Adult acute leukemia.Frequency of central nervous system involvement in long term survivors

Abstract

The incidence and frequency of CNS relapses in long term surviving adults, age eighteen and over, covering the period 1967-1972, were presented. Four of 20 patients with ANLL and 12 of 24 patients with ALL were demonstrated to have CNS leukemia during the course of their illness. The onset of neurologic manifestation in three of four ANLL patients with CNS leukemia w a s observed within three months of the diagnosis, whereas it was delayed to 6-12 months interval in eight of 12 ALL patients. CNS relapses, a major determinant for CNS prophylactic and maintenance therapy, were observed in 75% of the patients with ALL and none in ANLL patients who were treated with I.T. chemotherapy and cranial radiation of 2000 R. Therefore, our observation suggests that CNS prophylactic and maintenance therapy should be of value in adults with ALL as in children; whereas, in ANLL, further observation is warranted before any definite therapy can be advocated.cac~r 40:1304-1306, 1977. ITH THE INCREASED RECOGNITION OF CEN-tral nervous system (CNS) involvement in children with acute lymphoblastic leukemia (ALL) and the subsequent introduction of CNS prophylactic and maintenance therapy, the overall survival in childhood acute leukemia has improved tremendously. In the past few years, our observationse and others"" have also shown an increase in CNS complications in adults with acute leukemia. However, the applicability of CNS prophylactic and maintenance therapy is still unsettled. This paper reports our follow-up observations on adult long-term survivors with acute leukemia, which show that the increased frequency of CNS relapses, a major determinant for CNS maintenance therapy, was seen only in ALL and not in ANLL patients, once adequately treated. were evaluated. Patients with acute stem cell and undifferentiated leukemia were included under acute lymphoblastic leukemia (ALL), and all granulocytic leukemia and its subtypes were included under acute non-lymphocytic leukemia (ANLL). All patients who presented initially as lymphoma with subsequent leukemic conversion (lymphosarcoma cell leukemia) were considered to be a lymphoma from inception and have been recently reported7 and were excluded from this study. MATERIALS AND METHODS AllSeventy-six ANLL and thirty-seven ALL patients were seen at Walter Reed General Hospital during that period. Excluding all ALL patients who were on CNS prophylaxis, there were 20 patients with ANLL and 24 ALL patients who survived over 12 months to four years. Among the long survivors, four ANLL and 12 ALL patients were demonstrated to have CNS leukemia by the following criteria: 1) the presence at lumbar puncture of ten or more mononuclear and/or blast cells/mmain the absence of positive bacteriologic and fungal cultures or of gross blood contamination and/or 2) the presence of leukemic infiltration of the brain and/or the leptomeninges at autopsy.The diagnosis of acute leukemia was made by examinations of the peripheral blood and bone marrow aspirates including bone marrow biopsies and cytochemical st...

VE-cadherin and PECAM-1 enhance ALL migration across brain microvascular endothelial cell monolayers

“…[13, 20, 21] As adhesion of a circulating leukemic cell to the endothelial cells that compose the BBB may represent the first step of invasion into the CNS and models of immune cell invasion of the CNS are derived from inflammatory settings, we first explored the role of inflammation in our model. While exposure of HBMEnd to TNF-α and thrombin increased ICAM-1 and VCAM-1 expression and disrupted endothelial barrier resistance as is seen in inflammation, respectively, exposure of HBMEnd to REH, Nalm-27, or SUP-B15 cells did not promote upregulation of HBMEnd ICAM-1 or VCAM-1 and disrupt barrier function as measured by ECIS (Figure 1A and B).…”

Central Nervous System Prophylaxis and Treatment in Acute Leukemias

“…In the absence of CNS prophylaxis, over 30% of patients with ALL who achieve a complete response may develop CNS relapse, and risk has decreased in the modern era with better systemic control of disease [7,8]. With modern regimens with improved CNS penetrance, including high-dose methotrexate and cytarabine and tailored intrathecal (IT) therapy, the risk of isolated CNS relapse is low and thus the toxicity and benefit of CNS prophylaxis must be weighed [9].…”

“…Using induction and consolidation with regimens containing cytarabine and an anthracycline, followed by allogeneic stem cell transplant when feasible, CNS relapse occurred in 0.3% of patients, compared to marrow relapse in 51% [15]. In one older study, young age, increased white blood cell count, a prominent monocytic component, corebinding factor (CBF) AML (i.e., inversion 16 or t [8,21]), chromosome 11q23 abnormalities, trisomy 8, and FLT3-ITD mutations may be associated with increased risk of CNS involvement. However, the use of high-dose cytarabinebased regimens for patients with CBF AML may mitigate the risk in this population.…”

Central nervous system prophylaxis in haematological malignancies

“…Before CNS prophylaxis was introduced, between 50 and 75 per cent of children relapsed in the CNS, presenting a major barrier to cure. Adults who do not receive CNS prophylaxis have a likelihood of CNS recurrence of approximately 30% 5 . These differences could reflect the more aggressive treatment approaches used to treat adults.…”