Quality of life (QL) of patients (pts) treated for muscle invasive bladder cancer (MIBC) with radiotherapy (RT) +/- chemotherapy (CT) in the BC2001 trial (CRUK/01/004): Analysis of impact of treatment at an individual level.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 292-292 ◽  
Author(s):  
Robert Anthony Huddart ◽  
Emma Hall ◽  
Miguel Miranda ◽  
Malcolm Crundwell ◽  
Peter Jenkins ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Significant Proportion ◽  
Disease Free Survival ◽  
Similar Proportion ◽  
High Dose ◽  
Exact Test ◽  
Change Scores ◽  
Individual Level ◽  
Significant Difference ◽  
The Impact

292 Background: BC2001 showed that adding 5FU+MMC CT (cRT) to RT significantly improved locoregional disease free survival [James 2012] & using reduced high dose volume RT (RHDVRT) rather than standard RT (stRT) did not reduce late side effects [Huddart 2013]. Here we report the impact of treatment on QL at the individual level. Methods: 458 (pts) were randomised to RT (178) vs. cRT (182) (CT comparison) &/or to stRT (108) vs. RHDVRT (111) (RT comparison). Pts completed Functional Assessment of Cancer Therapy-Bladder (FACT-BL) questionnaires at baseline (bl), end of treatment (EoT), 6, 12, 24, 36, 48 & 60 months (m). Mean changes from bl were compared between randomised groups. A minimal clinically relevant change from bl score was defined as 3 points in bladder cancer subscale (BLCS) & 7 points in total FACT-BL (TOTAL). The proportion of pts with an improvement, no difference & worsening at 12m were compared by Chi squared/Fishers exact test (1% significance). Results: Data were available for 331 (92%) & 204 (93%) pts at bl & 181 (50%) & 107 (49%) at 12m for the CT & RT comparison respectively. QL scores were significantly reduced at EoT but recovered to bl levels by 12m with no significant difference in TOTAL or BLCS mean change scores between randomised groups. By EoT ~60% pts reported worsening of QL. At 12m & beyond, whilst mean change scores were not different to bl, ~30-40% reported worsening of QL (-) with a similar proportion reporting an improvement (+) (Table 1). No statistically significant differences were found between randomised groups. Conclusions: Following (c)RT a significant proportion of pts have a decline in QL at EoT but after 12m overall QL is, on average, similar to bl. At an individual level approximately equal proportions of pts report an improvement in QL as report a worsening. There is no evidence of additional impairment in QL by the addition of CT to RT. Clinical trial information: ISRCTN6832433. [Table: see text]

Short and Long Term Efficacy of Autologous Bone Marrow Cells To Support Intensive Chemotherapy in Patients Failing Peripheral Blood Stem Cell Mobilization.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2999-2999 ◽  
Author(s):  
Tara Seshadri ◽  
Khalil Al-Farsi ◽  
Julie Stakiw ◽  
Clement Ma ◽  
Ronnie Saragosa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
Intensive Therapy ◽  
Significant Proportion ◽  
Rank Test ◽  
High Dose ◽  
Transfusion Requirements ◽  
Significant Difference ◽  
The Impact

Abstract Introduction: Most autologous hematopoietic cell transplants (AHCT) are performed using peripheral blood mobilized progenitor cells (PBSC). However a small but significant proportion of patients (pts) are unable to mobilize adequate numbers of PBSC. The use of G-CSF-stimulated bone marrow (BM) derived progenitor cells is one method to circumvent this problem and enable AHCT to be performed. However, the long and short-term ability to engraft and the impact of this method on overall and progression free survival (OS and PFS) have not been established. Methods: We reviewed 52 pts (17 AML, 24 NHL, 11 HL) who failed PBSC collection between Jan 1999-Dec 2006 (<2×5106 CD34+cells/kg) and underwent G-CSF stimulated BM harvest to permit high dose therapy (etoposide 60 mg/kg + melphalan 160–180 mg/m2, + TBI 500 or 1200 cGy for pts with AML). 23 pts were supported by harvested BM (44%) and 29 (56%) with a mixture (Mx) of BM and PBSC. Overall and PFS was compared to pts undergoing AHCT using chemotherapy-mobilized PBSCs (n=440) in the same time period (AML n=32, NHL n=273, HL=135) who had a similar median age, pre-transplant induction, salvage therapy and intensive therapy regimens. Kaplan-Meier curves and the Log-rank test were used to compare the OS and PFS between cases and controls. Due to skewed data, the non-parametric Wilcoxon Rank Test was used for simple comparisons of clinical factors. Results: Median age of the cohort at AHCT was 43 years (range 24–68, 67% females). Status prior to AHCT was CR 44%, PR 54%, and SD 2%. Number of chemotherapy regimens (median):AML: 3; NHL: 3; HL: 2. Median BM CFU-GM infused was 4.4×104/kg and median PBSC infused was 0.1×106/kg (n=29). Median follow up times for AML/NHL/HL was 20, 18 and 50 months respectively. Twenty-three pts died:18 from disease progression, 4 treatment-related (TRM) and one of second cancer. Median engraftment time for neutrophils (>0.5×109/L) was 14 days and platelets (>20×109/L) was 27 days and was significantly longer compared to pts who received PBSC alone (10 and 11 days, respectively, p<0.0001). Pts receiving Mx grafts had significantly faster engraftment vs those receiving BM alone (p<0.001). Transfusion requirements (median) during the ASCT admission were 4 units for RBC and 25 units for platelets. Median 12 month Hb, platelet and neutrophil counts were 116 g/L (70–149), 113×109/L (21–238) and 2.4×109/L (0.3–6.2). Two year OS of patients who received harvested BM versus PBSC alone was: 63%/71% (AML, p=0.51), 57%/70% (NHL, p=0.04) and 71%/94% (HL, p=0.04). There was no significant difference in PFS between BM recipients and controls. Non relapse mortality was 5/52 (9.6%) for pts receiving BM compared to 18/440 (4%) supported by PBSCs. Conclusion: Performing an AHCT with BM in patients failing PBSC collection is feasible. Although engraftment is significantly delayed it appears sustained at 12 months post AHCT. Overall survival is inferior compared with patients receiving PBSC alone. Reasons for inferior disease-specific outcomes for pts with lymphoma receiving BM need to be determined.

scholarly journals Evaluation of The Effectiveness and Side Effects of Radiotherapy in Patients With Primary Nervous System Lymphoma. A Single Center Experience

2020 ◽  
Vol 7 ◽  
Author(s):  
Timur Koca ◽  
Aylin Fidan Korcum ◽  
Yasemin Şengün ◽  
Melek Gamze Aksu ◽  
Mine Genç
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Nervous System ◽  
Side Effects ◽  
Disease Free Survival ◽  
Central Nervous System Lymphoma ◽  
Field Size ◽  
High Dose ◽  
Free Survival ◽  
Significant Difference

Aim: In this study, we aimed to evaluate the overall and progression-free survival, the radiotherapy process and the early and late adverse effects in patients who underwent radiotherapy (RT) for primary nervous system lymphoma in our clinic.Method: Between January 2010 and September 2019, 16 patients who received radiotherapy due to primary central nervous system lymphoma in our clinic were examined according to their statistically significant differences in terms of survival and side effects.Results: The median disease-free survival of the patients was 6 months, and the median overall survival was 12.5 months. 18.75% of the patients could not receive chemotherapy but only radiotherapy. Radiotherapy doses were range from 2600 to 5000 cGy. When patients were evaluated in terms of radiotherapy dose, field size and chemotherapy, no statistically significant difference in overall survival was detected. Cognitive disorders were observed as the most common late side effects while the most common acute side effects in patients were headaches.Conclusion: In the treatment of primary central nervous system lymphoma, changes in radiotherapy portals and radiotherapy doses can be predicted in patients who received high-dose methotrexate chemotherapy or not. Furthermore, it has been considered that more comprehensive studies are needed to increase the success of treatment and provide standardization in treatment, especially in patients with elderly and comorbid diseases.

scholarly journals Clopidogrel Pharmacokinetics in Malaysian Population Groups: The Impact of Inter-Ethnic Variability

2018 ◽  
Vol 11 (3) ◽  
pp. 74 ◽  
Author(s):  
Zaril Zakaria ◽  
Alan Fong ◽  
Raj Badhan
Keyword(s):  
Plasma Concentration ◽  
Plasma Concentrations ◽  
High Dose ◽  
Population Groups ◽  
Adjunct Treatment ◽  
Malaysian Population ◽  
Significant Difference ◽  
Target Plasma Concentration ◽  
Ethnic Variability ◽  
The Impact

Malaysia is a multi-ethnic society whereby the impact of pharmacogenetic differences between ethnic groups may contribute significantly to variability in clinical therapy. One of the leading causes of mortality in Malaysia is cardiovascular disease (CVD), which accounts for up to 26% of all hospital deaths annually. Clopidogrel is used as an adjunct treatment in the secondary prevention of cardiovascular events. CYP2C19 plays an integral part in the metabolism of clopidogrel to the active metabolite clopi-H4. However, CYP2C19 genetic polymorphism, prominent in Malaysians, could influence target clopi-H4 plasma concentrations for clinical efficacy. This study addresses how inter-ethnicity variability within the Malaysian population impacts the attainment of clopi-H4 target plasma concentration under different CYP2C19 polymorphisms through pharmacokinetic (PK) modelling. We illustrated a statistically significant difference (P < 0.001) in the clopi-H4 Cmax between the extensive metabolisers (EM) and poor metabolisers (PM) phenotypes with either Malay or Malaysian Chinese population groups. Furthermore, the number of PM individuals with peak clopi-H4 concentrations below the minimum therapeutic level was partially recovered using a high-dose strategy (600 mg loading dose followed by a 150 mg maintenance dose), which resulted in an approximate 50% increase in subjects attaining the minimum clopi-H4 plasma concentration for a therapeutic effect.

A single-center qualitative study evaluating the safety and efficacy of a pharmacist-driven protocol for high-dose methotrexate management

2020 ◽  
pp. 107815522092745
Author(s):  
Stephanie F Matta ◽  
Leslie A Gieselman ◽  
Robert S Mancini
Keyword(s):  
Length Of Stay ◽  
Kidney Injury ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Improvement Project ◽  
Treatment Delays ◽  
Dose Methotrexate ◽  
Significant Difference ◽  
The Impact ◽  
Inpatient Length Of Stay

Introduction Delayed methotrexate clearance in several patients admitted to the oncology unit at a regional medical center necessitated the development of a pharmacist-driven protocol for supportive therapy with high-dose methotrexate. This performance improvement project evaluated the impact of the protocol on inpatient length of stay, patient safety, and clinical outcomes. Methods Retrospective data were collected over 14 months pre-implementation and prospective data were collected over 19 months post-implementation. Primary outcomes included mean length of stay and incidence of kidney injury. Secondary outcomes included myelosuppression, treatment delays, mucositis, protocol adherence, and pharmacist interventions. Chi-squared and unpaired two sample t-test were used for data analysis. Intervention A literature review of consensus recommendations for supportive care post high-dose methotrexate administration was conducted to develop the protocol. Education on implementation was provided to involved disciplines. Results One-hundred ten high-dose methotrexate admissions for 23 patients were analyzed: 24 pre-protocol and 86 post-protocol. Mean length of stay was 5.17 nights pre-protocol and 3.91 nights post-protocol ( p = 0.026). Incidence of kidney injury significantly decreased (16.7% pre-protocol versus 3.5% post-protocol; p = 0.0394). Lower incidences of all-grade anemia (83.3% versus 58.1%), neutropenia (62.5% versus 29.1%), and thrombocytopenia (58.3% versus 33.7%) as well as treatment delays (29.2% versus 11.6%; p = 0.036) were reported post protocol. No statistically significant difference in mucositis was detected. Pharmacist adherence to protocol was ≥80% resulting in 348 interventions with 99.4% provider acceptance. Conclusion The implementation of a pharmacist-driven high-dose methotrexate management protocol resulted in a statistically significant decrease in inpatient length of stay and kidney injury. Further studies are needed to assess the impact on additional outcomes.

Intensification of Adjuvant Chemotherapy: 5-Year Results of a Randomized Trial Comparing Conventional Doxorubicin and Cyclophosphamide With High-Dose Mitoxantrone and Cyclophosphamide With Filgrastim in Operable Breast Cancer With 10 or More Involved Axillary Nodes

2001 ◽  
Vol 19 (3) ◽  
pp. 612-620 ◽  
Author(s):  
Pierre Fumoleau ◽  
Franck Chauvin ◽  
Moïse Namer ◽  
Roland Bugat ◽  
Michèle Tubiana-Hulin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Randomized Trial ◽  
Disease Free Survival ◽  
Dose Intensity ◽  
High Dose ◽  
Free Survival ◽  
Axillary Nodes ◽  
Significant Difference ◽  
Disease Free

PURPOSE: To determine whether intensifying the dose of adjuvant chemotherapy improves the outcome of women with primary breast cancer and 10 or more involved axillary nodes. PATIENTS AND METHODS: Patients (n = 150) were randomized to receive either four cycles of standard doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 every 3 weeks (arm A) or four courses of intensified mitoxantrone 23 mg/m2 plus cyclophosphamide 600 mg/m2, with filgrastim 5 g/kg/d from days 2 to 15, every 3 weeks (arm B). Disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) were determined using life-table estimates. RESULTS: There were no significant differences in DFS (P = .44), DDFS (P = .67), or OS (P = .99) between the two groups at 5 years; DDFS was 45% (arm A) versus 50% (arm B), and DFS was 41% versus 49%, respectively. Five-year survival was similar in both arms (61% v 60%, respectively). Failure to note an intergroup difference in outcome was unrelated to relative dose-intensity. Analysis of patients with 15 or more positive nodes revealed a significant difference in 5-year DDFS (19% v 49% in arm B; P = .01). Toxicity was generally mild in both groups, with no toxic death. The incidence of febrile neutropenia was low (0.3% v 3%). Alopecia was less frequent in arm B (P < .001). CONCLUSION: This randomized trial confirms the feasibility of administering mitoxantrone 23 mg/m2 with cyclophosphamide and filgrastim. Although there was no significant difference between conventional and intensified arms at 5 years, according to subgroup analysis, intensified treatment may decrease the risk of relapse in patients with 15 or more positive nodes compared with doxorubicin an cyclophosphamide.

The Impact of Medical Scribes on Patient Satisfaction in an Academic Otolaryngology Clinic

2019 ◽  
Vol 129 (3) ◽  
pp. 238-244 ◽  
Author(s):  
Katherine R. Keefe ◽  
Jessica R. Levi ◽  
Christopher D. Brook
Keyword(s):  
Patient Satisfaction ◽  
Wait Times ◽  
Exact Test ◽  
Significant Difference ◽  
The Press ◽  
Patient Responses ◽  
Student’S T ◽  
Survey Responses ◽  
Medical Scribes ◽  
The Impact

Objectives: Evidence shows that scribes can improve provider efficiency and satisfaction in several settings, but is mixed on whether scribes improve patient satisfaction. We studied whether scribes improved patient satisfaction in an academic otolaryngology clinic. Methods: The authors performed a retrospective review of patient responses to the Press Ganey survey between 12/2016 and 12/2017. Their responses about satisfaction with the provider and wait times were examined. Three providers worked with scribes during this year; each spent six months with a scribe and six without. The authors compared survey responses from periods with and without scribes using the Fischer exact test. Average overall provider ratings were compared using the Student’s t-test. Results: A total of 87 patients filled out Press Ganey surveys for the 3 providers over the year: 54 for visits without scribes, and 33 for visits with scribes. Fischer exact analysis demonstrated no significant difference in satisfaction with providers and wait times for both individual providers and all providers combined (all P > .05). There was also no difference in patients’ likelihood of recommending the provider’s office ( P = .91). Overall provider rating (0-10 scale) was high without scribes (9.48 ± 1.06) and was unchanged by the presence of scribes (9.53 ± 0.8) ( P = .97). Conclusion: Patient satisfaction with wait times and providers was high overall and was not affected by the presence of a medical scribe.

scholarly journals Adding team-based financial incentives to the Carrot Rewards physical activity app increases daily step count on a population scale: a 24-week matched case control study

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Emma Pearson ◽  
Harry Prapavessis ◽  
Christopher Higgins ◽  
Robert Petrella ◽  
Lauren White ◽  
...  
Keyword(s):  
Physical Activity ◽  
Financial Incentives ◽  
Step Count ◽  
Daily Step ◽  
Individual Level ◽  
Significant Difference ◽  
Daily Step Count ◽  
Steps Per Day ◽  
The Impact ◽  
Experimental Group

Abstract Background Mobile health applications (mHealth apps) targeting physical inactivity have increased in popularity yet are usually limited by low engagement. This study examined the impact of adding team-based incentives (Step Together Challenges, STCs) to an existing mHealth app (Carrot Rewards) that rewarded individual physical activity achievements. Methods A 24-week quasi-experimental study (retrospective matched pairs design) was conducted in three Canadian provinces (pre-intervention: weeks 1–12; intervention: weeks 13–24). Participants who used Carrot Rewards and STCs (experimental group) were matched with those who used Carrot Rewards only (controls) on age, gender, province and baseline mean daily step count (±500 steps/d). Carrot Rewards users earned individual-level incentives (worth $0.04 CAD) each day they reached a personalized daily step goal. With a single partner, STC users could earn team incentives ($0.40 CAD) for collaboratively reaching individual daily step goals 10 times in seven days (e.g., Partner A completes four goals and Partner B completes six goals in a week). Results The main analysis included 61,170 users (mean age = 32 yrs.; % female = 64). Controlling for pre-intervention mean daily step count, a significant difference in intervention mean daily step count favoured the experimental group (p < 0.0001; ηp2 = 0.024). The estimated marginal mean group difference was 537 steps per day, or 3759 steps per week (about 40 walking min/wk). Linear regression suggested a dose-response relationship between the number of STCs completed (app engagement) and intervention mean daily step count (adjusted R2 = 0.699) with each new STC corresponding to approximately 200 more steps per day. Conclusion Despite an explosion of physical activity app interest, low engagement leading to small or no effects remains an industry hallmark. In this paper, we found that adding modest team-based incentives to the Carrot Rewards app increased mean daily step count, and importantly, app engagement moderated this effect. Others should consider novel small-teams based approaches to boost engagement and effects.

The Impact of Different Mobilization Strategies in the Setting of Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3254-3254
Author(s):  
Francesco Mazziotta ◽  
Gabriele Buda ◽  
Nadia Cecconi ◽  
Giulia Cervetti ◽  
Lorenzo Iovino ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Peripheral Blood ◽  
High Dose ◽  
Roc Curve Analysis ◽  
Cd34 Cells ◽  
Significant Difference ◽  
The Impact

INTRODUCTION Multiple myeloma (MM) is considered an incurable disease. Despite the introduction of novel agents allowed deeper response, high-dose chemotherapy and autologous stem cell transplantation (ASCT) remain the standard of care for patients (pts) in good clinical conditions. The most used strategies to mobilize stem cells from bone marrow (BM) into peripheral blood are high-dose cyclophosphamide (HD-CTX) plus G-CSF and G-CSF plus plerixafor (G-CSF+P). The goal of this retrospective study is to investigate whether the two different mobilization strategies have an impact on the clearance of monoclonal PCs in the apheresis products and on pts' outcome. PATIENTS AND METHODS We analyzed 62 pts (median age 61, range 41-75, 37 males and 25 women) diagnosed with MM and treated with ASCT between Mar 2014 and Mar 2018 at our Hematology Division (Pisa, Italy). All pts received induction therapy with at least 4 cycles of bortezomib, thalidomide and dexamethasone (VTD). 9/62 pts obtained a less than partial response (PR) and received lenalidomide-based regimens. After induction, 8 (12,9%) pts achieved complete remission (CR), 26 (41,9%) were in PR, 28 (45,2%) obtained a very good partial response (VGPR). 43/62 fit pts received HD-CTX (2-3 g/sqm) on day 1 followed by G-CSF (30 MU/day) started on day 4 until day 7, increased to 60 MU/day from day 8 until the end of apheresis. In 19/62 pts, after 4 days of G-CSF (60 MU/day) administration and not sufficient mobilization, we added plerixafor (0,24 mg/kgbw) for up to 4 consecutive days. In 43/62 pts we collected apheresis samples (10μl) analyzed through flow citometry to enumerate clonal residual PCs. The panel used to asses clonality included: CD138 Per-Cp, CD38 APC, CD19 PE-Cy7, CD45 APC-Cy7, cytoplasmic immunoglobulin K chain and L chain. RESULTS At the end of the peripheral blood stem cell (PBSC) collection, pts treated with HD-CTX presented a higher CD34+ absolute count (p=0.0489) and achieved the threshold of 5x106 CD34+ cells/kgbw in a significantly (p=0.006) higher percentage. We found a nearly significant (p=0.0517) lower count of CD34+ PBSCs in pts who received lenalidomide-based regimens before the mobilization. Performing flow citometry on apheresis samples, we observed that the number of the harvested clonal PCs showed a significant correlation (p=0.0115) with the occurrence of post-ASCT relapse. ROC curve analysis investigating the predictive effect of the number of pathological PCs on disease relapse showed an area under the curve of 0,6978 (95% CI 0.5392-0.8564; p=0.0267). Neither BM residual PCs detectable on BM biopsies performed before apheresis (r=-0.1323; p=0.609) nor the type of mobilization scheme (p=0.707) had an impact on the proportion of clonal PCs in the graft. Additionally, we did not observe any statistically significant difference in progression free- (PFS) (p=0.8276) and overall survival (OS) (p=0.2475) between the HD-CTX and G-CSF+P groups. DISCUSSION PBSC mobilization has a succession rate > 85%. Despite the use of HD-CTX to increase PBSC yields and decrease tumor burden, there is not clear evidence of a superior mobilization strategy. Additionally, HD-CTX has a not negligible toxicity and approximately 10% of the pts require hospitalization. Conversely, G-CSF+P is a safe and effective approach also in poor mobilizers. In our study, we observed a significative difference in the apheresis yields (p=0.0489) and in the percentage of pts who achieved the threshold of 5x106 CD34+ cells/kgbw (p=0.006) in favor of HD-CTX. Additionally, the detection of harvested residual clonal PCs could be a promising strategy to recognise pts more likely to relapse after ASCT. Nonetheless, we failed to demonstrate a superior effect of HD-CTX in the clearance of harvested clonal PCs, in agreement with the absence of a different pts' outcome amongst the two mobilization strategies. In conclusion, the choice between the two regimens is challenging and requires careful consideration of multiple factors. Overall, young fit pts, especially in the high-risk setting, should be treated with all appropriate modalities including chemiomobilization followed by double-ASCT. Conversely, in pts candidate to a single-ASCT it is reasonable to use G-CSF+P, since HD-CTX does not improve PFS and OS and add toxicity. The absence of an in-vivo purging effect on apheresis products of chemiomobilization further strengthens a chemotherapy-free mobilization. Disclosures Galimberti: Roche: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau.

The Addition of Gemtuzumab Ozogamicin to Induction Chemotherapy for AML Improves Disease Free Survival without Extra Toxicity: Preliminary Analysis of 1115 Patients in the MRC AML15 Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 13-13 ◽  
Author(s):  
Alan K. Burnett ◽  
William J. Kell ◽  
Anthony H. Goldstone ◽  
Donald Milligan ◽  
Ann Hunter ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Preliminary Analysis ◽  
De Novo ◽  
Remission Rate ◽  
Pilot Trial ◽  
Disease Free Survival ◽  
Gemtuzumab Ozogamicin ◽  
Significant Difference ◽  
The Impact

Abstract The MRC AML15 Trial is primarily for patients with any form of AML who are under 60 years. One of the questions addressed was whether the addition of the immunoconjugate, Gemtuzumab Ozogamicin (GO) to induction (course 1) and/or consolidation (course 3) is beneficial. In induction patients are randomised to receive either DA (Daunorubicin/Ara-C) or ADE (Ara-C/Daunorubicin/Etoposide) or FLAG-Ida (Fludarabine/Ara-C/Idarubicin/G-CSF) and in consolidation either MACE (Amsacrine/Etoposide) or HD Ara-C (3.0g/m2 or 1.5g/m2 per dose). Our prior pilot trial had shown that GO 3mgs/m2 could be safely added to day 1 of each of these treatments (Kell et al Blood102, 4277–4283). Here we report the preliminary results of the effect of combining GO with induction chemotherapy. This randomisation achieved its recruitment target and was closed on 30 June 2006. All other comparisons in the trial, including GO in consolidation, remain open. Patients: A total of 1115 patients were randomised between July 2002 and June 2006. The median age was 49 (range 0–71) years: 53% of patients were male: 92% (n=1027) had de novo disease: 95% had WHO performance score of &lt;2: 43% received DA, 43% FLAG-Ida, and 14% ADE. (Recruitment to ADE+GO opened in June 2005). Patients with WBC &gt; 30 x 109/l and LFT’s &gt; normal were initially excluded but admitted from March 2004. APL patients were not eligible for entry. 15% of patients with data had favourable 71% intermediate, and 14% adverse cytogenetics. Over 83% were CD33 positive. Results: The overall remission rate was 85% with no differences between the arms for GO vs no GO in CR (85% vs 85%) induction death (8% vs 7%) or resistant disease (7% vs 8%). There was a modest increase in mucositis on the GO arm in course 1 only (p=0.04) and increased AST and Alt toxicity in C1 (p=.002; p=.03) but no difference in bilirubin grades. GO patients used more platelets (19 vs 14; p&lt;0.0001), but not red cells, and had more days on IV antibiotics (20.6 vs 18.6 p=0.001). The haemopoietic recovery and days in hospital were similar. With a median follow-up of 15 months (range 0–45), there is no significant difference in deaths in CR (GO vs no GO): 36 vs 45 (HR 0.75; CI.49–1.16 p=0.2), but relapse was reduced: 37% vs 52% at 3 years (HR 0.70 (0.52–0.92) p=0.01) resulting in an improved DFS: 51% vs 40% at 3 years (HR 0.72 (0.56–0.91) p=0.008). There is so far no significant difference in OS (53% vs 46% at 3 years; HR 0.91(0.73–1.14) p=0.4). Conclusion: This preliminary analysis of 1115 randomised patients indicates that the addition of GO to induction chemotherapy can reduce the relapse risk without adding significant extra toxicity and this has significantly improved the DFS in the GO arm. Longer follow up is required to determine the impact on survival.

Arsenic Trioxide with Ascorbic Acid and High-Dose Melphalan for Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3090-3090 ◽  
Author(s):  
Muzaffar H. Qazilbash ◽  
Rima M. Saliba ◽  
Marilyn S. Davis ◽  
Floralyn L. Mendoza ◽  
Chitra Hosing ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Ascorbic Acid ◽  
Arsenic Trioxide ◽  
Cell Transplantation ◽  
Hematopoietic Progenitor Cell ◽  
High Dose ◽  
Significant Difference ◽  
Preparative Regimen ◽  
The Impact

Abstract Backround: Arsenic trioxide (ATO) has been shown to be synergistic with melphalan both in vitro and in vivo. We conducted a phase I/II trial to determine the safety and efficacy of a combination of arsenic trioxide, melphalan and ascorbic acid (AA) as preparative regimen in patients undergoing high-dose therapy (HDT) and autologous hematopoietic progenitor cell transplantation for multiple myeloma (MM). We also assessed the impact ATO levels on melphalan pharmacokinetics (PK), engraftment and toxicity. Methods: Forty-eight patients with secretory myeloma (23 females, 25 males; median age: 54, range: 3570) were treated between 4/04 and 8/05. All patient received melphalan 100 mg/m2 IV on days -4 and -3 and AA 1000 mg/day IV on days -9 to -3. Patients were randomized to 3 arms; no ATO (arm 1), ATO 0.15 mg/kg IV on days -9 to -3 (arm 2) and ATO 0.25 mg/kg IV on days -9 to -3 (arm 3). Twelve patients had disease progression or relapse after a prior autograft. Median CD34 cells dose infused was 4.5 x 106/kg (range 2.3–10.9). Results: Patients in all 3 arms were evenly matched. With a median F/U of 14.0 months (range 6–25) post autograft, no dose-limiting toxicity or non-relapse mortality was seen. Toxicity was limited to grade I or II nausea, vomiting and diarrhea. Median ATO levels on day 0 in arms 1, 2 and 3 were 0.2, 26.3 and 46.2 ng/ml, respectively. Melphalan PK was not altered by ATO pretreatment. Median time to neutrophil engraftment (ANC >500/ dl) was 9 days. There were no engraftment failures or delays in the ATO arms. CR rate for the entire group was 23%, and total response rate (CR + PR) was 75%. 1-year Progression-free survival (PFS) and overall survival (OS) were 75% and 95%, respectively. There was no significant difference in CR, RR, PFS or OS between the 3 arms (p = 0.9, 0.9, 0.4 and 0.6, respectively). A prior autologous transplant (p = 0.02) and abnormal cytogenetics at transplant (p = 0.04) were associated with a significantly shorter remission. Conclusions: ATO + melphalan + ascorbic acid is a safe, effective and well tolerated preparative regimen for patients with multiple myeloma undergoing an autotransplant. A longer follow up is needed to assess the impact of ATO on progression-free and overall survival.

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