Long-Term Incidence of Secondary Malignancies after Allogeneic Hematopoietic Cell Transplantation: A Single-Center Experience

Abstract

To review the emergence of secondary malignancies (SMs) in recipients of allogeneic hematopoietic cell transplantation (HCT), we documented the occurrence of SMs in 2415 allogeneic HCT recipients, ages 18 to 71, in a single center over 4 decades. SMs were seen in 209 patients, including 58 with nonmetastatic squamous cell (SCC) and basal cell carcinoma (BCC) of the skin. Cumulative incidence of SM was 6.3% at 10 years, 13.5% at 20 years, and 17.6% at 30 years post-HCT. Median age at diagnosis of SMs was 61 years (range, 21 to 85). By multivariable analysis, older age at HCT was the only independent prognostic factor for SM (HR, 1.39 for ages 41 to 55 and HR, 1.92 for age > 55 compared with age ≤ 40; P = .001). The rate of SM (excluding nonmetastatic SCC/BCC of skin) after HCT was 2.07 times higher (P = .01) compared with the general population. Overall survival (OS) after diagnosis of SM (excluding nonmetastatic SCC/BCC of skin) was 58% at 5 years and 50% at 10 years postdiagnosis. Eastern Cooperative Oncology Group (ECOG) score was the only independent predictor of OS on multivariable analysis, with over 2-fold increased risk of death for patients with an ECOG score of 1 and over 6-fold for ECOG scores of 2 to 4, compared with ECOG score 0 (P < .0001). Forty of 209 patients (19%) diagnosed with SMs subsequently developed another new malignancy. OS was 68% and 51% at 5 and 10 years, respectively. The survival of SM patients post-HCT is favorable, thus warranting diligent long-term cancer screening and standard of care treatment. ECOG status of these patients is a predominant prognostic factor.

Comorbidity profile of adult survivors at 20 years following allogeneic hematopoietic cell transplantation

“…Interestingly, it has been reported that the 5‐year OS rates after the diagnosis of solid cancer in HCT recipients were not different from patients non‐transplant patients who developed de novo solid cancers, 25 indicating that the natural history of malignancies in HCT recipients is similar to that of the general population. Although the presence of prior secondary malignancy did not significantly alter the survival of our study cohort, the incidence of secondary malignancies in HCT recipients is known to be higher than the general population 12,24 . In addition, the estimated incidence of secondary malignancy rises in every decade after allogeneic HCT 26 .…”

“…The overall survival after the diagnosis of the secondary malignancy (excluding non-metastatic SCC/BCC of skin) was 63% at 3 years post-HCT, 58% 5 years post-HCT, and 50% 10 years post-HCT. 24 The overall survival after the diagnosis of secondary malignancy was dependent on the allogeneic HCT recipients' ECOG score at diagnosis of the secondary malignancy, with low ECOG associated with improved survival. 24 Interestingly, it has been reported that the 5-year OS rates after the diagnosis of solid cancer in HCT recipients were not different from patients non-transplant patients who developed de novo solid cancers, 25 indicating that the natural history of malignancies in HCT recipients is similar to that of the general population.…”

“…24 The overall survival after the diagnosis of secondary malignancy was dependent on the allogeneic HCT recipients' ECOG score at diagnosis of the secondary malignancy, with low ECOG associated with improved survival. 24 Interestingly, it has been reported that the 5-year OS rates after the diagnosis of solid cancer in HCT recipients were not different from patients non-transplant patients who developed de novo solid cancers, 25 indicating that the natural history of malignancies in HCT recipients is similar to that of the general population. Although the presence of prior secondary malignancy did not significantly alter the survival of our study cohort, the incidence of secondary malignancies in HCT recipients is known to be higher than the general population.…”

“…A retrospective study recently performed at our center found that the cumulative incidence of second malignancies was 6.3% at 10 years, and 13.5% at 20 years post‐HCT, with squamous cell and BCC of the skin having the highest incidence. The overall survival after the diagnosis of the secondary malignancy (excluding non‐metastatic SCC/BCC of skin) was 63% at 3 years post‐HCT, 58% 5 years post‐HCT, and 50% 10 years post‐HCT 24 . The overall survival after the diagnosis of secondary malignancy was dependent on the allogeneic HCT recipients' ECOG score at diagnosis of the secondary malignancy, with low ECOG associated with improved survival 24 …”

“…Although the presence of prior secondary malignancy did not significantly alter the survival of our study cohort, the incidence of secondary malignancies in HCT recipients is known to be higher than the general population. 12,24 In addition, the estimated incidence of secondary malignancy rises in every decade after allogeneic HCT. 26 Radiation therapy, length and intensity of immunosuppression, as well as chronic GVHD have been implicated in contributing to secondary malignancy risk in allogeneic HCT patients.…”