Incidence of second cancers after allogeneic hematopoietic stem cell transplantation using reduced-dose radiation

To the editor:

We read with interest the article by Rizzo et al¹  updating their earlier publication²  and describing the largest international retrospective analysis of second cancers after allogeneic hematopoietic stem cell transplantation (HSCT) to date. Their data demonstrate a cumulative incidence of second malignancies of 3.3% at 20 years. The greatest risk of solid tumors, such as melanoma, breast, thyroid, brain, and other tumors, was age younger than 30 at the time of HSCT and total body irradiation (TBI). This higher risk associated with younger age at time of transplantation is similar to the results from atomic bomb survivors,³  and these confirmatory data provide critical information in the counseling of patients considering HSCT. Their current analyses unfortunately grouped those who received doses below 12 Gy, and suggested that TBI doses lower than 12 Gy confer the same second cancer risk as TBI doses above 12 Gy. In contrast, previous analyses in atomic bomb survivors have shown a near-linear relationship between the TBI dose and second cancer risk, especially below 5 Gy.^3,4  Further, Curtis et al previously found that lower doses of TBI (< 12 Gy) were associated with a lower risk of second cancer.²  Because a growing number of allogeneic HSCTs employ substantially lower doses of TBI, including doses as low as 2 Gy, this point deserves further clarification. An analysis focusing on the second cancer risk with lower doses of TBI would complement the atomic bomb survivor data and greatly benefit the transplantation community. Additionally, including the incidence of second cancers in patients with nonmalignant disorders, such as hemoglobinopathies or aplastic anemia, would further broaden the applicability of their extensive data analyses.