P049 | INTENSIFIED CENTRAL NERVOUS SYSTEM (CNS)-DIRECTED THERAPY IMPROVES PROGNOSIS IN ADULT ACUTE LYMPHOBLASTIC LEUKEMIA PATIENTS WITH OCCULT CNS LOCALIZATION. PRELIMINARY RESULT OF A CAMPUS ALL OBSERVATIONAL PROSPECTIVE STUDY (NCT05772000)

Introduction. Multiparameter flow cytometry (FC) has demonstrated superior sensitivity over conventional cytology (CC) in detecting occult central system disease (OCNSD) in adult acute lymphoblastic leukemia (ALL) patients (pts), a condition associated with a more unfavorable outcome. This has led to intensified CNS-directed therapy (CNSDT) in OCNSD pts, though its impact on relapse risk remains uncertain. Aim. To prospectively assess disease-free survival (DFS) of OCNSD pts via a multicenter, observational Campus ALL study. Methods. We recorded data on all consecutive cerebrospinal fluid (CSF) samples from adult ALL pts (since 1 June 2020) analyzed by CC and FC. Data on demographics, ALL type, biology, CSF features, intrathecal (IT) prophylaxis/therapy, FC event count, treatments, complete remission (CR), relapse (RE), and mortality were also collected. Positivity by CC was defined by standard criteria. FC used 8–10 antibodies, with at least 10 clonal and abnormal events considered positive. CSF results identified 3 groups: manifest CNS disease (MCNSD, CC+FC+), OCNSD (CC–FC+), and CNS neg (CC–FC–). Results. A total of 134 pts (median age 48, range 19–81; M/F 52%/48%) were enrolled across 14 Italian centers. Treatments followed the GIMEMA/NILG or Hyper-CVAD protocols. CNSDT intensification consisted of biweekly IT therapy until CSF blast clearance, followed by two weekly doses. A CR was achieved in 82% of pts (111/134), with a RE in 38/110 (34.5%) including one isolated CNS RE. MCNSD, OCNSD and CNS neg were found in 14 (10%), 10 (8%), and 110 (82%) pts, respectively. CNSDT was intensified in all MCNSD and in 9/10 OCNSD pts. In the OCNSD, the median of the total acquired, and the leukemic events were 4548 (60-79697) and 61 (13-2100), respectively. No significant differences were observed among groups for gender, B/T lineage, cytogenetic/genetic features. Compared with CNS neg group, OCNSD pts had more frequent WBCc >30x109/L (p=.016). The 3-year DFS in CNS neg, OCNSD and MCNSD pts did not differ: 62% (95% CI, 51.1-75), 47% (95% CI, 21.5-100) and 35% (95% CI, 12.3-100), respectively (p<0.42) (Figure). Conclusions. Our data confirm that OCNSD is uncommon. Apart from high WBC, no other predictive feature was identified, highlighting the need of routine FC in all pts. Although preliminary, our findings suggest that intensified CNSDT may improve prognosis in OCNSD pts, which could be particularly relevant as systemic chemotherapy strategies are being de-escalated.