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

1995 ◽  
Vol 71 (5) ◽  
pp. 219-225 ◽  
Author(s):  
G. Heil ◽  
P. S. Mitrou ◽  
D. Hoelzer ◽  
M. Freund ◽  
H. Link ◽  
...  
Blood ◽  
1997 ◽  
Vol 90 (11) ◽  
pp. 4532-4538 ◽  
Author(s):  
Krzysztof Mrózek ◽  
Kristiina Heinonen ◽  
David Lawrence ◽  
Andrew J. Carroll ◽  
Prasad R.K. Koduru ◽  
...  

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.


Blood ◽  
1997 ◽  
Vol 90 (11) ◽  
pp. 4532-4538 ◽  
Author(s):  
Krzysztof Mrózek ◽  
Kristiina Heinonen ◽  
David Lawrence ◽  
Andrew J. Carroll ◽  
Prasad R.K. Koduru ◽  
...  

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.


2000 ◽  
Vol 79 (10) ◽  
pp. 533-542 ◽  
Author(s):  
M. Flasshove ◽  
P. Meusers ◽  
J. Schütte ◽  
R. Noppeney ◽  
D. W. Beelen ◽  
...  

Blood ◽  
1992 ◽  
Vol 79 (8) ◽  
pp. 1924-1930 ◽  
Author(s):  
PA Cassileth ◽  
E Lynch ◽  
JD Hines ◽  
MM Oken ◽  
JJ Mazza ◽  
...  

The Eastern Cooperative Oncology Group (ECOG) conducted a randomized trial in patients less than or equal to 65 years old (median, 44 years) to determine whether increasing the intensity of postremission therapy in acute myeloid leukemia (AML) would improve the outcome. After uniform induction therapy, patients in complete remission (CR) who were less than 41 years old and who had a histocompatible sibling underwent allogeneic bone marrow transplantation (alloBMT) (54 patients). The remainder of patients in CR were randomized to receive either 2 years of continuous outpatient maintenance therapy with cytarabine and 6- thioguanine (83 patients) or a single course of inpatient consolidation therapy consisting of 6 days of high-dose cytarabine plus 3 days of amsacrine (87 patients). The median duration of follow-up is now 4 years, and patients are included in the analyses of outcome regardless of whether they relapsed before starting the intended treatment. Four- year event-free survival (EFS) was 27% +/- 10% for consolidation therapy versus 16% +/- 8% for maintenance therapy (P = .068) and 28% +/- 11% versus 15% +/- 9% (P = .047) in patients less than 60 years old. The outcome for patients receiving alloBMT was compared with the subset of patients less than 41 years old who received consolidation therapy (N = 29) or maintenance therapy (N = 21). Four-year EFS was 42% +/- 13% for alloBMT, 30% +/- 17% for consolidation therapy, and 14% +/- 15% for maintenance therapy. AlloBMT had a significantly better EFS (P = .013) than maintenance therapy, but was not different from consolidation therapy. In patients less than 41 years old, 4-year survival after alloBMT (42% +/- 14%) did not differ from consolidation therapy (43% +/- 18%), but both were significantly better than maintenance therapy (19% +/- 17%), P = .047 and .043, respectively. The mortality rate for maintenance therapy was 0%, consolidation therapy, 21%; and alloBMT, 36%. Consolidation therapy caused an especially high mortality rate in the patients greater than or equal to 60 years old (8 of 14 or 57%). The toxicity of combined high-dose cytarabine and amsacrine is unacceptable, especially in older patients, and alternative approaches to consolidation therapy such as high-dose cytarabine alone need to be tested. In AML, a single course of consolidation therapy or alloBMT after initial CR produces better results than lengthy maintenance therapy. Although EFS and survival of alloBMT and consolidation therapy do not differ significantly, a larger number of patients need to be studied before concluding that they are equivalent.


Blood ◽  
2002 ◽  
Vol 99 (12) ◽  
pp. 4343-4349 ◽  
Author(s):  
Elihu H. Estey ◽  
Peter F. Thall ◽  
Francis J. Giles ◽  
Xue-Mei Wang ◽  
Jorge E. Cortes ◽  
...  

We investigated treatment with gemtuzumab ozogamicin (GO) in 51 patients aged 65 years or older with newly diagnosed acute myeloid leukemia (AML), refectory anemia (RA) with excess of blasts in transformation, or RA with excess blasts. GO was given in doses of 9 mg/m2 of body-surface area on days 1 and 8 or, therapeutically equivalently, on days 1 and 15, with or without interleukin 11 (IL-11; 15 μg/kg per day on days 3 to 28), with assignment to IL-11 treatment made randomly. Complete remission (CR) rates were 2 of 26 (8%) for GO without IL-11 and 9 of 25 (36%) for GO with IL-11. Regression analyses indicated that IL-11 was independently predictive of CR but not survival. We compared GO with or without IL-11 with idarubicin plus cytosine arabinoside (IA), as previously administered, in similar patients. The CR rate with IA was 15 of 31 (48%), and survival was superior with IA compared with GO with or without IL-11 (P = .03). Besides accounting for possible covariate effects on outcome, we also accounted for possible trial effects (TEs) arising because IA and GO with or without IL-11 were not arms of a randomized trial. Bayesian posterior probabilities that GO with or without IL-11 produced longer survival than IA, after accounting for covariates and TEs, were less than 0.01 in patients with abnormal cytogenetic findings (AC) and less than 0.15 in patients with normal cytogenetic findings (NC). Regarding CR, the analogous probabilities were less than 0.02 for GO without IL-11 (all cytogenetic groups), and for GO with IL-11, less than 0.25 for AC groups and about 0.50 for NC groups. TEs 2 to 5 times the magnitude of those previously observed would be needed to conclude that survival with GO with or without IL-11 is likely longer than with IA. Thus, there is little evidence to suggest that GO with or without IL-11 should be used instead of IA in older patients with newly diagnosed AML or myelodysplastic syndrome.


Blood ◽  
1987 ◽  
Vol 69 (3) ◽  
pp. 744-749 ◽  
Author(s):  
W Hiddemann ◽  
H Kreutzmann ◽  
K Straif ◽  
WD Ludwig ◽  
R Mertelsmann ◽  
...  

Abstract In a clinical phase I/II study, high-dose cytosine arabinoside and mitoxantrone (HAM) were given in combination to 40 patients with refractory acute myeloid leukemia. All patients had received a 9-day combination of thioguanine, Ara-C, and daunorubicin (TAD-9) as standardized first-line treatment. Refractoriness was defined as (a) nonresponse against two TAD-9 induction cycles, (b) early relapse within the first 6 months on monthly maintenance or after TAD-9 consolidation, (c) relapse after 6 months with nonresponse against one additional TAD-9 cycle, and (d) second and subsequent relapses after successful TAD-9 therapy at the preceding relapse. Therapy consisted of HD-Ara-C 3 g/m2 every 12 hours on days 1 through 4; mitoxantrone was started at 12 mg/m2/day on days 3, 4, and 5 and was escalated to 4 and 5 doses of 10 mg/m2/day on days 2 through 5 and 2 through 6. Of the 40 patients, 21 achieved a complete remission (53%), 1 patient had a partial remission, and 5 patients were nonresponders. Thirteen patients died in aplasia due to infections (n = 11), pericardiac effusion, or acute cardiomyopathy. Nonhematologic side effects consisted predominantly of nausea and vomiting, mucositis, and diarrhea. Central nervous system (CNS) symptoms were observed during six treatment courses. Recovery of blood counts occurred at a median of 27 days from the onset of treatment; the median time to complete remission was 36 days. Two of the 21 responders underwent successful bone marrow transplantations. The median remission duration for the remaining 19 patients is 4.5 months, and the median survival time is 9 months. These data emphasize that HAM has high antileukemic activity in refractory AML and strongly suggest starting the combination at earlier stages in AML therapy.


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