Abstract

Reporting of myelodysplastic syndromes (MDSs) and chronic myeloproliferative disorders (CMDs) to population-based cancer registries in the United States was initiated in 2001. In this first analysis of data from the North American Association of Central Cancer Registries (NAACCR), encompassing 82% of the US population, we evaluated trends in MDS and CMD incidence, estimated case numbers for the entire United States, and assessed trends in diagnostic recognition and reporting. Based on more than 40 000 observations, average annual age-adjusted incidence rates of MDS and CMD for 2001 through 2003 were 3.3 and 2.1 per 100 000, respectively. Incidence rates increased with age for both MDS and CMD (P < .05) and were highest among whites and non-Hispanics. Based on follow-up data through 2004 from the Surveillance, Epidemiology, and End Results (SEER) Program, overall relative 3-year survival rates for MDS and CMD were 45% and 80%, respectively, with males experiencing poorer survival than females. Applying the observed age-specific incidence rates to US Census population estimates, approximately 9700 patients with MDS and 6300 patients with CMD were estimated for the entire United States in 2004. MDS incidence rates significantly increased with calendar year in 2001 through 2004, and only 4% of patients were reported to registries by physicians' offices. Thus, MDS disease burden in the United States may be underestimated.

Introduction

Myelodysplastic syndromes (MDSs) comprise morphologically distinct disorders characterized by dysplastic and ineffective hematopoiesis. Although historically MDS has not been defined as a cancer, MDS results from the clonal expansion of an hematopoietic progenitor and progresses to acute myeloid leukemia in approximately 30% of patients.1  Incidence rates for MDS and chronic myeloproliferative disorders (CMDs) in the United States were unavailable prior to the addition of these stem cell malignancies to central cancer registries in 2001. Description of national incidence rates provides an important baseline for future studies of secular trends and allows for the examination of rates by selected demographic factors to define risk profiles of these hematologic malignancies in the American population.

Estimated incidence rates of MDS for the United States in 2001 to 2003 were recently published based on initial data reported from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program.2  Incidence rates increased with age and were higher among males than females,2  although rates were not analyzed for MDS subtypes or for CMD. SEER covers approximately 26% of the US population, and given the recent incorporation of MDS to cancer registry surveillance, we sought to extend national estimates to 33 additional geographic areas that are not included in SEER and assess possible patterns in diagnostic recognition that might affect reporting frequency. To investigate MDS and CMD incidence overall and by disease subtype, evaluate trends in incidence by demographic factors, estimate total numbers of cases expected to be diagnosed in the entire United States, and examine incidence and survival data updated through 2004, we conducted an extensive analysis of data obtained through both SEER and the North American Association of Cancer Registries (NAACCR), based on more than 40 000 patients, the largest number ever available for analysis of MDS and CMD.

Methods

Frequencies of reported MDS, CMD, and chronic myelomonocytic leukemia (CMML) cases were obtained from US state and regional population-based cancer registries. (Although CMML is classified as an MDS subtype in the French, American, British [FAB] system, CMML is not coded as MDS in the system by which cancer cases are reported to central cancer registries. Therefore, CMML was included as a disease entity separate from MDS in the present analysis.) These cancer registries collect information on new cancer diagnoses through the National Cancer Institute's SEER Program, Centers for Disease Control Prevention's National Program of Cancer Registries (NPCR) Program, or both.3  All cancer registries are members of NAACCR. The source of data in this paper for all analyses, except survival, is NAACCR's research data file, Cancer in North America (CINA); the December 2005 submission of the CINA Deluxe 1995 to 2003 file was used, and diagnosis years from 2001 to 2003 were included. To be included in the CINA deluxe database, registry data are required to meet specific certification criteria, details of which have been previously described.4 

In the CINA Deluxe database, SEER data are composed of 9 state areas (California, Connecticut, Hawaii, Iowa, New Mexico, Utah, Kentucky, Louisiana, and New Jersey) and 3 metropolitan areas (Atlanta, Detroit, and Seattle). The other state registries in the CINA Deluxe file include Alabama, Alaska, Arizona, Colorado, Delaware, Washington, DC, Florida, Georgia, Idaho, Illinois, Indiana, Maine, Massachusetts, Michigan, Minnesota, Missouri, Montana, Nebraska, Nevada, New Hampshire, New York, North Carolina, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, South Dakota, Texas, Washington, West Virginia, and Wisconsin. Since the SEER metropolitan areas of Atlanta, Detroit, and Seattle are also included in the Georgia, Michigan, and Washington registries, we excluded these 3 metropolitan areas from their respective states, thus avoiding double counting of patients and facilitating the comparison of incidence rates for MDS and CMD across 3 groups: SEER registries, NAACCR excluding SEER registries, and total registries.

Patients diagnosed between 2001 and 2003 were identified by International Classification of Diseases for Oncology Third Edition (ICD-O-3) codes (MDS: 9980-9989; CMD: 9950-9964; and CMML: 9945). ICD-O-3 includes codes for both topography and morphology and was implemented for data collection in cancer registries worldwide in 2001.5  Although ICD-O-3 was developed by the World Health Organization (WHO), there are subtle differences between ICD-O-3 and the “WHO classification” of myeloid neoplasms, published in 1997 by WHO in conjunction with the European Association of Hematopathologists and the Society for Hematopathology.6,7  As previously described,2  the WHO classification includes the following MDS subtypes: refractory anemia (RA), RA with ringed sideroblasts (RARS), refractory cytopenia with multilineage dysplasia (RCMD), RCMD with ringed sideroblasts (RCMD-RS), RA with excess blasts-1 (RAEB-1), RAEB-2, MDS associated with isolated 5q deletion, and MDS, unclassified. The ICD-O-3 similarly includes RA, RARS, RAEB (RAEB-1 and -2 combined), MDS associated with isolated 5q deletion, RCMD, and MDS, not otherwise specified. Additional codes exist in ICD-O-3 for RAEB in transformation (retained from the original FAB classification) and therapy-related MDS. Categories of myeloproliferative disease (or CMDs in ICD-O-3) also differ from the WHO classification. The WHO classification includes 7 CMD categories: BCR/ABL+ chronic myelogenous leukemia (CML), chronic neutrophilic leukemia, hypereosinophilic syndrome, polycythemia vera, chronic idiopathic myelofibrosis (synonymous with myelosclerosis with myeloid metaplasia), essential thrombocythemia, and CMD, unclassifiable. The same categories are included in ICD-O-3 with the exception of BCR/ABL+ CML, which is grouped with the leukemias in ICD-O-3. Incidence rates for CML have been previously reported from SEER,8  and are therefore not included in this report.

Patterns in case reporting were described for SEER, NAACCR minus SEER registries, and all registries combined, including the distribution of patients by reporting source and diagnostic confirmation of the malignancy. Incidence rates were expressed as the number of new primary cancers per 100 000 persons at risk per year and age-adjusted according to the 2000 US standard population based on 5-year age groups.9  To investigate patterns in MDS and CMD risk, incidence rates were stratified by demographic characteristics, including year of diagnosis, sex, age, and race (white, black, and other) and ethnicity (Hispanic vs non-Hispanic). (There were too few patients with CMML to conduct stratified analyses.) At the time of this analysis, data from 2004 were available from SEER Program but not from the CINA Deluxe file. Therefore, all analyses of incidence were based on the years 2001 through 2003. Statistical significance of the differences in age-adjusted incidence rates was assessed using analysis of variance (ANOVA).

To examine the national burden of disease, numbers of newly diagnosed patients with MDS, CMD, and CMML in 2004 were estimated for the entire US population based on the respective incidence rates calculated from the CINA Deluxe file for 2001 through 2003 and population estimates obtained from the US Census Bureau for 2004.10  Specifically, MDS, CMD, and CMML incidence rates, stratified by 5-year age groups and sex, were multiplied by corresponding stratified census counts and divided by 100 000. Numbers of cases were then summed across all age groups and both sexes to obtain the total projected count for 2004.

To evaluate patterns in survival, 3-year relative survival rates were calculated using the SEER limited-use database consisting of SEER-17 registries, for which data are available from 2001 to 2004.11  Relative survival rate is calculated by comparing observed survival with expected survival from a set of people with the same characteristics as the patient cohort with respect to age, race, sex, and calendar period.12  We used patients with MDS, CMD, and CMML diagnosed in 2001 through 2003 and followed through 2004 for 3-year relative survival rate calculations. Survival rates were stratified by sex, age and race, and 95% confidence interval (CI) are presented for each group. Survival by MDS subtype within SEER has been previously described2 ; thus, subtype analyses are presented only for CMD. The SEER*Stat program (version 6.2.4; National Cancer Institute) was used for all analyses in this paper, except for the statistical significance testing with ANOVA, which was conducted using SAS (Cary, NC).

Results

Reporting characteristics are presented in Table 1 for patients with MDS and CMD ascertained by SEER registries, by NAACCR registries that were not included in SEER (referred from here on out as “NAACCR minus SEER”), and for all patients combined. Between 2001 and 2003, 7076 and 17 722 patients with MDS were reported to SEER and NAACCR minus SEER registries, respectively, for a total of 24 798 patients with MDS overall. Roughly two-thirds as many patients with CMD were reported during the same time period (n = 16 119). As compared with patients with CMD, a greater proportion of patients with MDS were confirmed by positive histology in both SEER registries and NAACCR minus SEER registries (88% and 79% of patients with MDS and CMD, respectively, for SEER; 81% and 66% for NAACCR minus SEER). Conversely, a greater proportion of patients with CMD than with MDS were confirmed by a positive laboratory test (Table 1). The proportion of patients confirmed only by clinical diagnosis or other means was similar for MDS and CMD in both SEER and NAACCR minus SEER registries (4%-5%). Among patients with CMD and MDS reported to SEER registries, 92% were reported by a hospital or laboratory, as compared with 93% to 95% of patients with CMD and MDS in NAACCR minus SEER registries.

Table 1

Reporting characteristics of patients with MDS and CMD in the SEER and NAACCR registries, 2001-2003

SEER*
NAACCR − SEER
Total
Count%Count%Count%
MDS 7 076 100.0 17 722 100.0 24 798 100.0 
    Diagnostic confirmation       
        Positive histology 6 202 87.6 14 272 80.5 20 474 82.6 
        Positive laboratory test/marker study 266 3.8 1 070 6.0 1 336 5.4 
        Clinical diagnosis/others 308 4.4 705 4.0 1 013 4.1 
        Unknown 300 4.2 1 675 9.5 1 975 8.0 
    Reporting source       
        Hospital inpatient/laboratory 6 526 92.2 16 35 92.7 22 961 92.6 
        Physicians office/nursing, etc 416 5.9 572 3.2 988 4.0 
        Death certificate/autopsy only 134 1.9 715 4.0 849 3.4 
CMD 4 226 100.0 11 893 100.0 16 119 100.0 
    Diagnostic confirmation       
        Positive histology 3 355 79.4 7 893 66.4 11 248 69.8 
        Positive laboratory test/marker study 429 10.2 2 167 18.2 2 596 16.1 
        Clinical diagnosis/others 229 5.4 612 5.1 841 5.2 
        Unknown 213 5.0 1 221 10.3 1 434 8.9 
Reporting source       
        Hospital inpatient/laboratory 3 872 91.6 11 284 94.9 15 156 94.0 
        Physicians office/nursing, etc 304 7.2 357 3.0 661 4.1 
        Death certificate/autopsy only 50 1.2 252 2.1 302 1.9 
SEER*
NAACCR − SEER
Total
Count%Count%Count%
MDS 7 076 100.0 17 722 100.0 24 798 100.0 
    Diagnostic confirmation       
        Positive histology 6 202 87.6 14 272 80.5 20 474 82.6 
        Positive laboratory test/marker study 266 3.8 1 070 6.0 1 336 5.4 
        Clinical diagnosis/others 308 4.4 705 4.0 1 013 4.1 
        Unknown 300 4.2 1 675 9.5 1 975 8.0 
    Reporting source       
        Hospital inpatient/laboratory 6 526 92.2 16 35 92.7 22 961 92.6 
        Physicians office/nursing, etc 416 5.9 572 3.2 988 4.0 
        Death certificate/autopsy only 134 1.9 715 4.0 849 3.4 
CMD 4 226 100.0 11 893 100.0 16 119 100.0 
    Diagnostic confirmation       
        Positive histology 3 355 79.4 7 893 66.4 11 248 69.8 
        Positive laboratory test/marker study 429 10.2 2 167 18.2 2 596 16.1 
        Clinical diagnosis/others 229 5.4 612 5.1 841 5.2 
        Unknown 213 5.0 1 221 10.3 1 434 8.9 
Reporting source       
        Hospital inpatient/laboratory 3 872 91.6 11 284 94.9 15 156 94.0 
        Physicians office/nursing, etc 304 7.2 357 3.0 661 4.1 
        Death certificate/autopsy only 50 1.2 252 2.1 302 1.9 

Data source: NAACCR's CINA December 2005 submission of 1995 to 2003 patients.

*

Excludes Arizona Indians.

NAACCR registries minus SEER registries; excludes Seattle from Washington, Detroit from Michigan, and Atlanta from Georgia.

Age-adjusted incidence rates for MDS and CMD are presented in Table 2 for individual US states and geographic regions represented in NAACCR. MDS rates ranged from 1.5 per 100 000 in North Carolina to 5.6 per 100 000 in Detroit, while CMD rates ranged from 0.8 per 100 000 in Delaware to 4.1 per 100 000 in Idaho. The average annual age-adjusted incidence rate for MDS in 2001 through 2003 was 3.3 per 100 000, based on 24 798 cases reported by SEER and NAACCR minus SEER registries combined (Table 3). A slight but statistically significant increase in MDS incidence rates was observed with calendar year, ranging from 3.1 per 100 000 in 2001 to 3.5 per 100 000 in 2003 in all registries combined. Data for 2004 were available only for SEER at the time of this analysis, and the increase in MDS incidence continued through 2004, with an incidence rate of 3.8 per 100 000 based on 2720 reported patients (P < .05). Age-adjusted incidence of MDS was significantly higher among males (4.4 per 100 000) than females (2.5 per 100 000; P < .05; Table 3). A sharp increase in MDS incidence rates was observed with age, especially among the elderly: rates were 5 times greater among those aged 80 years and older (35.5 per 100 000) as compared with those aged 60 to 69 years (7.1 per 100 000). While no significant differences in MDS incidence rates were observed by race, non-Hispanics had a statistically significant increased risk of MDS compared with Hispanics. MDS incidence rates were highest among whites and non-Hispanics. Similar trends in MDS incidence rates with calendar year, sex, age, and race/ethnicity were observed between SEER and NAACCR minus SEER registries.

Table 2

Incidence rates for MDS and CMD by state, NAACCR 2001-2003

StatePopulation size*MDS
CMD
CountRateCountRate
Alabama 13 452 835 298 2.15 198 1.42 
Alaska 1 921 510 31 2.88 25 1.79 
Arizona 10 735 936 314 2.93 241 2.27 
California§ 104 983 136 2791 3.06 1,500 1.60 
    Greater Bay 19 699 167 430 2.37 217 1.15 
    Los Angeles 29 280 659 788 3.36 462 1.88 
Colorado 13 472 998 339 3.20 273 2.35 
Connecticut 10 379 209 244 2.10 144 1.27 
Delaware 2 419 904 84 3.38 20 0.81 
Washington, DC 1 691 671 30 1.81 26 1.58 
Florida 50 033 890 2630 3.94 1,238 1.98 
Georgia§ 25 607 477 504 2.52 385 1.76 
    Atlanta 9 092 312 137 2.47 101 1.63 
Hawaii 3 705 280 113 2.79 88 2.22 
Idaho 4 031 456 174 4.69 154 4.07 
Illinois 37 752 732 1186 3.23 749 2.04 
Indiana 18 485 630 681 3.71 323 1.75 
Iowa 8 808 345 422 4.01 268 2.67 
Kentucky 12 275 955 475 3.90 283 2.27 
Louisiana 13 437 239 425 3.38 285 2.20 
Maine 3 893 588 145 3.26 127 2.86 
Massachusetts 19 228 325 539 2.55 431 2.09 
Michigan§ 30 129 569 1229 4.09 825 2.74 
    Detroit 12 158 589 670 5.55 432 3.60 
Minnesota 15 074 919 675 4.54 447 3.04 
Missouri 17 041 549 522 2.87 252 1.40 
Montana 2 735 068 100 3.34 106 3.54 
Nebraska 5 182 752 145 2.62 121 2.19 
Nevada 6 505 746 87 1.52 113 1.83 
New Hampshire 3 823 495 116 3.08 141 3.69 
New Jersey 25 725 929 942 3.46 614 2.27 
New Mexico 3 687 478 89 2.55 112 3.09 
New York 57 449 353 2239 3.71 1500 2.51 
North Carolina 24 931 345 357 1.50 311 1.27 
Ohio 22 798 256 431 1.78 368 1.54 
Oklahoma 10 461 203 192 1.77 126 1.15 
Oregon 10 561 772 276 2.51 144 1.33 
Pennsylvania 36 997 707 1943 4.21 1117 2.56 
Rhode Island 3 203 585 82 2.18 102 2.82 
South Carolina 12 315 801 277 2.32 213 1.72 
South Dakota 2 283 574 65 2.54 34 1.41 
Texas 65 161 449 1920 3.70 1794 3.19 
Utah 6 953 023 154 3.16 86 1.65 
Washington§ 18 191 211 848 4.98 459 2.65 
    Seattle 12 474 150 614 5.36 313 2.64 
West Virginia 5 418 494 266 4.11 116 1.84 
Wisconsin 16 320 562 418 2.42 260 1.53 
StatePopulation size*MDS
CMD
CountRateCountRate
Alabama 13 452 835 298 2.15 198 1.42 
Alaska 1 921 510 31 2.88 25 1.79 
Arizona 10 735 936 314 2.93 241 2.27 
California§ 104 983 136 2791 3.06 1,500 1.60 
    Greater Bay 19 699 167 430 2.37 217 1.15 
    Los Angeles 29 280 659 788 3.36 462 1.88 
Colorado 13 472 998 339 3.20 273 2.35 
Connecticut 10 379 209 244 2.10 144 1.27 
Delaware 2 419 904 84 3.38 20 0.81 
Washington, DC 1 691 671 30 1.81 26 1.58 
Florida 50 033 890 2630 3.94 1,238 1.98 
Georgia§ 25 607 477 504 2.52 385 1.76 
    Atlanta 9 092 312 137 2.47 101 1.63 
Hawaii 3 705 280 113 2.79 88 2.22 
Idaho 4 031 456 174 4.69 154 4.07 
Illinois 37 752 732 1186 3.23 749 2.04 
Indiana 18 485 630 681 3.71 323 1.75 
Iowa 8 808 345 422 4.01 268 2.67 
Kentucky 12 275 955 475 3.90 283 2.27 
Louisiana 13 437 239 425 3.38 285 2.20 
Maine 3 893 588 145 3.26 127 2.86 
Massachusetts 19 228 325 539 2.55 431 2.09 
Michigan§ 30 129 569 1229 4.09 825 2.74 
    Detroit 12 158 589 670 5.55 432 3.60 
Minnesota 15 074 919 675 4.54 447 3.04 
Missouri 17 041 549 522 2.87 252 1.40 
Montana 2 735 068 100 3.34 106 3.54 
Nebraska 5 182 752 145 2.62 121 2.19 
Nevada 6 505 746 87 1.52 113 1.83 
New Hampshire 3 823 495 116 3.08 141 3.69 
New Jersey 25 725 929 942 3.46 614 2.27 
New Mexico 3 687 478 89 2.55 112 3.09 
New York 57 449 353 2239 3.71 1500 2.51 
North Carolina 24 931 345 357 1.50 311 1.27 
Ohio 22 798 256 431 1.78 368 1.54 
Oklahoma 10 461 203 192 1.77 126 1.15 
Oregon 10 561 772 276 2.51 144 1.33 
Pennsylvania 36 997 707 1943 4.21 1117 2.56 
Rhode Island 3 203 585 82 2.18 102 2.82 
South Carolina 12 315 801 277 2.32 213 1.72 
South Dakota 2 283 574 65 2.54 34 1.41 
Texas 65 161 449 1920 3.70 1794 3.19 
Utah 6 953 023 154 3.16 86 1.65 
Washington§ 18 191 211 848 4.98 459 2.65 
    Seattle 12 474 150 614 5.36 313 2.64 
West Virginia 5 418 494 266 4.11 116 1.84 
Wisconsin 16 320 562 418 2.42 260 1.53 

Data source: NAACCR's CINA December 2005 submission of 1995 to 2003 patients.

*

Sum of the population estimates in the indicated areas for the years 2001, 2002, and 2003.

Total number of cases observed for the years 2001, 2002, and 2003.

Rates per 100 000; age-adjusted based on 2000 US standard population.

§

Includes the one or more metropolitan SEER registries listed under the state.

Table 3

Age-adjusted incidence rates of MDS by demographic characteristics, 2001-2003

SEER
NAACCR − SEER*
Total
RateCount%RateCount%RateCount%
Total 3.42 7 076  3.22 17 722  3.27 24 798  
Year of diagnosis 
    2001 3.29 2 246 31.7 3.02 5 641 31.8 3.10 7 887 31.8 
    2002 3.38 2 349 33.2 3.25 6 159 34.8 3.29 8 508 34.3 
    2003 3.58 2 481 35.1 3.38 5 922 33.4 3.45 8 403 33.9 
Sex 
    Male 4.51 3 803 53.7 4.4 9 715 54.8 4.43 13 518 54.5 
    Female 2.71 3 273 46.3 2.47 8 007 45.2 2.53 11 280 45.5 
Age 
    Less than 40 y 0.14 186 2.6 0.14 406 2.3 0.14 592 2.4 
    40 to 49 y 0.71 246 3.5 0.58 482 2.7 0.62 728 2.9 
    50 to 59 y 2.05 524 7.4 1.90 1 203 6.8 1.95 1 727 7.0 
    60 to 69 y 7.57 1 135 16.0 6.98 2 796 15.8 7.14 3 931 15.9 
    70 to 79 y 20.94 2 393 33.8 19.72 6 170 34.8 20.05 8 563 34.5 
    80 y and older 36.41 2 592 36.6 35.14 6 665 37.6 35.49 9 257 37.3 
Race 
    White 3.48 6 068 86.9 3.28 16 239 93.1 3.33 22 307 91.4 
    Black 3.02 500 7.2 2.13 984 5.6 2.36 1 484 6.1 
    Asian/Pacific Islander 2.63 400 5.7 2.25 171 1.0 2.51 571 2.3 
    AI/AN 1.02 13 0.2 1.3 40 0.2 1.22 53 0.2 
Ethnicity§ 
    Hispanic 2.79 516 7.3 2.85 635 4.2 2.83 1 151 5.2 
    Non-Hispanic 3.47 6 560 92.7 3.13 14 457 95.8 3.23 21 017 94.8 
SEER
NAACCR − SEER*
Total
RateCount%RateCount%RateCount%
Total 3.42 7 076  3.22 17 722  3.27 24 798  
Year of diagnosis 
    2001 3.29 2 246 31.7 3.02 5 641 31.8 3.10 7 887 31.8 
    2002 3.38 2 349 33.2 3.25 6 159 34.8 3.29 8 508 34.3 
    2003 3.58 2 481 35.1 3.38 5 922 33.4 3.45 8 403 33.9 
Sex 
    Male 4.51 3 803 53.7 4.4 9 715 54.8 4.43 13 518 54.5 
    Female 2.71 3 273 46.3 2.47 8 007 45.2 2.53 11 280 45.5 
Age 
    Less than 40 y 0.14 186 2.6 0.14 406 2.3 0.14 592 2.4 
    40 to 49 y 0.71 246 3.5 0.58 482 2.7 0.62 728 2.9 
    50 to 59 y 2.05 524 7.4 1.90 1 203 6.8 1.95 1 727 7.0 
    60 to 69 y 7.57 1 135 16.0 6.98 2 796 15.8 7.14 3 931 15.9 
    70 to 79 y 20.94 2 393 33.8 19.72 6 170 34.8 20.05 8 563 34.5 
    80 y and older 36.41 2 592 36.6 35.14 6 665 37.6 35.49 9 257 37.3 
Race 
    White 3.48 6 068 86.9 3.28 16 239 93.1 3.33 22 307 91.4 
    Black 3.02 500 7.2 2.13 984 5.6 2.36 1 484 6.1 
    Asian/Pacific Islander 2.63 400 5.7 2.25 171 1.0 2.51 571 2.3 
    AI/AN 1.02 13 0.2 1.3 40 0.2 1.22 53 0.2 
Ethnicity§ 
    Hispanic 2.79 516 7.3 2.85 635 4.2 2.83 1 151 5.2 
    Non-Hispanic 3.47 6 560 92.7 3.13 14 457 95.8 3.23 21 017 94.8 

Data source: NAACCR's CINA December 2005 submission of 1995 through 2003 patients.

AI/AN indicates American Indian/Alaska Native.

*

NAACCR registries minus SEER registries; excludes Seattle from Washington, Detroit from Michigan, and Atlanta from Georgia.

Rate per 100 000; age-adjusted based on 2000 US standard population.

Differences in incidence rates across demographic categories (year of diagnosis, sex, or race) were statistically significant (P < .05) within SEER registries, NAACCR minus SEER registries, and all registries combined

§

Differences in incidence rates by ethnicity were statistically significant (P < .05) within NAACCR minus SEER registries, and all registries combined, but not for SEER registries alone.

Incidence rates for CMD were lower than those for MDS, with an average annual age-adjusted incidence rate of 2.1 per 100 000, based on 16 119 reported patients in 2001 through 2003 (Table 4). No differences in incidence rates were observed by calendar year. (The incidence of CMD for 2004 in SEER was 2.1 per 100 000, based on 1561 patients.) CMD incidence rates were significantly higher in males (2.5 per 100 000) than females (1.8 per 100 000; P < .05). CMD incidence rates also significantly increased with age, although to a lesser extent than MDS incidence rates. Among individuals aged 80 years and older, the CMD incidence rate was 13.3 per 100 000. Statistically significant differences in CMD incidence rates were observed by race in all registries combined, with whites being at highest risk. No differences were observed by ethnicity. Trends in CMD incidence were similar in SEER and NAACCR minus SEER registries.

Table 4

Age-adjusted CMD incidence rates by demographic characteristics, 2001-2003

SEER
NAACCR – SEER*
Total
RateCount%RateCount%RateCount%
Total 2.01 4 226  2.17 11 893  2.12 16 119  
Year of diagnosis 
    2001 2.09 1 451 34.3 2.24 4 157 35.0 2.20 5 608 34.8 
    2002 1.99 1 410 33.4 2.15 4 065 34.2 2.11 5 475 34.0 
    2003 1.94 1 365 32.3 2.11 3 671 30.9 2.06 5 036 31.2 
Sex 
    Male 2.44 2 250 53.2 2.58 6 190 52.0 2.54 8 440 52.4 
    Female 1.68 1 976 46.8 1.84 5 703 48.0 1.80 7 679 47.6 
Age 
    Less than 40 y 0.21 277 6.6 0.29 871 7.3 0.27 1 148 7.1 
    40 to 49 y 1.22 422 10.0 1.31 1 082 9.1 1.29 1 504 9.3 
    50 to 59 y 2.53 648 15.3 2.65 1 673 14.1 2.62 2 321 14.4 
    60 to 69 y 5.63 848 20.1 6.02 2 420 20.3 5.92 3 268 20.3 
    70 to 79 y 10.18 1 163 27.5 10.42 3 259 27.4 10.36 4 422 27.4 
    80 y and older 12.19 868 20.5 13.64 2 588 21.8 13.25 3 456 21.4 
Race§ 
    White 1.99 3 462 84.6 2.17 10 527 91.0 2.12 13 989 89.4 
    Black 2.09 378 9.2 1.67 857 7.4 1.78 1 235 7.9 
    Asian/Pacific Islander 1.38 238 5.8 1.36 143 1.2 1.38 381 2.4 
    AI/AN 0.75 13 0.3 0.95 37 0.3 0.89 50 0.3 
Ethnicity 
    Hispanic 1.46 324 7.7 1.85 542 5.1 1.67 866 5.8 
    Non-Hispanic 2.07 3 902 92.3 2.21 10 113 94.9 2.17 14 015 94.2 
SEER
NAACCR – SEER*
Total
RateCount%RateCount%RateCount%
Total 2.01 4 226  2.17 11 893  2.12 16 119  
Year of diagnosis 
    2001 2.09 1 451 34.3 2.24 4 157 35.0 2.20 5 608 34.8 
    2002 1.99 1 410 33.4 2.15 4 065 34.2 2.11 5 475 34.0 
    2003 1.94 1 365 32.3 2.11 3 671 30.9 2.06 5 036 31.2 
Sex 
    Male 2.44 2 250 53.2 2.58 6 190 52.0 2.54 8 440 52.4 
    Female 1.68 1 976 46.8 1.84 5 703 48.0 1.80 7 679 47.6 
Age 
    Less than 40 y 0.21 277 6.6 0.29 871 7.3 0.27 1 148 7.1 
    40 to 49 y 1.22 422 10.0 1.31 1 082 9.1 1.29 1 504 9.3 
    50 to 59 y 2.53 648 15.3 2.65 1 673 14.1 2.62 2 321 14.4 
    60 to 69 y 5.63 848 20.1 6.02 2 420 20.3 5.92 3 268 20.3 
    70 to 79 y 10.18 1 163 27.5 10.42 3 259 27.4 10.36 4 422 27.4 
    80 y and older 12.19 868 20.5 13.64 2 588 21.8 13.25 3 456 21.4 
Race§ 
    White 1.99 3 462 84.6 2.17 10 527 91.0 2.12 13 989 89.4 
    Black 2.09 378 9.2 1.67 857 7.4 1.78 1 235 7.9 
    Asian/Pacific Islander 1.38 238 5.8 1.36 143 1.2 1.38 381 2.4 
    AI/AN 0.75 13 0.3 0.95 37 0.3 0.89 50 0.3 
Ethnicity 
    Hispanic 1.46 324 7.7 1.85 542 5.1 1.67 866 5.8 
    Non-Hispanic 2.07 3 902 92.3 2.21 10 113 94.9 2.17 14 015 94.2 

Data source: NAACCR's CINA December 2005 submission of 1995 to 2003 patients.

AI/AN indicates American Indian/Alaska Native.

*

NAACCR registries minus SEER registries; excludes Seattle from Washington, Detroit from Michigan, and Atlanta from Georgia.

Rate per 100 000; age-adjusted based on 2000 US standard population.

Differences in incidence rates across demographic categories (sex and age) were statistically significant (P < .05) within SEER registries, NAACCR minus SEER registries, and all registries combined.

§

Differences in incidence rates by race were statistically significant (P < .05) within NAACCR minus SEER registries, and all registries combined, but not for SEER registries alone.

Frequencies and age-adjusted incidence rates are presented by disease subtype in Table 5. The distributions of disease subtypes were similar for SEER and NAACCR minus SEER registries. Refractory anemia (RA) comprised 16.8% and 13.4% of patients with MDS reported to SEER and NAACCR minus SEER registries, respectively. RA with sideroblasts and RA with excess blasts were the next most commonly reported MDS subtypes. More than half of all patients with MDS reported in SEER and NAACCR registries combined were of unspecified subtype. Polycythemia vera comprised 45% of patients with CMD, and 24% patients had essential thrombocythemia. Approximately 20% of patients with CMD were of unspecified subtype. The age-adjusted incidence rate for CMML was approximately one-tenth that of MDS, at 0.3 per 100 000.

Table 5

MDS, CMD, and CMML patient counts and rates by subtype for both sexes, 2001-2003

Disease type according to ICD-O-3ICD-O-3 morphology codeRateSEER
NAACCR – SEER*
Total
Count%RateCount%RateCount%
Total — 5.43 11 311 — 5.40 29 637 — 5.40 40 948 — 
MDS 998 3.42 7 076 100.0 3.22 17 722 100.0 3.28 24 798 100.0 
    RA 9980 0.57 1 186 16.8 0.43 2 375 13.4 0.47 3 561 14.4 
    RA with sideroblasts 9982 0.40 819 11.6 0.30 1 662 9.4 0.33 2 481 10.0 
    RA with excess blasts 9983 0.47 968 13.7 0.34 1 850 10.4 0.37 2 818 11.4 
    RA with excess blasts in transformation 9984 0.06 129 1.8 0.05 257 1.5 0.05 386 1.6 
    Refractory cytopenia with multilineage dysplasia 9985 0.13 262 3.7 0.06 342 1.9 0.08 604 2.4 
    MDS with 5q deletion 9986 0.06 119 1.7 0.06 311 1.8 0.06 430 1.7 
    Therapy-related MDS 9987 0.06 126 1.8 0.09 484 2.7 0.08 610 2.5 
    MDS, not otherwise specified (NOS) 9989 1.67 3 467 49.0 1.89 10 441 58.9 1.84 13 908 56.1 
CMD§ 995-996 2.01 4 226 100.0 2.17 11 893 100.0 2.13 16 119 100.0 
    Polycythemia vera 9950 0.79 1 679 39.7 1.01 5 504 46.3 0.95 7 183 44.6 
    Myelosclerosis with myeloid metaplasia 9961 0.25 514 12.2 0.21 1 160 9.8 0.22 1 674 10.4 
    Essential thrombocythemia 9962 0.53 1 108 26.2 0.51 2 766 23.3 0.51 3 874 24.0 
    Chronic neutrophilic leukemia 9963 0.01 10 0.2 0.01 32 0.3 0.01 42 0.3 
    Hypereosinophilic syndrome 9964 0.03 71 1.7 0.03 158 1.3 0.03 229 1.4 
    Chronic myeloproliferative disease, NOS 9960 0.41 844 20.0 0.41 2 273 19.1 0.41 3 117 19.3 
Chronic myelomonocytic leukemia (CMML), NOS 9945 0.37 751  0.34 1 850  0.34 2 601  
Disease type according to ICD-O-3ICD-O-3 morphology codeRateSEER
NAACCR – SEER*
Total
Count%RateCount%RateCount%
Total — 5.43 11 311 — 5.40 29 637 — 5.40 40 948 — 
MDS 998 3.42 7 076 100.0 3.22 17 722 100.0 3.28 24 798 100.0 
    RA 9980 0.57 1 186 16.8 0.43 2 375 13.4 0.47 3 561 14.4 
    RA with sideroblasts 9982 0.40 819 11.6 0.30 1 662 9.4 0.33 2 481 10.0 
    RA with excess blasts 9983 0.47 968 13.7 0.34 1 850 10.4 0.37 2 818 11.4 
    RA with excess blasts in transformation 9984 0.06 129 1.8 0.05 257 1.5 0.05 386 1.6 
    Refractory cytopenia with multilineage dysplasia 9985 0.13 262 3.7 0.06 342 1.9 0.08 604 2.4 
    MDS with 5q deletion 9986 0.06 119 1.7 0.06 311 1.8 0.06 430 1.7 
    Therapy-related MDS 9987 0.06 126 1.8 0.09 484 2.7 0.08 610 2.5 
    MDS, not otherwise specified (NOS) 9989 1.67 3 467 49.0 1.89 10 441 58.9 1.84 13 908 56.1 
CMD§ 995-996 2.01 4 226 100.0 2.17 11 893 100.0 2.13 16 119 100.0 
    Polycythemia vera 9950 0.79 1 679 39.7 1.01 5 504 46.3 0.95 7 183 44.6 
    Myelosclerosis with myeloid metaplasia 9961 0.25 514 12.2 0.21 1 160 9.8 0.22 1 674 10.4 
    Essential thrombocythemia 9962 0.53 1 108 26.2 0.51 2 766 23.3 0.51 3 874 24.0 
    Chronic neutrophilic leukemia 9963 0.01 10 0.2 0.01 32 0.3 0.01 42 0.3 
    Hypereosinophilic syndrome 9964 0.03 71 1.7 0.03 158 1.3 0.03 229 1.4 
    Chronic myeloproliferative disease, NOS 9960 0.41 844 20.0 0.41 2 273 19.1 0.41 3 117 19.3 
Chronic myelomonocytic leukemia (CMML), NOS 9945 0.37 751  0.34 1 850  0.34 2 601  

Data source: NAACCR's CINA December 2005 submission of 1995 to 2003 patients.

*

NAACCR registries minus SEER registries; excludes Seattle from Washington, Detroit from Michigan, and Atlanta from Georgia.

Rate per 100 000; age-adjusted based on 2000 US standard population.

Includes 9 and 22 patients with other malignant hematologic disorders (ICD-O-3 code 9970-9975) in SEER and NAACCR minus SEER, respectively.

§

Synonymous with myeloproliferative neoplasms; does not include BCR/ABL+ chronic myelocytic leukemia.

Synonymous with chronic idiopathic myelofibrosis (WHO classification) or primary myelofibrosis.

CMML is considered MDS in the FAB classification, but it is grouped with the leukemias in the WHO classification and ICD-O-3.

Applying the observed incidence rates from combined SEER and NAACCR registries to the total US Census population estimates for 2004, the estimated numbers of patients with MDS, CMD, and CMML diagnosed in the total US population for 2004 were 9730, 6328, and 1039, respectively (Table 6). Approximately 7000 patients with MDS and 3000 patients with CMD were estimated to occur in individuals aged 70 years and older.

Table 6

Estimated numbers of patients with MDS, CMD, and CMML for the total US population in 2004

Demographic characteristicMDS
CMD
CMML
TotalMaleFemaleTotalMaleFemaleTotalMaleFemale
Total 9730 5329 4400 6328 3329 2999 1039 638 401 
By age 
    Less than 40 y 223 116 107 432 245 187 13 
    40 to 49 y 284 135 149 586 335 251 21 12 
    50 to 59 y 709 370 339 950 572 378 84 59 25 
    60 to 69 y 1583 912 671 1319 729 590 163 113 50 
    70 to 79 y 3212 1884 1328 1656 866 790 388 249 139 
    80 y and older 3718 1913 1805 1384 582 802 370 201 169 
By race 
    White 8549 4710 3839 5463 2886 2577 914 564 350 
    Black 821 419 402 598 299 299 86 50 36 
    Other 359 200 159 268 144 124 39 25 14 
Demographic characteristicMDS
CMD
CMML
TotalMaleFemaleTotalMaleFemaleTotalMaleFemale
Total 9730 5329 4400 6328 3329 2999 1039 638 401 
By age 
    Less than 40 y 223 116 107 432 245 187 13 
    40 to 49 y 284 135 149 586 335 251 21 12 
    50 to 59 y 709 370 339 950 572 378 84 59 25 
    60 to 69 y 1583 912 671 1319 729 590 163 113 50 
    70 to 79 y 3212 1884 1328 1656 866 790 388 249 139 
    80 y and older 3718 1913 1805 1384 582 802 370 201 169 
By race 
    White 8549 4710 3839 5463 2886 2577 914 564 350 
    Black 821 419 402 598 299 299 86 50 36 
    Other 359 200 159 268 144 124 39 25 14 

Data source: Based on US Census population estimates for 2004 and age-specific rates for 2001 to 2003 from NAACCR's CINA December 2005 submission of 1995 to 2003 patients.

Trends in survival based on SEER data are presented in Table 7. Relative to the general population, 3-year survival with MDS was poorer than survival with CMD (45% vs 80%, respectively), while the worst 3-year survival was observed for CMML (21%). Males experienced poorer 3-year survival than did females for MDS, CMD, and CMML, a difference that was statistically significant for MDS (males, 41%; females, 50%). Survival for patients with MDS and CMD decreased with age: among those younger than 50 years of age at diagnosis, relative 3-year survival was greater than 60% and greater than 90% for MDS and CMD, respectively, while relative 3-year survival among those 80 years and older dropped to 37% and 66% for MDS and CMD, respectively. Although a similar inverse association between age at diagnosis and survival was observed for CMML, patients in the youngest age category for which there were reportable data (50-59 years) still experienced an extremely poor prognosis, with a relative 3-year survival of 33%. The 3-year survival was greatest for the most common CMD subtypes, polycythemia vera (n = 1615 patients; 88% 3-year survival) and essential thrombocythemia (n = 1028 patients, 92% 3-year survival). Similar survival was observed among 464 patients with hypereosinophilic syndrome (85%), while the poorest survival among patients with CMD was observed for myelosclerosis with myeloid metaplasia (synonymous with primary myelofibrosis; n = 464 patients; 53% 3-year survival) and CMD, not otherwise specified (n = 730; 63% 3-year survival).

Table 7

The 3-year relative survival rates for MDS, CMD, and CMML among cases diagnosed in 2001 through 2003 and followed through 2004 in SEER

Demographic characteristicMDS
CMD
CMML
No. patients3-year relative survival, % (95% CI)No. patients3-year relative survival, % (95% CI)No. patients3-year relative survival, % (95% CI)
Total 5597 45 (43-47) 3916 80 (78-82) 580 21 (16-26) 
Sex 
    Male 3001 41 (38-43) 2099 79 (77-82) 345 18 (12-23) 
    Female 2596 50 (47-53) 1817 81 (78-84) 235 27 (18-35) 
Age at diagnosis 
    Less than 40 y 159 63 (54-72) 281 92 (88-96) — — 
    40 to 49 y 212 66 (58-73) 429 90 (86-94) — — 
    50 to 59 y 442 54 (48-60) 654 89 (86-92) 35 33 (13-53) 
    60 to 69 y 951 48 (44-53) 807 80 (76-84) 116 28 (17-39) 
    70 to 79 y 1909 43 (40-46) 1007 73 (69-77) 212 22 (15-30) 
    80 y and older 1924 37 (34-41) 738 66 (63-70) 202 12 (5-20)  
Race 
    White 4740 44 (42-46) 3216 80 (78-82) 510 21 (16-26) 
    Black 422 49 (42-56) 344 72 (65-78) 33 15 (0-32)  
Demographic characteristicMDS
CMD
CMML
No. patients3-year relative survival, % (95% CI)No. patients3-year relative survival, % (95% CI)No. patients3-year relative survival, % (95% CI)
Total 5597 45 (43-47) 3916 80 (78-82) 580 21 (16-26) 
Sex 
    Male 3001 41 (38-43) 2099 79 (77-82) 345 18 (12-23) 
    Female 2596 50 (47-53) 1817 81 (78-84) 235 27 (18-35) 
Age at diagnosis 
    Less than 40 y 159 63 (54-72) 281 92 (88-96) — — 
    40 to 49 y 212 66 (58-73) 429 90 (86-94) — — 
    50 to 59 y 442 54 (48-60) 654 89 (86-92) 35 33 (13-53) 
    60 to 69 y 951 48 (44-53) 807 80 (76-84) 116 28 (17-39) 
    70 to 79 y 1909 43 (40-46) 1007 73 (69-77) 212 22 (15-30) 
    80 y and older 1924 37 (34-41) 738 66 (63-70) 202 12 (5-20)  
Race 
    White 4740 44 (42-46) 3216 80 (78-82) 510 21 (16-26) 
    Black 422 49 (42-56) 344 72 (65-78) 33 15 (0-32)  

Data source: SEER Program based on November 2006 NCI SEER data submission.

— indicates statistic could not be calculated due presence of fewer than 15 observations.

Discussion

The current analysis is the first to be based on NAACCR data, encompassing approximately 82% of the US population.13  Based on more than 40 000 observations, average annual age-adjusted incidence rates in the United States were highest for MDS, followed by CMD and CMML, for the years 2001 through 2003, with corresponding rates of 3.3, 2.1, and 0.3 per 100 000, respectively. Incidence rates were similar whether they were based on SEER or NAACCR minus SEER registries, with results from NAACCR minus SEER registries confirming the positive trends in MDS incidence with increasing age and male sex previously reported from SEER.2 

MDS may be misdiagnosed and/or underreported to population-based cancer registries. Elderly patients presenting to primary care physicians with anemia may not be assessed for a possible MDS diagnosis, and the likelihood of accurate MDS diagnoses may vary, depending on pathology expertise, physician, and patient characteristics. Although 88% of MDS diagnoses were confirmed by positive histology or laboratory test in NAACCR and SEER registries, 56% of diagnoses were of unspecified subtypes. Therefore, the observed subtype distribution may not be representative of the true MDS patient population if some subtypes were more likely to be characterized than others. No information or estimates are available on the number of patients in whom a possible diagnosis of MDS is not investigated by bone marrow studies.

Incidence rates for MDS increased with calendar year in 2001 to 2003 among the combined registry data, with the most recent 2004 SEER data indicating a rate of 3.8 per 100 000. Since MDS became a reportable malignancy only in 2001, it is possible that the increase in incidence rates over time reflect acclimation of those involved in the reporting process to the new guidelines resulting in rising capture rates. For example, only 4% of patients with MDS in NAACCR were reported by physicians' offices in 2001 through 2003. Since MDS is more commonly diagnosed and managed outside of hospitals compared with other cancers, it is possible that many of these cases are unreported to population-based registries. Although independent laboratories are also responsible for reporting MDS cases to local registries, the completeness of case reporting by out-of-state laboratories is unknown. As recently described by De Roos and colleagues,14  case-finding methods may affect the completeness of MDS case reporting; registries that rely on passive case-finding (ie, cases are reported to the registry by hospitals and other diagnostic facilities) may not capture as many patients with MDS as those that use active case-finding methods (ie, surveying billing, pathology, and cytogenetic and other laboratory testing records). Surveys of private physicians' offices and central referral laboratories are needed to estimate the proportion of patients with MDS not captured by hospital registries. Nevertheless, the incidence rate of MDS estimated for the United States in 2001 through 2003 (3.3 per 100 000) is remarkably similar to those previously reported from European countries,15  including England and Wales (3.6 per 100 000),16  Germany (4.1 per 100 000),17  Sweden (3.6 per 100 000)18  and France (3.2 per 100 000).19  Therefore, if substantial underreporting of MDS to cancer registries exists, the phenomenon is most likely not isolated to the United States. As clinicians, laboratories, and cancer registrars become more accustomed to reporting and recording MDS cases, incidence rates may continue to rise in the upcoming years.

In this first report of population-based incidence rates of CMD for the United States, demographic risk factors for CMD were similar to MDS, including older age, male sex, and white race. Although the CMD incidence rates did not increase with calendar year in 2001 through 2004 as they did for MDS, underreporting of CMD to population-based registries cannot be excluded. A recent analysis of medical claims data estimated the prevalence of polycythemia vera and essential thrombocythemia in the United States to be 136 000 patients as of 2003,20  far greater than what would be expected based on the incidence rates reported here from SEER and NAACCR.

The 3-year relative survival was greater in patients with CMD (80%) than patients with MDS (45%), even among those aged 80 years and older at diagnosis. In contrast, survival with CMML was extremely poor (21%), even among younger patients. These data suggest that treatments with potential to alter the natural history of disease or curative strategies such as hematopoietic stem cell transplantation should be considered for patients with CMML who are appropriate candidates.

In conclusion, continued surveillance of MDS, CMD, and CMML through population-based registries will be useful for investigating trends in incidence and survival so that future prevention and treatment strategies may be developed. Concurrent assessment of potential misdiagnosis and underreporting of these malignant conditions is paramount for the elucidation and interpretation of these rates and trends.

The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked “advertisement” in accordance with 18 USC section 1734.

Acknowledgments

The authors are grateful to Holly Howe at NAACCR and acknowledge Matthew Hayat for assistance with preliminary analyses.

Authorship

Contribution: A.F.L., B.K.E., L.R., W.D.M., S.S.S., M.S., and D.E.R. designed the research; N.H. analyzed the data, and D.E.R. wrote the paper with contributions from A.F.L., B.K.E., L.R., W.D.M., S.S.S., M.S., and N.H.

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Correspondence: Dana E. Rollison, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612; e-mail: dana.rollison@moffitt.org.

References

References
1
Disperati
 
P
Ichim
 
CV
Tkachuk
 
D
, et al. 
Progression of myelodysplasia to acute lymphoblastic leukaemia: implications for disease biology.
Leuk Res
2006
, vol. 
30
 (pg. 
233
-
239
)
2
Ma
 
X
Does
 
M
Raza
 
A
Mayne
 
ST
Myelodysplastic syndromes: incidence and survival in the United States.
Cancer
2007
, vol. 
109
 (pg. 
1536
-
1542
)
3
Espey
 
DK
Wu
 
XC
Swan
 
J
, et al. 
Annual report to the nation on the status of cancer, 1975-2004, featuring cancer in American Indians and Alaska Natives.
Cancer
2007
, vol. 
110
 (pg. 
2119
-
2152
)
4
North American Association of Central Cancer Registries
CINA Deluxe Standard File Instructions.
2006
Springfield, IL
pg. 
3
 
5
Fritz
 
A
Percy
 
C
Jack
 
A
, et al. 
International Classification of Diseases for Oncology
2000
3rd ed
Geneva
World Health Organization
6
Harris
 
NL
Jaffe
 
ES
Diebold
 
J
, et al. 
World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting—Airlie House, Virginia, November 1997.
J Clin Oncol
1999
, vol. 
17
 (pg. 
3835
-
3849
)
7
Vardiman
 
JW
Harris
 
NL
Brunning
 
RD
The World Health Organization (WHO) classification of the myeloid neoplasms.
Blood
2002
, vol. 
100
 (pg. 
2292
-
2302
)
8
Matasar
 
MJ
Ritchie
 
EK
Consedine
 
N
Magai
 
C
Neugut
 
AI
Incidence rates of the major leukemia subtypes among US Hispanics, Blacks, and non-Hispanic Whites.
Leuk Lymphoma
2006
, vol. 
47
 (pg. 
2365
-
2370
)
9
Ries
 
LAG
Melbert
 
D
Krpacho
 
M
, et al. 
SEER Cancer Statistics Review, 1975–2004.
2007
Accessed August 15, 2007
Bethesda, MD
National Cancer Institute
 
Based on November 2006 SEER data submission, posted to the SEER Web site, 2007
 
10
National Cancer Institute
SEER*Stat software.
Accessed August 15, 2007 
11
Surveillance, Epidemiology, and End Results (SEER) Program. SEER*Stat Database: Incidence, SEER 17 Regs Limited-Use, Nov 2006 Sub (2000-2004) - Linked To County Attributes - Total U.S. 1969-2004 Counties.
2007
4
Accessed August 15, 2007
Bethesda, MD
National Cancer Institute, DCCPS, Surveillance Research, Program, Cancer Statistics Branch
 
12
Ederer
 
F
Axtell
 
LM
Cutler
 
SJ
The relative survival rate: a statistical methodology.
Natl Cancer Inst Monogr
1961
, vol. 
6
 (pg. 
101
-
121
)
13
Howe
 
HL
Wu
 
X
Ries
 
LA
, et al. 
Annual report to the nation on the status of cancer, 1975–2003, featuring cancer among U. S. Hispanic/Latino populations.
Cancer
2006
, vol. 
107
 (pg. 
1711
-
1742
)
14
De Roos
 
AJ
Deeg
 
HJ
Davis
 
S
A population-based study of survival in patients with secondary myelodysplastic syndromes (MDS): impact of type and treatment of primary cancers.
Cancer Causes Control
2007
, vol. 
18
 (pg. 
1199
-
1208
)
15
Hamblin
 
T
Bennett
 
J
Epidemiology of the myelodysplastic syndromes.
The Myelodysplastic Syndromes: Pathology and Clinical Management
2002
New York, NY
Marcel Dekker, Inc
(pg. 
15
-
25
)
16
Cartwright
 
R
Alexander
 
F
McKinney
 
P
Ricketts
 
T
Leukaemias and lymphoma: an atlas of distribution within areas of England and Wales 1984-88.
1990
London
Leukaemia Research Fund
17
Aul
 
C
Gattermann
 
N
Schneider
 
W
Age-related incidence and other epidemiological aspects of myelodysplastic syndromes.
Br J Haematol
1992
, vol. 
82
 (pg. 
358
-
367
)
18
Radlund
 
A
Thiede
 
T
Hansen
 
S
Carlsson
 
M
Engquist
 
L
Incidence of myelodysplastic syndromes in a Swedish population.
Eur J Haematol
1995
, vol. 
54
 (pg. 
153
-
156
)
19
Maynadie
 
M
Verret
 
C
Moskovtchenko
 
P
, et al. 
Epidemiological characteristics of myelodysplastic syndrome in a well-defined French population.
Br J Cancer
1996
, vol. 
74
 (pg. 
288
-
290
)
20
Ma
 
X
Vanasse
 
G
Cartmel
 
B
Wang
 
Y
Selinger
 
HA
Prevalence of polycythemia vera and essential thrombocythemia.
Am J Hematol
2008
, vol. 
83
 (pg. 
359
-
362
)