Abstract
Background:
Compared to privately insured patients, recipients of Medicaid have been reported to have worse outcomes in several clinical conditions and following various surgical and medical procedures. However, the relationship between health insurance status and allogeneic hematopoietic cell transplant (alloHCT) outcomes among patients with sickle cell disease (SCD) is not well described.
Objective:
We sought to compare alloHCT outcomes among patients with SCD who received an alloHCT while enrolled on Medicaid versus private health insurance.
Study design:
We conducted a retrospective multicenter study utilizing data reported to the Center for International Blood and Marrow Transplant Research. US patients enrolled on Medicaid or private insurance, who received a first alloHCT for SCD between 2008 and 2018 were eligible for this study. The primary outcome was event-free survival (EFS), defined as time to death or graft failure. Secondary outcomes included overall survival (OS), graft failure, acute and chronic graft-versus-host disease (GVHD). Univariate analysis was performed using Kaplan-Meier Method for EFS and OS. The proportion of patients with graft failure, acute and/or chronic GVHD was calculated using the cumulative incidence estimator to accommodate competing risks (ie, death). Cox regression was used to identify factors associated with EFS, OS, graft failure, acute and chronic GVHD.
Results:
A total of 399 patients (Medicaid: 225; private insurance: 174) were included in this study. The median follow-up was 34 months (range 1.0–134.7) and 38.7 months (range 0.3–139.3) for patients enrolled on Medicaid and private insurance, respectively. Patients on Medicaid compared to private insurance had significantly lower 3-year EFS 75.4 (95%CI: 69.4–81)% vs. 82.2 (95%CI: 76.9–87.8)%, p= 0.0279 and significantly higher 3-year cumulative incidence of graft failure 17.2 (95%CI: 12.5–22.5)% vs. 10.5 (95%CI: 6.4–15.4)%, p= 0.0372. There were no significant differences in 3-year OS p= 0.6337, the cumulative incidence of aGVHD p=0.4556 or cGVHD p=0.6878 between the two groups. Cox-regression analysis, adjusting for other significant variables showed that patients enrolled on Medicaid compared to private insurance had lower EFS (hazard ratio (HR): 2.36, 95% CI: 1.44–3.85; p= 0.0006) and higher cumulative incidence of graft failure (HR: 2.57, 95% CI: 1.43–4.60; p=0.0015 with no significant difference in OS (HR: 0.99, 95% CI: 0.47–2.07; p=0.9765); aGVHD (HR: 0.94, 95% CI: 0.59–1.49; p=0. 7905), or cGVHD (HR: 0.98, 95 CI: 0.65–1.48; p=0.9331).
Conclusion:
That EFS is worse in patients with Medicaid as compared to privately insured individuals following alloHCT for SCD provides the rationale for research to better understand the mechanisms by which insurance status impacts alloHCT outcomes among patients with SCD.
Keywords: Sickle cell disease, Medicaid, health disparities
Introduction
Sickle cell disease (SCD) is the most common inherited hemoglobin disorder affecting approximately 100,000 people in the United States (U.S.), a majority of whom are Black/African American, with an incidence rate of 1 in every 365 births.1 SCD is a chronic health condition associated with acute painful vaso-occlusive crisis (VOC), acute chest syndrome (ACS), stroke, chronic organ damage and culminates in a life expectancy that is less than half that of the general American population.2–4
Allogeneic hematopoietic cell transplantation (alloHCT) is currently the only established curative option for SCD.5 However, alloHCT carries the risk of mortality and morbidity from graft-versus-host disease (GVHD).6–8 Hence, the indications and risk-to-benefit ratio associated with alloHCT compared to management therapy with hydroxyurea and/or chronic transfusions remains unclear to non-transplant physicians.6,9 Although the prognostic impact of transplant- and disease- related variables, including donor type and age at transplantation on alloHCT outcomes among patients with SCD have been well documented 6–8, there is a paucity of information on the impact of socioeconomic factors, such as health insurance coverage.10
Insurance status has been shown to be independently associated with health outcomes in several malignant diseases.11–17 Patients on Medicaid have higher rates of cancer specific mortality, present with more advanced disease, and are less likely to receive cancer-directed therapy compared to privately insured patients in several solid tumor and hematologic malignancies.11–17 A study using data from the Surveillance, Epidemiology, and End Results database found that patients 15–64 years old, with chronic myeloid leukemia who were on Medicaid had poorer 5-year overall survival (OS) compared to privately insured patients (HR 1.83, p<0.001), with no significant difference in 5-year OS between Medicaid insured and uninsured patients.12 A study of younger patients with acute myelogenous leukemia (AML) found that Medicaid beneficiaries experienced poorer survival, with increased risk of both early and late mortality compared to privately insured patients.18
A recent study by Bona et al. found that pediatric patients with hematologic malignancies who were enrolled on Medicaid experienced decreased OS and increased transplant-related mortality following alloHCT compared to those on privately insurance.15 However, they did not find a similar relationship between insurance type and alloHCT outcomes among children transplanted for non-malignant diseases.15 Although the authors speculate that differences in referral patterns among pediatric patients transplanted for malignant compared to non-malignant diseases may be a factor, further investigation of the relationship between insurance status and alloHCT outcomes is warranted among a larger cohort of patients with SCD.15
More than half of patients with SCD are enrolled on Medicaid.19 However, it is unknown if patients with SCD who are insured by Medicaid have similar alloHCT outcomes compared to those on private insurance. Hence, the objective of this study was to compare alloHCT outcomes among Medicaid and privately insured patients with SCD. We hypothesized that patients on Medicaid have poorer event-free survival (EFS) following alloHCT compared to patients on private insurance. Hence, the results of this study could help identify additional factors associated with alloHCT outcomes among patients with SCD.
Methods
Data source and patient selection
We conducted a retrospective multicenter study utilizing clinical outcomes data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). The CIBMTR is a research affiliation between the National Marrow Donor Program® (NMDP)/Be The Match® and the Medical College of Wisconsin. CIBMTR collaborates with the global scientific community to advance cellular therapy worldwide to increase survival and enrich quality of life for patients. It facilitates critical research through medical, scientific, and statistical expertise; a network of more than 500 participating centers worldwide; a database with clinical data on 535,000 patients; and a biospecimen repository. Accuracy of data reported to the CIBMTR is supported through a series of electronic data validations at the time of data submission and a 4-year cycle of on-site source documentation audits. Consent for research is sought from patients or their legal guardians.
Centers submit transplant data to CIBMTR at two levels: A Transplant Essential Data (TED) level, which captures basic data, and a Comprehensive Report Form (CRF) level, which captures more detail. US patients with available CRF data, who were reported to be enrolled on Medicaid or private insurance and received a first alloHCT for SCD between 2008 and 2018 were eligible for this study. We excluded patients from embargoed centers (n=16), patients who did not consent to using their data for research (n=19) and patients missing baseline and/or 100-day forms (n=7). Patients on Ex vivo T-cell depletion (n=3) and CD34 (n=24) GVHD prophylaxis and patients with a human leucocyte antigen (HLA)-mismatched unrelated donor (n=2), multiple donors (n=1) and other relative matched donor (n=9) were excluded due to low numbers. The Institutional Review Board of the National Marrow Donor Program approved this study.
Study outcomes and variables analyzed
The primary outcome, EFS, was defined as time from transplantation to death or graft failure assessed throughout the entire follow up period. Primary and secondary graft failure were considered as a single outcome. Primary graft failure was defined as failure to achieve absolute neutrophil count (ANC) of 0.5 × 109/L by 28 days, or donor chimerism <5% in any compartment (T-cell chimerism <5%, unsorted blood or marrow chimerism).20 Secondary graft failure was defined as initial engraftment followed by graft loss evidenced by a sustained drop in neutrophil recovery to less than 0.5 × 109/L for at least 3 consecutive days without subsequent recovery, or loss of donor chimerism to <5% in any compartment (T-cell chimerism <5%, unsorted blood or marrow chimerism), or a second donor cell infusion or transplant.20 Time to graft failure is the interval between date of ANC decline/date of chimerism <5%/date of second infusion and date of transplant; patients who are engrafted (full donor or mixed) were censored at 12 months. Secondary outcomes included OS, defined as time from transplant to death (death from any cause was considered an event) assessed throughout the entire follow up period and acute and chronic GVHD, graded using the Glucksberg grading system.21,22
Patient-, disease- and transplant-related variables were obtained from CIBMTR. Patient-related variables included age at alloHCT, sex, race, sickle cell genotype, Karnofsky/Lansky score, HCT comorbidity index and region. Distance to transplant center based on patient 5-digit zip code was calculated using Environmental Systems Research Institute Geographic Information System mapping software. Median household income based on patient zip code was extracted from the 2019 American Community Survey. Disease-related variables included utilization of chronic blood transfusion and/or hydroxyurea at any time prior to HCT, incidence of stroke and/or ACS at any point prior to HCT and/or VOC requiring hospitalization within 2 years prior to HCT. Transplant-related variables included conditioning regimen, recipient cytomegalovirus (CMV), donor type (HLA-matched sibling; haploidentical related; HLA-mismatched relative; HLA-matched unrelated; cord blood); GVHD prophylaxis, in vivo T-cell depletion, and year of transplant.
Statistical analysis
Comparisons between groups were conducted using the Chi-square test for categorical variables and the Kruskal-Wallis test for non-normal continuous data. Univariate analysis was performed using the Kaplan-Meier Method for EFS and OS. The proportion of patients with graft failure, and acute or chronic GVHD was calculated using the cumulative incidence estimator to accommodate for competing risks (i.e., death). Comparison of probability estimates was performed using the log-rank test for EFS and OS, and Gray’s test for cumulative incidence of graft failure, and acute and/or chronic GVHD. Multivariate analyses were performed using Cox proportional hazard model for EFS, OS, graft failure, acute and chronic GVHD. Hazard ratios (HRs) and their associated 95% CIs were estimated for all outcomes. A stepwise model selection procedure with a significance level of 0.05 was used to identify variables to include in the multivariate models, for each study outcome. Variables considered included age, sex, race, genotype, Karnofsky /Lansky score, HCT comorbidity index, region, distance to transplant center, median household income, utilization of chronic blood transfusion and/or hydroxyurea at any time prior to alloHCT, number of SCD-related complications prior to alloHCT (binary variable, <2 vs. ≥2 complications), conditioning regimen, recipient CMV, donor type, GVHD prophylaxis, in vivo T-cell depletion and year of transplant. We analyzed for significant transplant center effect using a random effects test on EFS, OS, graft failure, acute and chronic GVHD, and adjusted for transplant center when it was significant. The assumption of proportional hazards was tested in a time-dependent covariate fashion. We tested for first-order interactions between the variables held in Cox models. Surviving patients were censored at last follow-up. All p-values are two-sided. All statistical analyses were performed using SAS Enterprise Guide (EG) version 7.1.
Results
A total of 399 patients were included in this study; 225 had Medicaid and 174 were privately insured (Table 1). The median follow-up time after alloHCT was 34.0 months (range 1.0–134.7) and 38.7 months (range 0.3–139.3) for patients on Medicaid and private insurance, respectively. There were no significant differences in patient-related variables including age at transplant, sex, race, genotype, Karnofsky score, HCT-comorbidity, or region of residence between the groups. However, median household income was higher among patients on private insurance compared to those on Medicaid (p<0.0001). Patients on Medicaid also resided closer to their transplant center compared to those privately insured (p=0.026). There were no significant differences in disease-related variables including the prevalence of SCD complications and receipt of hydroxyurea and/or chronic transfusion prior to alloHCT. There were no significant differences across transplant-related variables except for CMV serostatus, for which patients on Medicaid were less likely to have a negative CMV serostatus compared to patients on private insurance (p=0.0295).
Table 1.
Characteristics of United States patients with Sickle Cell Disease who received first Allogeneic Hematopoietic Cell Transplant between 2008 and 2018
| Characteristic No. of patients | Medicaid N=225 | Private Insurance N=174 | p-value |
|---|---|---|---|
| Patient-related | |||
|
| |||
| Median age at transplant- median (min-max) | 11.1 (1.7 – 56.0) | 11.4 (0.99–50.1) | 0.1711 |
| Age | 0.1419 | ||
| <18 | 176 (78) | 125 (72) | |
| ≥18 | 49 (22) | 49 (28) | |
| Sex | 0.5941 | ||
| Male | 122 (54) | 99 (57) | |
| Female | 103 (46) | 75 (43) | |
| Race | 0.2139 | ||
| Black/African American | 203 (90) | 163 (94) | |
| Other/missinga | 22 (10) | 11 (6) | |
| Genotype | 0.4860 | ||
| Hb SS | 198 (88) | 149 (86) | |
| Other/missingb | 27 (12) | 25 (14) | |
| Karnofsky score | 0.3101 | ||
| ≥ 90 | 187 (83) | 149 (86) | |
| < 90 | 30 (13) | 23 (13) | |
| Missing | 8 (4) | 2 (1) | |
| HCT-comorbidity index | 0.9560 | ||
| 0–2 | 152 (68) | 118 (68) | |
| ≥3 | 73 (32) | 56 (32) | |
| Region | 0.0955 | ||
| Northeast | 43 (19) | 25 (14) | |
| South | 103 (46) | 82 (47) | |
| Midwest | 58 (26) | 36 (21) | |
| West | 20 (9) | 29 (17) | |
| Missing | 1 (0) | 2 (1) | |
| Distance to transplant center (miles)- median (min-max) |
20.0 (0.3 – 1,608) | 25.2 (2 – 2,112) | 0.0201* |
| Household income by zip code | <0.001* | ||
| < 48,000 | 80 (36) | 31 (18) | |
| 48,000–60,999 | 62 (28) | 30 (17) | |
| 61,000–79,999 | 54 (24) | 50 (29) | |
| ≥ 80,000 | 26 (12) | 61 (35) | |
| Missing | 3 (1) | 2 (1) | |
|
| |||
| Disease-related | |||
|
| |||
| Chronic transfusion | 0.4967 | ||
| Yes | 213 (94) | 161 (93) | |
| No/Missingc | 13 (6) | 13 (7) | |
| Hydroxyurea | 0.9333 | ||
| Yes | 162 (72) | 125 (72) | |
| No | 59 (26) | 45 (26) | |
| Missing | 4 (2) | 4 (2) | |
| Sickle cell related complications | |||
| Stroke | 69 (31) | 41 (24) | 0.1153 |
| Acute chest syndrome | 140 (62) | 99 (57) | 0.2818 |
| Recurrent vaso-occlusive | 136 (60) | 99 (57) | |
| pain | 0.4751 | ||
| Number of sickle cell related complications | 0.0851 | ||
| <2 | 102 (45) | 94 (54) | |
| ≥2 | 123 (55) | 80 (46) | |
|
| |||
| Transplant-related | |||
|
| |||
| Transplant Indication | 0.0627 | ||
| Stroke | 46 (20) | 23 (13) | |
| Acute chest syndrome | 34 (15) | 30 (17) | |
| Recurrent vaso-occlusive pain | 80 (36) | 51 (29) | |
| Excessive transfusion requirements | 22 (10) | 17 (10) | |
| Other/Missing (includes recurrent priapism)d | 43 (19) | 53 (31) | |
| Donor Type | 0.8143 | ||
| HLA-matched sibling | 110 (49) | 82 (47) | |
| HLA-mismatched relative | 22 (10) | 20 (11) | |
| HLA-matched unrelated donor | 56 (25) | 39 (22) | |
| Cord blood | 37 (16) | 33 (19) | |
| Graft type | 0.7048 | ||
| Bone marrow | 165 (73) | 121 (70) | |
| Peripheral Blood | 23 (10) | 20 (11) | |
| Cord blood | 37 (16) | 33 (19) | |
| Recipient CMV serostatus | 0.0295* | ||
| Negative | 102 (45) | 98 (56) | |
| Positive | 123 (55) | 76 (44) | |
| Conditioning regimen | 0.0557 | ||
| Myeloablative | 154 (68) | 103 (59) | |
| Reduced intensity/Non-myeloablative | 71 (32) | 71 (41) | |
| GVHD prophylaxis | 0.3135 | ||
| Post-CY + other(s) | 24 (11) | 21 (12) | |
| TAC/CSA + MMF ± other(s) (except post-Cy) | 87 (39) | 53 (30) | |
| TAC/CSA + MTX ± other(s) (except post-Cy and MMF) | 96 (43) | 80 (46) | |
| TAC/CSA ± other(s) | 3 (1) | 5 (3) | |
| Other/missinge | 15 (7) | 15 (9) | |
| In vivo T-Cell depletion | 0.5681 | ||
| ATG alone | 89 (36) | 73 (42) | |
| CAMPATH alone | 128 (57) | 90 (52) | |
| No ATG or CAMPATH | 14 (6) | 11 (6) | |
| ATG + CAMPATH | 1 (<1) | 0 (0) | |
| Year of alloHCT | 0.4373 | ||
| 2008–2012 | 36 (16) | 33 (19) | |
| 2013–2018 | 189 (84) | 141 (81) | |
Abbreviations: CSA - cyclosporine; MMF - mycophenolate mofetil; MTX - methotrexate; TAC - tacrolimus; Post-CY - Post-transplant cyclophosphamide; ATG - Antithymocyte globulin; GVHD - graft-versus-host disease.
Other/Missing race: White (n=19), missing (n=7), Asian (n=4), native American (n=2)
Other/Missing genotype: Hb Sβ (n=19), other (n=20) missing (n=13).
Other/Missing chronic blood transfusion: No (n=13), Missing (n=13).
Other/Missing (includes recurrent priapism): missing (n=17), other (n=78), recurrent priapism (n=1).
Other/missing GVHD prophylaxis: Other (n=19), missing (n=11).
In univariate analysis, patients on Medicaid compared to private insurance had significantly lower 3-year EFS: 75.4% (95% CI: 69.4–81.0) vs. 82.2% (95% CI: 76.9–87.8), p= 0.0279 (Figure 1a) and significantly higher 3-year cumulative incidence of graft failure: 17.2% (95% CI: 12.5–22.5) vs. 10.5% (95%CI: 6.4–15.4), p= 0.0372 (Figure 1b). There were no significant differences in 3-year OS: 91.5% (95% CI: 87.1–95) vs. 92.3% (95% CI: 87.5–96), p= 0.6337 (Figure 1c). Cause of death among the 30 patients who died included interstitial pneumonitis/acute respiratory distress syndrome (n=9, 30%), organ failure (n=8, 27%), GVHD (n=5, 17%), other/unknown (n=5, 17%) and infection (n=3, 10%), with no significant difference by insurance type. There were no significant differences in the 6-month cumulative incidence of acute GVHD: 22.0% (95% CI: 6.8–27.6) VS. 19.7 (95% CI: 14.1–25.9), p=0.4556 (Figure 1d) or 3-year cumulative incidence of chronic GVHD: 30.4% (95% CI: 24.0–37.0) vs. 26.4% (95% CI: 19.8–33.6), p=0.6878 (Figure 1e) between the two groups.
Figure 1.
Event-free survival (A) graft failure (B), overall survival (C), acute graft-versus-host disease (D), and chronic graft-versus-host disease (E) among Medicaid and privately insured patient with sickle cell disease who received first allogeneic hematopoietic cell transplant in the United States between 2008 and 2018, stratified by insurance type.
In multivariate analysis adjusting for significant prognostic variables, patients on Medicaid had lower EFS compared to those privately insured (hazard ratio [HR] 2.36, 95% CI 1.44–3.85; p= 0.0006) (Table 2). Age > 12 years, Karnofsky score ≥ 90; grafts from HLA-matched unrelated donors and cord blood, and reduced intensity conditioning regimens were also associated with lower EFS. Graft failure occurred in a greater proportion of patients on Medicaid compared to those privately insured (HR: 2.57, 95% CI: 1.43–4.60; p=0.0015); grafts from cord blood and reduced intensity conditioning regimens also had increased cumulative incidence of graft failure. There were no significant differences in OS by insurance type (HR: 0.99, 95% CI: 0.47–2.07; p=0.9765); however, age >12 years, not receiving chronic transfusion prior to alloHCT and grafts from HLA-matched unrelated donors were associated with lower OS. There were no significant differences in acute GVHD by insurance type (HR: 0.94, 95% CI: 0.59–1.49; p=0.7905); not receiving chronic transfusion prior to alloHCT, grafts from HLA-matched unrelated donors and cord blood and not receiving ATG or Campath increased the risk of experiencing acute GVHD. There were no significant differences in chronic GVHD by insurance type (HR: 0.98, 95% CI: 0.65 −1.48; p=0.9331); Karnofsky score < 90 and grafts from HLA-matched unrelated donors were associated with higher incidence of chronic GVHD.
Table 2.
Multivariate models for event-free survival, graft failure, overall survival, acute and chronic GVHD.
| Variable | Events/patients | HR (95% CI) | p-value |
|---|---|---|---|
| Event-free survival | |||
|
| |||
| Main effect: Insurance Type | |||
| Private | 29/174 | 1 (ref) | |
| Medicaid | 57/225 | 2.36 (1.44–3.85) | 0.0006 |
| Age, years | |||
| ≤12 | 39/210 | 1 (ref) | |
| >12 | 47/189 | 1.77 (1.06–2.98) | 0.0304 |
| Karnofsky score | |||
| ≥ 90 | 8/53 | 1 (ref) | |
| < 90 | 76/336 | 0.44 (0.20–0.95) | 0.0368 |
| Donor Type | <0.0001 | ||
| HLA-matched sibling | 23/192 | 1 (ref) | |
| HLA-mismatched relative | 8/42 | 1.68 (0.62–4.50) | 0.3064 |
| HLA-matched unrelated donor | 31/95 | 2.65 (1.43–4.91) | 0.002 |
| Cord blood | 24/70 | 7.71 (3.83–15.52) | <.0001 |
| Conditioning regimen | |||
| Myeloablative | 42/142 | 1 (ref) | |
| Reduced intensity/Non- myeloablative | 44/257 | 3.12 (1.85–5.25) | <.0001 |
|
| |||
| Graft failure | |||
|
| |||
| Main effect: Insurance Type | |||
| Private | 19/174 | 1 (ref) | |
| Medicaid | 41/225 | 2.57 (1.43–4.60) | 0.0015 |
| Donor Type | <0.0001 | ||
| HLA-matched sibling | 17/192 | 1 (ref) | |
| HLA-mismatched relative | 6/42 | 1.83 (0.61–5.54) | 0.2843 |
| HLA-matched unrelated donor | 16/95 | 1.66 (0.77–3.57) | 0.1975 |
| Cord blood | 21/70 | 8.01 (3.60–17.79) | <0.0001 |
| Conditioning regimen | |||
| Myeloablative | 28/142 | 1 (ref) | <0.0001 |
| Reduced intensity/Nonmyeloablative | 32/257 | 4.05 (2.17–7.57) | |
|
| |||
| Overall survival | |||
|
| |||
| Main effect: Insurance Type | |||
| Private | 12/174 | 1 (ref) | |
| Medicaid | 18/225 | 0.99 (0.47–2.07) | 0.9765 |
| Age, years | |||
| ≤12 | 4/210 | 1 (ref) | |
| >12 | 26/189 | 8.42 (2.71–26.16) | 0.0002 |
| Donor Type | 0.0024 | ||
| HLA-matched sibling | 6/192 | 1 (ref) | |
| HLA-mismatched relative | 2/42 | 0.93 (0.19–4.68) | 0.9305 |
| HLA-matched unrelated donor | 18/95 | 5.11 (1.98–13.19) | 0.0008 |
| Cord blood | 4/70 | 2.87 (0.78–10.51) | 0.1124 |
| Chronic transfusion | |||
| Yes | 27/371 | 1 (ref) | |
| No | 3/13 | 7.03 (2.05–24.19) | 0.002 |
|
| |||
| Acute GVHD | |||
|
| |||
| Main effect: Insurance Type | |||
| Private | 35/173 | 1 (ref) | |
| Medicaid | 52/225 | 0.94 (0.59 – 1.49) | 0.7905 |
| Sex | |||
| Male | 41/220 | 1 (ref) | |
| Female | 46/178 | 1.43 (0.93–2.20) | 0.1006 |
| Donor Type | 0.0012 | ||
| HLA-matched sibling | 27/192 | 1 (ref) | |
| HLA-mismatched relative | 8/42 | 1.11 (0.49–2.52) | 0.809 |
| HLA-matched unrelated donor | 32/94 | 2.79 (1.64 – 4.75) | 0.0002 |
| Cord blood | 20/70 | 1.99 (1.09–3.60) | 0.0241 |
| In vivo T-Cell depletion | 0.0036 | ||
| Campath alone | 41/218 | 1 (ref) | |
| ATG alone | 33/154 | 1.37 (0.83–2.25) | 0.2146 |
| No ATG or Campath | 13/25 | 3.07 (1.60–5.91) | 0.0008 |
| Chronic transfusion | |||
| Yes | 80/370 | 1 (ref) | |
| No | 6/13 | 2.83 (1.21–6.60) | 0.0163 |
|
| |||
| Chronic GVHD | |||
|
| |||
| Main effect: Insurance Type | |||
| Private | 45/172 | 1 (ref) | |
| Medicaid | 65/222 | 0.98 (0.65 −1.48) | 0.9331 |
| Karnofsky score | |||
| ≥ 90 | 25/53 | 1 (ref) | |
| < 90 | 81/331 | 1.91 (1.13–3.24) | 0.0159 |
| HCT comorbidity index | |||
| 0–2 | 62/266 | 1 (ref) | |
| ≥3 | 45/128 | 1.53 (0.97–2.41) | 0.0706 |
| Donor Type | |||
| HLA-matched sibling | 41/191 | 1 (ref) | 0.0004 |
| HLA-mismatched relative | 7/42 | 0.756 (0.31–1.85) | 0.5398 |
| HLA-matched unrelated donor | 43/94 | 2.35 (1.45–3.79) | 0.0005 |
| Cord blood | 16/67 | 0.87 (0.45 −1.66) | 0.6663 |
Abbreviations: GVHD - graft-versus-host disease; ATG - Antithymocyte globulin
Discussion
We report for the first time to the best of our knowledge that patients with SCD on Medicaid experienced lower EFS and higher cumulative incidence of graft failure compared to those on private insurance, with no significant difference in OS, acute or chronic GVHD, by insurance type. Our study findings are notable as they demonstrate an independent effect of health insurance type on alloHCT outcomes among patients with SCD. A prior study in children with non-malignant diseases did not find a significant association between insurance type and OS, acute and/or chronic GVHD, however, study outcomes did not include EFS or graft failure.15 Given the excellent OS reported among alloHCT recipients with SCD,6–8 it is not surprising that we did not find a significant difference in OS by insurance type. In contrast, 17.2% and 10.5% of Medicaid and privately insured patients with SCD experienced graft failure, associated with reduced EFS. Thus, EFS might be a more relevant outcome than OS in patients with SCD who often experience excellent OS.23
Several reasons may explain lower EFS and higher cumulative incidence of graft failure among Medicaid compared to privately insured patients with SCD, including limited access to primary care prior to alloHCT and/or delayed referrals cited in hematologic malignancies. 24 However, very few studies, with mixed results have compared health care utilization and patient and disease related variables among Medicaid and privately insured patients with SCD.25,26 A small (n=53), single institution study of children 8–18 years old with SCD found that children with public insurance (Medicaid and Medicare) experienced more SCD-related complications and lower quality of life compared to privately insured patients.26 However, Mvundura et al., did not find a significant difference in the prevalence of inpatient discharge diagnoses for SCD-related complications including VOCs, ACS, splenic sequestration and cerebrovascular disease among patients with SCD enrolled on Medicaid compared to private insurance.25 Consistent with Mvundura et al., we did not find a significant difference in the prevalence of SCD related complications prior to alloHCT by insurance type. Thus, it is likely that the relationship between insurance type and alloHCT outcomes might be more complex than can be explained by currently collected clinical variables pre-alloHCT. They also underscore the need for more sensitive markers of disease severity among patients with SCD. It is noteworthy that Mvundura et al found that children on Medicaid were more likely to have had diagnoses of asthma, fever, or heart disease compared to those on private insurance, suggesting the need for further research on the role of other comorbidities on outcomes, as well as more in depth studies into the influence of social determinants of health.25
Poorer follow-up care post-alloHCT may also explain lower EFS and higher cumulative incidence of graft failure among Medicaid compared to privately insured patients with SCD. Patients on Medicaid may experience additional barriers including limited access to resources such as transportation and/or limited ability to pay co-payments for prescribed medication, limiting compliance to medical follow up and/or medication adherence post-alloHCT.13,26 A single institution study of patients with SCD (n=101) found that 59% of patients with SCD reported at least one household material hardship (HMH), a measure of housing and food insecurity, difficulty paying for utilities and/or difficulty getting transportation to medical appointments.27 Screening for HMH maybe an effective intervention at the clinic level and presents an opportunity to collect information on a broad range of socioeconomic variables that may be associated with alloHCT outcomes among patients with SCD.
Although several studies have reported an association between household income and alloHCT outcomes in several hematologic malignancies,15,28 we did not find a significant association between median household income and alloHCT outcomes among patients with SCD. This may be because Medicaid insurance is associated with household income, with significantly lower median household income among Medicaid versus privately insured patients, included in our study population. Consistent with our study findings, a study among pediatric HCT recipients with malignant disease found that insurance type but not poverty level was associated with OS.15 Another study among pediatric patients with SCD, found that insurance type but not neighborhood sociodemographic risk factors, was significantly associated with SCD-related complications and quality of life.26 Hence, our study findings build on prior work suggesting that insurance type may be a better proxy measure of SES compared to median household income.15,26
Race has been shown to be associated with alloHCT outcomes in several clinical conditions, with poorer outcomes among Black/African American compared to White patients. 15,28 The homogeneous nature of the study population by race (92% Black/African American) offers a unique model for studying health disparities associated with private insurance versus Medicaid without the interaction of race and ethnicity. In this study, we identified health insurance type as a source of disparity even within racial and ethnic minorities to which most patients with SCD patients belong.
It is striking that insurance type was significantly associated with EFS and graft failure, even after adjusting for disease- and transplant-related variables including age and graft type.6–8 A better understanding of the contribution of insurance type on EFS and graft failure may provide important insight into the development of targeted interventions aimed at improving alloHCT outcomes among patients with SCD.29 For example, several patient and clinic level interventions have been proposed such as screening for social determinants of health.27,30 One such study demonstrated the feasibility of 1) universal screening for social determinants of health and 2) facilitating referrals to community organizations among patients with SCD seen at a pediatric hematology clinic.30
However, this study has several limitations. First, our study cohort includes patients who received an alloHCT. Hence, we are unable to explore the relationship between insurance type and access to alloHCT among patients with SCD. Future studies using Medicaid and private insurance claims data may help characterize access to alloHCT by insurance type. Secondly, we only had available information on insurance enrollment at the time of HCT. However, patients can change insurance both pre- and post-transplant which could impact outcomes and alter our analysis. We estimated median household income based on patient 5-digit zip code. However, median household income based on zip code is limited by the inherent heterogeneity of household income within a zip code. Hence, collection of individual household income may help better characterize the role of household income on alloHCT outcomes.
Despite these limitations, the results from the current study expand on previous research on health disparities in HCT and the impact of health insurance on health outcomes. We found that patients with SCD on Medicaid experienced lower EFS and higher cumulative incidence of graft failure compared to those on private insurance even after adjusting for patient, disease, and transplant-related variables. These results provide the rationale for further research aimed at better understanding the contribution of insurance type on alloHCT outcome among patients with SCD. The results of such studies are crucial to help identify strategies to mitigate the impact of insurance status on alloHCT outcomes among patients with SCD.
Highlights.
Patients with SCD on Medicaid had lower EFS compared to those on private insurance.
Patients on Medicaid had higher graft failure compared to those on private insurance.
There were no differences in OS, acute or chronic GVHD by insurance type.
Acknowledgements:
The CIBMTR is supported primarily by Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); HHSH250201700006C, SC1MC31881-01-00 and HHSH250201700007C from the Health Resources and Services Administration (HRSA); and N00014-18-1-2850, N00014-18-1-2888, and N00014-20-1-2705 from the Office of Naval Research; Additional federal support is provided by P01CA111412, R01CA152108, R01CA215134, R01CA218285, R01CA231141, R01HL126589, R01AI128775, R01HL129472, R01HL130388, R01HL131731, U01AI069197, U01AI126612, and BARDA. Support is also provided by Be the Match Foundation, Boston Children’s Hospital, Dana Farber, Japan Hematopoietic Cell Transplantation Data Center, St. Baldrick’s Foundation, the National Marrow Donor Program, the Medical College of Wisconsin and from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies; Adienne SA; Allovir, Inc.; Amgen, Inc.; Anthem, Inc.; Astellas Pharma US; AstraZeneca; Atara Biotherapeutics, Inc.; bluebird bio, Inc.; Bristol Myers Squibb Co.; Celgene Corp.; Chimerix, Inc.; CSL Behring; CytoSen Therapeutics, Inc.; Daiichi Sankyo Co., Ltd.; Gamida-Cell, Ltd.; Genzyme; GlaxoSmithKline (GSK); HistoGenetics, Inc.; Incyte Corporation; Janssen Biotech, Inc.; Janssen Pharmaceuticals, Inc.; Janssen/Johnson & Johnson; Jazz Pharmaceuticals, Inc.; Kiadis Pharma; Kite Pharma; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Mallinckrodt LLC; Medac GmbH; Merck & Company, Inc.; Merck Sharp & Dohme Corp.; Mesoblast; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; Novartis Oncology; Novartis Pharmaceuticals Corporation; Omeros Corporation; Oncoimmune, Inc.; Orca Biosystems, Inc.; Pfizer, Inc.; Phamacyclics, LLC; Regeneron Pharmaceuticals, Inc.; REGiMMUNE Corp.; Sanofi Genzyme; Seattle Genetics; Sobi, Inc.; Takeda Oncology; Takeda Pharma; Terumo BCT; Viracor Eurofins and Xenikos BV. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government. SDA is supported by a K23 award from the National Institutes of Health (1K23HL143164-01).
Footnotes
Authorship and conflict-of-interest statements
Declarations of interest: none
Financial Disclosure Statement: None of the authors have any financial conflicts of interest to report.
Conflicts of Interest:
All the authors report no conflicts of interest.
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