Total body irradiation dose and risk of subsequent neoplasms following allogeneic hematopoietic cell transplantation

K. Scott Baker, Wendy M. Leisenring, Pamela J. Goodman, Ralph P. Ermoian, Mary E. Flowers, G. Shoch, Rainer Storb, Brenda M. Sandmaier and H. Joachim Deeg

Key Points

  • SMN risk was highest in survivors exposed to high dose unfractionated (600-1,200 cGy) or very high dose fractionated (1,440-1,750 cGy) TBI.

  • With low-dose TBI (200-450 cGy), SMN risk was comparable to chemotherapy alone, though still 2-fold higher than in the general population.


We examined the impact of total body irradiation (TBI) dose and fractionation on risk of subsequent malignant neoplasms (SMN) in the era of reduced intensity and non-myeloablative conditioning regimens for hematopoietic cell transplantation (HCT). Among 4,905 one-year survivors of allogeneic HCT for hematologic malignancies (N=4,500) or non-malignant disorders (N=405) transplanted between 1969-2014 we identified 581 SMNs (excluding squamous and basal cell of skin) in 499 individuals. With a median length of follow-up of 12.5 years, the cumulative incidence of SMN by 30 years after HCT was 22.0%. Compared to age, sex and calendar year matched SEER population rates, the standardized incidence ratio (SIR) of SMNs was increased 2.8-fold. The highest SIRs were for SMNs of bones (SIR 28.8), oral cavity (SIR 13.8), skin (SIR 7.3), central nervous system (SIR 6.0), and endocrine organs (SIR 4.9). The highest excess absolute risks (EAR) were seen with breast cancer (EAR 2.2) and cancers of the oral cavity (EAR 1.5) and skin (EAR 1.5) per 1000 person-years. The highest incidence of SMNs was in survivors exposed to unfractionated (600-1,00 cGy) or high dose fractionated (1,440-1,750 cGy) TBI. For patients receiving low-dose TBI, the incidence was comparable to myeloablative chemotherapy alone, although still 2-fold higher than in the general population. These data demonstrate a strong effect of TBI dose, and dose fractionation, and risk of SMNs after HCT. The cumulative incidence of SMN increases with follow-up time, thus HCT survivors require lifetime monitoring for early detection and effective therapy of SMNs.

  • Submitted September 7, 2018.
  • Revision received April 5, 2019.
  • Accepted April 3, 2019.