Characteristics of patients developing secondary myelodysplastic syndrome or acute myeloid leukemia after autotransplantation for lymphoma, and matched controls
| Characteristics . | Cases, n = 56 (no., %) . | Controls, n = 168 (no., %) . |
|---|---|---|
| Pretransplantation characteristics | ||
| Primary disease | ||
| Hodgkin disease | 19 (33.9) | 57 (33.9) |
| Nodular sclerosis | 14 (25.0) | 38 (22.6) |
| Mixed cellularity | 5 (8.9) | 10 (6.0) |
| Other types1-a | 0 (0) | 9 (5.4) |
| Non-Hodgkin lymphoma1-b | 37 (66.1) | 111 (66.1) |
| Low grade | 17 (30.4) | 35 (20.8) |
| Intermediate grade | 7 (12.5) | 46 (27.4) |
| High grade | 7 (12.5) | 16 (9.5) |
| Other types1-c | 6 (10.7) | 14 (8.3) |
| Male sex | 30 (53.6) | 90 (53.6) |
| Splenectomy | 3 (5.4) | 22 (13.2) |
| Pretransplantation chemotherapy with alkylating agents | ||
| MOPP/MOPP-like regimen (mechlorethamine/procarbazine-based) | 20 (35.7) | 55 (32.7) |
| Other regimens (non-MOPP) | 36 (64.3) | 113 (67.3) |
| Cyclophosphamide-based regimen, no other alkylating agents1-d | 8 (14.3) | 59 (35.1) |
| Chlorambucil-based regimen ± other alkylating agents1-e | 9 (16.1) | 7 (4.2) |
| No chlorambucil, other alkylating agents1-f | 18 (32.1) | 47 (28.0) |
| No alkylating agents1-g | 1 (1.8) | 0 (0) |
| Pretransplantation chemotherapy with etoposide | 27 (48.2) | 82 (48.8) |
| Pretransplantation radiotherapy fields | ||
| No radiotherapy | 30 (53.6) | 97 (57.7) |
| Mantle/mediastinum1-h | 10 (17.9) | 28 (16.7) |
| Inverted Y and/or other fields below diaphragm1-i | 3 (5.4) | 17 (10.1) |
| Total lymphoid irradiation or subtotal lymphoid irradiation1-j | 4 (7.1) | 14 (8.3) |
| Other fields1-k | 9 (16.1) | 12 (7.1) |
| Disease status at transplantation | ||
| Never in complete remission | 12 (21.4) | 41 (24.4) |
| First complete remission | 6 (10.7) | 19 (11.3) |
| Second or third complete remission | 14 (25.0) | 30 (17.9) |
| First relapse | 13 (23.2) | 55 (32.7) |
| 2 or more relapses | 11 (19.7) | 23 (13.7) |
| Interval between lymphoma diagnosis and transplantation | ||
| Mean/median | 3.5 y/2.0 y | 3.0 y/2.0 y |
| Range | 3 mo-21 y | 3 mo-24 y |
| Transplantation characteristics | ||
| Age at transplantation, y | ||
| 8 to 30 | 12 (21.4) | 36 (21.4) |
| 31 to 40 | 24 (42.9) | 62 (36.9) |
| 41 to 61 | 20 (35.7) | 70 (41.7) |
| Calendar year of transplantation | ||
| 1989-1990 | 24 (42.9) | 47 (28.0) |
| 1991-1993 | 23 (41.1) | 90 (53.6) |
| 1994-1995 | 9 (16.1) | 31 (18.5) |
| Source of stem cells | ||
| Bone marrow | 19 (33.9) | 90 (53.6) |
| Peripheral blood | 31 (55.4) | 64 (38.1) |
| Bone marrow and peripheral blood | 6 (10.7) | 14 (8.3) |
| Conditioning regimen | ||
| TBI + cyclophosphamide | 16 (28.6) | 23 (13.7) |
| TBI + VP-16 ± cyclophosphamide | 10 (17.9) | 34 (20.2) |
| VP-16 + cyclophosphamide ± other drugs | 21 (37.5) | 76 (45.2) |
| VP-16, no cyclophosphamide ± other drugs | 7 (12.5) | 21 (12.5) |
| Others | 2 (3.6) | 14 (8.3) |
| TBI dose, Gy | ||
| None | 30 (53.6) | 111 (66.1) |
| 5.0 or 10.0 | 4 (7.1) | 13 (7.7) |
| 12.0 | 14 (25.0) | 39 (23.2) |
| 13.2 | 8 (14.3) | 5 (3.0) |
| Purging of harvested stem cells1-l | 6 (11.1) | 20 (12.7) |
| Mobilization (priming) chemotherapy1-m | 7 (12.5) | 14 (8.5) |
| Posttransplantation characteristics | ||
| Disease status | ||
| Complete remission | 36 (64.3) | 124 (73.8) |
| Persistent or recurrent disease | 19 (33.9) | 40 (23.8) |
| Unknown disease status | 1 (1.8) | 4 (2.4) |
| Posttransplantation chemotherapy with alkylating agent1-n | 6 (10.7) | 17 (10.1) |
| Posttransplantation chemotherapy with etoposide | 4 (7.1) | 14 (8.3) |
| Posttransplantation radiotherapy | 13 (23.2) | 22 (13.1) |
| Posttransplantation growth factors1-m | 41 (73.2) | 112 (68.3) |
| Characteristics . | Cases, n = 56 (no., %) . | Controls, n = 168 (no., %) . |
|---|---|---|
| Pretransplantation characteristics | ||
| Primary disease | ||
| Hodgkin disease | 19 (33.9) | 57 (33.9) |
| Nodular sclerosis | 14 (25.0) | 38 (22.6) |
| Mixed cellularity | 5 (8.9) | 10 (6.0) |
| Other types1-a | 0 (0) | 9 (5.4) |
| Non-Hodgkin lymphoma1-b | 37 (66.1) | 111 (66.1) |
| Low grade | 17 (30.4) | 35 (20.8) |
| Intermediate grade | 7 (12.5) | 46 (27.4) |
| High grade | 7 (12.5) | 16 (9.5) |
| Other types1-c | 6 (10.7) | 14 (8.3) |
| Male sex | 30 (53.6) | 90 (53.6) |
| Splenectomy | 3 (5.4) | 22 (13.2) |
| Pretransplantation chemotherapy with alkylating agents | ||
| MOPP/MOPP-like regimen (mechlorethamine/procarbazine-based) | 20 (35.7) | 55 (32.7) |
| Other regimens (non-MOPP) | 36 (64.3) | 113 (67.3) |
| Cyclophosphamide-based regimen, no other alkylating agents1-d | 8 (14.3) | 59 (35.1) |
| Chlorambucil-based regimen ± other alkylating agents1-e | 9 (16.1) | 7 (4.2) |
| No chlorambucil, other alkylating agents1-f | 18 (32.1) | 47 (28.0) |
| No alkylating agents1-g | 1 (1.8) | 0 (0) |
| Pretransplantation chemotherapy with etoposide | 27 (48.2) | 82 (48.8) |
| Pretransplantation radiotherapy fields | ||
| No radiotherapy | 30 (53.6) | 97 (57.7) |
| Mantle/mediastinum1-h | 10 (17.9) | 28 (16.7) |
| Inverted Y and/or other fields below diaphragm1-i | 3 (5.4) | 17 (10.1) |
| Total lymphoid irradiation or subtotal lymphoid irradiation1-j | 4 (7.1) | 14 (8.3) |
| Other fields1-k | 9 (16.1) | 12 (7.1) |
| Disease status at transplantation | ||
| Never in complete remission | 12 (21.4) | 41 (24.4) |
| First complete remission | 6 (10.7) | 19 (11.3) |
| Second or third complete remission | 14 (25.0) | 30 (17.9) |
| First relapse | 13 (23.2) | 55 (32.7) |
| 2 or more relapses | 11 (19.7) | 23 (13.7) |
| Interval between lymphoma diagnosis and transplantation | ||
| Mean/median | 3.5 y/2.0 y | 3.0 y/2.0 y |
| Range | 3 mo-21 y | 3 mo-24 y |
| Transplantation characteristics | ||
| Age at transplantation, y | ||
| 8 to 30 | 12 (21.4) | 36 (21.4) |
| 31 to 40 | 24 (42.9) | 62 (36.9) |
| 41 to 61 | 20 (35.7) | 70 (41.7) |
| Calendar year of transplantation | ||
| 1989-1990 | 24 (42.9) | 47 (28.0) |
| 1991-1993 | 23 (41.1) | 90 (53.6) |
| 1994-1995 | 9 (16.1) | 31 (18.5) |
| Source of stem cells | ||
| Bone marrow | 19 (33.9) | 90 (53.6) |
| Peripheral blood | 31 (55.4) | 64 (38.1) |
| Bone marrow and peripheral blood | 6 (10.7) | 14 (8.3) |
| Conditioning regimen | ||
| TBI + cyclophosphamide | 16 (28.6) | 23 (13.7) |
| TBI + VP-16 ± cyclophosphamide | 10 (17.9) | 34 (20.2) |
| VP-16 + cyclophosphamide ± other drugs | 21 (37.5) | 76 (45.2) |
| VP-16, no cyclophosphamide ± other drugs | 7 (12.5) | 21 (12.5) |
| Others | 2 (3.6) | 14 (8.3) |
| TBI dose, Gy | ||
| None | 30 (53.6) | 111 (66.1) |
| 5.0 or 10.0 | 4 (7.1) | 13 (7.7) |
| 12.0 | 14 (25.0) | 39 (23.2) |
| 13.2 | 8 (14.3) | 5 (3.0) |
| Purging of harvested stem cells1-l | 6 (11.1) | 20 (12.7) |
| Mobilization (priming) chemotherapy1-m | 7 (12.5) | 14 (8.5) |
| Posttransplantation characteristics | ||
| Disease status | ||
| Complete remission | 36 (64.3) | 124 (73.8) |
| Persistent or recurrent disease | 19 (33.9) | 40 (23.8) |
| Unknown disease status | 1 (1.8) | 4 (2.4) |
| Posttransplantation chemotherapy with alkylating agent1-n | 6 (10.7) | 17 (10.1) |
| Posttransplantation chemotherapy with etoposide | 4 (7.1) | 14 (8.3) |
| Posttransplantation radiotherapy | 13 (23.2) | 22 (13.1) |
| Posttransplantation growth factors1-m | 41 (73.2) | 112 (68.3) |
Controls matched to cases on primary disease (NHL, HD), sex, race, age at transplantation (± 5 years) and latency (time between transplantation and MDS for the cases and corresponding interval in controls).
Co indicates control(s); Ca, case patient(s); AA, alkylating agents; CTX, cyclophosphamide; CDDP, cisplatin; IFO, ifosfamide; BCNU, carmustine; LPAM, melphalan; PROC, procarbazine; DTIC, dacarbazine; VCR, vincristine; DNM, daunomycin; MTX, methotrexate; CHLB, chlorambucil; and NITM, nitrogen mustard.
Other histologic types include: lymphocyte predominant (1 Co), lymphocyte depleted (2 Co), and unclassified or ill-defined type (6 Co).
Lymphomas are defined according to the International Working Formulation, National Cancer Institute.
Other histologic types include: composite lymphoma (2 Ca/6 Co); large cell (Ki-1+) lymphoma (1 Ca/1 Co); and unclassified lymphoma (3 Ca/7 Co).
One case and 8 controls received ifosfamide in addition to cyclophosphamide; category includes patients treated with etoposide.
AA in addition to chlorambucil include: CTX (6 Ca/1 Co); CTX + CDDP (1 Ca/1 Co); CDDP (1 Ca); CTX + IFO (2 Co); CTX + BCNU + LPAM (1 Co); PROC (1 Co); PROC + CTX (1 Co).
AA include: CTX + CDDP (7 Ca/23 Co); CTX + PROC (1 Ca/6 Co); CTX + BCNU (1 Ca/3 Co); CTX + IFO + CDDP (4 Ca/4 Co); CTX + CDDP + PROC (1 Ca/4 Co); CTX + BCNU + LPAM + CDDP (1 Ca); CTX + IFO + PROC (2 Co); LPAM + BCNU (2 Ca/2 Co); CDDP (1 Ca); CDDP + IFO + BCNU (1 Co); DTIC (2 Co).
One case received VCR + DNM + MTX.
One control received mantle and pelvic irradiation.
Includes the following fields alone or in combination: inverted-Y, para-aortic field, abdomen, spleen, and pelvis.
Subtotal lymphoid irradiation (STLI) includes mantle field, splenic pedicle, and para-aortic field; total lymphoid irradiation (TLI) includes S-TLI and inverted-Y.
Includes the following fields alone or in combination: head/neck, chest, spine, sacrum, limb, groin, and TBI (low dose).
Data were not available for 2 case patients and 10 controls.
Data were not available for 4 controls.
AA include: CTX (3 Ca/6 Co); CDDP (2 Co); CTX + CDDP (1 Co); IFO + CDDP (1 Ca/2 Co); CHLB (1 Co); PROC + CHLB (1 Ca/1 Co); PROC + CTX (1 Co); NITM + BCNU (1 Co); NITM + BCNU + CTX (1 Co); NITM + PROC (1 Ca/1 Co).