Shimonodan Hidemi, Nagayama Jun, Nagatoshi Yoshihisa, Hatanaka Michiki, Takada Akiko, Iguchi Haruo, Oda Yoshinao, Okamura Jun
Section of Pediatrics, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka 811-1395, Japan.
Pediatr Blood Cancer. 2005 Sep;45(3):333-9. doi: 10.1002/pbc.20357.
Osteopathy is one of the common initial symptoms of acute lymphocytic leukemia (ALL) in children and adolescents, but multiple osteolysis accompanied by hypercalcemia is rarely observed.
We treated a 14-year-old female who had multiple osteolytic lesions and hypercalcemia at initial onset of ALL. In this case we examined some humoral factors, which are known to associate with hypercalcemia in malignancies.
Parathyroid hormone-related peptide (PTHrP) was elevated in serum, and reverse transcriptase-polymerase chain reaction and immunohistochemistry revealed that the lymphoblasts produced PTHrP directly. Other humoral factors related to hypercalcemia were not detected. ALL relapsed in the bone marrow 3 months after achieving complete remission, and hypercalcemia and elevation of serum PTHrP were also observed. A second remission could not be achieved and hypercalcemia continued. The patient received allogeneic bone marrow transplantation. The serum calcium level became normal after the conditioning therapy. Before engraftment, however, the patient died of infection.
The present case suggests that blast-producing PTHrP might be associated with multiple osteolytic lesions and hypercalcemia. PTHrP expressed in the lymphoblasts may, in itself, confer a survival advantage to lymphoblasts and contribute to the refractory nature of the disease.
骨病是儿童和青少年急性淋巴细胞白血病(ALL)常见的初始症状之一,但伴有高钙血症的多发性骨质溶解很少见。
我们治疗了一名14岁女性,她在ALL初发时就有多处溶骨性病变和高钙血症。在该病例中,我们检测了一些已知与恶性肿瘤高钙血症相关的体液因子。
血清中甲状旁腺激素相关肽(PTHrP)升高,逆转录聚合酶链反应和免疫组织化学显示淋巴母细胞直接产生PTHrP。未检测到其他与高钙血症相关的体液因子。在完全缓解3个月后,ALL在骨髓中复发,同时也观察到高钙血症和血清PTHrP升高。未能实现第二次缓解,高钙血症持续存在。患者接受了异基因骨髓移植。预处理治疗后血清钙水平恢复正常。然而,在植入前,患者死于感染。
本病例提示,产生PTHrP的母细胞可能与多发性溶骨性病变和高钙血症有关。淋巴母细胞中表达的PTHrP本身可能赋予淋巴母细胞生存优势,并导致疾病的难治性。