Risk of myelodysplastic syndrome and acute myeloid leukemia according to pretransplantation therapy and transplantation-related factors
| Risk factors . | Cases/controls . | Model 1: transplantation-related factors only . | Model 2: transplantation-related factors, adjusting for pretransplantation chemotherapy . | ||||
|---|---|---|---|---|---|---|---|
| RR . | 95% CI . | P . | RR . | 95% CI . | P . | ||
| TBI dose, Gy4-150 | |||||||
| None | 30/111 | 1.0 | — | — | 1.0 | — | — |
| 12.0 or less | 18/52 | 1.5 | 0.68-3.32 | .32 | 1.3 | 0.59-3.10 | .48 |
| 13.2 | 8/5 | 6.6 | 1.90-27.11 | .003 | 4.6 | 1.15-20.70 | .03 |
| Ptrend.008 | Ptrend .04 | ||||||
| Source of stem cells | |||||||
| Bone marrow | 19/90 | 1.0 | — | — | 1.0 | — | — |
| Peripheral blood ± bone marrow | 37/78 | 2.3 | 1.20-4.53 | .01 | 1.8 | 0.86-3.74 | .12 |
| Pretransplantation chemotherapy4-151 | |||||||
| Cyclophosphamide, no other AA | 9/59 | 1.0 | — | — | |||
| MOPP, mechlorethamine dose less than 50 mg/m2 | 8/31 | 2.0 | 0.45-8.67 | .36 | |||
| MOPP, mechlorethamine dose 50 mg/m2 or higher | 12/24 | 4.3 | 0.97-19.69 | .06 | |||
| Ptrend.04 | |||||||
| Chlorambucil, duration less than 10 months | 4/5 | 3.8 | 0.68-20.09 | .13 | |||
| Chlorambucil, duration 10 months or longer | 5/2 | 8.4 | 1.34-72.97 | .02 | |||
| Ptrend.009 | |||||||
| Other AA, no MOPP, no chlorambucil | 18/47 | 1.9 | 0.73-5.21 | .20 | |||
| Risk factors . | Cases/controls . | Model 1: transplantation-related factors only . | Model 2: transplantation-related factors, adjusting for pretransplantation chemotherapy . | ||||
|---|---|---|---|---|---|---|---|
| RR . | 95% CI . | P . | RR . | 95% CI . | P . | ||
| TBI dose, Gy4-150 | |||||||
| None | 30/111 | 1.0 | — | — | 1.0 | — | — |
| 12.0 or less | 18/52 | 1.5 | 0.68-3.32 | .32 | 1.3 | 0.59-3.10 | .48 |
| 13.2 | 8/5 | 6.6 | 1.90-27.11 | .003 | 4.6 | 1.15-20.70 | .03 |
| Ptrend.008 | Ptrend .04 | ||||||
| Source of stem cells | |||||||
| Bone marrow | 19/90 | 1.0 | — | — | 1.0 | — | — |
| Peripheral blood ± bone marrow | 37/78 | 2.3 | 1.20-4.53 | .01 | 1.8 | 0.86-3.74 | .12 |
| Pretransplantation chemotherapy4-151 | |||||||
| Cyclophosphamide, no other AA | 9/59 | 1.0 | — | — | |||
| MOPP, mechlorethamine dose less than 50 mg/m2 | 8/31 | 2.0 | 0.45-8.67 | .36 | |||
| MOPP, mechlorethamine dose 50 mg/m2 or higher | 12/24 | 4.3 | 0.97-19.69 | .06 | |||
| Ptrend.04 | |||||||
| Chlorambucil, duration less than 10 months | 4/5 | 3.8 | 0.68-20.09 | .13 | |||
| Chlorambucil, duration 10 months or longer | 5/2 | 8.4 | 1.34-72.97 | .02 | |||
| Ptrend.009 | |||||||
| Other AA, no MOPP, no chlorambucil | 18/47 | 1.9 | 0.73-5.21 | .20 | |||
RR indicates relative risk; CI, confidence interval; AA, alkylating agents; MOPP, mechlorethamine, vincristine, procarbazine, prednisone; and —, reference group.
Conditioning regimens with TBI given in the 12 participating transplant centers consisted of 4 dose protocols: 5, 10, 12, and 13.2 Gy. Risks of MDS/leukemia associated with TBI doses of 5.0 or 10.0, 12, and 13.2 Gy were 2.1 (95% CI, 0.51-7.24), 1.4 (95% CI, 0.58-3.19), and 6.5 (95%CI, 1.86-21.54), respectively (Model 1).
Pretransplantation chemotherapy is included only in Model 2.