1536
`
`Myelodysplastic Syndromes
`IncidenceandSurvivalintheUnitedStates
`
`1
`Xiaomei Ma, PhD
`Monique Does, BA
`3
`Azra Raza, MD
`Susan T. Mayne, PhD
`
`2
`
`1
`
`1 Department of Epidemiology and Public Health,
`Yale University School of Medicine, New Haven,
`Connecticut.
`
`2 School of Public Health, University of California
`at Berkeley, Berkeley, California.
`
`3 Division of Hematology, University of Massa-
`chusetts Medical Center, Worcester, Massachu-
`setts.
`
`Supported by a supplement to contract N01-PC-
`35133 between the National Cancer
`Institute’s
`Surveillance, Epidemiology, and End Results Pro-
`gram and the Connecticut Department of Public
`Health and by a grant awarded by the National
`Cancer Institute (K07 CA119108).
`
`Address for reprints: Xiaomei Ma, PhD, Depart-
`ment of Epidemiology and Public Health, Yale
`University School of Medicine, 60 College Street,
`Box 208034, New Haven, CT 06520-8034; Fax:
`(203) 785-6980; E-mail: xiaomei.ma@yale.edu
`
`Received December 19, 2006; revision received
`December 23, 2006; accepted January 3, 2007.
`
`BACKGROUND. Myelodysplastic syndromes (MDS) became reportable to the
`Surveillance, Epidemiology, and End Results (SEER) Program (the United States
`
`cancer surveillance program) in 2001. This provided the first opportunity to
`
`examine the incidence and survival of patients with MDS in the United States
`
`using a large, population-based database.
`METHODS. The SEER 17 regions public-use database (November 2005 submis-
`sion) was accessed to obtain data on the frequency, incidence, and survival of
`
`patients with MDS. Geographic areas were selected for inclusion in the SEER
`
`Program based on their ability to operate and maintain a high-quality, popula-
`
`tion-based cancer reporting system and for their epidemiologically significant
`
`population subgroups.
`RESULTS. SEER data from 2001 through 2003 indicated that the risk of MDS
`increased with age, and approximately 86% of MDS cases were diagnosed in indi-
`viduals aged 60 years (median age at diagnosis ¼ 76 years). Men had a signifi-
`cantly higher incidence rate than women (4.5 vs 2.7 per 100,000 per year).
`
`Among racial groups, white individuals had the highest incidence rate. In 2003,
`
`approximately 10,300 incident cases of MDS were diagnosed in the United States.
`
`The survival of MDS patients was poor, with an observed 3-year survival rate of
`
`only 35% (5-year survival data were not available at the time of the current
`
`report). Male patients and patients who were diagnosed at an older age had
`
`significantly worse survival. MDS survival also varied by clinical subtype, and the
`
`survival of patients who had refractory anemia was somewhat worse than
`
`reported previously. The availability of descriptive epidemiologic data on MDS
`
`can be used now to facilitate much needed research on the etiology and outcome
`
`of MDS.
`CONCLUSIONS. The current results indicated that >10,000 incident cases of MDS
`are diagnosed annually in the United States, and the survival of patients with
`
`MDS is poor. The availability of descriptive epidemiologic data on MDS can be
`
`used now to facilitate much needed research on the etiology and outcomes of
`MDS. Cancer 2007;109:1536–42. Ó 2007 American Cancer Society.
`
`KEYWORDS: myelodysplastic syndromes, incidence, survival, Surveillance, Epide-
`miology, and End Results Program.
`
`T he myelodysplastic syndromes (MDS), also known as myelodys-
`
`plasia, are a group of chronic conditions that involve persistent
`peripheral blood cytopenias. Because of the lack of large, population-
`based studies, the incidence of MDS in the United States has not
`been well documented. Estimates from 1995 suggest that there
`were approximately 1500 new cases each year in the United States,1
`whereas a more recent estimate was as high as 15,000 new cases
`each year.2 Population-based survival data in the United States also
`are lacking. In 2001, MDS became reportable to the Surveillance,
`
`ª 2007 American Cancer Society
`DOI 10.1002/cncr.22570
`Published online 7 March 2007 in Wiley InterScience (www.interscience.wiley.com).
`
`CELGENE 2098
`APOTEX v. CELGENE
`IPR2023-00512
`
`

`

`Epidemiology, and End Results (SEER) Program,
`which consists of high-quality, population-based
`cancer registries that are supported and sponsored
`by the National Cancer Institute.3 The SEER Program
`is the authoritative source on cancer incidence and
`survival in the United States. The current analysis,
`which was based on SEER data from 2001 through
`2003, is the first assessment to our knowledge of the
`incidence and survival of MDS using a large, popu-
`lation-based database in the United States. SEER
`data from more recent years were not available at
`the time of this report.
`
`MATERIALS AND METHODS
`Source of Data
`The SEER 17 regions public-use database (November
`2005 submission) was accessed to obtain data on
`the frequency, incidence, and survival of MDS.4 Geo-
`graphic areas were selected for inclusion in the SEER
`Program based on their ability to operate and main-
`tain a high-quality, population-based cancer report-
`ing system and for their epidemiologically significant
`population subgroups. The population covered by
`SEER is comparable to the general United States
`population with regard to measures of poverty and
`education. The SEER population tends to be some-
`what more urban and has a higher proportion of
`foreign-born individuals than the general United
`States population.5 The 17 SEER regions cover
`approximately 26.2% of the United States population
`and include the states of Connecticut, Hawaii, Iowa,
`Kentucky, Louisiana, New Jersey, New Mexico, and
`Utah; the metropolitan areas of Atlanta, Detroit, Los
`Angeles, San Francisco-Oakland, San Jose-Monterey,
`and Seattle (Puget Sound); as well as California (ex-
`cluding San Francisco-Oakland, San Jose-Monterey,
`and Los Angeles),
`rural Georgia, and American
`Indians/Alaska Natives residing in the state of Alaska.
`In 2003, the most recent year for which SEER data
`are available, the total population in the 17 regions
`exceeded 76 million. All incident MDS cases (histol-
`ogy type International Classification of Diseases for
`Oncology, 3rd edition [ICD-O-3] codes 9980, 9982–
`9987, and 9989) diagnosed from 2001 to 2003 that
`were reported to the SEER Program were included in
`this analysis.
`MDS is heterogeneous both biologically and clini-
`cally. The development of diagnostic criteria was
`addressed first
`in 1974 and 1975 by a group of
`prominent hematologists known as
`the French-
`American-British (FAB) Cooperative Group.6 The FAB
`classification of MDS includes 1) refractory anemia
`(RA), 2) RA with ringed sideroblasts (RARS), 3) RA
`
`MDS: Incidence and Survival/Ma et al.
`
`1537
`
`with excess blasts (RAEB), 4) RAEB in transformation
`(RAEB-T), and 5) chronic myelomonocytic leukemia
`with white blood cell counts 12,000 lL.7 The World
`Health Organization (WHO) published its recom-
`mendation for classification of MDS in 19998 and
`published a clarification and rationale for differences
`between the FAB and WHO classifications in 2002.9
`The WHO recommendation for the classification of
`MDS includes 1) RA, 2) RARS, 3) refractory cytopenia
`with multilineage dysplasia (RCMD), 4) RCMD and
`ringed sideroblasts (RCMD-RS), 5) RAEB-1, 6) RAEB-
`2, 7) MDS associated with isolated 5q deletion, and
`8) MDS, unclassified.
`The MDS histology types recorded in SEER are
`based onICD-O-3 codes, which are not 100% consist-
`ent with either the FAB classification or the WHO
`recommendation. The 8 ICD-O-3 codes that are in-
`cluded in SEER for MDS are 9980 (RA), 9982 (RARS),
`9983 (RAEB, including RAEB under the FAB classifi-
`cation and both RAEB-1 and RAEB-2 under the WHO
`recommendation), 9984 (RAEB-T), 9985 (RCMD),
`9986 (MDS associated with 5q deletion), 9987
`(therapy-related MDS), and 9989 (MDS, not other-
`wise specified).
`
`Data Analyses
`The SEER*Stat program (version 6.2.4; National
`Cancer Institute) was used to 1) estimate incidence
`rates and corresponding confidence intervals, 2) cal-
`culate observed survival and relative survival, and 3)
`generate a list of MDS patients with information on
`other
`tumors
`recorded in SEER. The CanSurv
`program (version 1.0; National Cancer Institute) was
`used to fit semiparametric proportional hazard mod-
`els to evaluate factors that influence survival. The
`SAS statistical software package (version 9.1.3 for
`Windows; SAS Institute) was used to assess the time
`interval between the diagnosis of previous primary
`tumors (when relevant; see below) and the diagnosis
`of MDS.
`The incidence of MDS was described by age, sex,
`and race (white, African-American, American Indian/
`Alaska Native, and Asian/Pacific Islander). Included
`in the survival analysis was a subgroup of patients
`with MDS who fulfilled the following criteria: 1) diag-
`nosed in 2001 or 2002, 2) actively followed by SEER
`for survival, 3) not identified from death certificates
`or autopsies only, and 4) did not have other primary
`tumors recorded in SEER prior to the diagnosis of
`MDS. The last criterion was applied because there
`was a concern that the survival of patients with MDS
`who had previous tumors may be affected by their
`other primary tumors or by the treatment they receiv-
`ed for those tumors. Patients who were diagnosed in
`
`

`

`1538
`
`CANCER April 15, 2007 / Volume 109 / Number 8
`
`2003 were excluded because they would not have
`had >12 months of follow-up by the end of 2003,
`when the survival data were censored. Because the
`November 2005 submission of SEER data only in-
`cluded survival information through December 2003,
`the survival of patients with MDS beyond 36 months
`could not be evaluated with the data available.
`Observed survival was calculated using the ac-
`tuarial method, also known as the life-table method,
`with 3-month intervals. For an individual patient, the
`expected survival is generated based on United States
`life tables matched to the individual on age, sex,
`race, and year of diagnosis, and the relative survival
`equals observed survival divided by expected sur-
`vival. A relative survival <1 indicates that an indivi-
`dual has a poorer survival than the United States
`general population with the same age, sex, and race
`at the same calendar time. Survival measures were
`reported by age, sex, race, and major MDS subtypes,
`including RA (histology type ICD-O-3 code 9980),
`RARS (histology type ICD-O-3 code 9982), and RAEB
`(histology type ICD-O-3 code 9983).
`In addition,
`hazard ratios and their corresponding 95% confi-
`dence intervals (95% CIs) were estimated for demo-
`graphic factors that were associated significantly
`with the relative survival of patients with MDS. The
`survival of other subtypes was not described sepa-
`rately because of
`the small number of patients
`reported to SEER.
`Patients with MDS who had previous primary
`tumors were identified. The type of their previous
`tumors and the time intervals between the diagnosis
`of previous tumors and the diagnosis of MDS were
`assessed. Two different time intervals were calcu-
`lated: 1) the interval between the diagnosis of the
`first primary tumor and the diagnosis of MDS and
`2) the interval between the diagnosis of the most
`recent non-MDS primary tumor and the diagnosis of
`MDS.
`
`RESULTS
`The SEER 17 regions public-use database (November
`2005 submission) included a total of 7131 MDS diag-
`noses during 2001 to 2003, of which 3828 (53.7%)
`were men, and 3303 (46.3%) were women. The ma-
`jority of MDS cases were diagnosed in older indivi-
`duals, and the median age at diagnosis was 76 years.
`The percentages of patients diagnosed in individuals
`aged 60 years, 65 years, 70 years, and 75 years
`were 86.4%, 80.0%, 70.3%, and 55.9%, respectively.
`For both men and women, the risk of MDS increased
`with age (Table 1).
`
`TABLE 1
`Age-Specific Incidence Rates of Myelodysplastic Syndromes in the
`United States, 2001–2003: The Surveillance, Epidemiology, and End
`Results Program 17 Regions Public-use Database, November 2005
`Submission
`
`Men and women
`
`Men
`
`Women
`
`Age, y
`
`Count
`
`Rate*
`
`Count
`
`Rate*
`
`Count
`
`Rate*
`
`0
`1–4
`5–9
`10–14
`15–19
`20–24
`25–29
`30–34
`35–39
`40–44
`45–49
`50–54
`55–59
`60–64
`65–69
`70–74
`75–79
`80–84
`85
`Total
`
`8
`26
`10
`12
`17
`12
`18
`30
`58
`100
`148
`216
`314
`460
`686
`1032
`1374
`1406
`1204
`7131
`
`0.2
`0.2
`0.1
`0.1
`0.1
`0.1
`0.1
`0.2
`0.3
`0.6
`0.9
`1.5
`2.8
`5.4
`10
`16.6
`25.7
`36.2
`36.4
`
`3
`13
`2
`5
`8
`9
`11
`22
`33
`56
`72
`112
`161
`257
`386
`599
`785
`729
`565
`3828
`
`0.2
`0.2
`0
`0.1
`0.1
`0.1
`0.1
`0.3
`0.4
`0.6
`0.9
`1.6
`2.9
`6.3
`12.2
`21.8
`35.7
`48.9
`54.7
`
`5
`13
`8
`7
`9
`3
`7
`8
`25
`44
`76
`104
`153
`203
`300
`433
`589
`677
`639
`3303
`
`* Rates are per 100,000 per year.
`
`0.3
`0.2
`0.1
`0.1
`0.1
`0
`0.1
`0.1
`0.3
`0.5
`0.9
`1.4
`2.6
`4.6
`8.1
`12.6
`18.7
`28.3
`28
`
`Men had a significantly higher incidence rate
`than women. The age-adjusted incidence rate for
`MDS in men was 4.5 per 100,000 per year with a
`95% confidence interval (95% CI) of 4.3 to 4.6 per
`100,000 per year, whereas the rate for women was
`2.7 per 100,000 per year (95% CI, 2.6–2.8 per 100,000
`per year). Of all racial groups, whites had the highest
`incidence rate, whereas American-Indians/Alaska
`Natives and Asian/Pacific Islanders had lower rates
`(Table 2).
`The incidence of MDS varied slightly by calendar
`year. The age-adjusted incidence rate was 3.28 per
`100,000 per year (95% CI, 3.15–3.42 per 100,000 per
`year) in 2001, 3.37 per 100,000 per year (95% CI,
`3.23–3.51 per 100,000 per year) in 2002, and 3.56 per
`100,000 per year (95% CI, 3.42–3.70 per 100,000 per
`year) in 2003.
`Applying the age-, sex-, and race-specific inci-
`dence rates of MDS in the SEER population for 2003
`to the entire United States population (based on
`Census estimates) resulted in an estimated total of
`10,301 incident MDS patients who were diagnosed in
`the United States in 2003. Applying the 2003 age-
`adjusted incidence rate of 3.56 to the entire United
`
`

`

`States population generated an estimated total of
`10,351 (95% CI, 9951–10,764) incident MDS patients.
`Included in the survival analysis was a subgroup
`of 3389 MDS patients who were 1) diagnosed during
`2001 and 2002, 2) followed actively by SEER for sur-
`vival, 3) not
`identified from death certificates or
`autopsies only, and 4) had MDS as their first primary
`tumor. Observed and relative survival percentages
`are presented by demographic factors (Table 3). The
`3-year observed survival for patients with MDS was
`35%, and the 3-year relative survival rate was 42%.
`When age, sex, and race were included simulta-
`neously in a multivariate proportional hazard model,
`age and sex were associated significantly with the
`relative survival of patients with MDS, whereas race
`did not appear to be an important determinant.
`Based on estimates from a model with both age
`and sex, men with MDS were 25% more likely to die
`than women (hazard ratio, 1.25; 95% CI, 1.14–1.36).
`
`TABLE 2
`Age-Adjusted Incidence Rates of Myelodysplastic Syndromes by
`Sex and Race in the United States, 2001–2003: The Surveillance,
`Epidemiology, and End Results Program 17 Regions Public-use
`Database, November 2005 Submission
`
`Rate (95% Confidence interval)*
`
`Variable
`
`Men and women
`
`Men
`
`Women
`
`All races
`White
`Black
`American Indian/Alaska Native
`Asian or Pacific Islander
`
`3.4 (3.3–3.5)
`3.5 (3.4–3.6)
`3 (2.7–3.3)
`1.3 (0.8–2.1)
`2.6 (2.3–2.9)
`
`4.5 (4.3–4.6)
`4.6 (4.5–4.8)
`3.5 (3–4)
`1.8 (0.9–3.5)
`3.2 (2.7–3.6)
`
`2.7 (2.6–2.8)
`2.7 (2.6–2.8)
`2.7 (2.4–3.1)
`1 (0.5–2)
`2.2 (1.9–2.5)
`
`95% CI indicates 95% confidence interval.
`* All rates are per 100,000 per year and age-adjusted to the 2000 US standard population.
`
`MDS: Incidence and Survival/Ma et al.
`
`1539
`
`Compared with patients who were diagnosed at age
`<60 years, the mortality hazard ratios for those who
`were diagnosed at ages 60 to 69 years, 70 to 79 years,
`and 80 years were 1.21 (95% CI, 1.03–1.43), 1.33
`(95% CI, 1.15–1.54), and 1.71 (95% CI, 1.47–1.98),
`respectively. The observed survival percentages of
`patients with MDS who were diagnosed at ages <50
`years (n ¼ 221 patients) and 50 years (n ¼ 3168
`patients) are presented in Figure 1. Again, patients
`with MDS who were younger at the time of diagnosis
`had better survival.
`Of the patients with MDS who were included in
`the survival analysis, 1687 patients had no subtype
`specified, 563 patients had RA, 404 patients had
`RARS, 478 patients had RAEB, 67 patients had RAEB-
`T, 104 patients had RCMD, 64 patients had MDS with
`5q deletion, and 22 patients had therapy-related
`MDS. The observed survival percentages of these
`groups are plotted in Figure 2. The observed survival
`for the period from 33 to 36 months after diagnosis
`is not presented, because no deaths occurred in
`patients with RARS or RAEB during that period, and
`the probability of surviving through that period could
`not be calculated. The median survival was 28
`months for patients with RA and 11 months for
`patients with RAEB. Because >50% of patients with
`RARS survived for 3 years, the longest duration under
`observation, the median survival for patients with
`RARS could not be estimated with the current data,
`although it obviously exceeded 36 months.
`Of the 7131 patients who were diagnosed with
`MDS during 2001 to 2003 and were reported to SEER
`registries, 998 patients (14%) had other primary
`tumors diagnosed prior to their diagnosis of MDS. Of
`998 patients with MDS, 811 patients (81.3%) had
`
`TABLE 3
`Survival of Patients With Myelodysplastic Syndromes by Demographic Characteristics in the United States: The Surveillance, Epidemiology, and
`End Results Program 17 Regions Public-use Database, November 2005 Submission
`
`Cumulative observed survival (Cumulative relative survival), %
`
`Age, y
`
`Sex
`
`Race*
`
`Months
`since
`diagnosis
`
`6
`12
`18
`24
`30
`36
`
`Overall
`n = 3389
`
`79 (81)
`66 (69)
`54 (59)
`47 (53)
`41 (47)
`35 (42)
`
`<60
`n = 477
`
`89 (89)
`76 (76)
`66 (67)
`60 (61)
`54 (55)
`47 (48)
`
`60–69
`n = 563
`
`82 (83)
`70 (72)
`61 (63)
`54 (56)
`50 (52)
`y
`—
`
`70–79
`n = 1187
`
`81 (82)
`67 (70)
`56 (60)
`50 (55)
`42 (47)
`36 (42)
`
`80
`n = 1162
`
`72 (76)
`58 (65)
`44 (53)
`37 (46)
`31 (41)
`25 (35)
`
`Men
`n = 1828
`
`Women
`n = 1561
`
`White
`n = 2931
`
`African American
`n = 257
`
`78 (80)
`63 (67)
`51 (56)
`45 (51)
`38 (45)
`31 (37)
`
`81 (83)
`69 (72)
`58 (63)
`50 (56)
`45 (51)
`40 (47)
`
`79 (82)
`66 (70)
`54 (59)
`47 (53)
`41 (47)
`35 (43)
`
`78 (80)
`68 (72)
`59 (64)
`54 (61)
`46 (53)
`32 (38)
`
`* Survival was calculated only for whites and African Americans because of the small numbers of patients in other racial groups.
`y
`Survival could not be calculated because of the lack of deaths in the last 3-month interval (33–36 months postdiagnosis).
`
`

`

`1540
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`CANCER April 15, 2007 / Volume 109 / Number 8
`
`FIGURE 1. Observed survival of
`patients with myelodysplastic syn-
`drome by age at diagnosis in the
`United States (Surveillance, Epidemi-
`ology, and End Results data, Novem-
`ber 2005 submission4).
`
`FIGURE 2. Observed survival of
`patients with myelodysplastic syn-
`drome by subtype in the United
`States
`(Surveillance,
`Epidemiology,
`and End Results data, November
`2005 submission4). RA indicates re-
`fractory anemia; RARS, RA with rare
`sideroblasts; RAEB, RA with excess
`blasts.
`
`MDS as their second primary tumor, 161 patients
`(16.1%) had MDS as third primary tumor, and 26
`patients (2.6%) had 3 other primary tumors prior to
`their diagnosis of MDS. The sites of the primary
`tumors varied, but
`the most common sites were
`prostate (19.9%), breast (16.5%), non-Hodgkin lym-
`phoma (8.4%), urinary/bladder (6.0%), and lung and
`bronchus (5.6%). The median lag time between
`the diagnosis of the first primary tumor and MDS
`was 4.5 years (25th percentile ¼ 1.6 years, 75th
`percentile ¼ 9.4 years), and the median lag time
`between the diagnosis of the most recent non-MDS
`primary tumor and MDS was 3.8 years
`(25th
`percentile ¼ 1.3 years, 75th percentile ¼ 8.5 years).
`
`DISCUSSION
`To our knowledge, this analysis is the first to use
`large population-based data to evaluate the inci-
`dence and survival of MDS in the United States. The
`total population included in the SEER 17 regions
`ranged from 74 million to 76 million during 2001
`to 2003; and,
`in total, 7131 MDS diagnoses were
`included in the analysis. We believe that the sample
`size is the largest ever, and the MDS incidence that
`we estimated from SEER data generally was consist-
`ent with what was reported previously in 2 other
`population-based studies that were conducted in
`Germany and the United Kingdom.10,11 The German
`study estimated the incidence of MDS with approxi-
`
`

`

`mately 222 incident MDS patients among residents
`of Duesseldorf (n ¼ approxiamtely 575,000 residents),
`and the incidence rate was 4.9 per 100,000 per year
`in residents ages 50 to 69 years and 22.8 per 100,000
`per year in residents aged 70 years.10 The SEER-
`based incidence rates for the same 2 age groups
`were 4.1 (95% CI, 3.9–4.3) per 100,000 per year and
`26.8 (95% CI, 26.0–27.5) per 100,000 per year, respec-
`tively. The British study estimated the incidence of
`MDS with approximately 857 patients who had RA,
`RARS, RAEB, or chronic myelomonocytic leukemia
`and a study population of approximately 16 million.11
`The age-specific incidence rates reported in the
`British study were 4.1 per 100,000 per year, 5.1 per
`100,000 per year, 12.7 per 100,000 per year, 23.4 per
`100,000 per year, 42.5 per 100,000 per year, and 53.8
`per 100,000 per year in men ages 60 to 64 years,
`65 to 69 years, 70 to 74 years, 75 to 79 years, 80 to
`84 years, and 85 years, respectively.11 These age-
`specific rates in men were slightly lower than but still
`close to what we observed with in SEER data (Table 1),
`and the situation was similar for the rates among
`women. It appeared that the British study did not
`include RAEB-T, which is estimated to comprise of
`from 10% to 30% of all MDS diagnoses.6 Had the
`British study included RAEB-T, the incidence rates
`would have been more comparable to what the SEER
`data suggested.
`Our results indicate that the incidence of MDS
`varies by age, sex, and race. It is not clear whether
`the small differences observed in annual incidence
`rates (2001–2003) reflect an increase of disease risk
`over time, an increased awareness of the requirement
`of SEER reporting, both, or neither. With only 3 years
`of data, it is not feasible to evaluate temporal trends.
`The survival of patients with MDS varied by age
`and sex, but not by race. The median survival for
`patients with RA was 28 months, which was shorter
`than previous reports. Bennett et al. estimated that
`patients with RA had a median survival of 30 to 65
`months.7 The median survival based on the follow-
`up of 294 patients with RA from multiple institutions
`in the United States and Europe was between 3 and
`4 years in a study by Greenberg et al. (the estimated
`median survival was obtained from a survival curve
`that was included in the publication, because the
`authors did not describe the exact median survival in
`the text).12 Germing et al. reported a median survival
`of 37 months based on the follow-up of 418 patients
`who were diagnosed with RA at a single institution in
`Germany over a 30-year period.13 Our finding was
`based on a total of 563 patients with RA who were
`identified from population-based SEER cancer regis-
`tries during a 3-year period, and these patients prob-
`
`MDS: Incidence and Survival/Ma et al.
`
`1541
`
`ably are more representative than patients who were
`diagnosed at a single institution or at several institu-
`tions. Conversely, of all the patients with MDS who
`were included in our survival analysis (n ¼ 3389
`patients), a fairly large number (n ¼ 1687 patients;
`49.8%) had unspecified subtypes, and some of those
`patients actually may have had RA. Therefore, the
`survival experience observed for the 563 patients
`with RA may not be the same as that for all patients
`with RA who were included in the SEER data. All
`patients with MDS who had other primary tumors
`recorded in the SEER data prior to their diagnosis of
`MDS were excluded from the survival analysis, but
`some of
`the patients who were included in the
`survival analysis may have received chemotherapy or
`radiotherapy for tumors that were not recorded in
`SEER, or they may have received radiotherapy for
`nontumor conditions. The study by Greenberg et al.
`excluded patients who had received intensive chem-
`otherapy and those with secondary MDS,12 and the
`study by Germing et al. excluded patients who had
`been treated with antineoplastic drugs or ionizing
`radiation.13
`The median survival
`for patients with RAEB
`(n ¼ 478 patients) was 11 months, which is within
`the range of 8 to 18 months that was estimated in
`1982.7 The median survival based on the follow-up
`of 208 patients with RAEB from multiple institutions
`in the United States and Europe was between 1 and
`2 years in the study by Greenberg et al.12 Germing
`et al. reported a median survival of 12 months based
`on the follow-up of 344 patients with RAEB who
`were diagnosed at a German institution over a
`30-year period,13 and that finding is very similar to
`our current results.
`Fourteen percent of patients with MDS were
`diagnosed with other primary tumors prior to their
`diagnosis of MDS, and the most common sites of
`those tumors were prostate, breast, non-Hodgkin
`lymphoma, urinary/bladder, and lung and bronchus.
`Although prostate cancer and breast cancer have
`high incidence in the general population, it is note-
`worthy that a relatively high percentage of patients
`with MDS were diagnosed with non-Hodgkin lym-
`phoma before they were diagnosed with MDS. It is
`possible that the 2 malignancies share common risk
`factors or that clinical treatment for non-Hodgkin
`lymphoma increases the risk of MDS.
`The SEER Program is the authoritative source on
`cancer incidence and survival in the United States,
`and data generated by SEER are considered high-
`quality and reliable. Conversely, MDS did not become
`reportable to SEER until 2001; thus, under-reporting
`in the short term cannot be ruled out completely, and
`
`

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`CANCER April 15, 2007 / Volume 109 / Number 8
`
`conservative.
`estimated incidence may be
`our
`Because the presenting symptoms of MDS, such as fa-
`tigue, pallor, and mucosal hemorrhage, usually are
`nonspecific, under-diagnosis also is possible. By defi-
`nition, cases are confirmed histologically, but not all
`patients with symptoms suggestive of MDS in the
`SEER regions undergo exactly the same clinical exam-
`inations. With only 3 years of SEER data available,
`survival beyond 3 years cannot be calculated. These
`are the inherent limitations of the current analysis.
`To our knowledge, the current analysis included
`the largest number of patients with MDS in any sin-
`gle study to date, and the population-based nature of
`patient ascertainment represents a major strength.
`Our results indicate that >10,000 incident cases of
`MDS are diagnosed annually in the United States,
`and the survival of patients with MDS is poor. The
`availability of descriptive epidemiologic data on MDS
`can be used now to facilitate much needed research
`on the etiology and outcomes of MDS.
`
`REFERENCES
`1.
`Schumacher HR, Nand S. Myelodysplastic Syndromes:
`Approach to Diagnosis and Treatment. New York: Igaku-
`Shoin Medical Publishers; 1995.
`2. Cazzola M, Malcovati L. Myelodysplastic syndromes—cop-
`ing with ineffective hematopoiesis. N Engl J Med. 2005;
`352:536–538.
`3. Hankey BF, Ries LA, Edwards BK. The Surveillance,
`Epidemiology, and End Results Program: a national
`
`5.
`
`4.
`
`resource. Cancer Epidemiol Biomarkers Prev. 1999;8:1117–
`1121.
`Surveillance, Epidemiology, and End Results Program.
`SEER*Stat Database: Incidence-SEER 17 Regions Public-Use,
`November 2005 submission (1973–2003). Bethesda, MD:
`National Cancer Institute; 2006.
`Surveillance, Epidemiology, and End Results Program.
`SEER Registries 2006. Available at URL: http://seer.cancer.
`gov/registries/. Accessed November 20, 2006.
`6. Bennett J. The myelodysplastic syndromes: pathobiology and
`clinical management. In: Cheson B, editor Basic and Clinical
`Oncology, vol. 27 New York: Marcel Dekker; 2002:3–7.
`7. Bennett JM, Catovsky D, Daniel MT, et al. Proposals for the
`classification of
`the myelodysplastic syndromes. Br
`J
`Haematol. 1982;51:189–199.
`8. Harris NL, Jaffe ES, Diebold J, et al. World Health Organi-
`zation classification of neoplastic diseases of the hemato-
`poietic and lymphoid tissues:
`report of
`the Clinical
`Advisory Committee Meeting-Airlie House, Virginia, Novem-
`ber 1997. J Clin Oncol. 1999;17:3835–3849.
`9. Vardiman JW, Harris NL, Brunning RD. The World Health
`Organization (WHO) classification of
`the myeloid neo-
`plasms. Blood. 2002;100:2292–2302.
`10. Aul C, Gattermann N, Schneider W. Age-related incidence
`and other epidemiological aspects of myelodysplastic syn-
`dromes. Br J Haematol. 1992;82:358–367.
`11. Oscier DG. Myelodysplastic syndromes. Baillieres Clin
`Haematol. 1987;1:389–426.
`12. Greenberg P, Cox C, LeBeau MM, et al. International scor-
`ing system for evaluating prognosis in myelodysplastic
`syndromes. Blood. 1997;89:2079–2088.
`13. Germing U, Gattermann N, Strupp C, Aivado M, Aul C.
`Validation of the WHO proposals for a new classification of
`primary myelodysplastic syndromes: a retrospective analy-
`sis of 1600 patients. Leukemia Res. 2000;24:983–992.
`
`