The value of combination therapy in adult acute myeloid leukemia with central nervous system involvement.
OBJECTIVE
In adult patients with acute myeloid leukemia (AML), central nervous system (CNS) involvement is a rare event and treatment has not yet been defined. Because there are no definitive data as to the most appropriate therapeutic approach to CNS leukemia in AML, we retrospectively analyzed a cohort of AML patients with meningeal leukemia in order to increase our knowledge on this particular matter.


METHODS
Out of 410 patients with de novo AML observed at our Institute from 1986 to 1995, 9 (2.2%) showed CNS leukemia (CNSL) during the follow-up. CNSL was treated as follows: in a first group of 4 patients we combined systemic HD Ara-C 3 g/m2 (every 12 hours by 3-hour infusion, for 6 doses), cranial radiation therapy and intrathecal (IT) methotrexate (MTX); a second group of 4 patients was treated with HD Ara-C, IT MTX without cranial irradiation; HD Ara-C alone was administered in one patient.


RESULTS
All patients of the first group and 2 patients of the second who achieved a complete remission (CR) had a median survival of 10 months (range 5-25+) after CNS involvement, while for the non-remitters it was 2 months (range 1-5). The only patient still living underwent allogeneic bone marrow transplantation.


CONCLUSIONS
The combination treatment of HD Ara-C, IT MTX and cranial irradiation is well tolerated and seems to be an effective therapy for CNSL, presenting a high incidence of neurologic CR that correlates with a longer survival. As expected, the number of AML patients with CNSL was small, due to the fact that CNS in those patients is a rare complication. However, this study provides further information about the therapeutic possibilities in such restricted subsets of AML patients.
Castagnola
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Divisione di Ematologia, IRCCS Policlinico San Matteo di Pavia, Università degli Studi di Pavia, Italy.
Nozza
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Corso
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Bernasconi
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D000293:Adolescent; D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015331:Cohort Studies; D003561:Cytarabine / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy / Q000473:pathology; D007948:Leukemia, Monocytic, Acute / Q000188:drug therapy / Q000473:pathology; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology*; D015479:Leukemia, Myelomonocytic, Acute / Q000188:drug therapy / Q000473:pathology; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008577:Meningeal Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged
D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D008727:Methotrexate