Influence of Race and Nutritional Status on the Long Term Event Free Survival in Childhood Acute Lymphoblastic Leukemia (ALL): A 14-year Follow-up with a Reduced BFM-Based Treatment Protocol (GBTLI ALL-93)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 13-13
Author(s):  
Silvia Regina Brandalise ◽  
Maria Pombo-de-Oliveira ◽  
Vitoria Régia Pereira Pinheiro ◽  
Maria Jose Mastellaro ◽  
Waldir Veiga Pereira ◽  
...  
Keyword(s):  
High Risk ◽  
Complete Remission ◽  
Nutritional Status ◽  
Risk Group ◽  
Treatment Protocol ◽  
Low Risk ◽  
Event Free Survival ◽  
Free Survival ◽  
All Treatment

Abstract Background: Different event-free survival rates (EFS) of childhood ALL treatment regarding race, were published in the literature. However, a better consensus exists considering the bad prognosis of undernutrition. Taking into account the social economic reality of a low-income country such as Brazil, the systematic evaluation of these variables is of utmost importance, while inserted in a modern ALL treatment protocol. Objective: To compare, prospectively, the long-term EFS rates of previously untreated children with ALL, according to race and nutritional status at diagnosis. Methods: Patients were classified as Low Risk and High Risk according to NCI Criteria. Treatment schedule: Low Risk group: Remission induction therapy with DEXA 6mg/m2/d × 28 days, VCR 1.5 mg/m2/wk × 4, Daunomycin 25 mg/m2/wk × 4, L-ASP 10.000 U/m2/dose × 8, Ara-C 75mg/m2/dose × 8 and TIT therapy (day 0,28 and 42). Intensification therapy with MTX 2g/m2/wk × 4, 24 h continuous infusion with LCV rescue 15mg/m2/dose × 4, 6MP-50mg/m2 d × 21days and TIT therapy (x 4). Re-induction therapy: Dexa 6mg/m2 d × 21days, VCR 1.5mg/m2/wk × 4, L-ASP 10.000 U/m2/d × 4, 6-MP 50mg/m2/d × 14days, Ara-C 75 mg/m2/d × 4 and TIT therapy (x3). Central randomization was done for maintenance therapy duration (130 vs 103 wk). Maintenance: 6-MP 50mg/m2/d, MTX 25mg/m2/wk and TIT therapy every 8 weeks during all treatment. No CNS radiation was done. For High Risk patients, an induction intensification with intermediate dose of AraC (750 mg/m2/d × 6) was introduced, as well as, a rotational maintenance therapy with different pair of drugs were proposed (AraC 750mg/m2 × 4/Asp 6 000 U; Dexa/VCR/wk × 3 and 6-MP 75 mg/m2/d × 21 days/MTX 40 mg/m2/wk × 3). Prophylatic CNS radiation(18Gy) was done at wks 19–21 of therapy. Statistical analysis: EFS is defined as the time from diagnosis till any failure, relapse, death, or the development of a second malignancy. Continuous complete remission duration (CCR) is defined as EFS, contingent upon induction of a complete remission. EFS and CCR rates have been estimated by Kaplan and Meier’s method. Results: From October 1993 to September 1999, 867 patients were consecutively enrolled in the protocol GBTLI ALL-93. Fourteen pts were excluded (1.5%), due to wrong diagnosis or previous corticosteroid treatment. 853 pts were evaluated in this study. 447 pts were classified as Low Risk group (52%) and 406(48%) as High Risk. According to race, 226 pts (26.5%)were classified as black and 627 (73.5%) as white. Overall undernutrition was diagnosed among 7.0 % of the patients. In the black population 10.4% were undernourished, comparing with 5.7% in the white group. The 14yrs-EFS for all the study patients is 80% ± 2% and 55% ± 2.5% for the Low Risk and High Risk pts, respectively. Concerning race, the 14yrs-EFS is of 71.7% ± 4.5% for the black children, comparatively to 83% ± 2.1% for the white ones (p=0.01). According to the nutritional status, the EFS is of 70.2%± 1.7% and 53.0%± 6.8% for the nourished and undernourished children, respectively. Malnutrition had the worst desfavorable impact among the High Risk pts, with a 14yrs-EFS of 40.1% ± 8.7%, compared to those without malnutrition of 57.8% ± 2.7% (p = 0.05). Social and economical issues directly involved with treatment, were provided by means of free medical attention and drugs supplies. Treatment abandon was < 1%. Conclusion: The black race and undernutrition had significant adverse effect on the long-term EFS among the patients of this study.

The Importance of Pharmacogenomic Variations in the Treatment of Children with Acute Lymphoblastic Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4847-4847
Author(s):  
Chung-Yi Hu ◽  
Sheng-Kai Chang ◽  
Yung-Li Yang ◽  
Shu-Wha Lin ◽  
Rong-Jing Chiu ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Standard Error ◽  
Poor Prognosis ◽  
Lymphoblastic Leukemia ◽  
Treatment Protocol ◽  
Event Free Survival ◽  
Free Survival ◽  
Kaplan Meier

Abstract In adaptation of risk-directed combined chemotherapies, the initial remission rate in treatment of childhood acute lymphoblastic leukemia (ALL) has exceeded 95%. Hematological relapse during maintenance therapy, in which methotrexate (MTX) and thiopurine are applied, is the major cause of treatment failure. A retrospective study was performed to evaluate the role of pharmacogenomic effects in the treatment of children with ALL in the southern Chinese population. A total of 105 Taiwanese children with ALL, who received combined chemotherapy of different intensities based on risk-directed Taiwan Pediatric Oncology Group (TPOG)-ALL-93 protocols between Oct. 1993 to Dec. 2001, were recorded in long-term follow-up (6.5 to 13.7 years) for events (hematological relapse or death) occurrence (Figure 1). Seventeen genetic polymorphisms in 13 pharmacogenomic targets that implicated in MTX/thiopurine metabolism were analyzed by PCR-based restriction length polymorphism (RFLP) or sequence-specific oligonucleotide (SSO) probe hybridization. Pharmacogenomic polymorphisms were correlated with long-term event-free survival (EFS) of patients, with confounding effects adjusted by multivariate regression. Homozygosity of the 2677–3435 G-C allele in the multi-drug resistance gene (MDR-1, ABCB1) was highly associated with a significant reduction in long-term EFS in those patients treated with the standard risk protocol (TPOG-ALL-93-SR) (Figure 2). In the 36 patients receiving TPOG-ALL-93-SR treatment protocol, 6 out of 12 (50%) subjects carried homozygotic MDR1 2677–3435 G-C/G-C genotype suffered hematological relapse in 2 years, compared to 21 of 24 (88%) the non-homozygotic subjects remained event-free after 5 years (hazard ratio: 6.8, p=0.01). Among patients treated with the a high risk protocol (TPOG-ALL-93-HR) due to the presence of myeloid markers on the leukemic cells or manifested central nervous system leukemia, the thymidylate synthase (TYMS) enhancer 28-bp repeats 3R3R, and the glutathione-S-transferase M1 (GSTM1) null genotypes were associated with inferior clinical outcomes (p=0.029 and 0.058, respectively). Moreover, for patients with T-cell ALL that received the very high risk protocol (TPOG-ALL-97-VHR), the methionine synthase reductase (MTRR) 66AA genotype correlated with a superior prognosis compared to the AG or GG genotypes. These findings indicated independent pharmacogenomic determinants could be identified in subsets of Taiwanese children with ALL and correlated to the treatment outcome. In conclusion, we propose the pharmacogenomic determinants disclosed in the context of TPOG-ALL-93 protocols could be used to refine protocols for the treatment of pediatric ALL patients. Fig. 1 Kaplan-Meier plot depicting event-free survival of the ALL patients. The estimate of five-year event-free-survival (and the standard error) is illustrated for 105 patients received TPOG-ALL-93 protocols. Fig. 1. Kaplan-Meier plot depicting event-free survival of the ALL patients. The estimate of five-year event-free-survival (and the standard error) is illustrated for 105 patients received TPOG-ALL-93 protocols. Fig. 2 MDR1 2677–3435 G-C/G-C genotype identified a subset with poor prognosis in the 36 ALL patients received TPOG-ALL-93-SR treatment protocol. Fig. 2. MDR1 2677–3435 G-C/G-C genotype identified a subset with poor prognosis in the 36 ALL patients received TPOG-ALL-93-SR treatment protocol.

scholarly journals Impact of Thromboembolism on Overall and Event-Free Survival in Children with Acute Lymphoblastic

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 51-52
Author(s):  
Marie-Claude Pelland-Marcotte ◽  
Ketan Kulkarni ◽  
Uma Athale ◽  
Jason Pole ◽  
Leonardo R. Brandao ◽  
...  
Keyword(s):  
High Risk ◽  
Cancer Diagnosis ◽  
Risk Group ◽  
Low Risk ◽  
Rank Test ◽  
Event Free Survival ◽  
Free Survival ◽  
Log Rank Test ◽  
Life Threatening ◽  
Very High

Introduction: Thromboembolism (TE) is a well-known complication of cancer and its treatments. The impact of TE on survival outcomes remains unclear, especially in children. We assessed whether TE development was associated with overall survival (OS) and event-free survival (EFS) in children with acute lymphoblastic leukemia (ALL). Methods: We performed a population-based retrospective cohort study using the national registry Cancer in Young People Canada (CYP-C). Children 0-<15 years of age diagnosed with ALL (2000-2018) and treated at one of 12 Canadian pediatric centers outside of Ontario were included. OS was defined as the time between the date of cancer diagnosis and death and, EFS, as the time between the date of cancer diagnosis and the date of relapse, subsequent malignancy or death (whichever came first). Patients were categorized as to whether they experienced a radiologically-confirmed TE during treatment graded 3, 4 or 5 as per the Common Terminology Criteria for Adverse Events v.4 (i.e. requiring medical treatment, life-threatening or fatal). Only TEs that occurred before relapse or subsequent malignancy were considered. The Kaplan-Meier survival method estimated the 5-year OS and EFS of children with TE compared to those without TE. Univariate and multivariable Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of death or an event between groups, adjusted for age, sex, and leukemia risk group. A sub-analysis stratified the analysis by leukemia risk group. Results: The study included 2,208 children (median age: 4 years [interquartile range: 2-7 years], 54.9% male). Precursor B-cell ALL was the most common diagnosis (1,789, 89.1%). Patients were stratified as standard/low risk ALL in 58.0% of cases, and high/very high risk ALL in 42.0%. Of these, 121 (6.0%) developed a TE, at a median time of 100 days (interquartile range: 30-183 days) after cancer diagnosis. Eight patients (0.4%) had a life-threatening or fatal TE. Patients with TE were more likely to be aged 10 years or older, to present with T-cell ALL, and to have high risk leukemia. The 5-year OS (95% CI) of patients with and without TE was 80.2% (72.9-87.5%) and 93.7% (92.5-94.9%) respectively (log-rank test: p<0.001, Figure 1). The adjusted HR (95% CI) of death in children with TE was 2.09 (1.33-3.27, p=0.001). Similarly, as shown in Figure 2, the 5-year EFS (95% CI) of patients with and without TE was 68.7% (59.7-77.7%) and 88.6% (87.1-90.1%), respectively (log-rank test: p<0.001). The adjusted HR (95% CI) of an event was 2.01 (1.39-2.90, p<0.001). When stratified by leukemia risk group, no statistically significant difference was seen in standard/low risk ALL for both OS and EFS but TE was associated with a significantly lower OS and EFS in children with high/very high risk ALL (Table 1). In this group, the increased risk of death was attributable to both deaths following relapsed disease (HR [95% CI]: 2.37 [1.39-4.04]) and death not following relapse (HR [95% CI]: 2.93 [1.35-6.35]). Sensitivity analyses in which 1) patients with very high risk ALL were removed and 2) only grade 3 or 4 TE were considered showed similar results. Conclusions: Clinically relevant TE led to a statistically significant reduction in OS and EFS in children with high risk/very high risk leukemia. Further research is needed to assess whether TE prevention may improve anti-cancer outcomes. Disclosures Brandao: Boehringer Ingelheim: Other: Member of a paediatric expert working group.

Abstract TP387: Abcd 2 Score Predicts The Long-term Risk Of Stroke After Transient Ischemic Attack: Fukuoka Stroke Registry

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Yasuhiro Kumai ◽  
Takuya Kiyohara ◽  
Masahiro Kamouchi ◽  
Sohei Yoshimura ◽  
Hiroshi Sugimori ◽  
...  
Keyword(s):  
High Risk ◽  
Transient Ischemic Attack ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Rank Test ◽  
Moderate Risk ◽  
Stroke Registry ◽  
Ischemic Attack

Background and Purpose— ABCD 2 score has been developed to predict the early risk of stroke after transient ischemic attack (TIA). The aim of this study was to clarify whether ABCD 2 score predicts the occurrence of stroke in the long term after TIA. Methods— Fukuoka Stroke Registry (FSR) is a multicenter epidemiological study database on acute stoke. From June 2007 to June 2011, 496 (305 males, 70 ± 13 years of age) patients who had suffered from TIA and were hospitalized in the 7 stroke centers within 7 days after the onset of TIA were enrolled in this study. The patients were divided into three groups according to the risk: low-risk (ABCD 2 score 0-3; n=72), moderate-risk (4-5; n=229) and high-risk group (6-7; n=195). They were followed up prospectively for up to 3 years. Cox proportional hazard regression model was used to elucidate whether ABCD 2 score was a predictor for stroke after TIA after adjusting for confounding factors. Results— Among three groups, there were significant differences in age, hypertension, diabetes mellitus and the decrease in estimated glomerular filtration rate (P<0.01, significantly). During a mean follow-up of 1.3 years, Kaplan-Meier analysis demonstrated that the stroke rate in TIA patients was significantly lower in low-risk group than in moderate-risk or high-risk group (log rank test, p<0.001). The adjusted hazard ratios for stroke in patients with TIA increased with moderate-risk group (Hazard ratio [HR]: 3.47, 95% CI: 1.03-21.66, P<0.05) and high-risk group (HR: 4.46, 95% CI: 1.31-27.85, P<0.05), compared to low-risk group. Conclusions— The ABCD 2 score is able to predict the long-term risk of stroke after TIA.

P5730Do hypertensive women with coronary artery disease benefit from lowering systolic blood pressure under 130 mmHg? Long-term mortality in the INternational VErapamil SR-trandolapril STudy (INVEST)

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
R I Sava ◽  
Y Chen ◽  
Y K Taha ◽  
Y Gong ◽  
S M Smith ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Blood Pressure ◽  
Coronary Artery Disease ◽  
High Risk ◽  
Risk Group ◽  
Low Risk ◽  
High Risk Women ◽  
Artery Disease ◽  
Long Term Mortality

Abstract Background Hypertension (HTN) and coronary artery disease (CAD) are a prevalent combination in women, however limited data are available to guide blood pressure (BP) management. We hypothesize older women with HTN and CAD may not derive the same prognostic benefit from systolic BP (SBP) lowering <130 mmHg. Purpose To investigate the long-term mortality implications of different achieved SBP levels in hypertensive women with CAD. Methods Long-term, all-cause mortality data were analyzed for 9216 women, stratified by risk attributable to clinical severity of CAD (women with prior myocardial infarction or revascularization considered at high, all others at low risk) and by age (50 - <65 or ≥65 yo). The prognostic impact of achieving mean in-trial SBP <130 (referent group) was compared with 130 to <140 and ≥140 mmHg using Cox proportional hazards, adjusting for demographic and clinical characteristics. Results During 108,838 person-years of follow-up, 2945 deaths occurred. High risk women (n=3011) had increased long-term mortality in comparison to low risk women (n=6205) (adjusted HR 1.38, CI 1.28–1.5, p<0.001). Within risk groups, crude mortality percentages decreased according to BP values (table). As expected, high risk women were more likely to be ≥65 yo (68.68% vs. 50.51%, p<0.0001) or have SBP ≥140 mmHg (43.08% vs. 31.18%, p<0.0001). In adjusted analyses, an SBP ≥140 mmHg was associated with worse outcomes than SBP <130 mmHg in the entire cohort (HR 1.3, CI 1.2–1.5, p<0.0001) and when stratifying by risk (low risk group, HR = 1.47, CI 1.28–1.7, p<0.0001; high risk group, HR = 1.71, CI 1.01–1.35, p=0.03). In analyses stratified by age and risk, women ≥65 years and at high risk had decreased mortality in the 130 - <140 SBP category vs. <130 mmHg (HR 0.812, 95% CI 0.689–0.957, p=0.0133; figure). Women and deaths by risk and SBP group Group SBP category Women (n) Mortality (n) Mortality (%) High risk <130 773 338 44 130–<140 941 414 44 ≥140 1297 694 54 Low risk <130 2187 390 18 130–<140 2083 451 22 ≥140 1935 658 34 SBP = systolic blood pressure; n = number; % = percent per each group. Mortality adjusted HRs Conclusion In women ≥65 yo with hypertension and prior myocardial infarction and/or coronary revascularization enrolled in INVEST, a SBP between 130 to <140 mmHg was associated with lower all-cause, long-term mortality versus SBP <130 mmHg. Acknowledgement/Funding The main INVEST (International Verapamil [SR]/Trandolapril Study) was funded by grants from BASF Pharma, Ludwigshafen, Germany; Abbott Laboratories, A

scholarly journals Chemotherapy in 998 unselected childhood acute lymphoblastic leukemia patients. Results and conclusions of the multicenter trial ALL-BFM 86

Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 3122-3133 ◽  
Author(s):  
A Reiter ◽  
M Schrappe ◽  
WD Ludwig ◽  
W Hiddemann ◽  
S Sauter ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
Multicenter Trial ◽  
Low Risk ◽  
Event Free Survival ◽  
Free Survival ◽  
Risk Patients ◽  
To Receive

Abstract In trial ALL-BFM 86, the largest multicenter trial of the Berlin- Frankfurt-Munster (BFM) study group for childhood acute lymphoblastic leukemia (ALL), treatment response was used as an overriding stratification factor for the first time. In the previous trial ALL-BFM 83, the in vivo response to initial prednisone treatment was evaluated prospectively. A blast cell count of > or = 1,000/microL peripheral blood after a 7-day exposure to prednisone and one intrathecal dose of methotrexate (MTX) identified 10% of the patients as having a significantly worse prognosis. In trial ALL-BFM 86 patients with > or = 1,000/microL blood blasts on day 8 were included in an experimental branch EG. Patients with < 1,000/microL blood blasts on day 8 were stratified by their leukemic cell burden into two branches, Standard Risk Group (SRG) and Risk Group (RG). SRG patients received an eight- drug induction followed by consolidation protocol M (6-mercaptopurine, high-dose [HD] MTX 4 x 5 g/m2) and maintenance. RG patients were treated with an additional eight-drug reinduction element. For EG patients protocol M was replaced by protocol E (prednisone, HD-MTX, HD- cytarabine, ifosfamide, mitoxantrone). All patients received intrathecal MTX therapy; only those of branches RG and EG received cranial irradiation. In branch RG, patients were randomized to receive or not to receive late intensification (prednisone, vindesine, teniposide, ifosfamide, HD-cytarabine) in the 13th month. During the trial reinduction therapy was introduced in branch SRG, because in the follow-up of trial ALL-BFM 83 the randomized low-risk patients receiving reinduction did significantly better. Nine hundred ninety- eight evaluable patients were enrolled, 28.6% in SRG, 61.1% in RG, 10.3% in EG. At a median follow-up of 5.0 (range 3.4 to 6.9) years, the estimated 6-year event-free survival was 72% +/- 2% for the study population, 58% +/- 5% in branch SRG for the first 110 patients without reinduction therapy, 87% +/- 3% for the next 175 patients with reinduction therapy, 75% +/- 2% in branch RG, and 48% +/- 5% in branch EG. Late intensification did not significantly affect treatment outcome of RG patients; however, only 23% of the eligible patients were randomized. Prednisone poor response remained a negative prognostic parameter despite intensified therapy. The results confirmed the benefit of intensive reinduction therapy even for low-risk patients. The strategy of induction, consolidation, and intensive reinduction may offer roughly 75% of unselected childhood ALL patients the chance for an event-free survival.

Long-term outcomes of endovascular aneurysm repair for challenging aortic necks using the Talent endograft

Vascular ◽  
2011 ◽  
Vol 19 (3) ◽  
pp. 132-140 ◽  
Author(s):  
Jeffrey Jim ◽  
Brian G Rubin ◽  
Patrick J Geraghty ◽  
Luis A Sanchez
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Endovascular Aneurysm Repair ◽  
High Risk Group ◽  
Low Risk ◽  
Long Term Results ◽  
Long Term Outcomes ◽  
Aneurysm Repair ◽  
Related Mortality

The aim of the present paper is to evaluate the long-term outcomes of endovascular aneurysm repair (EVAR) for challenging aortic necks. Subgroup analyses were performed on 156 patients from the prospective multicenter Talent eLPS (enhanced Low Profile Stent Graft System) trial. Patients with high-risk aortic necks (length < 15 mm or diameter ≥28 mm) were compared with the remaining patients. Patients with high-risk ( n = 86) and low-risk necks ( n = 70) had similar age and gender distribution. Despite similar prevalences of co-morbidities, the high-risk group had higher Society for Vascular Surgery scores. The high-risk group also had larger maximum aneurysm diameters (56.6 versus 53.0 mm, P < 0.02). There were lower freedoms from major adverse events (MAEs) for the high-risk group at 30 days (84.9 versus 95.7%; P < 0.04) and 365 days (73.4 versus 89.2%; P = 0.02). Effectiveness endpoints at 12 m showed no significant differences. Freedom from all-cause mortality at 30 days (96.5 versus 100%) and aneurysm-related mortality at 365 days (96.0 versus 100%) were similar. At five years, there were no differences in endoleaks or change in aneurysm diameter. All migrations occurred in the high-risk group. The five-year freedom from aneurysm-related mortality for the high- and low-risk groups was 93.2 and 100%, respectively. In conclusion, despite a higher rate of MAEs within the first year and higher migration rates at five years, EVAR in aneurysms with challenging aortic necks can be treated with acceptable long-term results.

Application of Risk-Adapted Therapy for Acute Myeloid Leukemia to a Population. Effects of Stem Cell Transplantation on Outcome.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4449-4449
Author(s):  
Anders Wahlin ◽  
Mats L. Brune ◽  
Rolf Billstrom
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
Relapse Free Survival ◽  
Free Survival ◽  
First Remission

Abstract We introduced a risk-adapted treatment program for non-APL AML in four Swedish health regions. The aim was to optimise treatment results by the use of risk group stratification, mainly based on cytogenetic findings at diagnosis. All patients received induction therapy with idarubicin-cytarabine 3+7 and consolidation cycles containing high-dose cytarabine. Stem cell transplantation was done in CR1 in selected patients, sparing patients with low/intermediate risk of relapse the risks associated with transplantation. 279 patients, 77% of all AML patients 18–60 years (median 51 yrs), in the population were included in the program. Cytogenetics was performed in 98%. Excluding APL, 19 patients had low-risk. The intermediate-risk group consisted of 165 patients, 96 with a normal karyotype. 95 patients were allocated to the high-risk group. 6% died < 30 days after diagnosis. CR rate was 80%. 111 transplants, 78 allogeneic/URD and 33 autologous, were performed in CR1. 40% of all patients were alive after five years. Median overall survival time was 887 days in low-risk, 611 days in intermediate risk, 345 days in high-risk patients. Relapse-free survival times were also significantly (p<0.001) different between the three risk groups. 43% of responding patients were alive in first remission after four years. 4-year relapse-free survival was significantly better for both intermediate risk (67%) and high-risk (41%) with allogeneic/URD transplantation than with autologous transplant or chemotherapy alone. Relapse was observed more often among patients treated with chemotherapy alone (42%, p=0.03) or with autologous transplants (42%, p=0.09) than among patients receiving allogeneic/URD transplants in CR1, 22%. Our results do not support the use of autologous transplantation in AML in first remission.

Long-Term Outcome of Iron-Induced Cardiac Disease in Patients with Thalassemia Major Treated with Combined DFP/DFO or DFO Alone.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1764-1764
Author(s):  
Maria Eliana Lai ◽  
Stefania Vacquer ◽  
Alessia Pepe ◽  
Aurelio Maggio ◽  
Maria P. Carta ◽  
...  
Keyword(s):  
High Risk ◽  
Cardiac Disease ◽  
Risk Group ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
Low Risk ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction

Abstract We conducted a 4-yr prospective trial to evaluate the long-term effects of combined deferiprone (DFP)/deferoxamine (DFO) on reversal of cardiac complications in thalassemia major compared to those of DFO alone. Twenty-eight patients (pts) with cardiac disease requiring medication were stratified according to their risk for cardiac death. Fourteen pts were high risk, serum ferritin (SF) > 2500 ug/L on two-thirds of occasions since the onset of cardiac disease. Of those with a SF < 2500 ug/L (low risk), six had progressive decrements of left ventricular ejection fraction (LVEF). Nine high-risk pts and six low-risk pts were placed on DFP/DFO (DFP, 75 mg/kg/d divided t.i.d.; DFO, 40 – 50 mg/kg over 8 – 12 h at night 5 – 7 d/wk. The others infused DFO alone. If SF fell below 500 ug/L, DFO infusions were reduced to 2 d/wk. Cardiac follow-up (including blood work and ECG) was done at 4-m intervals. M-mode and two-dimensional echocardiograms were done at 4- to 6-m intervals. Cardiac T2* was not available at the beginning of the study. All but eight patients (3 death, 1 refusal, 2 claustrophobic, 2 pacemaker) subsequently had at least one T2* assessment. Routine lab tests were done at 1- to 6-m intervals. Blood counts were done at 7- to 10-d intervals for those taking DFP. Mean follow-up was approximately 40 m. Compliance with DFO was significantly better among low-risk pts in both treatment groups (DFP/DFO, 82% vs 61%; DFO alone, 83% vs 52%) as was that with DFP (94% vs 76%). At baseline, no statistically significant differences were observed between the SF levels, LVEFs or left ventricular shortening fractions (LVSFs) of pts on DFP/DFO or DFO alone in either risk group except for the LVEFs of the low-risk group (DFP/DFO, 56.5% +/− 5.5%; DFO alone, 65.4% +/− 5.0%; p = 0.032). In the high-risk group, four cardiac events (3 deaths, 1 worsening of CHF) occurred in the group getting DFO alone vs none in the DFP/DFO-treated group. The latter pts showed a decrease in SF and an increase in both LVEF and LVSF at the end of study (EOS). The three pts who died (at 17 to 35 m) had increased SFs. These pts were not rescued by IV DFO (98 +/− 12 mg/kg/d). The two DFO-treated pts who survived had marginally improved T2*s (1.5 to 3.0 ms and 7.6 to 8.8 ms) over the year prior to EOS. Only one of the seven evaluable pts on DFP/DFO had a T2* < 10 ms, the others averaging 19.4 +/− 6.7 ms. Among the low-risk pts, those on DFP/DFO showed a reduction in SF and an improvement in both LVEF and LVSF. Those on DFO alone had increased SF but essentially no change in LVEFs or LVSFs. Five pts on DFP/DFO had T2* evaluations. In two pts, T2* rose from 9.0 to 37 ms (38 m) and from 9.3 to 11.8 ms (17 m). The remaining three had T2* values > 20 ms at EOS. Similar results were seen in low-risk pts on DFO alone. These finding clearly support the notion that DFP/DFO has a beneficial effect upon the heart, even in well established disease. Moreover, our finding of low T2* values associated with low SF levels indicates the importance of tailoring treatment to each individual.

Ninety Percent Sustained Complete Response (CR) Rate Projected 4 Years after Onset of CR in Gene Expression Profiling (GEP)-Defined Low-Risk Multiple Myeloma (MM) Treated with Total Therapy 3 (TT3): Basis for GEP-Risk-Adapted TT4 and TT5

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 162-162 ◽  
Author(s):  
Bart Barlogie ◽  
Elias J. Anaissie ◽  
John D. Shaughnessy ◽  
Frits van Rhee ◽  
Mauricio Pineda-Roman ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Risk ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Complete Response ◽  
Low Risk ◽  
Event Free Survival ◽  
Free Survival ◽  
Response Onset ◽  
Dose Dense

Abstract We have previously reported on the remarkable activity of the TT3 program that incorporated both bortezomib (V) and thalidomide (T) into the up-front management of 303 patients. TT3 consisted of 2 cycles each of induction prior to and of dose-reduced consolidation therapy with VTD-PACE (cisplatin, doxorubicin, cyclophosphamide, etoposide) after melphalan 200mg/m2 (M200)-based tandem transplants, followed by maintenance therapy for 3 years with VTD and, in later stages, VRD (substituting T for lenalidomide, R). Characteristics included a median age of 59yr (range, 33–75yr), B2M &gt;=4mg/L in 37%, albumin &lt;3.5g/dL in 26%, ISS stages II and III in 33% and 21%, cytogenetic abnormalities (CA) in 33% and gene expression profiling (GEP)-defined high-risk MM in 15% of the 275 patients with such data. With a median follow-up of 39 months, 4-yr overall survival (OS) and event-free survival (EFS) estimates were 78% and 71%, respectively, including 84% and 77% among the 85% with GEP-defined low-risk MM contrasting with 43% and 33% in the remainder with high-risk MM (both p&lt;0.0001). Near-CR and CR, attained in 86% and 63%, were sustained at 4 years from response onset in 78% and 87%, which pertained to 83% and 90% with low-risk MM but to only 44% and 57% with high-risk MM (all p &lt;0.0001). These results were corroborated in a TT3 extension trial (TT3E) that enrolled 175 additional patients, comprising higher proportions of CA (42%) and GEP-defined high-risk MM (21%). Two-year estimates of OS and EFS are 85% and 85%, with 94% and 92% in low-risk patients versus 61% and 62% in high-risk MM (p=0.0001, p=0.0003); the 2-yr estimate of remaining in CR is 93% including 100% in low-risk and 77% in high-risk MM (p=0.01). Multivariate analysis of features linked to OS in TT3 included GEP-defined high-risk, CA, B2M and LDH elevation, collectively accounting for 41% of outcome variability by R2 statistics; the corresponding R2 values for EFS and n-CR duration were 38% and 39%. Compared to the predecessor trial, TT2, that evaluated the role of T in a randomized trial design in 668 patients, TT3 data were superior for OS (p=0.08), EFS (&lt;0.0001), n-CR duration (p&lt;0.0001) and CR duration (p=0.0002). In the low-risk subgroup, EFS (p=0.0001), n-CR duration (p&lt;0.0001) and CR duration (Figure 1a; p=0.0002) all were superior in TT3 versus TT2; whereas, in the high-risk MM group, outcomes remained poor also with TT3 despite superior EFS (Figure 1b; p=0.03). Based on these data, we have now started a GEP-risk-based algorithm of assigning separate therapies to good-risk (TT4) and poor-risk MM (TT5). As the TT3 results for low-risk are difficult to improve upon, TT4 randomizes patients between standard TT3 and TT3-LITE that employs only 1 cycle each of induction and consolidation (with anticipated further improvement in compliance) and 4-day-fractionated M50×4 to enable the addition of VTD and thus exploit synergistic drug interactions to occur. In order to sustain tolerable effective therapies for at least 3 years and prevent recurrence from previous drug-free or insufficiently effective phases in TT3, TT5 for high-risk MM employs less dose-intense and more dose-dense highly synergistic combination therapy, utilizing M10-VTD-PACE for induction, M80 (in 4 daily fractions of M20) plus VRD-PACE tandem transplants, separated by 2 cycles of M20 (in 4 daily fractions of M5) plus VTD-PACE, and followed by 2 years of monthly alternating R-VD and M-VD. Figure 1a: Superior CR duration with TT3 v TT2 in GEP-low-risk MM: Figure 1a:. Superior CR duration with TT3 v TT2 in GEP-low-risk MM: Figure 1b: Superior event-free survival with TT3 v TT2 in GEP-high-risk MM: Figure 1b:. Superior event-free survival with TT3 v TT2 in GEP-high-risk MM:

scholarly journals BEACOPP chemotherapy is a highly effective regimen in children and adolescents with high-risk Hodgkin lymphoma: a report from the Children's Oncology Group

Blood ◽  
2011 ◽  
Vol 117 (9) ◽  
pp. 2596-2603 ◽  
Author(s):  
Kara M. Kelly ◽  
Richard Sposto ◽  
Raymond Hutchinson ◽  
Vickie Massey ◽  
Kathleen McCarten ◽  
...  
Keyword(s):  
High Risk ◽  
Hodgkin Lymphoma ◽  
Treatment Strategies ◽  
Stage Iv ◽  
Disease Stage ◽  
Oncology Group ◽  
Event Free Survival ◽  
Free Survival ◽  
Field Radiation

AbstractDose-intensified treatment strategies for Hodgkin lymphoma (HL) have demonstrated improvements in cure but may increase risk for acute and long-term toxicities, particularly in children. The Children's Oncology Group assessed the feasibility of a dose-intensive regimen, BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) in children with high-risk HL (stage IIB or IIIB with bulk disease, stage IV). Rapidity of response was assessed after 4 cycles of BEACOPP. Rapid responders received consolidation therapy with guidelines to reduce the risk of sex-specific long-term toxicities of therapy. Females received 4 cycles of COPP/ABV (cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine) without involved field radiation therapy (IFRT). Males received 2 cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) with IFRT. Slow responders received 4 cycles of BEACOPP and IFRT. Ninety-nine patients were enrolled. Myelosuppression was frequent. Rapid response was achieved by 74% of patients. Five-year event-free-survival is 94%, IFRT with median follow-up of 6.3 years. There were no disease progressions on study therapy. Secondary leukemias occurred in 2 patients. Overall survival is 97%. Early intensification followed by less intense response-based therapy for rapidly responding patients is an effective strategy for achieving high event-free survival in children with high-risk HL. This trial is registered at http://www.clinicaltrials.gov as #NCT00004010.

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