Bmi-1 Expression Is Useful To Design Therapy and To Predict Prognosis in Patients with Acute Myeloid Leukemia.

Abstract Since prognosis of patients with acute myeloid leukemia (AML) is highly variable even in a single subpopulation in FAB classification, it would be useful to find prognostic molecular markers for AML. Thus, we investigated Bmi-1 expression in AML cells by flow cytometry and analyzed whether it predicts prognosis in AML patients and further it is helpful to choose therapies in the modalities of treatment options, because it is known to be required for self-renewal mechanism of leukemic stem cells. Bmi-1 expression in bone marrow or peripheral blood cells was analyzed in 49 patients with AML (M0(n=5), M1(n=7), M2(n=6), M3(n=5), M4(n=8), M5(n=5), M6(n=1)), granulocytic sarcoma(n=1), MDS-AML (n=9), and secondary AML(n=2). Freshly isolated AML cells were stained with a PE-conjugated anti-CD34-antibody followed by fixation and then with anti-Bmi-1-antibody-FITC. All of patients with low Bmi-1 positivity (<35%, n=11) except for de novo AML(M0) entered in complete remission (CR) with single induction chemotherapy(n=5) and accordingly had better overall survival, even though lower dose of chemotherapy (60% of standard dose) was given (n=3). Alternatively, patients with higher percentage of Bmi-1 expression in AML cells (> 70%, n=19) except for AML(M3) progressed to death within two years, unless they were treated with highly intensive therapy such as high dose AraC or allogeneic stem cell transplantation (n=3). Patients with intermediate degree of Bmi-1 expression (35–60%, n=5) responded to standard intensity of chemotherapy (n=2) and are alive for more than two years. Interestingly, patients with MDS-AML (n=9) had high Bmi-1 expression (79%) and all of them have died within 20 months. Binary logistic regression model showed that significant correlation was found among survival status as dependent variable, Bmi-1, and treatment intensity as independent variable (p = 0.004). On the other hand, Univariate analysis did not reveal any relation of Bmi-1 expression to karyotype, age, WBC count, or FAB subtype. In conclusion, Bmi-1 expression could be an independent prognostic marker and useful tool to design therapy for the AML patients.

Download Full-text

Pretreatment platelet count predicts survival outcome of patients with de novo non-M3 acute myeloid leukemia

PeerJ ◽

10.7717/peerj.4139 ◽

2017 ◽

Vol 5 ◽

pp. e4139 ◽

Cited By ~ 6

Author(s):

Qianying Zhang ◽

Kanchun Dai ◽

Laixi Bi ◽

Songfu Jiang ◽

Yixiang Han ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Platelet Count ◽

Predictive Value ◽

Myeloid Leukemia ◽

De Novo ◽

Univariate Analysis ◽

Survival Outcome ◽

Cox Regression Analysis ◽

High Platelet Count ◽

Acute Myeloid

Background Pretreatment platelet count has been reported as a potential tool to predict survival outcome in several solid tumors. However, the predictive value of pretreatment platelet count remains obscure in de novo acute myeloid leukemia (AML) excluding acute promyelocytic leukemia (M3). Methods We conducted a retrospective review of 209 patients with de novo non-M3 AML in our institute over a period of 8 years (2007–2015). Receiver operating characteristic (ROC) curve analysis was used to determine the optimal platelet (PLT) cutoff in patients. We analyzed the overall survival (OS) and disease free survival (DFS) using the log-rank test and Cox regression analysis. Results By defining the platelet count 50 × 109/L and 120 × 109/L as two cut-off points, we categorized the patients into three groups: low (<50 × 109/L), medium (50–120 × 109/L) and high (>120 × 109/L). On univariate analysis, patients with medium platelet count had longer OS and DFS than those with low or high platelet count. However, the multivariate analysis showed that only longer DFS was observed in patients with medium platelet count than those with low or high platelet count. Conclusion Our findings indicate that pretreatment platelet count has a predictive value for the prognosis of patients with non-M3 AML.

Download Full-text

A randomized study of high-dose cytarabine in induction in acute myeloid leukemia [see comments]

Blood ◽

10.1182/blood.v87.5.1710.1710 ◽

1996 ◽

Vol 87 (5) ◽

pp. 1710-1717 ◽

Cited By ~ 333

Author(s):

JF Bishop ◽

JP Matthews ◽

GA Young ◽

J Szer ◽

A Gillett ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Univariate Analysis ◽

Disease Free Survival ◽

Dose Effect ◽

Induction Treatment ◽

High Dose ◽

Remission Duration ◽

High Dose Cytarabine ◽

Acute Myeloid

Abstract High-dose cytarabine (ara-c) may overcome cytarabine resistance in leukemic blasts. It has been used as a successful salvage and in postremission therapy but not as initial induction treatment. Patients aged 15 to 60 years, presenting with newly diagnosed acute myeloid leukemia (AML) were randomized to receive either high-dose cytarabine, 3 g/m2 12 hourly on days 1, 3, 5, and 7 for 8 doses, daunorubicin 50 mg/m2 days 1 to 3, etoposide 75 mg/m2 days 1 to 7, (HIDAC-3–7) or standard dose cytarabine 100 mg/m2 continuous intravenous infusion for 7 days with daunorubicin and etoposide at the same dose and schedule as above (7–3–7). Patients could receive a second or third induction course if complete remission (CR) was not achieved. All patients received the same postinduction consolidation therapy (5–2–5) for 2 courses. Eligible patients had no prior chemotherapy or myelodysplastic disease. Patients have been followed for a median of 4.5 years. Of 301 patients treated, complete response (CR) was achieved in 71% with HIDAC- 3–7 and 74% with 7–3–7. For patients in CR, the estimated median remission duration was 45 months with HIDAC-3–7 and 12 months with 7–3– 7 (P = .0005 univariate analysis, P = .0004 multivariate analysis). The estimated percentage of patients relapse free 5 years after achieving a CR was 49% on HIDAC-3–7 and 24% on 7–3–7. Patients in CR tended to survive longer with HIDAC-3–7 but there were no overall survival differences between the two arms. HIDAC-3–7 was associated with significantly more toxicity in induction with more leukopenia, thrombocytopenia, nausea, and vomiting and eye toxicity (all P < .001) but a similar incidence of severe central nervous system and cerebellar toxicity compared to 7–3–7. The consolidation treatment was the same in both arms but caused significantly more leukopenia and thrombocytopenia in patients previously treated with HIDAC-3–7 induction (P < .0001). We conclude that a dose-effect exists for cytarabine in AML and that HIDAC- 3–7 prolongs remission duration and disease-free survival and is tolerable when used as initial induction therapy in patients with de novo AML.

Download Full-text

Adult Patients With De Novo Acute Myeloid Leukemia and t(9; 11)(p22; q23) Have a Superior Outcome to Patients With Other Translocations Involving Band 11q23: A Cancer and Leukemia Group B Study

Blood ◽

10.1182/blood.v90.11.4532 ◽

1997 ◽

Vol 90 (11) ◽

pp. 4532-4538 ◽

Cited By ~ 124

Author(s):

Krzysztof Mrózek ◽

Kristiina Heinonen ◽

David Lawrence ◽

Andrew J. Carroll ◽

Prasad R.K. Koduru ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

De Novo ◽

Extra Chromosome ◽

Response To Therapy ◽

High Dose ◽

Postremission Therapy ◽

De Novo Aml ◽

Group B ◽

Acute Myeloid

Abstract Following reports of childhood acute myeloid leukemia (AML) showing that patients with t(9; 11)(p22; q23) have a better prognosis than those with translocations between 11q23 and other chromosomes, we compared response to therapy and survival of 24 adult de novo AML patients with t(9; 11) with those of 23 patients with other 11q23 translocations [t(11q23)]. Apart from a higher proportion of French-American-British (FAB) M5 subtype in the t(9; 11) group (83% v 43%, P = .006), the patients with t(9; 11) did not differ significantly from patients with t(11q23) in terms of their presenting clinical or hematologic features. Patients with t(9; 11) more frequently had an extra chromosome(s) 8 or 8q as secondary abnormalities (46% v 9%, P = .008). All patients received standard cytarabine and daunorubicin induction therapy, and most of them also received cytarabine-based intensification treatment. Two patients, both with t(9; 11), underwent bone marrow transplantation (BMT) in first complete remission (CR). Nineteen patients (79%) with t(9; 11) and 13 (57%) with t(11q23) achieved a CR (P = .13). The clinical outcome of patients with t(9; 11) was significantly better: the median CR duration was 10.7 versus 8.9 months (P = .02), median event-free survival was 6.2 versus 2.2 months (P = .009), and median survival was 13.2 versus 7.7 months (P = .009). All patients with t(11q23) have died, whereas seven (29%) patients with t(9; 11) remain alive in first CR. Seven of eight patients with t(9; 11) who received postremission regimens with cytarabine at a dose of 100 (four patients) or 400 mg/m2 (2 patients) or who did not receive postremission therapy (2 patients) have relapsed. In contrast, 7 (64%) of 11 patients who received intensive postremission chemotherapy with high-dose cytarabine (at a dose 3 g/m2) (5 patients), or underwent BMT (2 patients) remain in continuous CR. We conclude that the outcome of adults with de novo AML and t(9; 11) is more favorable than that of adults with other 11q23 translocations; this is especially true for t(9; 11) patients who receive intensive postremission therapy.

Download Full-text

Intermediate-risk acute myeloid leukemia therapy: current and future

Hematology ◽

10.1182/asheducation.v2014.1.34.3882398 ◽

2014 ◽

Vol 2014 (1) ◽

pp. 34-43 ◽

Cited By ~ 2

Author(s):

Konstanze Döhner ◽

Peter Paschka

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Intensive Therapy ◽

Standard Of Care ◽

Gemtuzumab Ozogamicin ◽

High Dose ◽

Genetic Profile ◽

Molecular Heterogeneity ◽

Intermediate Risk ◽

Acute Myeloid

Abstract In recent years, research in molecular genetics has been instrumental in deciphering the molecular heterogeneity of acute myeloid leukemia (AML), in particular the subset of patients with “intermediate-risk” cytogenetics. However, at present, only the markers NPM1, CEBPA, and FLT3 have entered clinical practice. Treatment of intermediate-risk AML patients eligible for intensive therapy has not changed substantially. The “3 + 7” induction therapy still represents the standard of care. The addition of the immunoconjugate gemtuzumab ozogamicin to therapy has been shown to improve outcome; however, the drug is not approved for this use. A common standard for postremission therapy is the administration of repeated cycles of intermediate- to high-dose cytarabine. Allogeneic stem cell transplantation may offer a survival benefit for many patients with intermediate-risk AML. Patients are best selected based on the genetic profile of the leukemia cells and the risk associated with the transplantation itself. A myriad of novel agents targeting mutant leukemia drivers or deregulated pathways are in clinical development. In the past, many novel compounds have not met expectations; nonetheless, with the rapid developments in comprehensive molecular profiling and new drug design, there is the prospect of personalizing therapy and improving patient outcome.

Download Full-text

EZH2 Mutations Are Associated with Low Blast Percentage in Bone Marrow and −7/Del(7q) Karyotype in De Novo Acute Myeloid Leukemia.

Blood ◽

10.1182/blood.v120.21.2544.2544 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2544-2544

Author(s):

Xiuli Wang ◽

Haiping Dai ◽

Qian WANG ◽

Qinrong Wang ◽

Yang Xu ◽

...

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

De Novo ◽

Conflicts Of Interest ◽

Univariate Analysis ◽

Myelogenous Leukemia ◽

Prognostic Impact ◽

Coding Region ◽

Acute Myeloid

Abstract Abstract 2544 Somatic mutation of the EZH2 gene is seen in myelodisplastic syndrome, myelofibrosis, and chronic myelomonocytic leukemia patients. The prevalence and prognostic impact of somatic mutations of EZH2 in patients with acute myelogenous leukemia (AML) remains unknown. In this study, we sought to determine the incidence and clinical implications of somatic EZH2 mutations in 714 patients with de novo AML by PCR amplification of the entire coding region followed by direct bidirectional DNA sequencing. EZH2 mutations were identified in 13/714 (1.8%) of AML patients and occurred almost exclusively in males (11/13, P=0.033). In univariate analysis, the presence of EZH2 mutations was significantly associated with lower blast percentage (21–30%) in bone marrow (P=0.0001) and −7/del(7q) (P=0.025). There was no difference in the incidence of mutations in 13 genes, including ASXL1, CBL, c-KIT, DNMT3A, FLT3, IDH1, IDH2, MLL, NPM1, NRAS, RUNX1, TET2, and WT1, between patients with and without EZH2 mutations. Complete remission, event-free survival or overall survival was similar between AML patients with and without EZH2 mutation (p>0.05). These results demonstrated EZH2 mutation as a recurrent genetic abnormality associated with lower blast percentage in BM and −7/del(7q) in de novo acute myeloid leukemia. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Randomized study of induction therapy comparing standard-dose idarubicin with high-dose daunorubicin in adult patients with previously untreated acute myeloid leukemia: the JALSG AML201 Study

Blood ◽

10.1182/blood-2010-03-273243 ◽

2011 ◽

Vol 117 (8) ◽

pp. 2358-2365 ◽

Cited By ~ 147

Author(s):

Shigeki Ohtake ◽

Shuichi Miyawaki ◽

Hiroyuki Fujita ◽

Hitoshi Kiyoi ◽

Katsuji Shinagawa ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Complete Remission ◽

Induction Therapy ◽

Myeloid Leukemia ◽

Standard Dose ◽

Randomized Study ◽

Survival Rates ◽

Adult Patients ◽

High Dose ◽

Acute Myeloid

Abstract We conducted a multi-institutional randomized study to determine whether high-dose daunorubicin would be as effective as standard-dose idarubicin in remission-induction therapy for newly diagnosed adult patients younger than 65 years of age with acute myeloid leukemia. Of 1064 patients registered, 1057 were evaluable. They were randomly assigned to receive either daunorubicin (50 mg/m2 daily for 5 days) or idarubicin (12 mg/m2 daily for 3 days) in combination with 100 mg/m2 of cytarabine by continuous infusion daily for 7 days as induction therapy. Complete remission was achieved in 407 (77.5%) of 525 patients in the daunorubicin group and 416 (78.2%) of 532 in the idarubicin group (P = .79). Patients achieving complete remission received intensive postremission therapy that consisted of either 3 courses of high-dose cytarabine or 4 courses of standard-dose therapy. Overall survival rates at 5 years were 48% for the daunorubicin group and 48% for the idarubicin group (P = .54), and relapse-free survival rates at 5 years were 41% and 41% (P = .97), respectively. Thus, high-dose daunorubicin and standard-dose idarubicin were equally effective for the treatment of adult acute myeloid leukemia, achieving a high rate of complete remission and good long-term efficacy. This study is registered at http://www.umin.ac.jp/ctrj/ as C000000157.

Download Full-text

A randomized trial comparing standard versus high-dose daunorubicin induction in patients with acute myeloid leukemia

Blood ◽

10.1182/blood-2011-06-361410 ◽

2011 ◽

Vol 118 (14) ◽

pp. 3832-3841 ◽

Cited By ~ 93

Author(s):

Je-Hwan Lee ◽

Young-Don Joo ◽

Hawk Kim ◽

Sung Hwa Bae ◽

Min Kyoung Kim ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Young Adults ◽

Randomized Trial ◽

Myeloid Leukemia ◽

Standard Dose ◽

Survival Duration ◽

High Dose ◽

Different Doses ◽

Acute Myeloid

Abstract We conducted a phase 3 randomized trial comparing 2 different doses of daunorubicin as induction chemotherapy in young adults (60 years of age or younger) with acute myeloid leukemia (AML). Of 383 patients who were analyzed, 189 received standard-dose daunorubicin (SD-DN, 45 mg/m2 per day times 3 days) and 194 received high-dose daunorubicin (HD-DN, 90 mg/m2 per day times 3 days) in addition to cytarabine (200 mg/m2 per day times 7 days) to induce complete remission (CR). The CR rates were 72.0% in the SD-DN arm and 82.5% in the HD-DN arm (P = .014). At a median follow-up of 52.6 months, overall (OS) and event-free (EFS) survival were higher in the HD-DN arm than in the SD-DN arm (OS, 46.8% vs 34.6%, P = .030; EFS, 40.8% vs 28.4%, P = .030). Differences in CR rate and both OS and EFS remained significant after adjusting for other variables (CR, hazard ratio [HR], 1.802, P = .024; OS, HR, 0.739, P = .032; EFS, HR, 0.774, P = .048). The survival benefits of HD-DN therapy were evident principally in patients with intermediate-risk cytogenetic features. The toxicity profiles were similar in the 2 arms. In conclusion, HD-DN improved both the CR rate and survival duration compared with SD-DN in young adults with AML. This study is registered at www.clinicaltrials.gov as #NCT00474006.

Download Full-text

High-dose cytosine arabinoside and daunorubicin postremission therapy in adults with de novo acute myeloid leukemia

Annals of Hematology ◽

10.1007/bf01744371 ◽

1995 ◽

Vol 71 (5) ◽

pp. 219-225 ◽

Cited By ~ 6

Author(s):

G. Heil ◽

P. S. Mitrou ◽

D. Hoelzer ◽

M. Freund ◽

H. Link ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Cytosine Arabinoside ◽

Myeloid Leukemia ◽

De Novo ◽

High Dose ◽

Postremission Therapy ◽

Acute Myeloid

Download Full-text

Retrospective Comparison between MEC and FLAG-Ida Regimens for Refractory or Relapsed Acute Myeloid Leukemia in Adults

Blood ◽

10.1182/blood-2019-127202 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1354-1354

Author(s):

Wellington F Silva ◽

Lidiane Inês Da Rosa ◽

Fernanda S Seguro ◽

Douglas R. A. Silveira ◽

Luciana Nardinelli ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Univariate Analysis ◽

Multivariable Analysis ◽

High Dose ◽

Npm1 Mutation ◽

Baseline Characteristics ◽

One Year ◽

Relapsed Acute Myeloid Leukemia ◽

Acute Myeloid

Introduction: There is no consensus regarding the best salvage regimen for refractory or relapsed acute myeloid leukemia (r/rAML), with classic regimens traditionally based on high-dose cytarabine in a changeable combination with anthracyclines, purine analogs, and etoposide. Outcomes of r/rAML patients in developing countries are underreported, even though the same regimens are widely used. Methods: This is a retrospective single-center study, conducted in an academic center in Brazil. Local research ethics committee approved this analysis. All patients above 16 years of age who received MEC (mitoxantrone, etoposide and cytarabine) or FLAG-IDA (fludarabine, cytarabine, filgrastim and idarubicin) as originally reported (Amadori, S. et al. and Steinmetz, H. T. et al.) for r/rAML between December/2009 and January/2019 were included. Only patients with refractory or relapsed disease following standard upfront therapy ("7+3" regimen) were included in this analysis, being divided among refractory (less than partial response after one cycle of "7+3"), early relapsed (relapse within one year from first complete response [CR]) and late relapsed (relapse after one year of CR). Only the first salvage was considered for this study. Results: Sixty patients were included in the final analysis, with a median age of 45 years (range, 17 - 69). There were no cases of therapy-related AML. Four AML cases (7%) were secondary to myeloproliferative neoplasm (MPN) or myelodysplastic syndrome (MDS). All FLT3-ITD positive cases had an associated NPM1 mutation. Two patients had chronic human immunodeficiency virus infection and received antiretroviral therapy. Baseline characteristics of the whole cohort are summarized in Table 1. Three patients had undergone SCT in first CR and were post-SCT relapses. Twenty-eight patients received MEC and 32 received FLAG-IDA. By comparing the baseline characteristics of both groups, no difference statistically significant was found except for the indication for salvage treatment, in which there were more refractory cases in FLAG-IDA group (56 vs. 28%, p=0.029) (Table 2). Overall, 17/60 achieved CR and 12/60 CRi, with a total CR rate (CR+CRi) of 48.3% (95% confidence interval [CI], 35.4 - 61.5). Sixteen patients (27%) early died before a response assessment. By univariate analysis, only age affected the CR rate (p=0.045). No difference in CR rate was found between the two protocols (MEC 53.5 vs. FLAG-IDA 43.7%, p=0.447). Looking into this data, it can be seen that there were more refractory patients in FLAG-IDA arm (37.5 vs. 4%, p=0.02) but more patients early-died in MEC arm (35.7 vs. 18.7%, p=0.137), even though the latter was not statistically significant. After correcting the initial differences between the two groups regarding indication for salvage through a propensity score calculation, a post-matching cohort with 44 subjects was found. In this cohort, no difference in refractoriness rate could be detected (p=0.077). In the whole cohort, 17 patients proceeded to allogeneic SCT - 15 in CR/CRi and 2 with active disease, with no difference in SCT execution rate between the two groups (p=0.470). 4/17 transplanted patients were alive. Median follow-up was 48 months. Median survival for total cohort was 4 months (95% CI, 2.7 - 9.2), with a 3-year OS of 9.7% (95% CI, 4 - 23.7) and a 3-year EFS of 7.5% (95% CI, 2.5 - 22.4). In the univariate analysis for OS, age (p=0.04), FLT3 status (p<0.001) and SCT procedure (p=0.002) were statistically significant. Chosen regimen did not influence OS or EFS as well as the genetic risk, colonization or time of relapse (Figure 1). In a multivariable model for EFS including age, FLT3 status and SCT procedure, only the last two indicators remained significant: FLT3-ITD mutation (Hazard ratio [HR] = 4.6 [95% CI 1.9 - 11.4], p<0.001) and SCT procedure (HR = 0.43 [95% CI 0.22 - 0.82], p=0.01). Conclusion: In this analysis, there was no difference concerning the chosen regimen for r/rAML, even though a possible higher refractoriness rate could be seen in FLAG-IDA arm. High early toxicity was found, emphasizing the role of supportive care and judicious selection of patients to intensive salvage therapy in our setting. FLT3-ITD mutation and SCT remained as significant factors for survival in a multivariable analysis, which is in line with previous studies. Disclosures No relevant conflicts of interest to declare.

Download Full-text

A randomized investigation of high-dose versus standard-dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group study

Blood ◽

10.1182/blood.v88.8.2841.bloodjournal8882841 ◽

1996 ◽

Vol 88 (8) ◽

pp. 2841-2851 ◽

Cited By ~ 290

Author(s):

JK Weick ◽

KJ Kopecky ◽

FR Appelbaum ◽

DR Head ◽

LL Kingsbury ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Standard Dose ◽

High Dose ◽

Consolidation Therapy ◽

Oncology Group ◽

Free Survival ◽

Southwest Oncology Group ◽

To Receive ◽

Acute Myeloid

Interest in high-dose cytarabine (HDAC) for both induction and postremission therapy for acute myeloid leukemia (AML) prompted the Southwest Oncology Group (SWOG) to initiate a randomized trial comparing HDAC with standard-dose cytarabine (SDAC) for remission induction of previously untreated AML and to compare high-dose treatment versus conventional doses for consolidation therapy. Patients less than 65 years of age with de novo or secondary AML were randomized for induction between SDAC 200 mg/ m2/d for 7 days by continuous infusion or HDAC at 2 g/ m2 intravenously every 12 hours for 12 doses; both groups received daunorubicin (DNR) at 45 mg/m2/d intravenously for 3 days. Complete responders to SDAC were randomized to receive either two additional courses of SDAC plus DNR or one course of HDAC plus DNR. Complete responders to HDAC were nonrandomly assigned to receive one additional course of HDAC plus DNR. Of patients randomized between SDAC (n = 493) and HDAC (n = 172) induction, 361 achieved complete remission (CR). The CR rate was slightly poorer with HDAC: 55% versus 58% with SDAC for patients aged less than 50, and 45% (HDAC) versus 53% (SDAC) for patients aged 50 to 64 (age-adjusted one-tailed P = .96). With a median follow-up time of 51 months, survival was not significantly better with HDAC (P = .41); the estimated survival rate at 4 years was 32% (HDAC) versus 22% (SDAC) for those aged less than 50, and 13% (HDAC) versus 11% (SDAC) for those aged 50 to 64. However, relapse-free survival was somewhat better following HDAC Induction (P = .049): 33% (HDAC) versus 21% (SDAC) at 4 years for those aged less than 50, and 21% (HDAC) versus 9% (SDAC) for those aged 50 to 64. Induction with HDAC was associated with a significantly increased risk of fatal (P = .0033) and neurologic (P < .0001) toxicity. Among patients who achieved CR with SDAC, survival and disease-free survival (DFS) following consolidation randomization were not significantly better with HDAC compared with SDAC (P = .77 and .46, respectively). Patients who received both HDAC induction and consolidation had the best postremission outcomes; however, the proportion of CR patients who did not go on to protocol consolidation therapy was more than twice as high after HDAC induction compared with SDAC. Induction therapy with HDAC plus DNR was associated with greater toxicity than SDAC plus DNR, but with no improvement in CR rate or survival. Following CR induction with SDAC, consolidation with HDAC increased toxicity but not survival or DFS. In a nonrandomized comparison, patients who received both HDAC induction and consolidation had superior survival and DFS compared with those who received SDAC induction with either SDAC or HDAC consolidation.

Download Full-text