Role of Brain-Type Natriuretic Peptide and Cardiac Troponins as Predictors of Outcome in Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4457-4457
Author(s):  
Ebru Koca ◽  
Gaurav Parikh ◽  
Ali Imran Amjad ◽  
Floralyn L Mendoza ◽  
Chitra M Hosing ◽  
...  
Keyword(s):  
Overall Survival ◽  
Natriuretic Peptide ◽  
Prognostic Markers ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
Cancer Center ◽  
High Dose ◽  
Cardiac Events ◽  
Significant Difference ◽  
Cardiac Troponins

Abstract BACKGROUND: High circulating levels of cardiac troponins, T and I (cTnT and cTnI) and brain-type natriuretic peptide (BNP) are associated with shorter overall survival and increased transplant-related mortality (TRM) in patients with amyloidosis undergoing high-dose chemotherapy and autologous stem cell transplantation (auto SCT). Their role as prognostic markers in myeloma is not clearly defined. We evaluated the utility of BNP, cTnT and cTnI as prognostic markers in patients undergoing auto SCT for myeloma. METHODS: We retrospectively analyzed patients who received high-dose chemotherapy followed by auto SCT at MD Anderson Cancer Center between January 1 and December 31, 2006. Pre auto SCT levels of BNP, cTnT and cTnI were available in all patients. The upper limit of BNP was 100 ng/L, cTnT 0.01 ng/ml and cTnI 0.03 ng/ml. RESULTS: A total of 105 patients (68 male and 37 female) with a median age of 57 (31–73) received auto SCT during the study period. Seventy-seven patients received high-dose melphalan 200 mg/m2 as preparative regimen, while 28 patients received a combination of melphalan 140 mg/m2 + busulfan 130 mg/m2 × 4 days. Median follow up of surviving patients was 21 months (1–30). Twenty-four (23%) patients had a high BNP level (>100 ng/L) prior to transplantation, 7 patients had a high cTnT level (>0.01ng/ml) and 12 patients had a high cTnI level (>0.03 ng/ml). In 101 evaluable patients, responses (complete 22 + partial 53) were seen in 75 (74%) patients. Overall survival (OS) and progression-free survival (PFS) at 24 months was 86 and 58%, respectively. There was no significant difference in 24-month OS in the high BNP group (p=0.7). Eight patients died of non-relapse causes, with only one death in patients with high BNP (p=0.67). Grade 3–4 cardiac adverse events were reported in 2 patients only, one of whom had elevated BNP (p=0.54). An increase in either BNP, cTnT or cTNI was seen in 30 patients. These patients did not have a significant increase in TRM (p=0.68) or cardiac toxicity, or a decrease in OS. CONCLUSION: High pretransplant levels of BNP, cTnT or cTnI levels, either individually or together, did not adversely impact cardiac events, TRM or OS.

The Utility of Consolidative Upfront High Dose Chemoradiotherapy and ASCT in Patients with Mantle Cell Lymphoma (MCL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2072-2072
Author(s):  
Daniel Persky ◽  
Carol S. Portlock ◽  
Simone Lessac-Chenen ◽  
Alexia Iasonos ◽  
Andrew D. Zelenetz ◽  
...  
Keyword(s):  
Bone Marrow Involvement ◽  
Conditioning Regimen ◽  
Stage Iv ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Significant Difference ◽  
Dose Dense

Abstract Introduction: Two approaches to improve progression-free survival (PFS) in MCL are intensifying induction, as with hyperCVAD/M-A regimen, or intensifying consolidation with high dose chemoradiotherapy (HDT) and ASCT as in the prospective European MCL Network Trial. At MSKCC the strategy is to incorporate both approaches by administering an anthracycline-containing regimen in a dose dense fashion (CHOP- or R-CHOP-14) followed by consolidation with ICE (ifosfamide, carboplatin, etoposide) and HDT/ASCT. Patients: Forty six patients with newly diagnosed MCL underwent HDT/ASCT between 11/96 and 2/05. The median age was 55 years; 74% were male; 72% had bone marrow involvement, 39% had GI involvement, 7% were in leukemic phase, and 91% presented with stage IV disease. Splenomegaly was seen in 35%, B symptoms in 9%, KPS>70 in 93%, elevated LDH in 23%, and blastoid histology in 9%. Results: Induction was 4 to 6 cycles of CHOP-14 (43%), R-CHOP-14 (37%), or other doxorubicin-containing regimen (20%). Consolidation was performed with 2–3 cycles of ICE in 53% or R-ICE in 39%. Upfront treatment was well tolerated and permitted adequate stem cell collection and prompt transition to HDT/ASCT. Conditioning regimens were TBI/CY/VP-16 (59%) and BEAM (41%). Involved field radiation therapy was administered to 65%. Post-ASCT rituximab maintenance was given to 39%, with 57% of patients receiving rituximab as part of their treatment. Anthracycline-based induction led to CRu of 44% and ORR of 98%. Seventy two percent of patients were transplanted in CR, while the remaining 28% were in PR. At a median follow-up of 2.5 years (range 0.4–8.0 years) 17% of the patients have died and 24% have had progressive disease. The median OS and PFS have not been reached (lower 95% CI, 5.7 years and 4.4 years, respectively). The 5-year PFS and OS are 58% and 83%, respectively. The use of rituximab at any point during treatment prolonged PFS - only 1 of 26 patients receiving rituximab relapsed, as compared to 10 of 20 patients who were rituximab naive (p=0.03); thus far there is no significant difference in OS. There was no day 100 treatment related mortality. One patient developed bronchiolitis obliterans after ASCT and died of pulmonary fibrosis 6.5 years later; 3 patients have died of secondary cancers - one case each of MDS (1.6 years after ASCT), melanoma and lung cancer. Conclusion: These data provide evidence that dose-dense induction with CHOP-14 or R-CHOP-14 and consolidation with ICE/HDT/ASCT appears to be safe and effective, with minimal acute toxicity. Although the median follow-up is short, the use of rituximab appears to improve PFS. This contrasts with the findings of German LGLSG and may be a consequence of in vivo rituximab purging. Future therapy could incorporate all the successful elements of prior treatment programs, including R-CHOP-14, R-ICE, and radioimmunotherapy with high dose chemotherapy conditioning regimen, followed by ASCT and rituximab-based maintenance. PFS stratified by Rituximab PFS stratified by Rituximab

scholarly journals Comparison of Two Post-Transplant Predictive Indexes: Day 100 is a Better Time-Point for Response Evaluation after Autologous Stem Cell Transplantation in Multiple Myeloma: Ass Retrospective Study

2020 ◽  
Vol 7 (8) ◽  
Author(s):  
Ma’koseh M ◽  
◽  
Sa’deh S ◽  
Halahleh K ◽  
Abu-Jazar H ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Progression Free Survival ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cell Transplant ◽  
Response Evaluation ◽  
Therapeutic Implications ◽  
Significant Difference

In Multiple Myeloma (MM), response to High-Dose Chemotherapy (HDC) and Autologous Stem Cell Transplant (ASCT) has important prognostic and therapeutic implications. Best timing for response evaluation after ASCT is not well studied. Our study evaluated the correlation between response on day 30 and day 100 after ASCT with Progression Free Survival (PFS) and Overall Survival (OS) in 119 MM patients. Median follow-up was 39.8 months. Complete Response (CR) was achieved in 53.8% and 55.5% of patients on D 30 and D 100, respectively. On D30, there was no significant difference in PFS or OS in CR vs. no CR group (35.4 vs. 22.1 months, p: 0.058) and (92.6 months vs. not reached p: 0.96) respectively nor in responders (R) vs. Non-Responders (NR) group (97.8 vs. 47.1 months p: 0.08) and (30.2 vs. 18.9 months, p: 0.09) respectively. While on D100, PFS was significantly better in CR vs. no CR group (33.8 vs. 18.1 months, p: 0.0047) as well as in R vs. NR (30.6 vs. 16.9 months p: 0.015). However, OS was not better in either (92.6 vs. 52.1 months p: 0.46) and (92.6 months vs. not reached p: 0, 88) respectively. In conclusion, after HDC and ASCT for MM, we recommend doing response evaluation on D100 rather than D30 as it better correlates with PFS. Further studies are required to confirm this finding in the era of consolidation and maintenance treatment.

The Survival of Multiple Myeloma Patients: A Single Institution Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5223-5223
Author(s):  
Zwi N. Berneman ◽  
An-Sofie Verstraete ◽  
Alain Gadisseur ◽  
Ann Van de Velde ◽  
Wilfried A. Schroyens
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Conventional Chemotherapy ◽  
Free Survival

Abstract Background: For a long time, multiple myeloma has been a disease with a poor outcome. High dose (melphalan) chemotherapy followed by autologous stem cell transplantation has been reported to improve the overall and progression-free survival of these patients. Objective: To determine the survival of multiple myeloma patients treated with conventional chemotherapy and compare it with that of patients treated with high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation. Design/Methods: 83 myeloma patients treated at a single institution were included in this retrospective study. They were divided into two groups: one group of patients who were received high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (n=42) and one group of patients who only received conventional chemotherapy and were eventually also treated with thalidomide and/or corticosteroids (n=41). The distribution of the stages of the disease according to Salmon and Durie were similar in both groups of patients. For both groups, the overall and progression-free survival was calculated. Results: In the general analysis, myeloma patients who underwent an autologous transplant had a significantly longer overall survival (58.8 vs. 52.2 months, p=0.036) and progression-free survival (39.6 vs. 11.8 months, p < 0.001) in comparison with the conventional chemotherapy group. If analysis was restricted to those patients who were transplanted as a first-line treatment, there was no significant difference in overall survival in comparison with conventional chemotherapy (51.8 vs. 52.2 months, p= 0.422); progression-free survival was significantly better in the first-line transplant arm as compared to the conventional chemotherapy arm (35.4 vs. 11.8 months, p= 0.003). As the median age in the transplant arm was significantly lower than in the conventional chemotherapy arm, we also performed a sub-analysis of patients who were between 60 and 70 years of age at diagnosis; there was no significant difference in overall survival between the two groups (60.7 vs. 69.5 months, p= 0.656), while the progression-free survival was again better in the autologous transplant group as compared to the conventional chemotherapy group (41.0 vs. 8.4 months, p= 0.020). Conclusion: High-dose chemotherapy and autologous stem cell transplantation in the treatment of myeloma is associated with improved progression-free survival and in the general analysis, with improved overall survival. The overall survival of patients who were only treated with conventional chemotherapy is somewhat higher (more than 4 years) as compared to that of historical controls (2–3 years).

High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Support for Relapsed or Refractory Primary CNS Lymphoma - a Prospective Multicentre Trial By the German Cooperative PCNSL Study Group

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 781-781
Author(s):  
Benjamin Kasenda ◽  
Gabriele Ihorst ◽  
Roland Schroers ◽  
Agnieszka Korfel ◽  
Ingo GH Schmidt-Wolf ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Research Funding ◽  
Primary Cns Lymphoma ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
Cns Lymphoma ◽  
High Dose ◽  
Free Survival ◽  
High Dose Cytarabine

Abstract Purpose To investigate safety and efficacy of high-dose chemotherapy followed by autologous stem cell transplantation (HCT-ASCT) in patients with relapsed or refractory primary CNS lymphoma (PCNSL). Patients and methods We conducted a single-arm multicentre phase 2 study for immunocompetent patients (<66 years of age) with PCNSL failing prior HD-MTX based chemotherapy. Induction treatment consisted of 2 courses of rituximab (rituximab 375mg/m2), high-dose cytarabine (2 x 3g/m2) and thiotepa (40mg/m2) with collection of autologous stem cells in between. Conditioning treatment for HCT-ASCT consisted of rituximab 375mg/m2, carmustine 400mg/m2 and thiotepa (4 x 5mg/kg). Patients commenced HCT-ASCT irrespective of response status after induction. Only patients not achieving complete remission (CR) after HCT-ASCT received whole brain radiotherapy (WBRT). The primary endpoint was CR after HCT-ASCT by intention-to-treat (ITT). Secondary endpoints included safety, progression free survival (PFS, time to progression or death) and overall survival (OS, time to death due to any cause). Results Between May 2007 and July 2012, we enrolled 39 patients from 12 German centres. The median age and Karnofsky performance score was 57 years (range 37 to 65) and 90% (range 60% to 100%), respectively. 28 (71.8%) patients had relapsed and 8 (28.2%) refractory disease. 22 (56.4%) patients responded to induction (4 CR, 18 partial remissions [PR]) and 32 (82.1%) patients commenced HCT-ASCT. 22 patients (56.4%, 95% CI 39.6% to 72.2%) achieved CR after HCT-ASCT, 6 (15.4%) achieved PR, and 1 (2.6%) had stable disease. In 9 (17.8%) patients the final scan was not done, because 7 (18.0%) did not undergo HCT-ASCT and 2 died (5.1%) during HCT-ASCT procedure. After a median follow-up of 45.2 months, the respective 2-year PFS and OS rates were 46.0% (95% CI 30.3% to 61.7%, median PFS 12.4 months, Figure 1) and 56.4% (95% CI 40.8% to 72.0%); median OS not reached (Figure 2). The non-relapse mortality rate was 10.3% (95% CI 4.1% to 26.0%) at 1 year without any further increase afterwards. In the subset of 32 patients who received HCT-ASCT, 14 (56.3%) experienced progression or died translating into 1 and 2-year PFS rates (calculated from date of HCT-ASCT) of 62.5% (95% CI 45.7% to 79.3%) and 56.1% (95% CI 38.8% to 73.3%) with no further decrease afterwards. Main grade 3 or higher toxicities were hematological as expected. We recorded four (10.3%) treatment-related deaths, 2 during induction and 2 during HCT-ASCT. Conclusions In eligible PCNSL patients failing HD-MTX based chemotherapy, a short induction with high-dose cytarabine and thiotepa followed by HCT-ASCT is an effective treatment option. Our data provide a reliable benchmark for future comparative studies needed to further scrutinize the role of HCT-ASCT in the salvage setting for PCNSL. Figure 1. Progression free survival Figure 1. Progression free survival Figure 2. Overall survival Figure 2. Overall survival Disclosures Kasenda: Riemser: Other: Travel Support. Schmidt-Wolf:Janssen: Research Funding; Novartis: Research Funding. Röth:Alexion Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria. Stilgenbauer:Amgen: Consultancy, Honoraria, Other: Travel grants, Research Funding; Genentech: Consultancy, Honoraria, Other: Travel grants , Research Funding; Boehringer Ingelheim: Consultancy, Honoraria, Other: Travel grants , Research Funding; Janssen: Consultancy, Honoraria, Other: Travel grants , Research Funding; Hoffmann-La Roche: Consultancy, Honoraria, Other: Travel grants , Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: Travel grants , Research Funding; Novartis: Consultancy, Honoraria, Other: Travel grants , Research Funding; Sanofi: Consultancy, Honoraria, Other: Travel grants , Research Funding; Gilead: Consultancy, Honoraria, Other: Travel grants , Research Funding; AbbVie: Consultancy, Honoraria, Other: Travel grants, Research Funding; Mundipharma: Consultancy, Honoraria, Other: Travel grants , Research Funding; Genzyme: Consultancy, Honoraria, Other: Travel grants , Research Funding; GSK: Consultancy, Honoraria, Other: Travel grants , Research Funding; Celgene: Consultancy, Honoraria, Other: Travel grants , Research Funding. Illerhaus:Riemser: Honoraria; Amgen: Honoraria.

Incidence and Prognostic Value of Chromosomal Abnormalities in Elderly Patients with myeloma: The IFM Experience on 1095 Patients

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 994-994
Author(s):  
Hervé Avet-Loiseau ◽  
Cyrille Hulin ◽  
Loic Campion ◽  
Murielle Roussel ◽  
Gerald Marit ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Prognostic Value ◽  
Plasma Cells ◽  
Chromosomal Abnormalities ◽  
Young Patients ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Prognostic Impact ◽  
Significant Difference

Abstract Abstract 994 The outcome of patients with multiple myeloma (MM) is highly influenced by chromosomal abnormalities, and especially translocation t(4;14) and del(17p). However, these data have been mostly demonstrated in young patients, less than 65 years of age, treated with high-dose chemotherapy. Almost no data is available in elderly patients. In order to address this issue, we retrospectively analyzed patients over 66 years old, treated with various regimens in the Intergroupe Francophone du Myélome (IFM). Since chromosomal abnormalities are centrally analyzed in the IFM, we focused our analyses on 1890 patients (age=65–94, median=71 y). The patients were divided in two groups: 66–74 y (1239 patients) and over 75 y (651 patients). We first analyzed the incidence of the following abnormalities: del(13), del(17p) (defined by a deletion present in at least 60% of the plasma cells), and t(4;14). The incidence of del(13) was 43.6% in the first group, and 37% in the second one (p=.007). For del(17p), the incidences were 5.9% and 6.1%, respectively (p=NS). Finally, for t(4;14), the incidences were 10.9% and 8.3%, respectively (p=.09). When compared to patients < 65 y, we observed a highly significant lower incidence of t(4;14) in elderly patients (14% vs 10.9% vs 8.3%, p<.0001), vs no significant difference for del(13) and del(17p). Treatment and follow-up data were available for 1095 of these patients. Fifteen % of the patients were treated with high-dose chemotherapy (median age=66 y), 246 received melphalan-prednisone (MP), 434 receined MP-thalidomide (MPT), the others receiving various schemas, including MP-bortezomib (84 patients), lenalidomide-dexamethasone (118 patients), or intermediate-dose melphalan (45 patients). Global prognostic analyses showed that both t(4;14) and del(17p) influenced both the progression-free survival (PFS) and overall survival (OS). Even after stratification on treatment schema, both chromosomal abnormalities retained prognostic value: <10−6 for both t(4;14) and del(17p) for PFS, and <10−4 and <10−6 for OS, respectively. When restricted to the largest treatment group, i.e., patients treated with MPT, the respective p values were <10−4 and <0.002 for PFS, and <0.006 and <10−3 for OS. To conclude, this is by far the largest series analyzing the prognostic impact of chromosomal abnormalities in elderly patients. As demonstrated in younger patients, both t(4;14) and del(17p) negatively impact the PFS and OS survival of these elderly patients. Disclosures: Hulin: Janssen-Cilag: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Facon:Celgene: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria.

Updated 12-year results of a randomized clinical trial comparing standard-dose to high-dose myeloablative chemotherapy in the adjuvant treatment of breast cancer with more than three positive nodes (LN+)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 549-549 ◽  
Author(s):  
A. M. Gianni ◽  
G. Bonadonna ◽  
G. Michelangelo
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Standard Dose ◽  
Survival Rates ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
Survival Advantage ◽  
High Dose ◽  
Free Survival ◽  
Intent To Treat

549 Aims: We conducted a multicenter randomized trial comparing sequential adjuvant standard-dose with high-dose chemotherapy in breast cancer patients younger than 60 years, with 4 or more positive nodes. Patients: Following surgery, patients were stratified by number of positive nodes (4–9 or 9), and randomly assigned to either conventional Epi–CMF (3 courses of epirubicin 120 mg/m2, followed by 6 courses of CMF), or high-dose chemotherapy (HDS) with stem cells support (one course of cyclophosphamide 7 g/m2, followed by one course of methotrexate 8 g/m2 with leukovorin rescue, by two courses of epirubicin 120 mg/m2, and by one course of thiotepa 600 mg/m2 plus melphalan 160–180 mg/m2 with stem cell autografting). Tamoxifen (20 mg/d × 5 yr) was also planned regardless of menopausal and receptor status. The study was designed with a power of 80% to detect a 15% increase in progression-free survival at 5 years in the HDS arm. Results: Of the initially enrolled 398 patients, 16 were ineligible, and the remaining 382 patients (Epi–CMF: 197 patients, HDS: 185 patients) were analyzed according to intent-to- treat. One patient treated with HDS (0.5%) died of interstitial pneumonia. With a median follow-up of 136 months, the 12-year progression-free survival rates were 44% and 52% for the Epi–CMF and the HDS groups, respectively, and the overall survival rates were 51% and 60%, respectively. However, among the 68 patients younger than 36 years, and the 189 patients with 4–9 LN+, those in the HDS group showed a trend for a progression-free survival advantage (HR 0.76 and 0.74, respectively). Conclusions: In the intent-to-treat analysis the 9% overall survival advantage associated with the HDS regimen failed to reach statistical significance in a study powered to detect a 15% difference. To reliably define the role of high-dose therapy, meta-analysis of patient data from all relevant randomized trials (such as that planned by the Early Breast Cancer Trialists’ Collaborative Group) is needed. Supported in part by AIRC and Pharmacia & Upjohn, Milano, Italy. No significant financial relationships to disclose.

Cardiac anthracycline risk: Prognostic value of troponin I (TnI) and B-natriuretic peptide (BNP)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20726-e20726
Author(s):  
A. S. Bertolini ◽  
A. Croce ◽  
O. Fusco ◽  
E. Berardi ◽  
F. Malugani ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Troponin I ◽  
Strong Predictor ◽  
High Dose Chemotherapy ◽  
Left Ventricular ◽  
High Dose ◽  
Cardiac Events ◽  
Patients With Cancer ◽  
Time Period ◽  
Significant Difference

e20726 Background: In patients with cancer who are undergoing to high-dose chemotherapy (HDC), even minimal elevation of TnI is associated with late left ventricular dysfunction. A TnI increase soon after HDC is a strong predictor of poor cardiological outcome. BNP elevation seems to have same prognostic value. Patients treated by standard Anthracycline-based chemotherapy (ADM-CT) doses could not have benefit from TnI/BNP evaluation; on the contrary the method could adsorb too much resources and may not be rational. Methods: To evaluate cardio toxicity trend we studied TnI and BNP in plasma samples of 28 breast cancer pts (female, adjuvant setting, mean age 50), treated with ADM-CT. The samples were detected before (a) one hour (b) and ten days (c) after each course. TnI was considered positive for values ≥ 0.044 ng/mL; BNP for values ≥ 100pg/mL .Comparison between TnI and BNP values were made with the ANOVA method. A probability value < 0.05 was considered statistically significant. Each patient was followed also with LVEF (basal & 3 months after). Results: At present we observed 135 events, mean TnI: (a) 0,00672, (b) 0,006512, (c) 0,005791; BNP (a) 33.8, (b) 36.4, (c) 35.2. We performed 405 detections for both tests; costs: 8.707$ BNP, 10.327$ TnI. No significant difference in test values has been observed between the different time periods. We can't indicate a trend referring to therapy or a particular time period. No patients had LVEF variation. Conclusions: TnI and BNP release pattern after ADM-CT doesn't identify patients at different risk of cardiac events. The program appears useful for HDC treatments, while in normal chemotherapy the data are ongoing and expensive. No significant financial relationships to disclose.

Assessment of absolute lymphocyte count (ALC) as a predictor of progression-free survival (PFS) and overall response rate (ORR) in metastatic melanoma (MM) patients (pts) treated with high-dose interleukin-2 (HD IL-2).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9096-9096
Author(s):  
Jeffrey Thomas Yorio ◽  
Patricia S Fox ◽  
Richard Wayne Joseph ◽  
Roland Bassett ◽  
Michael A. Davies
Keyword(s):  
Metastatic Melanoma ◽  
Clinical Benefit ◽  
Hematological Parameters ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
Absolute Lymphocyte Count ◽  
Cancer Center ◽  
High Dose ◽  
Continuous Variables ◽  
Significant Difference

9096 Background: HD IL-2 is an approved immunotherapy that can achieve durable cures in MM pts. Due to toxicity and low ORR, identification of predictors of clinical benefit would enhance pt selection and outcomes with HD IL-2. Recent research identified a positive correlation for ALC ≥ 1000 (either at baseline or at dose 3) with OS among MM pts treated with the immunotherapy agent ipilimumab. We tested the hypothesis that ALC (≥ 1000) or other hematological parameters correlates with clinical benefit from HD IL2. Methods: Results of hematologic testing in patients (n=98) treated with HD IL2 at MD Anderson Cancer Center were collected, including absolute levels of neutrophils (ANC), lymphocytes (ALC), monocytes (AMC), eosinophils (AEC), and platelets (APC) at baseline, after cycle 1 (C1), and after cycle 2 (C2) of HD IL-2; changes in each parameter for each interval were also calculated. Hematologic values were assessed as categorical (for ALC, ≥ 1000 Yes/No; other parameters, above upper limit of normal [ULN] Yes/No) and continuous variables. Associations between these parameters and PFS and ORR were analyzed. Results: ALC was≥ 1000 in 75 pts (76%) at baseline, in 81 (83%) after C1, and in 80 of 86 pts (93%) after completion of C2 of HD IL-2. PFS was not significantly associated with ALC ≥ 1000 at baseline (HR 0.69, p=0.13), after C1 (HR 1.32, p=0.33), or after C2 (HR 1.01, p=0.98). ALC ≥ 1000 at each timepoint was not significantly associated with ORR or OS. There was no significant difference in the change in ALC with HD IL2 treatment among responders versus non-responders. Among baseline hematological factors, APC > ULN was significantly associated with PFS (p=0.001), but it was rare (2/98 patients). Exploratory analyses identified significantly shorter PFS for patients with baseline APC > 300 (11%, HR 2.75, p=0.002). Analysis of hematologic factors as continuous values identified significant associations with PFS for AMC (HR 2.42, p=0.03) and AEC (HR 1.73, p=0.009) after C2. Conclusions: ALC ≥ 1000 did not correlate with PFS, ORR, or OS with HD IL-2 therapy in this cohort of metastatic melanoma pts.

scholarly journals High-Dose Chemotherapy Compared With Standard Chemotherapy and Lung Radiation in Ewing Sarcoma With Pulmonary Metastases: Results of the European Ewing Tumour Working Initiative of National Groups, 99 Trial and EWING 2008

2019 ◽  
Vol 37 (34) ◽  
pp. 3192-3202 ◽  
Author(s):  
Uta Dirksen ◽  
Bernadette Brennan ◽  
Marie-Cécile Le Deley ◽  
Nathalie Cozic ◽  
Henk van den Berg ◽  
...  
Keyword(s):  
Overall Survival ◽  
Ewing Sarcoma ◽  
High Dose Chemotherapy ◽  
P Value ◽  
High Dose ◽  
Event Free Survival ◽  
Standard Chemotherapy ◽  
Free Survival ◽  
Significant Difference ◽  
Pleural Metastases

PURPOSE The R2Pulm trial was conducted to evaluate the effect of busulfan-melphalan high-dose chemotherapy with autologous stem-cell rescue (BuMel) without whole-lung irradiation (WLI) on event-free survival (main end point) and overall survival, compared with standard chemotherapy with WLI in Ewing sarcoma (ES) presenting with pulmonary and/or pleural metastases. METHODS From 2000 to 2015, we enrolled patients younger than 50 years of age with newly diagnosed ES and with only pulmonary or pleural metastases. Patients received chemotherapy with six courses of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) and one course of vincristine, dactinomycin, and ifosfamide (VAI) before either BuMel or seven courses of VAI and WLI (VAI plus WLI) by randomized assignment. The analysis was conducted as intention to treat. The estimates of the hazard ratio (HR), 95% CI, and P value were corrected for the three previous interim analyses by the inverse normal method. RESULTS Of 543 potentially eligible patients, 287 were randomly assigned to VAI plus WLI (n = 143) or BuMel (n = 144). Selected patients requiring radiotherapy to an axial primary site were excluded from randomization to avoid excess organ toxicity from interaction between radiotherapy and busulfan. Median follow-up was 8.1 years. We did not observe any significant difference in survival outcomes between treatment groups. Event-free survival was 50.6% versus 56.6% at 3 years and 43.1% versus 52.9% at 8 years, for VAI plus WLI and BuMel patients, respectively, resulting in an HR of 0.79 (95% CI, 0.56 to 1.10; P = .16). For overall survival, the HR was 1.00 (95% CI, 0.70 to 1.44; P = .99). Four patients died as a result of BuMel-related toxicity, and none died after VAI plus WLI. Significantly more patients in the BuMel arm experienced severe acute toxicities than in the VAI plus WLI arm. CONCLUSION In ES with pulmonary or pleural metastases, there is no clear benefit from BuMel compared with conventional VAI plus WLI.

High-Producer Haplotypes of Tumor Necrosis Factor Alpha and Lymphotoxin Alpha Are Associated With an Increased Risk of Myeloma and Have an Improved Progression-Free Survival After Treatment

2000 ◽  
Vol 18 (15) ◽  
pp. 2843-2851 ◽  
Author(s):  
Faith E. Davies ◽  
Sara J. Rollinson ◽  
Andrew C. Rawstron ◽  
Eve Roman ◽  
Stephen Richards ◽  
...  
Keyword(s):  
Overall Survival ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Necrosis Factor Alpha ◽  
Free Survival ◽  
Increased Risk ◽  
Factor Alpha ◽  
Lymphotoxin Alpha ◽  
Necrosis Factor

PURPOSE: To determine the effect of polymorphic variations in the tumor necrosis factor alpha (TNFα) and lymphotoxin alpha (LTα) genes on the predisposition to myeloma and the effect of these polymorphisms on response to treatment and overall survival. PATIENTS AND METHODS: Genotype distribution was determined in 63 patients with monoclonal gammopathy of uncertain significance (MGUS) and 198 patients with myeloma and compared with that in 250 age- and sex-matched population-based controls. The effect on treatment response and survival was determined in 171 myeloma patients treated with either conventional or high-dose chemotherapy. RESULTS: Comparison of the extended TNFα/LTα haplotype in the myeloma cases and controls showed a significant excess of high-producer alleles in the cases. The double heterozygotes TNF1/2 and LT10.5/5.5 were present in 35.8% of cases but in only 18% of the controls; this presence was associated with a significant increased risk of myeloma (odds ratio, 2.05; 95% confidence interval, 1.26 to 3.35). A similar odds ratio was seen in the MGUS cases, suggesting that this genotype is associated with the initiation of plasma-cell disorders rather than the progression of MGUS to myeloma. The median overall survival time of myeloma patients was 53.8 months and showed no difference with regard to TNFα/LTα polymorphic status. A trend toward an improved progression-free survival was apparent in cases with a high-producer haplotype, although this effect was seen only in patients receiving high-dose chemotherapy. CONCLUSION: Individuals with polymorphisms associated with a high production of TNFα/LTα are at a significantly increased risk of developing MGUS and myeloma. The impact of polymorphic status on overall survival is minimal, although there is a trend toward an increased progression-free survival in the high-producer group.

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