Risk factors for high-dose cytarabine neurotoxicity: an analysis of a cancer and leukemia group B trial in patients with acute myeloid leukemia.

1992 ◽  
Vol 10 (6) ◽  
pp. 948-953 ◽  
Author(s):  
E H Rubin ◽  
J W Andersen ◽  
D T Berg ◽  
C A Schiffer ◽  
R J Mayer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Elevated Serum ◽  
High Dose ◽  
Increased Risk ◽  
High Dose Cytarabine ◽  
Group B ◽  
Leukemia Group ◽  
Acute Myeloid

PURPOSE We analyzed pretreatment characteristics of patients with postremission acute myeloid leukemia (AML) treated with high-dose cytarabine (HIDAC) during a recent Cancer and Leukemia Group B (CALGB) trial to determine risk factors associated with HIDAC neurotoxicity. PATIENTS AND METHODS One hundred seventy-six patients received at least one course of HIDAC as part of a CALGB protocol designed to determine the optimal dose of cytarabine (ara-C) for postremission treatment of AML. HIDAC consisted of 3 g/m2 ara-C infused over 3 hours at 12-hour intervals on days 1, 3, and 5. The pretreatment characteristics of 170 patients were available for risk analyses. RESULTS Eighteen patients (10%) experienced neurotoxicity. Univariate analyses demonstrated associations between the occurrence of neurotoxicity and elevated serum creatinine, age, and alkaline phosphatase (AP). Multivariate analysis showed that these variables were independent risk factors. These findings were used to construct a risk model with the following parameters: creatinine greater than or equal to 1.2 mg/dL, age greater than or equal to 40 years, and AP greater than or equal to 3 x normal. Seventeen of 46 (37%) patients with two or more of these criteria developed neurotoxicity compared with one of 124 (1%) patients with one or none. The sensitivity and specificity of this model were 94% and 81%, respectively. CONCLUSION We conclude that patients with two or more of the following parameters may be at increased risk for HIDAC neurotoxicity: (creatinine greater than or equal to 1.2 mg/dL, age greater than or equal to 40, and AP greater than or equal to 3 x normal). However, this model should be confirmed by analysis of additional groups of patients treated with HIDAC.

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.

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.

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, Feasibility, and Cost-Effectiveness with Outpatient Administration of High-Dose Cytarabine Consolidation in Acute Myeloid Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2405-2405 ◽  
Author(s):  
Gene A. Wetzstein ◽  
Jeffrey E. Lancet ◽  
Jennifer E. Kallner ◽  
Jeffrey M. Sivik ◽  
Viet Q. Ho ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
High Dose ◽  
Inpatient Setting ◽  
Institutional Review ◽  
High Dose Cytarabine ◽  
Inpatient Group ◽  
Grade Iii ◽  
Acute Myeloid

Abstract Introduction: High-dose cytarabine (HiDAC) consolidation chemotherapy is frequently used in acute myeloid leukemia (AML) patients less than 60 years of age. Traditionally, the potential risk for neurotoxicity, which has been reported to occur in 8–26% of patients, has limited its administration to the inpatient setting with a median length of stay of 5 days. Institutional retrospective data revealed the incidence to be much lower than previously reported with grade III/IV neurotoxicity in only 0.7% of cycles (N=267). As a result, we developed a comprehensive outpatient (OP) approach for the administration of HiDAC utilizing a pre-printed order and monitoring forms, pre-defined eligibility criteria/risk factors, administration/screening checklist, standard ancillary medications, designated scheduling, patient counseling, and written instructions for follow up. The benefits of OP administration may include improved patient satisfaction and decreased institutional costs and constraints on inpatient resources. However, there does not appear to be any published literature to date describing the OP administration of HiDAC. We report herein on the safety, feasibility, and outcomes of 43 patients receiving HiDAC consolidation therapy (n=88 cycles) between September 2006 and July 2008. Methods: Patients &lt; 60 yo received 3 g/m2 over 1 hour every 12 hours on days 1, 3, and 5 and the dose was reduced to 1.5 g/m2 for pts ≥ 60 yo. All cycles of HiDAC were dosed based on age, renal, and hepatic function. There were no empiric dosage adjustments based on renal function alone. Post-treatment, patients received antibiotic prophylaxis and growth-factor support. Patients returned twice weekly for blood work until neutrophil and count recovery. Results: Forty-three patients received 88 cycles of HiDAC as an OP. The median patient age was 49 yrs (23–74) with 16% being over 60. Patient baseline characteristics of the OP group were similar to the inpatient group from our institutional review with respect to age, body surface area, gender, and race. Diagnosis, history of CNS radiation/disease, intrathecal chemotherapy, alcohol abuse, cumulative cytarabine dosage, and concurrent medications were also similar between the two groups. Only 1 patient was ineligible to receive OP therapy which was the result of both renal (estCL &lt; 60mL/min) and hepatic (alk phos &gt; 3X ULN) risk factors. Two patients with moderate renal insufficiency (est CL 30–60 mL/min) received full dose HiDAC without adverse event. All 43 patients successfully completed their full course of therapy. During the 88 cycles, there were no cases of clinically significant neurotoxicity (≥ grade III). There were 3 instances of grade I nystagmus. In all cases, therapy was completed without interruption. Rates of admission to the hospital post HiDAC OP consolidation for neutropenic fever (NF) was comparable to the inpatient group from our institutional review, occurring in 26% and 37% (p=0.07), respectively. All admissions post HiDAC OP was secondary to NF with the exception of one patient who was admitted for mucosal bleeding. Conclusions: In the present analysis, we confirm the safety and feasibility of OP-based HiDAC chemotherapy for the management of AML patients in remission. If patients are dosed and monitored properly, HiDAC can be successfully transitioned to the OP setting. With the implementation of this approach, we have improved patient convenience and satisfaction, decreased pressure on inpatient resources (nearly 450 days of hospital bed use), while maintaining similar rates of hospital re-admission. With proper patient selection, dosing, and education of both providers and patients, HiDAC can be safely administered in the OP setting and has become our standard of care.

Sign in / Sign up

Export Citation Format

Share Document