This cohort study aims to identify risk factors for subsequent cutaneous malignant neoplasms among patients who underwent blood or marrow transplant.
Key Points
Question
What is the risk of subsequent cutaneous malignant neoplasms (basal cell carcinoma [BCC], squamous cell carcinoma, or melanoma) after blood or marrow transplant (BMT), and who is at risk?
Findings
In this cohort study of 3880 BMT survivors, the 30-year cumulative incidence of any cutaneous malignant neoplasm was 27.4% (BCC, 18.0%; squamous cell carcinoma, 9.8%; melanoma, 3.7%). Risk factors included age of 50 years and older at BMT, chronic graft-vs-host disease among allogeneic BMT recipients, pretransplant monoclonal antibody exposure, posttransplant immunosuppression, and site of transplant, while total body irradiation was a risk factor for BCC among participants younger than 50 years at transplant.
Meaning
These findings can inform counseling and dermatologic surveillance.
Abstract
Importance
Cutaneous malignant neoplasms are the most common subsequent neoplasm after blood or marrow transplant (BMT), but a full assessment among survivors is lacking.
Objective
To identify risk factors for subsequent cutaneous malignant neoplasms using the BMT Survivor Study (BMTSS).
Design, Setting, and Participants
This retrospective cohort study included patients who underwent transplant from 1974 to 2014 at City of Hope, University of Minnesota, or University of Alabama at Birmingham and survived 2 years or longer, as well as a comparison cohort of siblings. Both groups completed the BMTSS survey. Data analysis took place from October 2022 to October 2024.
Exposures
Demographics, pre-BMT and BMT-related therapeutic exposures, chronic graft-vs-host disease (cGVHD), and posttransplant immunosuppression.
Main Outcomes and Measures
Incident cutaneous malignant neoplasms (basal cell carcinoma [BCC], squamous cell carcinoma [SCC], and melanoma) after BMT. Exposures were evaluated for association with subsequent neoplasms using proportional subdistribution hazards models (reported as subdistribution hazard ratio [SHR] and 95% CI).
Results
Among the 3880 BMT survivors (median [range] age at BMT, 44.0 [0-78.0] years; 2165 [55.8%] male; 190 [4.9%] Black, 468 [12.1%] Hispanic, 2897 [74.7%] non-Hispanic White, and 325 [8.4%] of other race [including Asian and Pacific Islander] and multiracial) who were followed up for a median (range) of 9.5 (2.0-46.0) years, 605 developed 778 distinct cutaneous neoplasms (BCC, 321; SCC, 231; melanoma, 78; and unknown type, 148). The 30-year cumulative incidence of any cutaneous malignant neoplasm was 27.4% (BCC, 18.0%; SCC, 9.8%; and melanoma, 3.7%). Seventy-year cumulative probabilities of BCC, SCC, and melanoma were considerably higher in BMT survivors than siblings (18.1% vs 8.2%, 14.7% vs 4.2%, and 4.2% vs 2.4%, respectively). Among BMT survivors, risk factors for subsequent cutaneous malignant neoplasms included age of 50 years and older at BMT (BCC: SHR, 1.76; 95% CI, 1.36-2.29; SCC: SHR, 3.37; 95% CI, 2.41-4.72), male sex (BCC: SHR, 1.39; 95% CI, 1.10-1.75; SCC: SHR, 1.85; 95% CI, 1.39-2.45), pre-BMT monoclonal antibody exposure (BCC: SHR, 1.71; 95% CI, 1.27-2.31), allogeneic BMT with cGVHD (BCC: SHR, 1.48; 95% CI, 1.06-2.08; SCC: SHR, 2.61; 95% CI, 1.68-4.04 [reference: autologous BMT]), post-BMT immunosuppression (BCC: SHR, 1.63; 95% CI, 1.24-2.14; SCC: SHR, 1.48; 95% CI, 1.09-2.02; melanoma: SHR, 1.90; 95% CI, 1.16-3.12), and transplant at City of Hope (BCC: SHR, 3.55; 95% CI, 2.58-4.89; SCC: SHR, 3.57; 95% CI, 2.34-5.47 [reference: University of Minnesota]) or University of Alabama at Birmingham (BCC: SHR, 2.35; 95% CI, 1.35-4.23; SCC: SHR, 2.63; 95% CI, 1.36-5.08 [reference: University of Minnesota]). Race and ethnicity other than non-Hispanic White were protective for BCC (Black: no cases; Hispanic: SHR, 0.27; 95% CI, 0.16-0.44; other race and multiracial: SHR, 0.26; 95% CI, 0.14-0.50 [reference: non-Hispanic White]) and SCC (Black: SHR, 0.17; 95% CI, 0.04-0.67; Hispanic: SHR, 0.28; 95% CI, 0.16-0.50; other race and multiracial: SHR, 0.13; 95% CI, 0.05-0.37 [reference: non-Hispanic White]). Total body irradiation was associated with BCC risk among those younger than 50 years at BMT (SHR, 1.92; 95% CI, 1.27-2.92).
Conclusions and Relevance
In this cohort study, the high risk of cutaneous malignant neoplasms and malignant-specific risk factors suggest a need for personalized patient counseling and posttransplant dermatologic surveillance.
Introduction
Survivors of blood or marrow transplant (BMT) have heightened risk of subsequent neoplasms.1,2,3 Therapeutic exposures, younger age, chronic graft-vs-host disease (cGVHD), and prolonged immunosuppression increase BMT survivors’ vulnerability to subsequent neoplasms.1,2,4,5,6 Cutaneous neoplasms are the most common solid neoplasms observed after BMT and include basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma.7 Prior evaluations of subsequent cutaneous malignant neoplasms after BMT excluded nonmelanoma skin cancers (NMSCs), evaluated SCC but not BCC, or restricted the cohorts to allogeneic BMT recipients.1,8,9,10 Furthermore, there were small sample sizes with limited follow-up. Due to differences in underlying mechanisms of tumorigenesis, the etiologies of post-BMT BCC, SCC, and melanoma likely differ. In this study, we sought to determine the magnitude of risk of BCC, SCC, and melanoma after BMT in a large cohort of BMT survivors followed up long term using the BMT Survivor Study (BMTSS).
Methods
Study Cohort
BMTSS is a multi-institutional retrospective cohort study with longitudinal follow-up that examines long-term complications after BMT, including subsequent neoplasms. Participants are pediatric and adult patients who underwent BMT between 1974 and 2014 at City of Hope (COH), University of Minnesota (UMN), or University of Alabama at Birmingham (UAB) and survived at least 2 years after BMT. Participants completed up to 3 surveys over a 15-year period. The survey captured sociodemographics (race and ethnicity [Black, Hispanic, non-Hispanic White, and other race and multiracial, including Asian and Pacific Islander, which were grouped together for analytical purposes], annual household income, education, insurance), chronic health conditions, subsequent neoplasms, cGVHD, and posttransplant medications, including immunosuppression. Survivors’ age at BMT, sex, history of prior skin cancer, primary diagnosis (indication for BMT), type of transplant (autologous, allogeneic), and therapeutic exposures were retrieved from institutional transplant databases and/or participants’ medical records. BMTSS also examines outcomes in an unaffected comparison group drawn from the survivors’ siblings by asking the siblings to complete a similar survey.
The UAB Institutional Review Board approved the study. Participants provided written informed consent. The present cohort was restricted to individuals who underwent a single transplant and completed at least 1 BMTSS survey and the sibling cohort. We linked the study participants with the National Death Index Plus to determine date and cause of death for deceased participants. This study followed Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines.
Outcome
The primary outcomes were development of subsequent cutaneous malignant neoplasms (BCC, SCC, or melanoma). Participants were asked “At any time after your BMT, were you diagnosed with cancer, leukemia, tumor, or similar illness [include skin cancers]?” The diagnosing health care professional, facility, and month and year of diagnosis were requested. When available, melanoma cases were confirmed by obtaining pathology reports and/or physician notes.
Statistical Analysis
Separate analyses were performed for BCC, SCC, and melanoma. For each cutaneous malignant neoplasm type, cumulative incidence plots and 95% CIs were computed using competing risk methods, with incident cutaneous malignant neoplasm as the primary event and death as competing risk. For patients with more than 1 type of cutaneous malignant neoplasm during follow-up, all reported events were considered. Difference in cumulative incidence between groups was assessed using the Gray test. Participants were censored at time of last survey. The association of demographic and treatment variables with the risk of cutaneous malignant neoplasms was assessed using Fine-Gray proportional subdistribution hazard models, with time at risk from the date of BMT to development of the cutaneous malignant neoplasm, last known follow-up, or death.
Clinical/therapeutic variables examined included primary diagnosis, total body irradiation (TBI), conditioning intensity (myeloablative, nonmyeloablative/reduced intensity), type of BMT (autologous, allogeneic without cGVHD, allogeneic with cGVHD), pre-BMT exposures (radiation, alkylating agents, anthracyclines, antimetabolites, bleomycin, platinum compounds, topoisomerase II inhibitors, steroids, plant alkaloids, monoclonal antibodies, and targeted agents), post-BMT immunosuppression, site of transplant (UMN, COH, or UAB), and year of transplant (before 2000, 2000 and later) (eTable 1 in Supplement 1). Magnitude of association was presented as a subdistribution hazard ratio (SHR) with corresponding 95% CI. Backward selection was used to select covariates for inclusion in the adjusted models based on the effect of their stepwise removal on model explanatory power, measured by Akaike information criterion. Low melanoma event rates precluded effective use of backward selection for model inclusion, and these covariates were selected a priori: age, sex, race and ethnicity, prior skin cancer, pretransplant radiation, TBI, conditioning intensity, posttransplant immunosuppression, year of transplant, and site of transplant.
To evaluate the age-dependent impact of treatment exposures on cancer risk, we performed analyses stratified by age at BMT (<50 years, ≥50 years). Additional sensitivity analyses included models with posttransplant immunosuppression categorized as calcineurin inhibitor (CNI) or non-CNI, pretransplant monoclonal antibody exposure categorized as rituximab or other, and a melanoma model limited to validated cases.
Standardized incidence ratios (SIRs) quantified the excess risk of melanoma among BMT survivor participants compared to the general population. Age- and sex-specific incidence rates of melanoma in the general population were obtained from the Surveillance, Epidemiology, and End Results (SEER) Program using SEER*Stat.11 The expected number of cases was calculated by multiplying the person-years at risk in the BMT cohort by incidence rates for the general population. SIRs were calculated as the ratio of observed to expected cases. The exact 95% CIs were estimated by assuming Poisson distribution for SIR, where the offset was the number of total log person-years and the outcome was the number of melanoma cases. Because population-level data are not available from SEER for NMSCs, we compared the risk of cutaneous malignant neoplasms in BMT survivor participants to the sibling cohort using Kaplan-Meier analysis and multivariable logistic regression (adjusting for age at survey completion, sex, race and ethnicity, education, and income).
Statistical analyses were performed from October 2022 to October 2024 using SAS, version 9.4 (SAS Institute). The level of statistical significance was set at P = .05, and all P values and 95% CIs were 2-sided.
Results
Participant Characteristics
Characteristics of the 3880 BMT survivor participants and the 1415 sibling participants are summarized in Table 1. BMT survivor participants were younger at survey completion when compared with the sibling cohort (median [range] age, 56.0 [4.0-89.0] years vs 57.5 [2.4-90.5] years). Among the BMT cohort, there were 2165 male participants (55.8%) and 1715 female participants (44.2%); 190 (4.9%) Black participants, 468 (12.1%) Hispanic participants, 2897 (74.7%) non-Hispanic White participants, and 325 (8.4%) participants of other race and multiracial; and the median (range) age at BMT was 44.0 (0-78.0) years. The most common indications for BMT among participants were non-Hodgkin lymphoma (NHL; 953 [24.6%]), acute myeloid leukemia/myelodysplastic syndrome (930 [24.0%]), and plasma cell disorders (594 [15.3%]). A total of 2056 participants (53.0%) received an allogeneic BMT, and 508 (13.1%) received pretransplant radiation. A majority of the cohort received myeloablative conditioning (2981 [76.8%]), and 1819 (46.9%) received TBI. Among allogeneic transplant recipients, 1045 (50.8%) had cGVHD (356 [34.0%] with skin involvement). Additionally, 836 participants (21.5%) reported posttransplant immunosuppression, and 430 (51.0%) of these received a CNI. The cohort was followed up for a median (range) of 9.5 (2.0-46.0) years. Among the BMT survivor participants, 605 (15.6%) reported 778 distinct cutaneous malignant neoplasms (Table 1), including 78 with melanoma, 231 with SCC, 321 with BCC, and 148 with skin cancer of unknown type. The 30-year cumulative incidence of any cutaneous malignant neoplasm was 27.4% (Figure); by individual malignant neoplasm type, the 30-year cumulative incidence was 18.0% for those with BCC, 9.8% for those with SCC, and 3.7% for those with melanoma. Four patients died due to a cutaneous malignant neoplasm after completing the survey, comprising less than 1% of the 800 deceased individuals.
Table 1. Characteristics of the Study Cohort.
| Characteristic | No. (%) | |
|---|---|---|
| BMT cohort (n = 3880) | Sibling cohort (n = 1425) | |
| Age at transplant, y | ||
| Mean (SD) | 40.7 (19.6) | NA |
| Median (range) | 44.0 (0-78.0) | NA |
| <18 | 609 (15.7) | NA |
| 18-49 | 1716 (44.2) | NA |
| ≥50 | 1555 (40.1) | NA |
| Age at survey completion, y | ||
| Mean (SD) | 51.8 (17.3) | 53.3 (16.8) |
| Median (range) | 56.0 (4.0-89.0) | 57.5 (2.4-90.5) |
| Sex | ||
| Female | 1715 (44.2) | 851 (59.7) |
| Male | 2165 (55.8) | 574 (40.3) |
| Race and ethnicity | ||
| Black | 190 (4.9) | 33 (2.3) |
| Hispanic | 468 (12.1) | 99 (6.9) |
| Non-Hispanic White | 2897 (74.7) | 1213 (86.4) |
| Other race and multiraciala | 325 (8.4) | 62 (4.4) |
| Highest level of education | ||
| ≤High school | 869 (22.4) | 217 (15.2) |
| Some college | 1385 (35.7) | 463 (32.5) |
| ≥College degree | 1598 (41.2) | 733 (51.4) |
| Decline to answer/missing | 28 (0.7) | 12 (0.8) |
| Annual income, $ | ||
| <50 000 | 1255 (32.3) | 288 (20.2) |
| 50 000-74 999 | 627 (16.2) | 254 (17.8) |
| ≥75 000 | 1542 (39.7) | 736 (51.6) |
| Decline to answer/missing | 456 (11.8) | 147 (10.3) |
| Prior skin cancer | 65 (1.7) | NA |
| Primary cancer diagnosis | ||
| Acute lymphoblastic leukemia | 346 (8.9) | NA |
| Acute myeloid leukemia/myelodysplastic syndrome | 930 (24.0) | NA |
| Chronic myelogenous leukemia | 356 (9.2) | NA |
| Hodgkin lymphoma | 260 (6.7) | NA |
| Non-Hodgkin lymphoma | 953 (24.6) | NA |
| Plasma cell disorder | 594 (15.3) | NA |
| Severe aplastic anemia | 138 (3.6) | NA |
| Other | 303 (7.8) | NA |
| Pretransplant chemotherapy | ||
| Any chemotherapeutic agent | 3311 (85.3) | NA |
| Alkylating agents | 1613 (41.6) | NA |
| Anthracyclines | 2247 (57.9) | NA |
| Antimetabolite | 1578 (40.7) | NA |
| Bleomycin | 295 (7.6) | NA |
| Monoclonal antibody | 716 (18.5) | NA |
| Platinum compounds | 639 (16.5) | NA |
| Targeted agent | 556 (14.3) | NA |
| Topoisomerase II inhibitor | 906 (23.4) | NA |
| Steroid | 2085 (53.7) | NA |
| Plant alkaloid | 1546 (39.8) | NA |
| Pretransplant radiation | 508 (13.1) | NA |
| Transplant type | ||
| Autologous | 1824 (47.0) | NA |
| Allogeneic | 2056 (53.0) | NA |
| Conditioning intensity | ||
| Myeloablative | 2981 (76.8) | NA |
| Nonmyeloablative/reduced intensity | 895 (23.1) | NA |
| Total body irradiation | 1819 (46.9) | NA |
| Year of transplant | ||
| Before 2000 | 1284 (33.1) | NA |
| 2000 or later | 2596 (66.9) | NA |
| Site of transplant | ||
| University of Minnesota | 1313 (33.8) | NA |
| City of Hope | 2246 (57.9) | NA |
| University of Alabama at Birmingham | 321 (8.3) | NA |
| cGVHD among allogeneic BMT recipients (n = 2056) | 1045 (26.9) | NA |
| Posttransplant immunosuppression | ||
| Calcineurin inhibitor | 430 (51.4) | NA |
| Non–calcineurin inhibitor immunosuppression | 406 (48.6) | NA |
| None | 3044 (78.5) | NA |
| Follow-up time, median (range), yb | 9.0 (2.0-46.0) | 57.5 (2.4-90.5) |
| Status at follow-up | ||
| Skin cancer | 605 (15.6) | NA |
| Alive without skin cancer | 2659 (68.5) | NA |
| Deceased without skin cancer | 616 (15.9) | NA |
| First skin cancer subtypec | ||
| Melanoma | 50 (1.3) | NA |
| Squamous cell carcinoma | 174 (4.5) | NA |
| Basal cell carcinoma | 233 (6.0) | NA |
| Unknown/not specified | 148 (3.8) | NA |
| Any skin cancer subtyped | ||
| Melanoma | 78 (2.0) | 20 (1.4) |
| Squamous cell carcinoma | 231 (6.0) | 29 (2.0) |
| Basal cell carcinoma | 321 (8.3) | 63 (4.4) |
| Unknown/not specified | 148 (3.8) | NA |
Abbreviations: BMT, bone or marrow transplant; cGVHD, chronic graft-vs-host disease; NA, not applicable.
Other race and multiracial includes Asian and Pacific Islander participants and was grouped together for analytical purposes.
Follow-up time for BMT survivor participants was time from BMT to survey completion; for sibling participants, follow-up time was measured from birth to survey completion.
Type of first secondary cutaneous malignant neoplasm diagnosed during posttransplant follow-up period.
Type of secondary cutaneous malignant neoplasm diagnosed at any time during posttransplant follow-up period (participants may have more than 1 event). For BMT survivor participants, events occurred between BMT and survey completion, whereas for sibling participants events occurred from birth to survey completion.
Figure. Cumulative Incidence Curves for Skin Cancer Events.
Shaded areas represent 95% CIs. BCC indicates basal cell carcinoma; HCT, hematopoietic cell transplant; HR, hazard ratio; SCC, squamous cell carcinoma.
Any Cutaneous Malignant Neoplasm
Multivariable analysis identified age of 50 years or older at BMT (SHR, 2.23; 95% CI, 1.83-2.71 [reference: <50 years]), male sex (SHR, 1.40; 95% CI, 1.18-1.65), pretransplant skin cancer (SHR, 3.35; 95% CI, 2.14-5.23), pretransplant monoclonal antibody exposure (SHR, 1.29; 95% CI, 1.00-1.66), cGVHD among allogeneic BMT recipients (SHR, 1.84; 95% CI, 1.37-2.47 [reference: autologous BMT]), TBI (SHR, 1.32; 95% CI, 1.08-1.63), site of transplant (COH: SHR, 2.03; 95% CI, 1.62-2.54; UAB: SHR, 1.99; 95% CI, 1.35-2.93 [reference: UMN]), and posttransplant immunosuppression (SHR, 1.53; 95% CI, 1.26-1.86) to be associated with cutaneous malignant neoplasm. Race and ethnicity other than non-Hispanic White was protective against cutaneous malignant neoplasm (Black: SHR, 0.14; 95% CI, 0.05-0.37; Hispanic: SHR, 0.29; 95% CI, 0.20-0.42; other race and multiracial: SHR, 0.22; 95% CI, 0.13-0.37 [reference: non-Hispanic White]) (Table 2 and Table 3).
Table 2. Patient and Treatment-Related Factors Associated With Subsequent Cutaneous Malignant Neoplasms.
| Patient or treatment characteristic | No. (%) | |||
|---|---|---|---|---|
| Any skin cancer (n = 605) | Squamous cell carcinoma (n = 231) | Basal cell carcinoma (n = 321) | Melanoma (n = 78) | |
| Age at transplant, y | ||||
| <50 | 290 (12.5) | 78 (3.4) | 165 (7.1) | 41 (1.8) |
| ≥50 | 315 (20.2) | 153 (9.8) | 156 (6.7) | 37 (2.4) |
| Sex | ||||
| Female | 223 (36.9) | 73 (31.6) | 118 (36.8) | 30 (38.5) |
| Male | 382 (63.1) | 158 (68.4) | 203 (63.2) | 48 (61.5) |
| Race and ethnicity | ||||
| Black | 4 (0.7) | 2 (0.9) | 0 | 1 (1.3) |
| Hispanic | 31 (5.1) | 12 (5.2) | 17 (5.3) | 5 (6.4) |
| Non-Hispanic White | 555 (91.7) | 213 (92.2) | 294 (91.6) | 70 (89.7) |
| Other race and multiraciala | 15 (2.5) | 4 (1.7) | 10 (3.1) | 2 (2.6) |
| Prior skin cancer | 30 (5.0) | 19 (8.2) | 27 (8.4) | 5 (6.4) |
| Primary cancer diagnosis | ||||
| Leukemia | 268 (44.3) | 106 (45.9) | 144 (44.9) | 33 (42.3) |
| Lymphoma | 238 (39.4) | 81 (35.0) | 131 (40.9) | 32 (41.0) |
| Other | 99 (16.4) | 44 (19.1) | 46 (14.3) | 10 (16.7) |
| Transplant type/cGVHD | ||||
| Autogenous | 271 (44.8) | 91 (39.4) | 147 (45.8) | 40 (51.3) |
| Allogeneic without cGVHD | 123 (20.3) | 31. (13.4) | 62 (19.3) | 16 (20.5) |
| Allogeneic with cGVHD | 211 (34.9) | 109 (47.2) | 112 (34.9) | 22 (28.2) |
| Total body irradiation | 310 (51.2) | 86 (37.2) | 163 (50.8) | 40 (51.3) |
| Conditioning intensity | ||||
| Myeloablative | 452 (74.7) | 147 (63.6) | 245 (76.3) | 58 (74.4) |
| Nonmyeloablative/reduced intensity | 153 (25.3) | 84 (36.4) | 76 (23.7) | 20 (25.6) |
| Pretransplant chemotherapy | ||||
| Alkylator | 294 (48.6) | 103 (44.6) | 164 (51.1) | 40 (51.3) |
| Anthracycline | 402 (66.4) | 152 (65.8) | 220 (68.5) | 52 (66.7) |
| Antimetabolite | 278 (46.0) | 103 (44.6) | 158 (49.2) | 35 (44.9) |
| Bleomycin | 51 (8.4) | 18 (7.8) | 31 (9.7) | 5 (6.4) |
| Monoclonal antibody | 148 (24.5) | 54 (23.4) | 79 (24.6) | 17 (21.8) |
| Platinum | 115 (19.0) | 46 (19.9) | 60 (18.7) | 20 (25.6) |
| Targeted agent | 55 (9.1) | 28 (12.1) | 25 (7.8) | 9 (11.5) |
| Topoisomerase II inhibitor | 151 (25.0) | 55 (23.8) | 79 (24.6) | 26 (33.3) |
| Steroid | 348 (57.5) | 126 (54.5) | 190 (59.2) | 40 (51.3) |
| Plant alkaloid | 294 (48.6) | 101 (43.7) | 159 (49.5) | 38 (48.7) |
| Pretransplant radiation | 86 (14.2) | 26 (11.3) | 52 (16.2) | 8 (10.3) |
| Year of transplant | ||||
| Before 2000 | 224 (37.0) | 56 (24.2) | 127 (39.6) | 23 (29.5) |
| 2000 or later | 381 (63.0) | 175 (75.8) | 194 (60.4) | 55 (70.5) |
| Site of transplant | ||||
| University of Minnesota | 156 (25.8) | 33 (14.3) | 59 (18.4) | 27 (34.6) |
| City of Hope | 402 (66.4) | 181 (78.4) | 241 (75.1) | 47 (60.3) |
| University of Alabama at Birmingham | 47 (7.8) | 17 (7.4) | 21 (6.5) | 4 (5.1) |
| Posttransplant immunosuppression | 154 (25.5) | 66 (28.6) | 79 (24.6) | 22 (28.2) |
Abbreviation: cGVHD, chronic graft-vs-host disease.
Other race and multiracial includes Asian and Pacific Islander participants and was grouped together for analytical purposes.
Table 3. Factors Associated With Specific Subsequent Cutaneous Malignant Neoplasms After Blood or Marrow Transplanta.
| Participant or treatment characteristic | Subdistribution hazard ratio (95% CI) | |||
|---|---|---|---|---|
| Any skin cancer | Squamous cell carcinoma | Basal cell carcinoma | Melanoma | |
| Age at transplant, y | ||||
| <50 | 1 [Reference] | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| ≥50 | 2.23 (1.83-2.71)b | 3.37 (2.41-4.72)b | 1.76 (1.36-2.29)b | 1.49 (0.88-2.51)b |
| Sex | ||||
| Female | 1 [Reference] | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| Male | 1.40 (1.18-1.65)b | 1.85 (1.39-2.45)b | 1.39 (1.10-1.75)b | 1.31 (0.82-2.07) |
| Race and ethnicity | ||||
| Black | 0.14 (0.05-0.37)b | 0.17 (0.04-0.67)b | NI | 0.25 (0.03-1.86) |
| Hispanic | 0.29 (0.20-0.62)b | 0.28 (0.16-0.50)b | 0.27 (0.16-0.44)b | 0.41 (0.16-1.07) |
| Non-Hispanic White | 1 [Reference] | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| Other race and multiracialc | 0.22 (0.13-0.37)b | 0.13 (0.05-0.37)b | 0.26 (0.14-0.50)b | 0.24 (0.06-0.99) |
| Prior skin cancer | ||||
| No | 1 [Reference] | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| Yes | 3.35 (2.14-5.23)b | 4.30 (2.51-7.35)b | 5.71 (3.67-8.89)b | 5.14 (1.91-13.82)b |
| Primary cancer diagnosis | ||||
| Leukemia | 1 [Reference] | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| Lymphoma | 1.28 (0.96-1.70) | NI | NI | NI |
| Other mixed | 0.87 (0.66-1.14) | NI | NI | NI |
| Transplant type/cGVHD | ||||
| Autologous | 1 [Reference] | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| Allogeneic without cGVHD | 1.27 (0.91-1.78) | 1.29 (0.73-2.27) | 1.17 (0.78-1.77) | NI |
| Allogeneic with cGVHD | 1.84 (1.37-2.47)b | 2.61 (1.68-4.04)b | 1.48 (1.06-2.08)b | NI |
| Total body irradiation | ||||
| No | 1 [Reference] | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| Yes | 1.32 (1.08-1.63)b | 1.09 (0.76-1.57) | 1.29 (0.98-1.70) | 1.39 (0.84-2.31) |
| Conditioning intensity | ||||
| Myeloablative | 1 [Reference] | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| Nonmyeloablative/reduced intensity | 1.01 (0.78-1.30) | 1.15 (0.75-1.79) | 1.09 (0.77-1.54) | 1.07 (0.62-1.83) |
| Pretransplant monoclonal antibody | ||||
| No | 1 [Reference] | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| Yes | 1.29 (1.00-1.66)b | NI | 1.71 (1.27-2.31)b | 1.06 (0.59-1.91) |
| Pretransplant radiation | ||||
| No | 1 [Reference] | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| Yes | NI | NI | NI | NI |
| Site of transplant | ||||
| University of Minnesota | 1 [Reference] | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| City of Hope | 2.03 (1.62-2.54)b | 3.57 (2.34-5.47)b | 3.55 (2.58-4.89)b | 1.48 (0.89-2.44) |
| University of Alabama at Birmingham | 1.99 (1.35-2.93)b | 2.63 (1.36-5.08)b | 2.35 (1.30-4.23)b | 0.81 (0.24-2.67) |
| Year of transplant | ||||
| Before 2000 | 1 [Reference] | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| 2000 or later | NI | NI | NI | 2.18 (1.21-3.93)b |
| Posttransplant immunosuppression | ||||
| No | 1 [Reference] | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| Yes | 1.53 (1.26-1.86)b | 1.48 (1.09-2.02)b | 1.63 (1.24-2.14)b | 1.90 (1.16-3.12)b |
Abbreviations: cGVHD, chronic graft-vs-host disease; NI, not included.
All listed variables were included in the multivariable analysis. Variables with NI were not included in the final multivariable models due to not meeting criteria for variable selection.
Value is statistically significant.
Other race and multiracial includes Asian and Pacific Islander participants and was grouped together for analytical purposes.
In the subanalyses stratified by age at BMT, pretransplant exposure to monoclonal antibodies was identified as an additional risk factor for subsequent cutaneous malignant neoplasm among individuals younger than 50 years at transplant (SHR, 1.17; 95% CI, 1.18-2.66) and 50 years and older (SHR, 1.46; 95% CI, 1.15-1.86) (eTable 2 in Supplement 1). There was a differential association of TBI, with greater risk of cutaneous malignant neoplasm for younger transplant recipients (<50 years: SHR, 1.68; 95% CI, 1.20-2.35; ≥50 years: SHR, 1.15; 95% CI, 0.84-1.58). Male sex was a risk factor for cutaneous malignant neoplasm among those who were 50 years and older at BMT (SHR, 1.69; 95% CI, 1.33-2.14 [reference: female]).
BCC
BMT recipients developed BCC at a median (range) of 6.1 (2.0-32.0) years after transplant. Risk factors for BCC in the adjusted model included age of 50 years and older at BMT (SHR, 1.76; 95% CI, 1.36-2.29 [reference: <50 years), male sex (SHR, 1.39; 95% CI, 1.10-1.75 [reference: female]), pretransplant skin cancer (SHR, 5.71; 95% CI, 3.67-8.89), pretransplant monoclonal antibody exposure (SHR, 1.71; 95% CI, 1.27-2.31), cGVHD among allogeneic BMT recipients (SHR, 1.48; 95% CI, 1.06-2.08 [reference: autologous BMT]), site of transplant (COH: SHR, 3.55; 95% CI, 2.58-4.89; UAB: SHR, 2.35; 95% CI, 1.30-4.23 [reference: UMN]), and posttransplant immunosuppression (SHR, 1.63; 95% CI, 1.24-2.14). Race and ethnicity other than non-Hispanic White was protective (Black: no cases; Hispanic: SHR, 0.27; 95% CI, 0.16-0.44; other race and multiracial: SHR, 0.26; 95% CI, 0.14-0.50 [reference: non-Hispanic White]) (Table 2 and Table 3). An association between TBI and risk of BCC was observed for participants younger than 50 years at BMT (SHR, 1.83; 95% CI, 1.27-2.64) but not among those 50 years and older at BMT (SHR, 0.54; 95% CI, 0.36-0.80) (eTable 2 in Supplement 1). Other differential risk factors by age at transplant were posttransplant immunosuppression, which was a risk factor for BCC in participants younger than 50 years (SHR, 1.83; 95% CI, 1.27-2.64) but not in those 50 years and older at transplant (SHR, 1.21; 95% CI, 0.82-1.78), and nonmyeloablative/reduced intensity conditioning, which was a risk factor for BCC among participants 50 years and older (SHR, 2.16; 95% CI, 1.48-3.14) but not younger than 50 years (SHR, 0.63; 95% CI, 0.37-1.08).
The cumulative probability of BCC by 70 years of age in BMT survivor participants with and without a history of skin cancer and in siblings was 45.0%, 16.9%, and 8.2%, respectively (P < .001). BMT survivors had higher odds of BCC than siblings (with pretransplant skin cancer: odds ratio [OR], 13.50; 95% CI, 7.67-23.78; without pretransplant skin cancer: OR, 2.07; 95% CI, 1.55-2.75) (eTable 3 and eFigure in Supplement 1).
SCC
SCC cases occurred at a median (range) of 3.9 (2.0-35.2) years after transplant. In the multivariable model, SCC was associated with age 50 years and older at BMT (SHR, 3.37; 95% CI, 2.41-4.72 [reference: <50 years]), male sex (SHR, 1.85; 95% CI, 1.39-2.45 [reference: female]), pretransplant skin cancer (SHR, 4.30; 95% CI, 2.51-7.35), cGVHD among allogeneic BMT recipients (SHR, 2.61; 95% CI, 1.68-4.04 [reference: autologous BMT]), site of transplant (COH: SHR, 3.57; 95% CI, 2.34-5.47; UAB: SHR, 2.63; 95% CI, 1.36-5.08 [reference: UMN]), and posttransplant immunosuppression (SHR, 1.48; 95% CI, 1.09-2.02). Race and ethnicity other than non-Hispanic White was protective against SCC (Black: SHR, 0.17; 95% CI, 0.04-0.67; Hispanic: SHR, 0.28; 95% CI, 0.16-0.50; other race and multiracial: SHR, 0.13; 95% CI, 0.05-0.37 [reference: non-Hispanic White]) (Table 2 and Table 3).
The cumulative probability of SCC by age of 70 years in BMT survivor participants with and without a history of skin cancer and siblings was 29.9%, 14.3%, and 4.2%, respectively (P < .001). BMT survivors were at higher odds of SCC compared with siblings (with pretransplant skin cancer: OR, 16.34; 95% CI, 8.46-31.57); without pretransplant skin cancer: OR, 3.15; 95% CI, 2.12-4.69) (eTable 3 and eFigure in Supplement 1).
Melanoma
BMT survivor participants developed melanoma a median (range) of 4.0 (2.0-32.0) years after transplant. In the multivariable model, risk factors for melanoma included pretransplant skin cancer (SHR, 5.14; 95% CI, 1.91-13.82), transplant after 2000 (SHR, 2.61; 95% CI, 1.25-5.46), and posttransplant immunosuppression (SHR, 1.90; 95% CI, 1.16-3.12) (Table 2 and Table 3). Relative to the general population, the SIR for melanoma among BMT survivors was 4.9 (95% CI, 3.9-6.1). In the cohort with only validated cases, the SIR was 3.6 (95% CI, 2.7-4.6) (eTable 4 in Supplement 1). Relative to the sibling participants, BMT survivor participants with pretransplant skin cancer had greater odds of melanoma (OR, 5.19; 95% CI, 1.88-14.34); those without pretransplant skin cancer had comparable risk (OR, 1.59; 95% CI, 0.96-2.63) (eTable 3 and eFigure in Supplement 1).
Sensitivity Analyses
Stratified analyses were performed to investigate the observed association between pretransplant monoclonal antibody exposure and BCC. Monoclonal antibodies were used among recipients more often during or after 2000 (658 of 674 [97.6%]), in those 50 years or older at BMT (459 of 674 [68.1%]) and for those with NHL (600 of 674 [89.0%]). For each strata (before 2000, 2000 or later; <50 years, ≥50 years; NHL, other), the observed association between monoclonal antibodies and BCC persisted, suggesting a true association rather than confounding by indication (eTables 5 and 6 in Supplement 1). Rituximab, in particular (the monoclonal antibody used in 674 [94.5%] cases), was associated with BCC (SHR, 1.70; 95% CI, 1.26-2.31). While the association between monoclonal antibodies other than rituximab and BCC had a similar magnitude, it was not statistically significant (SHR, 1.92; 95% CI, 0.67-5.52) (eTable 7 in Supplement 1).
The sensitivity analysis of CNI vs non-CNI immunosuppression demonstrated that both were associated with BCC (CNI: SHR, 1.83; 95% CI, 1.30-2.60; non-CNI: SHR, 1.45; 95% CI, 1.01-2.07). Non-CNI agents were associated with SCC (SHR, 1.61; 95% CI, 1.07-2.43) and melanoma (SHR, 2.23; 95% CI, 1.21-4.11); however, CNIs were not (eTable 7 in Supplement 1).
Discussion
In this multi-institutional cohort of BMT survivor participants followed for a median of 9.5 years, the 30-year cumulative incidence of subsequent cutaneous malignant neoplasms exceeded 25%. Risk factors included being 50 years or older at BMT, male sex, cGVHD among allogeneic transplant recipients, and posttransplant immunosuppression. Novel risk factors for BCC included pretransplant treatment exposure to monoclonal antibody at any age and TBI at a younger age. Finally, BMT survivors were at a 5-fold greater risk of melanoma than the general population. Relative to sibling participants, BMT survivor participants had a 2- to 15-fold greater risk of BCC and a 2- to 20-fold greater risk of SCC. These findings may be used to provide targeted counseling to patients and plan post-BMT dermatologic surveillance.
Most BMT survivors do not undergo routine dermatologic surveillance, highlighting the need to understand risk factors and incorporate risk-informed dermatologic surveillance into survivorship care plans.12 While available tools predict risk to guide screening recommendations in solid organ transplant recipients, resources are lacking for BMT recipients.13 The current study comprises, to our knowledge, the largest of its kind to specifically examine risk factors for post-BMT BCC, SCC, and melanoma, and may be used for future development of a risk prediction tool specific for BMT survivors to tailor the frequency of dermatologic surveillance intervals and heighten the threshold for biopsy of lesions suspected of being malignant.3,14,15
To our knowledge, no prior work has established an association between pretransplant exposure to monoclonal antibodies and BCC. Though monoclonal antibodies were used more commonly in certain subgroups (older age at BMT, NHL, contemporary transplant era), stratified analyses suggest a true association between monoclonal antibody exposure (specifically rituximab) and BCC, rather than confounding by indication. In a systematic review and meta-analysis of 12 studies examining patients with autoimmune disorders,16 biologic agents were associated with NMSCs, but this was largely attributable to agents other than rituximab. One study of more than 3500 patients with inflammatory diseases found no association between rituximab and SCC (BCC cases were not included).16 A large Medicare-based cohort study also did not find increased risk of NMSCs among patients receiving rituximab for autoimmune disorders or transplant.17,18 Considering prior work, the present novel finding of an association between pre-BMT monoclonal antibody exposure and subsequent cutaneous malignant neoplasms warrants further investigation.
We observed an association between TBI and subsequent BCC among BMT survivor participants younger than 50 years at transplant, though not among older participants. The association between TBI and BCC aligns with findings from other post-BMT cohorts. The Center for International Blood and Marrow Transplant Research (CIBMTR)/Fred Hutchinson Cancer Research Center (FHCRC) cohort had a 2-fold increased risk of BCC after TBI, and a Danish Cancer Registry cohort had a 4-fold increased risk of BCC.15,19,20 In the CIBMTR/FHCRC cohort, increased BCC risk was observed in patients younger than 40 years at time of transplant.19 Of note, the association between ionizing radiation at younger ages and BCC was also observed among atomic bomb survivors.21
In the present study, history of cGVHD and chronic posttransplant immunosuppression were associated with subsequent SCC or BCC. An association between cGVHD, posttransplant immunosuppression, and subsequent cutaneous SCC has been reported previously.10,22 A CIBMTR/FHCRC study found that cGVHD duration and severity, as well as treatment with azathioprine, were risk factors for post-BMT SCC.22 SCC often develops at sites of prior cGVHD and may be caused by chronic inflammation and frequent cell division.23 Similar to the present findings, another study identified an association between cGVHD and BCC.15 Although prior work in kidney transplant recipients demonstrated an association between CNIs and BCC, SCC, and melanoma relative to non-CNI therapies,24 we found that both CNIs and non-CNIs were risk factors for BCC, while non-CNI immunosuppression was associated with SCC and melanoma. Of note, treatments for cGVHD with UV-light phototherapy or extracorporeal photopheresis with photosensitization could potentially increase risk of cutaneous malignant neoplasms; however, these treatment details were not available.
We found a nearly 5-fold greater risk of melanoma in BMT survivor participants compared with an age- and sex-matched population. Melanoma risk was greater among those who underwent transplant after 2000, consistent with the increasing melanoma incidence in the general population.25 Prior analyses of other BMT recipients have identified a 3.5- to 5-fold greater risk of melanoma compared to matched populations.2,20 Previously identified risk factors for melanoma in BMT recipients include allogeneic transplant, TBI, and T-cell depletion. Rizzo et al2 reported an association between female sex and incident melanoma, though this was not observed in the present cohort.3,15 We did not observe an association between TBI and melanoma, but the direction of association in our model was consistent with prior work.
There was a non-Hispanic White and male predominance for all cutaneous malignant neoplasm types, which mirrors national trends and the racial and ethnic distribution of childhood cancer survivors.26,27 Among patients who underwent transplant at an age younger than 18 years, more women developed BCC. A prior study in a general US cohort similarly found more BCC than SCC cases in younger women.28 Proposed mechanisms include higher estrogen levels and greater use of indoor tanning. Although national racial and ethnic epidemiologic data are not available for BCC or SCC, there were notably no cases of BCC among Black patients in the present cohort. Similarly, the St. Jude Lifetime Cohort Study identified no cases of BCC in Black childhood cancer survivors.29 Future research should seek to better understand the epidemiology of skin cancer to optimize post-BMT surveillance in diverse populations.
Limitations
This study needs to be considered in the context of its limitations. Use of survey-based self-report for case identification is a possible limitation. However, 73% of melanoma cases were validated, and sensitivity analyses in these cases found comparable associations and magnitude of risk. Prior work suggests that melanoma cases may be underreported to SEER.30,31,32,33 It is unknown how possible underreporting of melanoma to SEER would impact the magnitude of SIRs. Furthermore, patients with unknown skin cancer type could not be included in the individual models of BCC, SCC, and melanoma. The BMTSS survey did not query other risk factors for cutaneous malignant neoplasms, such as skin phototype, UV-light exposure, or family history. The inclusion of site of transplant may be considered a surrogate for UV-light exposure; indeed, we found higher risk of cutaneous malignant neoplasms among individuals who underwent transplant in California or Alabama. Duration of posttransplant immunosuppression was not collected. Surveys were administered at variable intervals, though all were completed more than 2 years post-BMT, allowing time for important risk factors such as cGVHD to manifest.
Conclusions
In this cohort study, risk factors for post-BMT cutaneous malignant neoplasms included pretransplant treatment with a monoclonal antibody, cGVHD, and posttransplant immunosuppression. TBI was associated with increased risk of subsequent BCC when exposure occurred at a younger age. These findings could inform targeted surveillance of BMT survivors.
eTable 1. Chronic immunosuppressive medications reported by blood or marrow transplant recipients
eTable 2. Risk factors for squamous cell carcinoma, basal cell carcinoma, and melanoma by age at blood or marrow transplant
eTable 3. Risk of cutaneous malignancies among BMT survivors compared with a sibling cohort
eTable 4. Risk factors for melanoma in all cases (validated and self-report) versus validated cases only
eTable 5. Factors associated with receipt of pre-transplant rituximab
eTable 6. Association between monoclonal antibodies and post-BMT cutaneous neoplasms
eTable 7. Association between monoclonal antibodies and BCC
eTable 8. Factors associated with subsequent cutaneous neoplasms after blood or marrow transplant with post-transplant immunosuppression categorized as calcineurin inhibitor versus other
eFigure. Cumulative probability for skin cancer among BMT survivors and siblings
Data Sharing Statement
References
- 1.Curtis RE, Rowlings PA, Deeg HJ, et al. Solid cancers after bone marrow transplantation. N Engl J Med. 1997;336(13):897-904. doi: 10.1056/NEJM199703273361301 [DOI] [PubMed] [Google Scholar]
- 2.Rizzo JD, Curtis RE, Socié G, et al. Solid cancers after allogeneic hematopoietic cell transplantation. Blood. 2009;113(5):1175-1183. doi: 10.1182/blood-2008-05-158782 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.DePry JL, Vyas R, Lazarus HM, Caimi PF, Gerstenblith MR, Bordeaux JS. Cutaneous malignant neoplasms in hematopoietic cell transplant recipients: a systematic review. JAMA Dermatol. 2015;151(7):775-782. doi: 10.1001/jamadermatol.2015.121 [DOI] [PubMed] [Google Scholar]
- 4.Socié G, Curtis RE, Deeg HJ, et al. New malignant diseases after allogeneic marrow transplantation for childhood acute leukemia. J Clin Oncol. 2000;18(2):348-357. doi: 10.1200/JCO.2000.18.2.348 [DOI] [PubMed] [Google Scholar]
- 5.Bhatia S, Louie AD, Bhatia R, et al. Solid cancers after bone marrow transplantation. J Clin Oncol. 2001;19(2):464-471. doi: 10.1200/JCO.2001.19.2.464 [DOI] [PubMed] [Google Scholar]
- 6.McDonald AM, Chen Y, Wu J, et al. Total body irradiation and risk of breast cancer after blood or marrow transplantation: a Blood or Marrow Transplantation Survivor Study report. J Clin Oncol. 2020;38(25):2872-2882. doi: 10.1200/JCO.20.00231 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Kolb HJ, Socié G, Duell T, et al. ; Late Effects Working Party of the European Cooperative Group for Blood and Marrow Transplantation and the European Late Effect Project Group . Malignant neoplasms in long-term survivors of bone marrow transplantation. Ann Intern Med. 1999;131(10):738-744. doi: 10.7326/0003-4819-131-10-199911160-00004 [DOI] [PubMed] [Google Scholar]
- 8.Turcotte LM, Whitton JA, Friedman DL, et al. Risk of subsequent neoplasms during the fifth and sixth decades of life in the Childhood Cancer Survivor Study cohort. J Clin Oncol. 2015;33(31):3568-3575. doi: 10.1200/JCO.2015.60.9487 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Turcotte LM, Liu Q, Yasui Y, et al. Chemotherapy and risk of subsequent malignant neoplasms in the Childhood Cancer Survivor Study cohort. J Clin Oncol. 2019;37(34):3310-3319. doi: 10.1200/JCO.19.00129 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Berano Teh J, Abdulla F, Peng K, et al. Incidence and risk factors for de novo cutaneous squamous cell carcinoma in a contemporary cohort of long-term hematopoietic cell transplantation survivors. J Invest Dermatol. 2021;141(8):2073-2076.e5. doi: 10.1016/j.jid.2021.01.018 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.SEER*Stat software. National Cancer Institute . Accessed November 11, 2024. https://seer.cancer.gov/seerstat
- 12.Hahn T, Paplham P, Austin-Ketch T, et al. Ascertainment of unmet needs and participation in health maintenance and screening of adult hematopoietic cell transplantation survivors followed in a formal survivorship program. Biol Blood Marrow Transplant. 2017;23(11):1968-1973. doi: 10.1016/j.bbmt.2017.07.024 [DOI] [PubMed] [Google Scholar]
- 13.Jambusaria-Pahlajani A, Crow LD, Lowenstein S, et al. Predicting skin cancer in organ transplant recipients: development of the SUNTRAC screening tool using data from a multicenter cohort study. Transpl Int. 2019;32(12):1259-1267. doi: 10.1111/tri.13493 [DOI] [PubMed] [Google Scholar]
- 14.Friedman DL, Whitton J, Leisenring W, et al. Subsequent neoplasms in 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study. J Natl Cancer Inst. 2010;102(14):1083-1095. doi: 10.1093/jnci/djq238 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Leisenring W, Friedman DL, Flowers MED, Schwartz JL, Deeg HJ. Nonmelanoma skin and mucosal cancers after hematopoietic cell transplantation. J Clin Oncol. 2006;24(7):1119-1126. doi: 10.1200/JCO.2005.02.7052 [DOI] [PubMed] [Google Scholar]
- 16.Liu R, Wan Q, Zhao R, Xiao H, Cen Y, Xu X. Risk of non-melanoma skin cancer with biological therapy in common inflammatory diseases: a systemic review and meta-analysis. Cancer Cell Int. 2021;21(1):614. doi: 10.1186/s12935-021-02325-9 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Scott FI, Mamtani R, Brensinger CM, et al. Risk of nonmelanoma skin cancer associated with the use of immunosuppressant and biologic agents in patients with a history of autoimmune disease and nonmelanoma skin cancer. JAMA Dermatol. 2016;152(2):164-172. doi: 10.1001/jamadermatol.2015.3029 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Bachelet T, Visentin J, Davis P, et al. The incidence of post-transplant malignancies in kidney transplant recipients treated with rituximab. Clin Transplant. 2021;35(2):e14171. doi: 10.1111/ctr.14171 [DOI] [PubMed] [Google Scholar]
- 19.Schwartz JL, Kopecky KJ, Mathes RW, Leisenring WM, Friedman DL, Deeg HJ. Basal cell skin cancer after total-body irradiation and hematopoietic cell transplantation. Radiat Res. 2009;171(2):155-163. doi: 10.1667/RR1469.1 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Omland SH, Gniadecki R, Hædersdal M, Helweg-Larsen J, Omland LH. Skin cancer risk in hematopoietic stem-cell transplant recipients compared with background population and renal transplant recipients: a population-based cohort study. JAMA Dermatol. 2016;152(2):177-183. doi: 10.1001/jamadermatol.2015.3902 [DOI] [PubMed] [Google Scholar]
- 21.Sugiyama H, Misumi M, Kishikawa M, et al. Skin cancer incidence among atomic bomb survivors from 1958 to 1996. Radiat Res. 2014;181(5):531-539. doi: 10.1667/RR13494.1 [DOI] [PubMed] [Google Scholar]
- 22.Curtis RE, Metayer C, Rizzo JD, et al. Impact of chronic GVHD therapy on the development of squamous-cell cancers after hematopoietic stem-cell transplantation: an international case-control study. Blood. 2005;105(10):3802-3811. doi: 10.1182/blood-2004-09-3411 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Landgren O, Gilbert ES, Rizzo JD, et al. Risk factors for lymphoproliferative disorders after allogeneic hematopoietic cell transplantation. Blood. 2009;113(20):4992-5001. doi: 10.1182/blood-2008-09-178046 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Kulbat A, Richter K, Stefura T, et al. Systematic review of calcineurin inhibitors and incidence of skin malignancies after kidney transplantation in adult patients: a study of 309,551 cases. Curr Oncol. 2023;30(6):5727-5737. doi: 10.3390/curroncol30060430 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Paulson KG, Gupta D, Kim TS, et al. Age-specific incidence of melanoma in the United States. JAMA Dermatol. 2020;156(1):57-64. doi: 10.1001/jamadermatol.2019.3353 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.SEER*Explorer. National Cancer Institute . Accessed December 8, 2023. https://seer.cancer.gov/statistics-network/explorer/
- 27.Delavar A, Barnes JM, Wang X, Johnson KJ. Associations between race/ethnicity and US childhood and adolescent cancer survival by treatment amenability. JAMA Pediatr. 2020;174(5):428-436. doi: 10.1001/jamapediatrics.2019.6074 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Lukowiak TM, Aizman L, Perz A, et al. Association of age, sex, race, and geographic region with variation of the ratio of basal cell to cutaneous squamous cell carcinomas in the United States. JAMA Dermatol. 2020;156(11):1192-1198. doi: 10.1001/jamadermatol.2020.2571 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Ehrhardt MJ, Bhakta N, Liu Q, et al. Absence of basal cell carcinoma in irradiated childhood cancer survivors of Black race: a report from the St. Jude Lifetime Cohort Study. Cancer Epidemiol Biomarkers Prev. 2016;25(9):1356-1360. doi: 10.1158/1055-9965.EPI-16-0280 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Watson M, Johnson CJ, Chen VW, et al. Melanoma surveillance in the United States: overview of methods. J Am Acad Dermatol. 2011;65(5)(suppl 1):S6-S16. doi: 10.1016/j.jaad.2011.04.037 [DOI] [PubMed] [Google Scholar]
- 31.Raji KO, Payne L, Chen SC. Reporting melanoma: a nationwide surveillance of state cancer registries. J Skin Cancer. 2015;2015:904393. doi: 10.1155/2015/904393 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Dougall B, Gendreau J, Das S, et al. Melanoma registry underreporting in the Veterans Health Administration. Fed Pract. 2016;33(suppl 5):55S-59S. [PMC free article] [PubMed] [Google Scholar]
- 33.Svoboda RM, Glazer AM, Farberg AS, Cowdrey MCE, Rigel DS. Melanoma reporting practices of United States dermatologists. Dermatol Surg. 2018;44(11):1391-1395. doi: 10.1097/DSS.0000000000001561 [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
eTable 1. Chronic immunosuppressive medications reported by blood or marrow transplant recipients
eTable 2. Risk factors for squamous cell carcinoma, basal cell carcinoma, and melanoma by age at blood or marrow transplant
eTable 3. Risk of cutaneous malignancies among BMT survivors compared with a sibling cohort
eTable 4. Risk factors for melanoma in all cases (validated and self-report) versus validated cases only
eTable 5. Factors associated with receipt of pre-transplant rituximab
eTable 6. Association between monoclonal antibodies and post-BMT cutaneous neoplasms
eTable 7. Association between monoclonal antibodies and BCC
eTable 8. Factors associated with subsequent cutaneous neoplasms after blood or marrow transplant with post-transplant immunosuppression categorized as calcineurin inhibitor versus other
eFigure. Cumulative probability for skin cancer among BMT survivors and siblings
Data Sharing Statement