Late Mortality, Subsequent Malignant Neoplasms and Hospitalisations in Long-Term Survivors of Adolescent and Young Adult Hematological Cancers

Annalisa Trama, Claudia Vener, Paolo Lasalvia, Alice Bernasconi, Manuel Zorzi, Anita Andreano, Paolo Contiero, Gianfranco Manneschi, Fabio Falcini, Marine Castaing, Rosa Angela Filiberti, Cinzia Gasparotti, Claudia Cirilli, Rosalba Amodio, Isabella Bisceglia, Silvia Iacovacci, Maria Francesca Vitale, Fabrizio Stracci, Maria Adalgisa Gentilini, Rosario Tumino, Simona Carone, Giuseppe Sampietro, Anna Melcarne, Luciana Gatti, Lorenza Boschetti, Mariangela Corti, Magda Rognoni, Enzo Coviello, Maria Teresa Pesce, Giancarlo D’Orsi, Anna Clara Fanetti, Lucia De Lorenzis, Giuseppa Candela, Fabio Savoia, Cristiana Pascucci, Maurizio Castelli, Cinzia Storchi

Increased success in the treatment of hematological cancers contributed to the increase of 5-year survival for most adolescent and young adults (AYAs) with these tumours. However, as 5-year survival increased, it became clear that AYA long-term survivors were at increased risk for severe late effects. Moreover, limited information on long-term cancer impact is available for AYAs, since most studies focused on children and adolescents. We aimed to assess various long-term outcomes on AYA survivors of hematological cancers. We selected patients diagnosed with a first primary hematological cancer between 1997 and 2006, in the Italian nationwide population-based cohort of AYA cancer survivors (i.e. alive at least 5 years after cancer diagnosis). Long-term outcomes of interest were: second malignant neoplasms (SMNs), hospitalizations and overall mortality. We calculated standardized incidence ratios (SIRs), standardized hospitalization rate ratios (SHRs) and standardized mortality rate ratios (SMRs). To study morbidity patterns over time, we modeled observed incidence rates by fitting flexible parametric models for nonlinear patterns and we used linear regression for linear patterns. The study cohort included 5,042 AYA hematological cancer survivors of which 1,237 and 3,805 had a leukaemia and lymphoma diagnosis, respectively. AYA survivors were at substantially increased risk for SMN (SIR=2.1; 95%CI=1.7; 2.6), hospitalisation (SHR=1.5; 95%CI=1.5; 1.6), and mortality (SMR=1.4; 95%CI=1.2; 1.6) with differences between leukaemia and lymphoma survivors. The highest excess risks of hospitalisations were for infectious diseases, respiratory diseases, and diseases of blood and blood-forming organs. The morbidity pattern differs over time by morbidity type. Our results support the need for strict follow-up plans for survivors, and call for further study to better personalised follow-up plans for AYA cancer survivors.