Osteonecrosis: An emerging complication of intensive chemotherapy for childhood acute lymphoblastic leukemia.
OBJECTIVE
Osteonecrosis (ON) is a potentially disabling complication of combination chemotherapy including high doses of steroids. The incidence and main risk factors for symptomatic ON have been investigated in a large group of children treated with high-dose steroids, prednisone and dexamethasone for childhood acute lymphoblastic leukemia (ALL).


METHODS
From May 1995 to December 1999, 1421 patients <18 years old, with newly diagnosed non-B ALL, were registered in the AIEOP-ALL 95 study. Their data were reviewed to identify patients who developed symptomatic ON. For those who were positively identified additional data were requested concerning ON-related symptoms, treatment and outcome.


RESULTS
Overall, 15 of the 1421 patients developed symptomatic ON (1.1%) in a total of 29 sites. The estimated 5-year cumulative risk for clinically diagnosed ON was 1.6% (SE 0.4). The incidence was significantly higher among females (p=0.01) and older patients, with a peak rate of 7.4% (2.3) among those aged 10 to 17 years (p<0.0001). When the two factors, i.e. age and gender were combined, there was a striking increase in the risk among female patients aged 10 to 17 years. The median time between the diagnosis of ALL and that of ON was 17 months (range 8-45). The hip was the most frequently involved (19/29) site.


CONCLUSIONS
Symptomatic ON occurred in only 1.1% of patients treated with BFM-type, intensive chemotherapy for childhood ALL. Female adolescents appear to be the subset of patients with the highest risk of ON, especially when categorized as having high risk leukemia and thus administered higher cumulative doses of dexamethasone.
Aricò
Maurizio
M
OncoEmatologia Pediatrica, Ospedale dei Bambini G. Di Cristina, via Benedettini 1, 90134 Palermo, Italy. arico@ospedalecivicopa.org
Boccalatte
Marie France Pinta
MF
Silvestri
Daniela
D
Barisone
Elena
E
Messina
Chiara
C
Chiesa
Robert
R
Santoro
Nicola
N
Tamaro
Paolo
P
Lippi
Alma
A
Gallisai
Domenico
D
Basso
Giuseppe
G
De Rossi
Giulio
G
D000293:Adolescent; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D003907:Dexamethasone / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D010020:Osteonecrosis / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology / Q000628:therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy*; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D012307:Risk Factors; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D003907:Dexamethasone; D011241:Prednisone