Long-Term Follow-Up Analysis of HD9601 Trial Comparing ABVD Versus Stanford V Versus MOPP/EBV/CAD in Patients With Newly Diagnosed Advanced-Stage Hodgkin's Lymphoma: A Study From the Intergruppo Italiano Linfomi

2011 ◽  
Vol 29 (32) ◽  
pp. 4227-4233 ◽  
Author(s):  
Teodoro Chisesi ◽  
Monica Bellei ◽  
Stefano Luminari ◽  
Antonella Montanini ◽  
Luigi Marcheselli ◽  
...  

Purpose The Intergruppo Italiano Linfomi HD9601 trial compared doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) versus doxorubicin, vinblastine, mechloretamine, vincristine, bleomycin, etoposide, and prednisone (Stanford V [StV]) versus the combination of mechlorethamine, vincristine, procarbazine, prednisone (MOPP) with epidoxorubicin, bleomycin, vinblastine (EBV), lomustine, doxorubicin, and vindesine (CAD) (MOPP/EBV/CAD [MEC]) for the initial treatment of advanced-stage Hodgkin's lymphoma to select which regimen would best support a reduced radiotherapy program (limited to two or fewer sites of either previous bulky or partially remitting disease). Superiority of ABVD and MEC to StV was demonstrated. We report analysis of long-term outcome and toxicity. Patients and Methods Patients with stage IIB, III, or IV were randomly assigned among six cycles of ABVD, three cycles of StV, and six cycles of MEC; radiotherapy was administered in 76, 71, and 50 patients in the three arms, respectively. Results Currently, the median follow-up is 86 months; in the prolonged observation period, eight additional failures, including two relapses, both in the StV arm, and six additional deaths in complete response were recorded. The 10-year overall survival rates were 87%, 80%, and 78% for ABVD, MEC, and StV, respectively (P = .4). The 10-year failure-free survival was 75%, 74%, and 49% in the ABVD, MEC, and StV arms, respectively (P < .001). The 10-year disease-free survival of patients treated or not with radiotherapy (RT) showed no difference for ABVD or MEC (85% v 80% and 93% v 68%), and a statistically significant difference for StV (76% v 33%; P = .004). No significant long-term toxicity was recorded. Conclusion The long-term analysis confirmed ABVD and MEC superiority to StV. The use of RT after StV was established as mandatory. ABVD is still to be considered as the standard treatment with a good balance between efficacy and toxicity.

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 499-499 ◽  
Author(s):  
Francesco Merli ◽  
Stefano Luminari ◽  
Caterina Mammi ◽  
Nicola Cascavilla ◽  
Alessia Bari ◽  
...  

Abstract PURPOSE: The HD2000 trial compared doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) versus bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) versus the combination of cyclophosphamide, vincristine, procarbazine, prednisone (COPP) with epidoxorubicin, bleomycin, vinblastine (EBV), lomustine, doxorubicin, and vindesine (CAD) (MOPP/EBV/CAD [CEC]) in 305 eligible patients with advanced-stage Hodgkin's lymphoma (HL). The previous analysis with 41 months median follow-up had indicated that BEACOPP was associated with a significantly improved Progression Free Survival (PFS) compared with ABVD, with a predictable higher acute toxicity. At time of previous analysis none of the study arms resulted in a better Overall Survival (OS). We here report analysis of long-term outcome and toxicity. PATIENTS AND METHODS: Three hundred and five eligible patients with stage IIB, III, or IV were randomly assigned to receive six courses of ABVD (n=103), four escalated plus two standard courses of BEACOPP (n=100), or six courses of CEC (n=102), plus a limited radiation therapy program; radiotherapy was administered in 46, 42, and 42 patients in the three arms, respectively. Study enrolment was completed in June 2007. In January 2014 we updated the study follow-up with the aim of providing data on survival and on late events. RESULTS: At time of current analysis the median follow-up was 119 months (range 1-169) with 92% of patients with a last contact later than January 2012. In the prolonged observation period 23 additional failures (cumulative=82)were recorded, including 17 new relapses/progression (cum=71) and 6 deaths not related to lymphoma progression (cum=11). Additional relapses and progressions were observed in 5, 7 and 5 patients treated with ABVD (cum=31), BEACOPP (cum=17), and CEC (cum=23), respectively. No death unrelatedto lymphoma progression was recorded among patients treated with ABVD, while 8 (+4) and 3 (+2) events were documented among patients treated with BEACOPP or CEC, respectively. The 10-year PFS was 69%, 74% and 74% in the ABVD, BEACOPP and CEC arm, respectively (P=0.639). Using ABVD as reference, Hazard Ratio for PFS for BEACOPP and CEC was 0.73 (CI95% 0.43-1.25) and 0.80 (0.47-1.36); this result was adjusted by IPS. Overall 42 patients died (+19), 13 (+5) in the ABVD arm, 15 (+7) in the BEACOPP arm and 14 (+7) in the CEC arm. The 10-year overall survival rates were 84%, 84% and 86% for ABVD, BEACOPP and CEC, respectively (P =0.883). A total of 11 second malignancies were documented including 2 MDS/AML (1 BEACOPP and 1 CEC), 2 non-Hodgkin’s Lymphoma (1 BEACOPP and 1 CEC), and 7 solid cancers: 2 lung cancer (BEACOPP), 2 bladder cancer (2 CEC), 1 sarcoma (BEACOPP), 1 Kaposi sarcoma (BEACOPP) and 1 thyroid cancer (ABVD). The risk of second malignancy at 10-year was 6.7, 4.4 and 0.9 for BEACOPP, CEC and ABVD, respectively; the difference between BEACOPP and ABVD was statistically significant (P=0.027). CONCLUSION : With the updated follow-up of the HD2000 trial we confirm that patients with advanced HL have similar high chances of survival when treated with ABVD, BEACOPP or CEC. With this long-term analysis we were not able to confirm the previously observed superiority of BEACOPP over ABVD in terms of PFS mainly due to a higher rate of secondary malignancies observed after BEACOPP. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4827-4827
Author(s):  
Michele Spina ◽  
Jean Gabarre ◽  
Salvatrice Mancuso ◽  
Alessandro Re ◽  
Clara Schiantarelli ◽  
...  

Abstract Abstract 4827 Background: The introduction of HAART has significantly improved the outcome of pts with HD-HIV. However there are no data on the long term follow-up of HD-HIV pts treated with conventional chemotherapy (CT) regimens. In 2002, we reported the results of a prospective phase II study with the intensive 12-week CT with adjuvant radiotherapy (Stanford V) and concomitant HAART in 59 pts (Spina et al. Blood 2002;100:1984-1988). Methods: To analyze the long term outcome of patients included in the Stanford V and HAART protocol. Results: The median follow-up is 67months (range 3–156 months The 5-yr overall survival (OS), freedom from progression (FFP), disease free survival and event free survival are 54%, 52%, 60% and 37%, respectively. The 5-year OS is significantly different in pts with an international prognostic score (IPS) >2 in comparison to that of pts with an IPS <3 (84% vs 36%, p= 0.0005). Similarly, the percentages of FFP at 5 years in these groups are 72% and 45% (p= 0.03). Conclusions: Our data confirm the long term efficacy of Stanford V regimen in combination with HAART in HD-HIV. However, Stanford V is significantly less effective in pts with IPS>2 and therefore new strategies be tested in this setting. Supported by AIRC and ISS grants. Disclosures: No relevant conflicts of interest to declare.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7583-7583
Author(s):  
M. Spina ◽  
J. Gabarre ◽  
M. Fasan ◽  
A. Re ◽  
C. Schiantarelli ◽  
...  

7583 Background: The introduction of HAART has significantly improved the outcome of pts with HD-HIV. However there are no data on the long-term follow-up of HD-HIV pts treated with conventional chemotherapy (CT) regimens and concomitant HAART. In 2002, we reported the results of a prospective phase II study with the intensive 12-week CT with adjuvant radiotherapy (Stanford V) and concomitant HAART in 59 pts with HD-HIV, a well-known unfavorable subgroup of HD (Spina et al. Blood 2002; 100:1984–1988). Methods: To analyze the long-term outcome of patients included in the Stanford V and HAART protocol. Results: The median follow-up is 53 months (range 3–104 months The overall survival (OS) is 59%, the freedom from progression (FFP) is 62% and the disease free survival (DFS) is 72%. The 5-year probability of OS was significantly different in pts with an international prognostic score (IPS) <3 in comparison to that of pts with an IPS >2 (84% vs 36%, p = 0.001). Similarly, the percentages of FFP at 5 years in these groups were 72% and 45% (p = 0.03). No significant side effects have been observed so far. Conclusions: After a median follow-up of 4.5 years, 72% of pts with this unfavorable subgroup and IPS <3 is free from progression, superimposable to that observed in the general population with comparable adverse prognostic factors. Therefore, Stanford V is a very effective regimen in pts with HD-HIV in the long-term analysis. Supported by AIRC and ISS grants. No significant financial relationships to disclose.


Gut ◽  
2017 ◽  
Vol 67 (2) ◽  
pp. 237-243 ◽  
Author(s):  
D Laharie ◽  
A Bourreille ◽  
J Branche ◽  
M Allez ◽  
Y Bouhnik ◽  
...  

ObjectiveCiclosporin and infliximab have demonstrated short-term similar efficacy as second-line therapies in patients with acute severe UC (ASUC) refractory to intravenous steroids. The aim of this study was to assess long-term outcome of patients included in a randomised trial comparing ciclosporin and infliximab.DesignBetween 2007 and 2010, 115 patients with steroid-refractory ASUC were randomised in 29 European centres to receive ciclosporin or infliximab in association with azathioprine. Patients were followed until death or last news up to January 2015. Colectomy-free survival rates at 1 and 5 years and changes in therapy were estimated through Kaplan-Meier method and compared between initial treatment groups through log-rank test.ResultsAfter a median follow-up of 5.4 years, colectomy-free survival rates (95% CI) at 1 and 5 years were, respectively, 70.9% (59.2% to 82.6%) and 61.5% (48.7% to 74.2%) in patients who received ciclosporin and 69.1% (56.9% to 81.3%) and 65.1% (52.4% to 77.8%) in those who received infliximab (p=0.97). Cumulative incidence of first infliximab use at 1 and 5 years in patients initially treated with ciclosporin was, respectively, 45.7% (32.6% to 57.9%) and 57.1% (43.0% to 69.0%). Only four patients from the infliximab group were subsequently switched to ciclosporin. Three patients died during the follow-up, none directly related to UC or its treatment.ConclusionsIn this cohort of patients with steroid-refractory ASUC initially treated by ciclosporin or infliximab, long-term colectomy-free survival was independent from initial treatment. These long-term results further confirm a similar efficacy and good safety profiles of both drugs and do not favour one drug over the other.Trial registration numberEudraCT: 2006-005299-42; ClinicalTrials.gouv number: NCT00542152; post-results.


2014 ◽  
Vol 112 (07) ◽  
pp. 176-182 ◽  
Author(s):  
Michael Humenberger ◽  
Martin Andreas ◽  
Bassam Redwan ◽  
Klaus Distelmaier ◽  
Günter Klappacher ◽  
...  

SummaryEndothelin (ET)-1 is a pro-fibrotic vasoconstrictive peptide causing microvascular dysfunction and cardiac remodelling after acute ST-elevation myocardial infarction (STEMI). It acts via two distinct receptors, ET-A and ET-B, and is involved in inflammation and atherogenesis. Patients with posterior-wall STEMI were randomly assigned to intravenous BQ-123 at 400 nmol/minute (min) or placebo over 60 min, starting immediately prior to primary percutaneous coronary intervention (n=54). Peripheral blood samples were drawn at baseline as well as after 24 hours and 30 days. Myeloperoxidase (MPO), as a marker of neutrophil activation and matrix metalloproteinase 9 (MMP-9), a marker of extracellular matrix degradation were measured in plasma. Clinical follow-up was conducted by an investigator blinded to treatment allocation over three years. During the median follow-up period of 3.6 years (interquartile range [IQR] 3.3–4.1) we observed a longer event-free survival in patients randomised to receive BQ-123 compared with patients randomised to placebo (mean 4.5 years (95% confidence interval: 3.9–5) versus mean 3 years (2.2–3.7), p=0.031). Patients randomised to ET-A receptor blockade demonstrated a greater reduction of MPO levels from baseline to 24 hours compared to placebo-treated patients (-177 ng/ml (IQR 103–274) vs –108 ng/ml (74–147), p=0.006). In addition, a pronounced drop in MMP-9 levels (-568 ng/ml (44–1157) vs –117 ng/ml (57–561), p=0.018) was observed. There was no significant difference in amino-terminal propetide of pro-collagen type III levels. In conclusion, short-term administration of BQ-123 leads to a reduction in MPO, as well as MMP-9 plasma levels and to a longer event-free survival in patients with STEMI.ClinicalTrials.gov Identifier: NCT00502528


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1866-1866
Author(s):  
Min Kyoung Kim ◽  
Chang-Ki Min ◽  
Myung Soo Hyun ◽  
Kihyun Kim ◽  
Sung-Soo Yoon ◽  
...  

Abstract Abstract 1866 Background: In multiple myeloma (MM), the association between the response to induction before autologous stem cell transplantation (ASCT) and long-term outcome is less clear but the situation may change with the introduction of novel agents. We therefore assessed the clinical relevance of response of bortezomib induction treatment or post-ASCT response for patients who received bortezomib-combined induction chemotherapy followed by ASCT. Methods: We retrospectively assessed 183 MM patients who received bortezomib-containing induction therapy (BTZ-IT) followed by ASCT in 24 institutions throughout Korea between 2003 and 2010. Records of these patients were reviewed using the Korean Myeloma Registry database (www.myeloma.or.kr). Each institution was requested to reconfirm the data using additional case report forms. Patients who had overt MM based on International Myeloma Working Group diagnostic criteria were selected. Results: One-hundred seventy eight patients were eligible. Their median age was 56 years (range, 28–69 years) and 96 (53.9%) were male. Forty nine (27.5%) received bortezomib as front-line therapy and 129 (72.5%) as second-line treatment. All patients underwent ASCT and 22 (12.4%) were treated with tandem ASCT. Ninety-seven (54.5%) patients were treated with maintenance therapy after ASCT. After BTZ-IT, the response rates in this selected series of patients were 37.6% CR, 12.4% VGPR, 41.0% PR, 7.3% SD and 1.7% PD (Figure 1A, 1B, 1C); the corresponding post-ASCT rates were 69.2% CR, 14.0% VGPR, 11.0% PR, 2.9% SD and 2.9% PD. At a median follow-up of 46.6 months, the 3-year overall survival (OS) and event-free survival (EFS) rates were 70.0% and 31.9%, respectively. Multivariate analysis showed that factors independently predictive of OS and EFS included achievement of BTZ-IT response °Ã PR (P=0.025 and P=0.014, respectively) and the treatment with maintenance therapy (P=0.048 and P=0.001, respectively). Post-ASCT CR vs. °Â VGPR was also an independent prognostic factor for OS and EFS (P=0.0001 and P=0.002, respectively). Conclusion: At least PR to BTZ-IT and CR after ASCT were predictive of survival. These findings suggest that patients who responded to BTZ-IT may benefit from ASCT due to an enhanced quality of response. Maintenance therapy can also affect patient outcomes. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2030-2030
Author(s):  
Dietger Niederwieser ◽  
Leo F Verdonck ◽  
Jan J Cornelissen ◽  
Michael Cross ◽  
Rainer Krahl ◽  
...  

Abstract Abstract 2030 HSCT after reduced or minimal intensity conditioning is increasingly used to treat AML patients not eligible for conventional HSCT. Short term outcome has been reported frequently and risk factors have been identified; long term results still await in depth evaluation. We report here 5 years follow up results from a prospective phase II study conducted by two AML study groups in Europe. Patients were recruited from AML protocols HOVON/SAKK AML 43 and the OSHO AML 1997 study. The regimen consisted of fludarabine (FLU), 30 mg/m2/d on days −4, −3, and −2, 2 Gy TBI on day 0 (the day of HSCT) with mycophenolate mofetil, [15 mg/kg p.o. b.i.d. from 5 hours after HSCT to day +40], and cyclosporine, [CSP; 6.25 mg/kg p.o. bid from day –3 to day +180] after HSCT. Cyclosporine was adjusted to trough levels and reduced according to a predetermined tapering schedule and donor type. A total of 96 patients were recruited between 5/2002 and 8/2005 in the study. Age was median 62 (range 40 – 74) years, 54 patients were male (56%) and 73 patients (76%) had de novo AML. The remission status on entry was CR1 in 83 (86%) patients and CR2 in 13 (14%). Of the 96 patients, 20% had high risk cytogenetics and SCT was performed a median of 75 days after chemotherapy. There were no statistical differences in the above described characteristics except for more secondary AML (p=0.04) and more CR2 patients (p=0.07) among the 59 unrelated SCT (61%) as compared to the 37 related SCT (39%). Graft rejection at two years was observed in 6% of the patients. Absence of chronic GvHD was diagnosed in 40% and limited chronic GvHD in 29% of the patients, with no difference between related and unrelated SCT. Probability of overall survival (OS) at 6 years with a median follow up of 64 (49–92) months reaches a plateau after 5 years at 0.33±0.05 and was not significantly better in CR1 than in CR2. However, there was a trend towards better OS at 6 years for unrelated 0.41±0.11 as compared to related 0.29±0.07 SCT (p=0.08) in CR1 only. This difference was significant for disease free survival (DFS) (0.48±0.09 unrelated vs 0.27±0.06 related; p=0.04), the major reason being a higher relapse rate in related as compared to unrelated SCT (0.62±0.08 vs 0.40±0.09). The overall non-relapse mortality at 6 years was 0.21±0.05. We conclude that OS and DFS reach a stable plateau from 5 years after SCT to more than 8 years after SCT. In CR1 patients, DFS is superior after unrelated as compared to related SCT. Accordingly, strategies designed to decrease relapse, especially after related SCT, have already been implemented in the ongoing protocols. The preferential use of unrelated rather than related donors may be beneficial and should be considered in future protocols. Disclosures: Off Label Use: Transplantation in elderly patients.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Seigo Yamashita ◽  
Michifumi Tokuda ◽  
Saagar Mahida ◽  
Hidenori Sato ◽  
Hirotsugu Ikewaki ◽  
...  

AbstractThe optimal ablation strategy for persistent atrial fibrillation (PsAF) remains to be defined. We sought to compare very long-term outcomes between linear ablation and electrogram (EGM)-guided ablation for PsAF. In a retrospective analysis, long-term arrhythmia-free survival compared between two propensity-score matched cohorts, one with pulmonary vein isolation (PVI) and linear ablation including roof/mitral isthmus line (LINE-group, n = 52) and one with PVI and EGM-guided ablation (EGM-group; n = 52). Overall, 99% of patients underwent successful PVI. Complete block following linear ablation was achieved for 94% of roof lines and 81% of mitral lines (both lines blocked in 75%). AF termination by EGM-guided ablation was accomplished in 40% of patients. Non-PV foci were targeted in 7 (13%) in the LINE-group and 5 (10%) patients in the EGM-group (p = 0.76). During 100 ± 28 months of follow-up, linear ablation was associated with superior arrhythmia-free survival after the initial and last procedure (1.8 ± 0.9 procedures) compared with EGM-group (Logrank test: p = 0.0001 and p = 0.045, respectively). In multivariable analysis, longer AF duration and EGM-guided ablation remained as independent predictors of atrial arrhythmia recurrence. Linear ablation might be a more effective complementary technique to PVI than EGM-guided ablation for PsAF ablation.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Mladoniczky ◽  
M Szegedi ◽  
Z S Piroth ◽  
J Nemeth ◽  
L Ablonczy ◽  
...  

Abstract Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a thrombotic pulmonary disease associated with pulmonary vasculopathy. Pulmonary endarterectomy (opus, PEA) is the first treatment choice in CTEPH, and specific PAH medication when there is a contraindication for surgery or residual pulmonary arterial hypertension (rPAH) occurs. In the presence of PAH balloon pulmonary angioplasty (BPA) might be also recommended if available. Objective We investigated the long term outcome of our CTEPH patients. Methods CTEPH from our institution retrospectively analyzed (data between 2003 and 2018). Baseline, treatment and outcome data were documented. We compared the outcome, together with mortality in those with and without surgery (PEA vs. non PEA group). NYHA class, 6 minutes walking distance (6MWD) and NT-proBNP were also reported during follow-up. Results Of 29 CTEPH patients (mean age was 62±19 years, 52% male) 16 (55%) were accepted for PEA, and further 12 of them had a long term follow-up post surgery (n=3 periop exit, n=1 waiting for surgery). Half of the PEA patients were cured (n=6) and the other half (n=6) required specific PAH treatment (n=1, in combination with BPA) for rPAH. All patients from the non-PEA group (n=13) were started on specific PAH treatment (n=1 in combination with BPA). Patients with or without PEA did not differ hemodynamically. At the late follow-up there was a significant improvement in PEA group for NYHA class and NT-proBNP (p<0,001, and p=0,046), and in non PEA group for NYHA class and the 6MWD (p=0,012, and 0,006). We found significant difference in mortality at 1,3,5 year (Kaplan-Meier survival analysis) follow-up, for PEA group 100%-100%-100% and non PEA group 100%-85%-78% (p=0,013), respectively. Conclusions 55% of CTEPH patients were suitable for PEA, and those who survived the surgery 50% were cured. Non PEA patients improved functionally on the long term, but had worse survival.


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