Alpha Hemolytic Streptococcal Infection During Intensive Treatment for Acute Myeloid Leukemia: A Report From the Children’s Cancer Group Study CCG-2891

2000 ◽  
Vol 18 (9) ◽  
pp. 1845-1855 ◽  
Author(s):  
Alan S. Gamis ◽  
William B. Howells ◽  
Joetta DeSwarte-Wallace ◽  
James H. Feusner ◽  
Jonathan D. Buckley ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Marrow Transplant ◽  
Infectious Complications ◽  
High Dose ◽  
Cancer Group ◽  
High Dose Cytarabine ◽  
Associated Risk Factors ◽  
Acute Myeloid

PURPOSE: Past reports indicate that alpha hemolytic streptococcal (AHS) organisms are a common cause of infection among acute myeloid leukemia (AML) patients. This study was intended to ascertain the population incidence and rate (infections per 100 patient-days of treatment) of AHS and to identify associated risk factors. PATIENTS AND METHODS: Patients (n = 874 with 151,350 days of risk) enrolled on the Children’s Cancer Group (CCG) protocol for newly diagnosed AML, CCG-2891, which randomly assigned intensity of induction and intensification, were prospectively evaluated for infectious complications. RESULTS: AHS occurred in 21% of patients, was primarily blood borne (86%), made up 21% of bacteremic infections, and had a recurrent incidence of 31% during subsequent therapy. AHS was more often life-threatening (59%) than other infections (41%) (P = .001). AHS rates increased with age less than 10 years (odds ratio [OR], 2.0; P = .007), intensively timed induction (OR, 1.8 to 1.9; P = .02), and high-dose cytarabine intensification (OR, 3.7; P < .0001). Among all courses, the greatest incidence (19%) and rate (0.41) were associated with the use of high-dose cytarabine. Gastrointestinal toxicity correlated significantly with AHS bacteremia (P < .01). Infection with AHS resulted in increased hospital days (P = .0001). Only among bone marrow transplant patients were overall survival (OR, 2.8; P = .0001) and disease-free survival (OR, 2.1; P = .008) decreased after AHS bacteremia. CONCLUSION: This study, the first to prospectively examine AHS incidence among uniformly treated patients in multiple institutions, established that as the intensity of AML therapy has increased, so has the rate of AHS. Young children, those with previous AHS bacteremias, and those receiving high-dose cytarabine are at particularly high risk of AHS bacteremia.

scholarly journals A randomized study of high-dose cytarabine in induction in acute myeloid leukemia [see comments]

Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1710-1717 ◽  
Author(s):  
JF Bishop ◽  
JP Matthews ◽  
GA Young ◽  
J Szer ◽  
A Gillett ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Dose Effect ◽  
Induction Treatment ◽  
High Dose ◽  
Remission Duration ◽  
High Dose Cytarabine ◽  
Acute Myeloid

Abstract High-dose cytarabine (ara-c) may overcome cytarabine resistance in leukemic blasts. It has been used as a successful salvage and in postremission therapy but not as initial induction treatment. Patients aged 15 to 60 years, presenting with newly diagnosed acute myeloid leukemia (AML) were randomized to receive either high-dose cytarabine, 3 g/m2 12 hourly on days 1, 3, 5, and 7 for 8 doses, daunorubicin 50 mg/m2 days 1 to 3, etoposide 75 mg/m2 days 1 to 7, (HIDAC-3–7) or standard dose cytarabine 100 mg/m2 continuous intravenous infusion for 7 days with daunorubicin and etoposide at the same dose and schedule as above (7–3–7). Patients could receive a second or third induction course if complete remission (CR) was not achieved. All patients received the same postinduction consolidation therapy (5–2–5) for 2 courses. Eligible patients had no prior chemotherapy or myelodysplastic disease. Patients have been followed for a median of 4.5 years. Of 301 patients treated, complete response (CR) was achieved in 71% with HIDAC- 3–7 and 74% with 7–3–7. For patients in CR, the estimated median remission duration was 45 months with HIDAC-3–7 and 12 months with 7–3– 7 (P = .0005 univariate analysis, P = .0004 multivariate analysis). The estimated percentage of patients relapse free 5 years after achieving a CR was 49% on HIDAC-3–7 and 24% on 7–3–7. Patients in CR tended to survive longer with HIDAC-3–7 but there were no overall survival differences between the two arms. HIDAC-3–7 was associated with significantly more toxicity in induction with more leukopenia, thrombocytopenia, nausea, and vomiting and eye toxicity (all P < .001) but a similar incidence of severe central nervous system and cerebellar toxicity compared to 7–3–7. The consolidation treatment was the same in both arms but caused significantly more leukopenia and thrombocytopenia in patients previously treated with HIDAC-3–7 induction (P < .0001). We conclude that a dose-effect exists for cytarabine in AML and that HIDAC- 3–7 prolongs remission duration and disease-free survival and is tolerable when used as initial induction therapy in patients with de novo AML.

High-Dose Cytarabine Consolidation With or Without Additional Amsacrine and Mitoxantrone in Acute Myeloid Leukemia: Results of the Prospective Randomized AML2003 Trial

2013 ◽  
Vol 31 (17) ◽  
pp. 2094-2102 ◽  
Author(s):  
Markus Schaich ◽  
Stefani Parmentier ◽  
Michael Kramer ◽  
Thomas Illmer ◽  
Friedrich Stölzel ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Treatment Outcome ◽  
Myeloid Leukemia ◽  
Standard Dose ◽  
Disease Free Survival ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Significant Difference ◽  
High Dose Cytarabine ◽  
Acute Myeloid

Purpose To assess the treatment outcome benefit of multiagent consolidation in young adults with acute myeloid leukemia (AML) in a prospective, randomized, multicenter trial. Patients and Methods Between December 2003 and November 2009, 1,179 patients (median age, 48 years; range, 16 to 60 years) with untreated AML were randomly assigned at diagnosis to receive either standard high-dose cytarabine consolidation with three cycles of 18 g/m2 (3× HD-AraC) or multiagent consolidation with two cycles of mitoxantrone (30 mg/m2) plus cytarabine (12 g/m2) and one cycle of amsacrine (500 mg/m2) plus cytarabine (10 g/m2; MAC/MAMAC/MAC). Allogeneic and autologous hematopoietic stem-cell transplantations were performed in a risk-adapted and priority-based manner. Results After double induction therapy using a 3 + 7 regimen including standard-dose cytarabine and daunorubicin, complete remission was achieved in 65% of patients. In the primary efficacy population of patients evaluable for consolidation outcomes, consolidation with either 3× HD-AraC or MAC/MAMC/MAC did not result in any significant difference in 3-year overall (69% v 64%; P = .18) or disease-free survival (46% v 48%; P = .99) according to the intention-to-treat analysis. Furthermore, MAC/MAMAC/MAC led to additional GI and hepatic toxicity and a higher rate of infection and bleeding, resulting in significantly shorter 3-year overall survival in the per-protocol analysis compared with 3× HD-AraC (63% v 72%; P = .04). Conclusion In younger adults with AML, multiagent consolidation using mitoxantrone and amsacrine in combination with high-dose cytarabine does not improve treatment outcome and confers additional toxicity.

Impact of high-dose cytarabine and asparaginase intensification on childhood acute myeloid leukemia: a report from the Childrens Cancer Group.

1993 ◽  
Vol 11 (3) ◽  
pp. 538-545 ◽  
Author(s):  
R J Wells ◽  
W G Woods ◽  
B C Lampkin ◽  
M E Nesbit ◽  
J W Lee ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Maintenance Therapy ◽  
Myeloid Leukemia ◽  
Survival Rates ◽  
Remission Induction ◽  
High Dose ◽  
Cancer Group ◽  
High Dose Cytarabine ◽  
Childhood Acute Myeloid Leukemia ◽  
Acute Myeloid

PURPOSE The purpose of this review was to determine the impact of high-dose cytarabine and asparaginase intensification, administered shortly after remission induction, on the outcome of childhood acute myeloid leukemia (AML). MATERIALS AND METHODS Three consecutive Childrens Cancer Group (CCG) trials of acute myeloid leukemia, CCG 251 (1979 to 1983), CCG 213P (1983 to 1985), and CCG 213 (1985 to 1989) with a total of 1,294 patients, were reviewed and provide the basis of this report. RESULTS CCG 213P demonstrated the importance of dose interval, in that two courses of cytarabine and asparaginase administered at 7-day intervals gave superior 5-year survival rates (58% v 41% from the end of induction, P < .04) to the same therapy administered at 28-day intervals. CCG 213 showed that there was no advantage to the maintenance therapy used for patients who received two courses of cytarabine and asparaginase at 7-day intervals (5-year survival, 68% [no maintenance] v 44% [maintenance] from the end of consolidation, P < .01). Inclusion of the 7-day interval cytarabine/asparaginase intensification was accompanied by an overall improvement in 5-year survival rates from diagnosis when compared with historical controls (CCG 213, 36% v CCG 251, 29%, P < .02) although other differences between these studies could also be responsible for the improvement seen. CONCLUSION High-dose cytarabine and asparaginase intensification eliminated the benefit of prolonged maintenance therapy in childhood AML and was accompanied by an overall improvement in survival.

scholarly journals Outcomes of Six-Dose High-Dose Cytarabine as a Salvage Regimen for Patients with Relapsed/Refractory Acute Myeloid Leukemia

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Brandi Anders ◽  
Lauren Veltri ◽  
Abraham S. Kanate ◽  
Alexandra Shillingburg ◽  
Nilay Shah ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Single Agent ◽  
Disease Free Survival ◽  
High Dose ◽  
Free Survival ◽  
High Dose Cytarabine ◽  
Refractory Acute Myeloid Leukemia ◽  
Acute Myeloid

Relapsed/refractory acute myeloid leukemia (RR-AML) is associated with poor prognosis and long-term disease-free survival requires allogeneic hematopoietic cell transplantation (allo-HCT). Limited data exists, regarding the optimal regimen to obtain remission prior to allo-HCT. Single agent high-dose cytarabine (10–12 doses administered every 12 hours) has been previously used as induction therapy. Six-dose high-dose cytarabine (HiDAC-6), commonly used as a consolidation regimen, has never been evaluated as induction therapy. We present a retrospective review of 26 consecutive patients with RR-AML receiving single agent cytarabine 3 g/m2intravenously every 12 hours on days 1, 3, and 5 for a total of six doses (HiDAC-6). Median follow-up for surviving patients was 10.4 months (range 1.6–112.2 months). Complete remission was obtained in 62% (54% CR and 8% CRi) of the patients. The median relapse-free survival (RFS) was 22.3 months (range 0.7–112 months), event-free survival (EFS) was 4.7 months (range 0.5–112 months), and the overall survival (OS) was 9.6 months (range 1–112 months). Thirty-five percent of patients were able to subsequently proceed to allo-HCT. Treatment-related toxicities included neutropenic fever (38%), infection (35%), neurotoxicity (8%), and skin toxicity (8%). This is the first study to demonstrate HiDAC-6 as an active treatment option for younger patients with RR-AML which can effectively serve as a bridge to allo-HCT without significant toxicity.

scholarly journals Acute Hepatotoxicity After High-Dose Cytarabine for the Treatment of Relapsed Acute Myeloid Leukemia: A Case Report

2018 ◽  
Vol 54 (3) ◽  
pp. 160-164 ◽  
Author(s):  
Samuel H. Fu ◽  
Alexander H. Flannery ◽  
Melissa L. Thompson Bastin
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Standard Of Care ◽  
The Elderly ◽  
Liver Function Tests ◽  
Marrow Transplant ◽  
Multiple Organ ◽  
High Dose ◽  
High Dose Cytarabine ◽  
Acute Myeloid

Purpose: Cytarabine is considered the standard of care for induction therapy in patients with acute myeloid leukemia (AML) who are preparing for bone marrow transplant. Summary: We report a case of a 72-year-old female presenting to the intensive care unit with hepatic failure after high-dose cytarabine (HiDAC) for the treatment of relapsed AML. The patient’s liver function tests (LFTs) were elevated acutely, with a mildly elevated bilirubin and a normal alkaline phosphatase. HiDAC was discontinued but her LFTs remained high for 9 days post discontinuation, and the patient eventually expired due to sepsis and multiple organ failure. We estimated the probability of the hepatotoxicity observed with HiDAC as probable based on a score of 5 on the Naranjo scale. Conclusion: Clinicians should be aware of the potential hepatotoxicity associated with HiDAC for patients with AML, specifically in the elderly population.

scholarly journals A randomized study of high-dose cytarabine in induction in acute myeloid leukemia [see comments]

Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1710-1717 ◽  
Author(s):  
JF Bishop ◽  
JP Matthews ◽  
GA Young ◽  
J Szer ◽  
A Gillett ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Dose Effect ◽  
Induction Treatment ◽  
High Dose ◽  
Remission Duration ◽  
High Dose Cytarabine ◽  
Acute Myeloid

High-dose cytarabine (ara-c) may overcome cytarabine resistance in leukemic blasts. It has been used as a successful salvage and in postremission therapy but not as initial induction treatment. Patients aged 15 to 60 years, presenting with newly diagnosed acute myeloid leukemia (AML) were randomized to receive either high-dose cytarabine, 3 g/m2 12 hourly on days 1, 3, 5, and 7 for 8 doses, daunorubicin 50 mg/m2 days 1 to 3, etoposide 75 mg/m2 days 1 to 7, (HIDAC-3–7) or standard dose cytarabine 100 mg/m2 continuous intravenous infusion for 7 days with daunorubicin and etoposide at the same dose and schedule as above (7–3–7). Patients could receive a second or third induction course if complete remission (CR) was not achieved. All patients received the same postinduction consolidation therapy (5–2–5) for 2 courses. Eligible patients had no prior chemotherapy or myelodysplastic disease. Patients have been followed for a median of 4.5 years. Of 301 patients treated, complete response (CR) was achieved in 71% with HIDAC- 3–7 and 74% with 7–3–7. For patients in CR, the estimated median remission duration was 45 months with HIDAC-3–7 and 12 months with 7–3– 7 (P = .0005 univariate analysis, P = .0004 multivariate analysis). The estimated percentage of patients relapse free 5 years after achieving a CR was 49% on HIDAC-3–7 and 24% on 7–3–7. Patients in CR tended to survive longer with HIDAC-3–7 but there were no overall survival differences between the two arms. HIDAC-3–7 was associated with significantly more toxicity in induction with more leukopenia, thrombocytopenia, nausea, and vomiting and eye toxicity (all P < .001) but a similar incidence of severe central nervous system and cerebellar toxicity compared to 7–3–7. The consolidation treatment was the same in both arms but caused significantly more leukopenia and thrombocytopenia in patients previously treated with HIDAC-3–7 induction (P < .0001). We conclude that a dose-effect exists for cytarabine in AML and that HIDAC- 3–7 prolongs remission duration and disease-free survival and is tolerable when used as initial induction therapy in patients with de novo AML.

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