Outcome of Pediatric Patients with Acute Myeloid Leukemia and -5/5q-Abnormalities Enrolled On Five Children's Oncology Group Acute Myeloid Leukemia Treatment Protocols

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1414-1414
Author(s):  
Donna L Johnston ◽  
Todd A. Alonzo ◽  
Robert B. Gerbing ◽  
Betsy A. Hirsch ◽  
Nyla A. Heerema ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Pediatric Patients ◽  
Oncology Group ◽  
Event Free Survival ◽  
Free Survival ◽  
Number Of Patients ◽  
Acute Myeloid

Abstract Abstract 1414 Introduction: Studies of acute myeloid leukemia (AML) in adults have documented that abnormalities of chromosome 5q (-5/5q-), primarily deletions, confer a poor prognosis. However, there are no large studies that specifically focus on -5/5q- in pediatric AML. Methods: To elucidate the disease correlates of this group, we retrospectively analyzed cytogenetic data from 5 studies of childhood AML: Children's Oncology Group (COG-AAML03P1), Children's Cancer Group (CCG-2961 and 2891) and Pediatric Oncology Group (POG-8821 and 9421). Data from all patients whose cytogenetic clones included -5/5q-, with the exception of those with acute promyelocytic leukemia (M3) or Down syndrome, were included. A total of 2035 patients from these 5 studies had cytogenetic data available for review. Results: Twenty-two (1.1%) of the 2035 patients had −5 or 5q-. The majority of these patients were male (63.6%). The median age was 12.9 years (range 0.3–20.7 years) with a significant number of patients in the 11–21 year age range (63.6%, p=0.032). The median white blood cell count was 17.4 ×103/μL (range 1.4–98 ×103/μL) and the median bone marrow blast percentage was 77% (range 15–99%). Patients with -5/5q- had a significantly higher median platelet count at diagnosis than those without this abnormality (88×103/μL versus 53×103/μL, p=0.015). Of the 22 patients with -5/5q-, their FAB classification showed that a significant number of patients had M0 morphology (28.6%, p<0.001) versus patients without -5/5q- (2.6%). The remaining patients had M1 morphology (23.8%), M2 (19%), M4 (9.5%), M5 (9.5%), M6 (4.8%) and M7 (4.8%) morphology. Eighteen of the 22 patients (81.8%) had a complete response (CR) to induction chemotherapy. The 5-year event free survival (EFS) from the time of diagnosis for these 22 patients was 27% (±19%) and the 5-year overall survival (OS) was 32% (±20%). The 5-year EFS and OS for the patients on these studies without -5/5q- were 41% (±2%) and 51% (±2%) respectively. The 5-year EFS and OS rates were not significantly different between the two groups (p=0.182 and 0.120 respectively). For the 18 patients who achieved a CR with induction chemotherapy, from time of CR the 5-year disease free survival (DFS) was 33% (±22%), the 5-year OS was 39% (±25%), the 5-year relapse risk (RR) was 61% (±23%) and the 5-year treatment related mortality (TRM) was 6% (±11%). For the 1674 patients without -5/5q- who obtained a CR after induction, from the time of CR the 5-year DFS was 47% (±2%), OS was 57% (±2%), RR was 44% (±3%) and TRM was 9% (±5%). None of these values were significantly different between the groups (p>0.1). Conclusions: In this, the largest retrospective study of pediatric patients with AML and -5/5q- to date, this cytogenetic subgroup was found to have a poor outcome. The median 5-year overall survival across studies was 32%, and the median 5-year event free survival was 27%. These findings support the use of more aggressive therapy for the treatment of children with -5/5q- AML, as has been previously supported based on data from adults with -5/5q- AML. This subset of patients may also benefit from treatment with innovative agents. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Favorable effect of priming with granulocyte colony-stimulating factor in remission induction of acute myeloid leukemia restricted to dose escalation of cytarabine

Blood ◽  
2012 ◽  
Vol 119 (23) ◽  
pp. 5367-5373 ◽  
Author(s):  
Thomas Pabst ◽  
Edo Vellenga ◽  
Wim van Putten ◽  
Harry C. Schouten ◽  
Carlos Graux ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Favorable Effect ◽  
Remission Induction ◽  
Event Free Survival ◽  
Entire Study ◽  
Free Survival ◽  
Acute Myeloid

Abstract The clinical value of chemotherapy sensitization of acute myeloid leukemia (AML) with G-CSF priming has remained controversial. Cytarabine is a key constituent of remission induction chemotherapy. The effect of G-CSF priming has not been investigated in relationship with variable dose levels of cytarabine. We randomized 917 AML patients to receive G-CSF (456 patients) or no G-CSF (461 patients) at the days of chemotherapy. In the initial part of the study, 406 patients were also randomized between 2 cytarabine regimens comparing conventional-dose (199 patients) versus escalated-dose (207 patients) cytarabine in cycles 1 and 2. We found that patients after induction chemotherapy plus G-CSF had similar overall survival (43% vs 40%, P = .88), event-free survival (37% vs 31%, P = .29), and relapse rates (34% vs 36%, P = .77) at 5 years as those not receiving G-CSF. However, patients treated with the escalated-dose cytarabine regimen benefited from G-CSF priming, with improved event-free survival (P = .01) and overall survival (P = .003), compared with patients without G-CSF undergoing escalated-dose cytarabine treatment. A significant survival advantage of sensitizing AML for chemotherapy with G-CSF was not apparent in the entire study group, but it was seen in patients treated with escalated-dose cytarabine during remission induction. The HOVON-42 study is registered under The Netherlands Trial Registry (www.trialregister.nl) as #NTR230.

A Prospective Randomized Comparison of Idarubicin and High-Dose Daunorubicin in the Induction Chemotherapy for Acute Myeloid Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2535-2535 ◽  
Author(s):  
Je-Hwan Lee ◽  
Hawk Kim ◽  
Young-Don Joo ◽  
Won Sik Lee ◽  
Sung Hwa Bae ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
High Dose ◽  
Event Free Survival ◽  
Consolidation Chemotherapy ◽  
Free Survival ◽  
Acute Myeloid

Abstract Introduction: We conducted a randomized trial comparing two different doses of daunorubicin as induction chemotherapy in young adults with acute myeloid leukemia (AML) and showed intensification of induction therapy using a high daily dose of daunorubicin (90 mg/m2/d x 3d) improved both complete remission (CR) rate and survival duration compared to standard daunorubicin dose (45 mg/m2/d x 3d) (Lee JH et al. Blood 2011;118:3832). As it is necessary to compare the effects of high-dose daunorubicin with that of other agents, especially idarubicin, we performed another randomized trial comparing two induction regimens in young adults with AML: idarubicin vs. high-dose daunorubicin (ClinicalTrials.gov #NCT01145846). Here, we present final results of the study. Methods: Between May 2010 and March 2014, a total of 316 patients (65 years or younger) with newly diagnosed AML except acute promyelocytic leukemia were registered in this study. Seventeen patients were removed from the study (change of diagnosis in 11, patient's refusal to be randomized in 3 and other in 3) and the remaining 299 patients were analyzed. After random assignments, 149 patients received idarubicin (AI, 12 mg/m2/d x 3d) and 150 patients received high-dose daunorubicin (AD, 90 mg/m2/d x 3d) in addition to cytarabine (200 mg/m2/d x 7d) for induction of CR. Patients with persistent leukemia received the second attempt of induction chemotherapy, consisting of idarubicin (AI, 12 mg/m2/d x 2d) or daunorubicin (AD, 45 mg/m2/d x 2d) plus cytarabine (5d). Patients who attained CR received 4 cycles of high-dose cytarabine (3 g/m2 x 6 doses) in patients with good- or intermediate-risk cytogenetics and 4 cycles of cytarabine (1 g/m2 x 6d) plus etoposide (150 mg/m2 x 3d) in those with high-risk cytogenetics. Hematopoietic cell transplantation (HCT) was performed according to attending physician's discretion after one or two cycles of consolidation chemotherapy in most transplant cases. Results: CR was induced in 232 (77.6%) of 299 patients. Reasons for induction failure were resistant disease in 50, hypoplastic death in 5, and indeterminate cause in 12. As postremission therapy, 3 patients received no further treatment, 71 received consolidation chemotherapy without HCT, 137 underwent allogeneic HCT, and 21 underwent autologous HCT. The CR rates were not significantly different between two arms: 80.5% (120 of 149, AI) vs. 74.7% (112 of 150, AD) (P=0.224). With a median follow-up of 1046 days, overall survival probabilities at 4 years were 51.1% in AI vs. 54.7% in AD (P=0.756). The probabilities at 4 years for relapse-free survival were 63.5% in AI vs. 74.2% in AD (P=0.181) and those for event-free survival were 44.8% in AI vs. 50.7% in AD (P=0.738). Toxicity profiles were similar between two arms. Interestingly, overall and event-free survivals of 44 patients with FLT-ITD mutants (27 in AI and 17 in AD) were significantly different according to the induction regimens (AI vs AD; overall survival, 30.8% vs. 61.9%, P=0.030; event-free survival, 31.4% vs. 61.9%, P=0.025). Conclusions: The results of this phase 3 trial, which compared idarubicin (12 mg/m2/d x 3d) with high-dose daunorubicin (90 mg/m2/d x 3d), did not show significant differences between two arms in the outcomes of patients in terms of CR rates and overall, relapse-free or event-free survivals. In subset analysis, high-dose daunorubicin seems to be more effective than idarubicin in patients with FLT-ITD mutants. Disclosures Kim: Celgene: Research Funding; Alexion Pharmaceuticals: Research Funding; Il-Yang: Research Funding; Novartis: Research Funding.

scholarly journals Myeloid sarcoma is associated with superior event-free survival and overall survival compared with acute myeloid leukemia

Cancer ◽  
2008 ◽  
Vol 113 (6) ◽  
pp. 1370-1378 ◽  
Author(s):  
Apostolia-Maria Tsimberidou ◽  
Hagop M. Kantarjian ◽  
Sijin Wen ◽  
Michael J. Keating ◽  
Susan O'Brien ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Myeloid Sarcoma ◽  
Event Free Survival ◽  
Free Survival ◽  
Acute Myeloid

scholarly journals High Expression of Myocyte Enhancer Factor 2C (MEF2C) Is Associated with Adverse Risk Features and Poor Outcome in Pediatric Acute Myeloid Leukemia: A Report from the Children's Oncology Group

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2570-2570
Author(s):  
George S. Laszlo ◽  
Todd A. Alonzo ◽  
Chelsea J. Gudgeon ◽  
Kimberly H. Harrington ◽  
Alex Kentsis ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Event Free Survival ◽  
Free Survival ◽  
Expression Levels ◽  
Acute Myeloid ◽  
Enhancer Factor

Abstract Background: Myocyte enhancer factor 2C (MEF2C) was initially identified as essential transcription factor for cardiac muscle development. However, subsequent studies have indicated that MEF2C plays a much broader biological role, including in the normal hematopoietic system. Recent studies have now identified MEF2C as cooperating oncogene in acute myeloid leukemia (AML) and suggested a contribution to the aggressive nature of at least some subtypes of AML. These findings raised the possibility that MEF2C could serve as marker of poor-risk disease and, therefore, have prognostic significance in AML. To test this hypothesis, we retrospectively quantified MEF2C expression in participants of the AAML0531 trial and correlated expression levels with disease characteristics and clinical outcome. Patients and Methods: AAML0531 (NCT00372593) was a multicenter phase 3 study that determined the addition of gemtuzumab ozogamicin to intensive chemotherapy among 1,022 eligible patients aged <30 yearswith newly diagnosed de novo non-APL AML, excluding those with bone marrow failure syndromes, juvenile myelomonocytic leukemia, or Down syndrome (if ≤3 years of age) between 2006 and 2010. Cryopreserved pretreatment ("diagnostic") specimens from patients enrolled on AAML0531 who consented to the biology studies and had bone marrow samples were available were included in this study. Total RNA from unsorted specimens was extracted, quantified, and subjected to quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) using TaqMan primers to determine expression of MEF2C and, for normalization, the housekeeping gene, β-glucuronidase (GUSB). Patient samples were run in duplicate, and the ΔΔCT method quantified as 2(-ΔΔCT) was used to determine the expression levels of MEF2C relative to GUSB. Results: In all 751 available patient specimens, MEF2C mRNA was detectable and varied >3,000-fold relative to GUSB (0.0091-29.1272 [median: 0.7978]). Patients with the highest relative MEF2C expression (4th quartile) less likely achieved a complete remission after one course of chemotherapy than the other patients (67% vs. 78%, P=0.005). They also had an inferior overall survival (P=0.014; at 5 years: 55±8% vs. 67±4%), inferior event-free survival (P<0.001; at 5 years: 38±7% vs. 54±4%), and higher relapse risk than patients within the lower 3 quartiles of MEF2C expression (P<0.001; at 5 years: 53±9% vs. 35±5%). Of note, exploratory multiple cutpoint analyses for overall and event-free survival indicated that the most statistically significant results were centered around the Q4 cutpoint region, supporting our approach of comparing patients with the highest quartile of relative MEF2C expression with those having lower relative MEF2C expression. Importantly, MEF2C expression was strongly associated with cytogenetic and molecular abnormalities. Specifically, patients with high MEF2C expression less likely had CBF translocations (inv(16): P=0.007, and t(8;21): P<0.001) or normal karyotype AML (P<0.001); conversely, they were more likely to have leukemia with monosomy 7 (P<0.001) and abnormalities involving 11q23 (P<0.001). Furthermore, patients with high MEF2C less likely had a FLT3/ITD (P =0.018) or a mutation in either NPM1 (P=0.010) or CEBPA (P =0.002). Consistently, patients with high MEF2C expression less likely had low-risk disease (16% vs. 46%, P<0.001) and more likely had standard-risk disease (68% vs. 42%, P <0.001) than those with lower MEF2C expression. Indeed, after adjustment for disease risk, age, FAB category, and treatment arm, high MEF2C expression was no longer statistically significantly associated with inferior overall survival (hazard ratio [HR]=0.99 [95% confidence interval: 0.72-1.36], P=0.929), inferior event-free survival (HR: 1.14 [0.86-1.49], P=0.365), or higher relapse risk (HR: 1.32 [0.91-1.92], P=0.137), suggesting that MEF2C cooperates with additional pathogenic abnormalities. Conclusion: High MEF2C expression identifies a subset of AML patients with adverse-risk disease features and poor outcome. These findings provide the rationale for therapeutic targeting of MEF2C transcriptional activation in AML. Disclosures Walter: AstraZeneca, Inc.: Consultancy; Covagen AG: Consultancy; Seattle Genetics, Inc.: Research Funding; Amgen, Inc.: Research Funding; Pfizer, Inc.: Consultancy; Amphivena Therapeutics, Inc.: Consultancy, Research Funding.

Response Rate, Event-Free Survival, and Overall Survival in Newly Diagnosed Acute Myeloid Leukemia: US Food and Drug Administration Trial-Level and Patient-Level Analyses

2021 ◽  
Author(s):  
Kelly J. Norsworthy ◽  
Xin Gao ◽  
Chia-Wen Ko ◽  
E. Dianne Pulte ◽  
Jiaxi Zhou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Strong Association ◽  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Free Survival ◽  
Patient Level ◽  
Acute Myeloid

PURPOSE To explore trial-level and patient-level associations between response (complete remission [CR] and CR + CR with incomplete hematologic [CRi] or platelet [CRp] recovery), event-free survival (EFS), and overall survival (OS) in newly diagnosed acute myeloid leukemia (AML) trials of intensive chemotherapy. METHODS We identified data from eight randomized, active-controlled trials of intensive chemotherapy submitted to the US Food and Drug Administration for treatment of newly diagnosed AML (N = 4,482). Associations between trial-level odds ratios (ORs) for CR and CR + CRi or CRp, and hazard ratios (HRs) for EFS and OS were analyzed using weighted linear regression models. We performed patient-level responder analyses to compare OS by response using pooled data from all studies. RESULTS In trial-level analyses, association between HR for OS and OR for CR was moderate (R2 = 0.49; 95% CI, 0.05 to 0.86), as was the association with OR for CR + CRi or CRp (R2 = 0.48; 95% CI, 0.05 to 0.99). For OS versus EFS, a strong association was observed (R2 = 0.87; 95% CI, 0.47 to 0.98) when EFS definitions were harmonized across trials using raw data. In the patient-level responder analyses, patients who achieved CR had better OS compared with CRi or CRp responders (0.73; 95% CI, 0.64 to 0.84) and nonresponders (HR, 0.33; 95% CI, 0.31 to 0.37). CONCLUSION On a trial level, there is a moderate association between OS and CR rate. A strong association between EFS and OS was observed. However, CIs were wide, and results became moderate using alternative definitions for EFS. Patient-level analyses showed CR responders have better OS compared with CRi or CRp responders and nonresponders. A therapy in newly diagnosed AML with benefit in EFS or substantial benefit in CR rate would be likely to have an OS effect.

Nonanthracycline Induction Chemotherapy (T-FLAG) for Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4356-4356
Author(s):  
Amit Mahipal ◽  
Emmanuel C. Besa ◽  
Anne Marie Valorie-Oberlie ◽  
Isaac Matthias ◽  
Adam Thode
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Progression Free Survival ◽  
Free Survival ◽  
Related Mortality ◽  
Acute Myeloid

Abstract Abstract 4356 Introduction: Prognosis of elderly patients (age>60 years) with acute myeloid leukemia (AML) is poor as compared to younger patients with a higher incidence of cardiac co-morbidities. With standard induction therapy, complete remission (CR) is achieved in 35% to 50% of elderly patients. However, the induction anthracycline containing chemotherapy related mortality is in this population has been reported to be approximately 30%. We attempted to decrease this by replacing the anthracycline with topotecan. Alternative therapies are needed that are less toxic but equally efficacious. In a phase I/II trial of the combination of topotecan, fludarabine, cytarabine and G-CSF (T-FLAG) in elderly AML and MDS, there was 50% CR and 15% treatment related deaths. In this study, we report patients >60 years of age treated with T-FLAG as an initial therapy for AML at our institute. Methods: We retrospectively reviewed the charts of elderly patients with AML treated with T-FLAG at our institution. Elderly patients were defined as more than 60 years of age. IRB approval was obtained for the study. All patients received topotecan 2mg/m2, fludarabine 30 mg/m2, and cytarabine 2000 mg/m2 all given over 30 min from day 1 to day 4 and G-CSF 400 μ g/m2/day from the day 5 to neutrophil counts recovery. International working group criteria was used to assess responses. All statistical analysis was done using SAS statistical software. Descriptive statistics were used. Progression free survival was defined from the time of diagnosis to progression, death or last follow up, whichever comes first. Overall survival and progression free survival was calculated using Kaplan and Meier method. Results: Thirteen elderly patients were treated with T-FLAG. The median age of diagnosis was 73 years (Range: 60–86 years). There were 10 male and 3 female patients. Ten (77%) patients had complex cytogenetics. Cardiomyopathy (EF <50%) or elevated liver function tests precluding anthracycline use was present in 54% of the patients. Response rate was 69% with 7 (54%) patients achieving CR and 2 (15%) patients achieving partial remission. Out of 10 patients with abnormal cytogenetics at baseline, 7 (70%) patients had cytogenetic CR. Eleven (85%) patients were alive at day 30. Median progression free survival and overall survival was 36 weeks and 54 weeks respectively. The median time for the recovery of neutrophil counts (>500/μ L) was 22 days (Range: 10–47 days). Conclusions: In this study of unfavorable risk group elderly patients, T-FLAG induction chemotherapy results in comparable remission rates with low induction chemotherapy related mortality. It may be an alternative regimen for elderly patients with complex cytogenetics or patients who cannot tolerate anthracyclines. More studies are needed to confirm these results. This however, may be useful to bridge patients to transplant or maintenance demethylating agents to improve survival. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Wilms Tumor 1 Mutations Are Independent Poor Prognostic Factors in Pediatric Acute Myeloid Leukemia

2021 ◽  
Vol 11 ◽  
Author(s):  
Yin Wang ◽  
Wen-Jun Weng ◽  
Dun-Hua Zhou ◽  
Jian-Pei Fang ◽  
Srishti Mishra ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Prognostic Factors ◽  
Myeloid Leukemia ◽  
Wilms Tumor ◽  
Event Free Survival ◽  
Free Survival ◽  
Wilms Tumor 1 ◽  
Pediatric Aml ◽  
Acute Myeloid

The prognostic impact of Wilms tumor 1 (WT1) mutations remains controversial for patients with acute myeloid leukemia (AML). Here, we aimed to determine the clinical implication of WT1 mutations in a large cohort of pediatric AML. The clinical data of 870 pediatric patients with AML were downloaded from the therapeutically applicable research to generate effective treatment (TARGET) dataset. We analyzed the prevalence, clinical profile, and prognosis of AML patients with WT1 mutations in this cohort. Our results showed that 6.7% of total patients harbored WT1 mutations. These WT1 mutations were closely associated with normal cytogenetics (P&lt;0.001), FMS-like tyrosine kinase 3/internal tandem duplication (FLT3/ITD) mutations (P&lt;0.001), and low complete remission induction rates (P&lt;0.01). Compared to the patients without WT1 mutations, patients with WT1 mutations had a worse 5-year event-free survival (21.7 ± 5.5% vs 48.9 ± 1.8%, P&lt;0.001) and a worse overall survival (41.4 ± 6.6% vs 64.3 ± 1.7%, P&lt;0.001). Moreover, patients with both WT1 and FLT3/ITD mutations had a dismal prognosis. Compared to chemotherapy alone, hematopoietic stem cell transplantation tended to improve the prognoses of WT1-mutated patients. Multivariate analysis demonstrated that WT1 mutations conferred an independent adverse impact on event-free survival (hazard ratio 1.910, P = 0.001) and overall survival (hazard ratio 1.709, P = 0.020). In conclusion, our findings have demonstrated that WT1 mutations are independent poor prognostic factors in pediatric AML.

scholarly journals Gemtuzumab Ozogamicin in Children and Adolescents With De Novo Acute Myeloid Leukemia Improves Event-Free Survival by Reducing Relapse Risk: Results From the Randomized Phase III Children's Oncology Group Trial AAML0531

2014 ◽  
Vol 32 (27) ◽  
pp. 3021-3032 ◽  
Author(s):  
Alan S. Gamis ◽  
Todd A. Alonzo ◽  
Soheil Meshinchi ◽  
Lillian Sung ◽  
Robert B. Gerbing ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Children And Adolescents ◽  
Myeloid Leukemia ◽  
Gemtuzumab Ozogamicin ◽  
Newly Diagnosed ◽  
Oncology Group ◽  
Event Free Survival ◽  
Free Survival ◽  
Group Trial ◽  
Acute Myeloid

Purpose To improve survival rates in children with acute myeloid leukemia (AML), we evaluated gemtuzumab-ozogamicin (GO), a humanized immunoconjugate targeted against CD33, as an alternative to further chemotherapy dose escalation. Our primary objective was to determine whether adding GO to standard chemotherapy improved event-free survival (EFS) and overall survival (OS) in children with newly diagnosed AML. Our secondary objectives examined outcomes by risk group and method of intensification. Patients and Methods Children, adolescents, and young adults ages 0 to 29 years with newly diagnosed AML were enrolled onto Children's Oncology Group trial AAML0531 and then were randomly assigned to either standard five-course chemotherapy alone or to the same chemotherapy with two doses of GO (3 mg/m2/dose) administered once in induction course 1 and once in intensification course 2 (two of three). Results There were 1,022 evaluable patients enrolled. GO significantly improved EFS (3 years: 53.1% v 46.9%; hazard ratio [HzR], 0.83; 95% CI, 0.70 to 0.99; P = .04) but not OS (3 years: 69.4% v 65.4%; HzR, 0.91; 95% CI, 0.74 to 1.13; P = .39). Although remission was not improved (88% v 85%; P = .15), posthoc analyses found relapse risk (RR) was significantly reduced among GO recipients overall (3 years: 32.8% v 41.3%; HzR, 0.73; 95% CI, 0.58 to 0.91; P = .006). Despite an increased postremission toxic mortality (3 years: 6.6% v 4.1%; HzR, 1.69; 95% CI, 0.93 to 3.08; P = .09), disease-free survival was better among GO recipients (3 years: 60.6% v 54.7%; HzR, 0.82; 95% CI, 0.67 to 1.02; P = .07). Conclusion GO added to chemotherapy improved EFS through a reduction in RR for children and adolescents with AML.

scholarly journals Wilms Tumor 1 Mutations are Independent Poor Prognostic Factors in Pediatric Acute Myeloid Leukemia

2020 ◽  
Author(s):  
Yin Wang ◽  
Wen-Jun Weng ◽  
Dun-Hua Zhou ◽  
Jian-Pei Fang ◽  
Li Chai ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Prognostic Factors ◽  
Myeloid Leukemia ◽  
Wilms Tumor ◽  
Event Free Survival ◽  
Free Survival ◽  
Wilms Tumor 1 ◽  
Pediatric Aml ◽  
Acute Myeloid

Abstract Background: The role of Wilms tumor 1 (WT1) mutations remains controversial for patients with acute myeloid leukemia (AML) with regard to the prognostic impact. Here, we aimed to determine the clinical implication of WT1 mutations in a large cohort of pediatric AML. Methods: The clinical data of 870 pediatric patients with AML were downloaded from the therapeutically applicable research to generate effective treatment (TARGET) dataset. We analyzed the prevalence, clinical profile and prognosis of WT1 mutations in these patients. Results: WT1 mutations were founded in 6.7% of total patients. WT1 mutations were closely associated with normal cytogenetics (P<0.001), FMS-like tyrosine kinase 3/internal tandem duplication (FLT3/ITD) mutations (P<0.001), and low complete remission induction rates (P<0.01). Compared to patients without WT1 mutations, patients with WT1 mutations had worse 5-year event-free survival (21.7±5.5% vs 48.9±1.8%, P<0.001) and overall survival (41.4±6.6% vs 64.3±1.7%, P<0.001). Moreover, patients with both WT1 and FLT3/ITD mutations had a dismal prognosis. Compared to chemotherapy alone, hematopoietic stem cell transplantation had a tendency to improve prognoses of WT1-mutated patients. In multivariate analysis, WT1 mutations conferred an independent adverse impact on event-free survival (hazard ratio 1.910, P = 0.001) and overall survival (hazard ratio 1.709, P = 0.020). Conclusion: Our findings demonstrate that WT1 mutations are independent poor prognostic factors in pediatric AML.

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