Nationwide survey of bisphosphonate therapy for children with reactivated Langerhans cell histiocytosis in Japan.
BACKGROUND
Several studies have suggested that Langerhans cell histiocytosis (LCH) is responsive to treatment with bisphosphonates (BPs). However the efficacy and safety of BPs therapy for childhood LCH is unknown.


METHODS
Data on children with LCH who had received BPs therapy were collected retrospectively from hospitals participating in the Japanese Pediatric Leukemia/Lymphoma Study Group.


RESULTS
Twenty-one children with histologically proven LCH were identified. Of these, the case histories of 16 children who had been treated with pamidronate (PAM) for disease reactivation were analyzed in detail. The median post-PAM therapy follow-up period was 2.8 years (range: 0.9-9.3 years). The median age at commencement of PAM therapy was 9.4 years (range: 2.3-15.0 years). All children had one or more bone lesions but none had risk organ (RO) involvement. In the majority of the children, six courses of PAM were administered at a dose of 1.0 mg/kg/course at 4-week intervals. In 12 of the 16 children, all active lesions including lesions of the skin (n = 3) and soft tissues (n = 3) resolved. Of these children, eight children had no active disease for a median of 3.3 years post-PAM therapy (range: 1.8-9.3 years). Progression-free survival (PFS) was 56.3 ± 12.4% at 3 years. PFS was significantly higher in children with a first reactivation compared with children experiencing a second or subsequent reactivation.


CONCLUSIONS
PAM may be an effective treatment for reactivated LCH with bone lesions. A prospective trial of the efficacy of PAM in recurrent pediatric LCH is warranted.
Department of Pediatrics, Jichi Medical University School of Medicine, Shimotsuke, Japan. akira@jichi.ac.jp
Akira
A
Morimoto
Yoko
Y
Shioda
Toshihiko
T
Imamura
Hirokazu
H
Kanegane
Takashi
T
Sato
Kazuko
K
Kudo
Shinichiro
S
Nakagawa
Hisaya
H
Nakadate
Hisamichi
H
Tauchi
Asahito
A
Hama
Masahiro
M
Yasui
Yoshihisa
Y
Nagatoshi
Akitoshi
A
Kinoshita
Ryosuke
R
Miyaji
Tadashi
T
Anan
Miharu
M
Yabe
Junji
J
Kamizono
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004164:Diphosphonates / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004341:Drug Evaluation; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006646:Histiocytosis, Langerhans-Cell / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007564:Japan; D008297:Male; D000077268:Pamidronate; D012008:Recurrence; D012189:Retrospective Studies; D016896:Treatment Outcome
D004164:Diphosphonates; D000077268:Pamidronate