryosupernatant plasma (CSP) was used as the replacement fluid. TPE was performed daily until normalization of serum LDH and recovery of the platelet count to >150 × 10 9/dL; TPE was then slowly tapered. Clinical, laboratory data, the number of TPE, other given therapy modalities, treatment outcomes and survival rate were evaluated retrospectively. Results Overall response (OR) and complete response (CR) rates were 77% and 60%, respectively. Response was excellent in 82.8% of the patients with primary TTP among whom 74.2% were CR. Additionally, there were statistical differences in terms of CR rate between patients with primary TTP and secondary TTP (74.2% vs. 29.4%; p = 0.005). OR and CR rates were 79% and 57.9% in patients on TPE alone and 75.8% and 60.6% in patients on TPE + prednisolone, respectively ( p = 1 and p = 0.8). Additionally, there were no statistical differences in terms of OR and CR rates between patients on TPE with FFP and CSP ( p = 0.25 and p = 0.16, respectively). The presence of fever and the number of TPE were statistically important factors influencing the probability of response in multivariate logistic regression analysis ( p < 0.01 and p < 0.01, respectively). Additionally, in multivariate Cox’s regression analysis, the probability of survival was higher in patients who were responsive to treatment compared to patients who were unresponsive ( p < 0.001). Conclusion TPE is an effective treatment for primary TTP; however, it may be used as adjunctive therapy for secondary TTP until it is under control. The addition of steroids to TPE had no advantage compared to TPE alone. CSP as replacement fluid is not superior compared to FFP. Fever appears to be a bad prognostic indicator. Therefore, prolonged treatment with TPE may be needed in patients with fever.