Clinical trial NCT03410407: Central Nervous System (CNS) Involvement in Acute Myeloid Leukemia (AML)
Official title: Central Nervous System (CNS) Involvement in Acute Myeloid Leukemia (AML): an Observational Retrospective Multicentre Study on Patients Previously Registered in GIMEMA Clinical Trials
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Acute Myeloid Leukemia
Keywords: Acute Myeloid Leukemia
Central Nervous System
Relapse
Prognostic factors
Lead sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
Sponsor class: OTHER
First posted: 2018-01-25
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: AML patients previously enrolled in GIMEMA studies for AML treatment

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of CNS relapses
timeFrame: At 12 months from study start
Secondary outcomes:
measure: Number of patients in complete response
timeFrame: At 12 months from study start
measure: Number of patients alive
timeFrame: At 12 months from study start
Other outcomes:
Locations:
city: Alessandria
country: Italy
facility: Aon Ss. Antonio E Biagio E C. Arrigo - Alessandria - Soc Ematologia
city: Ancona
country: Italy
facility: Aou Ospedali Riuniti "Umberto I - G.M. Lancisi - G. Salesi"- Ancona - Sod Clinica Ematologica
city: Bari
country: Italy
facility: Aou Consorziale Policlinico - Bari - Uo Ematologia Con Trapianto
city: Cagliari
country: Italy
facility: Ao Brotzu, Presidio Ospedaliero A. Businco - Cagliari - Sc Ematologia E Ctmo
city: Milano
country: Italy
facility: Fondazione Irccs Ca' Granda, Ospedale Maggiore Policlinico - Milano - Ematologia - Padiglione Marcora
city: Napoli
country: Italy
facility: Aou Federico Ii - Napoli - Uoc Ematologia
city: Novara
country: Italy
facility: Aou Maggiore Della Carita' Di Novara - Scdu Ematologia
city: Perugia
country: Italy
facility: Ao Di Perugia, Ospedale S. Maria Della Misericordia - Ematologia E Trapianto Midollo Osseo
city: Piacenza
country: Italy
facility: Asl Di Piacenza, Ospedale "Guglielmo Da Saliceto" - Ematologia E Centro Trapianti
city: Roma
country: Italy
facility: Aou Policlinico Tor Vergata - Roma - Uoc Trapianto Cellule Staminali
city: Roma
country: Italy
facility: Dipartimento di Biotecnologie Cellulari ed Ematologia, "Sapienza", Università di Roma
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli Irccs - Roma - Area Ematologica
city: San Giovanni Rotondo
country: Italy
facility: Ente Ecclesiastico Casa Sollievo Della Sofferenza - San Giovanni Rotondo - Ematologia
city: Udine
country: Italy
facility: Asui Di Udine - Presidio Ospedaliero "Santa Maria Della Misericordia" - Clinica Ematologica
Study officials:
affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, "Sapienza", Università di Roma
name: Alessandro Pulsoni
role: STUDY_CHAIR
affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, "Sapienza", Università di Roma
name: Livio Pagano
role: STUDY_DIRECTOR
References: