Improved Treatment Results in High-Risk Pediatric Acute Myeloid Leukemia Patients After Intensification With High-Dose Cytarabine and Mitoxantrone: Results of Study Acute Myeloid Leukemia–Berlin-Frankfurt-Münster 93

2001 ◽  
Vol 19 (10) ◽  
pp. 2705-2713 ◽  
Author(s):  
U. Creutzig ◽  
J. Ritter ◽  
M. Zimmermann ◽  
D. Reinhardt ◽  
J. Hermann ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Rank Test ◽  
High Dose ◽  
Free Survival ◽  
Log Rank Test ◽  
Risk Patients ◽  
Standard Risk ◽  
Acute Myeloid

PURPOSE: To improve outcome in high-risk patients, high-dose cytarabine and mitoxantrone (HAM) was introduced into the treatment of children with acute myelogenous leukemia (AML) in study AML-BFM 93. Patients were randomized to HAM as either the second or third therapy block, for the purpose of evaluation of efficacy and toxicity. PATIENTS AND METHODS: A total of 471 children with de novo AML were entered onto the trial; 161 were at standard risk and 310 were at high risk. After the randomized induction (daunorubicin v idarubicin), further therapy, with the exception of HAM, was identical in the two risk groups and also comparable to that in study Acute Myeloid Leukemia–Berlin-Frankfurt-Münster (AML-BFM) 87. RESULTS: Overall, 387 (82%) of 471 patients achieved complete remission, and 5-year survival, event-free survival (EFS), and disease-free survival rates were 60%, 51%, and 62%, respectively. Idarubicin induction resulted in a significantly better blast cell reduction in the bone marrow on day 15. Estimated survival and probability of EFS were superior in study AML-BFM 93 compared with study AML-BFM 87 (P = .01, log-rank test). This improvement, however, was restricted to the 310 high-risk patients (remission rate and probability of 5-year EFS in study AML-BFM 93 v study AML-BFM 87: 78% v 68%, P = .007; and 44% v 31%, P = .01, log-rank test). Probability of 5-year EFS among standard-risk patients in study AML-BFM 93 was similar to that in study AML-BFM 87 (65% v 63%, P = not significant). Whether HAM was placed as the second or third therapy block was of minor importance. However, patients who received the less intensive daunorubicin treatment during induction benefited from early HAM. CONCLUSION: Improved treatment results in children with high-risk AML in study AML-BFM 93 must be attributed mainly to the introduction of HAM.

scholarly journals Measurable Residual Disease at Induction Redefines Partial Response in Acute Myeloid Leukemia and Stratifies Outcomes in Patients at Standard Risk Without NPM1 Mutations

2018 ◽  
Vol 36 (15) ◽  
pp. 1486-1497 ◽  
Author(s):  
Sylvie D. Freeman ◽  
Robert K. Hills ◽  
Paul Virgo ◽  
Naeem Khan ◽  
Steve Couzens ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
High Risk Factors ◽  
Risk Patients ◽  
Standard Risk ◽  
Acute Myeloid

Purpose We investigated the effect on outcome of measurable or minimal residual disease (MRD) status after each induction course to evaluate the extent of its predictive value for acute myeloid leukemia (AML) risk groups, including NPM1 wild-type (wt) standard risk, when incorporated with other induction response criteria. Methods As part of the NCRI AML17 trial, 2,450 younger adult patients with AML or high-risk myelodysplastic syndrome had prospective multiparameter flow cytometric MRD (MFC-MRD) assessment. After course 1 (C1), responses were categorized as resistant disease (RD), partial remission (PR), and complete remission (CR) or complete remission with absolute neutrophil count < 1,000/µL or thrombocytopenia < 100,000/μL (CRi) by clinicians, with CR/CRi subdivided by MFC-MRD assay into MRD+ and MRD−. Patients without high-risk factors, including Flt3 internal tandem duplication wt/− NPM1-wt subgroup, received a second daunorubicin/cytosine arabinoside induction; course 2 (C2) was intensified for patients with high-risk factors. Results Survival outcomes from PR and MRD+ responses after C1 were similar, particularly for good- to standard-risk subgroups (5-year overall survival [OS], 27% RD v 46% PR v 51% MRD+ v 70% MRD−; P < .001). Adjusted analyses confirmed significant OS differences between C1 RD versus PR/MRD+ but not PR versus MRD+. CRi after C1 reduced OS in MRD+ (19% CRi v 45% CR; P = .001) patients, with a smaller effect after C2. The prognostic effect of C2 MFC-MRD status (relapse: hazard ratio [HR], 1.88 [95% CI, 1.50 to 2.36], P < .001; survival: HR, 1.77 [95% CI, 1.41 to 2.22], P < .001) remained significant when adjusting for C1 response. MRD positivity appeared less discriminatory in poor-risk patients by stratified analyses. For the NPM1-wt standard-risk subgroup, C2 MRD+ was significantly associated with poorer outcomes (OS, 33% v 63% MRD−, P = .003; relapse incidence, 89% when MRD+ ≥ 0.1%); transplant benefit was more apparent in patients with MRD+ (HR, 0.72; 95% CI, 0.31 to 1.69) than those with MRD− (HR, 1.68 [95% CI, 0.75 to 3.85]; P = .16 for interaction). Conclusion MFC-MRD can improve outcome stratification by extending the definition of partial response after first induction and may help predict NPM1-wt standard-risk patients with poor outcome who benefit from transplant in the first CR.

Optimization of Chemotherapy for Younger Patients With Acute Myeloid Leukemia: Results of the Medical Research Council AML15 Trial

2013 ◽  
Vol 31 (27) ◽  
pp. 3360-3368 ◽  
Author(s):  
Alan K. Burnett ◽  
Nigel H. Russell ◽  
Robert K. Hills ◽  
Ann E. Hunter ◽  
Lars Kjeldsen ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Remission Induction ◽  
High Dose ◽  
Younger Patients ◽  
High Risk Patients ◽  
High Dose Cytarabine ◽  
Risk Patients ◽  
Acute Myeloid

Purpose Treatment outcomes in younger patients with acute myeloid leukemia (AML) have improved, but optimization and new combinations are needed. We assess three combinations in induction and consolidation. Patients and Methods Younger untreated patients with AML (median age, 49 years; range, 0 to 73 years) were randomly allocated to two induction courses of daunorubicin and cytarabine (DA) with or without etoposide (ADE; n = 1983) or ADE versus fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-Ida; n = 1268), and to amsacrine, cytarabine, etoposide, and then mitoxantrone/cytarabine (MACE-MidAC) or high-dose cytarabine (n = 1,445) 3 g/m2 or 1.5 g/m2 (n = 657) in consolidation, and finally to a fifth course (cytarabine) or not (n = 227). Results Overall remission rates were similar for DA versus ADE (84% v 86%; P = .14) and ADE versus FLAG-Ida (86% v 85%; P = .7), with more course 1 remissions after FLAG-Ida (77%) reducing relapse (38% v 55%; P < .001) and improving relapse-free survival (45% v 34%; P = .01), overall and in subgroups, but with increased myelosuppression, reducing participation in the consolidation randomization. Overall outcomes were similar between MACE/MidAc and high-dose cytarabine (1.5/3.0 g/m2), but cytarabine required less supportive care. MACE/MidAc was superior for high-risk patients. A fifth course provided no benefit. The outcome for recipients of only two FLAG-Ida courses were not different from that with DA/ADE with consolidation. Conclusion FLAG-Ida is an effective remission induction treatment, with a high complete remission rate after course 1 and reduced relapse. Consolidation with MACE/MidAc is similar overall to high-dose cytarabine, but superior in high-risk patients. Cytarabine at 1.5 g/m2 is equivalent to a 3 g/m2 dose. A fifth course is unnecessary. In patients receiving FLAG-Ida (two courses) and cytarabine (two courses), 8-year survival was 63% for patients with intermediate-risk and 95% for those with favorable-risk disease.

The Addition of Bortezomib to Standard Chemotherapy for Pediatric Acute Myeloid Leukemia Has Increased Toxicity without Therapeutic Benefit: A Report from the Children's Oncology Group

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 899-899 ◽  
Author(s):  
Richard Aplenc ◽  
Soheil Meshinchi ◽  
Lillian Sung ◽  
Todd A. Alonzo ◽  
Jessica Pollard ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Oncology Group ◽  
Standard Chemotherapy ◽  
Free Survival ◽  
Risk Patients ◽  
De Novo Aml ◽  
Acute Myeloid

Abstract Introduction: Despite the very high intensity of current chemotherapy regimens for children with acute myeloid leukemia (AML), approximately 50% of patients will experience disease relapse. New therapeutic strategies to improve clinical outcomes have centered on improving the efficacy of standard chemotherapy with novel agents such as gemtuzumab and other agents designed to augment standard chemotherapy. Bortezomib, a proteasome inhibitor, is one such agent. The Children's Oncology Group (COG) Phase III clinical trial AAML1031 tested the hypothesis that the addition of bortezomib to standard chemotherapy would improve treatment outcomes in pediatric patients with newly diagnosed AML. Methods: The COG AAML1031 trial randomized patients younger than 30 years of age with de novo AML to either standard chemotherapy (Arm A) or standard chemotherapy with bortezomib (Arm B). Patients with high allelic ratio FLT3 ITD were offered enrollment on a standard chemotherapy plus sorafenib (Arm C, n = 102) and are excluded from this efficacy analysis. All patients received induction chemotherapy with cytarabine, daunorubicin, and etoposide (ADE). Risk stratification occurred at the end of ADE induction and was based on the presence of high risk cytogenetic/molecular markers and/or minimal residual disease (MRD) >0.1% determined by multidimensional flow cytometry. Low risk patients received three additional courses of chemotherapy consisting of a second course of ADE, a third course of cytarabine/etoposide and a fourth course of cytarabine/mitoxantrone. High risk patients received a second course of cytarabine/mitoxantrone, a third course of cytarabine/etoposide, and then allogeneic stem cell transplant (SCT) from the best available donor. Bortezomib 1.3 mg/m2 was given on days 1, 4 and 8 of each cycle with one dose de-escalation to 1 mg/m2 allowed for dose limiting toxicity. Results: A total of 1097 patients were randomized to either standard therapy (Arm A, n = 542) or standard chemotherapy with bortezomib (Arm B, n = 555). No statistically significant differences in sex, age, race, ethnicity, WHO classification, initial blast count, or initial CNS status was observed between arms. Remission induction rate did not differ between treatment arms 89% vs 91%, p = 0.457. MRD was negative in 75% of patients on both treatment arms at the end of Induction I and mean MRD measures did not differ significantly: 2.8% vs 1.9%, p = 0.247. For all patients, event free survival (EFS) and overall survival (OS) at 3 years were 44.4% ± 3.8% and 60.6% ± 4.4%. EFS was not significantly different between Arms A and B (44.0% ± 5.2% vs 44.6% ± 5.6%, p = 0.285) (Figure 1). Likewise, OS was similar between arms (59.0 ± 6.7 vs 62.2 ± 6.0, p = 0.732) (Figure 1). One year cumulative treatment related mortality (TRM) was 14.6 ± 9.3 and 10.8 ± 7.5, p = 0.49 for Arms A and B, respectively. No significant differences were seen in OS, disease-free survival, and TRM from the end of Induction I in low and high risk groups. Cox proportional hazards analysis demonstrated that initial WBC count at diagnosis was the only consistently identified risk factor for OS, DFS, and TRM. Targeted toxicity monitoring identified increased toxicity risks in Arm B for peripheral neuropathy (Induction I/II), dose reductions (all chemotherapy courses), and PICU admissions (Induction I/II) and Intensification I). Serial monitoring of cardiac ejection fraction/shortening fraction in all patients did not demonstrate a clinically meaningful difference in drop in ejection fraction/shortening fraction by treatment arm. No other consistent differences in targeted toxicity rates were identified. Conclusions: The addition of bortezomib to standard chemotherapy increased toxicity but did not improve EFS or OS in children with newly diagnosedAML Consequently, bortezomib should not be used in children with de novo AML in combination with standard chemotherapy. Future work will evaluate the role of intensifying Induction II therapy for patients with high risk AML, further refine risk stratification, and define a more optimal role for allogeneic donor SCT in pediatric AML. Figure 1 Figure 1. Disclosures Loken: Hematologics: Employment, Equity Ownership.

Less Toxicity by Optimizing Chemotherapy, but Not by Addition of Granulocyte Colony-Stimulating Factor in Children and Adolescents With Acute Myeloid Leukemia: Results of AML-BFM 98

2006 ◽  
Vol 24 (27) ◽  
pp. 4499-4506 ◽  
Author(s):  
Ursula Creutzig ◽  
Martin Zimmermann ◽  
Thomas Lehrnbecher ◽  
Norbert Graf ◽  
Johann Hermann ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Event Free Survival ◽  
Free Survival ◽  
Risk Patients ◽  
Standard Risk ◽  
Stimulating Factor ◽  
Acute Myeloid

Purpose To improve prognosis in children with acute myeloid leukemia (AML) by randomized comparisons of (1) two short consolidation cycles versus the Berlin-Frankfurt-Muenster (BFM) -type biphasic 6-week consolidation and (2) the prophylactic administration of granulocyte colony-stimulating factor (G-CSF) versus no G-CSF. Further, therapy for standard risk patients was intensified by addition of a second induction, HAM (high-dose cytarabine and mitoxantrone). Patients and Methods Four hundred seventy-three patients younger than 18 years with de novo AML were enrolled in trial AML-BFM 98. Patients received five courses of intensive chemotherapy, cranial irradiation, and 1-year maintenance therapy. Results Four hundred eighteen patients (88%) achieved remission. Compared with trial AML-BFM 93, early deaths decreased from 7.4 to 3.2% (P = .005), and 5-year overall survival increased from 58% to 62% (log-rank P = .03). Both types of consolidation therapy led to similar outcome (event-free survival, 51% v 50%), but in the two-cycle arm, treatment duration was shorter (median duration, 15 days), and treatment related mortality was lower (five v nine patients). G-CSF shortened neutropenia, but did not reduce the rate of severe infections. Intensification of induction therapy did not improve prognosis of standard-risk patients (event-free survival, 62% v 67%). Conclusion Overall results were improved by neither the administration of G-CSF nor by cycle therapy; however, the latter was easier to perform. Compared with study AML-BFM 93, therapy intensification with HAM in standard-risk patients did not result in improved prognosis. Future treatment designs have to balance intensification of treatment with higher toxicity, improve supportive care, and to consider alternative treatment strategies.

Prognostic Value of Cytogenetics in Patients with Acute Myeloid Leukemia Aged More Than 60 Years at Diagnosis: Identification of Subgroups Taking Benefit from Intensive Chemotherapy. Results from a Large Single Center Retrospective Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3503-3503
Author(s):  
Nicolas Blin ◽  
Pascaline Talmant ◽  
Richard Garand ◽  
Francoise Accard ◽  
Philippe Moreau ◽  
...  
Keyword(s):  
High Risk ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
Rank Test ◽  
Intensive Chemotherapy ◽  
Secondary Aml ◽  
Log Rank Test ◽  
Group 3 ◽  
Standard Risk ◽  
Acute Myeloid

Abstract Cytogenetic analysis performed at diagnosis is known as the most important independent prognostic factor in adult acute myeloid leukemia (AML) treated with intensive chemotherapy. This major predictor of outcome has been mostly identified in younger patients who are categorized into three risk groups: favorable, intermediate and adverse. However, the prognostic value of chromosome abnormalities in elderly patients with AML aged 60 years or older has been evaluated in much fewer studies and overall prognosis remains very poor in this population with a very small number of long-term survivors using current standard chemotherapy. To further investigate the prognostic relevance of cytogenetic abnormalities in older patients, we reviewed 376 patients with de novo or secondary AML aged 60 years or more and available cytogenetic data at diagnosis. APL were excluded and no patient received allogeneic bone marrow transplantation. Of 376 patients, 280 (74%) received induction chemotherapy based on association with cytarabine (ara-C) and anthracyclins according to GOELAMS SA2, SA3, SA4 and SA2002 prospective trials between 1988 and 2005. Patients who were not treated with induction regimen received best supportive care or low dose ara-C. Overall complete remission rate was 42%, induction failure 38% and induction death 20%. With a median follow-up of 11.5 years for survivors, overall survival (OS) was 4.5% at 5 years (95% confidence interval [CI], 3.8%–5.8%) and disease free survival (DFS) was 4.3% at 5 years (95% CI, 3.7%–5.9%). Using a proportional hazards model with normal cytogenetics as reference group, 3 prognostic subgroups were identified for OS: low-risk (t(8;21) and inv(16)) in 20 of 280 patients (7%), standard-risk (+8, +11, −13/del(13q), t(11q23), +22, all in no complex karyotypes) in 175 of 280 patients (63%) and high-risk (−5/del(5q), −7/del(7q), −17/del(17p), −20/del(20q), +21, rare aberrations, complex≥3 and complex≥5) in 85 of 280 patients (30%). In multivariate analyses using a Cox model with backward selection procedure, high-risk cytogenetics (p<0.001), age>65 years (p=0.01), multilineage dysplasia on marrow at diagnosis (p=0.008) and white blood cell count (WBC) (p=0.03) appeared as independent prognostic factors on OS and DFS. Secondary AML did not appear as prognostic factor in multivariate analysis (p=0.18) but in a log-rank test, AML secondary to hematologic malignancy did significantly worse than AML secondary to solid tumors in both OS and DFS (p=0.01 and p=0.04, respectively). OS distribution between treated and untreated patients was compared using a log-rank test with homogeneous subgroups based on cytogenetic risk group and age. Three-years OS was significantly better in patients <70 years with standard-risk cytogenetics (p=0.008 if age<65years and p=0.02 if age <70 years). For high-risk cytogenetic group, 3-years OS was improved only in patients <65 years with WBC<30G/L (p=0.03). These results confirm the independent prognostic value of pretreatment karyotype, age >65 years, WBC and associated multilineage dysplasia in elderly patients with AML. Overall prognosis remains very poor and intensive chemotherapy does not improve OS in patients aged >70 years and high-risk cytogenetic groups.

Attempts to Optimize Induction and Consolidation Treatment in Acute Myeloid Leukemia: Results of the MRC AML12 Trial

2010 ◽  
Vol 28 (4) ◽  
pp. 586-595 ◽  
Author(s):  
Alan K. Burnett ◽  
Robert K. Hills ◽  
Donald W. Milligan ◽  
Anthony H. Goldstone ◽  
Archibald G. Prentice ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Standard Dose ◽  
New Agents ◽  
Free Survival ◽  
All Trans Retinoic Acid ◽  
Risk Patients ◽  
To Receive ◽  
Acute Myeloid

Purpose To optimize treatment for younger patients with acute myeloid leukemia and high-risk myelodysplastic syndrome by comparing induction options and the number of consolidation courses and whether consolidation should include transplantation. Patients and Methods We randomly assigned 1,658 patients younger than age 60 years to receive mitoxantrone/cytarabine/etoposide versus cytarabine/daunorubicin/etoposide and subsequently 1,193 patients to daunorubicin/cytarabine/thioguanine (DAT) where the cytarabine dose was standard (S-DAT) versus double the standard dose (H-DAT). Patients in this randomization were randomly assigned to all-trans-retinoic acid or not. In consolidation, 992 patients were randomly assigned between a total of four courses versus five courses, and 324 patients who were not good risk were randomly assigned to transplantation or chemotherapy as the final course. Results Complete remission (CR) was achieved in 74% of patients and CR without recovery was achieved in an additional 11%; overall survival (OS) at 8 years was 38%. No differences in CR, relapse-free survival, relapse, or OS were seen between any of the induction randomizations except for a reduction in relapse risk (RR) on the mitoxantrone arm, which was offset by increased myelosuppression and deaths in CR. The addition of a fifth course did not improve OS and may be detrimental in older patients. Although transplantation reduced RR, it did not improve OS for the intermediate-risk group but was probably of benefit in high-risk patients. Conclusion Several chemotherapy schedules achieved similar remission rates and OS. Four courses of chemotherapy are adequate, but the addition of transplantation as a final course does not improve OS. New agents are required to enhance conventional chemotherapy.

scholarly journals Fludarabine, Melphalan, and Alemtuzumab Conditioning in Adults With Standard-Risk Advanced Acute Myeloid Leukemia and Myelodysplastic Syndrome

2005 ◽  
Vol 23 (24) ◽  
pp. 5728-5738 ◽  
Author(s):  
Koen van Besien ◽  
A. Artz ◽  
S. Smith ◽  
D. Cao ◽  
S. Rich ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
Performance Status ◽  
Progression Free Survival ◽  
Free Survival ◽  
High Risk Disease ◽  
Standard Risk ◽  
Acute Myeloid

Purpose This prospective phase II study evaluated toxicity, relapse rate, progression-free survival, and overall survival after allogeneic transplantation and conditioning with fludarabine, melphalan, and alemtuzumab in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Patients and Methods Fifty-two consecutive adults with AML and MDS were enrolled onto the study. Median age was 52 years (range, 17 to 71 years) and the majority of patients had high-risk disease, comorbidities, and/or modest reduction in performance status. Fifty-six percent of patients had unrelated or mismatched related donors. Results After a median follow-up of 18 months (range, 2 to 34 months), 1-year survival was 48% (95% CI, 34% to 61%), progression-free survival was 38% (95% CI, 25% to 52%), relapse rate was 27% (95% CI, 15% to 40%), and treatment-related mortality was 33% (95% CI, 20% to 46%). The cumulative probability of extensive chronic graft-versus-host disease (GVHD) was only 18% (95% CI, 8% to 40%); extensive chronic GVHD was only observed in recipients of unrelated donor transplants. Performance score and disease status were the major predictors of outcome. High-risk disease (ie, active AML or MDS with > 5% blasts) or even modest decreases in performance status were associated with poor outcomes. Patients with standard-risk leukemia (first or second complete remission) or MDS (< 5% blasts) had excellent outcomes despite unfavorable disease characteristics. Conclusion Fludarabine and melphalan combined with in vivo alemtuzumab is a promising transplantation regimen for patients with AML or MDS and low tumor burden. For patients with active disease, this regimen provides at best modest palliation. Despite a low incidence of GVHD, transplantation is still associated with considerable nonrelapse mortality in patients with decreased performance status.

Prospective Evaluation of Allogeneic Hematopoietic Stem-Cell Transplantation From Matched Related and Matched Unrelated Donors in Younger Adults With High-Risk Acute Myeloid Leukemia: German-Austrian Trial AMLHD98A

2010 ◽  
Vol 28 (30) ◽  
pp. 4642-4648 ◽  
Author(s):  
Richard F. Schlenk ◽  
Konstanze Döhner ◽  
Silja Mack ◽  
Michael Stoppel ◽  
Franz Király ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Younger Adults ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Risk Patients ◽  
Unrelated Donors ◽  
Acute Myeloid

Purpose To assess the impact of allogeneic hematopoietic stem-cell transplantation (HSCT) from matched related donors (MRDs) and matched unrelated donors (MUDs) on outcome in high-risk patients with acute myeloid leukemia (AML) within a prospective multicenter treatment trial. Patients and Methods Between 1998 and 2004, 844 patients (median age, 48 years; range, 16 to 62 years) with AML were enrolled onto protocol AMLHD98A that included a risk-adapted treatment strategy. High risk was defined by the presence of unfavorable cytogenetics and/or by no response to induction therapy. Results Two hundred sixty-seven (32%) of 844 patients were assigned to the high-risk group. Of these 267 patients, 51 patients (19%) achieved complete remission but had adverse cytogenetics, and 216 patients (81%) had no response to induction therapy. Allogeneic HSCT was actually performed in 162 (61%) of 267 high-risk patients, after a median time of 147 days after diagnosis. Graft sources were as follows: MRD (n = 62), MUD (n = 89), haploidentical donor (n = 10), and cord blood (n = 1). The 5-year overall survival rates were 6.5% (95% CI, 3.1% to 13.6%) for patients (n = 105) not proceeding to HSCT and 25.1% (95% CI, 19.1% to 33.0%; from date of transplantation) for patients (n = 162) receiving HSCT. Multivariable analysis including allogeneic HSCT as a time-dependent covariable revealed that allogeneic HSCT significantly improved outcome; there was no difference in outcome between allogeneic HSCT from MRD and MUD. Conclusion Allogeneic HSCT in younger adults with high-risk AML has a significant beneficial impact on outcome, and allogeneic HSCT from MRD and MUD yields similar results.

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