Causes of Death in Childhood Acute Lymphoblastic Leukemia: A Single-Center Experience

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Excellent overall survival rate of about 90% are the result of improvements in risk stratification and risk-adapted therapy, intensive chemotherapy regimens, hematopoietic stem cell transplanta-tion and supportive care. Background and Objectives: The aim of this study is to review the epi-demiology, prognostic factors, and causes of death of pediatric ALL in a terciary center. Mate-rials and Methods: A retrospective study was conducted at the Croatian Referral Center for Pe-diatric Hematology and Oncology, University Hospital Centre Zagreb, including 302 children (0–18 years) diagnosed with ALL between January 2001 and December 2015, accounting for about 70% of national cases. Results: Two hundred fifty-one children survived (5-year overall survival 83%). Relapse occurred in 13.6% of patients. Relapse rates were higher for B-cells pre-cursor ALL than for T-cell ALL (14.3% vs. 10.4%), and no patient with relapsed T-cell ALL survived. Main causes of death were refractory/relapsed disease (43% of patients), followed by infections (35%) and GVHD (8%). The most frequent causes of infectious death were Pseudo-monas aeruginosa and Aspergillus fumigatus. The most critical treatment periods were induc-tion and reinduction phases, especially de-escalation of corticosteroids. The time of relapse and risk group were independent factors in predicting the outcome. Conclusions: Our study con-firmed that relapse and infections are major causes of mortality in children with ALL. To im-prove the outcome, we should encourage participation in collaborative international trials, im-provement of supportive care and implementation of new treatment modalities.