Secondary Solid Cancer Following Hematopoietic Cell Transplantation in Patients with Thalassemia Major

Hematopoietic cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers (SSC). There is limited information about the incidence of SSC following HCT for patients with thalassemia major (TM).

The aim of this retrospective cohort study was to compare the incidence of SSC in a large monocentric cohort of TM patients (n=122; 67 males) who received HCT and survived for at least 3 years after the transplant versus:

- an hematopoietic cell donors monocentric cohort (n=122; HLA genotipically identical siblings in 113 cases, HLA phenotipically identical family members in 6 cases, and matched unrelated in 3 cases);

- a large multicenter cohort of age- and sex-matched TM patients (n=244) well treated with conventional therapy and enrolled in the Myocardial Iron Overload in Thalssemia (MIOT) Network.

During a median follow-up of 24 years, 8 transplanted patients were diagnosed with SSC (one Merkel-cell carcinoma, one carcinoma of parotid gland, one colorectal cancer, one carcinoma of the uterine cervix, one thyroid carcinoma, three cancers of the oral cavity) at a median of 18 (range, 3.2 to 29) years after HCT. The median age of 8 patients at time of SSC diagnosis was 33 years. Three patients died for cancer progression and 5 are living and doing well after a follow-up ranging from 10 months to 16 years after SSC diagnosis.

Noteworthy, all 3 patients who were diagnosed with oropharingeal cancer were affected by mild to moderate chronic GvHD with particular extension to oral cavity. The cumulative incidence of SSC was 0.82% (95% confidence interval [CI], 0.12-5.68%) at 10 years from transplant, 3.86% (95% CI, 1.46-9.99) at 20 years from transplant and 13.24% (95% CI, 6.01-27.81) at 30 years from transplant (Figure 1A).

Among the hemopoietic stem cell donors, only one developed a SSC (triple negative breast cancer) 28 years after donation at age of 38. At 10 and 20 years after hemopoietic stem cell donation, the cumulative incidence of SSC was 0 while at 30 years it was 3.23% (95% CI, 0.46-20.77). Compared to the cumulative incidence of transplanted patient, the difference was statistically significant (P=0.02) (Figure 1B).

Among the TM patients treated with conventional therapy, 3 cases of SSC were discovered: one thyroid carcinoma, one bilateral pheocromocytoma and one Hodgkin lymphoma. In this cohort of patients, the cumulative incidence of SSC was 1.32% (95% CI, 0.43-4.04) after 10, 20 and 30 years. Compared to the cumulative incidence of transplanted patient, the difference was statistically significant (P=0.005) (Figure 1C).

In conclusion, this study shows that the magnitude of increased risk of SST is fourfold to sixfold for patients treated with HCT as compared with hemopoietic cell donors or with an age- and sex-matched nontransplant well treated TM patients.