Outcome of Patients with Philadelphia Negative B-Cell Acute Lymphoblastic Leukemia (ALL) and Isolated Central Nervous System (CNS) Relapse

Abstract

Introduction: Since the increase in survival in patients with ALL with new induction regimens, extramedullary relapses in sanctuary sites such as central nervous system (CNS) became a common event. CNS prophylaxis has greatly reduced incidence of this. However, early or late relapses at extramedullary sites are still a clinical problem in these patients.Method: Patients with Philadelphia negative B-Cell ALL in first relapse treated at our institution between 2000 and 2014 were analyzed. Information regarding initial treatments, characteristics at the time of relapse, response to therapy and duration of remission was evaluated. Survival outcomes were analyzed in terms of presence of a CNS isolated relapse. Statistical analysis included Chi-squared for categorical variables, T-student for continuous variables and Kaplan-Meier for OS.Results: A total of 166 patients were evaluated. A total of 20 (12%) patients had isolated CNS relapse and 140 (88%) had systemic relapse. Patient characteristics are summarized in Table 1. Median time to relapse was 23 compared to 26 months (p=0.71) for patients with or without isolated CNS relapse, respectively. Patients with isolated CNS relapse tended to be younger (29 vs 41 years, p=0.08); No differences in baseline characteristics were observed between both groups. After relapse, data on therapy and response to therapy was available in 8 patients with isolated CNS disease and 71 patients with systemic relapse (Table 1). The 8 patients with isolated CNS relapse were treated with augmented HCVAD (3/8), HCVAD-R (2/8), and FLAG-Ida (2/8). All patients received intrathecal chemotherapy and 5 received radiation therapy. Response to therapy monitored as CSF clearance was observed in 6 patients with 2 patients not responding and progressing to systemic disease. 3 (38 %) received subsequent allogeneic stem cell transplantation (allo-SCT), with only one of them remaining alive in CR at the last follow-up. Median follow-up was 49 months (15-151). Median survival after relapse was significantly longer in patients with isolated CNS relapse compared to those with systemic relapse (39 vs 7 months, p=0.03) (Figure 1).Conclusions: Isolated CNS relapse occurs at a rate of 12% and is associated with significantly better outcome than systemic relapses in patients with B-cell ALL.Table 1Studied factorIsolated CNS RelapseN (%) [range]Systemic RelapseN (%) [range]p valueAge29 [16-62]41 [18-84]p=0.08SexMale14 [70%]82 [56%]Female6 [30%]64 [44%]TreatmentHCVAD-R12 (60)52 (37)HCVAD1 (5)54 (38)Augmented BFM7 (35)33 (24)Baseline CharacteristicsHemoblogin93. [7-13.4]8.9 [3.6-15.1]p=0.47White blood cell count17 [1.5-112]36 [0.6-602]p=0.39Platelet count66 [15-386]60 [0-393]p=0.16Bone marrow blasts80 [17-97]81 [0-100]p=0.86LDH2124 [649-7882]2277 [172-28261]p=0.87Cytogenetics at BaselineDiploid8 (40)53 (36)Hyperdiploid1 (5)17 (12)Hypodiploid06 (4)Complex2 (10)26 (18)Other9 (45)29 (20)Not available015 (10)Median overall survival (months)39 [range]8 [range]p=0.03 [Display omitted] DisclosuresCortes:Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; BerGenBio AS: Research Funding; Teva: Research Funding; BMS: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Ambit: Consultancy, Research Funding; Arog: Research Funding; Celator: Research Funding; Jenssen: Consultancy. Daver:ImmunoGen: Other: clinical trial, Research Funding.