Long-term follow up of patients in European Vasculitis Study Group clinical trials

2012 ◽  
Author(s):  
Kerstin Westman
Keyword(s):  
Clinical Trials ◽  
Study Group ◽  
Long Term Follow Up

scholarly journals Treatment of Stage IA Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL): An Analysis from the German Hodgkin Study Group (GHSG)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3058-3058 ◽  
Author(s):  
Dennis A. Eichenauer ◽  
Annette Pluetschow ◽  
Michael Fuchs ◽  
Karolin Behringer ◽  
Boris Böll ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Hodgkin Lymphoma ◽  
Combined Modality Treatment ◽  
Study Group ◽  
Excellent Outcome ◽  
German Hodgkin Study Group ◽  
Long Term Follow Up ◽  
Stage Ia

Abstract Introduction: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity accounting for about 5% of all HL cases. As compared with classical HL (cHL), NLPHL is characterized by the absence of CD30 and the consistent expression of CD20 on the malignant lymphocyte predominant (LP) cells. Given a more indolent clinical course, especially early-stage NLPHL is often treated less aggressive than classical HL (cHL). In stage IA patients, radiotherapy (RT) alone is applied at most institutions. However, this clinical practice is not based on data from prospective clinical trials with sufficient follow-up. To shed more light on the optimal treatment of stage IA NLPHL, we performed an analysis including patients with long-term follow-up treated within German Hodgkin Study Group (GHSG) clinical trials. Patients: A total of 256 stage IA NLPHL patients treated within 7 prospective GHSG studies between 1988 and 2009 were included in the analysis. Treatment consisted of combined-modality treatment (CMT) (n=72), extended-field RT (EF-RT) (n=49), involved-field RT (IF-RT) (n=108) or four weekly doses of the anti-CD20 antibody rituximab (n=27). Results: The median age at NLPHL diagnosis was 38.5 years (range: 17-75); 194/256 (75.8%) patients were male and 62/256 (24.2%) patients were female. Median follow-up for the whole patient group was 91 months (98 months for CMT, 118 months for EF-RT, 87 months for IF-RT, 49 months for rituximab). All patients responded to treatment irrespective of the treatment modality applied. At 8 years, progression-free survival (PFS) and overall survival (OS) rates were 88.5% and 94.5% for CMT, 84.3% and 95.7% for EF-RT and 91.9% and 99.0% for IF-RT; 4-year PFS and OS rates for patients treated with rituximab were 81.0% and 100%. Seventeen patients developed a second malignancy in the course of follow-up (8 after CMT, 3 after EF-RT, 4 after IF-RT, 2 after rituxmab). Nine of these second malignancies were solid tumors (4 after CMT, 2 after EF-RT, 1 after IF-RT, 2 after rituximab) and 8 were hematologic malignancies (4 after CMT, 1 after EF-RT, 3 after IF-RT, none after rituximab). A total 12 deaths occurred. The most common cause of death was cardiac failure (n=3). Only one patient died from NLPHL. Conclusion: Based on this large analysis with long-term follow-up, IF-RT should be the standard of care for stage IA NLPHL. Treatment with single agent rituximab is associated with an increased event rate when compared with IF-RT and should therefore not be routinely used in stage IA NLPHL patients. However, given the shorter follow-up in comparison with CMT, EF-RT and IF-RT, final conclusions regarding rituximab especially in terms of treatment-related late sequelae cannot yet be drawn. Addition of chemotherapy does not improve the excellent outcome achieved with RT alone. Disclosures Off Label Use: Rituximab in NLPHL.

scholarly journals Disability improvement as a clinically relevant outcome in clinical trials of relapsing forms of multiple sclerosis

2021 ◽  
pp. 135245852110002
Author(s):  
Bruce AC Cree ◽  
Jeffrey A Cohen ◽  
Anthony T Reder ◽  
Davorka Tomic ◽  
Diego Silva ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Therapeutic Benefit ◽  
Disease Modifying Therapies ◽  
Long Term Follow Up ◽  
Post Hoc ◽  
Switch Group ◽  
Relevant Outcome

Background: Disease-modifying therapies (DMTs) can reduce the risk of disability worsening in patients with relapsing forms of multiple sclerosis (RMS). High-efficacy DMTs can lead to confirmed or sustained disability improvement (CDI and SDI). Objective and Methods: Post hoc analyses of data from the TRANSFORMS, FREEDOMS, and FREEDOMS II trials and their extensions assessed the effects of fingolimod (0.5–1.25 mg/day) on stabilizing or improving disability over ⩽8 years in participants with RMS. CDI and SDI rates were compared between participants initially randomized to fingolimod, interferon (IFNβ-1a), or placebo. Results: At 8 years’ follow-up in TRANSFORMS, 35.1% (95% confidence interval [CI], 28.2%–43.1%) of assessed participants in the IFNβ-1a–fingolimod switch group and 41.9% (36.6%–47.6%) on continuous fingolimod experienced CDI; disability did not worsen in approximately 70%. Similar results were seen in the combined FREEDOMS population. Proportionally fewer TRANSFORMS participants achieved SDI in the IFNβ-1a–fingolimod switch group than on continuous fingolimod (5.4% [3.0%–9.5%] vs 14.2% [10.8%–18.4%], p = 0.01). Conclusion: CDI and SDI are outcomes of interest for clinical trials and for long-term follow-up of participants with RMS. Monitoring CDI and SDI in addition to disability worsening may facilitate understanding of the therapeutic benefit of RMS treatments.

scholarly journals Survival Differences in Clinical Trials With Long-Term Follow-Up

2016 ◽  
Vol 67 (5) ◽  
pp. 600
Author(s):  
William J. Kostis ◽  
Abel E. Moreyra ◽  
Javier Cabrera ◽  
John B. Kostis
Keyword(s):  
Clinical Trials ◽  
Long Term Follow Up ◽  
Survival Differences

Long-Term Follow-Up of BEACOPPescalated Chemotherapy in Patients with Advanced-Stage Hodgkin Lymphoma on Behalf of the German Hodgkin Study Group.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 211-211
Author(s):  
Engert Andreas ◽  
Jeremy Franklin ◽  
Volker Diehl
Keyword(s):  
Hodgkin Lymphoma ◽  
Secondary Malignancy ◽  
Tumor Control ◽  
Study Group ◽  
Advanced Stage ◽  
Secondary Aml ◽  
German Hodgkin Study Group ◽  
Long Term Follow Up

Abstract The HD9 trial of the German Hodgkin Study Group (GHSG) compared two different doses (baseline and escalated) of the novel chemotherapy regimen BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) in patients with advanced-stage Hodgkin lymphoma (HL). The previous analysis with a median follow-up of 5 years showed improved tumor control (FFTF) and overall survival (OS) for BEACOPPescalated. Since BEACOPPescalated had been associated with more toxicity as compared with ABVD we report the results of long-term follow-up of 1196 patients enrolled and randomized in that study. The median follow-up was 112 months; a total of 370 centres contributed. Patients received one of three chemotherapy regimens: 8 cycles of COPP (cyclophosphamide, vincristine, procarbazine, and prednisone) alternating with ABVD (doxorubicin, bleomycin, vinblastin, and dacarbazine), 8 cycles of standard-dose BEACOPP or 8 cycles of escalated-dose BEACOPP. At 10 years, FFTF rates were 64%, 70% and 82%, OS rates were 75%, 80%, and 86 for COPP-ABVD (arm A), BEACOPPbaseline (arm B), and BEACOPPescalated, respectively (p < 0,001). Importantly, BEACOPPescalated was also significantly better than BEACOPPbaseline in terms of FFTF (p < 0.0001) and OS (p = 0.0053). Death due to HL occurred in 11.5%, 8.1% and 2.8% in arms A, B, and C, respectively. 74 second malignancies were documented, including secondary acute myeloid leukaemias (1,7,14), Non-Hodgkin lymphoma (7,8,5), and solid tumors (7,16,9) in arms A, B, and C respectively. The corresponding overall secondary malignancy rates were 6.7%, 8.9% and 6.8%. Importantly, the risk of secondary AML (sAML), although increased in this study after BEACOPPescalated, amounts to 0.9% in our follow-up study with BEACOPPescalated (HD12) in 1502 advanced-stage HL patients randomized and four years median follow-up. Although the higher rate of secondary AML after BEACOPPescalated in HD9 most likely occurred by chance, interestingly, 70% of patients in this group had additional radiotherapy whereas only 39% were radiated in HD12. Taken together, the 10 years follow-up of BEACOPPescalated chemotherapy demonstrates a stabilized significant improvement in long-term FFTF and OS for advanced-stage HL. Although for formal prove the results of ongoing prospective randomized comparisons with 8 cycles of ABVD might be required, these results clearly challenge ABVD as standard of care for this patient population.

Identification of Homozygous JAK2V617F Mutation in Unfractioned Blood Samples in a Substantial Proportion of Myeloproliferative Disorders: Long Term Follow-Up Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4644-4644
Author(s):  
Irina Panovska ◽  
Nadica Matevska ◽  
Martin Ivanovski ◽  
Sanja Trajkova ◽  
Aleksandar Stojanovik ◽  
...  
Keyword(s):  
Jak2 V617f ◽  
Jak2v617f Mutation ◽  
Study Group ◽  
Hematopoietic Progenitors ◽  
Blood Samples ◽  
Allele Burden ◽  
Long Term Follow Up ◽  
Thrombotic Complications

Abstract The discovery of the activating V617F mutation in the JAK2 tyrosine kinase gene in patients with myloproliferative disorders (MPD) provides a major breakthrough in the understanding of the pathogenesis, proving clonality and securing diagnosis of these diseases. The JAK2 V617F allele is an acquired somatic disease allele that arises in hematopoietic progenitors and confers a selective growth advantage. The mutation has been traced to a primitive stem cell that is capable of erythroid and myeloid differentiation. The data for the potential involvement of the B and T lymphocytes with the JAK2V617F mutation are still inconsistent. We present the results from the study designed the evaluate the prevalence of the JAK2V617F mutation in MPDs patients in our population and to investigate whether MPD patients that carry the JAK2V617F mutation differ in clinical course and outcome from JAK2V617F negative MPD patients. The study group consisted of 64 living MPD patients diagnosed according to standard WHO criteria for diagnosis of MPD (26 patients were diagnosed as polycythemia vera (PV), 34 as essential thrombocythemia (ET), 6 as idiopatic myelofibrosis (MF) and 8 were classified as atypical MPD) with the median follow-up of 7,4 years. DNA samples were obtained from unfractionated blood samples and the frequency of V617F JAK2 mutation was analyzed by allele-specific PCR assay. The mutant allele burden in mutation positive samples was analyzed by DNA sequencing. Our results showed that the JAK2 V617F mutation was present in 79% of patients with PV (36% were homozygous for the mutation), 58% with ET (11% homozygous), 69% with MF (28% homozygous) and in 33% of patients with atypical MPD. The mutant JAK2V617F allele burden was greater than 95% in two PV patients, which in the presence of 27% lymphocytes in the peripheral blood of the patients indicate lymphocytes involvement with the mutation. The high frequency of observed homozygosity for JAK2V617F in our study group was probably due to the long disease duration (median follow-up 11,4 years) and favors the theory of a time dependent increase in clonal dominance. Correlations of clinical and laboratory features at diagnosis and subsequent follow-up, including incidence of thrombo-hemorrhagic events, disease transformation and survival of JAK2V617F-positive and JAK2V617F-negative patients did not reveal significant differences except for the incidence of thrombotic complications. The JAK2V617F positive group had a higher incidence of thrombotic complications (30%) compared with the JAK2-V617F-negative group (14%, P< 0.05). Although we observed a disparity in the incidence of the JAK2V617F mutation in different MPD entities in our population with respect to the expected frequency of JAK2V617F from the literature, our results confirm the diagnostic significance of the JAK2V617F mutation in MPDs and support the notion that patients with this mutation should be classified in a new entity of MPDs. Identification of homozygous JAK2V617F mutation in unfractionated blood samples in a substantial proportion of long term follow-up MPD patients, together with the identification of the mutant JAK2V617F allele burden greater than 95% in two PV patients, suggests that acquisition of the JAK2V617F mutation arises in early multilineage hematopoietic progenitors and warrants further investigation.

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