Transient massive peripheral blood blastosis in patient with renal clear-cell carcinoma after treatment with high-dose recombinant interleuklin-2

A 35-year-old woman presented at the Orthopaedic Department with pain in the right hip. Pelvic CT showed a lytic lesion in the sacrum with an associated soft-tissue mass. CT-guided needle biopsy of the bone lesion disclosed clear-cell carcinoma metastasis. Further more, abdominal CT revealed a well-defi ned mass in the left kidney measuring 8×9 cm; thoracic CT showed other abnormalities. A nephrectomy was done for diagnostic and therapeutic purposes. As a result of the diagnosis of stage IV clear-cell renal carcinoma, which had a Fuhrman grade IV, an Eastern Cooperative Oncology Group grade 1, bone dissemination, and a high-risk level according to the University of California Los Angeles integrated staging system, high-dose recombinant interleukin-2 (HD-IL2) was started after recovery from surgery. The patient received 600 000 U/kg of intravenous IL-2 every 8 h for 5 days in two courses, the fi rst course beginning on day 1 and the second beginning on day 15. Throughout HD-IL2 administration, the patient also received commonly used concomitant medication. Baseline blood count before the second course of HD-IL2 was 11·1×10/L of leucocytes (44% neutrophils, 42% lymphocytes, 7% monocytes, 6% eosinophils, and 1% basophils), 114 g/L of haemoglobin, and 391×10/L of platelets. After the fourth dose of the second course of HD-IL2, the patient presented tachycardia (130 bpm), hypotension (70/30 mmHg), and oligoanuria with impairment of renal function (creatinine level 176·8 μmol/L). Metabolic acidosis (pH 7·2; HCO3 14·8 mEq/L) was also recorded. Finally, hypoxaemia (sO2 92%) and radiological bilateral interstitial infi ltrates, shown by chest radiography, revealed pulmonary oedema. The patient was subsequently admitted to the intensivecare unit where supplemental oxygen (3 L/min) and HCO3 were then initiated. Additionally, hypotension was treated with both crystalloids and norepinephrine administration (0·2 μg/kg per min). HD-IL2 was discontinued after the 12th dose of the second course because of its toxic eff ects. Symptoms resolved 2 days after the last dose of HD-IL2 was given; however, blood count showed leucocytosis (22×10/L) with mild anaemia (Haemoglobin 104 g/L) and thrombocytopenia (113×10/L). Diff erential blood count showed 53% undiff erentiated blast cells; 53% erythroblasts were also counted (fi gure). Acute leukaemia was ruled out by means of a bone marrow aspirate done 16 h later. Bone marrow smears showed a hypercellular marrow with a normal myeloid and erythroid ratio, a leftward shift of myeloid series with 2% undiff erentiated blast cells and 11% myeloid blast cells, and predominance (48%) of semimature and, to a lesser extent, mature granulopoietic cells with no dysplastic features. Megakaryocytic hyperplasia was also noted. No metastases were seen. Cytogenetic analysis done on 30 metaphases from unstimulated culture of the bone-marrow sample showed a 46XX karyotype with no structural chromosome anomaly. Blood count returned to baseline levels within the following 2 days. 6 weeks after the last dose of HD-IL2 had been given, an enlargement (35% increase in the larger diameter) of the bone mass was noted. Because the disease was refractory to immunotherapy, the patient has started treatment with sunitinib (SU11248) within a clinical trial. Clear-cell renal carcinoma is the most common adult renal neoplasm. HD-IL2 received approval from the Food and Drug Administration in 1992 for the treatment of patients with stage IV renal-cell carcinoma, on the basis of results of 255 patients who were included in seven phase II trials. In selected patients, the complete response rate was 7% (median follow up of 54 months, range 3–131 months) with actuarial curves predicting that 60% would be free Lancet Oncol 2007; 8: 275–76