Allogeneic Hematopoietic Cell Transplantation (HCT) for Advanced Mycosis Fungoides and Sezary Syndrome (MF/SS): Impact of Increasing the Use of Unrelated Donors (UD) - the EBMT Lymphoma Working Party Experience

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4403-4403
Author(s):  
Rafael F. Duarte ◽  
Ariane Boumendil ◽  
Francesco Onida ◽  
Herve Finel ◽  
Ian H Gabriel ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Univariate Analysis ◽  
Stage Iv ◽  
Working Party ◽  
Independent Effect ◽  
Independent Factor ◽  
Long Term Outcome ◽  
Allogeneic Hct

Abstract Introduction: The EBMT Lymphoma Working Party has previously reported on the long-term outcome of allogeneic HCT for patients with advanced MF/SS [J Clin Oncol 2014; 32: 3347-8 ]. Among a number of disease and transplant factors influencing patient outcome, the use of UD showed to be the strongest independent factor influencing overall survival (OS). The main shortcoming of the original reports was a limited number of 60 cases in the series, of which only 15 received allogeneic HCT from UD. As UD have been increasingly used during recent years, we sought to extend our previous analysis (1997-2007) to include patients with MF/SS allografted between 2008-2011. Patient and Methods: Endpoints were OS, progression-free survival (PFS), non-relapse mortality (NRM) and incidence of disease relapse/progression (DRP). Eligible were patients >= 18 years who were registered with the EBMT and had received an allogeneic HCT for MF/SS between 1997-2011. Centers with eligible patients were contacted to provide additional treatment and follow-up information including a written diagnostic report. Data were collected from the EBMT Registry (closed in July 2014), and endpoints were defined and analyses performed according to EBMT statistical guidelines (www.ebmt.org). Results: Eligible for final analysis were a total of 113 patients, including our original 60 cases (1997-2007) and 53 new cases (2008-2011): 71 men and 42 women, median age at HCT 48 years (21-72), 77 MF (68%) and 36 SS (32%), with 7 EORTC/ISCL stage IIB, 17 stage III, 46 stage IV-A and 26 stage IV-B (17 missing). Demographics of both time periods were comparable, except for a marked increase in the use of UD (15/60, 25% vs 29/53, 55%; p=0.001) and a reduction in the use of TBI for conditioning (30/60, 50% vs 15/53, 28%; p=0.031) in recent years. At HCT, 52 patients (46%) were refractory or in relapse/progression and 61 (54%) in complete or partial remission. Eighty-six patients (76%) received reduced-intensity (RIC) and 27 (24%) myeloablative (MAC) conditioning regimens, including TBI in 45 cases (40%). With a median follow up in survivors of 72 months (IQR: 39-97), allogeneic HCT for MF/SS offers an estimated OS of 56% at 1 year, 44% at 3 years and 38% at 5 years, and PFS of 34% at 1 year, 28% at 3 years and 25% at 5 years. NRM was 26% at 1 year and 28% at 3 years and thereafter. DRP was the main cause of treatment failure, with a probability of 40% at 1 year, 44% at 3 years and 47% at 5 years, and a mortality rate after DRP of 70% (35/50). It is worth noting that 15 patients (30%) remain alive at last follow up despite DRP, suggesting that some of these patients can be successfully rescued with donor lymphocyte infusions and other therapeutic interventions. The cumulative incidence of acute GVHD was 47% at day 100, and chronic GVHD 35% at 1 year, 45% at 3 years and 48% at 5 years. Interestingly, the univariate analysis showed a statistical trend towards a poorer OS in the cohort of new cases registered from 2008 (p=0.106). However, transplant period had no significant impact when included as a covariate in multivariate analysis, and appears to associate with the higher percentage of UD transplants in the new cohort. The use UD remained the main negative independent factor for OS (HR: 0.490; 95CI: 0.283-0.848; p=0.011) and PFS (HR: 0.468; 95CI: 0.259-0.843; p=0.011) in the multivariate models unstratified and stratified by inclusion period. The use of TBI in conditioning appears to have an independent effect to reduce the risk of DRP in the multivariate analysis (HR: 0.427; 95CI: 0.199-0.917; p=0.029), but does not translate into OS or PFS. Conclusions: This extended series confirms the existence of a clinically relevant graft-versus-lymphoma effect in MF/SS, permitting long-term disease control in a substantial proportion of high-risk patients. Follow-up studies need to address the still significant adverse effect of UD and the role of TBI conditioning in order to improve HCT results in these otherwise fatal disorders. Disclosures Mufti: Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Sureda:Takeda: Consultancy, Honoraria, Speakers Bureau.

scholarly journals Long-Term Outcome of Chronic Myelomonocytic Leukemia (CMML) Patients Treated with Hypomethylating Agents (HMA): A Single-Institution Experience

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1924-1924
Author(s):  
Adolfo Diaz Duque ◽  
Monica Cabrero ◽  
Farhad Ravandi ◽  
Naveen Pemmaraju ◽  
Gautam Borthakur ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Response Rate ◽  
Cox Regression ◽  
Continuous Variables ◽  
Hypomethylating Agents ◽  
Independent Factor ◽  
Term Outcome ◽  
Long Term Outcome

Abstract CMML is a myelodysplastic/myeloproliferative disease considered a separate entity by WHO, but from a therapeutic perspective, most clinicians consider CMML a subtype of myelodysplastic syndromes (MDS), for which hypomethylating agents (HMA) are the standard of therapy. Herein, we report on the long-term outcome of patients with CMML treated with HMA as well as prognostic associated factors. Methods: We reviewed the records of 102 consecutive patients with CMML treated between March 2004 and June 2014. Patients who underwent ASCT were excluded (n=5), and thus a total of 97 patients were analyzed. Responses were assessed according to IWG 2006. Differences among variables were evaluated by the Chi-square test and Mann–Whitney U test for categorical and continuous variables, respectively. Progression-free survival (PFS) was defined as the time from start of therapy to leukemia transformation or death. Overall survival (OS) was defined as the time from start of therapy to death. Patients who were alive were censored at the last follow-up date. PFS and OS were estimated using Kaplan-Meier analysis, and multivariate analysis was performed by Cox regression. Results: Median age at diagnosis was 71 years (50-87). Treatment was azacitidine (AZA) in 30 patients (31%) and decitabine (DEC) in 67 (69%), and they received a median of 6 courses of therapy (1-70). IPSS risk score was low in 18 patients (18.6%), int-1 in 47 (48.5%), int-2 in 23 (23.7%), and high in 4 (4.1%). Fourteen patients (14.4%) had poor-risk cytogenetics. Among patients with available mutation data, we found RAS mutations in 18 out of 79 analyzed cases (22.7%), FLT3-ITD mutations in 3 out of 86 (3.5%), NPM1 mutations in 2 out of 40 (5%), and Jak2 mutations in 1 out of 36 (2.8%). Overall response rate (ORR) was 51%, and best responses to HMA were complete remission (CR) in 51 (52%) patients, partial response (PR) in 3 (3.1%), and hematological improvement (HI) in 7 (7.2%). Median duration of response was 11.5 months (range, 1.1 to 67.5). There was no difference in response rate between DAC and AZA therapies. With a median follow-up of 11 months (1-73), 27 cases (28%) transformed into AML after a median of 19 months (5-59). At the last follow-up, 32 patients (33%) remained alive. The median PFS and OS were 18 and 23 months, respectively. The 1- and 2-year OS rates were 94.7% and 85.6%, respectively, and the 1- and 2-year PFS rates were 92.7% and 81.3%, respectively. By multivariate analysis, patients with higher hemoglobin levels (HR=0.83, 95%CI [0.72-0.97]; p=0.024) and those who achieved CR (HR=0.46 [0.26-0.81]; p=0.007) had better OS, whereas high-risk cytogenetics was associated with poorer OS (HR: 2.89 [1.34-6.21]; p=0.007). Only achievement of CR was an independent factor with impact on PFS (HR: 0.32 [0.18 – 0.55]; p<0.001). We did not identify any independent factor with significant impact on response rate. Conclusions HMA is a suitable therapy for patients with CMML, and the achievement of CR is the most important goal to improve patient outcomes. Disclosures Cortes: Celgene: Research Support Other.

scholarly journals Impact of superselective intra-arterial and systemic chemoradiotherapy for gingival carcinoma; analysis of treatment outcomes and prognostic factors

2020 ◽  
Author(s):  
Yuki Mukai ◽  
Yuichiro Hayashi ◽  
Izumi Koike ◽  
Toshiyuki Koizumi ◽  
Madoka Sugiura ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Clinical Stage ◽  
Performance Status ◽  
Univariate Analysis ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Late Toxicity ◽  
Free Survival

Abstract Background: We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC).　Methods: We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n=66; SCRT group: n=18).Results: The median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8%, 95% confidence interval [CI]: 66.0–87.6; SCRT: 50.4%, 95% CI: 27.6–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6%, 95% CI: 62.7–85.2; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.028) and local control rates (LC; IACRT: 77.2%, 95% CI: 64.2–86.4; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups.Conclusions: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.

scholarly journals Long-term outcome of indigenous 177Lu-DOTATATE PRRT in patients with Metastatic Advanced Neuroendocrine Tumours: a single institutional observation in a large tertiary care setting

2021 ◽  
Vol 94 (1117) ◽  
pp. 20201041
Author(s):  
Keerti Sitani ◽  
Rahul V Parghane ◽  
Sanjay Talole ◽  
Sandip Basu
Keyword(s):  
Primary Tumour ◽  
Univariate Analysis ◽  
Tertiary Care ◽  
Previous History ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Wide Range ◽  
Grade 3

Objectives: Assessment of long-term outcome and toxicity of indigenous 177Lu-DOTATATE PRRT in patients of metastatic/advanced NETs in a large tertiary-care PRRT setting. Methods: A total of 468 metastatic/advanced NET patients (wide range of primary sites including CUP-NETs), who underwent at least two cycles of 177Lu-DOTATATE PRRT with available follow-up information, were included and analysed retrospectively in this study. In-house labelling of DOTATATE with 177Lu (direct route produced) was carried out in the hospital radiopharmacy and treatment administered in cycles (dose: 5.55 to 7.4 GBq per patient), at 10–12 weeks interval. The assessment of long-term outcome was undertaken under three broad headings: (a) Therapeutic response, (b) Survival outcome and (c) Toxicity assessment. The median point estimate with 95% CI for progression free survival (PFS) and overall survival (OS) were calculated by Kaplan–Meier method. Prognostic covariates for association with PFS and OS was investigated by Cox proportional hazards model (univariate and multivariate Hazard Ratios) and with disease control rate (DCR) by Chi-square test, with significant P value defined as <0.05. Results: Long-term outcome (follow-up ranging from 4 to 97.6 months; median period:46 months following first 177Lu-DOTATATE PRRT) results showed, (i) on symptomatic response evaluation scale, complete response (CR) in 214 patients (45.7%), partial response (PR) in 108 (23.1%), stable disease (SD) in 118 (25.2%), progressive disease (PD) in 28 (6%). (ii) Biochemical response evaluation showed CR in 52 (12%), PR in 172 (40%), SD in 161 (38%), and PD in 42 patients (10%). (iii) Molecular imaging response (by PERCIST criteria) showed CR in 29 (6%), PR in 116 (25%), SD in 267 (57%) and PD in 56 (12%) patients. (iv) On RECIST 1.1 criteria, CR was observed in 14 patients (3%), PR in 126 patients (27%), SD in 282 patients (60%) and PD in 46 patients (10%). The median PFS and OS were not reached at a median follow-up of 46 months. Observed PFS and OS at 7 years were 71.1% 95% CI (62.4–79.7%) and 79.4% 95% CI (71.4–86.9%) respectively. PFS was dependent on previous history of chemotherapy, baseline 68Ga-DOTATATE and 18F-FDG uptake, site of primary tumour, total cumulative dose and number of PRRT cycles on univariate analysis, whereas multivariate analysis showed significant association for previous history of chemotherapy, baseline 68Ga-DOTATATE and 18F-FDG uptake and number of PRRT cycles. The OS was dependent on baseline 68Ga-DOTATATE uptake, site of primary tumour, presence of bony metastatic disease, total cumulative dose and number of PRRT cycles on univariate analysis, whereas multivariate analysis showed significant association for bony metastatic disease and number of PRRT cycles. Transient haematological toxicity of Grade 1, Grade 2, and Grade 3 was found in 8 (1.7%), 1 (0.2%) and one patient (0.2%), respectively. Nephrotoxicity of Grade 1, Grade 2, Grade 3, and Grade 4 were seen in 16 (3.5%), 3 (0.6%), 2 (0.4%) and one patient (0.2%), respectively. On a separate sub-analysis of 322 NET patients with progressive disease at the initiation point of PRRT, overall response rates (CR + PR + SD) were 93.5%, 88.5%, 89.1 and 87.9% on symptomatic, biochemical, RECIST 1.1 and PERCIST criteria and PFS and OS at 7 years 68.3% and 79.2%, respectively. Conclusions: The present results demonstrate that 177Lu-DOTATATE PRRT improved symptoms and biochemical markers substantially in most of the NET patients, with disease stabilisation on both anatomical and molecular imaging in majority and response in a sizeable fraction. Additionally, the therapeutic protocol with lesser dose per cycle (mean 5.92 GBq/cycle) and prolonged duration (over 5 cycles and 1.5 years) in a metastatic NET setting proved equally efficacious (with superior PFS and OS rates) and relatively better tolerated with minimal toxicity. Advances in knowledge: The present work critically examines the long-term results, survival outcome and toxicity profile of the indigenous 177Lu-DOTATATE (produced through direct neutron activation of enriched 176Lu) in metastatic progressive NETs across a wide range of primary sites and malignancies. Such long-term outcome data establishes the favourable impact of PRRT in a wide patient base and also the therapeutic efficacy of the product.

scholarly journals Impact of superselective intra-arterial and systemic chemoradiotherapy for gingival carcinoma; analysis of treatment outcomes and prognostic factors

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yuki Mukai ◽  
Yuichiro Hayashi ◽  
Izumi Koike ◽  
Toshiyuki Koizumi ◽  
Madoka Sugiura ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Clinical Stage ◽  
Performance Status ◽  
Univariate Analysis ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Late Toxicity ◽  
Free Survival

Abstract Background We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC). Methods We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n = 66; SCRT group: n = 18). Results The median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8, 95% confidence interval [CI]: 66.0–87.6; SCRT: 50.4, 95% CI: 27.6–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6, 95% CI: 62.7–85.2; SCRT: 42.0, 95% CI: 17.7–70.9; P = 0.028) and local control rates (LC; IACRT: 77.2, 95% CI: 64.2–86.4; SCRT: 42.0, 95% CI: 17.7–70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups. Conclusions This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.

Long-Term Follow-Up of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) with Fludarabine and Melphalan (FM) Reduced Intensity Conditioning (RIC) for High-Risk AML/MDS.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 838-838
Author(s):  
B. Oran ◽  
R. Saliba ◽  
S. Giralt ◽  
D. Couriel ◽  
A. Carrasco-Yalan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
High Risk ◽  
Disease Progression ◽  
Disease Status ◽  
Independent Effect ◽  
Donor Type

Abstract RIC with FM has extended the use of HSCT to patients otherwise not eligible for this treatment. Longer follow-up and larger number of patients now allow for more robust evaluation of risk factors and outcomes. Herein are the results of such an evaluation. Patients and Methods: We evaluated outcomes of 112 patients with high-risk AML/MDS treated from August 1996 to December 2003 with FM (fludarabine 100–180 mg/m2 and melphalan 100–180 mg/m2) and unmanipulated HSCT. Eligibility included age &gt;54 yrs. or comorbidity precluding an ablative preparative regimen. Disease status at HSCT was relapsed/refractory (n=43, 38.4%), primary induction failure (n=32, 28.6%), untreated (n=7, 6.3%) or complete remission (CR, n=30, 26.8). Cytogenetic risk was intermediate (n=59, 53%), high (n=47, 42%), low (n=3, 2.5%) or unknown (n=3, 2.5%). Donors were HLA matched related (MRD; n=59) or unrelated (UD; n=53). GVHD prophylaxis was tacrolimus based in all but one patient. Anti-thymocyte-globulin was added in 31 UD HSCT. Stem cell sources were bone marrow (n=56) or peripheral blood (n=57). Median age was 55 (range 22–74). Evaluated were the following variables and their influence on disease progression and overall survival: - age, donor type, duration of first CR, disease status at transplant (categorized as CR, No CR with (NoCR/CB) and without circulating blasts (NoCR/NoCB)), cytogenetics, acute and chronic GVHD (time dependent variables), and blood counts on day 30 (lymphocytes, monocytes and platelets). We used a Cox’s regression analysis. Results: Median time of follow up among survivors (n=43) was 28.4 mo (3.3–88.9). CR rate at day 30 post transplant was 87% (n=97), 8 patients died early and 7 did not respond. 25 (26%) of 97 patients progressed after day 30. All but 3 patients relapsed within the first year post HSCT, and only one relapsed more than 2 years after HSCT. In a landmark analysis, disease status at transplant was the only significant risk factor for progression among these 97 patients (HR of 3.7 for the NoCR/CB group compared to the CR group). 69 of 112 patients died with a median survival of 4.6 mo. Seven deaths (10% of all deaths) were observed more than 2 yrs. after HSCT, due to GVHD (n=3), infection (n=2), relapse (n=1) and unknown causes (n=1). Two-year OS and PFS was 44% and 69% respectively. Disease status at HSCT and grade II-IV aGVHD were the only significant predictors of OS on univariate and multivariate analysis. Blood counts on day 30 were associated with disease status at transplant, donor type and aGVHD. Their independent effect on outcome could not be evaluated given sample size. Conclusion: A significant portion of older patients with high-risk AML/MDS may achieve long-term PFS, but early relapses are the major cause of treatment failure in this context. Prognostic factors for event-free and overall survival Variables Multivariate analysis for disease progression CB=circulating blasts Disease status n Events (n) HR 95% CI p 2-yr PFS CR 30 6 1.0 57% (39–72) NoCR/NoCB 41 7 1.1 0.4–3.2 0.9 46% (30–60) NoCR/CB 26 12 3.7 1.4–9.8 0.001 22% (9–38) Multivariate analysis for overall survival (OS) Disease status HR 95% CI p 2-yr OS CR 30 12 1.0 66% (48–80) NoCR/NoCB 49 29 1.8 0.9–3.5 0.06 40% (26–53) NoCR/CB 34 28 2.8 1.4–3.5 0.002 23% (11–37) gd II-IV aGVHD 2.8 1.8–4.6 &lt;0.001

Long-Term Outcome of Patients with Myelodysplastic Syndromes (MDS) Treated with Hypomethylating Agents (HMA): A Report on Behalf of the MDS Clinical Research Consortium

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4641-4641
Author(s):  
Elias Jabbour ◽  
Koji Sasaki ◽  
Mikkael A. Sekeres ◽  
Rami S Komrokji ◽  
David P. Steensma ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Median Survival ◽  
Regression Models ◽  
Low Risk ◽  
Intermediate Risk ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Duration Of Response

Abstract Background: Therapy with HMA is now the standard of care for pts with MDS and chronic myelomonocytic leukemia (CMML) with complete response (CR) rates of 7% to 35%, median response durations of 9 to 10 months, and median survival of 20 to 24 months. While allogeneic stem cell transplantation (ASCT) is curative in pts with MDS, the long-term outcome of pts treated with HMA remains unknown. Aims: The aims of the study are to assess the long-term outcome of pts with MDS treated with HMA and to identify prognostic factors of long-term outcome. This may help selecting patients for this long-term treatment in whom ASCT may not be indicated. Methods: We reviewed the records of 511 pts with diagnosed MDS (n=409) and CMML (n=102) treated from 4/2000 to 4/2014 and who were treated with HMA. Pts who received ASCT (n=65) were excluded. Thus, a total of 446 pts were evaluable for the study. The probabilities of leukemia-free survival (LFS) and overall survival (OS) were estimated using the method of Kaplan and Meier. Univariate and multivariate analyses were performed to identify potential factors associated with the achievement of response with logistic regression models and survival with Cox proportional hazard regression models. Results: The median follow-up for the entire cohort was 13.6 months. Pt characteristics are outcomes described in Table 1. Best responses to HMA were CR in 124 (28%) pts, CRp in 27 (6%), PR in 9 (2%), HI in 31 (7%). Median duration of response was 7 months (1-68). 130 (29%) transformed into AML after a median of 11 months (11-60). At the last follow-up 133 (30%) remained alive. The median LFS and OS were 16.1 and 16.2 months respectively. The 2- and 5-year LFS and OS rates were 29% and 11% and 34% and 12%, respectively. By multivariate analysis, baseline characteristics associated with OS included WBC (>4 vs. ≤4), ferritin (>500 vs. ≤500), hemoglobin (>10 vs. ≤10), platelets (>500 vs. ≤500) and cytogenetics (high vs. intermediate vs. low risk) (p<0.05). Since the relative impact of each of these 5 factors on survival was similar, we assigned an arbitrary value of 1 to each of them, except for cytogenetics (0=low risk; 1=intermediate risk; and 2=high risk). Patients with 0-2 (n=265) or 3-5 (n=180) adverse factors had a median survival of 18 and 14 months, respectively (p= 0.001). To assess the benefit of achieving a response, we repeated the multivariate survival analysis using an 8-week landmark that excluded 38 patients who died within 8 weeks. The median survival was 15 months overall (8 and 20 months for patients with and without CR/CRp, PR/HI, respectively; p<0.001). The multivariate analysis included 315 patients and selected the achievement of response (CR/CRp/PR/HI vs. others), WBC (>4 vs. ≤4), ferritin (>500 vs. ≤500), platelets (>500 vs. ≤500) and cytogenetics (0=low risk; 1=intermediate risk; and 2=high risk) as independently associated with survival improvement Patients with 0-2 (n=244) or 3-5 (n=162) adverse factors had a median survival of 19 and 13 months, respectively (p<0.001). Conclusion: Our current analyses identified a small subset of pts with MDS in whom outcome of therapy with HMA is excellent and can be differentially predicted. Table 1. Patient Characteristics and Outcomes Parameter (N=446) Number (%); Median [range] Age (years) 70 (13-92) White Blood Cell Count (x 109/L) 3.5 (0.5-212) Ferritin 465.0 (0-10971) Hemoglobin (g/dL) 9.7 (6-16) Platelets (x 109/L) 68.0 (4-987) Bone marrow blasts (%) 6.0 (0-19) Prior malignancy 198 (44) Prior chemotherapy 133 (30) Prior radiotherapy 85 (19) Prior Transfusion 134 (30) Cytogenetics (by IPSS) Low 213 (48) Intermediate 78 (17.5) High 144 (8) Missing 11 (2.5) WHO RA 47 (10.5) RARS 16 (4) RCMD 75 (17) RAEB 204 (46) MDS-U 8 (2) CMML 95 (21) Missing 1 (0.2) IPSS Low 46 (10) Intermediate-1 193 (43) Intermediate-2 156 (35) High 36 (8) Missing 15 (3) MDA Score Low 59 (13) Intermediate-1 113 (25) Intermediate-2 124 (28) High 113 (25) Missing 37 (8) Type of HMA Azacitidine/ AZA+ 189 (42) Decitabine/DAC 257 (58) Response to HMA CR 124 ( 28) CRp 27 (6) PR 9 (2) HI 31 (7) NR 121 (27) Died on therapy 23 (5) NE 6 (1.4) Missing 105 (23.5) Median duration of response (mos) 7.2 (1-68) Transformed into AML 130 (29) Dead 313 (70) Disclosures No relevant conflicts of interest to declare.

scholarly journals Sleep-related hypermotor epilepsy

Neurology ◽  
2016 ◽  
Vol 88 (1) ◽  
pp. 70-77 ◽  
Author(s):  
Laura Licchetta ◽  
Francesca Bisulli ◽  
Luca Vignatelli ◽  
Corrado Zenesini ◽  
Lidia Di Vito ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Age At Onset ◽  
Hazard Ratio ◽  
Seizure Freedom ◽  
Brain Disorder ◽  
Long Term Outcome

Objective:To assess the long-term outcome of sleep-related hypermotor epilepsy (SHE).Methods:We retrospectively reconstructed a representative cohort of patients diagnosed with SHE according to international diagnostic criteria, sleep-related seizures ≥75% and follow-up ≥5 years. Terminal remission (TR) was defined as a period of ≥5 consecutive years of seizure freedom at the last follow-up. We used Kaplan-Meier estimates to calculate the cumulative time-dependent probability of TR and to generate survival curves. Univariate and multivariate Cox regression analyses were performed.Results:We included 139 patients with a 16-year median follow-up (2,414 person-years). The mean age at onset was 13 ± 10 years. SHE was sporadic in 86% of cases and familial in 14%; 16% of patients had underlying brain abnormalities. Forty-five percent of patients had at least 1 seizure in wakefulness lifetime and 55% had seizures only in sleep (typical SHE). At the last assessment, 31 patients achieved TR (TR group, 22.3%), while 108 (NTR group, 77.7%) still had seizures or had been in remission for <5 years. The cumulative TR rate was 20.4%, 23.5%, and 28.4% by 10, 20, and 30 years from inclusion. At univariate analysis, any underlying brain disorder (any combination of intellectual disability, perinatal insult, pathologic neurologic examination, and brain structural abnormalities) and seizures in wakefulness were more frequent among the NTR group (p = 0.028; p = 0.043). Absence of any underlying brain disorder (hazard ratio 4.21, 95% confidence interval 1.26–14.05, p = 0.020) and typical SHE (hazard ratio 2.76, 95% confidence interval 1.31–5.85, p = 0.008) were associated with TR.Conclusions:Our data show a poor prognosis of SHE after a long-term follow-up. Its outcome is primarily a function of the underlying etiology.

scholarly journals Impact of Superselective Intra-Arterial and Systemic Chemoradiotherapy for Gingival Carcinoma; Analysis of Treatment Outcomes and Prognostic Factors

2020 ◽  
Author(s):  
Yuki Mukai ◽  
Yuichiro Hayashi ◽  
Izumi Koike ◽  
Toshiyuki Koizumi ◽  
Madoka Sugiura ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Clinical Stage ◽  
Performance Status ◽  
Univariate Analysis ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Free Survival

Abstract Background: We compared outcomes and toxicity between radiation therapy (RT) with concurrent retrograde super-selective intra-arterial chemotherapy (IACRT) and RT with concurrent systemic chemoradiotherapy (SCRT), for gingival carcinoma (GC).　Methods: We included 84 consecutive patients who were treated for GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n=66; SCRT group: n=18).Results: Median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT group: 60 Gy; SCRT group:69 Gy). At 3 years, the two groups significantly differed in overall survival (OS; IACRT: 78.75%, 95% confidence interval [CI]: 66.00–87.62; SCRT: 50.37%, 95% CI: 27.58–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.64%, 95% CI: 62.69–85.17; SCRT: 41.96%, 95% CI: 17.65–70.90; P = 0.028) and local control (LC; IACRT: 77.17%, 95% CI: 64.23–86.41; SCRT: 41.96%, 95% CI: 17.65–70.90; P = 0.015). In univariate analysis, age ≥ 65, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with poor OS (P < 0.05). Patients with poorer PS had significantly worse PFS.Conclusions: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. IACRT is an effective and organ-preserving treatment for GC.Trial registration: retrospectively registered

Treatment outcomes of 257 patients with locally advanced nasopharyngeal carcinoma treated with nimotuzumab plus intensity-modulated radiotherapy with or without chemotherapy: A single institution experience.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 6079-6079
Author(s):  
Wang Fang Zheng ◽  
Chuner Jiang
Keyword(s):  
Multivariate Analysis ◽  
Nasopharyngeal Carcinoma ◽  
Clinical Stage ◽  
Late Complication ◽  
Locally Advanced ◽  
Intensity Modulated Radiotherapy ◽  
Stage Iv ◽  
Long Term Outcome ◽  
Intensity Modulated

6079 Background: To report the long-term outcome and toxicitie of locally advanced nasopharyngeal carcinoma (NPC) treated with nimotuzumab plus intensity- modulated radiotherapy (IMRT) with or without chemotherapy. Methods: From October 2009 to March 2014, 257 newly histology-proven, non-metastatic NPC patients were retrospectively enrolled. They are aged 10-76 years. The distribution of disease was stage III in 150 (58.4%), stage IV A in 88 (34.2%), and stage IV B in 19 (7.4%). All the patients received the treatment of nimotuzumab plus IMRT, and 239 cases were used for cisplatin-based chemotherapy. Acute and late radiation-related toxicities were graded according to the Acute and Late Radiation Morbidity Scoring Criteria of Radiation Therapy Oncology Group. The accumulated survival was calculated according to the Kaplan-Meier method. Log-rank test was used to compare the survival difference. Multivariate analysis was performed using Cox’s proportional hazard model. Results: All patients had completed the combined treatment. With a median follow-up of 48 months (range, 13–94 months), the estimated 3-year and 5-year overall survival rates were 92.6% and 86.2%, respectively. Univariate analysis showed that age, T stage, clinical stage and neoadjvant chemotherapy were related with OS. Multivariate analysis indicated that age and clinical stage were independent prognosticators. The median cycle for nimotuzumab addition was 12 weeks. The incidence of grade 3–4 acute mucositis and leukocytopenia were 10.9% and 9.3%, respectively, with no cases of skin rash and infusion reaction. Xerostomia was the most common late complication, and the degree of dry mouth in most survivors was mild-to-moderate at the last follow-up time. Conclusions: Nimotuzumab plus IMRT with or without chemotherapy showed promising outcomes in terms of loco-regional control and survival, without increasing the incidence of radiation-related toxicities for patients.

Long-Term Outcome of Anemic Non Del 5q Lower-Risk MDS Refractory to or Relapsing After Erythropoiesis Stimulating Agents (ESAs)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 442-442
Author(s):  
Charikleia Kelaidi ◽  
Sophie Park ◽  
Rosa Sapena ◽  
Odile Beyne-Rauzy ◽  
Valérie Coiteux ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Lower Risk ◽  
Who Classification ◽  
Initial Response ◽  
Primary Resistance ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Median Serum

Abstract Abstract 442 Background. ESAs are usually the first line tx of anemia in non del 5q lower risk MDS. However, not all pts respond to ESAs and median response duration is only about 2 years (Park, Blood 2008;111:574). Long-term outcome of pts who do not respond to or relapse after response to ESAs is incompletely known. We analyzed this outcome by updating a previously reported lower-risk MDS cohort of 403 pts treated with ESA in centers of the GFM (Blood 2008;111:574). Methods. We analyzed in that cohort low and int-1 (lower risk) IPSS pts with Hb<10g/dL, requiring or not RBC transfusions, who did not respond to or relapsed after ESAs, according to IWG 2000 criteria. Pts with MPN/MDS, unclassified MDS, therapy related-MDS, del 5q or 3q, IPSS int-2/high and pts who, at the time of relapse of ESAs, had progressed to AML or higher risk MDS were excluded. Pts had started ESA tx between 1998 and 2006, and data were reanalyzed 4 years after the last pt inclusion (at the reference date of 1 July 2010). 93 pts of the cohort who responded to ESAs but had not relapsed at the end of this follow up period were used for comparisons. Results. 177 pts, including 94 with primary resistance to ESAs and 83 with relapse after an initial response were analyzed. In the 94 pts with primary resistance to ESAs, M/F was 2, median age 75, WHO classification at tx onset RA, RCMD, RARS, RAEB-1 in 17%, 27%, 28%, 27% of cases, respectively (resp), karyotype fav, intermediate (int) in 86% and 14% pts, resp, IPSS low, int-1 or assignable to low/int-1 in 35%, 60% and 5% pts, resp. Median serum ferritin was 658 ng/mL and median serum EPO level (sEPO) 125 IU/L. 63% of the pts were RBC transfusion dependent (TD) (median 2 RBC units/month). Median overall survival (OS) and 3-y cumulative incidence (CI) of AML from tx onset were 43 months (mo) and 18%, resp. Among pre-tx characteristics, age >75 was associated with shorter survival (median OS 31 mo vs. not reached for age <75, P=0.01) along with int karyotype (median 26 vs 56 mo in pts with fav karyotype, P=0.005). Using multivariate analysis, only cytogenetics maintained prognostic significance for OS. No prognostic factor of AML progression was found. 21% of the 94 pts were aged <65. Their 3-y CI of AML was 19.4% vs 7.4% in pts aged >65 (P=0.93), and their median OS was not reached vs 41 mo in pts aged >65 (P=0.03). 83 pts relapsed after an initial response (IWG 2000 major and minor in 60.2% and 39.8% pts, resp) of 16.5 mo median duration (range 3–74 mo). At tx onset, M/F was 1.35, median age 74.3, WHO classification RA, RCMD, RARS, RAEB-1 in 14%, 38%, 32%, 16% of cases, resp, karyotype fav, int in 92% and 8% pts, resp, IPSS low, int-1 in 51% and 49% of pts. Median serum ferritin was 695 ng/mL and median sEPO 64 IU/L. 45% of the pts were TD (median 2 RBC units/mo). Median OS and 3-y CI of AML after relapse were 53 mo and 9.7%, resp. Median OS after relapse was 26 mo in RAEB-1 and not reached in other WHO subtypes (P=0.06) and was not influenced by the presence of multilineage dysplasia. Pts who relapsed after 24 mo had a 4.1% 3-y CI of AML vs 12.8% in pts who relapsed before 24 mo (P=0.40). Median OS was not reached in pts who relapsed after 24 mo vs 53 mo in those relapsing before 24 mo (P=0.90). No pre-tx characteristic was predictive of relapse before or after 24 mo. 16% of the 83 pts were aged <65. Their median OS after relapse was not reached at 4 years vs also not reached in pts aged >65 (P=0.17), and their 3- CI of AML after relapse was 0% vs 12% in pts aged >65 (P=0.31). In the overall pt population (ie pts with primary resistance, pts with relapse and pts with sustained response), univariate competing risk modeling found CI of death from cardiovascular causes to be correlated with TD and older age at tx onset but not with response status, while only age remained significant in multivariate analysis (HR=1.12 [1.014-1.24], P=0.02). Both older age and early failure (ie primary failure or relapse <24 mo) were associated with increased CI of death from MDS-related causes (AML, hemorrhage, infection) (HR=1.05 [1.00-1.10], P=0.04; and HR=5.64 [1.85-17.22], P=0.002, resp). Conclusions. Failure to respond or loss of response to ESAs in the absence of frank disease progression to AML or higher risk MDS was not associated with poor outcome in lower-risk MDS, except in some pt subgroups (pts with intermediate karyotype and with a diagnosis of RAEB-1). Those figures have to be taken into account for therapeutic decisions, especially in pts aged <65 years, where median survival was not reached with relatively long term follow up. Disclosures: Off Label Use: ESAs for anemia in MDS. Fenaux:CELGENE, JANSSEN CILAG, ROCHE, AMGEN, MERCK, GSK, NOVARTIS, CEPHALON: Honoraria, Research Funding.

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