High-Dose Cytarabine Alone Versus Cytarabine Plus Anthracycline for Consolidation Therapy in Non-Promyelocytic Acute Myeloid Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4890-4890
Author(s):  
Sung-Hyun Kim ◽  
So Yeon Kim ◽  
Ji Hyun Lee ◽  
Suee Lee ◽  
Sung Yong Oh ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
High Dose ◽  
Consolidation Therapy ◽  
Free Survival ◽  
High Dose Cytarabine ◽  
Group A ◽  
Group B ◽  
Acute Myeloid ◽  
Intermediate Dose

Abstract Standard consolidation therapy of acute myeloid leukemia (AML) contains high-dose cytarabine (HiDC). However, optimal dose of cytarabine and benefit of additional chemotherapeutic agents remain unresolved problems. One hundred and forty-two patients among 173 newly diagnosed AML patients, who achieved complete remission following induction chemotherapy and subsequently received different consolidation therapies in 4 independent institutes, were retrospectively analyzed. Patients were divided into 3 groups by consolidation regimens: HiDC (1.5-3g/m2, bid, Days 1,3,5) alone in 44 patients (Group A), HiDC plus anthracycline in 46 patients (Group B), and intermediate-dose cytarabine (1g/m2, bid, Days 1,3,5) plus anthracycline in 52 patients (Group C). Overall survival (OS), relapse-free survival (RFS), disease-free survival (DFS), and event-free survival (EFS), were not significantly different in Group A vs. Group B. However, Group B showed longer RFS, DFS, and EFS, as compared with Group C. Treatment-related mortality was significantly higher in Group B, as compared with Group A (P=0.040) and Group C (P=0.013). Cytogenetic risk was the only significant prognostic factor in OS, RFS, DFS and EFS. In this study, the addition of anthracycline to HiDC as consolidation chemotherapy in AML patients did not improve treatment outcomes, and had more toxicity. HiDC enhanced RFS, DFS, and EFS, as compared with intermediate-dose cytarabine. Therefore, HiDC single therapy could be considered as standard consolidation therapy for non-promyelocytic AML Disclosures Choi: Alexion Pharmaceuticals: Research Funding.

Safety and feasibility of outpatient high-dose cytarabine and intermediate-dose cytarabine for consolidation therapy in acute myeloid leukemia

2021 ◽  
pp. 107815522110465
Author(s):  
Wenhui Li ◽  
Katherine Richter ◽  
Jamie Lee ◽  
Kevin McCarthy ◽  
Timothy Kubal
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Outpatient Setting ◽  
Cancer Center ◽  
High Dose ◽  
Consolidation Therapy ◽  
High Dose Cytarabine ◽  
Incidence Of Hospitalization ◽  
Acute Myeloid ◽  
Intermediate Dose

Introduction The standard of care consolidation therapy for acute myeloid leukemia is high-dose cytarabine or intermediate-dose cytarabine, which are traditionally given inpatient. At Moffitt Cancer Center, we have moved the administration of high-dose cytarabine and intermediate-dose cytarabine to the outpatient setting through the inpatient/outpatient program. To facilitate outpatient administration, high-dose cytarabine and intermediate-dose cytarabine are given in a shorter interval of every 10 h instead of 12 h. The safety of a shorter duration interval of high-dose cytarabine and intermediate-dose cytarabine is unknown. This study aims to assess the safety and feasibility of administering high-dose cytarabine and intermediate-dose cytarabine consolidation therapy in the inpatient/outpatient setting. Methods This is a retrospective chart review to analyze acute myeloid leukemia patients treated with inpatient/outpatient high-dose cytarabine or intermediate-dose cytarabine consolidation therapy at Moffitt Cancer Center from January 1, 2015, through November 1, 2018. The primary objective was to determine the incidence of hospitalization during the inpatient/outpatient administration of high-dose cytarabine or intermediate-dose cytarabine. Results Two hundred fifty-three of 255 cycles of high-dose cytarabine/intermediate-dose cytarabine were delivered outpatient over the reviewed time period to 118 patients. No patients receiving outpatient high-dose cytarabine/intermediate-dose cytarabine consolidation required hospitalization during chemotherapy. Our incidence of hospitalization (24%) after chemotherapy is consistent with the reported literature. Through the inpatient/outpatient administration of high-dose cytarabine and intermediate-dose cytarabine, 1265 inpatient days were saved with an approximate revenue of $3,135,176 generated in our study period. Conclusion Inpatient/outpatient administration of high-dose cytarabine and intermediate-dose cytarabine is both safe and feasible. Moving high-dose cytarabine/intermediate-dose cytarabine administration to the outpatient setting resulted in significant additional revenue vs. inpatient administration.

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 Varying intensity of postremission therapy in acute myeloid leukemia

Blood ◽  
1992 ◽  
Vol 79 (8) ◽  
pp. 1924-1930 ◽  
Author(s):  
PA Cassileth ◽  
E Lynch ◽  
JD Hines ◽  
MM Oken ◽  
JJ Mazza ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Mortality Rate ◽  
Maintenance Therapy ◽  
Myeloid Leukemia ◽  
High Dose ◽  
Allogeneic Bone ◽  
Consolidation Therapy ◽  
High Dose Cytarabine ◽  
Postremission Therapy ◽  
Acute Myeloid

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.

Repetitive Cycles of High-Dose Cytarabine Benefit Patients With Acute Myeloid Leukemia and inv(16)(p13q22) or t(16;16)(p13;q22): Results from CALGB 8461

2004 ◽  
Vol 22 (6) ◽  
pp. 1087-1094 ◽  
Author(s):  
John C. Byrd ◽  
Amy S. Ruppert ◽  
Krzysztof Mrózek ◽  
Andrew J. Carroll ◽  
Colin G. Edwards ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Statistical Significance ◽  
Multivariable Analysis ◽  
High Dose ◽  
Consolidation Therapy ◽  
High Dose Cytarabine ◽  
The Impact ◽  
To Receive ◽  
Acute Myeloid

Purpose To study the impact of repetitive (three to four courses) versus a single course of high-dose cytarabine (HDAC) consolidation therapy on outcome of patients with acute myeloid leukemia (AML) and inv(16)(p13q22) or t(16;16)(p13;q22). Patients and Methods We examined the cumulative incidence of relapse (CIR), relapse-free survival (RFS), and overall survival (OS) for 48 adults younger than 60 years with inv(16)/t(16;16) who had attained a complete remission on one of four consecutive clinical trials and were assigned to receive HDAC consolidation therapy. Twenty-eight patients were assigned to either three or four courses of HDAC, and 20 patients were assigned to one course of HDAC followed by alternative intensive consolidation therapy. Results Pretreatment features were similar for the two groups. The CIR was significantly decreased in patients assigned to receive three to four cycles of HDAC compared with patients assigned to one course (P = .03; 5-year CIR, 43% v 70%, respectively). The difference in RFS also approached statistical significance (P = .06). In a multivariable analysis that adjusted for potential confounding covariates, only treatment assignment (three to four cycles of HDAC) predicted for superior RFS (P = .02). The OS of both groups was similar (P = .93; 5-year OS, 75% for the three to four cycles of HDAC group v 70% for the one cycle of HDAC group), reflecting a high success rate with stem-cell transplantation salvage treatment administered among patients in both treatment groups. Conclusion We conclude that, in AML patients with inv(16)/t(16;16), repetitive HDAC therapy decreases the likelihood of relapse compared with consolidation regimens including less HDAC.

scholarly journals Patients With Acute Myeloid Leukemia and RAS Mutations Benefit Most From Postremission High-Dose Cytarabine: A Cancer and Leukemia Group B Study

2008 ◽  
Vol 26 (28) ◽  
pp. 4603-4609 ◽  
Author(s):  
Andreas Neubauer ◽  
Kati Maharry ◽  
Krzysztof Mrózek ◽  
Christian Thiede ◽  
Guido Marcucci ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
High Dose ◽  
Relapse Risk ◽  
Ras Mutations ◽  
High Dose Cytarabine ◽  
Group B ◽  
The Impact ◽  
Leukemia Group ◽  
Acute Myeloid

Purpose RAS mutations occur in 12% to 27% of patients with acute myeloid leukemia (AML) and enhance sensitivity to cytarabine in vitro. We examined whether RAS mutations impact response to cytarabine in vivo. Patients and Methods One hundred eighty-five patients with AML achieving complete remission on Cancer and Leukemia Group B study 8525 and randomly assigned to one of three doses of cytarabine postremission were screened for RAS mutations. We assessed the impact of cytarabine dose on cumulative incidence of relapse (CIR) of patients with (mutRAS) and without (wild-type; wtRAS) RAS mutations. Results Thirty-four patients (18%) had RAS mutations. With 12.9 years median follow-up, the 10-year CIR was similar for mutRAS and wtRAS patients (65% v 73%; P = .31). However, mutRAS patients receiving high-dose cytarabine consolidation (HDAC; 3 g/m2 every 12 hours on days 1, 3, and 5 or 400 mg/m2/d × 5 days) had the lowest 10-year CIR, 45%, compared with 68% for wtRAS patients receiving HDAC and 80% and 100%, respectively, for wtRAS and mutRAS patients receiving low-dose cytarabine (LDAC; 100 mg/m2/d × 5 days; overall comparison, P < .001). Multivariable analysis revealed an interaction of cytarabine dose and RAS status (P = .06). After adjusting for this interaction and cytogenetics (core binding factor [CBF] AML v non-CBF AML), wtRAS patients receiving HDAC had lower relapse risk than wtRAS patients receiving LDAC (hazard ratio [HR] = 0.67; P = .04); however, mutRAS patients receiving HDAC had greater reduction in relapse risk (HR = 0.28; P = .002) compared with mutRAS patients treated with LDAC. Conclusion AML patients carrying mutRAS benefit from higher cytarabine doses more than wtRAS patients. This seems to be the first example of an activating oncogene mutation favorably modifying response to higher drug doses in AML.

scholarly journals Does high-dose cytarabine cause cumulative toxicity in patients undergoing consolidation therapy for acute myeloid leukemia?

2013 ◽  
Vol 88 (6) ◽  
pp. 533-534 ◽  
Author(s):  
Andres Wiernik ◽  
Wolfgang R. Sperr ◽  
Daniel Weisdorf ◽  
Peter Valent ◽  
Celalettin Ustun
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
High Dose ◽  
Consolidation Therapy ◽  
Cumulative Toxicity ◽  
High Dose Cytarabine ◽  
Acute Myeloid

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.

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