Survival of patients (pts) treated with high-dose radiotherapy (RT) and concurrent chemotherapy for unresectable non-small cell lung cancer (NSCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7544-7544
Author(s):  
S. Schild ◽  
D. Graham ◽  
S. Hillman ◽  
S. Vora ◽  
G. Yolanda ◽  
...  
Keyword(s):  
Disease Control ◽  
Standard Dose ◽  
Secondary Analysis ◽  
Concurrent Chemotherapy ◽  
Phase Iii ◽  
High Dose ◽  
Entire Cohort ◽  
Prior Therapy ◽  
Technological Improvements ◽  
Improve Disease Control

7544 Background: NCCTG N0028 was a trial that determined the MTD of RT that could be given with carboplatin & paclitaxel was 74 Gy/34 fractions. This secondary analysis was performed to determine the survival of pts treated on this trial. Methods: Eligible pts had medically or surgically unresectable NSCLC, PS=0–1, weight loss <10% in the prior 3 months(mo), no prior therapy, adequate laboratory & pulmonary functions. Included were 25 pts with clinical stages I (4pts), II (1 pt), IIIa (12 pts), & IIIb (8 pts). Treatment included: weekly I.V. paclitaxel (50mg/m2) & carboplatin (AUC=2) during RT. The RT included 2 Gy daily to an initial dose of 70 Gy. The total dose was increased in 4 Gy increments until the MTD was determined. RT was delivered with 3-D treatment planning but no elective nodal RT. Three pts received 70 Gy, 18 pts received 74 Gy, & 4 pts received 78Gy. Results: Pts were followed until death or from 10–67 mo (median: 28mo) in those alive at last evaluation. The median survival (MS) of the entire cohort was 42mo. The 5 stages I-II pts had a MS of 53 mo & the 20 stage III pts had MS of 42mo. Conclusions: Standard dose RT is unable to sterilize disease in the majority of pts with unresectable NSCLC. While the addition of chemotherapy has significantly improved survival of these pts, the MS is generally 15–24 mo. These preliminary results suggest higher than standard doses of RT may improve disease control & prolong survival. A phase III trial comparing standard-dose RT(60Gy) to high-dose RT (74Gy) is open and should more definitively address the issue of RT dose with concurrent chemotherapy for unresectable NSCLC. Future technological improvements in imaging & targeting will provide methods to safely administer even greater RT doses which will likely further improve disease control. No significant financial relationships to disclose.

Survival of Patients Treated with High-dose Radiotherapy and Concurrent Chemotherapy for Unresectable Non-small-cell Lung Cancer

2010 ◽  
Vol 06 ◽  
pp. 32
Author(s):  
Steven E Schild ◽  
Helen J Ross ◽  
◽  
Keyword(s):  
Standard Dose ◽  
Small Cell Lung Carcinoma ◽  
Survival Rates ◽  
Therapeutic Index ◽  
Concurrent Chemotherapy ◽  
Small Cell ◽  
Phase Iii ◽  
High Dose ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma

Radiotherapy (RT) has been used to treat cancers for 110 years. Today, megavoltage RT is delivered with very precise linear accelerators. Computed tomography and/or positron-emission tomography are used to define both tumor and normal tissue volumes. Powerful computers analyze these volumes in 3D space and design complex treatment plans. Over time, the ratio of dose administered to tumor compared with dose administered to the normal structures has increased, resulting in a better therapeutic index and improved survival. In the 1970s and 1980s, the five-year survival rate of unresectable non-small-cell lung carcinoma was 5% with standard RT alone. Adding chemotherapy before or after radiation improved the five-year survival to about 15%. More recently, concurrent chemotherapy and RT has achieved five-year survival rates of up to 29%. Pilot trials employing chemotherapy and higher-dose RT have resulted in still better local control and survival. A phase III trial of chemotherapy plus either standard-dose RT (60Gy/30) or high-dose RT (74Gy/37) is ongoing. New technology is providing ways to improve the therapeutic ratio and administer greater RT doses more safely.

scholarly journals Standard-dose versus high-dose radiotherapy with concurrent chemotherapy in esophageal cancer: A prospective randomized study

2018 ◽  
Vol 07 (01) ◽  
pp. 27-30 ◽  
Author(s):  
Navin Nayan ◽  
M. Bhattacharyya ◽  
Vikas K. Jagtap ◽  
A. K. Kalita ◽  
R. Sunku ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Total Dose ◽  
Standard Dose ◽  
Randomized Study ◽  
Complete Response ◽  
Concurrent Chemotherapy ◽  
Prospective Randomized Study ◽  
High Dose ◽  
Large Sample Size

Abstract Objective: The objective of this study is comparision of local and distant control rates with high-dose versus standard-dose radiotherapy along with concurrent chemotherapy in esophageal cancer – a prospective randomized study. Materials and Methods: Histologically proven Stage I–III patients with carcinoma esophagus were randomized into two groups. One group has been treated with standard-dose radiotherapy, i.e., a total dose of 50.4 Gy (1.8 Gy/day, 28#, 5 days/week). The other group (study arm) has received high-dose radiotherapy, i.e. a total dose of 64.8 Gy (1.8 Gy/day, 36#, 5 days/week). Both groups have received 2 cycles of 3 weekly concurrent chemotherapy (cisplatin 75 mg/m[2] on day 1 and 5-fluorouracil 750 mg/m[2] continuous intravenous infusion over 24 h on day 1–4). Follow-up response evaluation was done by both endoscopy and computed tomography scan after 6–8 weeks and after 2 months thereafter. Results: Out of a total of 28 patients, 68% showed a complete response, 14% showed partial response, and 18% patients developed progressive disease at first and subsequent follow up (median follow-up of 21 months). Among the complete response patients, rates were higher in high-dose group compared to standard-dose radiotherapy group (71% vs. 64%, P = 0.38). Treatment-related toxicities were acceptable in both groups. Conclusion: High-dose radiotherapy with concurrent chemotherapy seems to be more effective with acceptable toxicity in our study. However, further follow-up and large sample size may be required to validate the current study conclusion.

scholarly journals Double-Blind, Randomized, Placebo-Controlled Phase II Dose-Finding Study To Evaluate High-Dose Rifampin for Tuberculous Meningitis

2018 ◽  
Vol 62 (12) ◽  
Author(s):  
S. Dian ◽  
V. Yunivita ◽  
A. R. Ganiem ◽  
T. Pramaesya ◽  
L. Chaidir ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Tuberculous Meningitis ◽  
Standard Dose ◽  
Geometric Mean ◽  
Phase Iii ◽  
High Dose ◽  
Treatment Area ◽  
Double Blind ◽  
Time Curve

ABSTRACT High doses of rifampin may help patients with tuberculous meningitis (TBM) to survive. Pharmacokinetic pharmacodynamic evaluations suggested that rifampin doses higher than 13 mg/kg given intravenously or 20 mg/kg given orally (as previously studied) are warranted to maximize treatment response. In a double-blind, randomized, placebo-controlled phase II trial, we assigned 60 adult TBM patients in Bandung, Indonesia, to standard 450 mg, 900 mg, or 1,350 mg (10, 20, and 30 mg/kg) oral rifampin combined with other TB drugs for 30 days. The endpoints included pharmacokinetic measures, adverse events, and survival. A double and triple dose of oral rifampin led to 3- and 5-fold higher geometric mean total exposures in plasma in the critical early days (2 ± 1) of treatment (area under the concentration-time curve from 0 to 24 h [AUC0–24], 53.5 mg · h/liter versus 170.6 mg · h/liter and 293.5 mg · h/liter, respectively; P < 0.001), with proportional increases in cerebrospinal fluid (CSF) concentrations and without an increase in the incidence of grade 3 or 4 adverse events. The 6-month mortality was 7/20 (35%), 9/20 (45%), and 3/20 (15%) in the 10-, 20-, and 30-mg/kg groups, respectively (P = 0.12). A tripling of the standard dose caused a large increase in rifampin exposure in plasma and CSF and was safe. The survival benefit with this dose should now be evaluated in a larger phase III clinical trial. (This study has been registered at ClinicalTrials.gov under identifier NCT02169882.)

Providing Additional “Muscle” for Older Adults Through Optimal Influenza Vaccine Selection

2018 ◽  
Vol 52 (9) ◽  
pp. 936-941 ◽  
Author(s):  
John A. Dougherty ◽  
Elias B. Chahine
Keyword(s):  
Older Adults ◽  
Influenza Vaccine ◽  
Disease Control ◽  
Older Patients ◽  
Standard Dose ◽  
Influenza Vaccines ◽  
High Dose ◽  
Control And Prevention ◽  
Reasonable Evidence ◽  
Age Appropriate

Immunization is the best strategy to protect individuals from influenza; however, older adults tend to respond less favorably to vaccines because of immunosenescence. The Centers for Disease Control and Prevention states that any licensed, recommended, and age-appropriate influenza vaccine may be used in older adults despite reasonable evidence suggesting that the high-dose and, to a lesser extent, the adjuvanted and recombinant influenza vaccines provide better protection than the standard-dose vaccines in this vulnerable population. In this era of precision medicine, clinicians can preferentially recommend these contemporary vaccines to equip their older patients with the best possible protection against influenza.

Imatinib 800 mg: Preliminary Results of a Phase II Trial of the GIMEMA CML Working Party in Intermediate Sokal Risk Patients and Status-of-the-Art of an Ongoing Multinational, Prospective Randomized Trial of Imatinib Standard Dose (400 mg Daily) vs High Dose (800 mg Daily) in High Sokal Risk Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1098-1098
Author(s):  
Gianantonio Rosti ◽  
Giovanni Martinelli ◽  
Fausto Castagnetti ◽  
Nicoletta Testoni ◽  
Giorgina Specchia ◽  
...  
Keyword(s):  
High Risk ◽  
Randomized Trial ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Standard Dose ◽  
Phase Iii ◽  
High Dose ◽  
Molecular Response ◽  
Risk Patients

Abstract The conventional treatment of chronic myeloid leukemia (CML) in early chronic phase (ECP) is imatinib 400 mg daily. The estimated rates of major (MCgR) and complete cytogenetic response (CCgR) at 42 months are 91% and 84%, respectively (IRIS Trial - F Guilhot, ASH 2004), with a survival free from accelerated and blastic phase of 84%. The rates of CCgR are significantly different according to Sokal score, being 91%, 84% and 69% for low, intermediate and high risk categories. Phase I and II trials of imatinib have clearly shown a dose-response effect; more importantly, a single center phase II trial of imatinib 800 mg in ECP showed significantly better results vs standard dose, in terms of CCgR (90% vs 74%) and of complete molecular response (28% vs 7% at 18 months) [H. Kantarjian et al, Blood 103 (8), 2004]. The GIMEMA (Gruppo Italiano Malattie Ematologiche dell’Adulto) CML WP is conducting a phase II trial of imatinib 800 mg in intermediate Sokal risk in ECP (trial CML/021). Overall, 89 pts (mean age 53 yrs) have been enrolled. Fourty-four patients completed 6 months of treatment: the complete hematological response rate is 100%; the MCgR and CCgR are 90% and 81%, respectively. The 6 months CCgR rate of this trial parallels the IRIS trial one in intermediate risk cases (84%), with a much shorter treatment period. The major molecular response rate at 6 months (RTQ-PCR as ratio BCR-ABL/ABL) is 56% (cut-off ≤ 0.12%) or 41% (cut-off ≤0.05%). The compliance to the treatment improved time by time, being 47% the patients receiving ≥ 80% of the scheduled dose between months 1–3 and 60% between months 4 - 6. A second project, exploring imatinib high dose, is reserved to high risk cases: a multinational working group, within the frame of Leukemianet CML WP, is conducting a phase III randomized trial (1:1) of imatinib 400 mg vs 800 mg in high Sokal risk in ECP. By July 31, 2005, 80 patients have been enrolled: GIMEMA CML WP (44 pts), Nordic Countries - Sweden, Denmark, Norway and Finland (25 pts), Turkey (10 pts) and Israel (1 pt).

High Dose (HD-AraC) vs Standard Dose Cytosine Arabinoside (SD-AraC) during Induction in Acute Myelogenous Leukemia (AML): Impact on Stem Cell Mobilization after Consolidation and on Autologous Transplantation (Second Report of the EORTC-Leukemia Group (LG) - GIMEMA AML-12 Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 609-609
Author(s):  
Roelof Willemze ◽  
Stefan Suciu ◽  
Franco Mandelli ◽  
T.M. de Witte ◽  
Boris Labar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Standard Dose ◽  
Autologous Transplantation ◽  
Early Death ◽  
Myelogenous Leukemia ◽  
Phase Iii ◽  
High Dose ◽  
No Donor ◽  
Platelet Recovery ◽  
Poor Risk

Abstract The AML-12 randomized phase III trial of EORTC-LG and GIMEMA assessed the efficacy and toxicity of HD-AraC (3 g/m2/12 hrs for 4 days) with daunorubicin (50 mg/sqm for 3 days) and etoposide (50 mg/sqm for 5 days) vs SD-AraC (100 mg/sqm for 10 days) with the same drugs. Patients (pts) in complete remission (CR) received consolidation (Co) consisting of AraC (500 mg/sqm/12 hrs for 6 days) and daunorubicin. Subsequently an allogeneic (allo-SCT) or autologous stem cell transplantation (auto-SCT) was planned according to donor availability and age. A 2nd randomization was performed after Co in pts without a donor: auto-SCT followed or not by low dose IL-2. From 9 1999 till 7 2006, 1675 AML pts (APL excluded), age &lt;61 years, from 67 centers (23 EORTC-LG and 44 GIMEMA) entered. Currently 1571 pts have been randomized for induction and 429 pts post-Co. During the induction toxicity was similar in the 2 arms except for conjunctivitis: 6% (HD-AraC) vs 0% (SD-AraC). HD-AraC given in the induction had no impact on the organ toxicity during Co but platelet recovery (&gt; 50x109/l) was longer (median 4.0 vs 3.3 weeks; P=0.01). Among 886 pts randomized until 7 2005 by EORTC centers and 6 large GIMEMA centers, median follow-up of 2.5 years, 815 were evaluable for response. Out of 643 pts who reached CR, 57 went off study (toxicity, early progression). Among the remaining 586 who received Co, 37 could not be evaluated (early death/relapse, too early) and 549 were still CR after Co: 297 pts had no donor/no sibling, 197 had a donor and 55 were not typed. In these 3 groups the present estimates of the SCT rates are: 63% (auto-SCT), 71% (allo-SCT) and 69% (auto-SCT), resp. The 2.5-yr DFS rates (SE%) were 45% (3%), 61% (4%), and 67% (7%), resp. In pts &lt; 50 yrs, 216 pts had no donor/no sibling, 135 had a donor and 14 have not been typed. For the first 2 groups, the 2.5 yr DFS rates (SE%) were 50% (4%) vs 68% (4.5%), hazard ratio=0.64, 95% CI (0.44, 0.93), P=0.02. In pts without a donor/a sibling successful mobilization of blood stem cells (b-SC) after Co was in HD-Ara-C vs SD-Ara-C arm 53 vs 69%, of failure/postponement 37 vs 24%, and other 9.5 vs 7%. The rate of auto-SCT was similar (65 vs 64%), but harvest of BM cells was more often required in the HD-AraC group (15 vs 4.5%). Pts with an insufficient/delayed b-SC harvest had a longer (P&lt;0.001) platelet recovery (&gt; 50x109/l) after Co than those with a successful harvest: median = 6.7 vs 3.3 wks. Among 393 pts with information on cytogenetics, 14% had good risk, 50% normal, 23% other and 13% poor risk (-5/5q-, -7/7q-, complex). The 2.5-year EFS (no CR, time to relapse or death in CR) rates (SE%) were 68% (7%), 42% (4%), 32% (5%) and 14% (5%), resp. So far: toxicity of HD-Ara-C was acceptable; in those who received HD-AraC in induction platelet recovery after Co was longer and the rate of successful b-SC collection was lower; SCT rates are high and similar in the 2 randomized arms; pts &lt;50 yrs with a donor do have a longer DFS; pts with poor risk cytogenetics continue to have a poor prognosis.

Imatinib High Dose (800 mg): Results of a Phase II Trial of the GIMEMA (Gruppo Italiano Malattie Ematologiche Dell’Adulto) CML Working Party in Intermediate Sokal Risk Patients and Status-of-the-Art of an Ongoing Multinational, Prospective Randomized Trial of Imatinib Standard Dose (400 mg Daily) vs High Dose (800 mg Daily) in High Sokal Risk Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4776-4776
Author(s):  
Gianantonio Rosti ◽  
Fausto Castagnetti ◽  
Marilina Amabile ◽  
Nicoletta Testoni ◽  
Angela Poerio ◽  
...  
Keyword(s):  
Phase Ii ◽  
Standard Dose ◽  
Chronic Phase ◽  
Working Party ◽  
Great Majority ◽  
Observation Time ◽  
Phase Iii ◽  
High Dose ◽  
Molecular Response ◽  
Risk Patients

Abstract Imatinib has become the treatment of choice for CML. The standard dose (SD) for CP CML is 400 mg daily: results are less favourable in pts at high or intermediate Sokal risk vs low Sokal risk ones. In intermediate Sokal risk, the IRIS trial (Hughes et al NEJM 349:15, 2003 ) reported at 12 mos a complete cytogenetic response (CCgR- 0% Ph-pos) rate of 67% and a major molecular response (MMolR) rate of 45%. Pre-clinical and clinical data suggest that high doses (HD - 800 mg daily) of ima may be more effective. The GIMEMA CML Working party is conducting a phase II, multi-istitutional prospective study (serial n. CML/021) to investigate the effects of imatinib HD in intermediate Sokal risk. Between Jan, 2004 and May, 2005, 25 centers enrolled 82 pts (80 eval); median age 56 yrs (26–79). Pts evaluable at 3,6 and 12 mos are 80, 77 and 65, respectively. The median observation time is 12 mos. At 3 and 6 mos, 83% and 97% of the pts reached a stable CHR. At 6 mos, 86% obtained a CCgR and 53% of CCgR pts a MMolR (Bcr-Abl/Abl × 100 ratio &lt; 0.1%). At 12 mos, the CCgR rate was 90% and the MMolR rate was 57%. One patient progressed to accelerated/blastic phase. The compliance to HD treatment was good: at 3, 6 and 12 mos 55%, 52% and 52% of the pts received a median daily dose of imatinib &gt; 600 mg. Non hematopoietic AEs accounted for the great majority of dose reductions. The results of this trial further indicate that imatinib HD induces higher and more rapid responses in intermediate Sokal risk CML pts in early chronic phase, being superior to the results obtained with SD (IRIS) and in the range of the MD Anderson results (Kantarjian et al Blood 2004 103:2873). A second project is reserved to high Sokal risk CML pts in early CP: a multinational group, within EuropeanLeukemianet CML WP, is conducting a phase III trial (1:1) of imatinib 400 mg vs 800 mg. By July 31, 2005, 141 patients have been enrolled: GIMEMA (88 pts), Nordic CML Study Group (Sweden, Denmark, Norway and Finland) (25 pts), Turkey (25 pts) and Israel (3 pt).

A Cost-Utility Analysis of Nilotinib for CML Patients Who Have Become Resistant to Imatinib.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5175-5175
Author(s):  
H. Pilgrim ◽  
K. Jewitt ◽  
S. Ward
Keyword(s):  
Standard Dose ◽  
Chronic Phase ◽  
Cost Utility ◽  
Phase Iii ◽  
High Dose ◽  
Lifetime Horizon ◽  
Imatinib Resistant ◽  
Cost Effective Treatment ◽  
The Uk ◽  
The Cost

Abstract Background: New generation BCR-ABL tyrosine kinase inhibitors are promising treatments for CML patients who are imatinib resistant or intolerant. The objective of this study was to consider the cost-utility of nilotinib in comparison to ‘high dose’ (800 mg) imatinib (the current standard comparator in the UK) for chronic-phase CML patients resistant to standard dose 400 mg imatinib using a lifetime horizon. The analysis is based on a UK NHS perspective. Methods: A Markov model was developed using interim data from the phase II CAMN107A2101 registration study of nilotinib and data from the 39 patients who were dose-escalated, due to a sub-optimal response, to 800 mg imatinib within the IRIS phase III trial of imatinib versus interferon. Based on this evidence, the estimated 18-month survival has been extrapolated over a lifetime using parametric Weibull regression. Since the price of nilotinib in the UK was still to be determined at the time of preparation, the cost was assumed to be £106.94 per day, price parity with high dose imatinib. The costs and utilities associated with adverse events have been incorporated during the first six months following treatment. All costs and utilities were discounted at 3.5%. Results: Nilotinib is estimated to cost an additional £49K and generate an additional 2.18 Quality-Adjusted Life Year’s (QALYs) in comparison to high dose imatinib over a patient’s lifetime. Therefore, the incremental cost-utility of nilotinib versus high dose imatinib is expected to be approximately £22K per QALY gained. This result is subject to uncertainty around data extrapolation. However availability of longer term data from the ongoing nilotinib trial will allow validation at a later date. Conclusions: Our analysis suggests that nilotinib provides a clinically and cost-effective treatment (according to conventionally acceptable thresholds) for CML patients who have become imatinib resistant, in an indication where limited alternative treatment options exist.

Phase III Randomized Stem Cell Mobilization Trial Comparing Standard Vs Double-Dose G-CSF Vs Standard Doses of G-CSF Plus GM-CSF in Hard to Mobilize Patients Undergoing An Autologous Hematopoietic Stem Cell Transplant (HSCT).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3228-3228
Author(s):  
Elizabeth Berger ◽  
Christopher Seet ◽  
Mala Parthasarathy ◽  
Tulio Rodriguez ◽  
Scott E. Smith ◽  
...  
Keyword(s):  
Stem Cell ◽  
Standard Dose ◽  
Stem Cell Mobilization ◽  
Phase Iii ◽  
Control Group ◽  
High Dose ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Cell Mobilization

Abstract Abstract 3228 Poster Board III-165 Introduction Using standard dose G-CSF (10 μg/kg) for stem cell mobilization, 25-40% of patients, deemed to be hard to mobilize based on prior therapy, will not collect sufficient HSC (> 2-2.5 × 106 CD34/kg) to proceed to a prompt autotransplant. Strategies to improve CD34/kg yields have included dose escalating G-CSF up to 30 μg/kg or combining G-CSF and GM-CSF. While dose escalated G-CSF is effective in increasing CD34 yields in normal donors as is the combination of G-CSF and GM-CSF, their comparative value in pre-treated patients has not been tested. To determine the value of these strategies, we performed a randomized comparison of high dose G-CSF (30 μg/kg as 2 doses 12 hours apart), to the combination of simultaneous single daily doses of G-CSF (10 μg/kg) plus GM-CSF (5 μg/kg), to a control group receiving G-CSF at an equivalent total dose of cytokine to the combination arm (15μg/kg) as a single dose. Patients and Methods Patients were eligible if heavily pre-treated, defined as: a minimum of 10 total cycles of combination chemotherapy and two prior regimens, or a total of 6 chemotherapy cycles if the patient also received RT to marrow bearing sites, platinum-based chemotherapy or 2 or more cycles of any BCNU or fludarabine containing regimen. Baseline WBC had to be > 3000/μl, ANC > 1500/μl and a platelets > 100,000/μl. Twelve liter aphereses began on day 5 of mobilization, and continued until ≥ 4 × 106 CD34/kg were collected or a maximum of 5 aphereses. Patients typically proceeded to transplant if they had ≥ 2.5 × 106 CD34/kg collected and were always re-mobilized if they collected < 2.0 × 106 CD34/kg. CD34 subsets (CD34+/CD33- and CD34+/CD38-) were also assessed for the 3 groups to determine if more primitive HSC were mobilized by the 2 novel strategies. The sample size was calculated based as follows: 60% of the control group would collect 2.5 × 106 CD34/kg and this would rise to 90% in one or both study arms. The detection of such differences with a power of 80% and a 2-sided alpha level of 0.025 required a total sample of 120 patients. Results A total of 120 patients were randomized; 119 were eligible. Patient demographics, shown in the Table, were matched among the three groups: The % of patients collecting ≥2.5 × 106 CD34/kg was: standard G: 60%, high dose G: 57% (p = 1.0), G + GM: 41% (p = 0.1). Median CD34 collected in first mobilization were, 3.6 × 106/kg, 3.0 × 106/kg (p = 0.22) and 2.0 × 106/kg (p = 0.05) respectively in a median of 4, 4, and 5 aphereses (p = NS). Re-mobilization rates: standard G; 37.5%, high dose G: 35%; G + GM: 50% (p = NS). Total median CD34 collected from first and any second mobilizations were: standard G: 4.8 × 106/kg, high dose G: 3.9 × 106/kg, and G + GM: 3.5 × 106/kg. One patient in the standard G arm and 3 in high dose G did not proceed to transplant due to poor initial mobilization and progression in 2, and one each for progression or poor mobilization alone. There were no significant differences in median engraftment times: for ANC, 10, 11 and 15 days respectively for the standard G-, high dose G- and G + GM arms and for platelets, 11, 13 and 14 days respectively. The overall survivals @ the median f/u time of 37 months were 59.8%, 61.8% and 48.1% respectively (p = 0.272) for the three groups. The % primitive HSC (CD34+/CD33- and CD34+/CD38-) from the first mobilization were identical in the 3 patient groups. Conclusions We found no advantage to dose escalated G-CSF nor to the combination of G-CSF and GM-CSF to mobilize HSC for autotransplantation in heavily pre-treated patients. We also did not find higher numbers of more primitive CD34 subsets mobilized by these newer strategies. Alternative approaches, e.g. the combination of plerixifor + standard dose G-CSF (Stiff et al: BBMT; 15:249-56, 2009) would appear to be the preferred method of initial HSC mobilization for heavily pre-treated patients. Disclosures Stiff: Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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