Acute Myelogenous Leukemia Patients Are at Low Risk for Invasive Fungal Infections after High-Dose Cytarabine Consolidations and Thus Do Not Require Prophylaxis

2010 ◽  
Vol 124 (4) ◽  
pp. 206-213 ◽  
Author(s):  
Grant Lewis ◽  
Patricia Hall ◽  
Nihal Eisa ◽  
David Deremer ◽  
Robin Dobbins ◽  
...  
Keyword(s):  
Acute Myelogenous Leukemia ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Low Risk ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
High Dose Cytarabine ◽  
Acute Myelogenous

Does cranial irradiation reduce the risk for bone marrow relapse in acute myelogenous leukemia? Unexpected results of the Childhood Acute Myelogenous Leukemia Study BFM-87.

1993 ◽  
Vol 11 (2) ◽  
pp. 279-286 ◽  
Author(s):  
U Creutzig ◽  
J Ritter ◽  
M Zimmermann ◽  
G Schellong
Keyword(s):  
Bone Marrow ◽  
Acute Myelogenous Leukemia ◽  
Cranial Irradiation ◽  
Low Risk ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Number Of Patients ◽  
Acute Myelogenous ◽  
Wbc Count ◽  
Group B

PURPOSE One of the goals of study AMA-BFM-87 was to test prospectively in acute myelogenous leukemia (AML) patients if cranial irradiation could be replaced by late intensification therapy with high-dose cytarabine (Ara-C) and etoposide (VP-16). PATIENTS AND METHODS Patients with a low risk of CNS relapses (ie, no initial CNS disease, WBC count at diagnosis < or = 70.000/microL) were randomized for irradiation (group A, 31 patients). In 25 patients (group B), randomization was refused. As interim results showed no increase of CNS relapses in nonirradiated patients, prophylactic irradiation was discontinued after 2 1/2 years to prevent unnecessary CNS toxicity. Forty-four patients (group C) entered the study after randomization had been stopped. RESULTS In all patients with a low risk of CNS recurrences (n = 100), a significantly higher probability of relapse-free interval (pRFI) of 5 years was found in irradiated patients (pRFI = .78) compared with nonirradiated patients (pRFI = .41) (P = .007). Moreover, a slightly higher incidence of CNS relapses was observed in nonirradiated patients. Due to the small number of patients, this was not observed when randomized patients only were analyzed. In accordance with these findings, the favorable outcome of low-risk patients in the preceding study, AML-BFM-83 (pRFI > .80), could only be reproduced in study AML-BFM-87 in patients who had received cranial irradiation. CONCLUSION These results indicate that cranial irradiation should be an integral part of the treatment of all AML patients not undergoing bone marrow transplantation. Residual blasts in the CNS may escape systemic chemotherapy and lead to recurrence of the initial disease not only in the CNS, but also in the bone marrow.

Synergy between high-dose cytarabine and asparaginase in the treatment of adults with refractory and relapsed acute myelogenous leukemia--a Cancer and Leukemia Group B Study.

1988 ◽  
Vol 6 (3) ◽  
pp. 499-508 ◽  
Author(s):  
R L Capizzi ◽  
R Davis ◽  
B Powell ◽  
J Cuttner ◽  
R R Ellison ◽  
...  
Keyword(s):  
Median Time ◽  
Acute Myelogenous Leukemia ◽  
Standard Dose ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Time To Failure ◽  
Cutaneous Toxicity ◽  
High Dose Cytarabine ◽  
Acute Myelogenous ◽  
Refractory Aml

One hundred ninety-five adult patients with refractory or first relapse acute myelogenous leukemia (AML) were randomly assigned to receive high-dose cytarabine (HiDAC), 3 g/m2 as a three-hour intravenous (IV) infusion every 12 hours for four doses, followed by 6,000 IU/m2 asparaginase (ASNase) administered at hour 42, or HiDAC without ASNase. Treatment was repeated on day 8. The median patient age was 52 years. There was an overall superior complete remission (CR) rate for HiDAC/ASNase (40%) v HiDAC (24%), P = .02. Subset analysis according to prior response and age showed the following CR rates: 54% from HiDAC/ASNase treatment of refractory AML in patients less than 60 years, and 31% in patients greater than 60 years; CR from HiDAC in the same refractory groups were 18% (less than 60) and 0% (greater than 60); 37% from HiDAC/ASNase treatment of relapsed AML in patients less than 60 years, and 43% in patients greater than 60 years; CRs from HiDAC in the same relapsed groups were 33% (less than 60) and 21% (greater than 60). Toxicity in the two treatment arms was comparable and consisted primarily of leukopenia, thrombocytopenia, mild hepatic dysfunction, diarrhea, conjunctivitis and serositis, and hyperglycemia. There was only one case of transient cerebellar toxicity and no cutaneous toxicity. Median time to full hematologic recovery was 5 weeks. There was an overall survival benefit for patients treated with HiDAC/ASNase (19.6 weeks) compared with HiDAC (15.9 weeks), P = .046, primarily attributable to effects in refractory patients. Median time to failure for refractory patients who achieved CR was 38.5 weeks with HiDAC/ASNase, and 13.3 weeks for those treated with HiDAC. For relapsed patients in CR from HiDAC/ASNase the median time to failure was 17.7 weeks and 18.3 weeks for HiDAC. The overall 42% CR rate from HiDAC/ASNase v 12% from HiDAC in patients with refractory AML indicates that HiDAC/ASNase is not cross-resistant with standard-dose cytarabine (SDAC) and anthracyclines. We conclude that HiDAC/ASNase has substantial activity in poor-prognosis AML and that this combination warrants further trials in earlier stage disease.

Severe palmar-plantar erythrodysesthesia and aplasia in an adult undergoing re-induction treatment with high-dose cytarabine for acute myelogenous leukemia: a possible drug interaction between posaconazole and cytarabine

2016 ◽  
Vol 23 (6) ◽  
pp. 476-480 ◽  
Author(s):  
Saeed K Alzghari ◽  
Susan E Seago ◽  
Christian T Cable ◽  
Jon D Herrington
Keyword(s):  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Induction Treatment ◽  
High Dose ◽  
Pharmacokinetic Studies ◽  
P Glycoprotein ◽  
High Dose Cytarabine ◽  
Acute Myelogenous ◽  
Hands And Feet ◽  
Glycoprotein Inhibition

High-dose cytarabine is recommended for re-induction chemotherapy in patients less than 60 years of age with acute myelogenous leukemia. This case describes a patient receiving high-dose cytarabine for re-induction and subsequently developed tingling and numbness in her hands and feet followed by severe pain, swelling, and erythema consistent with a diagnosis of palmar-plantar erythrodysesthesia. Furthermore, the patient’s hemoglobin, platelets, and neutrophils did not recover after over 30 days post high-dose cytarabine. The patient was concurrently receiving posaconazole for fungal prophylaxis which was initiated after the induction therapy. We speculate that posaconazole may inhibit the cytarabine efflux through P-glycoprotein inhibition leading to the patient’s palmar-plantar erythrodysesthesia and subsequent aplasia. Future pharmacokinetic studies need to be conducted to ascertain if posaconazole does influence the pharmacokinetics of cytarabine.

scholarly journals High-dose cytarabine and daunorubicin induction and postremission chemotherapy for the treatment of acute myelogenous leukemia in adults

Blood ◽  
1991 ◽  
Vol 77 (7) ◽  
pp. 1429-1435 ◽  
Author(s):  
GL Phillips ◽  
DE Reece ◽  
JD Shepherd ◽  
MJ Barnett ◽  
RA Brown ◽  
...  
Keyword(s):  
Acute Myelogenous Leukemia ◽  
Previous History ◽  
Myelogenous Leukemia ◽  
Remission Induction ◽  
High Dose ◽  
Free Survival ◽  
High Dose Cytarabine ◽  
Acute Myelogenous ◽  
History Of ◽  
Leukocyte Counts

Seventy consecutive adult patients with acute myelogenous leukemia (AML), median age 44 years, received high-dose cytarabine (3 g/m2 every 12 hours for 12 doses) followed by daunorubicin (45 mg/m2 daily for three doses) for remission induction. A single, identical course was planned for postremission therapy. Complete remission (CR) was achieved in 63 patients (90%, 95% confidence interval [CI] 83% to 97%), 60 after a single course. Eight patients were selected to undergo elective bone marrow transplantation (BMT) during first CR. Of the remaining 55 patients, 40 (73%) underwent planned post-CR therapy; 15 patients did not, owing to early relapse, excessive toxicity from the induction chemotherapy, or refusal. Nineteen patients, including 13 who received planned post-CR therapy, remain in continuous CR at a median follow-up of 5.2 years (range 3.0 to 7.1 years). The 5-year actuarial leukemia- free survival was 30% (95% Cl, 19% to 42%) for all patients achieving CR and 32% (95% Cl, 19% to 47%) for the 40 patients who received the planned post-CR chemotherapy. Analysis of various putative prognostic factors for CR and overall and leukemia-free survival showed significance for a previous history of myelodysplasia, higher initial leukocyte counts, certain French-American-British (FAB) types, and certain abnormal karyotypes. None of these factors was consistently significant regarding the above parameters, although small patient numbers in certain analyses may have obscured significant associations. Myelosuppression was occasionally prolonged after remission induction and especially post-CR therapy. Severe cerebellar toxicity was observed in 13 patients; in 11 cases, this toxicity was fully reversible. Other serious complications were infrequent. Intensive chemotherapy with high- dose cytarabine and daunorubicin has substantial antileukemic activity in adult AML, and may represent an improvement over conventional therapy. Relapses were common, however, even in patients who received planned therapy, and substantial toxicity was observed. The optimum use of this regimen in AML remains to be determined.

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