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

Abstract

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Good overall survival rates of about 90% are the result of improvements in risk stratification and risk-adapted therapy, intensive chemotherapy regimens, hematopoietic stem cell transplantation, and better supportive care. Background and Objectives: The aim of this study is to review the epidemiology, prognostic factors, and causes of death in pediatric ALL patients treated at a tertiary care center, and to identify risk factors influencing clinical outcomes. Materials and Methods: A retrospective study was conducted at the Department of Pediatric Hematology and Oncology, University Hospital Centre Zagreb, including 302 children (0-18 years) diagnosed with ALL between January 2001 and December 2015. 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-cell precursor (Bcp)-ALL than for T-cell ALL (14.3% vs. 10.4%), and no patient with relapsed T-cell ALL survived. The 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 Pseudomonas aeruginosa and Aspergillus fumigatus. The most critical treatment periods were the induction and reinduction phases, especially the de-escalation of corticosteroids. The time of relapse and risk group were independent factors in predicting the outcome. Conclusions: Relapse and infections were the leading causes of death in children with ALL, with the highest mortality observed during induction and reinduction phases. Survival was significantly influenced by relapse timing and risk group, with no survivors among relapsed T-ALL patients.

Keywords: children; death; infection; leukemia; prognostic factors; relapse.

Figure 1

The 5-year OS of relapsed patients according to the time of relapse (Kaplan–Meier curve).

Figure 2

This figure presents the distribution of causes of death among non-relapsed patients, highlighting infections as the leading cause (14 patients, approximately 75%). Other causes, including liver failure (11%), GVHD (5%), and hemorrhage (5%), were less frequently observed.

Figure 3

This figure illustrates the distribution of causes of death among relapsed patients, with relapse or resistant disease being the predominant cause (22 patients, approximately 70%). Other causes, such as infections, GVHD, hemorrhage, and abandoned treatment, account for progressively fewer deaths, representing 13%, 9%, 6%, and 3% of patients, respectively. Regarding infections, the most common isolated microorganisms were Pseudomonas aeruginosa (7 patients—5 non-relapsed and 2 relapsed), Aspergillus fumigatus (6 patients—5 non-relapsed and 1 relapsed), and Fusarium spp. (2 patients—1 non-relapsed and 1 relapsed).