Randomized trial of high-dose chemotherapy with autologous haematopoietic stem cell support vs. standard-dose chemotherapy in breast cancer patients with 10 or more positive lymph nodes: Overall survival after 6 years of follow up

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 672-672 ◽  
Author(s):  
A. R. Zander ◽  
N. Kroeger ◽  
C. Schmoor ◽  
W. Krueger ◽  
V. Moebus ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Standard Dose ◽  
Interactive Effect ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Event Free Survival ◽  
Free Survival ◽  
Grade Iii

672 Background: Investigation of high dose chemotherapy (HD-CT) supported by autologous hematopoietic stem cell transplantation compared with standard dose chemotherapy (SD-CT) as adjuvant treatment in patients with primary breast cancer and 10 or more axillary lymph nodes. Methods: Between November 1993 and September 2000 307 patients were randomized to receive the following cycles of Epirubicin (90 mg/m2), Cyclophosphamide (600 mg/m2) intervenously (every 21 days) either HD-CT of Cyclophosphamide (1500 mg/m2), Thiotepa (150 mg/m2) and Mitoxantrone (10 mg/m2) intervenously for 4 consecutive days followed by stem cell transplantation or standard dose chemotherapy SDCT in 3 cycles of Cyclophosphamide (500 mg/m2), Methotrexate (40 mg/m2) and Fluoruracil (600 mg/m2) intervenously on days 1 and 8 every 28 days. The primary end points were event-free survival and overall survival. Results: After a median follow-up of 6.1 years 166 events with respect to event-free survival (SD-CT: 91, HD-CT: 75) and 123 with respect to overall survival (SD-CT: 66 and HD-CT: 57) have been observed. The hazard ratio of HD-CT versus SD-CT is estimated as 0,80, p = 0,15. The hazard ratio for overall survival for high dose chemotherapy versus standard dose chemotherapy is estimated as 0,84, p = 0,33. Analysing the effect of treatment on event-free survival premenopausal patients, patients with tumor grade III and ER-positive patients had a better outcome with HD-CT with an interactive effect of 2.5 and 1.4. The significance was only shown in grade III patients in favour of HD-CT, (p = 0,049). The interactive effect of HD-CT with prognostic factors did not reach significance for overall survival. Conclusion: Even with a follow-up of 6.1 years there was only a trend in favour of high dose chemotherapy with respect to overall survival but without a statistical significance. A proper meta-analysis needs to be undertaken for an evaluation of subgroups of patients which might benefit from this treatment approach. No significant financial relationships to disclose.

High-Dose Chemotherapy With Autologous Hematopoietic Stem-Cell Support Compared With Standard-Dose Chemotherapy in Breast Cancer Patients With 10 or More Positive Lymph Nodes: First Results of a Randomized Trial

2004 ◽  
Vol 22 (12) ◽  
pp. 2273-2283 ◽  
Author(s):  
A.R. Zander ◽  
N. Kröger ◽  
C. Schmoor ◽  
W. Krüger ◽  
V. Möbus ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Standard Dose ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Event Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Stem Cell Support ◽  
Cell Support

Purpose Investigation of high-dose chemotherapy (HD-CT) followed by autologous hematopoietic stem-cell support compared with standard-dose chemotherapy (SD-CT) as adjuvant treatment in patients with primary breast cancer and 10 or more positive axillary lymph nodes. Patients and Methods Between November 1993 and September 2000, 307 patients were randomized to receive (following four cycles of epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2, intravenously every 21 days) either HD-CT of cyclophosphamide 1,500 mg/m2, thiotepa 150 mg/m2, and mitoxantrone 10 mg/m2, intravenously for 4 consecutive days followed by stem-cell support; or SD-CT in three cycles of cyclophosphamide 500 mg/m2, methotrexate 40 mg/m2, and fluorouracil 600 mg/m2 intravenously on days 1 and 8, every 28 days. The primary end point was event-free survival. Results After a median follow-up of 3.8 years, 144 events with respect to event-free survival have been observed (HD-CT: 63 events; SD-CT: 81 events). The first event of failure (HD-CT v SD-CT) was an isolated locoregional recurrence (nine v 11), a distant failure (52 v 68), and death without recurrence (two v two). The estimated relative risk of HD-CT versus SD-CT was 0.75 (95% CI, 0.54 to 1.06; P = .095). Overall survival showed no difference (HD-CT: 40 deaths; SD-CT: 49 deaths). Conclusion There was a trend in favor of HD-CT with respect to event-free survival, but without statistical significance. Further follow-up and a meta-analysis of all randomized studies will reveal the effect of HD-CT as compared with SD-CT as adjuvant treatment in high-risk primary breast cancer.

Standard chemotherapy with interferon compared with CHOP followed by high-dose therapy with autologous stem cell transplantation in untreated patients with advanced follicular lymphoma: the GELF-94 randomized study from the Groupe d'Etude des Lymphomes de l'Adulte (GELA)

Blood ◽  
2006 ◽  
Vol 108 (8) ◽  
pp. 2540-2544 ◽  
Author(s):  
Catherine Sebban ◽  
Nicolas Mounier ◽  
Nicole Brousse ◽  
Coralie Belanger ◽  
Pauline Brice ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Follicular Lymphoma ◽  
High Dose ◽  
Event Free Survival ◽  
High Dose Therapy ◽  
Standard Chemotherapy ◽  
Free Survival ◽  
Dose Therapy

AbstractThe purpose of this study is to compare our standard chemotherapy regimen (CHVP [cyclophosphamide, doxorubicin, teniposide, and prednisone]) plus interferon with 4 courses of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by high-dose therapy with autologous stem cell transplantation (ASCT) in treatment-naive patients with advanced follicular lymphoma. Four hundred one patients were included from July 1994 to March 2001: 209 received 12 cycles of CHVP plus interferon α for 18 months (CHVP-I arm) and 192 received 4 cycles of CHOP followed by high-dose therapy (HDT) with total body irradiation and ASCT (CHOP-HDT arm). Overall response rates were similar in both groups (79% and 78% after induction chemotherapy, respectively). One hundred thirty-one of the 150 patients eligible for HDT underwent transplantation (87%). Intent-to-treat analysis after a median follow-up of 7.5 years showed that there was no difference between the 2 arms for overall survival (P = .53) or event-free survival (P = .11). Patients with a complete response at the end of the induction therapy had a statistically longer event-free survival and overall survival (P = .02 and < .001, respectively). After long-term follow-up, our study showed that there was no statistically significant benefit in favor of first-line high-dose therapy in patients with follicular lymphoma. High-dose therapy should be reserved for relapsing patients.

Non-metastatic Ewing's family tumors: High-dose chemotherapy with stem cell rescue in poor responder patients. Preliminary results of the Italian/Scandinavian ISG/SSG III protocol

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10014-10014 ◽  
Author(s):  
S. Ferrari ◽  
T. Alvegard ◽  
R. Luksch ◽  
A. Tienghi ◽  
K. S. Hall ◽  
...  
Keyword(s):  
Stem Cell ◽  
Poor Response ◽  
High Dose Chemotherapy ◽  
Induction Treatment ◽  
Poor Responders ◽  
High Dose ◽  
Event Free Survival ◽  
Free Survival ◽  
Stem Cell Rescue

10014 Background: Poor response to induction chemotherapy negatively affects prognosis for Ewing's sarcoma (ES) patients. To improve outcome, high-dose chemotherapy (HDCT) with stem cell rescue was added to conventional chemotherapy in patients poor responders after induction treatment. Methods: Non-metastatic ES patients aged <= 40 years were eligible. All patients received VAC (vincristin 2 mg-doxorubicin 80 mg/m2-cyclofosfamide 1,200 mg/m2) weeks 0 and 6, IVAc (ifosfamide 9g/m2-vincristin 2 mg-actinomycin 2 mg) week 3 and IE (ifosfamide 9g/m2-etoposide 450 mg/m2) week 9 as induction therapy. Poor response was histologically defined as persistence of microfoci of viable tumor cells and radiologically as persistence of soft tissue mass. As maintenance treatment good responders (GR) received three cycles of VAC-IVAc-IE. Poor responders (PR) received VAC (weeks 13,19), IE (week 22), CE (mobilizing cycle, cyclophoshamide 4g/m2, etoposide 600 mg/m2, week 16) and HDCT with BuMel (busulfan 4 mg/kg × 4 days orally and melphalan 140 mg/m2 with stem cell support week 25). Results: Starting from 1999, 296 patients were enrolled with a median age of 15 years (3–40). 54 % of the tumors were located to the extremities and 46% in the axial skeleton. 274 patients underwent local treatment: surgery in 222 (81%) patients (with post operative Rxt in 70), RxT alone in 52 (19%). 10 patients progressed during treatment. No toxic deaths were recorded. Response evalutation was available for 262 patients: 135 (52%) were PR. 116 of them completed protocol treatment and 19 did not receive HDCT (5 poor harvest, 5 medical contraindication, 9 refusal).With a median follow-up of 37 months (1–89) 5-year overall and event-free survival were 74 % and 65.5% respectively. 5-year event-free survival was 71% (95% CI 62–81%) for GR, 68% (95% CI 58–78%) for PR treated with HDCT and 35% (95% CI 10–60%) for PR who did not receive HDCT. Conclusions: The preliminary survival data show for PR similar outcome as for GR. The treatment including HDCT is feasible with no toxic death recorded. Longer follow-up will confirm its efficacy. No significant financial relationships to disclose.

Total Therapy 1 (TT1): Status Report of the First Tandem Autotransplant (TAT) Trial for Multiple Myeloma (MM) - 15 Years Later.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1151-1151
Author(s):  
Bart Barlogie ◽  
Guido Tricot ◽  
Athanasios Fassas ◽  
Raman Desikan ◽  
Elias Anaissie ◽  
...  
Keyword(s):  
Overall Survival ◽  
Standard Dose ◽  
Detailed Account ◽  
Status Report ◽  
High Dose ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Long Term Outcome ◽  
Free Survival ◽  
Dose Therapy

Abstract Background: Melphalan-based high-dose therapy (HDT) with autologous peripheral blood stem cell support has become the standard of care for newly diagnosed patients with MM, based on IMF90 and MRC7 trial results of single HDT vs. standard-dose therapy and on IMF94 data demonstrating superior EFS and OS with TAT over single HDT. The aim of this report is to provide a detailed account of the long-term outcome of all 231 patients originally enrolled in TT1 between 8/1990 and 6/1995 of whom 63 remain alive. Patients and Methods: Outcome data on TT1 have been reported previously (Blood93, 1999; 101, 2003). Here we give final account of patient status with a median follow-up of 12 years (range, 9–15). Results: Of 231 patients, 195 had received at least 1 and 165 the 2 scheduled transplants; 7 without insurance coverage were given intermediate dose melphalan 70mg/sqm. Of 87 (38%) initially achieving CR (median, 27 mo), 17 (20%) remain in uninterrupted 1st CR. The median EFS duration was 31mo, and 32 (14%) remain continuously event-free. The median OS duration is 68 mo with a 12-yr estimate of almost 30%. Of all 63 survivors, 19% had cytogenetic abnormalities (CA) prior to therapy, and 38% had CA intermittently. Of the 17 patients in continuous CR, 10 never had CA at any time, 4 developed CA subsequently with resolution in 3; of 3 with baseline CA, 2 normalized and 1 persisted. A detailed account of CA type and frequency as well as salvage therapies such as thalidomide, bortezomib and further auto- or allotransplants will be provided. Conclusion: TT1 was the first tandem autotransplant protocol applied to 231 newly diagnosed patients MM that yielded an unprecedented positive outcome with 12-yr rates of CCR, EFS and OS of 20%, 14%, and 30%, respectively. The Figure displays a 3-phasic relapse pattern: an initial steep slope spanning years 1-3, a more shallow slope between years 4 to 10, merging into a cure-consistent “hockey-stick”. Event-Free Survival- TT1 Patients Event-Free Survival- TT1 Patients Overall Survival- TT1 Patients Overall Survival- TT1 Patients

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 &lt; 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).

Timing of Second Autologous Transplantations in Multiple Myeloma: Results of a Multicenter Sequential Randomized Clinical Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 59-59 ◽  
Author(s):  
Abderrahman Abdelkefi ◽  
Saloua Ladeb ◽  
Tarek Ben Othman ◽  
Lamia Torjman ◽  
Amel Lakhal ◽  
...  
Keyword(s):  
Overall Survival ◽  
Randomized Trial ◽  
Rank Test ◽  
Optimal Timing ◽  
High Dose ◽  
Consolidation Therapy ◽  
Event Free Survival ◽  
Free Survival ◽  
Log Rank Test

Abstract Background: Autologous stem cell transplantation (ASCT) is now considered standard therapy in young patients (<65 years) with multiple myeloma (MM). The Intergroupe Francophone du Myelome conducted a randomized trial of the treatment of MM with high-dose chemotherapy followed by either one or two successive ASCTs. The probabilities of event-free-survival and overall survival were doubled with a double transplant. However, no randomized trial has compared tandem transplant up-front with a strategy including planned second ASCT at relapse or progression. Therefore, we performed a multicenter, sequential, randomized trial designed to assess the optimal timing of a second ASCT. Methods: From May 2003 to April 2006, 140 patients with symptomatic MM (de novo) and less than 60 years of age, were randomly assigned to receive either tandem transplantation up-front (within 6 months of the first transplantation) [Arm A, n=69] or one ASCT followed by a consolidation therapy with thalidomide (day +90, 100 mg/per day during 5 months) [Arm B, n=71]. Patients included in the arm B received a second transplant in case of disease progression on consolidation therapy, or in case of relapse in responders. Clinical characteristics of each group were similar. In both arms of the study, ASCT was preceded by first-line therapy with thalidomide-dexamethasone and subsequent collection of peripheral blood stem cells with high-dose cyclophosphamide (4 g/m2) and G-CSF. Data were analyzed on an intent-to-treat basis. Results: With a median follow-up of 23 months (range: 6–34), the 2-year overall survival was 55% in the arm A and 75% in the arm B. Survival curves were not different (P=0.28, log-rank test). The 2-year event-free survival was 41% in the arm A and 60% in the arm B (P=0.4, log-rank-test). In the arm B, relapse-free survival of ≥ 16 months following the first transplantation was an important predictor of overall survival (p< 0.001). Conclusion: Data from the present study suggest that up-front single ASCT followed by a consolidation therapy with thalidomide and a second ASCT after relapse or progression is a safe and effective global strategy to treat MM patients. Longer follow-up is needed before definite conclusions can be given concerning the optimal timing of second autologous transplantations in patients with MM.

Ten Year Follow up Analysis of the OSHO Phase III Trial (AML 96) Comparing Different Application Modes of AraC in Patients below 60 Years with Acute Myeloid Leukemia (AML): No Impact of AraCApplication Mode on Remission Rate, Toxicity, Disease-Free Survival or Overall Survival

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2966-2966
Author(s):  
Cornelia Becker ◽  
Rainer Krahl ◽  
Antje Schulze ◽  
Georg Maschmeyer ◽  
Christian Junghanß ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Phase Iii ◽  
High Dose ◽  
Event Free Survival ◽  
Free Survival ◽  
Significant Difference

Abstract Clinical trials on different cytarabine doses for treatment of AML provide evidence of a dose response effect, but also for increase toxicity after high dose AraC (HDAC). Pharmacokinetic measurements of cytarabine-triphosphate (AraC-CTP), which is the most relevant cytotoxic metabolite of AraC, have revealed its formation in leukemic cells to be saturated with infusion rates above 250 mg/m2/h, this being significantly lower than used in HDAC schedules. Methods: Based on a pharmacological model and encouraging results of a phase II study we conducted a prospective randomized multicenter clinical trial comparing the effects of two different application modes of AraC in patients up to 60 years with untreated newly diagnosed AML. Patients were randomized to receive AraC at two different infusion rates (IR) during induction and consolidation treatment: arm A/experimental: 1 × 2 g/m2/d AraC over 8 hours (IR 250 mg/m2/h) arm B/standard: 2 × 1 g/m2/d AraC over 3 hours (IR 333 mg/m2/h). Induction and first consolidation consisted of AraC (days 1, 3, 5, 7) in combination with an anthracycline (Idarubicine 12 mg/m2 or Mitoxantrone 10 mg/m2, days 1–3). The final dosage points (AraC day 7 and anthracycline day 3) were excluded from the second consolidation. The third consolidation consisted of either allogeneic or autologous stem cell transplantation or of chemotherapy identical to second consolidation. Results: From 02/97 to 04/02 419 patients were enrolled in the study. The present analysis is based on 361 eligible and evaluable patients with a median follow up of 7 years. CR was reached in 249/361 (69%; 95%CI: 65%–74%) patients. No statistically significant differences were detected between arms A and B with regard to CR-rate (69% vs 69%) or early death rate (11% vs 8%). Hematological recovery of median white blood cell count (WBC) &gt; 109/l and median platelets (plt) &gt; 50 × 109/l revealed no difference between arms A and B after induction (WBC day 22 vs 22, p=0,68; plt day 25 vs 26, p=0,41) and consolidation (WBC day 28 vs 27, p=0,07; plt day 42 vs 40, p= 0,58). The event free survival (EFS) after 5 years is 0,25 ± 0,03 % for all patients with an overall survival of 0,31 ± 0,03 % after 5 years. For the purposes of analysis, the 83 transplant patients (23 allogeneic MRD, 14 allogeneic MUD and 46 autologous) were censored at time of transplant. No statistically significant difference between arms A and B in regard to EFS (0,25 ± 0,04 vs 0,25 ± 0,04, p=0,99), relapse incidence (0,63 ± 0,06 vs 0,60 ± 0,06, p=0,89), overall survival (0,32 ± 0,04 vs 0,30 ± 0,04, p=0,44) and therapy associated mortality (0,18 ± 0,04 vs 0,17 ± 0,03, p=0,95) were detectable after adjustment of prognostic factors. An analysis of risk factors by multivariate cox regression model confirmed cytogenetics at diagnosis to be the most important risk factor for CR rate (p&lt;10−6) and for EFS (p&lt;10−6). Other significant prognostic factors for EFS evaluated in the multivariate analysis were de novo vs secondary AML (p=0,0001), WBC (continuous) (p=0,001), LDH (&gt;1–4 × vs other ULN) (p=0,008) and FAB classification (FAB M0,6,7 vs FAB M1,2,4,5) (p=0,0005). EFS after 5 years shows a significant correlation to cytogenetics (p&lt;10−6) with 0,71±0,1, 0,27±0,05, 0,20±0,06 and 0,03±0,03 for favorable, normal, other and unfavorable cytogenetic karyotype, respectively. Conclusion: We conclude that the application of AraC at the presumptive saturating infusion rate of 250 mg/m2/h results in comparable remission rates, toxicity, event free survival and overall survival as compared to the standard IR with 333 mg/m2/h.

Outcomes of Eam Conditioned Autologous Haematopoietic Stem Cell Transplantation for Lymphoma. A Matched Pairs Retrospective Single Centre Study Analysis.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3088-3088
Author(s):  
Justin Ching Ting Loke ◽  
Janice Ward ◽  
Prem Mahendra ◽  
Sridhar Chaganti ◽  
Ram Malladi
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Lung Function ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Haematopoietic Stem Cell ◽  
Event Free Survival ◽  
Free Survival ◽  
Related Mortality

Abstract Abstract 3088 Background: High dose chemotherapy followed by autologous stem cell rescue is superior to salvage chemotherapy alone in relapsed Hodgkin's Lymphoma (HL) and Non-Hodgkin's lymphoma (NHL). A commonly used regimen is BEAM (BCNU, Etoposide, Cytarabine and Melphalan). Unfortunately, BCNU is associated with potentially lethal pulmonary interstitial toxicity, in a dose dependent manner. Therefore, it is often omitted in conditioning regimens for patients who have pre-existing impaired lung function. We aimed to determine the outcomes of patients given this EAM (Etoposide, Cytarabine, Melphalan) schedule in our centre. Method: At our unit, from 2000–2010, 338 patients had been transplanted with BEAM conditioning and 23 patients with an EAM regimen. BEAM chemotherapy involved cumulative doses of BCNU at 300 mg/m2, etoposide at 800 mg/m2, cytarabine at 1600 mg/m2 and melphalan at 140 mg/m2. The EAM regimen was the same, except for the omission of BCNU. We wanted to compare overall survival, event free survival and transplant related mortality between the two groups of patients. A matched-pair analysis based on age and sex on a 1:1 basis was conducted. Survival rates were estimated by the Kaplan-Meier method. Differences between the survival distributions were compared with the log-rank test. Results: 23 patients transplanted with an EAM regimen was matched with an equal number transplanted with a BEAM conditioning regimen. The median age was 53 in both groups. The median follow-up for patients alive was 3.2 years. Further baseline characteristics of the two groups are described in table 1. Other than a slight predominance of more advanced disease in the BEAM cohort, the two groups were evenly matched. Survival estimates were statistically significantly poorer for the EAM group compared to the BEAM group. The median overall survival for the EAM cohort was 29 months compared to 77 months (p=0.03) for the matched BEAM cohort. The median event free survival for the EAM cohort was 11 months compared to 63 months (p=0.02) for the BEAM cohort. The 100 day transplant related mortality was 8.7% for both cohorts. During the follow-up period 11 patients died of disease related causes in the EAM group compared to 6 in the BEAM group. Conclusion: Despite the prevalence of pre-existing lung disease in the EAM group of patients, the conditioning was reasonably well tolerated. Our analysis suggests that patient transplanted with an EAM regimen had an inferior survival outcome to patients treated with the standard BEAM regimen. This data provides evidence for the importance of BCNU in lymphoma control; consideration should be given to a reduction in BCNU dosage, rather than simple omission, for patients with borderline lung function results. Collaboration with other centres is warranted to determine if this experience with EAM is replicated elsewhere. Disclosures: No relevant conflicts of interest to declare.

Results of the ECOG E1900 Trial in Younger Adults with AML Using an Event Free Survival Endpoint Are Concordant with Results Based on Overall Survival: Potential for a Surrogate Endpoint to Facilitate Rapid Approval of Therapies in AML

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2599-2599 ◽  
Author(s):  
Marlise R. Luskin ◽  
Ju-Whei Lee ◽  
Hugo F. Fernandez ◽  
Hillard M. Lazarus ◽  
Jacob M. Rowe ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Treatment Failure ◽  
Induction Treatment ◽  
High Dose ◽  
Event Free Survival ◽  
Npm1 Mutation ◽  
Free Survival ◽  
The Impact

Abstract Background: Novel therapies are required to improve the outcome of patients with AML. New agents are asked to demonstrate an overall survival (OS) benefit before qualifying for FDA approval. The long duration of clinical trials required in order to achieve this endpoint hampers quick evaluation of candidate therapies, including novel agents. Identification of reliable surrogate endpoints for OS in AML is needed. Here we compare the results of therapy for patients with untreated AML ages 16-60 years on the Eastern Cooperative Oncology Group 1900 trial (E1900) of induction chemotherapy followed by consolidation and autologous transplant in order to evaluate the validity of an event free survival (EFS) endpoint as a surrogate for OS. Methods:OS was measured from randomization for induction therapy to death from any cause (censored at last contact). EFS was measured from randomization to induction treatment failure, relapse after compete response (CR), or death in remission (censored at last contact). Hazard ratios (HR) were computed using Cox proportional hazards models. The association between EFS and OS was evaluated using the Kendall tau-a rank correlation for censored data. Results:There were657 patients enrolled of which 426 patients relapsed or had induction treatment failure before death or date of last contact. Median EFS and OS were 8.0 months (95% CI, 6.3 to 9.7 months) and 23.6 months (95% CI, 16.9 to 23.6 months), respectively. With a median follow-up of 80.1 months, there is a statistically significant correlation between EFS and OS (Kendall tau-a = 0.467, 95% confidence interval (CI) = (0.425, 0.510), p<0.001). This correlation was similarly significant at a median follow-up of 25.2 months (Kendall tau-a = 0.361, 95% CI (0.323, 0.400), p <0.001) when the E1900 trial was originally reported (Fernandez et al. NEJM 2009). Key findings reported based on the original OS endpoint are similar when analyzed with an EFS endpoint (Table 1). High-dose daunorubicin (90 mg/m2) (DNR 90) confers both an EFS and OS benefit in patients aged < 50 years and patients with intermediate cytogenetic risk, and does not confer an EFS or OS benefit in older patients and patients with unfavorable cytogenetic risk, on univariate analysis. Divergent results are only seen in the small subset of favorable cytogenetic risk patients, where DNR 90 conferred an OS benefit (p=0.027) without an EFS benefit (p=0.32). Both EFS and OS endpoints consistently reflect the impact of mutation status on survival. The presence of a FLT3-ITD or DNMT3A mutation has a negative impact on both EFS and OS while an IDH2 mutation has a favorable impact on EFS and OS. The presence of a NPM1 mutation confers a favorable impact on EFS and OS in patients who received DNR 90 and did not impact EFS or OS in patients receiving standard-dose daunorubicin (45 mg/m2) (DNR 45). The presence of an IDH1 mutation does not impact EFS or OS. Conclusions:The results of E1900 demonstrating superiority of DNR 90 in AML induction in patients up to age 60 are concordant when using an EFS or OS endpoint. This is true for the group as a whole as well as for subgroups for which targeted agents are in development (FLT3/IDH2 inhibitors). Further investigation of whether EFS is a reliable surrogate for OS is warranted in AML. If confirmed, its use as a primary endpoint could be adopted by regulatory agencies in order to allow more rapid completion of clinical trials in AML and bring new therapies to AML patients in a timely fashion. Table 1. Results of E1900 based on an EFS endpoint versus an OS endpoint. Subgroup N OS HR (DNR 90/DNR 45) & 95% CI Wald P EFS HR (DNR 90/DNR 45) & 95% CI Wald P DNR 45 DNR 90 Age < 50 yrs ³ 50 yrs 188 142 172 155 0.66 (0.50, 0.85) 0.81 (0.62, 1.06) 0.002 0.118 0.64 (0.50, 0.82) 0.86 (0.67, 1.10) 0.0004 0.23 Cytogenetic Favorable Intermediate Unfavorable 38 141 59 51 127 63 0.51 (0.28, 0.93) 0.68 (0.50, 0.92) 0.79 (0.54, 1.16) 0.027 0.012 0.225 0.76 (0.44, 1.31) 0.63 (0.47, 0.83) 0.72 (0.49, 1.05) 0.32 0.001 0.09 Subgroup N OS HR (MUT/WT) & 95% CI Wald P EFS HR (MUT/WT) & 95% CI Wald P FLT3-ITD WT MUT 456 147 1.62 (1.31, 2.01) <.0001 1.48 (1.21, 1.82) 0.0002 DNMT3A WT MUT 371 119 1.30 (1.03, 1.65) 0.03 1.23 (0.98, 1.54) 0.07 IDH1 WT MUT 465 36 0.88 (0.59, 1.33) 0.55 0.91 (0.62, 1.34) 0.64 IDH2 WT MUT 451 50 0.63 (0.43, 0.93) 0.02 0.68 (0.48, 0.97) 0.03 NPM1 DNR 45 DNR 90 245 257 0.84 (0.61, 1.16) 0.60 (0.41, 0.89) 0.30 0.01 0.90 (0.66, 1.22) 0.59 (0.41, 0.84) 0.49 0.004 Disclosures No relevant conflicts of interest to declare.

scholarly journals MBCL-50. DISMAL OUTCOME OF HIGH RISK MEDULLOBLASTOMA TREATED WITH CHEMOTHERAPY FIRST APPROACH IN MALAYSIA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii398-iii398
Author(s):  
Shiao Wei Quah ◽  
E J Abdul Rahman ◽  
H Mohd Ibrahim ◽  
Z Muda ◽  
I S Othman ◽  
...  
Keyword(s):  
High Risk ◽  
Metastatic Disease ◽  
Residual Disease ◽  
High Dose Chemotherapy ◽  
Favourable Outcome ◽  
High Dose ◽  
Event Free Survival ◽  
Free Survival ◽  
Hyperfractionated Radiotherapy

Abstract INTRODUCTION Patients with high risk medulloblastoma are treated either with high dose chemotherapy or hyperfractionated radiotherapy. Both approaches are not feasible in resource-limited countries. POG9031 trial has reported favourable outcome for high risk medulloblastoma using standard chemotherapy and radiotherapy only. Hence, we have adopted the protocol using chemotherapy first approach due to logistical reasons. OBJECTIVE To review the outcome of children diagnosed with high risk medulloblastoma in Hospital Kuala Lumpur. METHODS Patients diagnosed with high risk medulloblastoma between January 2015 and June 2018 treated using the chemotherapy first approach as per POG9031 protocol were identified. Data was then extracted and analysed. RESULTS Nine patients were identified, 3 boys and 9 girls. Median age was 9.3 years (range 2.6 – 15.9 years). Median follow up for survivors are 3.6 years. Five patients (55.6%) had macroscopic metastatic disease at diagnosis. All patients had significant residual disease post-op. Only 3 patients are disease free till last follow up, giving a 3 years event free survival of 16%. Of the 6 patients who had relapsed, 4 have died, giving a 3 years overall survival of 46%. Patients with no metastasis at diagnosis (M0) fared better with 3 years event free survival of 38%, but 3 years event free survival for patients with macroscopic metastatic disease (M+) was 0%. CONCLUSION Outcome of children with high risk medulloblastoma treated with chemotherapy first approach was dismal.

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