Gemtuzumab-Ozogamicin Containing Regimens As Induction Therapy Give the Highest Complete Remission Rate and the Longest Overall Survival Compared with Other Induction Regimens in Patients with Newly Diagnosed Acute Myeloid Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2513-2513
Author(s):  
Cristina Papayannidis ◽  
Anna Candoni ◽  
Michele Malagola ◽  
Giovanni Marconi ◽  
Marco Manfrini ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Complete Remission ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Strong Predictor ◽  
Gemtuzumab Ozogamicin ◽  
Newly Diagnosed ◽  
Group 2 ◽  
The Impact ◽  
Group 1

Abstract Introduction. Conventional induction treatment in young non APL-Acute Myeloid Leukemia (AML) patients is still represented by the association of an antracycline and Cytarabine, which offers a complete remission (CR) rate not inferior to 60%. The addition of Gemtuzumab Ozogamicin (GO) as a third or fourth drug, already demonstrated to improve clinical outcome, in terms of CR rates. Aims of the study. We retrospectively evaluated and compared the efficacy of different induction schedules, in terms of CR rates and Overall Survival (OS), administered to two groups of AML patients. Group 1 (n=139) was treated with a GO containing course (MyFLAI or MyAIE schedules); Group 2 (n=270) received a non-GO based regimen including or not Fludarabine (FLAI, FLAN, FLAG, 3+7 or DAE). Patients and Methods. From 1997 to 2014,409 newly diagnosed AML patients were treated in 3 Italian Institutions. Their median age was 53 (range 19-74) and 52 (range 17-75) years, respectively. According to karyotype (performed in 392/409 patients), FLT3 (available for 244/409 patients), and NPM1 mutational status (available for 157/409 patients), based on the NCCN-2013 risk stratification criteria, 35.2% of the patients were considered at High Risk (HR) (31.6% and 36.4% in the two groups, respectively) and 7.6% at low risk (LR) (7.8% and 7.0%, respectively). Results. The complete remission (CR) rate after induction was 81.4% and 70.4% for Group 1 and 2, respectively (p=0.01). Deaths during induction (DDI), occurring in the first 50 days from 1st line therapy, were 4/139 (2.9%) in Group 1 and 22/270 (8.1%) in Group 2 (p=0.003). Patients treated with GO showed a better OS than patients of Group 2 (Figure 1); the 5-years OS in the two groups was 54.01% and 34.9%, respectively, and different according to age (54.0% and 34.9% respectively (p=0.0003) in patients <60 years, 30.2% and 13.5% respectively (p=0.001) in patients ³60 years). The 5-years Event Free Survival (EFS) in the two groups was 45.6% and 30.8% respectively (p=0.0003) (Figure 2). Then, with a logistic univariate regression analysis.,we explored the impact of GO therapy in terms of CR rate. The use of GO was identified as a strong predictor of the achievement of a 1st CR (p=0.008). Moreover, a logistic multivariate regression analysis (risk and age) confirmed the role of the compound as a predictor of higher CR rate (p=0.013). We also performed a Cox Regression analysis, to investigate the impact of GO therapy, age and risk on OS: the use of GO was confirmed to be an independent predictor of better OS (p<0.0001) with a Hazard Ratio of 1.966 (p<0.0001). In a sub-analysis performed on HR patients, we observed a significantly better outcome in Group 1 than in Group 2 in terms of OS (p=0.0074, 5-year OS 47.7%; in group 2 OS 21.0% respectively, Figure 3) and EFS (p=0.001). However, there was no difference in terms of CR rate (p=ns). In particular, HR patients with adverse karyotype, may benefit from GO induction therapy in terms of OS (5-years OS 42.9% and 12.8% in Group 1 and 2, respectively, p=0.02); nevertheless FLT3 mutations negative impact canÕt be overcome by the drug administration (5-years OS 66.6% and 61.3% in Group 1 and 2, respectively). In SR AML, GO offered a better OS (p=0.036, 5-years OS 51.4% and 41.9% respectively). Comparing with Fisher's exact test the rate of increment in 5-years OS between Group1 and Group2 in HR and SR AML, we demonstrate that treatment with GO gave the higher benefit in HR AML (p=0.0005). Conclusions. These data showed that a four-drugs intensified induction therapy is a feasible approach in AML patients: adding GO at any induction regimen is an independent and strong predictor of better OS and higher CR rates. In our population, GO was not associated with a higher incidence of DDI. This approach, could be strongly recommended in SR and HR AML patients, due to karyotype abnormalities, in which showed an advantage in term of OS if compared with other standard regimens. On the contrary, we donÕt suggest the same schedule in FLT3 mutated patients, in which no benefits have been observed. Acknowledgments Work supported by ELN, AIL, AIRC, Progetto Regione-Universitˆ 2010-12 (L.Bolondi), FP7 NGS-PTL project. Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures Soverini: Novartis, Briston-Myers Squibb, ARIAD: Consultancy. Fanin:Novartis Farma: Speakers Bureau. Cavo:BMS: Honoraria; Millenium Pharmaceuticals: Honoraria; Jansenn: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Onyx: Honoraria; Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Martinelli:Pfizer: Consultancy; BMS: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; ROCHE: Consultancy; MSD: Consultancy; AMGEN: Consultancy; Ariad: Consultancy.

Outcome of Adult AML at First Relapse Following a Risk-Oriented Strategy: The Northern Italy Leukemia Group (NILG) Experience.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5380-5380
Author(s):  
Irene M. Cavattoni ◽  
Enrico Morello ◽  
Michael Mian ◽  
Elena Oldani ◽  
Tamara Intermesoli ◽  
...  
Keyword(s):  
Regression Analysis ◽  
High Risk ◽  
Salvage Therapy ◽  
Cox Regression Analysis ◽  
Prognostic Features ◽  
First Relapse ◽  
Group 2 ◽  
The Impact ◽  
Standard Risk ◽  
Group 1

Abstract INTRODUCTION We retrospectively analyzed the impact on post-relapse survival of selected prognostic factors and salvage therapy (finalized to perform an allo-SCT) in 145 patients (pts) with non-APL AML who had been initially treated with standard induction and risk-adapted consolidation. The aim was to identify factors associated with a better outcome at first relapse. METHODS All pts were at first recurrence following consolidation of CR1 with (i) high-dose Ara-C (HiDAC) multicycle therapy supported by blood stem cells (standard risk, as defined by mixed clinico-cytogenetic criteria) or (ii) allo-SCT in case of high-risk prognostic profile. Median pt age was 55 y (range 21–68). CR1 duration was ≤ 6 months in 49 pts (34%), ranging from 0.6 to 6 mo (median 3.7). 25/68 pts (37%) had an unfavourable cytogenetics (CG), and 8.2 % had MDS-related AML. 96 pts (66%) had received HiDAC and 21 (15%) an allo-SCT according to study design. RESULTS 105 pts (72%) received salvage chemotherapy, 10 pts (7%) underwent directly allo-SCT, while the remaining 30 (21%) received palliation and all of them died. Salvage therapy consisted again of HiDAC alone or in combination with fludarabine or anthracyclines. After reinduction, 52/105 pts (49.5%) achieved CR2 and 15 (14%) died of complications. Altogether, 42 pts (29%, group 1) received an allo-SCT following relapse, 27 (64%) in CR2, 5 beyond CR2 and 10 soon after relapse. Of 20 more pts (14%, group 2) in CR2 but without HLA identical donor, 13 could be given further intensive consolidation therapy. Both groups were comparable regarding adverse prognostic features such as age >55 y, WBC count>50,000/μL, unfavourable CG, presence of FLT-3 ITD, prior allo-SCT and 1st CR lasting ≤ 6 mo. At the end of treatment, 37/42 pts (88%) receiving SCT and all 20 pts (100%) given only chemotherapy were in CR2. Logistic regression analysis showed that intensive treatment without HiDAC at induction (p=0.04) as well as CR1 lasting <6 mo (p=0.01) negatively affected CR2 rate. Median duration of CR2 was 7.5 mo (range 1–49) in group 1 compared to 4 mo (range 1–15) in group 2. Day 100 non-relapse mortality in the 2 groups was 7% and 10%. After a median follow-up of 9.4 mo in group 1 (range 3–49) and 10 mo in group 2 (range 2–65), 2-y OS was 24% and 15.5%, respectively. Notably, 2-y OS in allo-SCT group ranged from 42% in pts ≤ 45 years to 14% in older ones. Moreover, survival was affected by risk category. In fact 2-y OS of 14/37 (38%) standard risk pts undergoing allo-SCT at salvage was 41% vs 17% in 28/108 (26%) comparable high risk pts. Cox regression analysis revealed achievement of CR2 being the only independent prognostic factor related to overall survival (p=0.0001). CONCLUSIONS AML patients receiving intensive chemotherapy including HiDAC at 1st relapse reached a high CR2 rate, regardless of type of prior risk-adapted consolidation. Further intensification with allo-SCT may offer substantial salvage rates to younger standard risk patients, thus adding value to the underlying concept of a risk-oriented first-line therapy.

Introduction of Combined Chemotherapies Plus Rituximab (R) Has Improved Outcome of Previously Untreated and Relapsed Follicular Lymphoma (FL) Patients (pts).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4703-4703
Author(s):  
Stefano Sacchi ◽  
Samantha Pozzi ◽  
Luigi Marcheselli ◽  
Alessia Bari ◽  
Stefano Luminari ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Cox Regression ◽  
Clinical Stage ◽  
Cox Regression Analysis ◽  
Prognostic Features ◽  
Significant Difference ◽  
The Difference ◽  
Group 2 ◽  
The Impact ◽  
Group 1

Abstract Some data suggest that there are been no improvement in survival of FL Pts in the last three decades of the 20th century. However that review ended in 1992, before the introduction of R treatment. Most recently reported data, show that evolving chemotherapies, including the incorporation of R has led to outcome improvement. Between 1994 and 2004, 344 Pts with FL were enrolled in different GISL Trials. For the purpose of this study we considered 270 Pts with similar characteristics enrolled in trials including or not R. The first group accounts for 176 naive Pts treated with Antracycline plus Fludarabine containing regimens (Cohort #1: 125 Pts) or plus R (Cohort #2: 51Pts). The second group accounts for 99 relapsed Pts treated with Antracycline plus Fludarabine containing regimens (Cohort #3: 40 Pts) or plus R (Cohort #4: 59 Pts). To evaluate the impact of the incorporation of R in front line and salvage therapies we assessed the patients OS, FFS, TTF, SAR in these different Cohorts of Pts. Descriptive analysis of prognostic features showed differences in the distribution among groups. To compensate for these variations we also performed Cox regression analysis. Previously Untreated patients. Regarding group #1 and #2 that enrolled Pts with clinical stage IIB, III and IV, FFS and OS according to treatment did not show any statistical differences. The univariate analysis of baseline clinical features showed an impact on OS and FFS for clinical stage, LDH level, involvement of more than 4 nodal sites and presence of extranodal involvement. The prevalence of this characteristics were higher in group #2 than group #1. Thus the FFS from group #2 vs. group #1 was adjusted for variation in prognostic features by Cox regression analysis, that shows a failure Hazard Radio reduction (HR) of 40 % in Pts who received R. Because of difference in follow up (FU) (49 months in Cohort #1 vs 21 months in Cohort #2), to evaluate differences in OS we utilized exact Log Rank test for unequal FU. So far, a trend exists for better OS in R treated patients, although the difference is not statistically significant. Relapsed Patients. Clinical characteristics were similar in the two Cohorts of pts. TTF was better in R treated Pts and the difference was statistically significant (66% vs. 53% at 3 yrs, p=0.023) The analysis of SAR demonstrated a better result for R Cohort with a statistically significant difference (88% vs. 68% at 3 yrs, p=0.022). OS according to treatment protocol, showed advantage for patients in R Cohort and the difference was statistically significant (92% vs. 70% at 5 yrs, p=0.004). Conclusion. In naïve patients our retrospective analysis showed a reduction of HR for FFS and a trend toward better OS in R treated Pts. In relapsed Pts all outcome parameters as OS, TTF and SAR had significant improvement in the Cohort treated with R. Although any conclusions between nonrandomized groups maybe subject to differences in observed and unobserved prognostic features, we believe that improvement have occurred in the management of FL Pts with the introduction of combined chemotherapy with R.

Autologous Peripheral Blood Stem-Cell (PBSC) Collection Is Not Impaired by Bortezomib-Thalidomide-Dexamethasone (VTD) Induction Therapy in Newly Diagnosed Multiple Myeloma (MM)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 317-317 ◽  
Author(s):  
Annamaria Brioli ◽  
Giulia Perrone ◽  
Silvestro Volpe ◽  
Silvana Pasini ◽  
Anna Mele ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Induction Therapy ◽  
Phase Iii ◽  
Study Endpoint ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Cd34 Cells ◽  
Group 2 ◽  
The Impact

Abstract Abstract 317 Introduction: The novel agents bortezomib, thalidomide and lenalidomide have been successfully incorporated into autologous stem-cell transplantation (ASCT) as up-front therapy for newly diagnosed MM. However, several reports have raised concerns about the impact of novel agent-based induction regimens on PBSC collection. Furthermore, the ability to successfully collect PBSCs following initial therapy with two of these newer drugs needs to be confirmed in large phase III clinical trials. Methods: The GIMEMA Italian Myeloma Network designed a phase III study to compare VTD with thalidomide-dexamethasone (TD) as induction therapy prior to double ASCT. Primary study endpoint was the rate of complete or near complete response to each of these two induction regimens, while their toxicity profile – including the impact on PBSC mobilization and collection - was a secondary study endpoint. To address this latter issue, we performed a post-hoc analysis to compare the effect of the triplet VTD induction regimen versus the doublet TD combination on CD34+ cell collection. After three 21-day cycles of VTD or TD induction therapy, patients received intermediate dose cyclophosphamide (CTX 4 g/m2) followed by G-CSF (10 mcg/Kg/die) to mobilize and collect PBSCs. The target threshold to safely perform double ASCT was 4 × 106 CD34+ cells/Kg. Results: Patients evaluable for PBSC collection were 435 out of the 474 who received induction therapy. Of these, 223 were initially randomized to VTD and 212 to TD induction therapy. The median number of collected CD34+ cells was 9.7 × 106/Kg in the VTD arm and 10.7 × 106/Kg in the TD arm (p= n.s.). The planned yield of 4 × 106 CD34+ cells/Kg was achieved with a single harvest in more than 90% of patients in both treatment groups (96% in VTD and 92% in TD, p= n.s.). A yield of CD34+ cells >10 × 106 /Kg was reported in 51% and 56% of patients treated with VTD and TD, respectively (p= n.s.). Only 5 patients (2%) in VTD group and 2 patients (1%) in the TD arm failed to collect more than 2 × 106 CD34+ cells/Kg (p= n.s.). The majority of patients (86% in VTD and 82% in TD, p=n.s.) received CTX as an in-patient procedure, the median time of hospitalization being 4 days. Less than 5% of patients developed grade 3–4 infectious complications (2% in the VTD group vs 3% in TD, p=n.s.) which required hospitalization in only 2 patients. Following ASCT, no significant difference was observed between the two treatment arms in terms of hematologic recovery and non hematological toxicity. Kaplan-Meier curves of TTP and PFS were almost superimposable for patients with a CD34+ yield >10 × 106/Kg and in the range between 4 and 10 × 106/Kg (group 1). These curves were very similar also for patients who collected between 2 and 4 × 106/Kg CD34+ cells or <2 × 106/Kg (group 2). These two groups had significantly different clinical outcomes. Indeed, the 40-month estimates of TTP and PFS were 75% for group 1 vs 40% for group 2 and 60% vs 25%, respectively. OS at 40 months for patients with >10 × 106/Kg CD34+ cells was in the 90% range, a value significantly better than what was seen in the remaining subgroups. In a multivariate Cox regression analysis, yields of CD34+ cells >10 × 106/Kg and in the range of 4 to 10 × 106/Kg were independently associated with prolonged PFS (p=0.001 and =0.027, respectively), while CD34+ cells >10 × 106/Kg predicted for extended OS (p=0.002). Absence of t(4;14) and/or del(17q), and ISS stage 1 or 2 were additional favorable prognostic factors for both PFS and OS, while randomization to VTD independently predicted for longer PFS. Conclusions: Results of the present analysis showed that both TD and VTD shared the advantage of no adverse impact on PBSC collection and the engraftment potential of collected PBSCs. The target for CD34+ cell collection (>4 × 106/Kg) was achieved with a single harvest in more than 90% of patients in both treated groups and a collection failure was reported in 1% to 2% of patients. These favorable results are due to early PBSC collection, which was performed after 3 cycles of TD and VTD, and use of CTX plus G-CSF which allows better stem cell collection and less likelihood of a collection failure. Of particular note, both VTD and TD were associated with a 50% to 59% probability to collect >10 × 106 CD34+ cells/Kg, a variable independently associated with extended PFS and OS. Disclosures: Off Label Use: bortezomib and thalidomide used as induction therapy for newly diagnosed multiple myeloma patients. Baccarani:Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Cavo:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Genzyme: Honoraria.

Gemtuzumab ozogamicin, mitoxantrone, and etoposide in newly diagnosed acute myeloid leukemia patients with persistent leukemia after a course of induction therapy

2010 ◽  
Vol 90 (6) ◽  
pp. 733-735 ◽  
Author(s):  
Michael Boyiadzis ◽  
Robert L. Redner ◽  
Anastasios Raptis ◽  
Jing-Zhou Hou ◽  
Mounzer Agha ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Gemtuzumab Ozogamicin ◽  
Newly Diagnosed ◽  
Acute Myeloid

scholarly journals Venetoclax Plus Decitabine for Young Adults with Newly Diagnosed ELN Adverse-Risk Acute Myeloid Leukemia: Interim Analysis of a Prospective, Multicenter, Single-Arm, Phase 2 Trial

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 35-35
Author(s):  
Suning Chen ◽  
Jundan Xie ◽  
Xiaofei Yang ◽  
Hongjie Shen ◽  
Jiannong Cen ◽  
...  
Keyword(s):  
Young Adults ◽  
Complete Remission ◽  
Induction Therapy ◽  
Interim Analysis ◽  
Myeloid Leukemia ◽  
Risk Category ◽  
Phase 2 ◽  
Newly Diagnosed ◽  
Rt Pcr

Abstract Background: The standard of induction therapy for fit patients(pts) with acute myeloid leukemia (AML) has not changed much since 1973, when the 7+3 regimen of cytarabine and anthracycline was born. This combination of agents produces complete remission (CR) in about 60-80% of younger adults and in 40-60% of older adults (60 years) depending on genetic risk group. However, compared with AML in favorable- and intermediate-risk categories, induction therapy for fit AML pts in adverse-risk category had significantly lower CR rates and dismal outcome. Recently, combination therapy with venetoclax and azacitidine or decitabine for the treatment of older pts with de novo AML unsuitable for intensive chemotherapy, has resulted in response rates of 60-70%. Currently, the role of venetoclax in combination with azacitidine or decitabine in young adults with newly diagnosed ELN adverse-risk AML remains unclear. This study aims to evaluate the safety and efficacy of venetoclax plus decitabine as induction therapy in young adults with newly diagnosed ELN adverse-risk AML. Methods: This is an interim analysis of an ongoing phase 2 clinical trial (NCT04752527) of a planned 42 untreated ELN adverse-risk AML pts 18-59. The fast next-generation sequencing (NGS) for the most commonly mutated genes in AML using Oncomine TM myeloid research assay on Ion S5 and Chef platform (Thermo Fisher) was completed within 72 hours, which could screen for the ELN adverse-risk features in AML pts together with multiplex RT-PCR and fluorescence in situ hybridization (FISH). In cycle 1, pts receive decitabine 20mg/m 2 on d1-5 and venetoclax escalated from 100mg to 200mg to 400mg until 28-day cycle is finished. For pts with high FLT3-ITD allelic ratio, sorafenib was optional administered at a dose of 400mg orally twice daily. Bone marrow assessments were performed on d28 before subsequent cycle. Pts who achieve composite complete remission (defined as complete remission [CR], CR with incomplete hematologic recovery [CRi], CR with partial hematological recovery [CRh], and morphologic leukemia free state [MLFS]) receive 1 or 2 cycles of consolidation with high dose of cytarabine followed by allogeneic hematopoietic stem cell transplantation. Non-responders or pts who achieve partial remission (PR) receive 1 additional cycle of combination of venetoclax plus decitabine. The primary objective is to determine the composite complete remission rate (CR+CRi+CRh+MLFS). The endpoint is to show that venetoclax plus decitabine is superior to historical control (HC) of cytarabine combined with idarubicin (12 mg/m 2) in young adults with newly diagnosed ELN adverse-risk AML. Results: From February 1, 2021 to July 31, 2021, a total of 104 newly-diagnosed AML pts underwent screening, and 30 pts were classified as ELN adverse-risk category by NGS (within 72 hours) together with multiplex RT-PCR and FISH. Totally, 19 pts with ELN adverse-risk were enrolled, comprising 14 males and 5 females. 2 (10%) pts had secondary AML (sAML). Median age was 38 years (range, 19-57 years). The baseline patient characteristics are summarized in Table 1. Outcome data were updated as of July 2021, for a median follow-up of 2.7 months. Among 14 evaluable pts, 4 (28.6%) achieved a CR, 5 (35.7%) achieved a CRh and 5 (35.7%) had a PR in cycle 1. Individual pts data of this study (n = 14) was compared to a HC, combining individual pts data of AML with adverse-risk from the SZ3202 registry (n = 42) and the pts treated with IA (IDA:12 mg/m 2) in the same period (n = 18). The venetoclax plus decitabine cohort demonstrated higher rates of CR than the HC cohort, with an observed CR/CRh rate of 64.3%, compared with 38.3% (Figure 1). The regimen was well tolerated, with 4- and 8-week mortality rates of 0% and 0%, respectively. The most frequent nonhematologic adverse events of any grade were neutropenic fever (n=6) and pneumonia (n=3). With a median follow-up of 2.7 months, the median remission duration and overall survival (OS) have not been reached. Tumor lysis syndrome occurred in one patient and resolved with medical management. Conclusions: Preliminary results indicate that venetoclax plus decitabine is an effective, lower-intensity regimen that is well tolerated for young adults with newly diagnosed ELN adverse-risk AML, producing high rates of CR, low rates of infections, and low rates of early death. Recruitment of young adults with newly diagnosed ELN adverse-risk AML pts for this trial is ongoing. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Early ICU Admission Of Newly Diagnosed Acute Myeloid Leukemia With No Organ Failure

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3896-3896
Author(s):  
Elodie Elkaim ◽  
Djamel Mokart ◽  
Norbert Vey ◽  
Aude Charbonnier ◽  
Evelyne D’Incan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Organ Failure ◽  
Myeloid Leukemia ◽  
Control Group ◽  
Newly Diagnosed ◽  
Initial Management ◽  
Failure Group ◽  
Group 2 ◽  
Acute Myeloid ◽  
Group 1

Abstract Background and Aim Acute myeloid leukemia (AML) at diagnosis can be an emergency. Induction mortality reaches 5 to 15% for patients under 60 years of age, and 15 to 30% for subjects over 60. 10 to 34% of patients will require a shift to intensive care unit (ICU) during induction and most of organ failures occur in the first few days. To optimize and improve the initial management of AML, we selected patients with high risk of induction mortality based on white blood cell count (WBC) ≥ 50 G/l and thrombocytopenia ≤ 50G/l at diagnosis. These patients were systematically admitted into ICU even without organ failure. Patients and Methods Our study was conducted in two hospitals, between 1st January 2000 and 31thDecember 2010. We included patients with newly diagnosed AML, aged 18 to 75 years, with both WBC ≥ 50G/l and platelets ≤ 50G/l, and no organ failure (group 1). 41 patients transferred to ICU based on conventional criteria (organ failure) during this period were not included in the study. Patients were directly admitted in ICU for diagnosis and treatment of AML(induction chemotherapy), and were jointly managed by both the intensivist and the hematologist. Patients were discharged from ICU without any non-hematological organ failure. Results were compared to a control group of similar patients admitted in another university hospital were high-risk patients are managed conventionnaly (ie no systematic ICU transfer in the absence of organ failure) (group 2). We defined organ failure by the requirement of mechanical ventilation for respiratory deficiency, renal remplacement therapy for renal failure, vaso-active drugs for hemodynamic and heart failure and when glasgow score was<7 for neurological failure. Results 130 patients were included, 50 patients in group 1 and 79 patients in group 2. Neither age at diagnosis and AML characteristics differed significantly between the two groups, nor complete remission rate(80% versus 70,5%) and relapse rate(55% versus 49%). 18 patients (36%) presented organ failure in group 1, 9 (11%) in group 2. The median time between induction and organ failure was 1 day(1-6) in group 1 and 3 days (1-24) in group 2. The main organ failure was acute respiratory failure, with 10 patients (56%) who needed invasive mechanical ventilation in group 1 and 8 (89%) in group 2. In group 1, renal replacement therapy and vaso-active drugs was used in 4 (22%) and 6 (33%) patients, respectively, versus 3 (33%) and 7 patients (78%), respectively, in group 2. The median length of stay in ICU was 5 days in patients without organ failure in group 1 (2-18), 11,5 days in patients with organ failure in group 1 (4-45), and 6 days in group 2 (1-37). Overall survival was not significantly different between the two groups (p 0.28). Six patients (12%) died in the group 1 at day 30 of induction chemotherapy, 14 patients (18%) in the group 2. Concerning patients who developed organ failure, the 30 days survival was significantly better in patients already monitored in ICU (group 1), 67 %, versus 22% in group 2 (p=0.02). The overall survival of patients of group 1 who had presented organ failure but alive after their ICU stay, was not statistically different compared to patients of group 1 without organ failure during induction (median 8 months versus 16 months, p 0,09). Conclusion There were more critical patients in the study group, but their 30 days survival was significantly better than in patients with organ failure in the control group. However, overall survival of the two groups was comparable. This study highlights a new strategy to improve initial management of AML. The rapid onset of complications (<3 days in more than 90%) allows considering short stays in ICU for patients who will not presented organ failure in the first 3 days of induction. The main limiting factor for this management is its applicability. These results have to be confirmed by a multicentric comparative study. Disclosures: No relevant conflicts of interest to declare.

Results of consecutive trials for children newly diagnosed with acute myeloid leukemia from the Australian and New Zealand Children's Cancer Study Group

Blood ◽  
2002 ◽  
Vol 100 (8) ◽  
pp. 2708-2716 ◽  
Author(s):  
Tracey A. O'Brien ◽  
Susan J. Russell ◽  
Marcus R. Vowels ◽  
Cecilia M. Oswald ◽  
Karin Tiedemann ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Allogeneic Bone Marrow Transplantation ◽  
Remission Induction ◽  
Allogeneic Bone ◽  
Newly Diagnosed ◽  
Group 2 ◽  
Acute Myeloid ◽  
Group 1

Despite improvements in the treatment of acute myeloid leukemia (AML), approximately 50% of children die of the disease. Clinical trials in adult patients with AML indicate that idarubicin may have superior efficacy when compared to daunorubicin in the remission-induction phases of chemotherapy. We conducted consecutive clinical trials in children with newly diagnosed AML in which daunorubicin (group 1, n = 102) or idarubicin (group 2, n = 160) was used during the remission-induction (RI) and the early consolidation phases of chemotherapy. Idarubicin was given at a dose of either 10 mg/m2 (group 2A, n = 106) or 12 mg/m2 (group 2B, n = 53). A high rate of RI was achieved for all groups (95% group 1, 90% group 2A, 94% group 2B). There were no significant differences in 5-year event-free survival (EFS) or in overall survival (OS) when the 3 groups were compared (group 1: EFS 50%, OS 56%; group 2A: EFS 50%, OS 60%; group 2B: EFS 34%, OS 50%). RI deaths resulting from treatment toxicity were low—2% for group 1 and 5% for group 2. More gastrointestinal, pulmonary, and renal toxicity but fewer infections were observed in patients receiving idarubicin (P < .001, P = .04,P = .03, respectively). Following RI chemotherapy, all patients received 3 to 4 more courses of identical chemotherapy and then underwent either autologous (n = 156) or an allogeneic bone marrow transplantation (BMT) (n = 35). OS was higher in allogeneic BMT patients than in autologous BMT patients (79% vs 63%;P = .23). We conclude that daunorubicin is as effective as idarubicin for remission-induction therapy for childhood AML and has reduced toxicity.

Pharmacokinetic and biological study of erlotinib in children as monotherapy for refractory brain tumors or with radiation for newly diagnosed brain stem gliomas

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10019-10019
Author(s):  
B. Geoerger ◽  
D. Hargrave ◽  
F. Thomas ◽  
F. Andreiuolo ◽  
P. Varlet ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Brain Stem ◽  
Biological Study ◽  
Pharmacokinetic Data ◽  
Brain Stem Glioma ◽  
Newly Diagnosed ◽  
Group 2 ◽  
The Impact ◽  
Brain Stem Gliomas ◽  
Group 1

10019 Background: This multicenter phase I study was designed to determine the recommended dose (RD) of erlotinib, a small-molecule EGFR TKI, in patients ≤ 21 years as monotherapy or in combination with radiation therapy (RT). Methods: Group 1 included patients with brain tumors refractory to or relapsing after conventional therapy; receiving erlotinib alone. Group 2 included newly diagnosed patients with brain stem gliomas, who received RT (54Gy) and erlotinib. Conventional 3+3 dose escalation was used for Group 1; a continual reassessment method for Group 2. Four dose levels were planned: 75, 100, 125 and 150 mg/m2/day. Results: A total of 51 patients were enrolled (30 in Group 1; 21 in Group 2); 50 received treatment. Median age was 10 and 6 years, respectively. The RD of erlotinib was 125 mg/m2/day as monotherapy or in combination with RT. 203 adverse events in 44 patients were possibly treatment-related; 188 were G1/2; 9 G3, 2 G4, and 4 G5. Dermatologic and neurologic symptoms were most common; intratumoral hemorrhage was noted in 4 patients. In Group 1, 8 patients (27.6%) had stable disease, 2 with 45% tumor regression. In Group 2, 3 patients (14%) had partial response and 8 (38%) were stabilized; median OS was 12 months. Pharmacokinetic data of 46 patients were analyzed; patients’ weight and erlotinib clearance (CL) were significantly correlated. Mean (± SD) apparent CL and volume of distribution for erlotinib were 143.7 mL/h/kg (± 66.3) and 3.5 L/kg (± 3.0), respectively, and were independent of dose level. Mean half-life for erlotinib was 20.4 hours. Biomarker analyses on archived tumor or biopsy tissue prior to study entry for newly diagnosed brain stem glioma found 18/37 tumors tested were EGFR IHC+; 16/37 and 23/36 were pAKT+ and pMAPK+, respectively. High EGFR expression was more common in supratentorial gliomas; PTEN loss was most common in brain stem glioma (15/19) and was not observed in ependymomas. Conclusions: Erlotinib 125 mg/m2/day has an acceptable tolerability profile in pediatric patients with brain tumors, and can be safely combined with RT. Further studies are required to define the efficacy of this treatment approach and to establish the impact of biomarkers on outcomes in pediatric glial tumors. No significant financial relationships to disclose.

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