Comorbidity Predicts Outcome for AML in Older Adults
Comorbidity Predicts Outcome for AML in Older Adults
Abstract & Commentary
By Andrew S. Artz, MD, MS, Section of Hematology Oncology, University of Chicago. Dr. Artz reports no financial relationship to this field of study.
Synopsis: AML most commonly occurs in older adults. Predictors of chemotherapy tolerance are sorely needed. The haematopoietic cell transplantation comorbidity index (HCT-CI) has been validated to predict outcomes after allogeneic hematopoietic transplant. Using this index, Giles and colleagues studied 177 adults 60 years and over who received a uniform induction regimen of idarubicin and cytarabine. HCT-CI scores of 0, 1-2, and 3 were found in 22%, 30% and 48% of participants. Early death occurred 3% scoring a 0, 11% scoring 1-2, and 29% scoring a 3 or higher (P < 0.001). Lower median overall survival also correlated with higher HCT-CI scores. More comorbidity as defined by the HCT-CI is predicted for more early death and inferior overall survival for older AML patients receiving induction chemotherapy. Future studies are needed to validate this index and assess the additive value of functional status.
Source: F. Giles, et al. Br. J. Haematology. 2007;136:624-626.
The incidence of AML rises steeply with advancing age. Older age also portends a worse prognosis for AML, in part due to adverse biologic disease characteristics including prior MDS, unfavorable cytogenetics, and increased expression of the multi-drug resistance protein.1, 2 A recent cooperative group analysis of AML in adults 60 years and over reported 5 year survival at only 6.6%.3 The results probably paint an overly optimistic picture since cooperative group trials of intensive chemotherapy exclude many older and less fit patients.
The poor long-term outcome is compounded by concerns about acute toxicity and mortality related to intensive chemotherapy in older adults who frequently have complicating health conditions. Surprisingly, there has been scant data defining factors that increase the risk toxicity and death for receiving chemotherapy for AML.
Comorbidity indexes have been frequently used to summarize relevant medical conditions and predict toxicity and long-term survival. Typically, a numerical score is generated from known medical conditions. Higher scores reflect a greater burden of comorbid conditions. One of the first and most widely applied tools was the Charlson Comorbidity Index (CCI).4, 5 A modified instrument based upon the CCI was developed by researchers at the Fred Hutchinson Cancer Research Center to better predict toxicity from allogeneic hematopoietic cell transplantation. This hematopoietic cell transplant comorbidity index (HCT-CI) incorporated additional comorbid conditions and objective laboratory parameters and thus detected at least one abnormality in five times more patients than the CCI alone.6 Higher HCT-CI scores independently predicted for mortality related to transplant and overall survival.
In this study, researchers from the MD Anderson Cancer Center examined the HCT-CI among adults 60 years old who were undergoing induction chemotherapy for AML at their center since 1990. They evaluated 177 patients who received an idarubicin and cytarabine regimen. The median age was 70 years, 26% had an ECOG performance status of 2 or greater, and 90% had unfavorable cytogenetics.
Across all patients, scores of 0, 1-2, and 3 or greater were detected in 22%, 30%, and 48%, respectively. The most common comorbid diseases included cardiac (41%) and infectious (24%). The three strata of HCT-CI scores predicted outcomes for complete remission (CR), early death (death within 28 days of starting), and overall survival (OS). The CR rates were 64%, 43%, and 42%, and early death was 3%, 11%, and 29% (P < 0.001) based upon HCT-CI of 0, 1-2, and 3 or greater. A higher HCT-CI score also predicted worse overall survival (P = 0.04). Median overall survival was 45 weeks in those with an HCT-CI score of 0 as opposed to only 19 weeks in those scoring 3 or greater.
Commentary
This short report addresses the common problem for the practicing oncologist of determining whether an older adult with AML will tolerate intensive chemotherapy. Giles and colleagues, using standard intensive chemotherapy of idarubicin and cytarabine, showed that the HCT-CI can be useful in predicting not only early death but also overall survival.
For those harboring 3 or more conditions on the HCT-CI, a critical threshold reported in the original description of the HCT-CI, overall survival was only 19 weeks and early death was 29%. Alternatively, the early death rate was only 3% in the low risk group defined as having no comorbid conditions by the HCT-CI. The median OS was still only 10 months in this low risk group, reiterating the poor prognosis in older AML patients.
Several shortcoming in the HCT-CI tool itself warrants discussion. At least one of the elements of the tool (infections after therapy requiring treatment) cannot be assessed at baseline and thus must be revised in future studies. Second, the original HCT-CI required pulmonary function studies, which are not routinely performed before chemotherapy. Third, how one scores malignancy must be clarified. Most have advocated not scoring the hematologic condition for which therapy is being pursued (ie, no points would be given for AML). However, in older patients, a considerable fraction may have had a recently treated prior malignancy resulting in therapy related AML. Prior malignancy not only represents a comorbid condition to be scored by the HCT-CI, but also could be associated with more aggressive AML. Thus, we must determine if the HCT-CI has independent utility in therapy related AML.
Finally, the curious lack of adjustment for known prognostic factors, such as disease factors or performance status, limits our ability to independently attribute HCT-CI score and outcome.
The HCT-CI may have value now to account for patient health in comparative studies. Also, the HCT-CI may guide clinicians when providing prognostic information to patients and their families about treatment, particularly regarding early death rates.
Ultimately, prospective validation using a larger number of patients and various treatment regimens will be necessary to validate the HCT-CI in older AML patients. In the future, treatment could be dictated by not only the risk group defined by the disease (ie, cytogenetic risk groups), but also by patient health status. Nevertheless, more precision will be needed before we can allocate patients to different treatment regimens based upon a health score. It is likely that precise prognostic information mandates inclusion of functional status as well as comorbid conditions as even using performance status, a crude functional status measure, is a consistent and powerful adverse prognostic factor across cancers and treatments. Whether other novel prognostic factors such as measures of C-reactive protein (CRP) will further refine estimates of induction tolerance requires study.
In summary, the HCT-CI significantly predicted outcome among uniformly treated older AML patients.
References
1. Leith CP, et al. Acute myeloid leukemia in the elderly: assessment of multidrug resistance (MDR1) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy. A Southwest Oncology Group study. Blood. 1997;89:3323-3329.
2. Appelbaum FR, et al: Age and acute myeloid leukemia. Blood. 2006;107:3481-3485.
3. Farag SS, et al. Pretreatment cytogenetics add to other prognostic factors predicting complete remission and long-term outcome in patients 60 years of age or older with acute myeloid leukemia: results from Cancer and Leukemia Group B 8461. Blood. 2006;108:63-73.
4. Charlson ME, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373-83.
5. Charlson M, Szatrowski TP, Peterson J, et al: Validation of a combined comorbidity index. J Clin Epidemiol. 1994;47:1245-1251.
6. Sorror ML, et al: Hematopoietic cell transplantation-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106:2912-2919.
AML most commonly occurs in older adults. Predictors of chemotherapy tolerance are sorely needed. The haematopoietic cell transplantation comorbidity index (HCT-CI) has been validated to predict outcomes after allogeneic hematopoietic transplant.Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.