Volume 13, Issue 12 , Pages 1508-1514, December 2007
Disparity in Survival Outcome after Hematopoietic Stem Cell Transplantation for Hematologic Malignancies According to Area of Primary Residence
Article Outline
We evaluated whether or not a patient's area of primary residence is an independent risk factor for overall survival (OS) after HLA-identical sibling or autologous hematopoietic stem cell transplantation (HSCT). This retrospective cohort study included patients who underwent autologous (n = 1739) or HLA-identical sibling (n = 267) HSCT to treat a hematologic malignancy between 1983 and 2004 at the University of Nebraska Medical Center. Primary area of residence, using the patient's zip code, was categorized as either urban or rural (including isolated, small rural, or large rural) according to the Rural Urban Commuting Area Codes (RUCA) classification system. An association between area of primary residence and survival was examined using Cox proportional hazards regression analysis while adjusting for patient-, disease-, and treatment-related variables. Patients from rural areas who received autologous HSCT had a higher relative risk of death (relative risk = 1.18; P = .016) than urban patients who underwent the same procedure. Survival rates in patients from rural and urban locations are as follows: 1 year, 73% vs 78% (P = .04); 5 year, 48% vs 54% (P = .012). We failed to detect a significant difference in the risk of death according to primary area of residence in the HLA-identical sibling HSCT cohort, although this may be from lack of statistical power. Our findings suggest that the primary location of a patient's residence may be an independent risk factor for survival after HSCT.
Key Words: Autologous transplant, HLA-identical sibling transplant, Rural area
Introduction
Hematopoietic stem cell transplantation (HSCT) is performed to treat various malignant and nonmalignant hematologic disorders 1, 2, 3, 4, 5. Although HSCT is potentially curative and life-saving, it carries significant medical risks. Most deaths after HSCT result from disease recurrence; however, a significant number of deaths are from preventable causes, such as infectious complications, graft-versus-host disease (GVHD), and multiorgan dysfunction.
Because of the complex nature of HSCT, not all facilities are able to offer this treatment. Studies have shown that improved survival outcome after HSCT is associated with the number of transplantations that a center performs and the expertise of the transplantation physician 6, 7, 8, 9, 10. As such, patients who may benefit from HSCT are often referred to larger hospitals. Although patients stay in hospitals for a few weeks during the peritransplantation period, follow-up care is commonly brought back to the community or referring physician at some point.
Most transplantation centers, at least in the United States, are located in metropolitan areas and attract a wide range of patients, including many from small towns and rural areas. Physician shortages also force many of these patients to travel great distances for specific care 11, 12. Studies have shown that rural residents must travel roughly twice the distance of their urban counterparts to access advanced care 13, 14. Therefore, the geographical location of both the patient and his or her community physician could differentially affect follow-up and may be considered a risk factor that may or may not affect clinical outcomes.
Consequently, this retrospective study was designed to investigate whether disparities in survival outcome among patients undergoing HSCT exist according to patient's place of residence. We hypothesized that the patient's area of primary residence would be a significant factor associated with mortality post-HSCT after adjusting for patient-, disease-, and transplantation-related factors.
Materials and Methods
Data Source
Data for the study were obtained from the Adult Oncology Stem Cell Transplant Database at the University of Nebraska Medical Center (UNMC) in Omaha, Nebraska. This database contains patient-, disease-, and treatment-related factors of all patients who have undergone HSCT since UNMC started performing HSCT in the early 1980s. A systematic evaluation of outcomes after HSCT, including disease recurrence or progression and survival status, is performed annually at each patient's anniversary date by a trained clinical research associate. Data are also reported to the Center for International Blood and Marrow Transplant Registry. Each patient has signed an informed consent allowing UNMC clinical personnel to contact the patient and his or her physician to update clinical events of interest. Data are maintained in a password-secured Oracle-based relational database (ONCOBASE) that is also linked to the hospital's electronic medical records. This retrospective analysis was approved by UNMC's Institutional Review Board.
Patients
Because of the intrinsic differences in the complications and clinical outcomes of autologous and allogeneic HSCT, our study was designed to primarily examine the effect of primary area of residence on survival using prototype cohorts in which autologous or allogeneic transplants are most commonly indicated. Thus, the first cohort included 267 patients who underwent HLA-identical sibling (allogeneic) HSCT that was serologically matched for the 6 major HLA alleles. Only patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), or chronic myelogenous leukemia (CML) who underwent transplantation between 1983 and 2004 were included. We did not have a sufficient number of patients who received unrelated transplants to allow us to conduct a separate analysis for this cohort, which is also known to have a higher risk of mortality compared with those receiving HLA-identical sibling transplants. The second cohort included 1739 patients who underwent autologous transplantation for lymphoma (non-Hodgkin [NHL] or Hodgkin) or multiple myeloma (MM) between 1983 and 2004.
Variables Evaluated
The primary covariate evaluated in both of our study cohorts was location of the patient's primary area of residence. A patient was classified as living in either an urban area or a rural area according to his or her residential zip code provided at the time of transplantation. The rural category included the subcategories isolated rural towns, small rural towns, and large rural towns. These classifications were based on the Rural Urban Commuting Area Codes (RUCA) created in part by the US Department of Agriculture's Economic Research Service [15]. The RUCA defines patient location as urban (≥ 50,000 residents), large rural (10,000-49,000 residents), small rural (2500-9999 residents), or isolated (< 2499 residents) based on the US Census Bureau's definitions of urbanized areas and urban clusters, which in turn rely on complex criteria, including population density and population work commuting patterns. The RUCA classification system is based on the size of cities and towns and their functional relationships as measured by work commuting [15]. We also evaluated the distance traveled in miles from a patient's area of primary residence to the transplantation center, as well as average household income based on the patient's zip code of residence as obtained from Census 2000 data [16]. Categories for continuous data were first created using quartile distribution and further combined according to median when no differences in outcomes were noted between the first and second quartiles or between the third and forth quartiles. The following additional covariates were examined for their association with outcome: patient age, sex, race, disease type, interval from diagnosis to transplantation, disease stage at transplantation, use of irradiation as part of treatment, type of graft used, and the time period in which the patient underwent transplantation. Covariates were categorized according to conventional classifications used in many previous studies, as given in Table 1, Table 3 17, 18, 19, 20.
Table 1. Characteristics of patients undergoing autologous HCST according to location of residence
| Variable | Urban | Rural | P value |
|---|---|---|---|
| n | 1221 | 518 | |
| Median age, years (range) | 43 (3-80) | 46 (8-80) | < .001 |
 ≤ 20 | 76 (6) | 25 (5) | .003 |
| 20-40 | 428 (35) | 147 (28) | |
| 41-59 | 579 (47) | 261 (50) | |
| ≥ 60 | 138 (11) | 85 (16) | |
| Male sex | 725 (59) | 310 (60) | .86 |
| Caucasians | 1166 (96) | 512 (99) | < .001 |
| Diagnosis | |||
| Non-Hodgkin lymphoma | 823 (67) | 335 (65) | < .001 |
| Hodgkin lymphoma | 333 (27) | 120 (23) | |
| Multiple myeloma | 65 (5) | 63 (12) | |
| Disease stage at transplantation | |||
| First complete remission/PIF sensitive | 379 (31) | 154 (30) | < .001 |
| ≥ second complete remission | 133 (11) | 47 (9) | |
| Relapse | 511 (42) | 204 (39) | |
| PIF | 133 (11) | 50 (10) | |
| Multiple myeloma | 65 (5) | 63 (12) | |
| Interval for diagnosis to transplantation | |||
| ≤ 1 year | 448 (37) | 218 (42) | .03 |
| > 1 year | 773 (63) | 300 (58) | |
| Type of graft | |||
| Bone marrow | 327 (27) | 126 (24) | .28 |
| Peripheral blood | 894 (73) | 392 (76) | |
| Use of TBI for conditioning regimen | |||
| No | 1048 (86) | 445 (86) | .97 |
| Yes | 173 (14) | 73 (14) | |
| Year of transplantation | |||
| 1983-1989 | 211 (17) | 93 (18) | < .001 |
| 1990-1997 | 572 (47) | 194 (37) | |
| 1998-2004 | 438 (36) | 231 (44) | |
| Location according to population size | |||
| Urban | 1221 (100) | ---- | NA |
| Isolated | ---- | 182 (35) | |
| Small rural area | ---- | 124 (24) | |
| Large rural area | ---- | 212 (41) | |
| Distance of residence to transplant center, miles | |||
| ≤ 50 | 207 (17) | 18 (3) | < .001 |
| 51-99 | 74 (6) | 61 (12) | |
| 100-500 | 307 (25) | 335 (65) | |
| > 500 | 633 (52) | 104 (20) | |
| Average annual income | |||
| ≤ $40,000 | 115 (9) | 153 (30) | < .001 |
| $40,001-$49,999 | 241 (20) | 310 (60) | |
| $50,000-$65,000 | 424 (35) | 41 (8) | |
| > $65,000 | 398 (33) | 9 (2) | |
| Not available | 43 (4) | 5 (1) |
Table 2. Multivariate analysis of risk of death in patients who underwent autologous HCST according to location of residence, adjusting for statistically significant covariates
| Variable | n | Relative risk of death (95% confidence interval) | P value |
|---|---|---|---|
| Location of residence | |||
| Urban | 1221 | 1.00 | |
| Rural | 518 | 1.18 (1.03-1.36) | .02 |
| Other significant factors | |||
| Age at transplantation, years | <.001∗ | ||
| ≤ 20 | 101 | 1.00 | |
| 20-40 | 575 | 0.89 (0.67-1.18) | .41 |
| 41-59 | 840 | 1.03 (0.78-1.37) | .83 |
| ≥ 60 | 223 | 1.51 (1.08-2.11) | .02 |
| Disease stage at transplantation | < .001† | ||
| First complete remission/PIF-sensitive | 533 | 1.00 | |
| ≥ second complete remission | 180 | 1.01 (0.78-1.31) | .93 |
| Relapse | 715 | 1.27 (1.08-1.49) | .003 |
| PIF | 183 | 1.60 (1.29-1.98) | < .001 |
| Multiple myeloma | 128 | 1.16 (0.80-1.69) | .43 |
| Year of transplantation | < .001‡ | ||
| 1983-1989 | 304 | 1.00 | |
| 1990-1997 | 766 | 0.62 (0.52-0.72) | < .001 |
| 1998-2004 | 669 | 0.34 (0.28-0.42) | < .001 |
∗3 degree of freedom test. |
†4 degree of freedom test. |
‡2 degree of freedom test. |
Table 3. Characteristics of patients who underwent HLA-identical sibling HSCT according to location of residence
| Variable | Urban | Rural | P value |
|---|---|---|---|
| N | 172 | 95 | |
| Median age, years (range) | 35 (<1-70) | 35 (<1-70) | .61 |
| ≤ 20 | 40 (23) | 29 (30) | .17 |
| 20-40 | 69 (40) | 33 (35) | |
| 41-59 | 59 (34) | 27 (28) | |
| ≥ 60 | 4 (2) | 6 (6) | |
| Male sex | 109 (63) | 53 (56) | .22 |
| Caucasian | 161 (94) | 92 (97) | .26 |
| Diagnosis | |||
| Acute myelogenous leukemia | 79 (46) | 46 (48) | .93 |
| Acute lymphoblastic leukemia | 36 (21) | 19 (20) | |
| Chronic myelogenous leukemia | 57 (33) | 30 (32) | |
| Disease stage at transplantation | |||
| First complete remission or chronic phase | 84 (49) | 56 (59) | .22 |
| ≥ second complete remission or chronic phase, first accelerated phase | 32 (19) | 17 (18) | |
| Relapse, blastic phase, ≥ second accelerated phase | 56 (33) | 22 (23) | |
| Interval between diagnosis and transplantation | |||
| ≤ 1 year | 123 (72) | 72 (76) | .45 |
| > 1 year | 49 (28) | 23 (24) | |
| Type of graft | |||
| Bone marrow | 85 (49) | 59 (62) | .05 |
| Peripheral blood | 87 (51) | 36 (38) | |
| Use of TBI for conditioning regimen | |||
| No | 35 (20) | 29 (30) | .06 |
| Yes | 137 (80) | 66 (70) | |
| Year of transplantation | |||
| 1983-1989 | 21 (12) | 22 (23) | .02 |
| 1990-1997 | 105 (61) | 43 (45) | |
| 1998-2004 | 46 (27) | 30 (32) | |
| Location according to population size | |||
| Urban | 172 | --- | NA |
| Isolated | --- | 37 (39) | |
| Small rural area | --- | 17 (18) | |
| Large rural area | --- | 41 (43) | |
| Distance between residence and transplantation center, miles | |||
| ≤ 50 | 59 (34) | 5 (5) | < .001 |
| 51-99 | 20 (12) | 14 (15) | |
| 100-500 | 46 (27) | 67 (71) | |
| > 500 | 47 (27) | 9 (9) | |
| Average annual income | |||
| ≤ $40,000 | 22 (13) | 28 (29) | < .001 |
| $40,001-$49,999 | 26 (15) | 60 (63) | |
| $50,000-$65,000 | 63 (37) | 5 (5) | |
| > $65,000 | 56 (33) | 1 (1) | |
| Not available | 5 (3) | 1 (1) |
Outcomes Evaluated
Two outcomes were evaluated. The primary outcome was overall survival (OS), defined as death from any cause, and the secondary outcome was progression-free survival (inverse of treatment failure), defined as death or relapse and/or progression from primary disease. All time intervals were computed from the time of transplantation to the occurrence of event or last contact, whichever was applicable.
Statistical Analysis
Univariate comparisons according to place of residence were done using the χ2 test for categorical data and Wilcoxon's test for continuous data. The univariate probability of survival was computed using the Kaplan-Meier estimate [21]. The multivariate analysis was done using Cox proportional hazards regression analysis to examine the association between primary area of residence and the relative risk of death but adjusting for other covariates [22]. In the multivariate analyses, the main effect (area of primary residence), dichotomized into urban versus rural, was forced in all of the model building. We decided to combine the 3 categories of rural areas after noting no statistically significant differences among the groups. One by one, the covariates listed in both Table 1, Table 3 were examined for their effect on the outcome of interest while retaining the main effect term. The assumption of proportionality was tested in all of the model building. Stepwise model building was used, and only covariates found to have a P value ≤ .05 were included in the model. All factors found to be statistically significant were tested for first-order interaction (ie, whether the effect of a patients' place of primary residence on survival varies according to the categories of the other significant factor, eg, age strata or period of transplantation). An α level ≤ .01 was considered to indicate a statistically significant interaction.
Results
Table 1 shows that of the 1739 patients who underwent autologous HSCT, 1221 (70%) lived in urban areas and 518 (30%) lived in rural areas. Patients coming from rural areas were likely to be older, with a median age of 46 years, compared with 43 years in patients from urban areas. Patients from rural areas were more likely to be Caucasians, more likely to undergo autologous HSCT for MM, and more likely to undergo HSCT within 1 year of diagnosis. As expected, patients from rural areas undergoing autologous HSCT were more likely to live at least 100 miles away from the transplantation center and more likely to have an average income <$50,000. In addition, a trend toward increasing numbers of HSCTs in patients from rural areas can be seen.
Because primary area of residence is closely correlated with distance from the transplantation center and average income, we evaluated these 3 factors separately. In univariate analysis, patients living in rural areas had a greater risk of death (relative risk [RR] = 1.17; 95% confidence interval [CI] = 1.02-1.35; P = .02) compared with those living in urban areas. Patients living ≥ 100 miles from the transplantation center also had a greater risk of death (RR = 1.30; 95% CI = 1.09-1.53; P = .003) compared with those living < 100 miles from the transplantation center. Conversely, patients with an average annual income of ≥ $50,000 or more had a lower risk of death (RR = 0.84; 95% CI = 0.73-0.95; P = .007) compared with those with an average annual income of < $50,000. However, in stepwise multivariate analysis, the independent effects of distance from the transplantation center and average income analyzed based on area of residence and other prognostic covariates were no longer statistically significant. Table 2 shows the results of multivariate analysis evaluating the risk of death in patients who underwent autologous transplantation according to place of primary residence while adjusting for statistically significant covariates. Compared with patients from urban areas, those from rural areas had an 18% higher risk of death (RR = 1.18; 95% CI = 1.03-1.36; P = .02). Other factors found to be associated with survival included age (patients over age 60 at higher risk of death), disease stage (patients not in remission at transplantation at higher risk of death), and year of transplantation (more recent transplantation recipients at lower risk of death).
Table 5 and Figure 1 show the OS probability and plots of patients who underwent autologous HSCT according to primary area of residence at 100 days, 1 year, and 5 years post-HSCT.
Table 4. Multivariate analysis of risk of death in patients who underwent HLA-identical sibling HSCT according to location of residence, adjusting for statistically significant covariates
| Variable | n | Relative risk of death (95% confidence interval) | P value |
|---|---|---|---|
| Location of residence | |||
| Urban | 172 | 1.00 | |
| Rural | 95 | 0.93 (0.67 – 1.29) | .66 |
| Other significant factors | |||
| Age at transplantation, years | < .001∗ | ||
| ≤ 20 | 69 | 1.00 | |
| 20-40 | 102 | 1.20 (0.79-1.84) | .39 |
| 41-59 | 86 | 2.34 (1.53-3.58) | < .001 |
| ≥ 60 | 10 | 4.06 (1.91-8.59) | < .001 |
| Disease stage at transplantation | < .001† | ||
| First complete remission or chronic phase | 140 | 1.00 | |
| ≥ second complete remission or chronic phase, first accelerated phase | 49 | 1.44 (0.94-2.19) | .09 |
| Relapse, blastic phase, ≥ second accelerated phase | 78 | 2.81 (1.97-4.01) | < .001 |
∗3 degree of freedom test. |
†2 degree of freedom test. |
Table 5. Probability of overall survival (95% confidence interval) according to type of transplant and area of residence
| Urban | Rural | P value | |
|---|---|---|---|
| Autologous transplant | |||
| 100-day overall survival | 91 (89-92) | 88 (85-90) | .07 |
| 1-year overall survival | 78 (75-80) | 73 (69-77) | .04 |
| 5-year overall survival | 54 (52-57) | 48 (43-52) | .01 |
| HLA-identical sibling transplant | |||
| 100-day overall survival | 76 (68-81) | 81 (72-88) | .29 |
| 1-year overall survival | 56 (48-63) | 58 (47-67) | .74 |
| 5-year overall survival | 42 (34-49) | 42 (32-52) | .99 |
Figure 1
Survival probability by area of residence for autologous HSCT recipients.
Table 3 compares characteristics of the 267 patients who underwent HLA-identical sibling HSCT according to place of residence. Of these patients, 172 (64%) came from urban areas and 95 (36%) came from rural areas. Surprisingly, patients undergoing HLA-identical sibling HSCT had more similarities than differences. A higher percentage of rural patients used bone marrow as the graft tissue of choice compared with their urban counterparts. Similar to the autologous cohort, patients from rural areas were more likely to live at least 100 miles away from the transplantation center and more likely to have an average income < $50,000. In addition, the number of transplantations performed increased over time.
Our univariate analysis failed to demonstrate any association between risk of death and primary area of residence, distance from transplantation center, or average annual income in patients who received HLA-identical sibling transplants. This may result from the small sample size, which provided inadequate statistical power. Table 4 shows the results of multivariate analysis for the risk of death in patients who received an HLA-identical sibling transplant according to place of primary residence while adjusting for statistically significant covariates. We failed to detect any statistically significant differences in the risk of death according to place of residence (RR = 0.93; 95% CI = 0.67-1.29; P = .66). As expected, the RR of death was dramatically increased in older patients and in patients who underwent transplantation at an advanced disease stage. Table 5 and Figure 2 show the survival probability and plots of the patients who underwent HLA-identical sibling HSCT according to primary area of residence.
Figure 2
Survival probability by area of residence for HLA-identical sibling HSCT recipients.
Our multivariate analyses of the risk of treatment failure (inverse of progression-free survival; data not shown) according to primary area of residence in the autologous and HLA-identical sibling cohorts failed to detect significant differences according to primary area of residence in both cohorts. Table 6 shows the causes of early (within 1 year) and late (after 1 year) deaths in the patients who underwent autologous transplantation. Approximately 60% of the primary causes of death were from disease progression in patients from either rural or urban areas.
Table 6. Causes of death according to area of residence after autologous transplantation
| Urban | Rural | P value | |
|---|---|---|---|
| Early (within 1 year) | n = 271 | n = 138 | .22 |
| Graft failure | ---- | 1 (<1%) | |
| Infection | 19 (7%) | 11 (8%) | |
| IPN | 5 (2%) | 6 (4%) | |
| ARDS | 5 (2%) | 3 (2%) | |
| Relapse/progression | 180 (66%) | 95 (69%) | |
| Organ failure | 29 (11%) | 14 (10%) | |
| Hemorrhage | 15 (6%) | 1 (<1%) | |
| Accidental death | 2 (<1%) | 2 (1%) | |
| Others | 7 (2%) | 2 (1%) | |
| Unknown | 9 (3%) | 3 (2%) | |
| Late (after 1 year) | n = 379 | n = 152 | .35 |
| Infection | 17 (4%) | 3 (2%) | |
| IPN | ---- | 1 (<1%) | |
| ARDS | 4 (1%) | 1 (<1%) | |
| Relapse/progression | 279 (74%) | 109 (72%) | |
| Organ failure | 17 (4%) | 10 (6%) | |
| Secondary malignancy | 34 (9%) | 18 (12%) | |
| Hemorrhage | 5 (1%) | 2 (1%) | |
| Accidental death | ---- | 1 (<1%) | |
| Others | 14 (4%) | 5 (3%) | |
| Unknown | 9 (2%) | 2 (1%) |
Discussion
Our study found a greater risk of death in patients from rural areas, at least in the autologous HSCT setting. Our data consistently showed that patients from rural areas had at least a 5% lower probability of survival at 1 year and 5 years after undergoing autologous HSCT. But disparate survival rates were not observed between urban and rural patients undergoing HLA-identical sibling transplantation, possibly due to a lack of statistical power.
Because there was no significant difference in treatment failure according to primary area of residence in the 2 types of transplants that we evaluated, the disparity in survival that we found may result from treatment toxicity. Treatment-related complications that can result in death may include graft failure, infection, GVHD, and multiorgan dysfunction. These known complications post-HSCT should be monitored for closely according to the transplantation physician's recommendation [23]. Most of these clinical entities are preventable or treatable when detected early; however, there remains a lack of consensus on the optimum frequency of follow-up assessments. Commonly, allogeneic transplant recipients are seen more frequently and are closely monitored for complications (especially during the first 100 days posttransplantation), whereas autologous transplant recipients are discharged earlier and return home to the care of referring community oncologists or general internists. This has been the practice at our center since the first HSCTs were performed in the mid-1980s. The difference in the follow-up care plan in autologous and allogeneic transplant recipients serves as a plausible explanation as to why survival in allogeneic transplant recipients is similar regardless of location of residence. It also accounts for the reduced survival in autologous transplant recipients, in whom location of residence then becomes a potential independent risk factor.
Previous studies have shown that rural patients had to travel more than double the distance of their urban counterparts for advanced care and were significantly deterred by this prospect 13, 14. Their reluctance increased exponentially as they had to make repeated long trips for posttransplantation care that they may have considered unnecessary. Consequently, instead of returning to the transplantation physician, rural patients discharged early after autologous transplantation may opt to go to a local primary care physician or to avoid any follow-up care. Community general practitioners generally have neither the experience nor the resources to fully help these patients 12, 24; thus, these patients may be monitored and treated by health care personnel unfamiliar with the management of posttransplantation complications, possibly leading to misdiagnoses and untimely or inappropriate care. Although our study found only a modest 5% decrease in survival probability for rural patients, when applied to larger populations, this rate may represent a significant amount of preventable deaths. Although this problem is more relevant in a state like Nebraska, in which more than 2/3 of the counties qualify as underserved rural areas, our finding may be generalizable to other predominantly rural states and other states with significant underserved populations [25].
There are also multiple alternative explanations to our findings. Some believe that there are systematic differences in the type of patients (in terms of, eg, disease stage, disease type, timing of transplantation) undergoing HSCT coming from urban and rural areas. In addition, although patients undergoing HSCT represent a relatively select group of cancer patients (good performance scores, no major organ dysfunction, adequate insurance coverage), this is likely to be true for patients from both urban and rural areas.
It also should be noted that the retrospective nature of our study presents some limitations. We were not able to collect crucial information on the frequency and nature of patient visits to follow-up care providers posttransplantation, or on other comorbid medical conditions developing posttransplantation that usually lead patients to seek medical attention. Although instructions given to patients regarding posttransplantation hygiene practices, activities, food intake, and other aspects do not vary according to place of residence or transplant type, it would be useful to evaluate whether there are any differences in how the patient cohorts implement these instructions. It is also of interest that distance from transplantation center or average income was associated with survival after autologous HSCT in the univariate models, but the complex correlation of these factors with primary area of residence in a retrospective study design does not allow for a detailed exploration of these interactions. A carefully designed prospective study should provide more insight into the causal relationships among primary area of residence, income, and distance traveled as they relate to survival and other clinical prognostic factors. A prospective approach also should help elucidate the role of health behavior and medical utilization in differences in survival between patients from urban areas and those from rural areas.
Our findings may have significant implications for health policy makers, patients, and health care providers. We established an independent temporal relationship between the primary area of residence (at least in the autologous HSCT setting) and patient survival after HCST. Based on this, the transplanting physician may need to consider the patient's primary location of residence as an independent risk factor for survival. A comprehensive follow-up care plan may need to be considered in the discussion of prognostic factors, similar to how medical care providers consider a patients' age or disease stage in their decision of whether or not to perform transplantation. Further studies should evaluate how follow-up care of patients from rural areas are coordinated between community referring physicians and transplantation physicians to optimize outcomes. The medical community must define the frequency of follow-up care visits using a prospective study design to gain insight into inequities in health care provision.
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PII: S1083-8791(07)00452-1
doi:10.1016/j.bbmt.2007.09.006
© 2007 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
Volume 13, Issue 12 , Pages 1508-1514, December 2007
