SYSTEMIC HYPERTHERMIA IN THE TREATMENT OF HIV-RELATED DISSEMINATED KAPOSIS-SARCOMA - LONG-TERM FOLLOW-UP OF PATIENTS TREATED WITH LOW-FLOW EXTRACORPOREAL PERFUSION HYPERTHERMIA

Treatment Of HIV and related malignancies with pharmacologic and biolo gic agents has not appreciably modified the course of disease. Immunol ogic impairment remains the critical factor in response. We report the long-term results of a single session Of low-flow (0.3 L/min) extraco rporeal perfusion hyperthermia on 29 men and 2 women with disseminated Kaposi's sarcoma and profound immunologic impairment. Any antiretrovi ral drug employed by the patient was stopped 72 hours prior to treatme nt and withheld during the period of follow-up. Core temperature was r aised to 42-degrees-C and held for 1 hour with extracorPoreal perfusio n and ex vivo blood heating to 49-degrees-C as the means of temperatur e control. Of 31 patients, 2 died of complications secondary to treatm ent (cardiac arrhythmia; CNS bleed). There were two cases of intravasc ular coagulopathy. Pressure point skin damage may occur despite adequa te cushioning. At 30 days posttreatment complete or partial regression s were seen in 20/29 of those treated, with regressions persisting in 14/29 of those treated by 120 days posttreatment. At 360 days, 4/29 ma intain tumor regressions with 1 in complete remission (at 26 months). The Patient in complete remission remains culture-negative and PCR-neg ative for HIV. CD4+ counts rose from around 250 to, and remain around, 800 in this man. Selected healed lesions were biopsied to demonstrate tumor absence- Patients were selected for treatment if pretreatment t esting of the tumor showed regression in vitro with heat exposure. Ana lysis of the early and midterm failures showed little sustained rise o f the CD4+ cells if presenting total CD4+ counts were below 50 and had been at such low levels for extended periods, although other surrogat e markers of HIV activity declined (semiquantitative PCR) during this period and is felt to support the hypothesis of apoptosis Proposed in this illness. Analysis of the tumors of the few men not responding dem onstrated elevated levels of IL-6 as compared to resPOnders (12 vs <1 pg/ml). At 120 days 29/31 patients remained alive (expected, 20). At 3 60 days, 21/31 remained alive (expected, 11). In no patient was HIV ac tivity stimulated with heat exposure., CMV retinitis did clear in some patients treated (both techniques), but treatment alone did not preve nt later development of retinopathy. EBV parameters were markedly alte red in the short term with heat exposure in some patients. Few patient s showed herpes simplex activation. Varicella-zoster virus remitted in some patients. There is utility in the use of systemic hyperthermia t o control HIV and related malignancy. Further study of agents potentia ted heat is indicated.