The advent of more intensive chemotherapy and the improvement of supportive cares have dramatically changed the natural history of childhood acute lymphoblastic leukemia (ALL), with current estimated 5-year overall survival of about 80%. The increased survival rate and the establishment of follow-up survey for long term survivors (LTS) have allowed the identification of late chemo-radiotherapy adverse effects on psychological and general health. We retrospectively evaluate the incidence and type of sequelae and / or late effects in a cohort of 301 childhood ALL LTS, followed in a single pediatric AIEOP center.

From June 1986 to June 2013, 301 LTS (154 male and 147 female), aged <18 years at ALL diagnosis, were followed-up by a multidisciplinary team. The surveillance protocol is summarized in Figure 1. The timing of follow-up (FU) was modified, case by case, in relation to the appearance of adverse events or organ diseases. Survivors' results were compared with chronic medical and psychological conditions of siblings (n=89).
Mean FU time (time from the stop therapy to the last control) was 6 years (range 1.8-26.8 years). The majority of LTS were teenager or young adults : 35% ranged between 15 and 20 years; 19.7% was more than 21 years old and the 45.3% was less than 14 years old. During FU, 16 late recurrences (5.3%) were identified and 3 secondary malignancies (0.99%) such as one mesenteric paraganglioma and two Acute Myeloid Leukemia in second complete remission ALL LTS. 40 patients (13.3%) received cranial radiotherapy during treatment. 39 LTS (13%) reported at least one sequelae. The most frequent sequelae were neurological and orthopedic (6% and 3% respectively) as summarized in Figure 2 151 LTS (50.17%) presented at least one late effect as showed in Figure 3.

In our experience at least one late effect occurred in 50.17% of LTS; these late complications affect negatively the quality of life of survivors. Endocrine-metabolic events are the most frequent late effect (34,5%). 13% of LTS have at least one sequelae mainly neurological and orthopedic. Prevention and/or early identification of complications during follow-up survey of LTS are crucial in order to decrease the long-term health risks associated with curative treatment for childhood ALL.


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.