scholarly journals What Is the Best Choice and Dose of Anthracycline for Induction Chemotherapy in Acute Myeloid Leukemia?

2020 ◽  
Author(s):  
Sravanti Rangaraju ◽  
Omer Jamy
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Treatment Algorithm ◽  
Intensive Chemotherapy ◽  
Liposomal Daunorubicin ◽  
The Past ◽  
Treatment Plans ◽  
To Receive ◽  
Acute Myeloid

Treatment of patients with acute myeloid leukemia, medically fit to receive intensive chemotherapy, has been standardized over the past four decades and consists of an anthracycline administered along with continuous cytarabine. This combination is traditionally administered as seven days of cytarabine and three days of anthracycline, known as 7 + 3. Selecting the appropriate choice and dose of anthracycline for induction chemotherapy continues to be debated. Daunorubicin, used in three doses of either 45 mg/m2, 60 mg/m2 or 90 mg/m2, and idarubicin 12 mg/m2 are the two commonly used anthracyclines in clinical practice. Other anthracyclines including mitoxantrone and liposomal daunorubicin are incorporated in the treatment algorithm as well. Our understanding of the underlying biology of acute myeloid leukemia has significantly increased in the past decade, helping us formulate individualized treatment plans. In this chapter, we will discuss pivotal studies comparing the safety and efficacy of different types and doses of anthracyclines, focusing predominantly on daunorubicin and idarubicin. The details of the study design as well as subgroup analysis will be presented to determine which subset of patients with AML may benefit from a particular anthracycline.

Predicting Duration of Neutropenia After Successful Intensive Induction Chemotherapy for Acute Myeloid Leukemia or High-Grade Myelodysplastic Syndromes

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4336-4336 ◽  
Author(s):  
Sarah A. Buckley ◽  
Vladimir Vainstein ◽  
Janis L. Abkowitz ◽  
Elihu H. Estey ◽  
Roland B. Walter
Keyword(s):  
Mathematical Modeling ◽  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Intensive Chemotherapy ◽  
Blood Neutrophil ◽  
Neutrophil Recovery ◽  
Peripheral Blood Neutrophil ◽  
Acute Myeloid

Abstract Abstract 4336 Background: Chemotherapy-induced neutropenia (CIN) is a major cause of morbidity and mortality in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) due to the risk of overwhelming infection. Although the risk for infections increases with longer duration of neutropenia, no attempts have been undertaken to predict time of neutrophil recovery in AML/MDS patients following intensive chemotherapy. In unpublished work, we have successfully used mathematical modeling of peripheral blood blast kinetics following induction chemotherapy to accurately predict the likelihood of subsequent complete remission (CR). In this retrospective study, we investigated whether data derived from mathematical modeling of early peripheral blood neutrophil or blast dynamics could predict the duration of CIN in AML/MDS patients undergoing intensive induction chemotherapy. Patients and Methods: We retrospectively analyzed a cohort of 59 consecutive patients with newly diagnosed AML or MDS who achieved CR after induction chemotherapy after 1 course of chemotherapy with a 7 + 3-like regimen. Daily peripheral blood neutrophil and blast counts were recorded from the initiation of chemotherapy until the day of neutrophil recovery (defined as an absolute neutrophil count [ANC] ≥ 500 cells/μL). In patients with ≥ 3 measurable neutrophil or blast counts within the first five days of data collection, the rate of peripheral blood neutrophil and blast clearance was calculated by fitting an exponential decay curve to the data points starting on day 1 of chemotherapy. Results: The average age of the study cohort was 54 years (range 25 to 78). Seventy-six percent had primary AML. Cytogenetic risk was favorable in 32%, intermediate in 37%, and adverse in 27% of patients. The 23 patients with initial ANC < 500 cells/μL had a significantly longer duration of neutropenia than the 36 patients with initial ANC ≥ 500 cells/μL (mean: 29 versus 26 days, range: 21 – 39 versus 21 – 34, p=0.045). Neither age nor percentage of blasts in the bone marrow at diagnosis predicted neutropenia duration. In patients for whom decay rates could be modeled, there was no association between duration of neutropenia and decay rate for neutrophils (n = 36) or blasts (n = 20). There was also no association with the day that neutrophils first started to decline (defined as the first drop < 70% of the initial neutrophil count) or the first day of blast clearance from peripheral blood. Seven patients received granulocyte colony-stimulating factor (G-CSF; 1 prior to chemotherapy for antecedent myelodysplastic syndrome and 6 between days 15 and 43 for prolonged neutropenia and/or febrile neutropenia); the duration of neutropenia in this group did not differ significantly from that of the cohort as a whole. Conclusion: While kinetics of normal blood counts following initiation of intensive chemotherapy do not appear helpful to predict the duration of subsequent neutropenia, pre-treatment ANC levels provide limited information, with patients who are severely neutropenic prior to induction chemotherapy for AML having a longer average duration of CIN. This observation may provide some clinical guidance on the risk-adapted use of G-CSF in patients with AML/MDS undergoing induction chemotherapy. Disclosures: Vainstein: Neumedicines Inc: Employment.

Prospective genetically randomized comparison between intensive postinduction chemotherapy and bone marrow transplantation in adults with newly diagnosed acute myeloid leukemia.

1994 ◽  
Vol 12 (2) ◽  
pp. 262-267 ◽  
Author(s):  
E Archimbaud ◽  
X Thomas ◽  
M Michallet ◽  
J Jaubert ◽  
J Troncy ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Myeloid Leukemia ◽  
Allogeneic Bone ◽  
Intensive Chemotherapy ◽  
Sibling Donor ◽  
To Receive ◽  
Acute Myeloid

PURPOSE To compare intensive chemotherapy and HLA-identical allogeneic bone marrow transplantation (BMT) as postinduction therapy in young adults with acute myeloid leukemia (AML). PATIENTS AND METHODS Seventy-eight consecutive AML patients younger than 40 years of age were treated according to a prospective protocol in which every patient in complete remission (CR) with an HLA-identical sibling was scheduled to receive BMT rather than intensive chemotherapy consolidation. To minimize comparison biases, the availability or not of an HLA-identical sibling donor was considered to be the equivalent of genetic randomization to the BMT or chemotherapy arm, respectively. RESULTS Fifty-eight patients (74%) achieved a CR. A donor was found for 27 patients (BMT arm), and 20 of these patients were actually transplanted in first CR. The 31 patients without a donor were allocated to the chemotherapy arm. Patients in the two arms had similar disease characteristics at diagnosis and previous responses to induction therapy. The cumulative risk of relapse was 43% +/- 24% in the BMT arm and 67% +/- 19% in the chemotherapy arm (P = .01). The 7-year leukemia-free survival (LFS) rate was 41% +/- 20% in the BMT arm and 27% +/- 16% in the chemotherapy arm, a difference that is not statistically significant between the two arms. The overall survival rates were 41% +/- 20% and 46% +/- 19%, respectively. CONCLUSION In this study, the availability of an HLA-identical sibling donor was not associated with a better survival rate because of both the impossibility of some patients with a donor to receive BMT and the more efficient salvage treatment of patients who relapsed after intensive consolidation chemotherapy than of patients who relapsed after BMT.

Phase III Randomized Multicenter Study of a Humanized Anti-CD33 Monoclonal Antibody, Lintuzumab, in Combination With Chemotherapy, Versus Chemotherapy Alone in Patients With Refractory or First-Relapsed Acute Myeloid Leukemia

2005 ◽  
Vol 23 (18) ◽  
pp. 4110-4116 ◽  
Author(s):  
Eric J. Feldman ◽  
Joseph Brandwein ◽  
Richard Stone ◽  
Matt Kalaycio ◽  
Joseph Moore ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Phase Iii ◽  
Platelet Recovery ◽  
First Response ◽  
Refractory Acute Myeloid Leukemia ◽  
To Receive ◽  
Acute Myeloid

Purpose Lintuzumab (HuM195) is an unconjugated humanized murine monoclonal antibody directed against the cell surface myelomonocytic differentiation antigen CD33. In this study, the efficacy of lintuzumab in combination with induction chemotherapy was compared with chemotherapy alone in adults with first relapsed or primary refractory acute myeloid leukemia (AML). Patients and Methods Patients with relapsed or primary resistant AML (duration of first response, zero to 12 months) were randomly assigned to receive either mitoxantrone 8 mg/m2, etoposide 80 mg/m2, and cytarabine 1 g/m2 daily for 6 days (MEC) in combination with lintuzumab 12 mg/m2, or MEC alone. Overall response, defined as the rate of complete remission (CR) and CR with incomplete platelet recovery (CRp), was the primary end point of the study, with additional analyses of survival time and toxicity. Results A total of 191 patients were randomly assigned from November 1999 to April 2001. The percent CR plus CRp with MEC plus lintuzumab was 36% v 28% in patients treated with MEC alone (P = .28). The overall median survival was 156 days and was not different in the two arms of the study. Apart from mild antibody infusion–related toxicities (fever, chills, and hypotension), no differences in chemotherapy-related adverse effects, including hepatic and cardiac dysfunction, were observed with the addition of lintuzumab to induction chemotherapy. Conclusion The addition of lintuzumab to salvage induction chemotherapy was safe, but did not result in a statistically significant improvement in response rate or survival in patients with refractory/relapsed AML.

Effect of induction intensity on survival in patients with acute myeloid leukemia.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19004-e19004
Author(s):  
Kieran Sahasrabudhe ◽  
Melanie Rebechi ◽  
Ying Huang ◽  
Gregory Behbehani ◽  
Bhavana Bhatnagar ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Rank Test ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Kaplan Meier ◽  
To Receive ◽  
Acute Myeloid

e19004 Background: Acute Myeloid Leukemia (AML) has traditionally been treated frontline with intensive induction chemotherapy in patients fit enough for this treatment. The FDA has approved several oral targeted therapies for AML in recent years. The survival impact of these agents vs induction chemotherapy is unknown. Methods: In this single-center, retrospective study, patients diagnosed with AML from 2015-2020 were included if they received treatment with either high intensity chemotherapy (HiC) or lower intensity targeted therapy (LITT). HiC was defined as a regimen containing cytarabine + anthracycline given on a “7+3” based schedule. Patients treated with liposomal cytarabine-daunorubicin were excluded. LITT was defined as venetoclax, gilteritinib, enasidenib, or ivosidenib alone or in combination with a hypomethylating agent. Patients fell into four groups: HiC only, LITT only, HiC followed by LITT, and LITT followed by HiC with assignment censored at transplant. Overall survival (OS) was estimated using Kaplan-Meier method and patients receiving any HiC vs LITT only were compared using log-rank test. Results: A total of 332 patients were included: 177 received HiC only, 116 LITT only, 32 HiC before LITT, and 7 LITT before HiC. Baseline characteristics and OS data are outlined in the table. The any HiC group had a lower median age and more patients with WBC >10 K/µL at diagnosis, as well as more patients receiving allogeneic hematopoietic cell transplant (HCT). OS was superior in the any HiC group vs LITT only group. Receipt of any HiC remained predictive of OS after adjusting for age (HR 0.65, 95% CI 0.44-0.96, p = 0.03); however, was no longer predictive of OS after adjusting for age and receipt of HCT. Conclusions: While HiC was associated with superior OS compared to LITT only treatment in univariable analysis, the survival benefit was no longer apparent after adjusting for age and receipt of HCT. The results suggest that intensity of AML treatment is less impactful on prognosis than ability to receive HCT. Differences in age were likely confounded by clinical trial eligibility and prescribing information specifically affecting patients receiving LITT. In the era of LITT, prospective randomized studies of intensity of AML therapy, particularly in non-favorable risk disease, are imperative to striking a balance between toxicity and cure for patients of all ages.[Table: see text]

Phase II Studies of Different Schedules and Doses of the Farnesyl Transferase Inhibitor Tipifarnib (R115777, Zarnestra, NSC-702818) for Patients of Age 70 or Older with Previously Untreated Acute Myeloid Leukemia (AML): A North American Intergroup Study (S0432).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 440-440 ◽  
Author(s):  
Harry P. Erba ◽  
Kenneth J. Kopecky ◽  
Mark H. Kirschbaum ◽  
Martin S. Tallman ◽  
Richard A. Larson ◽  
...  
Keyword(s):  
Older Adults ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Farnesyl Transferase ◽  
Farnesyl Transferase Inhibitor ◽  
To Receive ◽  
Acute Myeloid

Abstract The prognosis of older adults with acute myeloid leukemia (AML) has not improved over the last three decades, despite the improvement in the outcome of younger adults during this same time due to the use of hematopoietic stem cell transplantation and intensive cytarabine consolidation. Older adults can not tolerate intensive therapy due to poor performance status, impaired organ function, and comorbid illnesses. Tipifarnib is an oral farnesyl transferase inhibitor with activity in the treatment of myelodysplastic syndrome (MDS) and high-risk AML patients. The primary objective of study S0432 was to test whether any of four different regimens of tipifarnib is sufficiently effective and tolerable therapy for previously untreated AML in patients of age 70 or over to warrant phase III study. Patients could not be considered candidates for, or must have declined, conventional induction chemotherapy. Patients had to have adequate renal and hepatic function, and the white blood cell (WBC) count had to be less than 30,000/cmm at the time of registration. Eligible patients could have a history of MDS, but could not have received AML induction chemotherapy or stem cell transplantation. Patients were randomized to receive either 600 mg or 300 mg of tipifarnib twice daily for either 21 consecutive days or 7 days every other week. Cycles were repeated every 28 days until disease progression or unacceptable toxicity. Patients achieving complete remission (CR) or CR with incomplete hematologic recovery (CRi) were to receive three additional cycles and then discontinue therapy. Patients achieving partial remission (PR) or with stable disease could continue treatment until progression of AML. If none of the first 15 patients on an arm achieved CR, CRi or PR, then accrual to that arm would be closed. However, all 4 treatment arms continued to full accrual. Three hundred forty-eight patients were registered between September 15, 2004 and February 15, 2006. Eighteen patients were excluded from analysis due to diagnosis other than AML, WBC above 30,000/cmm, no protocol therapy, and incorrect regimen administered. The median age in each arm was 78 years. The following are the treatment regimens: arm 1, 600 mg twice daily for 21 days; arm 2, 600 mg twice daily for 7 days every other week; arm 3, 300 mg twice daily for 21 days; arm 4, 300 mg twice daily for 7 days every other week. Responses were seen in each of the treatment arms with acceptable toxicities. The most common grade 3 or 4 adverse events were fatigue, febrile neutropenia, and infection in each treatment arm. However, the CR + CRi rates were less than 20% in each treatment arm, suggesting that further investigation of any of these regimens of tipifarnib is not warranted. Identification of predictors of response to tipifarnib, to further define the population of elderly AML patients most likely to benefit from this agent, should be investigated. Arm 1 Arm 2 Arm 3 Arm 4 CR 8% 4% 11% 1% CRi 5% 6% 4% 5% Fatal toxicity 8% 4% 2% 0% One year survival 14% 25% 28% 14%

Intensive Chemotherapy Does Not Prolong Survival Compared to 5-Azacitidine in Patients Aged 70 Years or More with Untreated Acute Myeloid Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3596-3596
Author(s):  
Luca Maurillo ◽  
Francesco Buccisano ◽  
Gianluca Gaidano ◽  
Mariagiovanna Cefalo ◽  
Giovanna Mansueto ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Randomized Clinical Trials ◽  
Normal Karyotype ◽  
Control Group ◽  
Intensive Chemotherapy ◽  
Blast Count ◽  
The Impact ◽  
To Receive ◽  
Acute Myeloid

Abstract Abstract 3596 Intensive chemotherapy (IC) is associated with significant mortality and morbidity in elderly with acute myeloid leukemia (AML); particularly in patients aged ≥ 70 years, it is currently debated whether or not to deliver IC. Recent findings suggest that hypomethylating agents have encouraging clinical and biological activity in AML, with limited toxicity. Based on this background we wanted to evaluate retrospectively: 1) the efficacy of azacitidine (AZA) in elderly patients with untreated AML, diagnosed according to WHO criteria; 2) the impact of AZA on overall survival (OS) of this category of patients. For comparative purposes a historical group of matched patients who received IC was also analyzed. The AZA group included 57 patients, median age was 76 yrs (range 63–88) with 91% (52) of the patients being 70 yrs old or more, 32 were males and 25 females. Forty-two (78%) had a white blood cell count (WBCc) < 10×109/L, 17 (30%) a secondary AML supervening after an antecedent hematological disorder and 28 (49%) a bone marrow (BM) blast count < 30%. Karyotype was evaluable in 38 (67%) patients and, according to the refined Medical Research Council criteria, 27 (47%) had intermediate-risk abnormalities (25 normal karyotype) and 11 (20%) an unfavorable risk karyotype. A diagnosis of AML according to WHO classification, absence of uncontrolled infections, adequate renal and hepatic function, life expectancy longer than 4 months were the criteria to receive AZA. IC historical control group consisted in 83 patients enrolled sequentially in the AML13 and AML17 EORTC/GIMEMA protocols between 1995 and 2008. In these prospective trials patients aged 61–80 years received an induction course consisting in mitoxantrone, cytarabine (ARA-C), and etoposide (ICE) followed by 2 consolidation cycles including idarubicin, ARA-C, and etoposide (mini-ICE). In AML17 trial, the patients were also randomized to receive or not gemtuzumab ozogamicin, during induction and consolidation courses. Median age was 67 yrs (range 61–78) with 34% (28) of the patients being 70 years old or more, 47 were males and 36 females; 43 (52%) had a WBCc < 10×109/L and 79 (95%) a BM blast count ≥ 30%. Karyotype was evaluable in 65 (78%) patients: 52 (63%) belonged to the intermediate category (43 normal karyotype), 2 (2%) and 11 (13%) carried a favorable and unfavorable risk karyotype, respectively. Thirty-nine patients (68%) received AZA subcutaneously at the conventional dose of 75 mg/m2, the remaining 18 at a flat dose of 100 mg daily; all patients were given a schedule of 7 consecutive days per month. The median number of cycles delivered was 6 (range 1–39) and 77% of the patients received at least 4 cycles of therapy. Median follow up was 244 days (range 30–1281). Overall response rate, estimated according to the revised recommendation of the International Working Group in AML, was 17% and consisted in 11 (8%) complete remission (CR), 4 (3%) CR with incomplete blood count recovery (CRi) and 9 (6%) partial remission (PR). The chance of obtaining a response to AZA was significantly associated with a WBCc < 10×109/L (p=0.002). The median duration of response was 183 days (range 60–1067). Projected 2-years OS for patients on AZA treatment vs IC was 14% and 38%, respectively (p=0.008). Since the median age of the AZA group was 76 years, we broke down the analysis focusing on patients aged 70 years or more. By doing so, we observed that the projected 2-years OS for patients receiving AZA vs those receiving IC was 12% and 28%, respectively (p=0.11). Finally, among the category of patients aged ≥ 70 yrs, we extrapolated those who achieved a response with AZA (22 patients) or IC (22 patients); for these individuals, 2-years OS rate was 25% and 36%, respectively (p=0.46). In conclusion, our retrospective analysis suggests that in AML patients aged ≥ 70 yrs and with a WBCc < 10×109/L, AZA is as effective as IC and could be considered a valid therapeutic option. In this context, the manageable and limited toxicity of AZA will also allow for the quality of life objective to be accomplished. Patients aged < 70 yrs or those who, whatever the age, have a WBCc ≥ 10×109/L are likely to benefit more from IC than AZA. Controlled, randomized, clinical trials are warranted to further explore this matter and confirm our conclusions. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia: Who, When, and How?

2021 ◽  
Vol 12 ◽  
Author(s):  
Justin Loke ◽  
Richard Buka ◽  
Charles Craddock
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Myeloid Leukemia ◽  
Treatment Algorithm ◽  
Unmet Need ◽  
Disease Assessment ◽  
Cell Transplant ◽  
Intensive Chemotherapy ◽  
Disease Relapse ◽  
Acute Myeloid

Although the majority of patients with acute myeloid leukemia (AML) treated with intensive chemotherapy achieve a complete remission (CR), many are destined to relapse if treated with intensive chemotherapy alone. Allogeneic stem cell transplant (allo-SCT) represents a pivotally important treatment strategy in fit adults with AML because of its augmented anti-leukemic activity consequent upon dose intensification and the genesis of a potent graft-versus-leukemia effect. Increased donor availability coupled with the advent of reduced intensity conditioning (RIC) regimens has dramatically increased transplant access and consequently allo-SCT is now a key component of the treatment algorithm in both patients with AML in first CR (CR1) and advanced disease. Although transplant related mortality has fallen steadily over recent decades there has been no real progress in reducing the risk of disease relapse which remains the major cause of transplant failure and represents a major area of unmet need. A number of therapeutic approaches with the potential to reduce disease relapse, including advances in induction chemotherapy, the development of novel conditioning regimens and the emergence of the concept of post-transplant maintenance, are currently under development. Furthermore, the use of genetics and measurable residual disease technology in disease assessment has improved the identification of patients who are likely to benefit from an allo-SCT which now represents an increasingly personalized therapy. Future progress in optimizing transplant outcome will be dependent on the successful delivery by the international transplant community of randomized prospective clinical trials which permit examination of current and future transplant therapies with the same degree of rigor as is routinely adopted for non-transplant therapies.

Randomized Clinical Trial of Induction Therapy Comparing Intensified Daunorubicin with Idarubicin in Patients with Previously Untreated De Novo Acute Myeloid Leukemia (JALSG AML201 Study).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2000-2000 ◽  
Author(s):  
Shigeki Ohtake ◽  
Shuichi Miyawaki ◽  
Hiroyuki Fujita ◽  
Hitoshi Kiyoi ◽  
Katsuji Shinagawa ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Standard Dose ◽  
Newly Diagnosed ◽  
Induction Regimen ◽  
To Receive ◽  
Acute Myeloid

Abstract We conducted a multicenter prospective randomized study to determine whether the intensified daunorubicin (DNR) induction chemotherapy would be as effective as idarubicin (IDR) in adult acute myeloid leukemia (AML). Newly diagnosed adult patients with AML excluding FAB-M3 were consecutively registered and randomized to receive either increased dose of DNR or standard dose of IDR induction chemotherapy. All patients received cytarabine 100mg/m2 daily for 7 days by continuous intravenous infusion, and either DNR 50mg/m2 daily for 5 days or IDR 12mg/m2 daily for 3 days according to randomization. If the patients did not achieve complete remission (CR) after the first induction therapy, the same induction therapy was given once more. Patients achieving CR were again randomized to receive either 3 courses of high-dose cytarabine or 4 courses of conventional multiagent consolidation therapy. The results of later randomization will be reported another abstract. From December 2001 to December 2005, 1064 newly diagnosed patients with de novo AML were registered and 1057 were eligible. Median age was 47 years old (range 15 to 64). Five hundred twenty five patients were randomized to DNR group, and 532 to IDR group. The two groups were well matched for pretreatment characteristics. CR was achieved in 407 patients (77.5%; 95% CI, 73.9% – 81.1%) with 321 (61.1%) after 1 induction course in DNR group and 418 patients (78.6%; 75.1% – 82.1%) with 341 (64.1%) after 1 course in IDR group (p = 0.68). Patients receiving IDR took slightly but significantly longer to recover from neutropenia and thrombocytopenia. There was a higher rate of sepsis in IDR (8.7%) than DNR (4.9%) (p = 0.02). The early death within 60 days occurred in 25 patients (4.7%) in IDR and 11 (2.1%) in DNR (p = 0.03). Logistic regression analysis revealed that induction regimen was not the independent prognostic factor, but CBF leukemia and the percentage of peroxidase positive leukemic blast were the significant independent factors for achieving remission. There was also no significant difference between the groups in the longer-time measures of efficacy: estimated overall survival at 4 years was 49.1% (42.4% – 55.8%) for DNR and 53.1% (47.6% – 58.6%)for IDR (p = 0.37); estimated relapse free survival at 4 years from CR was 42.2% (36.1% – 48.3%) for DNR and 41.8% (35.9% – 47.7%) for IDR (p = 0.62). The Cox proportional hazards analyses showed that the induction regimen did not affect these outcomes. In conclusion, increased dose of DNR and standard dose of IDR both achieve high remission rate and good long-term efficacy, and are equally effective for the treatment of AML patients up to 64 years, although the final assessment will have to be performed after longer follow up.

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