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Original Investigation
November 21, 2018

Evaluation of Second Solid Cancers After Hematopoietic Stem Cell Transplantation in European Patients

Author Affiliations
  • 1Hematology, University Hospital, Basel, Switzerland
  • 2EBMT Paris Study Office/CEREST-TC, Hôpital Saint Antoine, Paris, France
  • 3Department of Hematology–BMT, Hôpital St Louis, Paris, France
  • 4Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
  • 5EBMT Data Office Leiden, Leiden University Medical Center, Leiden, the Netherlands
  • 6Stem Cell Transplantation and Immunology, Hospital for Children and Adolescents, Frankfurt, Germany
  • 7Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Spain
  • 8Department of Hematology, Oncology and Internal Medicine, Central Clinical Hospital, the Medical University of Warsaw, Warsaw, Poland
  • 9Center for Haematology, Imperial College, London, United Kingdom
JAMA Oncol. Published online November 21, 2018. doi:10.1001/jamaoncol.2018.4934
Key Points

Question  What is the clinical outcome for patients who developed a second solid cancer after a stem cell transplant, when compared with a de novo cancer of the same subtype?

Findings  In this cohort study of 4065 European patients with 18 different second solid cancers after a stem cell transplant, 5-year overall survival was 47%, and after solid second cancer diagnosis, survival was poor in pancreas, lungs, hepatobiliary, esophageal, brain, and gastric cancers.

Meaning  This study provides observational evidence of the utility of screening and counseling for long-term survivors of second cancers.

Abstract

Importance  Incidence and risk factors of second solid cancers (SSCs) that occur after hematopoietic stem cell transplantation (HSCT) are well documented. However, clinical outcome data of patients who developed an SSC after HSCT are limited.

Objective  To assess the outcome of patients with an SSC occurring after HSCT from the time of SSC diagnosis.

Design, Setting, and Participants  This cohort study used data of 4065 patients from 26 countries registered with the European Society for Blood and Marrow Transplantation, which has maintained clinical data since 1977 of patients who received a transplant. Information from all patients who underwent a transplant in Europe and had an SSC diagnosis between January 1, 2000, and December 31, 2014, was extracted. The cohort included patients with 18 different cancers. Data analysis was conducted from September 3, 2017, to March 17, 2018.

Main Outcomes and Measures  Median and 5-year age-standardized overall survival, causes of death, risk factor multivariate analysis using a clustered Cox proportional hazard regression model, and standardized mortality ratio were calculated for each of the 18 types of SSC.

Results  In total, 220 617 patients underwent a transplant, of whom only 4065 (1.8%) patients with a second solid cancer after HSCT were included in the study. Among the 4065 patients, 2321 (57.1%) were men and 1744 (42.9%) were women, with a mean (range) age of 59.1 (3.2-82.3) years at diagnosis of second solid cancer. The 5-year age-standardized overall survival was 47% (95% CI, 45%-49%). The 5-year overall survival rate after SSC diagnosis was poor for pancreas, lung, hepatobiliary, esophageal, brain, and gastric cancers, with a median survival between 0.6 and 1 year. The 5-year overall survival was intermediate for endometrial, colorectal, sarcomas, ovarian, bladder, oropharyngeal, and kidney cancers, with a median survival between 2 and 10 years. The 5-year overall survival was more favorable for melanoma, breast, prostate, cervix, and thyroid cancers, with a median survival of 10 or more years. Additional transplant-associated factors for mortality for patients treated with allogeneic HSCT were age at transplant, donor type, conditioning regimen, and graft-vs-host disease. In total, 1777 patients (43.7%) died, of which 1256 (74.8%) were from SSC, 344 (20.5%) from primary disease, and 79 (4.7%) from other causes. Standardized mortality ratio was higher, compared with de novo solid cancers, for melanoma, prostate, breast, kidney, bladder, colorectal, and endometrial cancers but not for the other cancers.

Conclusions and Relevance  The outcome of SSC is mainly dependent on the type of second cancer; thus, future studies should investigate the reasons the standardized mortality ratio is higher for some cancers to identify whether patients with these cancers should be treated differently and to help in screening and counseling patients who developed an SSC after HSCT.

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