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The Outcomes and Costs of Acute Myeloid Leukemia Among the Elderly
Joseph Menzin, PhD;
Kathleen Lang, PhD;
Craig C. Earle, MD;
Donna Kerney, PhD;
Rajiv Mallick, PhD
Arch Intern Med. 2002;162:1597-1603.
ABSTRACT
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Background The incidence of acute myeloid leukemia (AML) among the elderly can
be expected to grow as the population continues to age. However, data on current
treatment practices and costs for this form of cancer are sparse.
Methods We used a retrospective inception cohort design and data from a linkage
between 11 Surveillance, Epidemiology, and End Results cancer registries and
Medicare administrative claims. We evaluated survival, use of health care
resources, use of chemotherapy, and Medicare payments among adults 65 years
and older with an initial diagnosis of AML between January 1, 1991, and December
31, 1996.
Results A total of 2657 elderly patients with AML and complete Medicare claims
data were identified. The prognosis for these patients was poor, with median
survival estimated to be 2 months and a 2-year survival rate of 6%. Mean ±
SE total Medicare payments were $41 594 ± $870 (in 1998 US dollars),
84% of which was attributed to inpatient payments. In the 2 years after the
AML diagnosis, 790 patients (30%) underwent chemotherapy treatment. These
patients had costs almost 3 times higher than those of other patients, and
their median survival was 6 months longer. The use of hospice care was rare
(17% of patients).
Conclusions Among the elderly, AML is associated with a poor prognosis and substantial
costs during the relatively few remaining months of life. Moreover, most patients
do not receive active treatment with chemotherapy or hospice services. Further
work is needed to characterize this disease and the patient-related factors
that influence treatment decisions and associated health outcomes.
INTRODUCTION
ACUTE MYELOID leukemia (AML) is the most common type of acute leukemia
among US adults, with about 10 000 new cases reported annually.1 The incidence of AML increases with age and is almost
10 times greater among persons 65 years and older than among those younger
than 65 years (12.2 vs 1.3 per 100 000).2
If left untreated, AML usually results in death within a few months of diagnosis.1-2 Conventional cytotoxic chemotherapy
for AML can be associated with serious adverse effects and, as a result, often
cannot be tolerated by older patients.2 Consequently,
5-year survival is only 2% among elderly patients and has not improved appreciably
in the past 2 decades.3-4
Limited data are available on treatment practices or the associated
outcomes and costs after a diagnosis of AML in older patients. Most previous
studies characterize prognosis after the initial AML diagnosis in terms of
cytogenetics, hematologic factors, performance status, organ function, multidrug
resistance gene expression, and age, but these studies are based on data from
relatively small numbers of patients from clinical trials or individual study
centers whose experience may not be applicable to patients with AML treated
in typical practice settings.5-6
This study therefore used linked data from the Surveillance, Epidemiology,
and End Results (SEER) registries and Medicare claims to address the following
questions in a national-level cohort of elderly patients: (1) How do survival
and use of health care services vary by age within the elderly population
with AML? (2) What is the prevalence of the use of chemotherapy among these
patients? and (3) What factors influence the receipt of chemotherapy and associated
outcomes of AML treatment? The answers to these questions can provide an important
baseline against which the benefits of emerging therapies can be compared.
PATIENTS AND METHODS
DATA SOURCE
This study used clinical data from the SEER registries linked to Medicare
claims data. The SEER-Medicare database is a collaborative effort of the National
Cancer Institute (Bethesda, Md), the SEER registries, and the Centers for
Medicare and Medicaid Services (formerly, the Health Care Financing Administration)
(Baltimore, Md). The SEER registries comprise an epidemiological surveillance
system consisting of 11 population-based tumor registries designed to track
cancer incidence and survival in the United States. The registries routinely
collect information on patients with newly diagnosed cancer in geographically
defined areas that represent approximately 14% of the US population.
The SEER-Medicare linkage includes data for all persons with cancer
reported by the SEER registries between January 1, 1991, and December 31,
1996, who could be identified as Medicare enrollees. The SEER data items include
demographics (eg, age, sex, and race), and diagnostic information for up to
10 different incident cancer cases for each person, including month and year
of cancer diagnosis, cancer site and type (eg, AML), and vital status. The
Medicare details include monthly enrollment data (ie, Part A or B), a monthly
indicator for health maintenance organization (HMO) enrollment, and hospital,
outpatient, physician, home health care, hospice, and skilled nursing facility
(SNF) claims containing dates of service, a primary and up to 9 secondary
diagnoses and procedure codes from the International Classification
of Diseases, Ninth Revision, Clinical Modification, a diagnosis-related
group code (in the inpatient file), a health care procedure code (in the outpatient,
home health care, and hospice claims), and Medicare payments from 1991 through
1998 for all SEER patients eligible for Medicare sometime during this period.
With these data, we created a patient-level analytic file containing
the date of AML diagnosis (assumed to be the first day of the month of diagnosis
because only month and year of diagnosis were recorded in the SEER data, which
may slightly overestimate survival), date of death (if applicable), and a
summary of the use of Medicare services by category of service for each health
care encounter during the first 2 years after the diagnosis of AML. A 2-year
time frame was chosen for the analysis because it was the maximum amount of
time for which all patients could be followed up, and it would be expected
to capture the remaining lifetime costs of most patients with AML, given the
high rate of short-term mortality associated with this disease.
PATIENT SELECTION
All patients 65 years and older with a diagnosis of AML in a SEER registry
between January 1, 1991, and December 31, 1996, were candidates for inclusion
in the analysis. We defined AML as coded in the SEER data file (ie, cancer
site recode 77). We excluded patients whose month of diagnosis was unknown
or who were younger than 65 years at diagnosis. In addition, persons who were
enrolled in HMOs or who were not entitled to Medicare Parts A and B benefits
during the study period were excluded from the analyses because complete claims
were not available for them.
STUDY MEASURES
Survival was evaluated in terms of the percentage of patients alive
each month after the AML diagnosis and the median number of months after the
AML diagnosis that patients survived. Use of health care resources for all
causes was evaluated in terms of the percentages of patients who were hospitalized
and who received SNF care, hospice care, and home health care and the total
numbers of days in the hospital and in SNFs in the 2 years after the diagnosis.
In addition, for patients who died during follow-up, the percentage of remaining
days spent in a hospital or an SNF was calculated. Medicare payments were
evaluated overall (calculated as the sum of payments for hospital, SNF, home
health care, hospice, outpatient, and physician services) and by individual
category of care. All payments were converted to 1998 US dollars using the
medical care component of the Consumer Price Index.
The receipt of chemotherapy was evaluated as the presence of an inpatient
claim in the 2 years after the AML diagnosis indicating chemotherapy, as follows:
diagnosis code v58.1 (chemotherapy) or procedure code 99.25 (injection or
infusion of chemotherapy) from the International Classification
of Diseases, Ninth Revision, Clinical Modification or diagnosis-related
group codes 410 (chemotherapy without acute leukemia as a secondary diagnosis)
or 492 (chemotherapy with acute leukemia as a secondary diagnosis). The proportion
of patients who received chemotherapy was compared across patient groups stratified
on the basis of age, sex, and comorbidities in the year before the AML diagnosis.
Retreatment (for relapse of AML) during the study period was defined as the
presence of a claim for chemotherapy after at least 120 days with no chemotherapy
claims. This method of identifying patients treated for relapse of AML has
been validated in an independent sample of patients with AML.7
DATA ANALYSES
Study patients were described in terms of baseline characteristics,
including age at diagnosis, sex, race, year of AML diagnosis, comorbidities
in the previous year, and residence in a metropolitan area, to identify characteristics
that might influence study outcomes. Survival, receipt of chemotherapy, use
of health care resources, and costs were analyzed descriptively overall and
stratified by age at diagnosis, sex, race, presence of comorbidities, and
year of diagnosis. In addition to overall and stratified descriptive analyses,
multivariate analyses were undertaken to estimate the impact on study outcomes
of potentially confounding influences, including age at diagnosis, sex, race,
year of diagnosis, and residence in a metropolitan county. Models including
comorbidities in the year before diagnosis also were estimated (for the subset
of patients whose condition was diagnosed between January 1, 1992, and December
31, 1996, only, since those whose condition was diagnosed in 1991 did not
have a 1-year history available), but are not reported herein, since findings
were similar. Comorbidity was assessed using the Charlson Comorbidity Index
as adapted by Deyo et al.8
Least squares regression analyses were performed for inpatient days
and the logarithm of Medicare payments (a semilogarithmic model was estimated
because of nonnormal payments), and a Cox proportional hazards model was estimated
for the number of months of survival, with censoring of those still alive
24 months after diagnosis. In addition, a logistic model was estimated, including
the same covariates listed above to identify the characteristics that were
potentially associated with receipt of chemotherapy. Finally, characteristics
and outcomes among the subset of patients who received chemotherapy were evaluated,
and study measures were assessed by length of survival (ie, among patients
who survived longer vs shorter than the median survival). In all multivariate
analyses, P values of less than .05 were deemed statistically
significant. We used SAS, Version 8.0 (SAS Institute Inc, Cary, NC), in all
analyses.
RESULTS
PATIENT CHARACTERISTICS
From an initial sample of 3738 Medicare beneficiaries with a diagnosis
of AML between 1991 and 1996, 1081 patients (29%) were excluded. The reasons
included unknown month of diagnosis (n = 29), AML diagnosis at younger than
65 years (n = 509), and enrollment in an HMO (n = 495), nonentitlement to
Medicare benefits (n = 44), or both (n = 4). This left a total of 2657 Medicare
beneficiaries 65 years and older with an initial diagnosis of AML in a SEER
registry between 1991 and 1996 for inclusion in the analyses. The average
age at diagnosis was 77 years, and 51% of the patients were male (Table 1). Most patients were white (87%),
and most resided in metropolitan counties (84%). Based on information available
for the year before the AML diagnosis, congestive heart failure (7%) and chronic
obstructive pulmonary disease (7%) were the most common preexisting comorbidities.
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Table 1. Demographic and Regional Characteristics of Medicare Beneficiaries
With AML*
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SURVIVAL
In the first year after the diagnosis, 2273 (86%) of 2657 elderly patients
with AML died, and 94% died within 2 years (Figure 1). Median survival was 2 months overall, ranging from 1
month among patients 85 years and older to 3 months among those aged 65 to
74 years. Differences in survival based on age were statistically significant
on the basis of results of the log-rank test (P<.001).
Survival did not differ by sex, race, year of diagnosis, or residence in a
metropolitan county in the stratified analyses. Findings were similar based
on a multivariate Cox proportional hazards model, which indicated that the
risk for death was 50% greater among patients aged 75 to 84 years (P<.001) and 150% greater among patients 85 years and older (P<.001), relative to those aged 65 to 74 years.
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Twenty-four month survival rates after acute myeloid leukemia (AML)
diagnosis among Medicare beneficiaries, overall and by age group. Differences
in median survival were significant across all age groups (P<.001).
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USE OF HEALTH CARE SERVICES AND COSTS
In the first 2 years after the AML diagnosis, 89% of study patients
were hospitalized (Table 2). Patients
had a mean of 2.3 hospitalizations, for a mean total of 28.1 hospital days,
77% of which occurred in the first 2 months after the diagnosis. Twelve percent
of patients received care in SNFs for a mean of 2.4 days. Thirty-nine percent
of patients received home health care, and 17% received hospice care. Among
the patients who died during follow-up (94% of the sample), an average of
31% of their remaining days were spent in inpatient facilities. Total Medicare
payments (mean ± SE) among study patients in the 2 years after the
AML diagnosis were $41 590 ± $870 (Table 3), with 84% attributable to hospitalization costs. Physician
costs constituted 7% of total costs, whereas outpatient, SNF, home health
care, and hospice costs constituted 4%, 2%, 2%, and 1%, respectively. Median
payments were $25 705 (interquartile range, $14 970-$54 386).
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Table 2. Outcomes Associated With AML Among Medicare Beneficiaries
in the First 2 Years After Diagnosis*
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Table 3. Medicare Payments Associated With AML Among Medicare Beneficiaries
in the First 2 Years After Diagnosis by Age at Diagnosis*
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In stratified analyses, only small differences in use and costs of health
care resources were observed by sex, race, previous comorbidities, and year
of AML diagnosis. However, sizable differences were detected by age and residence
in a metropolitan county. On average, patients 85 years and older used fewer
hospital days (10.8 days) than those aged 75 to 84 years (23.5 days) and those
aged 65 to 74 years (39.3 days) (Table 2), consistent with the shorter survival times among the oldest patients.
The oldest patients also were somewhat less likely to use home health care
services. Mean ± SE total costs for all services were lowest among
the oldest patients ($21 771 ± $1180) compared with patients aged
75 to 84 years ($35 978 ± $1050) and 65 to 74 years ($54 720
± $1625) (Table 3). A similar
pattern was observed in terms of median total costs ($19 265 among patients  85
years, $24 829 among patients aged 75-84 years, and $36 962 among
patients aged 65-74 years). The distribution of costs by category of service
was similar across the age groups, with most costs attributable to hospitalization.
Finally, compared with patients living in nonmetropolitan areas, those living
in metropolitan counties had more hospital days (mean, 29 vs 23 days; median,
15 vs 11 days) and higher costs (mean, $43 580 vs $31 540; median,
$26 680 vs $19 760).
Multivariate models of inpatient days and total Medicare payments confirmed
the stratified results, indicating more than a $20 000 mean total cost
difference between the youngest and oldest age groups and close to a $10 000
difference between metropolitan and nonmetropolitan patients (P<.01 for both).
RECEIPT OF CHEMOTHERAPY
In the 2 years after the diagnosis of AML, 790 study patients (30%)
received chemotherapy. Treated patients tended to be younger than untreated
patients (average age, 73 vs 78 years), slightly more likely to live in metropolitan
counties (88% vs 82%), and more likely to have been diagnosed as having congestive
heart failure (8% vs 3%) or chronic obstructive pulmonary disease (8% vs 4%).
Sex and race did not significantly influence the likelihood of receiving chemotherapy
treatment. In multivariate analyses (logistic model) of chemotherapy use,
findings (given as odds ratios [ORs] and 95% confidence interval [CIs]) were
consistent, indicating that age (ORs, 0.39 [95% CI, 0.32-0.48] for 75-84 years
of age and 0.08 [95% CI, 0.05-0.12] for 85 years vs 65-74 years of age),
the presence of congestive heart failure (OR, 0.45 [95% CI, 0.27-0.76]), and
the presence of chronic obstructive pulmonary disease (OR, 0.53 [95% CI, 0.34-0.85])
were negatively associated with chemotherapy use, whereas residence in a metropolitan
county was positively associated with treatment (OR, 1.83 [95% CI, 1.39-2.44]).
On an overall basis, median survival was 6 months longer among treated
patients (7 vs 1 month). Longer survival was observed among treated patients
regardless of age at diagnosis (ie, differences in median survival of 6, 3,
and 1 month among treated vs untreated patients aged 65-74, 75-84, and 85
years, respectively). Consistent with these longer survival times, patients
who received chemotherapy used more health care resources than those who did
not receive chemotherapy and had higher total costs (mean, $77 769 vs
$26 287) (Table 4). This
difference in total costs based on receipt of chemotherapy was consistent
across age groups, with treated patients having total costs 2 to 3 times higher
than those of untreated patients. Patients undergoing retreatment for relapsed
AML (n = 124) had the highest level of resource use, with an average of 105
total inpatient days and mean total costs of $128 630 during the 2-year
follow-up.
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Table 4. Total Medicare Payments per Patient in the First 2 Years After
AML Diagnosis, by Receipt of Chemotherapy and Age at Diagnosis*
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RELATIONSHIP BETWEEN LENGTH OF SURVIVAL, RECEIPT OF CHEMOTHERAPY, AND
USE OF HEALTH CARE RESOURCES
Patterns of resource use and Medicare costs differed substantially between
patients who survived shorter vs longer than the median 2-month length of
survival after the diagnosis of AML. Patients who survived more than 2 months
were more likely to use home health care and hospice services (55% and 20%,
respectively) than those who survived less than 2 months (20% and 14%, respectively).
Those who died rapidly spent an average of 37% of their remaining days in
institutions, whereas those who lived longer than the median spent an average
of 24% of their remaining days in institutions. Finally, patients who survived
more than 2 months were 3 times more likely to be treated with chemotherapy
than those who survived less (43% vs 15%, respectively), but had mean costs
that were 3 times higher than those who survived less than 2 months ($60 330
vs $19 950, respectively).
COMMENT
We found the prognosis among elderly patients with AML to be extremely
poor, with a median survival of 2 months and a 2-year survival rate of 6%.
The prognosis has not changed during the past decade, with similar survival
regardless of the year of diagnosis. Our findings are consistent with other
studies that have documented a poor prognosis among elderly patients with
AML.2, 4, 9 To our
knowledge, however, our investigation is the first comprehensive evaluation
of the outcomes and costs associated with AML.
Costs for the use of all health care resources after diagnosis were
substantial, exceeding $41 000 per patient on average, most of which
was incurred in the first few months. Costs were dominated by hospitalization,
as has been found in studies of patients with solid tumors.10-11
Costs varied only slightly by race, sex, comorbidities, and year of diagnosis,
but varied greatly by age at diagnosis, with the oldest patients having the
lowest overall costs. The lower overall costs among the oldest patients were
due to their shorter survival times, because the average cost per day alive
was similar for all 3 age groups (ranging from about $340-$370 per day) and
did not vary by receipt of chemotherapy. It should be noted that this analysis
focused on the use of all health care resources and not only those specifically
attributable to AML. Given the methodological issues involved in attributing
costs to AML, and given that more than 80% of hospitalizations had primary
diagnoses directly related to AML or complications of its treatment, we believed
that this approach was appropriate.
The infrequent use of chemotherapy in our sample may reflect the fact
that elderly patients cannot tolerate standard cytotoxic treatments for AML,
as noted in the literature.2, 12
This finding is consistent with data from the United Kingdom Medical Research
Council study, which reported that as many as 28% of all study patients and
38% of study patients older than 60 years received only palliative treatment.13 Furthermore, similar to our study in which patients
who received chemotherapy lived longer, patients who received only palliative
treatment in the UK Medical Research Council study were found to have a 1-year
survival of 11% (50/475 patients) relative to 32% (391/1221 patients) among
those who received chemotherapy. In our study, age, residence in a metropolitan
area, and the presence of congestive heart failure or chronic obstructive
pulmonary disease in the year before the AML diagnosis were the only factors
that appeared to influence chemotherapy use, perhaps reflecting the better
prognosis among the youngest and healthiest patients and more access to treatment
in metropolitan areas. It is encouraging to note that emerging treatment strategies
for AML are expected to be more effective for and better tolerated by the
elderly.14-23
The results from this study may provide a baseline for assessing the potential
benefits of these interventions, especially if they offer less unfavorable
risk-benefit choices between tolerability and survival.
Although Medicare hospice program costs have more than doubled in the
past decade,24 there was very little use of
hospice care in our sample, even among those who survived the longest. Instead,
the patients who died spent an average of 31% of their remaining days in hospitals
or nursing facilities rather than at home, which may have had a negative impact
on the health-related quality of life among these patients.25
Further research that assesses potential barriers to use of hospice services
would be beneficial.
Our study is subject to several limitations. We relied on administrative
claims data, which were not collected specifically for research purposes.26 Consequently, we were unable to address other cancer
outcomes, such as remission rates, disease-free survival, and quality of life.
In addition, patients from the SEER registries may not be representative of
all US patients with AML. Although the SEER data cover about 14% of all cancer
cases, certain groups are underrepresented or overrepresented (eg, blacks
and other races, respectively).27-28
Nonetheless, the linked SEER-Medicare database has proven extremely useful
for case selection and for profiling oncology treatment patterns and survival
for many different cancer types, including cancers of the breast, prostate,
lung, and ovaries.29-34
Costs were evaluated from a limited perspective (ie, patients eligible for
Medicare and not enrolled in HMOs). Because Medicare is a primary payer for
this age group, we expect that the bulk of costs were captured in our analysis.
The fraction of the sample excluded because of HMO enrollment (13%) is consistent
with HMO penetration in the United States (14.5%).35
Since the excluded HMO patients were similar to our study population in terms
of demographics and survival, their exclusion should not have greatly influenced
our results.
This study indicates that AML among the elderly is associated with a
poor prognosis and with substantial costs during the relatively few remaining
months of life. Moreover, most patients do not receive active treatment with
chemotherapy or hospice services. Further work is needed to characterize this
disease and the complex comorbidity- and patient preference–related
factors that influence treatment decisions and associated health outcomes.
AUTHOR INFORMATION
Accepted for publication November 20, 2001.
This study was funded in part by Wyeth-Ayerst Research, Radnor, Pa.
We thank Rick deFriesse, MA, for his expert programming assistance,
and the National Cancer Institute and the Centers for Medicare and Medicaid
Services for allowing us to use the linked SEER-Medicare data.
Wyeth-Ayerst Research has no direct financial interest in the findings
reported herein.
Corresponding author and reprints: Joseph Menzin, PhD, Boston Health
Economics, Inc, 20 Fox Rd, Waltham, MA 02451 (e-mail: jmenzin{at}bhei.com).
From Boston Health Economics, Inc, Waltham, Mass (Drs Menzin, Lang,
and Kerney); the Dana-Farber Cancer Institute, Boston, Mass (Dr Earle); and
Wyeth-Ayerst Research, Collegeville, Pa (Dr Mallick).
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