Characteristics of case patients with second squamous-cell carcinoma (SCC) and matched control patients
Characteristics . | Case patients, no. (%) . | Control patients, no. (%) . |
|---|---|---|
| SCC locationa | ||
| Buccal cavity | 24 (41.4) | - |
| Nonmelanoma skin, invasive | 19 (32.8) | - |
| Male and female genitalia | 9 (15.5) | - |
| Other | 6 (10.3) | - |
| Registryb | ||
| CIBMTR | 40 (69.0) | 102 (65.8) |
| FHCRC | 18 (31.0) | 53 (34.2) |
| Sexb | ||
| Male | 42 (72.4) | 114 (73.6) |
| Raceb | ||
| White | 52 (89.7) | 141 (91.0) |
| Black | 2 (3.4) | 1 (0.7) |
| Other | 4 (6.9) | 13 (8.4) |
| Geographic region of transplantation centerb | ||
| United States/Canada | 30 (51.7) | 78 (50.3) |
| Europe | 21 (36.2) | 61 (39.4) |
| Other | 7 (12.1) | 16 (10.3) |
| Primary diseaseb | ||
| Acute lymphoblastic leukemia | 6 (10.3) | 18 (11.6) |
| Acute non-lymphocytic leukemiac | 15 (25.9) | 35 (22.6) |
| Chronic myelogenous leukemia | 14 (24.1) | 40 (25.8) |
| Lymphoma, multiple myeloma | 1 (1.7) | 2 (1.3) |
| Severe aplastic anemia | 17 (29.3) | 47 (30.3) |
| Fanconi anemia | 4 (6.9) | 10 (6.5) |
| Hemoglobinopathies | 1 (1.7) | 3 (1.9) |
| Chemotherapy to treat primary disease | ||
| Any chemotherapy | ||
| No | 12 (20.7) | 31 (20.0) |
| Yes | 44 (75.9) | 123 (79.3) |
| Unknown | 2 (3.4) | 1 (0.7) |
| Alkylating agent therapy | 11 (19.0) | 33 (21.3) |
| Epipodophyllotoxins | 5 (8.6) | 11 (7.1) |
| Radiotherapy to treat the primary diseased | ||
| No | 52 (89.7) | 140 (90.3) |
| Yes | 5 (8.6) | 12 (7.7) |
| Unknown | 1 (1.7) | 3 (1.9) |
| Age at transplantationb | ||
| Younger than 10 y | 6 (10.3) | 16 (10.3) |
| 10-19 y | 13 (22.4) | 40 (25.8) |
| 20-29 y | 13 (22.4) | 29 (18.7) |
| 30-39 y | 13 (22.4) | 35 (22.6) |
| 40-49 y | 9 (15.5) | 24 (15.5) |
| 50 y or older | 4 (6.9) | 11 (7.1) |
| Interval between first transplantation and SCCb | ||
| Less than 1 y | 4 (6.9) | 10 (6.5) |
| 1-4 y | 15 (25.9) | 42 (27.1) |
| 5-9 y | 26 (44.8) | 67 (43.2) |
| 10-14 y | 9 (15.5) | 25 (16.1) |
| 15 y or more | 4 (6.9) | 11 (7.1) |
| Donor-recipient relationship | ||
| HLA-identical sibling | 54 (93.1) | 142 (91.6) |
| HLA-1 antigen mismatched, matched family member | 2 (3.5) | 10 (6.5) |
| Unrelated donor | 2 (3.5) | 3 (1.9) |
| Transplantation conditioning regimens | ||
| TBI + Cy ± other drugs | 28 (48.3) | 75 (48.4) |
| TBI ± other drugs, no Cy | 1 (1.7) | 8 (5.2) |
| TBI + LFI ± drugs | 2 (3.5) | 2 (1.3) |
| LFI ± drugs | 7 (12.1) | 13 (8.4) |
| Busulfan + Cy ± other drugs | 9 (15.5) | 16 (10.3) |
| Cy ± other drugs | 11 (19.0) | 39 (25.2) |
| Other | 0 (0.0) | 2 (1.3) |
| History of smoking and alcohol use at time of transplantation for SCC buccal cavity cases and controlse | ||
| Current or past smoker | 7 (29.2) | 15 (22.4) |
| Never smoker | 12 (50.0) | 34 (50.8) |
| History of smoking and alcohol use at time of transplantatione | ||
| Unknown smoker | 5 (20.8) | 18 (26.9) |
| Alcohol use | 5 (20.8) | 19 (28.4) |
| No alcohol use | 14 (58.3) | 34 (50.8) |
| Unknown alcohol use | 5 (20.8) | 14 (20.9) |
| GVHD prophylaxis | ||
| T-cell depletion of marrowf | 6 (10.3) | 9 (5.8) |
| GVHD prophylaxis, drugsg | ||
| CSP ± other, no MTX | 19 (32.8) | 47 (30.3) |
| MTX ± other, no CSP | 24 (41.4) | 63 (40.7) |
| CSP + MTX ± other | 12 (20.7) | 43 (27.7) |
| Other,h unknown | 3 (5.2) | 2 (1.3) |
| Acute GVHD, severity | ||
| None | 21 (36.2) | 57 (36.8) |
| Grade 1 | 11 (19.0) | 44 (28.4) |
| Grades 2-4 | 26 (44.8) | 53 (34.2) |
| Unknown | 0 (0.0) | 1 (0.6) |
| Acute GVHD therapyg,i | 29 (100.0) | 66 (100.0) |
| CSP ± other, no steroids | 2 (6.9) | 3 (4.6) |
| Steroids ± other, no CSP | 21 (72.4) | 48 (72.7) |
| CSP + steroids ± other | 3 (10.3) | 10 (15.2) |
| Other, unknown, no CSP, no steroids | 3 (10.3) | 5 (7.6) |
| Any ATG given for conditioning, prophylaxis, acute GVHD | 8 (13.8) | 20 (12.9) |
| Chronic GVHD | ||
| No | 16 (27.6) | 74 (47.7) |
| Yes | 42 (72.4) | 80 (51.6) |
| Unknown | 0 (0.0) | 1 (0.7) |
| Therapy for chronic GVHDg | 42 (100.0) | 80 (100.0) |
| CSP | 3 (7.1) | 6 (7.5) |
| CSP, steroids | 4 (9.5) | 18 (22.5) |
| CSP, steroids, otherj | 0 (0.0) | 4 (5.0) |
| CSP, AZA | 0 (0.0) | 1 (1.3) |
| CSP, AZA, steroids | 7 (16.7) | 5 (6.3) |
| CSP, AZA, steroids, other | 9 (21.4) | 3 (3.8) |
| AZA, steroids | 7 (16.7) | 12 (15.0) |
| AZA, steroids, other | 2 (4.8) | 2 (2.5) |
| Steroids | 3 (7.1) | 10 (12.5) |
| Steroids, other | 1 (2.3) | 5 (6.3) |
| Otherk | 0 (0.0) | 2 (2.5) |
| Chronic GVHD therapy, unknown | 1 (2.3) | 2 (2.5) |
| Chronic GVHD therapy, none | 5 (11.9) | 10 (12.5) |
| Relapse, recurrence after transplantationg | 1 (1.7) | 17 (11.0) |
Characteristics . | Case patients, no. (%) . | Control patients, no. (%) . |
|---|---|---|
| SCC locationa | ||
| Buccal cavity | 24 (41.4) | - |
| Nonmelanoma skin, invasive | 19 (32.8) | - |
| Male and female genitalia | 9 (15.5) | - |
| Other | 6 (10.3) | - |
| Registryb | ||
| CIBMTR | 40 (69.0) | 102 (65.8) |
| FHCRC | 18 (31.0) | 53 (34.2) |
| Sexb | ||
| Male | 42 (72.4) | 114 (73.6) |
| Raceb | ||
| White | 52 (89.7) | 141 (91.0) |
| Black | 2 (3.4) | 1 (0.7) |
| Other | 4 (6.9) | 13 (8.4) |
| Geographic region of transplantation centerb | ||
| United States/Canada | 30 (51.7) | 78 (50.3) |
| Europe | 21 (36.2) | 61 (39.4) |
| Other | 7 (12.1) | 16 (10.3) |
| Primary diseaseb | ||
| Acute lymphoblastic leukemia | 6 (10.3) | 18 (11.6) |
| Acute non-lymphocytic leukemiac | 15 (25.9) | 35 (22.6) |
| Chronic myelogenous leukemia | 14 (24.1) | 40 (25.8) |
| Lymphoma, multiple myeloma | 1 (1.7) | 2 (1.3) |
| Severe aplastic anemia | 17 (29.3) | 47 (30.3) |
| Fanconi anemia | 4 (6.9) | 10 (6.5) |
| Hemoglobinopathies | 1 (1.7) | 3 (1.9) |
| Chemotherapy to treat primary disease | ||
| Any chemotherapy | ||
| No | 12 (20.7) | 31 (20.0) |
| Yes | 44 (75.9) | 123 (79.3) |
| Unknown | 2 (3.4) | 1 (0.7) |
| Alkylating agent therapy | 11 (19.0) | 33 (21.3) |
| Epipodophyllotoxins | 5 (8.6) | 11 (7.1) |
| Radiotherapy to treat the primary diseased | ||
| No | 52 (89.7) | 140 (90.3) |
| Yes | 5 (8.6) | 12 (7.7) |
| Unknown | 1 (1.7) | 3 (1.9) |
| Age at transplantationb | ||
| Younger than 10 y | 6 (10.3) | 16 (10.3) |
| 10-19 y | 13 (22.4) | 40 (25.8) |
| 20-29 y | 13 (22.4) | 29 (18.7) |
| 30-39 y | 13 (22.4) | 35 (22.6) |
| 40-49 y | 9 (15.5) | 24 (15.5) |
| 50 y or older | 4 (6.9) | 11 (7.1) |
| Interval between first transplantation and SCCb | ||
| Less than 1 y | 4 (6.9) | 10 (6.5) |
| 1-4 y | 15 (25.9) | 42 (27.1) |
| 5-9 y | 26 (44.8) | 67 (43.2) |
| 10-14 y | 9 (15.5) | 25 (16.1) |
| 15 y or more | 4 (6.9) | 11 (7.1) |
| Donor-recipient relationship | ||
| HLA-identical sibling | 54 (93.1) | 142 (91.6) |
| HLA-1 antigen mismatched, matched family member | 2 (3.5) | 10 (6.5) |
| Unrelated donor | 2 (3.5) | 3 (1.9) |
| Transplantation conditioning regimens | ||
| TBI + Cy ± other drugs | 28 (48.3) | 75 (48.4) |
| TBI ± other drugs, no Cy | 1 (1.7) | 8 (5.2) |
| TBI + LFI ± drugs | 2 (3.5) | 2 (1.3) |
| LFI ± drugs | 7 (12.1) | 13 (8.4) |
| Busulfan + Cy ± other drugs | 9 (15.5) | 16 (10.3) |
| Cy ± other drugs | 11 (19.0) | 39 (25.2) |
| Other | 0 (0.0) | 2 (1.3) |
| History of smoking and alcohol use at time of transplantation for SCC buccal cavity cases and controlse | ||
| Current or past smoker | 7 (29.2) | 15 (22.4) |
| Never smoker | 12 (50.0) | 34 (50.8) |
| History of smoking and alcohol use at time of transplantatione | ||
| Unknown smoker | 5 (20.8) | 18 (26.9) |
| Alcohol use | 5 (20.8) | 19 (28.4) |
| No alcohol use | 14 (58.3) | 34 (50.8) |
| Unknown alcohol use | 5 (20.8) | 14 (20.9) |
| GVHD prophylaxis | ||
| T-cell depletion of marrowf | 6 (10.3) | 9 (5.8) |
| GVHD prophylaxis, drugsg | ||
| CSP ± other, no MTX | 19 (32.8) | 47 (30.3) |
| MTX ± other, no CSP | 24 (41.4) | 63 (40.7) |
| CSP + MTX ± other | 12 (20.7) | 43 (27.7) |
| Other,h unknown | 3 (5.2) | 2 (1.3) |
| Acute GVHD, severity | ||
| None | 21 (36.2) | 57 (36.8) |
| Grade 1 | 11 (19.0) | 44 (28.4) |
| Grades 2-4 | 26 (44.8) | 53 (34.2) |
| Unknown | 0 (0.0) | 1 (0.6) |
| Acute GVHD therapyg,i | 29 (100.0) | 66 (100.0) |
| CSP ± other, no steroids | 2 (6.9) | 3 (4.6) |
| Steroids ± other, no CSP | 21 (72.4) | 48 (72.7) |
| CSP + steroids ± other | 3 (10.3) | 10 (15.2) |
| Other, unknown, no CSP, no steroids | 3 (10.3) | 5 (7.6) |
| Any ATG given for conditioning, prophylaxis, acute GVHD | 8 (13.8) | 20 (12.9) |
| Chronic GVHD | ||
| No | 16 (27.6) | 74 (47.7) |
| Yes | 42 (72.4) | 80 (51.6) |
| Unknown | 0 (0.0) | 1 (0.7) |
| Therapy for chronic GVHDg | 42 (100.0) | 80 (100.0) |
| CSP | 3 (7.1) | 6 (7.5) |
| CSP, steroids | 4 (9.5) | 18 (22.5) |
| CSP, steroids, otherj | 0 (0.0) | 4 (5.0) |
| CSP, AZA | 0 (0.0) | 1 (1.3) |
| CSP, AZA, steroids | 7 (16.7) | 5 (6.3) |
| CSP, AZA, steroids, other | 9 (21.4) | 3 (3.8) |
| AZA, steroids | 7 (16.7) | 12 (15.0) |
| AZA, steroids, other | 2 (4.8) | 2 (2.5) |
| Steroids | 3 (7.1) | 10 (12.5) |
| Steroids, other | 1 (2.3) | 5 (6.3) |
| Otherk | 0 (0.0) | 2 (2.5) |
| Chronic GVHD therapy, unknown | 1 (2.3) | 2 (2.5) |
| Chronic GVHD therapy, none | 5 (11.9) | 10 (12.5) |
| Relapse, recurrence after transplantationg | 1 (1.7) | 17 (11.0) |
Fifty-eight case patients and 155 control patients were included in the analysis. Percentages do not always add to 100% because of rounding.
TBI indicates total body irradiation; LFI, limited field irradiation; Cy, cyclophosphamide; CSP, cyclosporine; MTX, methotrexate; GVHD, graft-versus-host disease; ATG, antithymocyte/antilymphocyte globulin or serum; and AZA, azathioprine.
Sites of buccal cavity SCC are lip (5), tongue (12), gum and other mouth (6), and hypopharynx (1). Sites of invasive skin SCC are face/jaw/cheek (3), lip (2), neck (2), shoulder (1), back (1), hand (1), leg (2), foot (2), unspecified (5). Sites for genital SCC include cervix (5 including 3 in situ), vulva (2 including 1 in situ), penis (2 including 1 in situ). Sites of other SCC include rectum (1), in situ anus (1), larynx/pharynx (1), lung (3 including 1 in situ)
Control patients were matched to second cancer case patients on the following factors: registry (CIBMTR, FHCRC), type of transplantation (allogeneic, syngeneic), primary disease, sex, age at transplantation (within 3 years), interval between transplantation date and date of second cancer for the case patient (control patient had to survive at least as long as this interval, and collection of treatment data stopped at the end of the interval), race (United States case patients only), and geographic region of transplantation team (United States/Canada, Europe, Australia/New Zealand, Asia, other)
Acute nonlymphocytic leukemia includes acute leukemia, unclassified
Radiotherapy to treat the primary disease includes radiation delivered to a field within or near the site of second SCC before the date of second cancer diagnosis or equivalent treatment cutoff date among control patients
Analysis based on 24 case patients with SCC of the buccal cavity and 67 matched controls
Category includes 1 patient with T cell depletion for second transplantation (2 case patients and 3 control patients who underwent second transplantation were included in the analysis)
Categories include all GVHD occurrence/therapy/relapse during the matched time interval (interval between transplantation and second cancer diagnosis for the case patient or matched time interval for the control patient)
Other includes T-cell depletion only, other, or no prophylactic drugs
In some transplantation centers, therapy for acute GVHD, which continued from GVHD prophylaxis, was listed on abstract forms under GVHD prophylaxis; therefore, prophylaxis therapy and treatment for acute GVHD were grouped for analysis
Other therapy for chronic GVHD included PUVA skin irradiation, limited field irradiation, and/or other less frequently used drugs (including cyclophosphamide, ATG, thalidomide, xomazyme, tacrolimus [FK506], procarbazine, 6 mercaptopurine [6-MP], interferon, pentaglobin, monoclonal antibodies, mycophenolate mofetil [MMF], methotrexate, and thymosin)
Chronic GVHD therapy for patients with other therapy alone included methotrexate only (1 control patient) and 6-MP only (1 control patient)