Central Nervous System (CNS) Involvement in Acute Myeloid Leukemia (AML)
Central Nervous System (CNS) Involvement in Acute Myeloid Leukemia (AML)
The present study aims at evaluating the prognostic factors at diagnosis predicting Central
 Nervous System (CNS) relapse in order to identify a group of patients with higher risk of CNS
 involvement in which prophylaxis with liposomal Ara-C or other drugs should be indicated.
CNS involvement in AML is a rare event, poorly detailed in literature. Few data are available
 in pediatric cases, and less frequent in adult cases. Predisposing factors for AML adult
 patients with CNS involvement include young age, higher level of lactate dehydrogenase and
 white blood cells (WBC) counts at diagnosis, FAB M4 and M5 morphology, chromosome 16
 inversion and chromosome 11 abnormality. No consensus exists regarding the treatment of AML
 patients with CNS involvement. Protocols used for AML treatment are largely based on high
 doses of cytarabine, which penetrate the blood brain barrier. On the contrary of acute
 lymphoid leukemia (ALL), prophylaxis with intrathecal chemotherapy is not routinely used in
 AML. Roudoski et al. showed that, when lumbar puncture (LP) was performed in 1,370 patients,
 only if clinically indicated, CNS disease was detected in 45 (3.3%) patients. Another 42
 patients underwent routine LP as part of an investigational protocol, and in 8 (19%) CNS
 disease was detected (P<0.0001). Risk factors included high LDH, African-American ethnicity,
 and young age. Patients receiving high-dose cytarabine and those that did not had similar
 rates of CNS involvement. Disease free survival (DFS) and overall survival were shorter in
 patients with CNS involvement. Treatment in case of CNS involvement is not well established;
 the potential acute and long-term complications associated with cranial irradiation often
 limit its use. Prognosis remains poor also with high doses of cytarabine and/or therapeutic
 intrathecal chemotherapy. Castagnola et al. reported showed the outcome of 9 patients woth
 CNS+ AML: NSL was treated as follows: 4 patients received combined systemic HD Ara-C, 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. 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 after CNS involvement, while for
 the non-remitters it was 2 months. The unique durable response was observed after allogeneic
 bone marrow transplantation. Sanders et al. reported that craniospinal irradiation with or
 without intrathecal chemotherapy appears to be effective at eliminating leukemia in the
 craniospinal axis. However, the eradication of disease in the CNS was not found to be
 effective at preventing disease recurrence in the bone marrow, and despite improved control
 of disease in the CNS, adult patients with a CNS recurrence still had a poor prognosis.
 Furthermore, the rapidly fatal course of disease prevented an assessment of the durability of
 CNS response to irradiation. Aoki et al reported that allogeneic haematopoietic stem cell
 transplantation (HSCT) might improve outcomes for CNS+AML and Bar et al, showed that presence
 of CNS pre-HCT had no independent influence on post transplant outcome, which was primarily
 influenced by status of systemic disease at time of HCT. Due to the rarity of the disease we
 want to collect the data about CNS involvement, either at diagnosis or along the course of
 the disease, in AML patients already registered in previous GIMEMA Studies, trying to
 identify incidence, prognosis, prognostic factors and the best adequate treatment.
Inclusion Criteria:

 -  Signed written informed consent according to ICH/EU/GCP and national local laws (if
 applicable).

 -  Patients aged ≥18 years affected by AML according to the FAB criteria, previously
 enrolled in GIMEMA Studies for AML treatment. AML patients with CNS involvement
 defined by the confirmation of leukemic blast cells in the centrifuged cerebrospinal
 fluid (CSF) with the presence of more than five WBCs in the CSF or the detection of a
 CNS granulocytic sarcoma using computed tomography or magnetic resonance imaging.

 Exclusion Criteria:

 -  Patients with acute promyelocytic leukemia (FAB M3 subtype), antecedent haematological
 diseases or therapy-related AML.