Hypercalcemia in childhood acute lymphoblastic leukemia: frequent implication of parathyroid hormone-related peptide and E2A-HLF from translocation 17;19.
Hypercalcemia is relatively rare but clinically important complication in childhood leukemic patients. To clarify the clinical characteristics, mechanisms of hypercalcemia, response to management for hypercalcemia, incidence of t(17;19) and final outcome of childhood acute lymphoblastic leukemia (ALL) accompanied by hypercalcemia, clinical data of 22 cases of childhood ALL accompanied by hypercalcemia (>12 mg/dl) reported in Japan from 1990 to 2005 were retrospectively analyzed. Eleven patients were 10 years and older. Twenty patients had low white blood cell count (<20 x 10(9)/l), 15 showed hemoglobin> or =8 g/dl and 14 showed platelet count > or =100 x 10(9)/l. Parathyroid hormone-related peptide (PTHrP)-mediated hypercalcemia was confirmed in 11 of the 16 patients in whom elevated-serum level or positive immunohistochemistry of PTHrP was observed. Hypercalcemia and accompanying renal insufficiency resolved quickly, particularly in patients treated with bisphosphonate. t(17;19) or add(19)(p13) was detected in five patients among 17 patients in whom karyotypic data were available, and the presence of E2A-HLF was confirmed in these five patients. All five patients with t(17;19)-ALL relapsed very early. Excluding the t(17;19)-ALL patients, the final outcome of ALL accompanied by hypercalcemia was similar to that of all childhood ALL patients, indicating that the development of hypercalcemia itself is not a poor prognostic factor.
Inukai
T
T
Department of Pediatrics, University of Yamanashi, School of Medicine, Yamanashi, Japan. tinukai@yamanashi.ac.jp
Hirose
K
K
Inaba
T
T
Kurosawa
H
H
Hama
A
A
Inada
H
H
Chin
M
M
Nagatoshi
Y
Y
Ohtsuka
Y
Y
Oda
M
M
Goto
H
H
Endo
M
M
Morimoto
A
A
Imaizumi
M
M
Kawamura
N
N
Miyajima
Y
Y
Ohtake
M
M
Miyaji
R
R
Saito
M
M
Tawa
A
A
Yanai
F
F
Goi
K
K
Nakazawa
S
S
Sugita
K
K
D000293:Adolescent; D002118:Calcium / Q000097:blood; D002648:Child; D002675:Child, Preschool; D002886:Chromosomes, Human, Pair 17; D002888:Chromosomes, Human, Pair 19; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000150:complications* / Q000235:genetics*; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000150:complications / Q000235:genetics*; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
D004268:DNA-Binding Proteins; C076554:E2a-Hlf fusion protein, human; D015514:Oncogene Proteins, Fusion; D044162:Parathyroid Hormone-Related Protein; D014157:Transcription Factors; D002118:Calcium