High-dose melphalan (MEL) based autotransplants (AT) for multiple myeloma (MM): The Arkansas experience since 1989 in more than 2,800 patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8043-8043 ◽  
Author(s):  
M. Pineda-Roman ◽  
J. Haessler ◽  
K. Hollmig ◽  
E. Anaissie ◽  
F. van Rhee ◽  
...  
Keyword(s):  
Platelet Count ◽  
Cox Regression ◽  
High Dose ◽  
Kaplan Meier ◽  
Long Term Follow Up ◽  
Previously Treated Patients ◽  
High Platelet Count ◽  
Previously Treated ◽  
Dose Response Effect ◽  
High Dose Melphalan

8043 Background: The dose-response effect for MEL has been safely exploited through the use of AT. Long-term follow-up studies from large centers are critical to understand who benefits most and who should be considered for alternative treatment approaches. Methods: 2,836 patients receiving at least one MEL AT were considered. Kaplan-Meier analysis was used to estimate median event-free survival (EFS) and overall survival (OS). Cox regression was used to evaluate independent prognostic factors of EFS and OS from AT. Results: Of the 2,836 patients, 979 were enrolled into front-line Total Therapy protocols 1/2/3 (TT); 1,064 were entered on protocols for previously treated patients (non-TT); and 793 were treated off protocol (non-P). Overall median EFS and OS from 1st AT are 31mo and 53 mo; 10-yr EFS and OS were 19% and 24%; 15% survived >15 yr. The 5 strongest favorable OS features included TT (HR 0.46, p<0.001), absence of cytogenetic abnormalities (no CA) (HR 0.48, p<0.001), B2M <3 mg/L (HR 0.46, p<0.001), albumin >=3g/dL (HR 0.45, p<0.001) and platelet count >=100.000/microL (HR 0.41, p<.001), so that 10-yr OS rates were 58% with 5, 24% with 4, 16% with 3, 4% with 2 and 0% with =<1 favorable parameter (p<0.0001). The corresponding median durations of EFS were 80 mo, 37 mo, 27 mo, 18 mo and 7 mo (p<0.0001). Conclusion: This large single institution experience demonstrates that > 10 yr OS can be accomplished in over one-half of the 16% of all patients presenting without CA, with low levels of B2M and albumin, high platelet count and receiving TT. The worst constellation affected 3% of all patients presenting with at most 1 good-risk feature whose 5-yr survival was only 7%. These data should serve as guidepost for MM investigators and patients alike, against which newer treatments should be measured. No significant financial relationships to disclose.

Incidence of secondary malignancies (SM) in patients (pts) with germ cell tumors (GCT) who received high-dose chemotherapy (HDCT): A retrospective study from the European Society for Blood and Marrow Transplantation (EBMT) database.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4549-4549
Author(s):  
Simona Secondino ◽  
Andrea Necchi ◽  
Giovanni Rosti ◽  
Manuela Badoglio ◽  
Daniele Raggi ◽  
...  
Keyword(s):  
Cox Regression ◽  
Germ Cell Tumors ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Survival Times ◽  
Blood And Marrow Transplantation ◽  
Kaplan Meier ◽  
European Database ◽  
Long Term Follow Up ◽  
Retrospective Nature

4549 Background: Little is still known about the incidence of SM in young adult pts with GCT after HDCT, owing to the rarity of the disease, and the need for registries with long term follow-up (FUP) data. In Europe, the EBMT may provide a suitable platform for such retrospective analyses. Methods: Criteria for patient selection included diagnosis of GCT, adult male gender, ≥2yr of FUP after the administration of HDCT. Summary statistics were used to describe pt characteristics and outcomes. χ2 tests were used to compare groups according to the length of FUP. Kaplan-Meier estimates were used to estimate overall survival (OS). Univariable Cox regression analyses examined clinical factors potentially associated with OS. Survival times were calculated from the HDCT administration date. To estimate the probability of developing SM, the cumulative incidence of SM was calculated for all pts. Results: From 1981 to 2014, 9,153 autografts, accounting for 5,100 pts, have been registered. Of them, 1,855 had ≥2yr of FUP. Among the latter, a total of 56 cases of SM were identified (3.0%). 28 (50%) had solid SM, 22 (39.3%) hematologic (hem) SM (5 had uncoded SM). Median age at first HDCT was 34 years (IQR: 30-42), median age at development of SM was 42 (37-51). 26 pts (46.4%) received single HDCT cycle, 22 (39.3%) multiple HDCT cycles (8 unknown). 31 pts had ≥5 yr FUP, 25 pts 2-5 yr FUP. The median latency of SM was 3.3yrs (IQR: 1.8-6.1) for hem SM and 5.6yrs (IQR: 1.2-10.8) for solid SM. Median FUP was 6.4yrs. Univariably, the type of SM (solid vs. hem) was significantly associated with OS. Hem vs solid SM: HR: 2.17 (95%CI: 1.19-4.97, p = 0.020). Median OS of pts who developed solid SM was 13.3yrs compared to 4.1yrs of those with hem SM. The retrospective nature of the data is the major limitation. Conclusions: In the largest European database of SM in GCT pts, we observed different trends for SM development according to the SM type. This information may be important for FUP guidelines of these pts. Dataset implementation is ongoing and we will compare the SM incidence from EBMT database with SM rates in the general EU population.

Arkansas Autotransplant (AT) Experience with > 2500 Myeloma (MM) Patients: Follow-Up Extending to >15 Years.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1149-1149
Author(s):  
Frits van Rhee ◽  
Guido Tricot ◽  
Elias Anaissie ◽  
Maureen Reiner ◽  
Maurizio Zangari ◽  
...  
Keyword(s):  
Cox Regression ◽  
Standard Of Care ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Kaplan Meier ◽  
Long Term Follow Up ◽  
Previously Treated Patients ◽  
The University

Abstract Background: AT’s have become the standard of care for MM. Long-term follow-up studies from large centers are critical to understand who benefits most and who should be considered for alternative treatment approaches. Patients and Methods: 2,605 MM patients receiving at least one AT at the University of Arkansas were considered for this study. Kaplan-Meier analysis was used to estimate median event-free (EFS) and overall survival (OS). Cox regression was used to evaluate independent prognostic factors of EFS and OS from AT. Results: Of the 2,605 patients, 891 were enrolled into front line Total Therapy (TT) protocols TT1/2/3 (TT); 1,012 were treated on protocols for previously treated patients (non-TT); and 702 were treated off protocol due to significant co-morbidities or patient/MD preference (non-P). Median EFS and OS for all patients are 29 mo and 51 mo; 10-yr EFS and OS are 18% and 23%; 12% survived &gt;15yr. Features independently predicting superior survival included TT (HR 0.51, p&lt;.001), absence of cytogenetic abnormalities (no CA) (HR 0.47, p&lt;.001), timely application of 2nd transplant (&lt; 6 months of 1st transplant) (HR 0.71, p&lt;.001) as well as B2M &lt; 3mg/L, CRP &lt; 6mg/dL, albumin &gt;=3g/dL, platelet count &gt;=100.000/microL (all p&lt;.001) and age &lt;65yr (p=.008). The figure depicts survival (landmarked at 6 months after 1st transplant) according to the number of favorable features present of the 5 strongest predictors (TT, 2 transplants within 6 months, no CA, low B2M, low CRP). Conclusion: This large single institution experience demonstrates that &gt; 10yr survival can be accomplished in over one-half of the patients presenting without CA (14%), with low levels of B2M and CRP and receiving TT and timely 2nd autotransplant. The worst constellation affected 5% of all patients presenting with at most 1 good-risk feature whose 5-yr survival was only 8%. Collectively, these data should serve as a standard for MM investigators and patients alike, against which long-term outcome of newer treatments should be measured. Figure Figure

Incidence of secondary malignancies (SM) in patients (pts) with germ cell tumors (GCT) who received high-dose chemotherapy (HDCT): A retrospective study from the European Society for Blood and Marrow Transplantation (EBMT) database.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 409-409
Author(s):  
Andrea Necchi ◽  
Giovanni Rosti ◽  
Manuela Badoglio ◽  
Patrizia Giannatempo ◽  
Simona Secondino ◽  
...  
Keyword(s):  
Cox Regression ◽  
Germ Cell Tumors ◽  
High Dose Chemotherapy ◽  
Rank Test ◽  
High Dose ◽  
Prognostic Impact ◽  
Patient Counselling ◽  
Kaplan Meier ◽  
Long Term Follow Up

409 Background: Little is still known about the incidence of SM in young adult pts with GCT after HDCT, owing to the rarity of the disease, and the need for long term follow-up (FUP) data registries. In Europe, the EBMT systematically collect relevant data and may provide a suitable platform for retrospective analyses. Methods: Criteria for patient selection included diagnosis of GCT, adult male gender, ≥ 2yr of FUP after the administration of HDCT. Summary statistics were used to describe pt characteristics and outcomes. χ2 tests were used to compare groups according to the length of FUP. Kaplan-Meier estimates were used to estimate overall survival (OS) since the diagnosis of SM. Log-rank test was used to compare OS in pt subgroups. Univariable Cox regression analyses examined clinical factors potentially associated with OS following SM diagnosis. Results: From 1981 to 2014, 9,153 autografts, accounting for 5,100 pts, have been registered. Of them, 1,855 had ≥ 2yr of FUP. Among the latter, a total of 56 cases of SM were identified (3.0%). 28 (50%) had solid SM, 22 (39.3%) hematologic SM (5 had uncoded SM). Median age at first HDCT was 34 years (IQR: 30-42), median age at development of SM was 42 (37-51). 26 pts (46.4%) received single HDCT cycle, 22 (39.3%) multiple HDCT cycles (8 unknown). 31 pts had ≥ 5 yr FUP, 25 pts 2-5 yr FUP. Solid SM were developed more frequently in those with longer FUP ( ≥ 5 yrs) compared to hematologic SM (p = 0.008). Median follow-up (FUP) was 76.9 months. Univariably, the type of SM (solid vs. hematologic) was significantly associated with OS. Hematologic vs solid SM: HR: 3.49 (95%CI: 2.09-10.47, p < 0.001). Median OS of pts who developed solid SM was 32.8 months compared to 7 months of those with hematologic SM. The retrospective nature of the data is the major limitation. Conclusions: The incidence of SM in GCT pts who have received HDCT is a concern. During the FUP, there seems to be a non-overlapping risk of developing solid or hematologic SM, with a significantly different prognostic impact. These data may be important to improve patient counselling and the planning of post-HDCT FUP.

Magnitude of progression-free survival (PFS) improvement and treatment (Tx) duration in metastatic colorectal cancer (mCRC) for bevacizumab (BV) in combination with oxaliplatin-containing regimens: An analysis of two phase III studies

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4073-4073 ◽  
Author(s):  
B. J. Giantonio ◽  
N. J. Meropol ◽  
P. J. Catalano ◽  
V. Ng ◽  
R. Oliver ◽  
...  
Keyword(s):  
Cox Regression ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Two Phase ◽  
Free Survival ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Phase Iii Studies

4073 Background: In trials of BV with FOLFOX (fluorouracil, leucovorin, oxaliplatin) for mCRC, variability in the magnitude of PFS improvement has been reported [HR=0.61 in E3200 vs HR= 0.83 (FOLFOX or CAPOX (capecitabine and oxaliplatin)) in NO16966]. We propose that differences in rates of treatment discontinuation (D/C) for adverse events (AE) between these studies may have resulted in differences in the observed benefits associated with BV. We explored Tx duration (proportion of patients on Tx) and Tx D/C data at median PFS for the BV containing arms of each study. Methods: ECOG study E3200 randomized previously treated patients with mCRC to FOLFOX ± BV (10 mg/kg). NO16966 employed a 2x2 design that randomized previously untreated patients with mCRC to CAPOX vs FOLFOX and to BV (5 mg/kg) or placebo. In both trials, study Tx was defined as any component of the prescribed regimen. PFS was estimated from Kaplan-Meier curves, and hazard ratios (HR) for PFS were estimated by Cox regression. Results: Median PFS for the BV containing arm of the study: 30 weeks for E3200; 42 weeks for NO16966 Conclusion: These data suggest possible differences between the two studies in Tx duration and Tx D/C patterns with a greater proportion of patients on NO16966 discontinuing Tx for any AE. Duration of study Tx might have affected both the incidence of AEs and the magnitude of PFS benefit observed for the addition of bevacizumab to oxaliplatin-based chemotherapy in these studies. Attention to Tx duration and Non-PD Tx D/C in future clinical trials will be important when considering PFS as a primary efficacy endpoint. [Table: see text] No significant financial relationships to disclose.

scholarly journals A phase I/II study of weekly high-dose erlotinib in previously treated patients with nonsmall cell lung cancer

Cancer ◽  
2006 ◽  
Vol 107 (5) ◽  
pp. 1034-1041 ◽  
Author(s):  
Daniel T. Milton ◽  
Christopher G. Azzoli ◽  
Robert T. Heelan ◽  
Ennapadam Venkatraman ◽  
Jorge E. Gomez ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase I ◽  
Cell Lung Cancer ◽  
Nonsmall Cell Lung Cancer ◽  
High Dose ◽  
Previously Treated Patients ◽  
Previously Treated

Trial of sequential trimetrexate, fluorouracil, and high-dose leucovorin in previously treated patients with gastrointestinal carcinoma.

1994 ◽  
Vol 12 (4) ◽  
pp. 695-700 ◽  
Author(s):  
J A Conti ◽  
N Kemeny ◽  
K Seiter ◽  
E Goker ◽  
W Tong ◽  
...  
Keyword(s):  
Rest Period ◽  
Maximum Tolerated Dose ◽  
High Dose ◽  
Gastrointestinal Carcinoma ◽  
Significant Toxicity ◽  
Previously Treated Patients ◽  
Advanced Colorectal Carcinoma ◽  
Previously Treated ◽  
Grade 3 ◽  
Almost All

PURPOSE Trimetrexate (TMTX) is a dihydrofolate reductase inhibitor, which, like methotrexate (MTX), has been shown to potentiate fluorouracil (FU) cytotoxicity by increasing phosphoribosylpyrophosphate (PRPP) levels. We investigated the safety and efficacy of a sequential TMTX/FU/leucovorin (LV) combination. PATIENTS AND METHODS Forty-one patients with advanced gastrointestinal carcinoma (mostly colorectal) received variable doses of TMTX followed 24 hours later by FU/LV (500 mg/m2 of each drug). Almost all patients had received previous chemotherapy. The initial 19 patients were treated on a 3-week-on/1-week-off schedule without any significant toxicity; the remaining patients were treated for 6 consecutive weeks followed by a 2-week rest period. TMTX was escalated in 30-mg/m2 increments from 20 to 110 mg/m2 in separate patient cohorts. When the 110-mg/m2 dose of TMTX was reached, the FU dose was escalated from 500 mg/m2 to 600 mg/m2. RESULTS The partial response (PR) rate in assessable patients with colorectal cancer (all previously treated) was 20% (seven of 35; 95% confidence interval, 7% to 33%), and with other gastrointestinal cancers was one of four patients. Median survival has not been reached with a median follow-up of 13.5 months. The maximum-tolerated dose (MTD) was 110 mg/m2 for TMTX, 500 mg/m2 for FU, and 500 mg/m2 for LV on a 6-weeks-on/2-weeks-off cycle. The principal toxicities were grade 3 or 4 diarrhea, which occurred in 17% of patients, and hypersensitivity reactions, which occurred in 26% of patients. CONCLUSION TMTX can be administered at maximal doses in combination with FU and LV without increasing toxicity. The PR rate of 20% in advanced colorectal carcinoma patients previously treated with chemotherapy is encouraging and merits further study.

scholarly journals Prognostic impact of cytogenetic aberrations in AL amyloidosis patients after high-dose melphalan: a long-term follow-up study

Blood ◽  
2016 ◽  
Vol 128 (4) ◽  
pp. 594-602 ◽  
Author(s):  
Tilmann Bochtler ◽  
Ute Hegenbart ◽  
Christina Kunz ◽  
Axel Benner ◽  
Christoph Kimmich ◽  
...  
Keyword(s):  
High Dose ◽  
Al Amyloidosis ◽  
Prognostic Impact ◽  
Favorable Prognosis ◽  
Cytogenetic Aberrations ◽  
Key Points ◽  
Long Term Follow Up ◽  
High Dose Melphalan

Key Points Translocation t(11;14) confers a favorable prognosis in AL amyloidosis patients treated with HDM.

Long-term follow-up of autotransplant (AT)-supported high-dose melphalan (hdm) for multiple myeloma (MM): Update of Intergroup Francophone du Myelome (IFM), Southwest Oncology Group (SWOG), and Arkansas (ARK) Total Therapy (TT) trials

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8519-8519
Author(s):  
B. Barlogie ◽  
M. Attal ◽  
J. Crowley ◽  
J. Harousseau
Keyword(s):  
Phase Iii ◽  
Long Term Results ◽  
High Dose ◽  
Long Term Follow Up ◽  
Phase Iii Trials ◽  
Trial Outcomes ◽  
Total Therapy ◽  
High Dose Melphalan

8519 Background: Clinical trial outcomes are usually published when statistical protocol objectives have been met, with short median follow-up not exceeding 5 years. Due to treatment innovations, MM survival beyond 10 years has become more common but formal long-term results are seldom reported. Methods: IFM, SWOG and ARK provide an update of their major trials. IFM-90: 1 AT v standard therapy (STD), IFM-94: 2 v 1 AT, IFM-9902: 2AT ± THAL, IFM-9904: 2AT for high-risk MM; SWOG-9321: 1 AT v STD; TT1: 2 AT with interferon, TT2: 2AT ± THAL, TT3: 2AT + THAL + bortezomib. Results: OS clustered in 3 groups with superior outcomes for TT3/TT2/IFM-99 v TT1 v IFM-94/ IFM-90/SWOG-9321 with 5/10/15-yr estimates of 70%/50%/TE v 57%/35%/20% v 43%/25%/15% (p<0.0001). EFS also clustered in 3 groups with superior outcomes for TT3 v TT2 v remainder with estimates of 71%/TE/TE v 50%/35%/TE v 27%/ 15%/10% (p<0.0001). Among phase III trials, added THAL in TT2 increased 10-yr OS/EFS from 40%/25% to 60%/40% (p=0.04/p=0.0005); 10-yr OS was 30% v 8% with 1 v 0 AT in IFM-90 (p=0.005), 31% v 21% with 2 AT v 1 AT in IFM-94 (p=0.08), and 20% for both arms of S9321. On multivariate analysis involving 2962 patients, OS was adversely affected by B2M >=3.5mg/L (p<0.001), LDH >=ULN (p<0.001), hemoglobin <10g/dL (p=0.001) and albumin <3.5g/dL (p=0.02). 2AT (65%) and THAL (21%) both contributed independently to superior OS (p<0.001, p=0.002); among individual trials, IFM-9902 (19%) and TT2/TT3 (33%) both improved OS significantly (both p<0.001). For each of the 3 major OS clusters, 228 patients could be matched on B2M, LDH, hemoglobin and albumin, with 10-yr OS/EFS estimates of 65%/30% for the TT3/TT2/IFM-9902 group significantly exceeding 30%/15% each for the other 2 groups (p=0.001/p=0.001). Conclusions: A 15-yr EFS plateau of 10% with older trials and superior 10-yr EFS/OS estimates of 50%/35% with recent studies emphasize that cure should be a realistic trial objective in contemporary MM therapy, requiring however very long-term follow-up beyond 15 years. [Table: see text]

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