6-Thioguanine, Cytarabine, and Daunorubicin (TAD) and High-Dose Cytarabine and Mitoxantrone (HAM) for Induction, TAD for Consolidation, and Either Prolonged Maintenance by Reduced Monthly TAD or TAD-HAM-TAD and One Course of Intensive Consolidation by Sequential HAM in Adult Patients at All Ages With De Novo Acute Myeloid Leukemia (AML): A Randomized Trial of the German AML Cooperative Group

2003 ◽  
Vol 21 (24) ◽  
pp. 4496-4504 ◽  
Author(s):  
Thomas Büchner ◽  
Wolfgang Hiddemann ◽  
Wolfgang E. Berdel ◽  
Bernhard Wörmann ◽  
Claudia Schoch ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Lactate Dehydrogenase Level ◽  
High Dose ◽  
Free Survival ◽  
Poor Risk ◽  
De Novo Aml ◽  
To Receive ◽  
Acute Myeloid

Purpose: To examine the efficacy of prolonged maintenance chemotherapy versus intensified consolidation therapy for patients with acute myeloid leukemia (AML). Materials and Methods: Eight hundred thirty-two patients (median age, 54 years; range, 16 to 82 years) with de novo AML were randomly assigned to receive 6-thioguanine, cytarabine, and daunorubicin (TAD) plus cytarabine and mitoxantrone (HAM; cytarabine 3 g/m2 [age < 60 years] or 1 g/m2 [age ≥ 60 years] × 6) induction, TAD consolidation, and monthly modified TAD maintenance for 3 years, or TAD-HAM-TAD and one course of intensive consolidation with sequential HAM (S-HAM) with cytarabine 1 g/m2 (age < 60 years) or 0.5 g/m2 (age ≥ 60 years) × 8 instead of maintenance. Results: A total of 69.2% patients went into complete remission (CR). Median relapse-free survival (RFS) was 19 months for patients on the maintenance arm, with 31.4% of patients relapse-free at 5 years, versus 12 months for patients on the S-HAM arm, with 24.7% of patients relapse-free at 5 years (P = .0118). RFS from maintenance was superior in patients with poor risk by unfavorable karyotype, age ≥ 60 years, lactate dehydrogenase level greater than 700 U/L, or day 16 bone marrow blasts greater than 40% (P = .0061) but not in patients with good risk by complete absence of any poor risk factors. Although a survival benefit in the CR patients is not significant (P = .085), more surviving patients in the maintenance than in the S-HAM arm remain in first CR (P = .026). Conclusion: We conclude that TAD-HAM-TAD-maintenance first-line treatment has a higher curative potential than TAD-HAM-TAD-S-HAM and improves prognosis even among patients with poor prognosis.

Postremission therapy in older patients with de novo acute myeloid leukemia: a randomized trial comparing mitoxantrone and intermediate-dose cytarabine with standard-dose cytarabine

Blood ◽  
2001 ◽  
Vol 98 (3) ◽  
pp. 548-553 ◽  
Author(s):  
Richard M. Stone ◽  
Deborah T. Berg ◽  
Stephen L. George ◽  
Richard K. Dodge ◽  
Paolo A. Paciucci ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Disease Free Survival ◽  
Free Survival ◽  
De Novo Aml ◽  
To Receive ◽  
Disease Free ◽  
Acute Myeloid

Abstract The treatment of older patients with acute myeloid leukemia (AML) remains unsatisfactory, with complete remission (CR) achieved in only approximately 50% and long-term disease-free survival in 10% to 20%. Three hundred eighty-eight patients (60 years of age and older) with newly diagnosed de novo AML were randomly assigned to receive placebo (P) or granulocyte-macrophage colony-stimulating factor (GM-CSF) or GM in a double-blind manner, beginning 1 day after the completion of 3 days of daunorubicin and 7 days of cytarabine therapy. No differences were found in the rates of leukemic regrowth, CR, or infectious complications in either arm. Of 205 patients who achieved CR, 169 were medically well and were randomized to receive cytarabine alone or a combination of cytarabine and mitoxantrone. With a median follow-up of 7.7 years, the median disease-free survival times were 11 months and 10 months for those randomized to cytarabine or cytarabine/mitoxantrone, respectively. Rates of relapse, excluding deaths in CR, were 77% for cytarabine and 82% for cytarabine/mitoxantrone. Induction randomization had no effect on leukemic relapse rate or remission duration in either postremission arm. Because cytarabine/mitoxantrone was more toxic and no more effective than cytarabine, it was concluded that this higher-dose therapy had no benefit in the postremission management of older patients with de novo AML. These results suggest the need to develop novel therapeutic strategies for these patients.

scholarly journals 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 ◽  
1997 ◽  
Vol 90 (11) ◽  
pp. 4532-4538 ◽  
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.

Patients With t(8;21)(q22;q22) and Acute Myeloid Leukemia Have Superior Failure-Free and Overall Survival When Repetitive Cycles of High-Dose Cytarabine Are Administered

1999 ◽  
Vol 17 (12) ◽  
pp. 3767-3775 ◽  
Author(s):  
John C. Byrd ◽  
Richard K. Dodge ◽  
Andrew Carroll ◽  
Maria R. Baer ◽  
Colin Edwards ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
High Dose ◽  
Free Survival ◽  
High Dose Cytarabine ◽  
Group B ◽  
To Receive ◽  
Leukemia Group ◽  
Acute Myeloid

PURPOSE: To examine the effect of single compared with repetitive (at least three) cycles of high-dose cytarabine after induction therapy for patients with acute myeloid leukemia (AML) who have the t(8;21)(q22;q22) karyotype. PATIENTS AND METHODS: Patients entered onto the study had AML and t(8;21) and attained a complete remission on four successive Cancer and Leukemia Group B studies. In these studies, either ≥ three cycles of high-dose cytarabine or one cycle of high-dose cytarabine was administered, followed by sequential cyclophosphamide/etoposide and mitoxantrone/diaziquone with or without filgrastim support. Outcomes of these two groups of t(8;21) patients were compared. RESULTS: A total of 50 patients with centrally reviewed AML and t(8;21) were assigned to receive one (n = 29) or ≥ three cycles (n = 21) of high-dose cytarabine as postinduction therapy. The clinical features of these two groups of patients were similar. Initial remission duration for t(8;21) patients assigned to one cycle of high-dose cytarabine was significantly inferior (P = .03), with 62% of patients experiencing relapse with a median failure-free survival of 10.5 months, compared with the group of patients who received ≥ three cycles, in which only 19% experienced relapse and failure-free survival is estimated to be greater than 35 months. Furthermore, overall survival was also significantly compromised (P = .04) in patients assigned to one cycle of high-dose cytarabine, with 59% having died as a consequence of AML, compared with 24% of those who received ≥ three cycles of high-dose cytarabine. CONCLUSION: These data demonstrate that failure-free survival and overall survival of patients with t(8;21)(q22;q22) may be compromised by treatment approaches that do not include sequential high-dose cytarabine therapy.

scholarly journals 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 ◽  
1996 ◽  
Vol 88 (8) ◽  
pp. 2841-2851 ◽  
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.

Homoharringtonine-Based Induction Regimens for Patients with De Novo Acute Myeloid Leukemia: A Multicenter Randomized Controlled Phase 3 Trial

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 45-45 ◽  
Author(s):  
Jie Jin ◽  
Jianxiang Wang ◽  
Feifei Chen ◽  
Depei Wu ◽  
Jiong Hu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Phase 3 ◽  
Free Survival ◽  
Cytogenetic Profile ◽  
To Receive ◽  
Acute Myeloid

Abstract Abstract 45 Background Homoharringtonine-based induction regimens have been widely used in China for patients with acute myeloid leukemia (AML), which have shown to improve the rate of complete remission (CR) and long-term survival. We aimed to further evaluate its efficacy and safety in treatment of de novo AML. Methods This phase 3 study was done in 17 institutions in China. Patients between the age of 14 and 59 with untreated AML were randomly assigned to receive HAA (homoharringtonine 2 mg/m2/day, days 1–7; cytarabine 100 mg/m2/day, days 1–7, aclarubicin 20 mg/day, days 1–7), HAD (homoharringtonine 2 mg/m2/day, days 1–7; cytarabine 100 mg/m2/day, days 1–7; daunorubicin 40 mg/m2/day, days 1–3) or DA (daunorubicin 40–45 mg/m2/day, days 1–3; cytarabine 100 mg/m2/day, days 1–7) regimen as induction therapy. Patients who achieved partial remission or had a decrease of blast ¡Ý60% could receive a same second induction course. All patients who had a complete remission were offered the same consolidation chemotherapy according to the cytogenetic-risk. The primary endpoints were CR and event-free survival (EFS). The trial is registered in Chinese Clinical Trial Register, number ChiCTR-TRC-06000054. Results 620 patients were randomly assigned to receive HAA (n=207), HAD (n=206) and DA (n=207) regimens. HAA or HAD regimen, as compared with DA regimen, resulted in a higher rate of CR in the first course of induction therapy (67.5% vs. 54.0%, P=0.005; 64.9% vs. 54.0%, P=0.026, respectively). The overall CR rate remained significantly higher in the HAA arm as compared with DA arm (75.0% vs. 61.9%, P=0.005). HAA or HAD regimen has similar rates of adverse events as compared with DA regimen, but was associated with significantly increased risk of induction death (5.8% vs. 1.0%, P=0.007; 6.6% vs. 1.0%, P=0.003, respectively). The EFS was greatly improved in the HAA arm (3-year EFS 35.4±3.5% vs.23.1±3.1%, P=0.002), while not significantly in the HAD arm (3-year EFS 32.7±3.5% vs.23.1±3.1%, P=0.078) as compared with the DA arm. Overall survival (OS) and relapse-free survival (RFS) did not differ significantly in the HAA or HAD arm as compared with DA arm, but an OS and RFS advantage of the HAA arm over the DA arm was observed in patients with favorable or intermediate cytogenetic profile (OS: P=0.014; RFS: P=0.022, respectively). Patients in the HAD arm with NPM1 but not FLT3ITD mutations, as compared with the patients in the DA arm, had an improved EFS (P=0.038). In intermediate cytogenetic profile, patients with mutant CEBPA had prolonged RFS in the HAA arm as compared with the DA arm (P=0.045). Conclusions Homoharringtonine-based induction regimens are associated with a higher rate of CR and improved survival as compared with DA regimen in AML. The toxicity is mild with the exception of a higher rate of induction death. Disclosures: No relevant conflicts of interest to declare.

CBFA2T3-GLIS2 Fusion Is Prevalent in Younger Patients with Acute Myeloid Leukemia and Associated with High-Risk of Relapse and Poor Outcome: A Children’s Oncology Group Report

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 13-13 ◽  
Author(s):  
Heather L Schuback ◽  
Todd A. Alonzo ◽  
Robert B. Gerbing ◽  
Kristen L. Miller ◽  
Samir Kahwash ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Disease Free Survival ◽  
Clinical Implications ◽  
Free Survival ◽  
Younger Patients ◽  
De Novo Aml ◽  
Disease Free ◽  
Acute Myeloid

Abstract The cryptic CBA2T3-GLIS2 fusion generated by the inv(16)(p13.3q24.3) was initially identified in megakaryocytic leukemia and later implicated in other acute myeloid leukemia (AML) subtypes. Presence of this fusion may lead to altered expression of the potentially targetable sonic hedgehog and bone morphogenic protein pathways. We determined the prevalence of CBA2T3-GLIS2 in children treated on COG AAML03P1 and AAML0531 protocols, which collectively enrolled 1361 eligible children, adolescents, and young adults with de novo AML, and correlated the presence of this fusion with patient demographics, laboratory features, and clinical outcomes. We also determined the prevalence and clinical implications of CBA2T3-GLIS2 in 71 children with FAB M7 AML treated on 4 consecutive COG AML trials. Of the 1042 diagnostic samples available and tested for CBFA2T3-GLIS2, 45 (4.3%) were positive for the fusion. Fusion-positive patients were significantly younger than fusion-negative patients (2.1 vs. 10.3 years; P<0.001). CBFA2T3-GLIS2 was most prevalent in the youngest patients (10.6% for 0 to <2 year olds and 8.6% for 2 to <5 year olds) [Figure A]. In contrast, no fusion transcripts were identified in 299 unselected adult patients. All FAB subtypes were represented in fusion-positive patients. Overall, FAB M5 and M7 were equally prevalent in fusion-positive patients, and each subtype accounted for 20% of cases [Figure B]. There was a preponderance of MLL rearrangements (N=7) in fusion-positive patients, and 3 more patients had either t(8;21) or inv(16), and 25.6% (N=11) without karyotypic alterations (CN-AML). None of the fusion-positive patients had the t(7;12) or 12p abnormality. There were few common AML-associated mutations: 1 patient had FLT3ITD and 1 had the WT1 mutation (no NPM1 or biallelic CEBPA mutations were identified). Figure 1 Figure 1. Rates of morphologic complete remission (CR) at the end of induction course 1 were similar for fusion-positive and -negative patients (68.9% vs. 77.7%; P=0.17). However, fusion-positive patients were more likely to have minimal residual disease (MRD) by flow cytometry at this time point (50% vs. 28.9%; P=0.006) with a correspondingly higher relapse rate (RR) from remission of 58% vs. 35% (p=0.005). Disease-free survival for those with and without fusion was 42% vs. 58% (p=0.060) In a subset analysis of 193 patients with CN-AML, the prevalence of CBFA2T3-GLIS2 was 4.7%. Fusion-positive patients were younger than fusion-negative patients (1.6 vs. 13.1 years; P<0.001) and more likely to have MRD at the end of induction (85.7% vs. 40.8%; P=0.043). CN-AML fusion-positive patients had significantly worse 5-year OS (36% vs. 67% P=0.025) and EFS (18% vs. 51%, P=0.017) than fusion-negative patients. All fusion-positive patients in CR had a higher 5-year RR than fusion-negative patients (88% vs. 33%; P<0.001), with a corresponding disease-free survival (DFS) of 13% vs. 59% (P<0.001). Implications of CBFA2T3-GLIS2 were evaluated in 71 cases of children with FAB M7 AML where the fusion was identified in 12 patients (17%). Fusion-positive FAB M7 patients had significantly lower CR rate than fusion-negative patients (33.3% vs. 77.6%, P=0.005) and all were MRD positive at the end of induction (100% vs. 30%, P=0.001). All FAB M7 fusion-positive patients relapsed (100% vs. 36%, P=0.007), with a DFS of 0% vs. 60% (p=0.013). As CBFA2T3-GLIS2 was most common in younger patients, we compared clinical implications in children <2 years of age. Although CR rates in fusion-positive and -negative patients were similar (68.2% vs. 74.9%; P=0.50), fusion-positive patients were more likely than fusion-negative patients to have MRD at the end of course 1 (63.2% vs. 24.8%, P=0.006). Five-year RR rates in fusion-positive and -negative patients were 71% vs. 39% (P=0.012), with corresponding DFS of 29% vs. 56% (P=0.030). This study provides a comprehensive evaluation of incidence and prognostic implications of the CBFA2T3-GLIS2 fusion in pediatric de novo AML. Along with MLL rearrangements, 12p abnormalities, and the recently described NUP98-JARID1A fusion, this cryptic inversion 16, as defined by presence of the CBFA2T3-GLIS2 fusion, represents a distinct, recurrent chromosomal abnormality associated with poor prognosis in infant AML and is a potential therapeutic target. Disclosures No relevant conflicts of interest to declare.

BAALC expression predicts clinical outcome of de novo acute myeloid leukemia patients with normal cytogenetics: a Cancer and Leukemia Group B Study

Blood ◽  
2003 ◽  
Vol 102 (5) ◽  
pp. 1613-1618 ◽  
Author(s):  
Claudia D. Baldus ◽  
Stephan M. Tanner ◽  
Amy S. Ruppert ◽  
Susan P. Whitman ◽  
Kellie J. Archer ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Risk Factor ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Free Survival ◽  
De Novo Aml ◽  
Normal Cytogenetics ◽  
Group B ◽  
Leukemia Group ◽  
Acute Myeloid

AbstractCytogenetic aberrations are important prognostic factors in acute myeloid leukemia (AML). Of adults with de novo AML, 45% lack cytogenetic abnormalities, and identification of predictive molecular markers might improve therapy. We studied the prognostic impact of BAALC (Brain And Acute Leukemia, Cytoplasmic), a novel gene involved in leukemia, in 86 de novo AML patients with normal cytogenetics who were uniformly treated on Cancer and Leukemia Group B 9621. BAALC expression was determined by comparative real-time reverse transcriptase–polymerase chain reaction in pretreatment blood samples, and patients were dichotomized at BAALC's median expression into low and high expressers. Low expressers had higher white counts (P = .03) and more frequent French-American-British M5 morphology (P = .007). Compared to low expressers, high BAALC expressers showed significantly inferior overall survival (OS; median, 1.7 vs 5.8 years, P = .02), event-free survival (EFS; median, 0.8 vs 4.9 years, P = .03), and disease-free survival (DFS; median, 1.4 vs 7.3 years, P = .03). Multivariable analysis confirmed high BAALC expression as an independent risk factor. For high BAALC expressers the hazard ratio of an event for OS, EFS, and DFS was respectively 2.7, 2.6, and 2.2. We conclude that high BAALC expression predicts an adverse prognosis and may define an important risk factor in AML with normal cytogenetics.

scholarly journals 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 ◽  
1997 ◽  
Vol 90 (11) ◽  
pp. 4532-4538 ◽  
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

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.

Multi-Course of Moderate Dose Cytosine Arabinoside and Fludarabin in the Consolidation Therapy of Patients with De Novo Acute Myeloid Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4251-4251
Author(s):  
Huiying Qiu ◽  
Wu Depei ◽  
Aining Sun ◽  
Zhengming Jin ◽  
Miao Miao ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cytosine Arabinoside ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Hematological Toxicity ◽  
Consolidation Therapy ◽  
Moderate Dose ◽  
Free Survival ◽  
De Novo Aml ◽  
Acute Myeloid

Abstract Abstract 4251 To investigate the long-term outcome of multi-course of moderate dose cytosine arabinoside and fludarabin in the consolidation therapy of patients with de novo acute myeloid leukemia (AML). Sixty-seven consecutive de novo AML patients, 38 males, 29 females, including M1 (5 cases), M2a (34 cases), M4 (11 cases), M5 (13 cases), M6 (2 cases), unclassified AML (1 cases), HAL (1 case), were enrolled in this retrospective analysis between 2006 to 2011. Their median age was 32.28 years (range 13–64 years). Cytogenetic analysis showed that 27 patients with normal karyotype, 11 patients with t(8; 21), 4 patients with inv(16), 16 patients with other karyotype. Forty-two cases were classified as low and intermediate risk groups based on karyotype analysis and fusion gene detection. Thirty-eight cases and twenth-nine cases achieved complete remission (CR) after one course and two course induction chemotherapy (such as cytarabine with idarubicin or daunorubicin and mitoxantrone etc), respectively. All patients received at least two-course consolidation therapy with moderate dose cytosine arabinoside (2g/m2) and fludarabin (30mg/m2) for 3 days (FA). Nineteen cases received two courses, 20 three courses, 20 four courses, 8 five courses and1 six courses. Quantitative RT-PCR and flow cytometry were used to detect minimal residual disease. Afterwards 3 patients underwent allogeneic stem cell transplantation. The median time for hematological recovery of neutrophils©ƒ500/microl and platelets©ƒ20,000/microl was 12 and 16 days, respectively. The median length of hospitalization was 18 days. Non-hematological toxicity consisted of mild gastrointestinal reaction and mild hepatic dysfunction, forty percent of patients experienced fever. There was no treatment-related mortality during consolidation. After follow up of 4–54 months, 10/19 (52.6%) cases were relapse-free survival (RFS) after two courses FA consolidation, 15/20 (75%) cases in three courses, 15/20 (75%) cases in four courses, respectively. 8 cases were all in RFS after five courses consolidation. 1 case was also in RFS after six courses FA consolidation. Three-year overall survival, event free survival and RFS was 67%, 67%, and 66%, respectively. Our results suggest that multi-course FA consolidation is effective in de novo AML patients with low-risk and moderate-risk diseases. To reduce the recurrence rate the number of courses should be increased. Non-hematological toxicity was mild and the toxicity is acceptable. Disclosures: No relevant conflicts of interest to declare.

Dose-dense induction with sequential high-dose cytarabine and mitoxantone (S-HAM) and pegfilgrastim results in a high efficacy and a short duration of critical neutropenia in de novo acute myeloid leukemia: a pilot study of the AMLCG

Blood ◽  
2009 ◽  
Vol 113 (17) ◽  
pp. 3903-3910 ◽  
Author(s):  
Jan Braess ◽  
Karsten Spiekermann ◽  
Peter Staib ◽  
Andreas Grüneisen ◽  
Bernhard Wörmann ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Early Death ◽  
High Dose ◽  
Kaplan Meier ◽  
De Novo Aml ◽  
Dose Dense ◽  
Acute Myeloid

AbstractDose density during early induction has been demonstrated to be one of the prime determinants for treatment efficacy in acute myeloid leukemia (AML). The German AML Cooperative Group has therefore piloted a dose-dense induction regimen sequential high-dose AraC and mitoxantrone followed by pegfilgrastim (S-HAM) in which 2 induction cycles are applied over 11 to 12 days instead of 25 to 29 days as used in conventional double induction, thereby increasing dose density 2-fold. Of 172 de novo AML patients (excluding acute promyelocytic leukemia), 61% reached a complete remission, 22% a complete remission with incomplete peripheral recovery, 7% had persistent leukemia, 10% died (early death) resulting in an overall response rate of 83%. Kaplan-Meier estimated survival at 2 years was 61% for the whole group (patients with unfavorable karyotypes, 38%; patients with favorable karyotypes, 69%; patients with intermediate karyotypes, 75%) after S-HAM treatment. Importantly, the compression of the 2 induction cycles into the first 11 to 12 days of treatment was beneficial for normal hematopoiesis as demonstrated by a significantly shortened duration of critical neutropenia of 31 days compared with 46 days after conventionally timed double induction. (European Leukemia Trial Registry LN_AMLINT_2004_230.)

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