Severe Hypercalcemia as Rare Manifestation of Acute Lymphoblastic Leukemia in Adolescent

Abstract

Background: Hypercalcemia is a rare manifestation of acute lymphoblastic leukemia (ALL). Several studies reported that severe hypercalcemia is very uncommon in pediatric ALL, but there is no report regarding ALL in adolescence and young adult (AYA) which comprises distinct entity with diverse prognosis. Clinical Case: A 18-year-old male presented with prolonged fever, general weakness, fatigue, pale and decrease of body weight for 3 months. He also complained visual disturbances which progressively worsened for 1 month. On admission, systemic examination showed that he was alert, had tachycardia, proptosis of both eyes and splenomegaly. There was neither lymphadenopathy nor thyroid/parathyroid abnormality. Initial laboratory investigation revealed pancytopenia (hemoglobin of 6.8 g/dl, hematocrit of 19.1%, white blood cell count of 3.8 x 109/L with platelets of 58 x 109/L and no blast). There was severe hypercalcemia of 18 mg/dL, hypomagnesemia 1.14 mg/dL, with normal phosphorus level. His serum creatinine level slightly increased to 1.3 mg/dL with filtration rate of 79 ml/min/1.73 m2. Bone marrow evaluation showed blast cells infiltration, consistent with ALL type L3. Leukemia phenotyping revealed B cell-lineage with aberrant exp CD5. CT scan orbita and brain showed bilateral retrobulbar mass and diffuse lytic lesion in skeletal bones due to leukemic cells infiltration. Patient was treated with supplemental oxygen, hydration targeting natriuresis, loop diuretic and steroid. The serum calcium level remained high, thus bisphosphonate was given. There was progressive decline of serum calcium level after therapy. The patient is then prepared to start chemotherapy. Discussion: Hypercalcemia is associated with both PTH or PTH-independent mechanism, including malignancy. It complicates 5–20% of malignancy, but only 0.6–4.8% reported in leukemia. Hypercalcemia in malignancy may present due to: (1) direct invasion of cancer cells to bone and (2) secretion of humoral PTH-related peptide (PTHrP) which mimics PTH. Severe hypercalcemia without inadequate treatment is fatal. Initial treatment of hypercalcemia includes hydration, loop diuretic, calcitonin and bisphosphonate targeting decline of serum calcium level of 3–9 mg/dL in 24–48 hours. The main treatment of leukemia-related hypercalcemia is chemotherapy. Several cases of pediatric ALL reported normocalcemia after starting induction phase of chemotherapy and exerted good prognosis. Conclusion: Hypercalcemia should be investigated in leukemia patients and vice versa. The main aim of therapy is to normalize the serum calcium level and treat underlying causes. In adolescent ALL, adequate treatment of hypercalcemia helps achieving better outcome.