Incidence of Major Adverse Cardiovascular Events (MACE) and Risk Factors (RF) in Patients Undergoing Autologous Stem Cell Transplantation (ASCT) for Lymphoma (original) (raw)
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Indian Journal of Hematology and Blood Transfusion, 2016
The aim of this study is to evaluate the results of relapsed or refractory Hodgkin (HL) and non-Hodgkin Lymphomas (NHL) patients who underwent autologous stem cell transplantation supported high-dose chemotherapy (HDC-ASCT). Forty patients who received HDC-ASCT between November 2004 and February 2014 for relapsed or refractory HL and NHL were analysed retrospectively. There were 22 patients with HL and 18 patients with NHL. Thirty-eight patients could be evaluated after transplantation, as two of the patients died in the early posttransplantation period. We identified complete response in 24 patients (63%), partial response in 8 patients (21%), stable disease in 4 patients (11%) and progressive disease in 2 patients (5%). In all patient groups, 5-year overall survival (OS) and event free survival (EFS) were 43 and 40%, respectively; however there was no statistically significant survival difference between HL and NHL patients after ASCT, and 5-year OS and EFS were 47, 40 and 53%, 23%, respectively (p = 0.43, p = 0.76). Chemosensitive relapse had a positive impact on OS (p = 0.02). This study provides evidence for the effectiveness of HDC-ASCT as salvage therapy for patients with relapsed/refractory NHL and HL. Chemosensitive relapse is the most important prognostic factor determining the outcome of the ASCT.
Biology of Blood and Marrow Transplantation, 2013
Achievement of a complete remission (CR) is considered an important goal of therapy in multiple myeloma (MM). High dose chemotherapy with autologous stem cell transplantation (ASCT) was the first treatment to reliably produce CR in MM. Several approaches have been tried to further increase the CR rate including polychemotherapy preparative regimens, tandem ASCT, consolidation and/or maintenance therapy. Since there is a dose response effect for melphalan, we evaluated an alternative single ASCT strategy using higher dose melphalan at 280 mg/m 2 (MEL 280). Methods: We completed a multicenter, phase II trial of MEL 280 in patients with MM undergoing ASCT after a median of 1 prior regimen. Two doses of amifostine (AF) 740 mg/m 2 IV over 5-15 minutes were administered 24 hour and 15 min before MEL 280 to ameliorate mucosal toxicity. Between 5/1999 and 10/2003, 58 MM patients (pts) received this high dose regimen after dexamethasone-based induction regimens. Lenalidomide or bortezomib were not used in induction. The median age was 50 yrs (35-66), 33 were male, median initial beta 2-microglobulin level was 3.0 mg/L (0.8-22.4). The subtypes included IgG (n¼ 32), IgA (n ¼15), light chain (n ¼ 8)and non-secretory (n¼ 3); 67% had Durie Salmon stage III disease; 90% of pts were chemosensitive to dexamethasone-based induction therapy. Median time from diagnosis to ASCT was 7.5 months. Toxicity: Bearman critieria were utilized for grading regimen-related toxicity (RRT): grade 1 mucositis was seen in 41%, grade 2 in 14% and grade 3 in 1.7%. Other grade 3 toxicities included: lung (1.7%) and renal (1.7%); 1 pt died from melphalan-induced interstitial pneumonitis; 7% experienced atrial fibrillation or flutter. Of the 57 evaluable pts, CR was achieved in 28 (49%), VGPR in 6 (11%), PR in 17 (30%), SD in 4 (7%) unknown in 1 (1.5%) and progression in 1 (1.5%). At a median follow-up of 7 yrs, 76% of pts have progressed and 57% have died. The cause of death was MM in 88% (29/33) and non-relapse causes in 4 (1 lung cancer,1 coronary disease, 1 sepsis and 1 complications of subsequent allogeneic transplant). The median overall survival (OS) is 67 months while the median progression-free survival (PFS) is 22 months. PFS and OS at 7 years was 10% and 39% respectively. Conclusions: MEL 280 + AF is well-tolerated with low transplant related mortality. Excellent VGPR+CR rates of 60% were achieved in the pre-novel agent era. However, the high CR + VGPR rate after ASCT did not translate into an improvement in PFS/OS from single or tandem ASCT trials in that era (Barlogie et al. J Clin Oncol. 2010; 28: 1209-14). In contrast to recent studies showing CR correlates with improved long term outcomes, MEL 280 dose escalation increased response depth, however, sustainability of response is not impacted.
Bone marrow transplantation, 2018
A recent shortage of melphalan has prompted the use of alternatives to BEAM (BCNU, Etoposide, Cytarabine, Melphalan) conditioning for autologous stem cell transplantion (ASCT). The BEAC (BCNU, Etoposide, Cytarabine, Cyclophosphamide) regimen has been employed as a conditioning regimen in lymphoma patients. However, there have been recent concerns about the toxicity of BEAC. We conducted a retrospective analysis of the EBMT database comparing the outcome of patients conditioned using BEAC with a matched cohort of patients conditioned with BEAM. In the BEAC cohort (n = 383), 25 patients died from non-relapse mortality (NRM) events (32% owing to MOF or cardiac toxicity). In the BEAM cohort (n = 766) there were 34 NRM events (23% owing to MOF or cardiac toxicity). The 1-year cumulative incidence of NRM was 4% in the BEAC cohort and 3% in the BEAM group (p = ns). The 2-year relapse/progression rate was 32% with BEAC and 33% with BEAM (p = ns). At 2 years the progression-free survival (PF...
Biology of Blood and Marrow Transplantation, 2006
Forty-nine patients with intermediate-and high-risk aggressive non-Hodgkin lymphoma underwent autologous hematopoietic stem cell transplantation (autoHSCT) using the regimen of busulfan (Bu), cyclophosphamide (Cy), and etoposide (E) that was originally developed for allogeneic HSCT. Eighteen patients treated before 1999 received Cy 2.5 g/m 2 on days ؊3 to ؊2 and E 1800 mg/m 2 on day ؊3 after oral (PO) administration of Bu 1 mg/kg every 6 hours ؋ 4 days for a total of 16 doses beginning on day ؊7. After April 1999, 31 patients similar in all pretransplantation risk assessments received the same regimen except that intravenous (IV) Bu was substituted for PO Bu and pharmacokinetic-directed (PKD) dosing was attempted to achieve an area under the concentration time curve of 1000-1500 mol/min for each dose. Nonrelapse mortality was 28% for PO Bu patients versus 3% for the IV PKD group (P ؍ .01, chi-square test). Actuarial 5-year overall survivals were 28% for patients who received the PO Bu regimen and 58% for patients who received the IV Bu regimen (P ؍ .010, log-rank test), and progression-free survivals were 17% and 50%, respectively (P ؍ .008, log-rank test). After substitution of PKD IV Bu in the BuCyE regimen, we observed lower nonrelapse mortality with increased overall and progression-free survivals in patients with intermediate-and high-risk aggressive non-Hodgkin lymphoma who underwent autoHSCT.
Prognostic factors for survival in lymphoma patients after autologous stem cell transplantation
Swiss medical weekly, 2013
OBJECTIVE: To assess the prognostic value of various parameters including positron emission tomography / computed tomography (PET/CT) and identify risk factors for survival of patients with non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL) treated with autologous stem cell transplantation (ASCT). METHODS: Patient charts and our prospective ASCT database were assessed for the impact of documented variables on event free survival (EFS) and overall survival (OS), including salvage and conditioning regimens used, and PET/CT results before and after ASCT. RESULTS: Overall, 180 patients with NHL (n = 134; 74%) or HL (n = 46; 26%) received ASCT from December 2000 to May 2011. Of the NHL patients, 59 (44%) had diffuse large B-cell lymphoma (DLBCL). Conditioning was mainly performed with cyclophosphamide, carmustine, etoposide (CBV) (n = 72; 40%) or carmustine, etoposide, cytarabine, melphalan (BEAM) (n = 103; 57%). Treatment-related mortality (TRM) was 1.7%. Outcome data are in line with previously reported studies, especially the data for salvage treatment and BEAM conditioning in DLBCL patients confirmed the outcome reported recently in a phase III study. Positive pre-and post-transplantation PET/CT was an adverse risk factor for survival (PET/CT+ before ASCT: hazard ratio (HR): 2.65 (1.11−6.33), p = 0.029; PET/CT+ after ASCT: HR: 7.11 (2.76−18.34), p <0.0001). Other risk factors for survival were primary refractory disease, initial lymphoma stage, number of previous chemotherapy lines, and high amounts of blood product transfusions. CONCLUSIONS: Conditioning with CBV or BEAM and subsequent ASCT was feasible and effective. Initial lymphoma stage and number of previous treatment lines were identified as independent risk factors for EFS in DLBCL and HL patients.
Bone Marrow Transplantation, 2005
Cardiotoxicity is potentially the most threatening nonhaematological side effect of high-dose CY. We prospectively evaluated the very acute cardiac effects of high-dose CY in 17 adult non-Hodgkin's lymphoma (NHL) patients receiving CY 1500 mg/m 2 /day as a part of BEAC high-dose therapy (HDT). Magnetic resonance imaging (MRI) and plasma natriuretic peptide (NT-proBNP, NT-proANP) measurements were performed prior to HDT (d-7) and just after completing HDT (d-2). After the high-dose CY left atrial end-systolic area increased from 15.271.2 to 18.571.4 cm 2 (P ¼ 0.001), left ventricular end-diastolic volume from 136.1712.3 to 156.6711.1 cm 3 (P ¼ 0.04) and left ventricular end-systolic volume from 67.477.8 to 75.377.1 cm 3 (P ¼ 0.018). However, no significant change in left ventricular ejection fraction (LVEF) was observed. At the same time, plasma levels of NT-proBNP increased from 134.9753.3 to 547.17168.4 pmol/l (P ¼ 0.003) and NT-proANP from 481.17105.5 to 1056.67193.1 pmol/l (P ¼ 0.001), respectively. To conclude, high-dose CY results in very acute cardiac toxicity characterised by enlargement of the heart chambers in NHL patients previously treated with anthracyclines. This toxicity can be detected with increased concentrations of circulating natriuretic peptides but not with LVEF measurement.
Journal of Clinical Oncology, 2008
Patients with angioimmunoblastic T-cell lymphoma (AITL) have poor prognoses with current conventional chemotherapy. The aim of this study was to evaluate the effect of high-dose therapy (HDT) followed by autologous stem-cell transplantation (ASCT) on patients with AITL. Patients and Methods We report a retrospective, multicenter study of 146 patients with AITL who received ASCT. The source of the stem cells was peripheral blood in 143 patients. The conditioning regimen varied, and 74% of the patients received carmustine and 1,3-bis(2-chloroethyl)-1-nitrosourea; etoposide; ara-C; and melphalan chemotherapy. Results After a median follow-up of 31 months (range, 3 to 174 months), 95 patients (65%) remained alive, and 51 patients (35%) died. Forty-two patients died as a result of disease progression, and nine died as a result of regimen-related toxicity. The cumulative incidence of nonrelapse mortality was 5% and 7% at 12 and 24 months, respectively. The actuarial overall survival (OS) was 67% at 24 months and 59% at 48 months. The cumulative incidence of relapse was estimated at 40% and 51% at 24 and 48 months, respectively. Disease status at transplantation was the major factor that impacted outcome. Patients who received a transplant during first complete remission (CR) had significantly superior progression-free survival and OS. The estimated PFS rates for patients who received their transplants in CR were 70% and 56% at 24 and 48 months, respectively; 42% and 30% for patients with chemotherapy-sensitive disease at those time points, respectively; and 23% at both time points for patients with chemotherapy-refractory disease. Conclusion This study shows that HDT and ASCT offers the possibility of long-term disease-free survival to patients with AITL. Early transplantation is necessary to achieve optimal results.
Bone Marrow Transplantation, 2000
We sought to define risk factors predisposing breast cancer and lymphoma patients to cardiac and pulmonary toxicity when undergoing high-dose chemotherapy (HDC) and autologous stem cell rescue (ASCR). Additionally, we evaluated in depth the predictive value of the ejection fraction measured prior to HDC in determining cardiac toxicity. In this retrospective analysis, 24 variables were examined in 138 patients undergoing HDC and ASCR from 1990 until 1995. Logistic regression models were used to model the probability of experiencing cardiac and pulmonary toxicity as a function of the 24 prognostic covariates. Cardiac toxicity occurred in 12% of patients and pulmonary toxicity in 24% of patients. Bivariate analyses showed that patients with lymphoma (as opposed to breast cancer) and those with a higher cardiac risk factor score were more likely to experience cardiac toxicity. Multivariate logistic regression models predicted lymphoma and older age to be risk factors for cardiac toxicity. History of an abnormal ejection fraction and higher doses of anthracyclines prior to HDC may also contribute to cardiac toxicity. Pulmonary toxicity occurred more commonly in lymphoma than breast cancer patients, likely due to the busulfan used in the HDC regimen. No other risk factors for pulmonary toxicity were identified. We conclude that older patients with lymphoma should be carefully evaluated prior to being accepted for HDC programs. Older patients with breast cancer may tolerate this procedure well. There is a trend towards cardiac toxicity in patients with a past history of low ejection fraction, although seemingly poor cardiac risk patients may fare well with HDC if carefully selected with the aid of a thorough cardiac evaluation. Bone Marrow Transplantation (2000) 25, 885-894.
Bone Marrow Transplantation, 2005
In an effort to improve the outcome of poor-risk lymphoma patients, we evaluated a novel regimen of tandem high-dose chemotherapy (THDC) with autologous stem cell transplantation. A total of 41 patients (median age 40 years, range 15-68 years) with poor-risk non-Hodgkin's lymphoma and Hodgkin's disease were enrolled. THDC consisted of melphalan (180 mg/m 2) and escalating dose mitoxantrone (30-50 mg/m 2) (MMt) for the first conditioning regimen, and thiotepa (500 mg/m 2), carboplatin (800 mg/m 2), and escalating dose etoposide phosphate (400-850 mg/m 2), (ETCb) as the second regimen. In all, 31 patients (76%) completed both transplants, with a median time between transplants of 55 days (range 26-120). The maximum tolerated dose was determined as 40 mg/m 2 for mitoxantrone and 550 mg/m 2 for etoposide phosphate. The overall toxic death rate was 12%. Following high-dose chemotherapy, 10 of 24 evaluable patients (42%) were in CR. The two-year overall survival and event-free survival is 67% (95% CI, 52-81%) and 45%, (95% CI, 29-61%) for the 41 patients enrolled; and 69% (95% CI, 525-586%) and 48% (95% CI, 30-67%) for the 31 patients completing both transplants. This THDC regimen is feasible but with notable toxicity in heavily pretreated patients; its role in the current treatment of high-risk lymphoma remains to be determined.
Annals of Oncology, 2004
Background: To evaluate the long-term benefit from high-dose chemotherapy (HDCT) with autologous stem-cell transplantation (ASCT), as part of the initial treatment for patients with chemosensitive, high-grade B non-Hodgkin's lymphoma (hg B-NHL), stratified according to the age-adjusted International Prognostic Index (aaIPI). Patients and methods: Eligible patients were 33 consecutive hg B-NHL patients responding to first-line chemotherapy and fulfilling at least one of the following criteria: stage III or IV, bulky disease, elevated lactate dehydrogenase or failure to achieve complete remission (CR). Twenty-two of 33 patients (67%) had two or three risk factors with respect to the aaIPI. All patients received HDCT with ASCT after a minimum of 6 weeks of VACOP-B standard therapy and VIP-E for mobilization. Results: After ASCT, 31 patients (94%) achieved CR. No treatment-related death occurred. The cumulative incidence of relapse at a medium follow-up of 10 years is 16% for 31 of 33 patients achieving CR. Twenty-five of 33 patients are in sustained CR with a disease-free survival of 76% [95% confidence interval (CI) 67% to 86%]. The overall survival at a median follow-up of 122 months (range 86 -148) is 79% (95% CI 68% to 89%).