Abstract
Background: Translocation involving chromosomes 1 and 19 (t (1; 19) [q23; p13]) is a well-described cytogenetic abnormality in both adult and pediatric ALL. The t(1;19) occurs in a small subset of pts with ALL, however, traditionally, it is known to be associated with poor prognosis. With the use of modern intensive chemotherapy regimens in ALL, its prognostic significance became controversial. Our goal is to analyze the prognostic implication of t(1; 19) [q23; p13] in adult pts with B-cell ALL who received intensive induction chemotherapy.
Methods: We reviewed adult pts with Philadelphia-negative B-cell ALL who received Hyper-CVAD or Augmented-BFM at The University of Texas MD Anderson Cancer Center between 01/1992 and 12/2016. Among 670 pts reviewed, 19 (3%) were found to have t(1;19) [q23; p13]; two pts were excluded from survival analysis due to missing data. Patients were separated into five cytogenetic groups; 1- t(1;19), 2-Diploid, 3- Complex Karyotype (≥5 abnormalities), 4- MLL-rearranged, 5- Miscellaneous. Clinical data for cytogenetic groups other than t(1;19) was collected from 01/2000 onwards (n=365). Complete response (CR) was defined as bone marrow with 5% or less blasts, a neutrophil count ≥1 x 109/L, and a platelet count ≥100 x 109/L. The study endpoints evaluated were CR rate, the CR duration (CRD), overall survival (OS), and event-free survival (EFS). EFS was defined as the time from start of treatment to death, transformation, relapse or at last follow up date. Overall survival (OS) was the time from start of treatment to death or at last follow up date. CRD was time from response to relapse. Survival estimates were computed by Kaplan-Meier approach and survival comparisons performed using the log rank test.
Results: Clinical characteristics of pts are summarized in Table 1. Patient with t(1;19) were younger than the pts with other cytogenetics groups. Of 19 pts with t(1;19), 16 induced with Hyper-CVAD based regimens and 3 with Augmented-BFM. In total, 17 of 17 evaluable pts with t(1;19) achieved CR with induction; three (18%) pts underwent allogeneic stem cell transplant in CR1, five (29%) pts relapsed. At a median follow up of 75 months [5-239], 13 pts were alive. Compared with other cytogenetic groups, pts with t(1;19) had significantly better survival; median CRD, EFS, OS were not reached (Figure 1). OS was 60, 44, and 10 months in pts with diploid, complex and MLL-rearranged karyotypes, respectively (p<0.001).
Conclusion: Adult pts with Philadelphia-negative B-cell ALL presenting with t(1;19) abnormality are likely to achieve CR when induced with intensive multi-agent chemotherapies. In our study, t(1;19) demonstrated a favorable prognostic effect for survival.
Khoury: Pfizer: Research Funding; Angle: Research Funding; Kiromics: Research Funding; Stemline Therapeutics: Research Funding. Cortes: ARIAD: Consultancy, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy, Research Funding; Sun Pharma: Research Funding; Teva: Research Funding; ImmunoGen: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; BMS: Consultancy, Research Funding. Wierda: Karyopharm: Research Funding; The University of Texas MD Anderson Cancer Center: Employment; Acerta: Research Funding; GSK/Novartis: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria, Research Funding; Merck: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Kite: Research Funding; Juno: Research Funding; Janssen: Research Funding; Genentech/Roche: Consultancy, Honoraria, Research Funding; Genzyme: Consultancy, Honoraria; Emergent: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding. Jain: Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novimmune: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Verastem: Research Funding; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Abbvie: Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Verstovsek: NS Pharma: Research Funding; Galena BioPharma: Research Funding; Seattle Genetics: Research Funding; Lilly Oncology: Research Funding; CTI BioPharma Corp: Research Funding; Seattle Genetics: Research Funding; Bristol Myers Squibb: Research Funding; Incyte: Research Funding; Galena BioPharma: Research Funding; Blueprint Medicines Corp: Research Funding; Pfizer: Research Funding; Incyte: Research Funding; Roche: Research Funding; Blueprint Medicines Corp: Research Funding; Pfizer: Research Funding; Celgene: Research Funding; Genentech: Research Funding; NS Pharma: Research Funding; Genentech: Research Funding; CTI BioPharma Corp: Research Funding; Astrazeneca: Research Funding; Lilly Oncology: Research Funding; Roche: Research Funding; Astrazeneca: Research Funding; Promedior: Research Funding; Celgene: Research Funding; Gilead: Research Funding; Promedior: Research Funding; Gilead: Research Funding; Bristol Myers Squibb: Research Funding. O'Brien: Gilead Sciences, Inc.: Consultancy, Other: Research Support: Honorarium, Research Funding; Sunesis: Consultancy; CLL Global Research Foundation: Membership on an entity's Board of Directors or advisory committees; Alexion: Consultancy; Acerta: Other: Research Support: Honorarium, Research Funding; Pharmacyclics: Consultancy, Other: Research Support: Honorarium, Research Funding; AbbVie: Consultancy; Pfizer: Consultancy, Research Funding; ProNAI: Other: Research Support: Honorarium, Research Funding; Vaniam Group LLC: Consultancy; TG Therapeutics: Consultancy, Other: Research Support: Honorarium, Research Funding; Janssen: Consultancy; Amgen: Consultancy; Astellas: Consultancy; GSK: Consultancy; Regeneron: Other: Research Support: Honorarium, Research Funding; Celgene: Consultancy; Aptose Biosciences, Inc.: Consultancy. Jabbour: Bristol-Myers Squibb: Consultancy. Kantarjian: Novartis: Research Funding; Pfizer: Research Funding; Delta-Fly Pharma: Research Funding; Bristol-Meyers Squibb: Research Funding; ARIAD: Research Funding; Amgen: Research Funding.
