scholarly journals Cerebral venous thrombosis in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma during induction chemotherapy withl-asparaginase: The GRAALL experience

2015 ◽  
Vol 90 (11) ◽  
pp. 986-991 ◽  
Author(s):  
Marie-Anne Couturier ◽  
Françoise Huguet ◽  
Patrice Chevallier ◽  
Felipe Suarez ◽  
Xavier Thomas ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Venous Thrombosis ◽  
Induction Chemotherapy ◽  
Cerebral Venous Thrombosis ◽  
Lymphoblastic Leukemia ◽  
Lymphoblastic Lymphoma ◽  
Adult Patients

scholarly journals The Clinical Outcomes and Genomic Landscapes of Acute Lymphoblastic Leukemia Patients with E2A-PBX1: A 10-Year Retrospective Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 212-212
Author(s):  
Biqi Zhou ◽  
Xinran Chu ◽  
Hong Tian ◽  
Tianhui Liu ◽  
Hong Liu ◽  
...  
Keyword(s):  
Dna Repair ◽  
Acute Lymphoblastic Leukemia ◽  
Induction Chemotherapy ◽  
Lymphoblastic Leukemia ◽  
Gene Mutations ◽  
Adult Patients ◽  
Follicle Cells ◽  
Repair Gene ◽  
Dna Repair Gene ◽  
Car T

Abstract Introduction Patients with E2A-PBX1 fusion are expected to have an aggressive disease course. Because of the rarity of this genotype (nearly 5% of pediatric and 3% of adult B-cell acute lymphoblastic leukemia (B-ALL) cases), a consensus on the clinical and prognostic characteristics of adult E2A-PBX1-positive B-ALL patients, especially in adult patients, has not yet been reached. Patients and Methods We retrospectively summarized our clinical findings from 137 B-ALL patients diagnosed with E2A-PBX at our centers from 2009 to 2019, including 56 adolescents/adults (≥15 years old) and 81 children (<15 years old). Genomic investigated analysis was performed on sufficient bone marrow at diagnosis, relapse and remission as well as matched hair follicle cells using somatic copy number variation detection (n=25), whole-exome sequencing (n=29), the next-generation sequencing pane (tumor only, n=14) and RNA sequencing (n=22). Results The proportions of E2A-PBX1-positive B-ALL in our centers were 5.3% (81/1526) in children, 4.6% (43/925) in AYA and 2.1% (15/713) in older adults. The complete remission rate among all E2A-PBX1-positive B-ALL patients in this study was 94.9% (129/136) after one course of induction chemotherapy. The 5-year overall survival (OS) and disease-free survival (DFS) rates of the whole cohort were 68.6% and 61.0%, respectively. Allo-HSCT at CR1 in adolescents/adults could dramatically improve the 5-year prognoses (OS: 80.8% vs. 25.7%, P<0.001; DFS: 73.3% vs. 15.5%, P<0.001; cumulative incidence of relapse (CIR): 20.0% vs. 80.5%, P<0.001) (Figure 1A). Haploidentical-HSCT decreased the CIR compared with HLA-matched-HSCT in adolescents/adults (12.5% vs 58.3%, P=0.017) (Figure 1B). A total of 12 patients received CD19-targeted CAR-T cell therapy for disease progression (Figure 1C), and 91.7% (11/12) of patients achieved remission. Two patients died of relapse, and 3 patients died of complications (One died of grade 4 CRS, one died of cerebral hemorrhage after transfusion, and the other one died of infection after 14 months). Three patients received CAR-T bridging to allo-HSCT, and all of them remained in remission within the follow-up period. Univariate and multivariate analysis showed that t(1;19)(q23;p13) only (OS: P=0.020, HR=0.387, 95% CI: 0.174-0.862; DFS: P=0.004, HR= 0.375, 95% CI: 0.193-0.729; CIR: P=0.009, HR= 0.400, 95% CI: 0.200-0.799), Age (DFS: P=0.037, HR=1.009, 95% CI: 1.001-1.018; CIR: P=0.005, HR=1.025, 95% CI: 1.008-1.044) and the level of minimal residual disease (MRD) after induction chemotherapy (OS: P=0.020, HR=2.971, 95% CI: 1.185-7.452; DFS: P=0.002, HR= 3.218, 95% CI: 1.510-6.861; CIR: P=0.006, HR= 3.190, 95% CI: 1.406-7.246) were independent risk factors in E2A-PBX1-positive B-ALL (Figure 1D). In the diagnosis samples, mutations in PBX1, PAX5, CTCF and SETD2, amplification of AKT3, and deletion of CDKN2A/B were common in the total cohort, while transcriptome differences were found in the cell cycle, NGF signaling pathway and transcriptional regulation by TP53 between adolescents/adults and children (Figure 2A,B). More DNA repair gene mutations were detected in the relapse samples (7.9% vs. 57.1%, P<0.001). The median number of subclones in E2A-PBX1-positive B-ALL at diagnosis was 2 (range 1-4). Patients with multiple subclones at diagnosis tended to have unfavorable 3-year prognoses (DFS: P=0.010; CIR: P=0.021). Leukemia clones with DNA repair gene mutations showed aggressive and treatment-refractory phenotypes in this subtype of ALL (Figure 2C). Conclusions Our study indicated that age, the level of MRD and DNA repair gene mutations were associated with E2A-PBX1-positive B-ALL outcomes. Allo-HSCT, especially haploidentical-HSCT, could improve the prognosis of adolescent/adult patients. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Impact of D-index and L-index on pulmonary infection in induction chemotherapy for acute lymphoblastic leukemia and lymphoblastic lymphoma

Hematology ◽  
2015 ◽  
Vol 21 (1) ◽  
pp. 19-25 ◽  
Author(s):  
Yuko Ishihara ◽  
Shun-ichi Kimura ◽  
Yu Akahoshi ◽  
Naonori Harada ◽  
Hirofumi Nakano ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Induction Chemotherapy ◽  
Pulmonary Infection ◽  
Lymphoblastic Leukemia ◽  
Lymphoblastic Lymphoma

Outcome of adult patients with T-lymphoblastic lymphoma treated according to protocols for acute lymphoblastic leukemia

Blood ◽  
2002 ◽  
Vol 99 (12) ◽  
pp. 4379-4385 ◽  
Author(s):  
Dieter Hoelzer ◽  
Nicola Gökbuget ◽  
Werner Digel ◽  
Thomas Faak ◽  
Michael Kneba ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Lymphoblastic Lymphoma ◽  
Adult Patients ◽  
Cure Rate ◽  
Mediastinal Irradiation ◽  
T Lymphoblastic Lymphoma ◽  
Age Range

We treated 45 adult patients with T-lymphoblastic lymphoma (T-LBL) (age range 15-61 years) with 2 protocols designed for adult acute lymphoblastic leukemia (ALL). An encouraging cure rate of 90% was recently reported for T-LBL in children treated with a similar approach. In our study, an 8-drug standard induction was administered over 8 weeks including prophylactic cranial (24 Gy) and mediastinal irradiation (24 Gy) followed by consolidation and reinduction therapy. At diagnosis, 91% of the 45 patients showed a mediastinal tumor and 40% had pleural/pericardial effusions; 73% of the patients had stage III/IV disease. Overall, 42 patients (93%) achieved a complete remission (CR), 2 patients (4%) achieved a partial remission, and 1 patient (2%) died during induction. In patients with stage I-III disease (n = 18) the CR rate was 100% compared with 89% in stage IV (n = 27). There were 15 patients who relapsed (36%) within 12 months. The majority of relapses (47%) occurred in the mediastinum (n = 7) despite mediastinal irradiation with 24 Gy in 6 out of 7 patients. The estimates for overall survival, continuous CR, and disease-free survival at 7 years are 51%, 65%, and 62%, respectively. Stage, age, lactate dehydrogenase, and all other parameters had no influence on achievement of CR or outcome. This study demonstrates in a large cohort of patients with adult T-LBL that a high CR rate and a favorable outcome can be achieved with an ALL-type regimen. Mediastinal recurrence was the major obstacle and further improvement by intensification of chemotherapy, increased dose of mediastinal irradiation (36 Gy), and extended indications for stem cell transplantation seem to be required.

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