Natural history of central nervous system acute leukemia in adults

Abstract

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.

In Vivo Therapy of Neoplastic Meningitis with Methotrexate and 5-[125I]iodo-2'-deoxyuridine

“…This disease develops in approximately 5% to 8% of patients with solid tumors, especially adenocarcinomas of the breast and lung as well as melanomas (1,2), in 5% to 29% of patients with non-Hodgkin's lymphoma (1,3), and in 11% to 70% of patients with leukemia (1,4). Tumor involvement of the leptomeninges is also a serious problem in certain primary neural tumors including medulloblastomas (5).…”

Central nervous system involvement at first relapse in patients with acute myeloid leukemia

“…Central nervous system involvement at first relapse was documented in 6 patients: 2 had isolated cases, one had another extramedullary relapse location, and half had simultaneous bone marrow involvement, as reported in other studies. 6,10 The median time to central nervous system relapse was seven months (range 1-16 months) compared with nine months (range 1-167 months) for isolated bone marrow relapse. The median time to central nervous system relapse reported here is sooner than the 12 and 19 months reported by Castagnola et al 10 and Holmes et al, 7 respectively, in adult AML patients, but similar to the four months described in a pediatric series.…”

“…3 The present study showed an overall 5-year cumulative incidence of central nervous system relapse of 1.3% (either isolated or combined with bone marrow relapse), which is lower than the previously reported incidence of 3-11%. [4][5][6][7][8][9][10] The different statistical methods used to calculate the incidence in our study (competing risk analysis using the CI) compared with others (crude incidence) may explain, at least in part, our different rate of central nervous system relapse. Another explanation is that most previous studies were performed exclusively in patients treated with old chemotherapy protocols in the 1980s, 4-9 whereas in our series most of the patients were treated with modern protocols.…”

“…In fact, the cumulative incidence of relapse was 3.9% in groups 1 and 2 (old protocols) which is consistent with the previously published series, 4-9 compared with 0.3% in groups 3 and 4 (modern protocols). Unlike other studies, 4,[6][7][8][9][10] patients with biological entities requiring characteristic treatment, such as those with acute promyelocytic leukemia, 2 were excluded from the present analysis. Our study included a series of unselected, consecutively diagnosed, adult acute myeloid leukemia patients and, therefore, shows an unbiased incidence of central nervous system relapse.…”

“…1 To our knowledge, this complication has been critically assessed in patients with acute promyelocytic leukemia (APL) 2 and children with acute myeloid leukemia. 3 However, the prevalence of and risk factors for central system involvement in adult patients with acute myeloid leukemia have been analyzed in only a few studies carried out in the 1980s [4][5][6][7][8] and 1990s. 9,10 No studies to date have analyzed the incidence of and risk factors for central nervous system relapse using the most appropriate statistical methods, i.e.…”