scholarly journals Impact of Blinatumomab Treatment on Bone Marrow Function in Patients with Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5607
Author(s):  
Hagop M. Kantarjian ◽  
Gerhard Zugmaier ◽  
Monika Brüggemann ◽  
Brent L. Wood ◽  
Heinz A. Horst ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Survival Benefit ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Event Free Survival ◽  
Cell Precursor ◽  
Survival Prognosis ◽  
Free Survival ◽  
Bone Marrow Function

Association of blinatumomab treatment with myelosuppression was examined in this study. Peripheral blood counts were assessed prior to, during, and after blinatumomab treatment in patients with relapsed/refractory Philadelphia chromosome-negative (Ph−) B-cell precursor (BCP) acute lymphoblastic leukemia (ALL; n = 267) and Ph+ BCP-ALL (n = 45) from the TOWER and ALCANTARA studies, respectively, or chemotherapy in patients with Ph− BCP-ALL (n = 109) from the TOWER study; all the patients with relapsed/refractory BCP-ALL and responders achieving complete remission (CR) or CR with partial/incomplete hematological recovery (CRh/CRi) were evaluated. Event-free survival (EFS) and overall survival (OS) were assessed in patients achieving CR and CRh/CRi. Median leukocyte, neutrophil, and platelet counts increased during two blinatumomab cycles but remained low longer after chemotherapy. Among the responders, there was a trend that a greater proportion of patients achieved CR with blinatumomab (Ph−, 76.5%; Ph+, 77.8%) versus with chemotherapy (Ph−, 63.6%). In the TOWER study, the survival prognosis for patients achieving CRh/CRi versus CR with blinatumomab was more similar (median OS, 11.9 (95% CI, 3.9–not estimable (NE)) vs. 15.0 (95% CI, 10.4–NE) months, p = 0.062) than with chemotherapy (5.2 (95% CI, 1.6–NE) vs. 18.9 (95% CI, 9.3–NE) months, p = 0.013). Blinatumomab treatment, with only temporary and transient myelosuppression, resulted in a greater survival benefit than chemotherapy.

scholarly journals Prognostic significance of CD20 expression in childhood B-cell precursor acute lymphoblastic leukemia

Blood ◽  
2006 ◽  
Vol 108 (10) ◽  
pp. 3302-3304 ◽  
Author(s):  
Sima Jeha ◽  
Frederick Behm ◽  
Deqing Pei ◽  
John T. Sandlund ◽  
Raul C. Ribeiro ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Prognostic Impact ◽  
Event Free Survival ◽  
Cell Precursor ◽  
Free Survival ◽  
Cd20 Expression ◽  
Therapy Studies

Abstract CD20 expression is associated with inferior survival in adults with acute lymphoblastic leukemia (ALL). We analyzed the prognostic impact of CD20 expression in 353 children with B-cell precursor ALL treated in 3 consecutive St Jude Total Therapy studies. CD20 expression (> 20%) was found in 169 patients (48%) and was more frequent in patients between 1 and 10 years of age than in those younger than 1 or older than 10 years (P = .001). None of 14 patients with MLL-AF4 expressed CD20. There was no association between CD20 expression and E2A-PBX, TEL-AML1, ploidy, white blood cell count at diagnosis, or sex. In contrast to the experience in adult ALL, our patients with CD20 expression tended to have a better treatment outcome than those without the expression: 5-year event-free survival 84% ± 2.9% versus 78% ± 3.1% (P = .08). These data suggest that CD20 expression is not associated with inferior outcome in pediatric patients treated with contemporary regimens.

scholarly journals IKZF1plus Defines a New Minimal Residual Disease–Dependent Very-Poor Prognostic Profile in Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia

2018 ◽  
Vol 36 (12) ◽  
pp. 1240-1249 ◽  
Author(s):  
Martin Stanulla ◽  
Elif Dagdan ◽  
Marketa Zaliova ◽  
Anja Möricke ◽  
Chiara Palmi ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Event Free Survival ◽  
Cell Precursor ◽  
Free Survival ◽  
Prognostic Profile ◽  
Minimal Residual

Purpose Somatic deletions that affect the lymphoid transcription factor–coding gene IKZF1 have previously been reported as independently associated with a poor prognosis in pediatric B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). We have now refined the prognostic strength of IKZF1 deletions by analyzing the effect of co-occurring deletions. Patients and Methods The analysis involved 991 patients with BCP ALL treated in the Associazione Italiana Ematologia ed Oncologia Pediatrica–Berlin-Frankfurt-Muenster (AIEOP-BFM) ALL 2000 trial with complete information for copy number alterations of IKZF1, PAX5, ETV6, RB1, BTG1, EBF1, CDKN2A, CDKN2B, Xp22.33/Yp11.31 (PAR1 region; CRLF2, CSF2RA, and IL3RA), and ERG; replication of findings involved 417 patients from the same trial. Results IKZF1 deletions that co-occurred with deletions in CDKN2A, CDKN2B, PAX5, or PAR1 in the absence of ERG deletion conferred the worst outcome and, consequently, were grouped as IKZF1plus. The IKZF1plus group comprised 6% of patients with BCP ALL, with a 5-year event-free survival of 53 ± 6% compared with 79 ± 5% in patients with IKZF1 deletion who did not fulfill the IKZF1plus definition and 87 ± 1% in patients who lacked an IKZF1 deletion ( P ≤ .001). Respective 5-year cumulative relapse incidence rates were 44 ± 6%, 11 ± 4%, and 10 ± 1% ( P ≤ .001). Results were confirmed in the replication cohort, and multivariable analyses demonstrated independence of IKZF1plus. The IKZF1plus prognostic effect differed dramatically in analyses stratified by minimal residual disease (MRD) levels after induction treatment: 5-year event-free survival for MRD standard-risk IKZF1plus patients was 94 ± 5% versus 40 ± 10% in MRD intermediate- and 30 ± 14% in high-risk IKZF1plus patients ( P ≤ .001). Corresponding 5-year cumulative incidence of relapse rates were 6 ± 6%, 60 ± 10%, and 60 ± 17% ( P ≤ .001). Conclusion IKZF1plus describes a new MRD-dependent very-poor prognostic profile in BCP ALL. Because current AIEOP-BFM treatment is largely ineffective for MRD-positive IKZF1plus patients, new experimental treatment approaches will be evaluated in our upcoming trial AIEOP-BFM ALL 2017.

scholarly journals Subclonal NT5C2 mutations are associated with poor outcomes after relapse of pediatric acute lymphoblastic leukemia

Blood ◽  
2020 ◽  
Vol 135 (12) ◽  
pp. 921-933 ◽  
Author(s):  
Malwine J. Barz ◽  
Jana Hof ◽  
Stefanie Groeneveld-Krentz ◽  
Jui Wan Loh ◽  
Annabell Szymansky ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Multivariable Analysis ◽  
Induction Treatment ◽  
Clinical Effects ◽  
Event Free Survival ◽  
Cell Precursor ◽  
Free Survival ◽  
Poor Outcomes

Abstract Activating mutations in cytosolic 5′-nucleotidase II (NT5C2) are considered to drive relapse formation in acute lymphoblastic leukemia (ALL) by conferring purine analog resistance. To examine the clinical effects of NT5C2 mutations in relapsed ALL, we analyzed NT5C2 in 455 relapsed B-cell precursor ALL patients treated within the ALL-REZ BFM 2002 relapse trial using sequencing and sensitive allele-specific real-time polymerase chain reaction. We detected 110 NT5C2 mutations in 75 (16.5%) of 455 B-cell precursor ALL relapses. Two-thirds of relapses harbored subclonal mutations and only one-third harbored clonal mutations. Event-free survival after relapse was inferior in patients with relapses with clonal and subclonal NT5C2 mutations compared with those without (19% and 25% vs 53%, P < .001). However, subclonal, but not clonal, NT5C2 mutations were associated with reduced event-free survival in multivariable analysis (hazard ratio, 1.89; 95% confidence interval, 1.28-2.69; P = .001) and with an increased rate of nonresponse to relapse treatment (subclonal 32%, clonal 12%, wild type 9%, P < .001). Nevertheless, 27 (82%) of 33 subclonal NT5C2 mutations became undetectable at the time of nonresponse or second relapse, and in 10 (71%) of 14 patients subclonal NT5C2 mutations were undetectable already after relapse induction treatment. These results show that subclonal NT5C2 mutations define relapses associated with high risk of treatment failure in patients and at the same time emphasize that their role in outcome is complex and goes beyond mutant NT5C2 acting as a targetable driver during relapse progression. Sensitive, prospective identification of NT5C2 mutations is warranted to improve the understanding and treatment of this aggressive ALL relapse subtype.

scholarly journals Outcome of treatment in children with hypodiploid acute lymphoblastic leukemia

Blood ◽  
2007 ◽  
Vol 110 (4) ◽  
pp. 1112-1115 ◽  
Author(s):  
James B. Nachman ◽  
Nyla A. Heerema ◽  
Harland Sather ◽  
Bruce Camitta ◽  
Erik Forestier ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Study Groups ◽  
Event Free Survival ◽  
Prognostic Implication ◽  
Monosomy 7 ◽  
Free Survival ◽  
Modal Chromosome Number

Abstract One-hundred thirty-nine patients with acute lymphoblastic leukemia (ALL) and hypodiploidy (fewer than 45 chromosomes) were collected from 10 different national ALL study groups and single institutions. Patients were stratified by modal chromosome number into 4 groups: 24 to 29 (N = 46); 33 to 39 (N = 26); 40 to 43 (N = 13); and 44 (N = 54) chromosomes. Nine patients were Philadelphia chromosome (Ph) positive (4 cases: 44 chromosomes; 5 cases: 40-43 chromosomes) and were not considered further. Event-free survival (EFS) and overall survival (OS) of the remaining 130 patients were 38.5% ± 4.4% and 49.8% ± 4.2% at 8 years, respectively. There were no significant differences in outcome between patients with 24 to 29, 33 to 39, or 40 to 43 chromosomes. Compared with patients with fewer than 44 chromosomes, patients with 44 chromosomes had a significantly better EFS (P = .01; 8-year estimate, 52.2% vs 30.1%) and OS (P = .017; 69% vs 37.5%). For patients with 44 chromosomes, monosomy 7, the presence of a dicentric chromosome, or both predicted a worse EFS but similar OS. Doubling of the hypodiploid clone occurred in 32 patients (24-29 chromosomes [n = 25] and 33-39 chromosomes [n = 7]) and had no prognostic implication. Children and adolescents with ALL and hypodiploidy with fewer than 44 chromosomes have a poor outcome despite contemporary therapy.

scholarly journals Effect of Blinatumomab vs Chemotherapy on Event-Free Survival Among Children With High-risk First-Relapse B-Cell Acute Lymphoblastic Leukemia

JAMA ◽  
2021 ◽  
Vol 325 (9) ◽  
pp. 843
Author(s):  
Franco Locatelli ◽  
Gerhard Zugmaier ◽  
Carmelo Rizzari ◽  
Joan D. Morris ◽  
Bernd Gruhn ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Event Free Survival ◽  
Free Survival ◽  
Cell Acute Lymphoblastic Leukemia ◽  
First Relapse

scholarly journals Dasatinib Plus Intensive Chemotherapy in Children, Adolescents, and Young Adults With Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia: Results of Children’s Oncology Group Trial AALL0622

2018 ◽  
Vol 36 (22) ◽  
pp. 2306-2314 ◽  
Author(s):  
William B. Slayton ◽  
Kirk R. Schultz ◽  
John A. Kairalla ◽  
Meenakshi Devidas ◽  
Xinlei Mi ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Cranial Irradiation ◽  
Intensive Chemotherapy ◽  
Event Free Survival ◽  
Free Survival ◽  
Risk Patients ◽  
Standard Risk ◽  
Philadelphia Chromosome Positive

Purpose Addition of imatinib to intensive chemotherapy improved survival for children and young adults with Philadelphia chromosome–positive acute lymphoblastic leukemia. Compared with imatinib, dasatinib has increased potency, CNS penetration, and activity against imatinib-resistant clones. Patients and Methods Children’s Oncology Group (COG) trial AALL0622 (Bristol Myers Squibb trial CA180-204) tested safety and feasibility of adding dasatinib to intensive chemotherapy starting at induction day 15 in patients with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia age 1 to 30 years. Allogeneic hematopoietic stem-cell transplantation (HSCT) was recommended for patients at high risk based on slow response and for those with a matched family donor regardless of response after at least 11 weeks of therapy. Patients at standard risk based on rapid response received chemotherapy plus dasatinib for an additional 120 weeks. Patients with overt CNS leukemia received cranial irradiation. Results Sixty eligible patients were enrolled. Five-year overall (OS) and event-free survival rates (± standard deviations [SD]) were 86% ± 5% and 60% ± 7% overall, 87% ± 5% and 61% ± 7% for standard-risk patients (n = 48; 19% underwent HSCT), and 89% ± 13% and 67% ± 19% for high-risk patients (n = 9; 89% underwent HSCT), respectively. Five-year cumulative incidence (± SD) of CNS relapse was 15% ± 6%. Outcomes (± SDs) were similar to those in COG AALL0031, which used the same chemotherapy with continuous imatinib: 5-year OS of 81% ± 6% versus 86% ± 5% ( P = .63) and 5-year disease-free survival of 68% ± 7% versus 60% ± 7% ( P = 0.31) for AALL0031 versus AALL0622, respectively. IKZF1 deletions, present in 56% of tested patients, were associated with significantly inferior OS and event-free survival overall and in standard-risk patients. Conclusion Dasatinib was well tolerated with chemotherapy and provided outcomes similar to those with imatinib in COG AALL0031, where all patients received cranial irradiation. Our results support limiting HSCT to slow responders and suggest a potential role for transplantation in rapid responders with IKZF1 deletions.

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