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

Byrd, John C.; Dodge, Richard K.; Carroll, Andrew J.; Edwards, Colin G.; Stamberg, Judith; Qumsiyeh, Mazin B.; Moore, Joseph O.; Mayer, Robert J.; Davey, Frederick R.; Schiffer, Charles A.; Bloomfield, Clara D.

doi:10.1200/jco.1999.17.12.3767

Cited by 286 publications

(154 citation statements)

References 20 publications

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“…This finding appears to be specifically due to the favorable outcome of t(8;21) patients when treated with the intensive induction/consolidation regimen, whereas the DFS of inv(16) patients seemed to be unaffected by the kind of therapy employed. A favorable outcome, in t(8;21) cases, could thus be related not only with the number of repeated cycles of high-dose AraC as previously reported, 40 but with alternative intensive chemotherapy schedules as well. In the 'intermediate' subgroup, intensive induction did not appear to improve DFS with respect to standard induction.…”

Section: Leukemiasupporting

confidence: 50%

The prognostic value of cytogenetics is reinforced by the kind of induction/consolidation therapy in influencing the outcome of acute myeloid leukemia – analysis of 848 patients

et al. 2001

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We studied the impact of cytogenetics and kind of induction/consolidation therapy on 848 adult acute myeloid leukemia (AML) patients (age 15-83). The patients received three types of induction/consolidation regimen: standard (daunorubicin and cytosine arabinoside (3/7); two cycles); intensive (idarubicin, cytosine arabinoside and etoposide (ICE), plus mitoxantrone and intermediate-dose Ara-C (NOVIA)); and low-dose (low-dose cytosine arabinoside). CR patients under 60 years of age, if an HLA-identical donor was available received allogeneic stem cell transplantation (allo-SCT); otherwise, as part of the program, they underwent autologous (auto)-SCT. CR rates significantly associated with 'favorable' (inv(16), t(8;21)), 'intermediate' ('no abnormality', abn(11q23), +8, del(7q)) and 'unfavorable' (del (5q), −7, abn(3)(q21q26), t(6;9), 'complex' (more than three unrelated cytogenetic abnormalities)) karyotypes (88% vs 65% vs 36%, respectively; P = 0.0001). These trends were confirmed in all age groups. On therapeutic grounds, intensive induction did not determine significant increases of CR rates in any of the considered groups, with respect to standard induction. Low-dose induction was associated with significantly lower CR rates. Considering disease-free survival (DFS), multivariate analysis of the factors examined (including karyotype grouping) showed that only age Ͼ60 years significantly affected outcome. However, in cases where intensive induction was adopted, 'favorable' karyotype was significantly related to longer DFS (P = 0.04). This was mainly due to the favorable outcome of t(8;21) patients treated with intensive induction. Patients receiving allo-SCT had significantly longer DFS (P = 0.005); in particular, allo-SCT significantly improved DFS in the 'favorable' and 'intermediate' groups (P = 0.04 and P = 0.048, respectively). In conclusion our study could provide some guidelines for AML therapy: (1) patients in the 'favorable' karyotype group seem to have a longer DFS when treated with an intensive induction/consolidation regimen, adopted before auto-SCT instead of standard induction; this underlines the importance of reinforcement of chemotherapy, not necessarily based on repeated high-dose AraC cycles. Allo-SCT, independently of induction/consolidation therapy, should be considered an alternative treatment; (2) patients in the 'intermediate' karyotype group should receive allo-SCT; (3) patients in the 'unfavorable' karyotype group should be treated using investigational chemotherapy, considering that even allo-SCT cannot provide a significantly longer DFS, but only a trend to a better prognosis. Leukemia (2001) 15, 903-909.

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Section: Leukemiasupporting

confidence: 50%

The prognostic value of cytogenetics is reinforced by the kind of induction/consolidation therapy in influencing the outcome of acute myeloid leukemia – analysis of 848 patients

et al. 2001

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“…4 However, relapses still occur in about 30% of the cases. Initial features such as a high initial white blood cell count (WBC), WBC index, CD56 expression, del (9q) in addition to t(8;21) or extramedullary disease have been associated with an increased risk of relapse.…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of real-time quantitative PCR (RQ-PCR) in AML with t(8;21)

et al. 2005

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Despite the favorable prognosis of patients with acute myeloid leukemia (AML) with t(8;21)(q22;q22) translocation, relapses still occur in about 30% of the cases but no initial factors can strongly predict the risk of relapse. Several recent studies suggest that monitoring minimal residual disease (MRD) may identify patients at risk of relapse. We prospectively monitored AML1-ETO rearrangement by real-time quantitative PCR (RQ-PCR) in 21 patients uniformly treated in our center. Blood (PB) and bone marrow (BM) samples were collected during and after therapy. At diagnosis, levels of AML1-ETO transcript showed large variations and there was a trend for a higher relapse rate in patients with high pretreatment expression levels (P ¼ 0.065). After induction therapy, absolute transcript levels (below 10 À3 , compared to Kasumi cell line), or a greater than 3 log decrease by comparison to diagnosis levels, were significant predictors of the absence of relapse (P ¼ 0.02 and P ¼ 0.02, respectively). MRD levels after consolidation therapy were also significant indicators of relapse (P ¼ 10 À5 ). Comparison of BM and PB samples showed similar sensitivity for detecting AML1-ETO transcript. In conclusion, RQ-PCR appears to be an early predictive factor of the relapse risk in AML with t(8;21). PB samples can be used adequately to evaluate the level of MRD by this technique.

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“…Historically, CBF AML was treated with standard cytarabine plus anthracycline induction chemotherapy followed by one or several consolidation courses of high-dose cytarabine. Studies comparing consolidation strategies reported cure rates in CBF AML of 30-40% with one highdose cytarabine consolidation versus 50-70% with 3-4 consolidation courses [67,68]. Recent studies have used induction and consolidation courses of high-dose cytarabine in combination with fludarabine and idarubicin, as well as the addition of GO 3 mg/m 2 3 1 during induction and one consolidation course.…”

Section: Core Binding Factor Amlmentioning

confidence: 99%

Acute myeloid leukemia—Major progress over four decades and glimpses into the future

2015

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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

Abstract: 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.

Cited by 286 publications

References 20 publications

The prognostic value of cytogenetics is reinforced by the kind of induction/consolidation therapy in influencing the outcome of acute myeloid leukemia – analysis of 848 patients

The prognostic value of cytogenetics is reinforced by the kind of induction/consolidation therapy in influencing the outcome of acute myeloid leukemia – analysis of 848 patients

Prognostic value of real-time quantitative PCR (RQ-PCR) in AML with t(8;21)

Acute myeloid leukemia—Major progress over four decades and glimpses into the future

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