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The frequency of prior occupational, accidental, or therapeutic radiation exposure was significantly higher for hairy cell leukemia patients than for a control group of solid tumor patients (8/23 vs. 4/56, P0.01). Hairy cell leukemia patients were also more frequently involved in occupations at high risk of radiation exposure such as chemist, engineer, physicist, and health care facility worker (7/23 vs. 4/56, P0.01). The observation that the incidence of thyroid disorders among hairy cell leukemia patients was also unusually high (5/23 vs. 2/56, P0.05) was interpreted as further indirect evidence of excessive radiation exposure. It appears that radiation exposure may be an important contribution factor in the development of some case of hairy cell leukemia.

Eighty-seven adult patients who had achieved bone marrow remission of leukemia developed one or more episodes of meningeal leukemia. Multiple patient characteristics were examined for their effect on probability of achieving complete remission from meningeal disease and for their effect on duration of meningeal remission. Presence of obtundation (P less than 0.01) or other symptoms of meningeal disease (P = 0.02) were associated with a low remission induction rate. Other factors which tended (P = 0.06-0.20) to be associated with low remission induction rates included high cerebrospinal fluid (CSF) opening pressure, absence of splenomegaly at initial diagnosis, high peripheral blood leukocyte count (WBC) at the episode of marrow disease most recently preceding the meningeal disease, and use of only one as opposed to two or more intrathecal drugs as treatment. Factors associated with long duration of meningeal remissions included diagnosis (AML greater than acute undifferentiated leukemia greater than ALL, P = 0.05), absence of symptoms (P = 0.04), low CSF WBC (P = 0.01), rapid attainment of meningeal remission (P = 0.01), rapid attainment of initial bone marrow remission (P = 0.02), and long duration of initial bone marrow remission (P less than 0.01). Absence of cranial or peripheral neuropathies, low CSF protein and opening pressure, and short time interval between diagnosis of marrow and meningeal disease also tended (P = 0.06-0.20) to be associated with long meningeal remissions. Patients treated according to an intensive protocol utilizing cranial irradiation and triple drug treatment via an Ommaya reservoir had substantially longer meningeal remissions than did patients treated with less intensive therapy (P = 0.01). Relapse-free survival curves suggest that some patients are cured of their meningeal disease.

Of 22 patients with hairy cell leukemia, 18 developed life-threatening infections. Susceptibility to infection appeared to be increased nonspecifically, in that a wide range of infecting organisms were noted. Pseudomonas aeruginosa was the organism isolated most frequently. Four patients had disseminated Mycobacterium kansasii, and one had bacillus Calmette-Guerin lymphadenitis. Two patients developed serious fungal infections (Candida albicans in one and Allescheria boydii in the other). One patient had disseminated cytomegalovirus infection and two had toxoplasmosis. Splenectomy did not appear to decrease the infection rate. The infection rate initially increased following chemotherapy (P less than 0.001), then returned to pretreatment levels by two months following treatment. Infections were most frequent during granulocytopenia (P less than 0.01), but granulocytopenia was not a prerequisite for either life-threatening or fatal infections. Monocytopenia may be a more important factor than granulocytopenia in risk of infection in hairy cell leukemia patients.

Thirty-five patients with malignant brain tumors (23 with primary brain tumors and 12 with brain metastases) progressing after cranial irradiation +/- chemotherapy received cisplatin, 60 to 120 mg/m2, into the internal carotid artery by a transfemoral approach. Courses of therapy were repeated every 4 weeks. Therapeutic evaluation was performed monthly using the CT scan of the brain and clinical neurologic examination. Thirty patients were evaluable for response. Of 20 evaluable patients with primary malignant brain tumors, 6 responded to therapy and 5 had stable disease. The median time to tumor progression for responding patients was 33 weeks, for stable patients 16 weeks, and 13 weeks for all patients. Five of 10 evaluable patients with brain metastases responded to intracarotid cisplatin, and 2 patients had stable disease. The estimated median time to progression for responding patients was 30+ weeks and 12+ weeks for patients with stable disease. Side effects included seizures in 5 courses, mental agitation and motor restlessness in 1, and transient hemiparesis in 7. One patient may have had a drug-related death, and one patient appeared to develop encephalopathy after treatment. Five patients had clinical deterioration in vision; in two patients it was bilateral. Intracarotid cisplatin has definite activity in patients with malignant primary brain tumors and in patients with brain metastases. The recommended starting dose for intracarotid cisplatin is 60 to 75 mg/m2. At this dose level side effects are uncommon, but includes the risk of neurologic and retinal toxicity.

Central nervous system (CNS) involvement occurred in 45 of 222 (20.3%) leukemic adults achieving bone marrow (BM) complete remission (CR), including 12 of 23 (52%) acute undifferentiated leukemia (AUL), 12 of 32 (39%) lymphoma leukemia, 5 of 26 (19%) acute lymphoblastic leukemia, and 16 of 142 (11%) acute myelogenous leukemia. Risk factors for CNS disease were lactic dehydrogenase (LDH) greater than or equal to 25,000/mm3. AUL morphology, age less than 20 years, and extramedullary involvement were most significant. Pattern of CNS involvement varied with morphology. Survival after CNS relapse depended most on BM status and symptoms. Duration of CNS CR was longest for asymptomatic patients with low CSF cell counts. Also important were duration of first BM CR, ease of achievement of initial BM CR, and leukocyte count (original and at most closely antecedent BM involvement), reflecting the common origin of BM and CNS leukemic cells. Central nervous system relapse generally did not shorten BM CR or survival, although early primary CNS relapse was associated with early BM relapse.

Prognostic factors were examined in 31 patients with hairy cell leukemia seen at M. D. Anderson Hospital. Long survival from presentation was significantly associated with ease of aspiration of iliac crest bone marrow, absence of major infection, hemoglobin greater than 10 g/dl, and absence of a prior history of pneumonia. Long survival from splenectomy was associated most closely with absence of a prediagnosis history of pneumonia, suggesting that a long-standing host defense abnormality may exist that is not corrected by splenectomy. Generally, patients with sustained improvement in hematologic parameters postsplenectomy lived longest from splenectomy, although the results were not statistically significant.