Depressed cellular immune function and increased susceptibility to infection characterize familial erythrophagocytic lymphohistiocytosis (FEL), a usually fatal autosomal recessive disease. One component of the immunodeficiency is plasma-mediated inhibition of lymphocyte proliferation. We have tested whether repeated plasma or blood exchange would decrease plasma inhibitory activity and improve cellular immune function in FEL. Following this treatment, reduction in plasma inhibitory activity, reversal of depressed antigen-specific lymphocyte proliferative responses and monocyte antibody-dependent cytotoxic function in vitro, and clinical improvement were complete in two and partial in one of three patients studied. Relapse, which was ultimately fatal, was associated with recurrence of the immune defects. These findings suggest that cellular immunodeficiency in FEL is acquired and possibly related to circulating immunosuppressive activity, the removal of which is associated with transient immunologic and clinical recovery.

Adriamycin and daunomycin are highly effective anti-tumor agents but have been known to be cardiotoxic in dosages > 500 mglm'. Echocardiograms were performed in 54 pediatric patients with a variety of malignant diseases in an attempt to detect early evidence of anthracycline-induced cardiac toxicity. Thirty baseline studies were performed while 81 studies were done during and/or following anthracycline chemotherapy. Baseline left ventricular (LV) function was normal; shortening fraction = 34 * 1% and percent heart rate predicted velocity of fiber shortening = 109 ?; 3%. No significant reduction in LV performance occurred until cumulative doses exceeded 250 mg/m2. Between 250 mg/m2 and 450 mg/m2 mean shortening fraction = 30 f 1% (p < 0.025) and percent of predicted shortening velocity = 93 * 4% (p < 0.005). Above 450 mg/m2 a further significant decrease in LV function was noted: shortening fraction = 21 * 3% and percent of predicted shortening velocity = 63 k 10%. Two of the five patients in this group developed congestive heart failure. We currently recommend that echocardiograms be performed prior to the start of anthracycline therapy and repeated every 80 to 120 mg/m2 until a cumulative dose of 250 mg/m2 is reached. Thereafter, echocardiograms should be performed prior to each additional dose. Therapy should be discontinued when shortening fraction < 20% and percent of predicted shortening velocity < 50%. However, selected patients with satisfactory LV performance who have received dosages of 500 mg/m2 may be considered for continued chemotherapy.