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- Lagerlöf, Ingemar, et al.
(författare)
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No excess long-term mortality in stage I-IIA Hodgkin lymphoma patients treated with ABVD and limited field radiotherapy
- 2020
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Ingår i: British Journal of Haematology. - : John Wiley & Sons. - 0007-1048 .- 1365-2141. ; 188:5, s. 685-691
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Tidskriftsartikel (refereegranskat)abstract
- When treating limited stage classical Hodgkin lymphoma (cHL), balancing treatment efficacy and toxicity is important. Toxicities after extended-field radiotherapy are well documented. Investigators have aimed at reducing toxicity without compromising efficacy, mainly by using combined modality treatment (CMT), i.e. chemotherapy and limited-field radiotherapy. In some clinical trials, radiotherapy has been omitted. We evaluated 364 patients with stage I-IIA cHL treated between 1999 and 2005. Patients were treated with two or four cycles of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) according to presence of risk factors, followed by 30 Gy limited-field (reduced compared to involved-field) radiotherapy. After a median follow-up of 16 years for survival, freedom from progression at five and ten years was 93% and overall survival at 5 and 10 years was 98% and 96%, respectively. Only two relapses, out of 27, occurred after more than 5 years. There was no excess mortality compared to the general population. Of the analysed subgroups, only patients with progression within five years showed significant excess mortality. The absence of excess mortality questions the concept of omitting radiotherapy after short-term chemotherapy, a strategy that has been associated with an elevated risk of relapse but not yet with a proven reduced long-term excess mortality.
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- Pulczynski, Elisa Jacobsen, et al.
(författare)
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Age-adjusted combined immunochemotherapy without radiotherapy in newly diagnosed PCNSL : A phase II trial of the Nordic Lymphoma Group
- 2011
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Ingår i: 53rd ASH Anual Meeting and Exposition. ; , s. 696-696
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Konferensbidrag (refereegranskat)abstract
- Patients and Methods: From May 2007 to October 2010, 66 newly diagnosed primary central nervous system lymphoma (PCNSL) patients (M/F ratio 1:1) were enrolled. Younger patients (≤65 yrs; N=39) received 6 three-weekly cycles of chemotherapy consisting of: high-dose (HD)-methotrexate (MTX) (cycles 1, 2, 4 and 5), HD-cytosine arabinoside (AraC) (cycles 3 and 6) in addition to Rituximab (cycle 1 only), ifosfamide (cycles 1 and 4), cyclophosphamide (cycles 2 and 5), vincristine (cycles 2 and 5), vindesine (cycles 3 and 6), and dexamethasone (all 6 cycles). Depocyte® was delivered intratechally during the HD-MTX cycles. Elderly patients (66-75 yrs; N=27) received an identical Rituximab-containing 1st cycle. Cyclophosphamide and ifosfamide were replaced by temozolamide (cycles 2 to 6), which was also given as maintenance in patients with chemosensitive disease, and vincristine was omitted. No radiotherapy was given. Response was determined after the 2nd, 4th and 6thchemotherapy cycle by cerebral MRI and assessed according to International Primary CNS Lymphoma Coordinating Group criteria. The primary endpoint was overall survival (OS), secondary endpoints were progression-free survival (PFS), overall response rate (ORR), systemic toxicity and neurotoxicity assessed as Mini Mental State Examination (MMSE) and Functional Independence Measure (FIM). Results: The median age was 64 yrs overall, 55 yrs (range 40-65) for younger and 70 yrs (range 66-75 years) for elderly patients. In 56 patients, the International Extranodal Lymphoma Study Group prognostic score was: 0-1 (N=5), 2-3 (N=36) and 4-5 (N=15). In the remaining 10 patients, lumbar puncture was not performed in five and spinal fluid protein concentration not reported in additional five cases. Response assessment after completion of induction treatment was performed in 43 out of 66 patients and showed complete remission (CR/CRu) in 30 patients, partial remission (PR) in 5 and progressive disease (PD) in 8. The ORR was 53 %. In 23 patients, response could not be evaluated due to early progression (n=8), toxic death (n=4), poor performance (n=3), neurotoxicity (n=5), or other causes (n=3). Of the 27 elderly patients, 15 continued to maintenance therapy. Of these, 14 have completed the maintenance schedule. Remission status at month 3 was CR in 13 and PD in 1 patient. With a median follow-up of 11.1 months (range 0.6-40.2) the 3-yr OS was 54.6% with no significant difference between younger and elderly patients (56.4% vs 51.9% respectively, p=0.32). The 3-yr PFS was 35.1% (32.9% in younger and 38.2 % in elderly patients; p=0.96). There were four septic deaths. Grade 3-4 hematological toxicity was seen in 79 % of the patients. Arachnoditis-like symptoms occurred in 13 patients. In all but two patients, the symptoms resolved within less than a week. MMSE and FIM were recorded both before and after therapy in 32 patients. Scores improved in 18 and 20 patients, respectively. Conclusion: In conclusion, the schedule applied in the present study led to a 3 yr PFS of 35%. Surprisingly, no significant outcome difference was found between the younger and the elderly patients. The majority of treatment failures were due to early progressive disease under induction therapy. Although the follow-up of our study is short, de-escalation of induction treatment intensity by introduction of a less toxic agent as temozolomide, and its subsequent use in a maintenance schedule may explain a possible survival benefit of this strategy in elderly patients. Disclosures: No relevant conflicts of interest to declare.
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- Pulczynski, Elisa J, et al.
(författare)
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Successful change of treatment strategy in elderly patients with primary central nervous system lymphoma by de-escalating induction and introducing temozolomide maintenance: results from a phase 2 study by The Nordic Lymphoma Group.
- 2015
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 100:4, s. 534-540
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Tidskriftsartikel (refereegranskat)abstract
- Background: Nordic Lymphoma Group has conducted a phase ll trial in primary central nervous system lymphoma patients applying age-adjusted multi-agent immunochemotherapy regimen, which in elderly patients included temozolomide maintenance treatment. Design and Methods: Patients with newly diagnosed PCNSL aged 18-75 years were eligible. Sixty-six patients (median age 64 years) were enrolled. Two age groups were predefined as those of 18-65 and 66-75 years of age. Results: The overall response rate was 90.8 %. With a median follow-up of 22 months, the 2-year overall survival probability was 60.7 % in patients < 65 years and 55.6% in patients > 65 years (p= 0.40). The estimated progression-free survival at 2 years was 33.1% (CI: 19.1%-47.9%) in patients < 65 years and 44.4% (CI: 25.6%-61.8%) in the elderly subgroup (p=0.74). Median duration of response was 10 months in the younger, not reached in the elderly patients (p=0.33). Four patients aged 64-75 years (6 %) died from treatment related complications. Conclusion: Survival in the two age groups was similar despite a de-escalation of induction treatment in patients > 65 years. Duration of response in elderly patients receiving maintenance temozolomide was longer than in the younger age subgroup. While toxicity during induction is still of concern especially in the elderly patients we conclude from these data that de-escalation of induction therapy in elderly PCNSL patients followed by maintenance treatment seems to be a promising treatment strategy. Trial registration: ClinicalTrials.gov number NCT01458730.
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- Riihijarvi, Sari, et al.
(författare)
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High serum vascular endothelial growth factor level is an adverse prognostic factor for high-risk diffuse large B-cell lymphoma patients treated with dose-dense chemoimmunotherapy
- 2012
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Ingår i: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 89:5, s. 395-402
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To determine whether serum vascular endothelial growth factor (s-VEGF) levels and VEGF gene expression in tumor tissue predict survival of diffuse large B-cell lymphoma (DLBCL) patients treated with chemoimmunotherapy. Methods VEGF levels were measured in serum samples from 102 patients <65yrs with high-risk DLBCL using a quantitative sandwich enzyme immunoassay technique. Exon array data set of tumor tissues from 32 patients was concurrently used to determine VEGF-A exon and gene expression. All patients were treated in a Nordic phase II study with six dose-dense chemoimmunotherapy courses followed by systemic central nervous system prophylaxis. Results After a median follow-up time of 40months, 3-yr progression-free survival (PFS) was inferior in patients with high s-VEGF levels compared to those with low levels (59% vs. 83%, P=0.005). The relative risk of progression or relapse was 3.1-fold (95% confidence interval 1.346.91, P=0.008). The predictive capacity of s-VEGF levels on PFS was most pronounced in the DLBCLs of non-germinal center subtype. In contrast to serum data, VEGF mRNA expression in the lymphoma tissue did not predict outcome, and no correlation was found between s-VEGF levels and lymphoma VEGF expression. Conclusion Pretreatment s-VEGF level is a predictor of PFS after chemoimmunotherapy and may help to further stratify high-risk DLBCL patients into low- and high-risk groups.
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