Contributions of host- and disease-related attributes to the outcome of patients with acute myelogenous leukemia.

1984 ◽  
Vol 2 (4) ◽  
pp. 253-259 ◽  
Author(s):  
J E Curtis ◽  
H A Messner ◽  
R Hasselback ◽  
T M Elhakim ◽  
E A McCulloch
Keyword(s):  
Acute Myelogenous Leukemia ◽  
Drug Sensitivity ◽  
Multivariate Analyses ◽  
Myelogenous Leukemia ◽  
Remission Induction ◽  
First Year ◽  
Similar Response ◽  
Acute Myelogenous ◽  
One Year ◽  
Sequential Trials

Three sequential trials of treatment for acute myelogenous leukemia (AML) involving 173 patients were analyzed to identify clinical and myeloblast-cell progenitor properties in culture related to outcome. The latter, including self-renewal capacity expressed as plating efficiency (PE2) and drug sensitivity, were determined for a representative group of 45 patients. Despite increasingly intensive remission induction therapy, similar response rates were achieved in the three trials and no increase in the duration of survival was observed. Clinical attributes at presentation by multivariate analyses were not consistently predictable of outcome. Of the blast cell attributes, only PE2 was predictive of duration of survival (p less than 10(-6)). For patients in remission the relapse rate during the first year was 0.63 compared with 0.15 in subsequent years. The percentage marrow myeloblasts at presentation, a measure of disease activity, was significantly higher for the patients having remissions lasting less than one year. These studies demonstrate the importance of disease-related attributes on the outcome of patients with AML.

Improved survival for patients with acute myelogenous leukemia.

1995 ◽  
Vol 13 (3) ◽  
pp. 560-569 ◽  
Author(s):  
A J Mitus ◽  
K B Miller ◽  
D P Schenkein ◽  
H F Ryan ◽  
S K Parsons ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Remission Induction ◽  
Term Survival ◽  
Free Survival ◽  
Significant Difference ◽  
Acute Myelogenous ◽  
To Receive

PURPOSE Despite improvement in chemotherapy and supportive care over the past two decades, overall survival for patients with acute myelogenous leukemia (AML) remains poor; only 25% to 30% of individuals with this disorder will be cured. In 1987, we initiated a prospective multiinstitution study designed to improve long-term survival in adults with AML. METHODS We modified the usual 7-day treatment scheme of daunorubicin and cytarabine with high-dose cytarabine (HiDAC) on days 8 through 10 (3 + 7 + 3). Allogeneic or autologous bone marrow transplantation (BMT) was offered to all patients who entered complete remission (CR) to decrease the rate of leukemic relapse. Data were analyzed by intention to treat. RESULTS CRs were achieved in 84 of 94 patients (89%; 95% confidence interval [CI], 83 to 95). Because of the high remission rate, factors previously thought to predict outcome, such as cytogenetics, WBC count, French-American-British (FAB) classification, sex, and age, were not useful prognostic variables. The overall survival rate for the entire cohort of patients from data of diagnosis is 55% at 5 years. Sixty percent of all patients who achieved a CR underwent marrow grafting. There was no significant difference in event-free survival (EFS) at 5 years comparing patients assigned to receive allogeneic BMT with patients assigned to receive autologous BMT (56% v 45%, P = .54). CONCLUSION The long-term disease-free survival observed in this study is excellent compared with historical data. This improvement in survival is probably due to the high rate of remission induction, as well as to the effective nature of the consolidation therapy.

scholarly journals Topoisomerase II levels and drug sensitivity in adult acute myelogenous leukemia

Blood ◽  
1994 ◽  
Vol 83 (2) ◽  
pp. 517-530 ◽  
Author(s):  
SH Kaufmann ◽  
JE Karp ◽  
RJ Jones ◽  
CB Miller ◽  
E Schneider ◽  
...  
Keyword(s):  
Acute Myelogenous Leukemia ◽  
Topoisomerase Ii ◽  
Drug Sensitivity ◽  
Myelogenous Leukemia ◽  
Clinical Samples ◽  
Immunoperoxidase Staining ◽  
Acute Myelogenous ◽  
Topo Ii

Abstract The topoisomerase (topo) II-directed agents etoposide, daunorubicin (DNR), and amsacrine (m-AMSA) are widely used in the treatment of acute myelogenous leukemia (AML). In the present study, multiple aspects of topo II-mediated drug action were examined in marrows from adult AML patients. Colony-forming assays revealed that the dose of etoposide, DNR, or m-AMSA required to diminish leukemic colony formation by 90% (LD90) varied over a greater than 20-fold range between different pretreatment marrows. Measurement of nuclear DNR accumulation in the absence and presence of quinidine revealed evidence of P-glycoprotein (Pgp) function in 8 of 82 samples at diagnosis and 5 of 36 samples at first relapse, but the largest quinidine-induced increment in DNR accumulation (< 2-fold) was too small to explain the variations in drug sensitivity. Restriction enzyme-based assays and sequencing of partial topo II alpha and topo II beta cDNAs from the most highly resistant specimens failed to demonstrate topo II gene mutations that could account for resistance. Western blotting of marrow samples containing greater than 80% blasts revealed that the content of the two topo II isoenzymes varied over a greater than 20-fold range, but did not correlate with drug sensitivity in vitro or in vivo. In addition, levels of topo II alpha and topo II beta in 46 of 47 clinical samples were lower than in human AML cell lines. Immunoperoxidase staining showed that these low topo II levels were accompanied by marked cell-to- cell heterogeneity, with topo II alpha being abundant in some blasts and diminished or absent from others. There was a trend toward increasing percentages of topo II alpha-positive cells in pretreatment marrows that contained more S-phase cells. Consistent with this observation, treatment of patients with granulocyte-macrophage colony- stimulating factor for 3 days before chemotherapy resulted in increases in topo II alpha-positive cells concomitant with increases in the number of cells traversing the cell cycle. These observations have implications for the regulation of topo II in AML, for the use of topo II-directed chemotherapy, and for future attempts to relate drug sensitivity to topo II levels in clinical material.

Short-term remission induction and consolidation therapy for adult acute myelogenous leukemia

2006 ◽  
Vol 9 (1) ◽  
pp. 43-52 ◽  
Author(s):  
R. Battista ◽  
R. Bassan ◽  
A. D'Emilio ◽  
P. Dragone ◽  
P. Viero ◽  
...  
Keyword(s):  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Remission Induction ◽  
Consolidation Therapy ◽  
Short Term ◽  
Acute Myelogenous

scholarly journals Levels of retinoblastoma protein expression in newly diagnosed acute myelogenous leukemia

Blood ◽  
1994 ◽  
Vol 84 (1) ◽  
pp. 256-261 ◽  
Author(s):  
SM Kornblau ◽  
HJ Xu ◽  
W Zhang ◽  
SX Hu ◽  
M Beran ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Acute Myelogenous Leukemia ◽  
Therapy Monitoring ◽  
Retinoblastoma Protein ◽  
Myelogenous Leukemia ◽  
Leukemic Cells ◽  
Remission Induction ◽  
Newly Diagnosed ◽  
Rb Protein ◽  
Acute Myelogenous

Abstract The relationship between the level of retinoblastoma protein (RB) expression and the survival of 113 newly diagnosed acute myelogenous leukemia (AML) patients was studied. Western blotting was used to determine the level of RB protein present in peripheral blood leukemia cells and results were confirmed in 26 patients by immunohistochemistry. The leukemic cells from 22/113 AML patients (19%) contained RB protein at levels that were equal to or less than the level of RB observed in the mononuclear cell fraction of peripheral blood from normal individuals (Low RB). Levels of RB greater than that of normal blood (Elevated RB) were seen in 91 patients (81%). The median survival of patients with low RB was significantly shorter than that seen in patients with elevated RB, 12 weeks versus 40 weeks (P = .02). Remission induction frequency was 36% in low RB patients compared with 68% in AML patients with elevated RB (P = .01). Multivariate analysis showed that low RB protein level was an independent prognostic factor predictive or poor survival after allowing for other known prognostic factors. These data suggest that a low level of the RB protein at the time of diagnosis is associated with shortened survival in AML patients because of inferior response to conventional therapy. Monitoring of the RB level could identify a subgroup of AML patients with an extremely poor prognosis when treated with chemotherapy alone, who would be eligible for alternative therapeutic strategies.

scholarly journals Levels of retinoblastoma protein expression in newly diagnosed acute myelogenous leukemia

Blood ◽  
1994 ◽  
Vol 84 (1) ◽  
pp. 256-261
Author(s):  
SM Kornblau ◽  
HJ Xu ◽  
W Zhang ◽  
SX Hu ◽  
M Beran ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Acute Myelogenous Leukemia ◽  
Therapy Monitoring ◽  
Retinoblastoma Protein ◽  
Myelogenous Leukemia ◽  
Leukemic Cells ◽  
Remission Induction ◽  
Newly Diagnosed ◽  
Rb Protein ◽  
Acute Myelogenous

The relationship between the level of retinoblastoma protein (RB) expression and the survival of 113 newly diagnosed acute myelogenous leukemia (AML) patients was studied. Western blotting was used to determine the level of RB protein present in peripheral blood leukemia cells and results were confirmed in 26 patients by immunohistochemistry. The leukemic cells from 22/113 AML patients (19%) contained RB protein at levels that were equal to or less than the level of RB observed in the mononuclear cell fraction of peripheral blood from normal individuals (Low RB). Levels of RB greater than that of normal blood (Elevated RB) were seen in 91 patients (81%). The median survival of patients with low RB was significantly shorter than that seen in patients with elevated RB, 12 weeks versus 40 weeks (P = .02). Remission induction frequency was 36% in low RB patients compared with 68% in AML patients with elevated RB (P = .01). Multivariate analysis showed that low RB protein level was an independent prognostic factor predictive or poor survival after allowing for other known prognostic factors. These data suggest that a low level of the RB protein at the time of diagnosis is associated with shortened survival in AML patients because of inferior response to conventional therapy. Monitoring of the RB level could identify a subgroup of AML patients with an extremely poor prognosis when treated with chemotherapy alone, who would be eligible for alternative therapeutic strategies.

scholarly journals A randomized comparison of postremission therapy in acute myelogenous leukemia: a Southeastern Cancer Study Group trial

Blood ◽  
1984 ◽  
Vol 63 (5) ◽  
pp. 1039-1045 ◽  
Author(s):  
WR Vogler ◽  
EF Winton ◽  
DS Gordon ◽  
MR Raney ◽  
B Go ◽  
...  
Keyword(s):  
Cytosine Arabinoside ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Remission Induction ◽  
Study Group ◽  
Cancer Study ◽  
Cancer Study Group ◽  
Acute Myelogenous ◽  
To Receive ◽  
Group Trial

Abstract The Southeastern Cancer Study Group conducted a post-remission induction randomized trial in adult acute myelogenous leukemia to assess the efficacy of alternate drug therapy during consolidation and of immunotherapy during maintenance. Of 508 evaluable patients entered into the study, 335 (66%) achieved a complete remission treated with a 7-day infusion of cytosine arabinoside at a dose of 100 mg/sq m/day and 3 days of daunorubicin at a dose of 45 mg/sq m/day. Those in remission were randomized to receive 3 courses of 1 of 3 consolidation regimens: (A) a continuous infusion of 5-azacytidine, 150 mg/sq m/day for 5 days; (B) 5-azacytidine plus beta-deoxythioguanosine, 300 mg/sq m/day for 5 days; or (C) cytosine arabinoside, 100 mg/sq m/day intravenously, and thioguanine, 100 mg/sq m orally every 12 hr, plus daunorubicin, 10 mg/sq m every 24 hr daily for 5 days. There was no difference in relapse rate among the 3 arms. Those completing consolidation and remaining in remission were randomized to 1 of 3 maintenance regimens: (D) chemotherapy, 5-day infusion of cytosine arabinoside and 2 days of daunorubicin (same doses as induction) given every 13 wk for 1 yr; (E) BCG given twice weekly for 1 mo and then monthly for 1 yr; or (F) the combination of regimens D and E. The median duration of remission was significantly better on regimen D (17.4 versus 9.4 and 9.5 mo), and median survival was 29 mo compared to 21 mo for the other regimens. Those given different drugs during consolidation than used for induction (regimens A and B) and subsequent chemotherapy for maintenance (regimen D) had the longest remission durations and survival. Immunotherapy was not as good as intensive chemotherapy for maintenance.

Cytarabine and Idarubicin (7 plus 3) Regimen for Remission Induction of Acute Myelogenous Leukemia

2002 ◽  
Vol 37 (11) ◽  
pp. 1158-1163
Author(s):  
Lanh Green ◽  
Dominic A. Solimando ◽  
J. Aubrey Waddell
Keyword(s):  
Cancer Chemotherapy ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Remission Induction ◽  
Malignant Diseases ◽  
Toxic Agents ◽  
Acute Myelogenous ◽  
Investigational Agents

The increasing complexity of cancer chemotherapy makes it mandatory that pharmacists be familiar with these highly toxic agents. This column focuses on the commercially available and investigational agents used to treat malignant diseases, reviewing issues related to the preparation, dispensing, and administration of cancer chemotherapy.

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