Trends in Leukemia Incidence and Survival in the United States ( )

2229 Trends in Leukemia Incidence and Survival in the United States (1973 1998) Yang Xie, M.D., M.P.H. 1,2 Stella M. Davies, M.D., Ph.D. 1,2 Ying Xiang, M.D. 1,2 Leslie L. Robison, Ph.D. 1,2 Julie A. Ross, Ph.D. 1,2 1 Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota. 2 University of Minnesota Cancer Center, Minneapolis, Minnesota. Supported by the University of Minnesota Children s Cancer Research Fund and by the National Cancer Institute (Grant R01 CA-79940). The authors thank Angela Smit and Ginny Oie for assistance in the preparation of this article. Dr. Davies s current address: Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio. Address for reprints: Julie A. Ross, Ph.D., University of Minnesota Cancer Center, MMC 422, 420 Delaware St. S.E., Minneapolis, MN 55455; Fax: (612) 626-4842; E-mail: ross@epi.umn.edu Received November 1, 2002; revision received December 31, 2002; accepted January 7, 2003. BACKGROUND. It is estimated that each year, approximately 30,800 individuals will be diagnosed with leukemia in the United States and 21,700 individuals will die of the disease. Although the overall incidence of leukemia has been declining in the United States, recent reports suggest that incidence rates may be increasing for certain age and racial groups. METHODS. Leukemia incidence (including acute lymphoblastic leukemia [ALL], acute myeloid leukemia [AML], chronic myeloid leukemia [CML], and chronic lymphoblastic leukemia [CLL]) and 5-year survival rates were obtained from the Surveillance, Epidemiology, and End Results (SEER) program. Specific rates for age (birth 19, 20 44, 45 64, and 65 years), gender, and race (black, white) were also examined. RESULTS. A total of 66,404 cases of leukemia were identified for the period 1973 1998 in the nine reporting SEER sites. For children younger than 20 years old, the overall incidence rate of leukemia increased significantly (estimated annual percent change [EAPC] 0.5%, 95% confidence interval [CI] 0.1 0.9), whereas the rate decreased significantly among the group 65 years and older (EAPC 0.3, 95% CI 0.5 to 0.1). Incidence rates for CLL and CML decreased significantly during this time period, whereas incidence rates for AML remained stable. Children younger than 20 years old experienced a 15% increase in the 5-year survival rates for both ALL and AML when comparing the two 10-year periods of 1974 1983 and 1984 1993. In contrast, there was little overall improvement in survival for adults 45 years and older. In particular, there was a notable decrease in the overall 5-year survival for blacks older than 65 years and for black males older than 44 years. CONCLUSIONS. Although the current study confirmed some of the results noted in other populations, the observed overall decline in leukemia survival for blacks is surprising and warrants further investigation. Cancer 2003;97:2229 35. 2003 American Cancer Society. DOI 10.1002/cncr.11316 KEYWORDS: leukemia, incidence, survival, trends, epidemiology. Each year, the American Cancer Society estimates that 30,800 individuals will be diagnosed with leukemia in the United States and that 21,700 individuals will die of the disease. 1 With the exception of a few established risk factors including benzene and alkylating agents, which account for a fraction of cases, little is known about the causes of leukemia. 2 Leukemias are a heterogeneous group of hematopoietic malignancies that include many diverse and biologically distinct subgroups. The four major subtypes of leukemia described by most cancer registries include acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphoblastic leukemia (CLL), and 2003 American Cancer Society

2230 CANCER May 1, 2003 / Volume 97 / Number 9 chronic myeloid leukemia (CML). Several reports have studied the trends in leukemia incidence and survival. 3 12 Many of these studies have either addressed leukemia overall or have focused on young patients. Ecologic data that explore trends in cancer incidence can provide important information regarding potential changes in risk factors and can reflect underlying changes in diagnostic classification. The purpose of this article is to describe age (birth 19, 20 44, 45 64, and 65 years), race (white, black), and gender patterns of leukemia incidence and survival in the United States during the period 1973 1998. MATERIALS AND METHODS Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute. 13 The SEER program collects demographic, medical, and follow-up data on all incident malignancies that occur in several geographic areas in the United States. Data for this analysis were derived from nine population-based SEER registries that cover approximately 10% of the total U.S. population and include the states of Connecticut, Hawaii, Iowa, New Mexico, and Utah and the metropolitan areas of Atlanta, Detroit, San-Francisco-Oakland, and Seattle. The SEER program is considered the standard for quality among cancer registries around the world. Case ascertainment is estimated at 98%. Leukemia diagnoses were defined using International Classification of Diseases for Oncology (ICD- O) 14 codes as follows: overall leukemia (9800 9941); ALL (9821, 9826, 9827, 9828); CLL (9823); AML (9840, 9841, 9861, 9866, 9867, 9871 9874, 9891, 9910); and CML (9863). The annual age-adjusted incidence rates for leukemia for the period 1973 1998 were calculated using the SEER public-use CD-ROM. 13 These data include information on all incident cases of malignancies and estimates of the population (based on U.S. Census data) in each of the SEER reporting areas. All nine SEER registries contributed data for the entire time period except for the Seattle registry, which began in 1974, and the Atlanta registry, which began in 1975. Age (birth 19, 20 44, 45 64, and 65 years), gender, race (black, white), and leukemia-specific trends were evaluated to determine if any observed trends might be accounted for by a subgroup of the population. Incidence and survival rates are expressed per million persons and were age adjusted using the world standard population. Survival rates are expressed as percentages and were adjusted for general population mortality. The estimated annual percent change (EAPC) for incidence rates and the corresponding 95% confidence intervals (CI) were calculated using the weighted least squares method. 15 Local regression methods (which take into account the incidence and survival rates immediately adjacent to each year s rates) were employed in the plots to assist in the visualization of trends. 16,17 RESULTS Incidence A total of 66,404 cases of leukemia were identified from 1973 to 1998 in the nine reporting areas of the SEER program. Overall leukemia incidence rates and trends among the four age groups are shown in Table 1. The age-specific incidence rate of leukemia was 15 times higher among the oldest group (545 per million persons) compared with the youngest group (36 per million persons). With the exception of the 20 44 year-old age group, blacks had lower rates of leukemia compared with whites. Males had higher incidence rates than females for all age groups. Among children and adolescents, the overall incidence rate of leukemia increased significantly during the time period (EAPC 0.5%, 95% CI 0.1 0.9), whereas the rate decreased significantly among the group 65 years and older (EAPC 0.3%, 95%CI 0.5 to 0.1). There were no significant trends for the young adult or middle-age group. When race and gender-specific incidence rates were evaluated, there was a statistically significant increase (EAPC 0.7%) among white females in the youngest age group. Among the oldest group, the incidence rate of leukemia in white males decreased significantly from 1973 to 1998. A similar decrease was observed for blacks, but it did not reach statistical significance. Although a model based on a constantly increasing incidence rate can be applied to overall leukemia incidence data to estimate the EAPC, a visual inspection of these data provided more revealing patterns over time (Fig. 1). For example, among white females in the youngest age group, the overall EAPC in incidence was 0.7 (95% CI 0.1 1.3; Table 1). As shown in Figure 1, there was a slight but steady increase in the incidence of leukemia in females younger than 20 years of age during the period 1973 1998. In contrast, for black males in the 20 44 year age group, the overall EAPC was 0.7 (95% CI 1.9, 0.6). However, visual inspection revealed a nonlinear pattern in the incidence rate. The rate increased until about 1980, decreased from 1981 to 1985, plateaued during the period 1985 1990, and then increased again. Leukemia subtypes revealed different patterns (Table 2). With the exception of the oldest group, ALL incidence rates increased significantly. This increase was particularly notable in the two middle age groups.

Leukemia in the United States/Xie et al. 2231 TABLE 1 Trends and Overall Leukemia Incidence (Rate per Million Persons), SEER 1973 1998 Total Male Female No. Rate a Change (%) b 95% CI No. Rate a Change (%) b 95% CI No. Rate a Change (%) b 95% CI Birth 19 6640 36 0.5 c 0.1, 0.9 3746 40 0.4 0.1, 0.9 2894 32 0.7 c 0.1, 1.3 20 44 6867 30 0.2 0.3, 0.6 4008 35 0.3 0.1, 0.8 2859 25 0.1 0.8, 0.5 45 64 16,289 144 0.1 0.4, 0.2 9960 183 0.2 0.6, 0.2 6329 108 0.1 0.4, 0.2 65 36,608 545 0.3 c 0.5, 0.1 19,915 758 0.5 c 0.7, 0.2 16,693 405 0.3 c 0.6, 0.1 Birth 19 5373 38 0.4 c 0, 0.8 3054 42 0.2 0.3, 0.8 2319 33 0.7 c 0.1, 1.2 20 44 5551 30 0.2 0.2, 0.6 3261 35 0.4 0, 0.8 2290 25 0 0.7, 0.7 45 64 14,155 148 0.1 0.4, 0.2 8730 188 0.2 0.6, 0.3 5425 110 0.1 0.2, 0.4 65 33,483 568 0.2 c 0.5, 0 18,181 798 0.4 c 0.7, 0.1 15,302 420 0.2 0.5, 0 Birth 19 568 25 0.9 0.2, 2.1 299 26 1 0.6, 2.6 269 24 0.4 1.2, 2 20 44 732 30 0.7 1.9, 0.6 411 36 0.4 1.7, 0.8 321 24 d d 45 64 1263 135 1.4 c 2.4, 0.4 731 172 1 2.3, 0.3 532 104 1.8 c 3.1, 0.5 65 1920 444 0.7 c 1.3, 0 1011 597 0.7 1.6, 0.1 909 344 0.6 1.5, 0.3 SEER: Surveillance, Epidemiology, and End Results program; CI: confidence interval. a Incidence rates are per million persons and are age adjusted to the 1970 U.S. standard million population. b Estimated annual percent change (EAPC) was calculated using the weighted least squares method. c The EAPC is significantly different from zero (P 0.05). d Statistic could not be calculated due to small numbers. time among the different age groups, although there was a slight increase among the oldest group. Race and gender-specific incidence rates and trends also were evaluated among the various leukemia subgroups (data not shown). For ALL among the youngest group, incidence rates have been increasing slightly,which was particularly apparent among blacks. The EAPC for black males and females was 2.2% (95% CI 0.1 4.3) and 1.8% (95% CI 0.4 4.0) in the birth 19 group, respectively. There was little other evidence for race or gender differences among the different subtypes of leukemia. FIGURE 1. Leukemia incidence during the period 1973 1998 by age and gender. Unbroken line: white males; dotted line: white females; dashed line: black males; dashed/dotted line: black females. Incidence rates increased by an average of 2.6% and 2.9% per year for the 20 44 and the 45 64 groups, respectively. In contrast, the incidence of both CLL and CML decreased significantly, with a decrease particularly remarkable among the oldest group with CML ( 2.2% per year, 95% CI 2.7 to 1.6). In general, incidence rates for AML have been stable over Survival Figure 2 shows the 5-year survival trends among the various age groups by race and gender for the period 1973 1998. The youngest age group demonstrated the most marked improvement in 5-year survival, with rates increasing from about 30% in the mid-1970s to approximately 60% in the late 1990s. However, survival rates decreased over time for blacks in the older age groups. In particular, the 5-year survival rate for blacks in the 45 64 year age group decreased from 1985 onward. We also compared the 5 and 10-year survival rates for the two 10-year periods (1974 1983 and 1984 1993; Table 3). Overall, there has been little

2232 CANCER May 1, 2003 / Volume 97 / Number 9 TABLE 2 Trends and Subtype Leukemia Incidence (Rate per Million Persons) SEER 1973 1998 No. Rate a Change (%) b 95% CI ALL (yrs) c Birth 19 4848 27 1.1 d 0.6, 1.6 20 44 1111 5 2.6 d 1.7, 3.6 45 64 698 6 2.9 d 1.7, 4.1 65 941 14 0.9 0.2, 2.0 AML (yrs) Birth 19 1187 7 0.5 0.4, 1.4 20 44 2774 12 0.2 0.6, 0.9 45 64 4756 42 0.3 0.3, 0.9 65 10,000 150 0.4 d 0.0, 0.8 CLL (yrs) Birth 19 3 0 e e 20 44 503 2 0.8 1.7, 0.2 45 64 6128 54 0.5 d 1.0, 0.1 65 14,657 219 0.6 d 1.1, 0.1 CML (yrs) Birth 19 206 1 0.1 2.0, 2.2 20 44 1586 7 0.6 1.3, 0.2 45 64 2323 21 1.2 d 1.7, 0.6 65 4114 61 2.2 d 2.7, 1.6 SEER: Surveillance, Epidemiology, and End Results program; CI: confidence interval; ALL: acute lymphoblastic leukemia; AML: acute myeloid leukemia; CLL: chronic lymphoblastic leukemia; CML: chronic myeloid leukemia. a Incidence rates are per million persons and are age adjusted to the 1970 U.S. standard million population. b Estimated annual percent change (EAPC) was calculated using the weighted least squares method. c Median age were 11, 66, 71, and 64 years for ALL, AML, CLL, and CML, respectively. d The EAPC is significantly different from zero (P 0.05). e Statistic could not be calculated due to small numbers. improvement in survival for individuals 45 years and older who were diagnosed with leukemia. Upon further inspection by race, the lack of improvement in survival was particularly evident for blacks in the older age groups. Table 4 shows 5-year survival rates by subtype of leukemia during the 10-year time periods of 1974 1983 and 1984 1993. There has been a 15% improvement in 5-year survival rates for ALL. Although survival rates almost doubled for AML in the youngest age group, outcomes in this category remain unsatisfactory. Adults with either ALL or AML have not fared well. In particular, there has been little improvement in survival for adults in the older age groups, with overall 5-year survival rates still less than 15%. In contrast, individuals with CLL who were younger than age 65 years continued to experience 5-year survival rates in excess of 70%. DISCUSSION In the current study, we describe incidence rates, survival rates, and trends for leukemia overall and for FIGURE 2. Five-year leukemia survival rates during the period 1973 1998 by age and gender. Unbroken line: white males; dotted line: white females; dashed line: black males; dashed/dotted line: black females. subtypes within different age and race groups in the United States during the period 1973 1998. Although leukemia is the most common malignancy among children and adolescents, the majority of cases of leukemia occur in older people. The highest incidence rates occur in the age group 65 years and older, followed by the 40 64 year age group. For children, ALL accounts for 73% of all leukemias diagnosed, whereas for young adults (age 20 40 years) AML is most common. For middle-age and elderly adults, CLL and CML are the most frequent. To our knowledge, the last comprehensive report on leukemia incidence and survival in the United States was published by Groves et al. 12 and covered the period 1973 1990. In a comparison of overall leukemia incidence rates during the 6-year periods of 1973 1978 and 1985 1990, they reported that rates generally decreased, particularly among individuals age 65 years. We also observed declines in leukemia incidence during the period 1973 1998, particularly among the groups of individuals age 45 years. We also noted a modest but statistically significant increase in incidence among children younger than 20 years of age. For subtypes, Groves et al. 12 reported declines in incidences of CML and CLL when comparing the period 1973 1978 with the period 1985 1990. They also noted that AML incidence decreased less rapidly and appeared to be increasing among black males. In contrast, ALL rates increased for all four race/gender groups. During the period 1973 1998, we observed increases among the four age groups for ALL, which were statistically significant for all but the oldest age group (65 years). This was accounted for primarily

Leukemia in the United States/Xie et al. 2233 TABLE 3 5 and 10-Year Survival Rates of Overall Leukemia by Gender, Age, Race, and Time Period, SEER 1974 1993 5-year survival rate (%) for 1974 1983 5-year survival rate (%) for 1984 1993 Total Male Female Total Male Female Rate 95% CI Rate 95% CI Rate 95% CI Rate 95% CI Rate 95% CI Rate 95% CI Birth 19 51.3 49.22, 53.38 48.63 45.86, 51.4 54.78 51.63, 57.93 Birth 19 66.77 64.91, 68.63 63.99 61.45, 66.53 70.28 67.57, 72.99 20 44 27.17 25.26, 29.08 27.4 24.88, 29.92 26.86 23.93, 29.79 20 44 40.37 38.44, 42.30 41.8 39.29, 44.31 38.27 35.28, 41.26 45 64 42.48 41.06, 43.90 43.4 41.57, 45.23 41.02 38.78, 43.26 45 64 46.39 45.00, 47.78 47.39 45.62, 49.16 44.68 42.42, 46.94 65 31.79 30.61, 32.97 29.39 27.79, 30.99 34.38 32.65, 36.11 65 35.99 34.89, 37.09 36.05 34.51, 37.59 35.92 34.33, 37.51 Birth 19 52.14 49.88, 54.40 49.76 46.78, 52.74 55.34 51.90, 58.78 Birth 19 69.09 67.04, 71.14 66.65 63.86, 69.44 72.24 69.25, 75.23 20 44 28.16 26.04, 30.28 28.84 26.03, 31.65 27.22 23.99, 30.45 20 44 42.05 39.90, 44.20 44.15 41.35, 46.95 38.9 35.54, 42.26 45 64 43.93 42.42, 45.44 44.58 42.64, 46.52 42.9 40.49, 45.31 45 64 48.73 47.24, 50.22 50.04 48.15, 51.93 46.44 43.99, 48.89 65 32.38 31.15, 33.61 30.02 28.34, 31.7 34.91 33.1, 36.72 65 37.30 36.13, 38.47 37.46 35.83, 39.09 37.12 35.44, 38.8 Birth 19 38.76 31.51, 46.01 33.04 23.18, 42.9 44.59 34.08, 55.10 Birth 19 54.69 48.19, 61.19 50.79 41.79, 59.79 59.05 49.71, 68.39 20 44 23.81 18.18, 29.44 21.54 14.3, 28.78 26.68 17.85, 35.51 20 44 34.73 29.06, 40.40 32.54 25.09, 39.99 37.51 28.83, 46.19 45 64 35.29 30.32, 40.26 38.59 31.81, 45.37 30.9 23.66, 38.14 45 64 36.06 31.26, 40.86 33.06 26.94, 39.18 40.42 32.79, 48.05 65 29.69 24.60, 34.78 26.71 19.71, 33.71 32.6 25.27, 39.93 65 26.31 22.19, 30.43 24.69 18.86, 30.52 27.81 21.99, 33.63 10-year survival rate (%) for 1974 1983 10-year survival rate (%) for 1984 1993 Birth 19 44.66 42.58, 46.74 41.51 38.77, 44.25 48.76 45.59, 51.93 Birth 19 61.30 59.26, 63.34 58.49 55.74, 61.24 64.85 61.84, 67.86 20 44 18.00 16.33, 19.67 18.37 16.15, 20.59 17.49 14.95, 20.03 20 44 31.86 29.87, 33.85 32.84 30.2, 35.48 30.44 27.41, 33.47 45 64 28.00 26.64, 29.36 28.27 26.49, 30.05 27.61 25.49, 29.73 45 64 31.15 29.63, 32.67 30.80 28.84, 32.76 31.61 29.21, 34.01 65 21.45 20.14, 22.76 18.83 17.06, 20.60 23.98 22.06, 25.9 65 23.03 21.65, 24.41 22.79 20.85, 24.73 23.30 21.35, 25.25 Birth 19 45.71 43.45, 47.97 42.83 39.86, 45.80 49.58 46.11, 53.05 Birth 19 63.35 61.08, 65.62 60.97 57.91, 64.03 66.41 63.04, 69.78 20 44 18.92 17.05, 20.79 19.63 17.14, 22.12 17.94 15.13, 20.75 20 44 33.78 31.54, 36.02 35.17 32.21, 38.13 31.71 28.31, 35.11 45 64 29.40 27.93, 30.87 29.31 27.41, 31.21 29.56 27.25, 31.87 45 64 33.55 31.89, 35.21 33.30 31.17, 35.43 33.82 31.20, 36.44 65 22.00 20.62, 23.38 19.53 17.65, 21.41 24.38 22.36, 26.4 65 24.32 22.84, 25.8 24.15 22.05, 26.25 24.54 22.44, 26.64 Birth 19 32.77 25.75, 39.79 27.6 18.15, 37.05 37.95 27.67, 48.23 Birth 19 49.97 43.02, 56.92 46.19 36.61, 55.7 54.20 44.25, 64.15 20 44 14.79 9.97, 19.61 12.57 6.55, 18.59 17.59 9.83, 25.35 20 44 21.97 16.32, 27.62 19.26 11.94, 26.58 24.99 16.27, 33.71 45 64 20.63 16.11, 25.15 24.09 17.57, 30.61 16.39 10.30, 22.48 45 64 15.64 11.19, 20.09 11.85 6.64, 17.06 20.70 13.15, 28.25 65 18.32 12.97, 23.67 13.96 6.95, 20.97 22.0 14.17, 29.83 65 11.29 7.02, 15.56 9.94 4.1, 15.78 12.70 6.58, 18.82 SEER: Surveillance, Epidemiology, and End Results Program; CI: confidence interval. by the youngest cases. In a recent evaluation of data from the Manchester Children s Tumour Registry, Mc- Nally et al. 8 also reported a statistically significant increase in childhood ALL during the time period 1954 1998 (average annual percent increase 0.7%, P 0.005). Moreover, for the period 1984 1998, they reported that the increase was highest among females in the youngest age group (1 4 years). Groves et al. 12 reported that the overall survival rates for all leukemia patients improved only slightly when comparing the periods 1974 1976 and 1983 1989, but were consistently higher in whites compared with blacks, with little gender difference. We analyzed survival rates in more detail and found that in comparing the period 1974 1983 with 1984 1993, overall survival rates improved notably among all races/age groups, whites, and blacks younger than the age of 45 years. However, for blacks 45 years and older, there was little improvement in overall survival. In particular, for blacks older than 65 years, survival rates were decreasing, which was not observed in the earlier data by Groves et al. 12 The improvement in survival among the youngest age group is likely attributable to the success of the cooperative clinical trials groups including the former Children s Cancer Group (CCG) and the Pediatric Oncology Group. These clinical trials groups are estimated to treat nearly 90% of pediatric patients in the United States. 18 The performance of large-scale systematic clinical trials has allowed the optimization of

2234 CANCER May 1, 2003 / Volume 97 / Number 9 TABLE 4 Five-Year Survival Rate by Subtype of Leukemia, SEER 1974 1993 5-year survival rate (%) for 1974 1983 95% confidence interval 5-year survival rate (%) for 1984 1993 95% confidence interval ALL (yrs) Birth 19 60.54 58.11, 62.97 75.52 73.56, 77.48 20 44 21.40 16.65, 26.15 31.32 27.04, 35.60 45 64 8.33 3.89, 12.77 14.47 10.22, 18.72 65 8.30 3.99, 12.61 5.32 2.42, 8.22 AML (yrs) Birth 19 22.00 17.91, 26.09 37.52 73.56, 77.48 20 44 13.83 11.54, 16.12 30.15 27.04, 35.60 45 64 6.52 5.20, 7.84 12.73 10.22, 18.72 65 2.49 1.78, 3.20 3.14 2.42, 8.22 CLL (yrs) Birth 19 a a 20 44 73.13 65.74, 80.52 81.30 75.62, 86.98 45 64 78.35 76.28, 80.42 79.79 77.83, 81.75 65 62.56 60.37, 64.75 68.75 66.81, 70.69 CML (yrs) Birth 19 36.54 25.73, 47.35 37.49 27.07, 47.91 20 44 34.27 30.10, 38.44 43.28 39.25, 47.31 45 64 29.44 26.20, 32.68 36.06 32.48, 39.64 65 17.55 14.95, 20.15 21.17 18.44, 23.90 SEER: Surveillance, Epidemiology, and End Results program; ALL: acute lymphoblastic leukemia; AML: acute myeloid leukemia; CLL: chronic lymphoblastic leukemia; CML: chronic myeloid leukemia. a Statistic could not be calculated due to small numbers. chemotherapy studies and the performance of highquality epidemiologic and biologic studies. 19,20 The lack of overall improvement in survival for adults is disappointing. This finding may reflect biologic differences in the leukemia cells of older persons, which may render them less curable, and differences in tolerance for intensive therapy. 21 In addition, young adults may receive chemotherapy regimens designed with consideration for the limited drug tolerance of elderly patients, reducing their survival. Stock et al. 22 compared outcomes for 103 patients aged 16 20 years enrolled on the adult trials of the Cancer and Leukemia Group B (CALGB) with the outcomes of 196 patients of the same age treated on CCG trials. Comparison of risk factors showed a higher incidence of adverse cytogenetics in the CALGB group, but similar frequencies of B- and T-cell lineage and a white cell count above 50,000 at presentation. The 6-year eventfree survival rate was 38% for patients treated on CALGB trials and 64% for those treated on CCG studies. These data underscore the importance of establishing large-scale clinical cancer trials for individuals older than the age of 21 years and using a doseintensive approach in younger adults who will tolerate this strategy. There are some limitations to our analyses. First, these rates reflect the SEER areas only. It is possible that there are geographic differences in leukemia incidence and survival rates in areas not covered by SEER. In an ad hoc analysis, we evaluated whether there were any notable differences in leukemia incidence or survival among the nine registries, as these registries represent different populations and perhaps different access to health care. Hawaii, which was the smallest registry (2179 cases), had both a lower overall leukemia incidence and survival compared with the other 8 registries. There were no notable differences in either leukemia incidence or survival among the remaining registries. Second, leukemia is a heterogeneous disease. 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