Continuous hemodiafiltration for hypercytokinemia in tumor lysis syndrome

Abstract

Tumor lysis syndrome (TLS) is a critical condition being presented with hyperuricemia, electrolyte disturbance and acute renal failure, and it is thought to be caused by massive release of cellular breakdown products due to substantial destruction of tumor cells. Some TLS patients develop multiple organ failure. Blood purification, such as hemodialysis is often performed on patients with TLS as a renal replacement therapy. We noticed that some TLS patients also had hypercytokinemia and speculated that such hypercytokinemia might be associated with the pathophysiology of TLS. On the other hand, we reported that continuous hemodiafiltration using a polymethyl methacryrate membrane hemofilter (PMMA-CHDF) can eliminate cytokines from the blood stream of patients. We therefore applied PMMA-CHDF on four patients with TLS with the expectation that PMMA-CHDF also can be an effective treatment against hypercytokinemia in TLS patients. All patients had hematological malignancy and received induction anti-tumor chemotherapy. During the chemotherapy, they developed hyperuricemia, hyperpotassemia and acute renal failure, and were diagnosed to have TLS. Two of them developed multiple organ failure. In one patient the failing organs were the lung and kidney, and in the other patient the failing organs were the heart, lung and kidney. In all TLS patients, blood levels of tumor necrosis factor alpha, IL-6 and IL-10 before the initiation of PMMA-CHDF were 102 ± 85 pg/ml, 1097 ± 546 pg/ml and 98 ± 83 pg/ml, respectively (mean ± standard deviation). After 3 days of CHDF treatment, blood levels of those cytokines were 37 ± 55 pg/ml, 326 ± 511 pg/ml, and 9 ± 8 pg/ml, respectively. All cytokine levels were thus significantly decreased with 3 days of PMMA-CHDF treatment (P < 0.05, P < 0.05, P < 0.05, paired t test). After the PMMA-CHDF treatment, their clinical conditions were improved, and all patients survived. In one of these patients, the blood levels of each cytokine before and after the PMMA membrane homofilter were measured and the clearance of these cytokines was calculated. The clearance of each cytokine is as follows; tumor necrosis factor alpha 13.9 ± 6.4 ml/min, IL-6 4.9 ± 2.4 ml/min, IL-8 21.6 ± 3.9 ml/min and IL-10 11.1 ± 6.4 ml/min,. From those results, we conclude that TLS could be caused by hypercytokinemia probably due to massive tumor cellular breakdown by chemotherapy and that PMMA-CHDF is an effective treatment for TLS patients not only as renal replacement therapy, but also as a cytokine modulator.