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2806 Central Nervous System Involvement Does Not Worsen Survival in Hematologic or Molecular Relapse of Adult Acute Lymphoblastic Leukemia Patients – Retrospective Analysis By the Czech Leukemia Study Group for Life (CELL)Clinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 612. Acute Lymphoblastic Leukemias: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research, Lymphoid Leukemias, ALL, Epidemiology, Clinical Research, Diseases, Real-world evidence, Registries, Lymphoid Malignancies
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Stepan Hrabovsky1,2*, Cyril Salek3,4, Frantisek Folber1,2*, Jan M Horacek, MD, PhD5,6*, Tomas Szotkowski7,8*, Zdenek Koristek9,10*, Jozef Lukas11,12*, Tomas Arpas1,2*, Denisa Bakesova2*, Martin Cernan7,8*, Veronika Bergerova13*, Jiri Sramek13*, Jan Novak14* and Michael Doubek1,2,15*

1Faculty of Medicine, Masaryk University, Brno, Czech Republic
2Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic
3Institute of Hematology and Blood Transfusion, Prague, Czech Republic
4Charles University in Prague, Prague, Czech Republic
5Department of Internal Medicine IV – Hematology, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic
6Department of Military Internal Medicine and Military Hygiene, University of Defence, Military Faculty of Medicine, Hradec Kralove, Czech Republic
7Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic
8Department of Haemato-oncology, University Hospital Olomouc, Olomouc, Czech Republic
9Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
10Department of Hematooncology, University Hospital Ostrava, Ostrava, Czech Republic
11Department of Hematology and Transfusiology, University Hospital Bratislava, Bratislava, Slovakia
12Faculty of Medicine, Comenius University Bratislava, Bratislava, Slovakia
13Hemato-oncology department, University Hospital Pilsen, Plzen, Czech Republic
14Charles University and Faculty Hospital Kralovske Vinohrady, Prague, Czech Republic
15Central European Institute of Technology (CEITEC), Brno, Czech Republic

Background

Intrathecal prophylaxis for central nervous system (CNS) relapse has been a standard part of adult acute lymphoblastic leukemia (ALL) treatment for years. However, the risk factors and outcomes associated with CNS relapses in adult ALL remain unclear, and there is no standardized treatment protocol for these patients. Given the rarity of CNS relapses, comprehensive data on this subject are lacking.

Methods

We conducted a retrospective analysis of risk factors and outcomes associated with CNS relapse in Czech adult ALL patients. Data were sourced from the ALL registry of the Czech Leukemia Study Group for Life (CELL), including patients from seven Czech and one Slovak hematology-oncology centers. All patients provided informed consent for data collection and scientific use.

Results

Data from 691 consecutive adult ALL patients diagnosed between May 2003 and June 2024 were available for the analysis. Thirty-three patients (4.8%) experienced thirty-seven CNS relapses. Of these, all but three cases (9.1%) were associated with concurrent bone marrow hematological (63.6%) or molecular (27.3%) relapse.

Increased white blood cell count (WBC) was identified as the only statistically significant independent risk factor for CNS relapse (median 35.0 (0.3–302) vs. 12.3 (0.3–830) ×109/L, p=0.05) in the time of diagnosis. Furthermore, no significant associations were found between CNS relapse rates and age, peripheral blasts percentage, CNS or other extramedullary infiltration, immunophenotype, aberrant cytogenetics, BCR::ABL1, or KMT2A-r in the time of diagnosis, although there was a trend towards higher CNS relapse rates in EGIL T-III (thymic/cortical) immunophenotype (5/45, 11.1% cases).

The type of initial therapy protocol (pediatric-inspired intensive, “adult-type” intensive, “adult-type” non-intensive, palliative) did not significantly influence CNS relapse rates (16/370, 4.3%; 5/116, 4.3%; 7/111, 6.3%; 3/53, 5.7%, respectively). Similarly, prophylactic neurocranium radiotherapy during induction did not significantly reduce CNS relapse rates compared to no radiotherapy (4/126, 3.2% vs. 25/524, 4.8%). Furthermore, neither allogeneic hematopoietic stem cell transplant (SCT), myeloablative conditioning, nor total body irradiation (TBI) reduced CNS relapse incidence (9/243, 3.7%; 7/192, 3.6%; 6/130, 4.6%, respectively).

Patients of this cohort experiencing a CNS-involved relapse were treated by a number of different intensive and non-intensive systemic immunochemotherapy regimens, intrathecal cytostatic drugs, monoclonal antibodies or radiotherapy. Survival analysis revealed comparable 5-year overall survival (OS) rates between patients with and without CNS involvement in the setting of hematologic (17.1% vs. 21.3%) or molecular (40.2% vs. 50.4%) bone marrow relapse. This trend persisted also in more consistent subgroup treated with the GMALL-based pediatric-inspired intensive protocol (N=369, 20.0% vs. 29.8%, 53.3% vs. 59.5%).

Conclusion

In concordance with other authors, increased WBC seems to be a consistent risk factor of subsequent CNS relapse in adult ALL. However, its practical utility is limited since it has previously been shown to be a risk factor for bone marrow relapse. Despite the relatively small sample size of our cohort, our findings suggest that CNS involvement in adult ALL relapse does not significantly impact overall survival, which is primarily influenced by the bone marrow tumor burden, i.e. molecular or hematologic relapse. Further validation of these findings in larger cohorts is warranted.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH