Abstract 2139

Introduction:

Secondary AML (sAML), a well recognized poor prognostic factor in AML, is a heterogeneous group of diseases, including both AML evolving from myelodysplastic syndromes (MDS, MDS→AML) and AML following chemotherapy for another malignancy, i.e. treatment-related AML (tAML). These two subtypes of poor risk AML have similar outcomes when treated with the same cytarabine-based chemotherapy regimen, supporting their inclusion into the same clinical category. A combined data set of patients from a single centre and a phase II study was analyzed to determine which patient and disease factors were of prognostic significance in predicting response to treatment. This is a large data set of sAML patients including patients treated with a variety of cytarabine-based induction regimens.

Materials and Methods:

Data from 77 newly diagnosed sAML patients treated with cytarabine-based induction chemotherapy at the Cleveland Clinic between 1997 and 2007 and 88 newly diagnosed sAML patients treated with amonafide + cytarabine in a phase II study were combined. The focus of the analysis was to ascertain the prognostic factors affecting overall survival (OS) from time of diagnosis. Initially, univariate Cox proportional hazard models for each prognostic factor were fitted. Hazard ratios and their associated 95% confidence intervals and Wald test p-values were produced. Prognostic factors were: age at diagnosis (<60 years, ≥60 years), gender (male, female), WBC (<20 x109/L, ≥20 x109/L), peripheral blasts (<20%, ≥20%), bone marrow blasts (<40%, ≥40%), cytogenetics CALGB class (unfavorable, intermediate, favorable, unknown), secondary disorder class (MDS, tAML), prior chemotherapy (yes, no), prior radiotherapy (yes, no). Subsequently a multivariate model was produced using the stepwise selection method and a significance level of 5%, having imputed missing data with mean/median values as appropriate.

Results:

In the combined data set of 165 patients with newly diagnosed sAML, the results for each significant prognostic factor are outlined in the table below.

Prognostic factorCategoryNP-valueHazard ratio
Age at diagnosis (years) <60 63 <0.01 0.60 
≥60* 102   
Gender Female 87 <0.01 0.60 
Male* 78   
Cytogenetics Favorable 12 <0.01 0.12 
Intermediate 63 <0.01 0.49 
Unfavorable* 60   
Unknown 30 0.08 0.65 
Secondary disorder class MDS 82 <0.01 1.68 
tAML* 83   
Prior chemotherapy No 89 0.02 1.52 
Yes* 76   
Prior radiotherapy No 117 <0.01 1.81 
Yes* 48   
Prognostic factorCategoryNP-valueHazard ratio
Age at diagnosis (years) <60 63 <0.01 0.60 
≥60* 102   
Gender Female 87 <0.01 0.60 
Male* 78   
Cytogenetics Favorable 12 <0.01 0.12 
Intermediate 63 <0.01 0.49 
Unfavorable* 60   
Unknown 30 0.08 0.65 
Secondary disorder class MDS 82 <0.01 1.68 
tAML* 83   
Prior chemotherapy No 89 0.02 1.52 
Yes* 76   
Prior radiotherapy No 117 <0.01 1.81 
Yes* 48   
*

Represents the prognostic factor category used as reference (i.e. to which other categories are compared).

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The final multivariate model (displayed in the table below) determined unfavorable cytogenetics, male gender and advanced age as prognostic factors predictive of worse OS.

Prognostic factorCategoryP-valueHazard ratio
Cytogenetics Favorable <0.01 0.13 
Intermediate <0.01 0.48 
Unfavorable*   
Unknown 0.12 0.68 
Gender Female <0.01 0.61 
Male*   
Age at diagnosis (years) <60 0.01 0.62 
≥60*   
Prognostic factorCategoryP-valueHazard ratio
Cytogenetics Favorable <0.01 0.13 
Intermediate <0.01 0.48 
Unfavorable*   
Unknown 0.12 0.68 
Gender Female <0.01 0.61 
Male*   
Age at diagnosis (years) <60 0.01 0.62 
≥60*   
*

Represents the prognostic factor category used as reference (i.e. to which other categories are compared).

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Conclusions:

In a combined data set of 178 patients with sAML from 22 US centers, cytogenetics, age and gender were identified as prognostic factors of significance in determining the outcome when treating sAML patients with induction chemotherapy. For patients with these risk factors, additional therapeutic strategies, including early stem cell transplantation, should be considered.

Disclosures:

Tejura: Antisoma: Employment. Sekeres: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Topics:
leukemia, secondary acute, prognostic factors, chemotherapy regimen, cytarabine, chemotherapy, neoadjuvant, radiation therapy, cancer, hematopoietic stem cell transplantation, myelodysplastic syndrome, myeloid leukemia, acute, therapy related

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2010 by The American Society of Hematology
2010
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