Transforming growth factor (TGF)-beta3 has been hypothesized to prevent or alleviate oral mucositis (OM) in cancer patients receiving high-dose chemotherapy (CT). Two double-blind, placebo-controlled, multicenter, phase II studies of TGF-beta3 were initiated in the United States, Europe, and Argentina in patients with lymphomas or solid tumors who were receiving highly stomatotoxic CT regimens. Patients were to apply 10-mL mouthwash applications of TGF-beta3 (25 microg/mL) or placebo four times daily (or twice daily) 1 day before and all days during CT. The patients were subsequently evaluated for OM incidence, severity, and duration using National Institute of Cancer Common Toxicity Criteria (NCI-CTC) criteria and an objective scoring system (1). After the start of the trials, negative results from new preclinical studies suggesting suboptimal formulation and/or dosing led to an interim analysis of the ongoing clinical trials. One hundred fifty-two patients from the combined studies were included in the interim analysis, with 116 patients on the TGF-beta3 four times daily and placebo arms. Most (72%) patients had breast cancer, 22% had lymphomas, and 6% had other solid tumors. Although 98% (149 of 152) of patients experienced adverse events, only 14% (22 of 152) experienced events that were judged as possibly or probably related to the study drug (primarily gastrointestinal symptoms). No clinically relevant differences were seen between the treatment and placebo arms regarding safety, nor was there evidence for systemic absorption of TGF-beta3. Finally, there was no advantage of TGF-beta3 treatment regarding the incidence (TGF-beta3 four times daily versus placebo [46% versus 47%]), onset, or duration of NCI-CTC grade 3 or 4 OM. For this dose, formulation, regimen. and patient population, TGF-beta3 was not effective in the prevention or alleviation of CT-induced OM.
Summary:In patients undergoing bone marrow transplant (BMT), reactive oxygen species (ROS) are released as a consequence of the events related to the preparative regimen. Total body irradiation (TBI), which is known to generate ROS, is a routine preconditioning procedure prior to BMT. Several studies have demonstrated that amifostine protects normal tissues. In the present report, we investigated the oxidative state of plasma and erythrocytes in 21 patients with hematological malignancies undergoing TBI. The dose fraction was 160 cGy, twice daily (eight sessions). For ROS detection, we used electron spin resonance spectroscopy and spin-trapping technique. In all, 15 patients received amifostine prior to the irradiation and six did not. No free radical signal was detected in the plasma samples spectrum of 15 amifostinetreated patients, and five of six samples of nontreated patients showed ROS signal. Only two of 15 treated patients had mucositis degree higher than 2, whereas five of six nontreated patients suffered this complication. The average hospitalization days in treated and nontreated patients were 23.5 and 29.7, respectively. This work represents an original observation; we found by direct measurements of free radicals that ROS are released during TBI, and confirmed the amifostine radical scavenger activity.
Background. Hematopoietic Stem Cell Transplant Comorbidity Index (HCT.CI) score, described by Sorror, is a useful tool to assess the risk for Non Relapse Mortality (NRM) after Allogeneic HSCT. The impact of this score in Autologous HSCT is still to be confirmed. Aims. To determine the impact of HCT.Ci score in the morbidity and mortality after autologous HSCT, assessing the 100 day morbidity defined as orothraqueal intubation (OTI), dialysis or shock (defined as vasopressors need), 100 day mortality, early morbi-mortality (combined end-point by any of the previous end-point) and long term NRM. Materials and Methods. We retrospectively reviewed 1478 medical records of adult patients who received an autologous HSCT in our centre between October 2002 and April 2016. Median age was 49 years (range 16-74 years), 58% were male, prevalent diseases were Multiple Myeloma (48%), Non Hodgkin Lymphoma (27%) and Hodgkin Lymphoma (18%), 49% were in complete remission, 46% received one chemotherapy scheme before transplant, 41% two schemes and 12% three or more (heavily pre-treated). In respect to conditionings, melphalan was used in 48% of the cases, CBV in 25%, BEAM in 8% as well as BendaEAM. Seventy five percent received an infusion of stem cells CD34+≥3x10.6/kg. Regarding comorbidities, 58% had low risk (LR) HCT.CI (score 0), 32% intermediate risk (IR) (1-2) and 11% high risk (HR) (≥3). For univariate analysis we use Chi2 for dichotomic variables, Kaplan-Meier for Overall Survival (OS) and cumulative incidence for NRM; for multivariate analysis we used logistic regression for dichotomic and Cox regression for time dependant variables. Results. Median follow up was 1.9 years. Early mortality (day 100) was 2.8%, 5.6% required OTI, 4.8% required vassopresors and 2.2% dialysis, 1-3 years NRM and OS were 4.3-5.2% and 89-77% respectively. High risk HCT.Ci patients had a significant increase in 100 day mortality compared to IR and LR (7% vs.3% vs. 2% respectively, p=0.002), OTI (12% vs. 7% vs. 4%, p<0.001), dialysis (4.5% vs.2.6% vs. 1.5%, p=0.04), shock (10% vs.6.4% vs. 3%, p<0.001), early morbi-mortality (15% vs.9 % vs. 4.6%, p<0.001) and NRM (1-3 years 9.2-13% vs. 3.8-3.8% vs. 3.5-4.5%, p<0.001) (figure 1). After multivariate analysis these outcomes remain significant (showed as OR with 95% CI, IR and HR compared to LR): early mortality (1.8, 0.8-4.2 and 3.9, 1.6-9.7, p=0.003), OTI (2.1, 1.2-3.7, p<0.01 and 3.9, 2.0-7.5, p<0.001), dialysis (2.2, 0.8-5.5 and 4.1, 1.4-11.7, p<0.01), shock (2.7, 1.4-4.9, p=0.001 and 4.4, 2.1-8.9, p<0.001), early morbi-mortality (2.4, 1.4-4.0, p=0.001 and 4.2, 2.3-7.6, p<0.001) and NRM (1.3, 0.7-2.4 and 3.0, 1.5-5.7, p=0.001) (table 1). No significant impact was observed in OS. Other than comorbidities, significant impact was observed in early mortality (pre-transplant status, heavily pre-treated patients and BendaEAM conditioning), OTI (NHL, heavily pre-treated patients, BendaEAM conditioning), dialysis (pre-transplant status and BendaEAM conditioning), shock (NHL, heavily pre-treated patients and BendaEAM conditioning), morbi-mortality (NHL and BendaEAM conditioning) and NRM (male patients, NHL, pre-transplant status, heavily pre-treated patients and BendaEAM conditioning). Conclusions. We observed that HCT.CI had a significant impact on Autologous HSCT treatment related mortality basically due to early toxicity express as 100 day mortality and the three main morbidity outcomes as well as the combined end point. This observation should be confirmed in larger series. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
Introduction Hodgkin´s Lymphoma (HL) is a highly curable disease. However, there are still patients with primary refractory disease or who relapse after first-line treatment, or even after high-dose chemotherapy with hematopoietic cell rescue. Allogeneic stem cell transplant (ASCT) is therapeutic for this patients. Objective To analyze the experience with relapsed HL patients that received ASCT with reduced intensity conditioning (RIC)regimen in 8 Argentine Medical Centers. Design and Population We performed a retrospective multicenter analysis from data obtained from medical records. Fifty-four patients with relapsed HL who received ASCT had a median age of 26years. The relationship between male / female was 1/1. Only 3 patients (5.5%) at the time of transplant had a performance status> 1 according to ECOG. Ninety-six percent of the patients had received previously autologous transplant. Most patients 43 (80%) received an identical sibling donor transplant. All patients receiving unrelated donor transplants had in vivo lymphocyte depletion as prophylaxis of graft versus host disease. Forty-three patients (79.6%) received as a conditioning regimen Fludarabine + Melphalan. The disease status at transplant was: complete remission (CR) 33%, partial remission (PR) 54%, stable disease / progressed (SD / PD) 13%. Results With a median follow up of 2.7 years, actuarial overall survival (OS) at 1 and 5 years was 65% and 20% respectively and disease free survival (DFS) at 1 and 5 years was 35 % and 18% respectively. The incidence of acute GVHD grade II-IV was 31%. Patients in CR at the time of transplant showed significant differences compared with those who were not in CR in DFS (1-5 years 52-27% vs 19-14%, p=0.01), OS (1-5 years 76-38% vs 59-13%, p=0.02) and non relapsed mortality (NRM) (1-5 years 6-12% vs 34-39%, p=0.04). Age, PS, the use Fludarabine + Melphalan as conditioning regimen, unrelated donor, aGVHD, were not variables that modified the overall survival and disease-free survival. Conclusion The ASCT with RIC regimen is a feasible therapeutic option in patients with HL, especially in patients who can achieve CR. The low rate of DFS is still an issue in this setting, may be new drugs may help in optimizing pretransplant response status to improve patients’ outcome. Disclosures: No relevant conflicts of interest to declare.
Materials and Methods We retrospectively reviewed 137 medical records of patients older than 50 years receiving an allogeneic hematopoietic stem cell transplant (HSCT) in 9 centers from Argentina. We evaluated the following characteristics: sex, age, diagnosis, stage, comorbidities (according to the HCT-CI score), type of donor, histocompatibility, source, conditioning and immunosupression. We analyzed the incidence and severity of acute Graft-vs-Host disease (aGVHD) with Chi Square, Overall Survival (OS) and Disease Free Survival (DFS) with Kaplan Meier and Relapse, Non Relapse Mortality y chronic GVHD (cGVHD) with CI. For multivariate analysis (MA) we included variables that in univariate had a p<0.2, used Cox regression model for time dependant outcomes and logistic regression for dichotomic variables, considering significant a p<0.05. Results Patients characteristics are listed in table 1. Between January 1997 and July 2013, 137 transplants were performed in adults older than 50 years, with a median follow up 1.3 years. Acute GVHD incidence was 41% (19% were grade II and 7.3% III-IV). The only variable associated with aGVH clinically significant (G II-IV) was AML that was protective (14% vs 35%, p<0.01; significant in MA, HR 0.29; 95% CI 0.12-0.72). Chronic GVHD incidence was 25%, extensive in 9.4% and the only risk factor for this outcome was MPN (1-3 years 40%-NA vs 12-20%, p=<0.01). Global OS 1 and 3 years was 44 and 20%, DFS was 33 and 20%, Relapse was 35 and 41% and NRM was 36 and 43% respectively. Co-morbid patients showed a significant increase in NRM (HCT.CI 0 vs 1 vs ≥2, 1-3 years 17-24%, 40-46% and 45-67%, p=0.01; significant in MA, for HCT.CI 0 vs ≥1, HR 2.4, 95% CI 1.12-5.25), as well as male patients (1-3 years 36-47% vs 23-27%, p=0.03), MPN (1-3 years 43-65% vs 29.34%, p=0.01) and Cyclosporine based immunosuppressant regimen (CSA) vs tacrolimus (1-3 years 47-53% vs 25-36%, p=0.01). AML patients experienced a higher relapse rate (1-3 years 50-50% vs 28-32%, p<0.01) as well as Fludarabine-Busulfan conditioning (1-3 years 45-48% vs 31-32%, p=0.02). Finally patients without comorbidities (HCT.CI 0 vs ≥1) had higher OS (1-3 years 54-30% vs 36-16%, p=0.03) and DFS (1-3 years 43-31% vs 30-15%, p=0.05) as well as tacrolimus vs CSA base regimen that had higher OS (1-3 years 49-25% vs 31-13%, p=0.01) and DFS (1-3 year 41-26% vs 20-11%, p<0.01; significant in MA, HR 0.56, 95% CI 0.33-0.98). Age (older than 60 vs younger), type of donor, use of myeloablative conditioning regimen and source did not showed any significant difference in the outcome analyzed. Conclusion HSCT is a valid therapeutic option for older patients. In this retrospective analysis of patients older than 50 years, we found that the main risk factors that impact in transplant outcome are patients comorbidities and not age, whereas transplant related toxicities increase with the number of comorbidities and therefore decrease OS and DFS. Beyond the fact that certain disease experienced more aGHVD (AML) or cGVHD and higher NRL (MPN) the other factor significantly related in transplant outcome was the use of tacrolimus vs CSA. Disclosures: No relevant conflicts of interest to declare.
Introduction Estimated incidence of cHL in Argentina is 842 cases/year (Globocan 2018). There is no local data regarding response rates (RR) to FL. GATLA (Grupo Argentino de Tratamiento de Leucemia Aguda) reported 3 years progression free survival (PFS) rates of 90% and overall survival (OS) of 98% regardless of stage. HL has a high cure rate; 10% are primary refractory and 30% relapse after achieving complete remission (CR). In stage I-IIa, 5 years OS is estimated around 90% and 60% in stage IV (Ann Hematol 2019). Objectives Primary: To learn the RR, PFS and associated variables after FL of cHL in public (PuI) and private institutions (PrI) in Argentina. Secondary: To learn the OS rates. To study epidemiological characteristics of the patients (Pts) in participating institutions and reveal differences which may affect the response to treatment. Materials and methods Retrospective analysis of consecutive Pts with diagnosis of cHL from 1/1/2008 to 2/1/2019 with available follow up data. Descriptive statistics was performed in clinical variables and histopathological findings. Quantitative variables were expressed as median an interquartile range (IQR) and qualitative variables as total number and percentage (%). Survival rates were estimated by the Kaplan-Meier method and compared by the log-rank test. OS was measured from the date of diagnosis to date of death or last follow-up visit. Results 520 Pts from 7 PuI and PrI in Buenos Aires and Rosario were examined. 22 Pts had nodular lymphocyte predominant HL. Data on the 498 Pts with cHL is presented. Median follow up: 37.4 months (CI95% 17.7-63.5). Pts characteristics: Table 1. The median time from diagnosis to FL was 22 days (IQR 14-42), significantly shorter in PrI (32.5 (IC95% 27-38) vs. 49.3 (IC95% 38.5-60.2); p=0.0027). 96.5% of Pts received ABVD as FL, dose modifications or transitory suspension were required in 17.1%, and 82.1% received all cycles properly. CR was achieved in 83.4% of Pts and partial remission (PR) in 6.3%. The % achieving CR was higher in PrI; more PR were achieved in PuI. 10.3% had progressive disease (PD) at the end-of FL. 85.4% (n=373) had negative end-of-treatment FDG-PET results (DS1-3). Interim PET scan was performed in 70% of Pts (n=357), with 83.8% achieving metabolic CR but only 15.5% (n=70) being treated with response-adapted strategies (6.5% deescalated to AVD). Regarding hematologic toxicity, anemia, neutropenia and thrombocytopenia were found in 28.5%, 56.4% and 7.2% of Pts, respectively. Febrile neutropenia was reported in 9 Pts. 28.6% developed non-hematologic toxicities (41/144 pulmonary toxicity). 51 Pts had primary refractory disease and 69 (14%) relapsed during follow-up (median time to relapse 4.4 months (CI95% 0-13)). 65 Pts died (12.5%), 34 due to lymphoma progression and the remaining 31 due to toxicity. 2 years OS rate was 91% (CI95% 88% - 94%) and 85% at 5 years (CI95% 80% - 89%). There was no difference in OS between PrI and PuI (p=0.27); every day of delay in the beginning of FL increased 0.89 (IC95% 0.6-1.8) the risk of achieving PR or PD at the end of FL. 5 years PFS rate was 76% (CI95% 70-81) (figure 1-2: OS according to risk group and PFS). Outcomes were statistically better in women, age younger than 60, non-bulky disease, absence of extranodal disease or risk factors such as leukocytosis, lymphopenia and hipoalbuminemia. Pts with normal ESD, stage I-III, early favorable and advanced favorable stages and Charlson score <3 also showed survival advantage (p<0.01). On multivariate analysis Charlsons score and end-of-treatment FDG-PET scan remained independent predictors of OS with HR of 1.2 (CI95%1.1-1.7; p=0.001) and 2.3 (CI95% 1.7-3.2; p<0.0001), respectively. Conclusions This is one of the largest retrospective cohorts reported in cHL. Epidemiology characteristics, RR, PFS, and associated variables are similar to the ones reported in literature. Five years OS proved to be higher than previously reported. ABVD is the chemotherapy regimen of choice in our country and as our study shows, is well tolerated but not exempt from toxicity. Early FL initiation improves outcome. PET scan was widely used but only 15.5% of the Pts were treated with response adapted strategies. Taking into account that in 47.6% of the Pts toxicity was the main cause of death, the use of PET-guided treatment in our population should be strongly considered. * The first four authors have equal contribution figure 1 Disclosures No relevant conflicts of interest to declare.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.