scholarly journals Improved Early Event-Free Survival With Imatinib in Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia: A Children's Oncology Group Study

2009 ◽  
Vol 27 (31) ◽  
pp. 5175-5181 ◽  
Author(s):  
Kirk R. Schultz ◽  
W. Paul Bowman ◽  
Alexander Aledo ◽  
William B. Slayton ◽  
Harland Sather ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Early Event ◽  
Intensive Chemotherapy ◽  
Event Free Survival ◽  
Free Survival ◽  
The Impact ◽  
Improved Outcome ◽  
Philadelphia Chromosome Positive

Purpose Imatinib mesylate is a targeted agent that may be used against Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL), one of the highest risk pediatric ALL groups. Patients and Methods We evaluated whether imatinib (340 mg/m2/d) with an intensive chemotherapy regimen improved outcome in children ages 1 to 21 years with Ph+ ALL (N = 92) and compared toxicities to Ph− ALL patients (N = 65) given the same chemotherapy without imatinib. Exposure to imatinib was increased progressively in five patient cohorts that received imatinib from 42 (cohort 1; n = 7) to 280 continuous days (cohort 5; n = 50) before maintenance therapy. Patients with human leukocyte antigen (HLA) –identical sibling donors underwent blood and marrow transplantation (BMT) with imatinib given for 6 months following BMT. Results Continuous imatinib exposure improved outcome in cohort 5 patients with a 3-year event-free survival (EFS) of 80% ± 11% (95% CI, 64% to 90%), more than twice historical controls (35% ± 4%; P < .0001). Three-year EFS was similar for patients in cohort 5 treated with chemotherapy plus imatinib (88% ± 11%; 95% CI, 66% to 96%) or sibling donor BMT (57% ± 22%; 95% CI, 30.4% to 76.1%). There were no significant toxicities associated with adding imatinib to intensive chemotherapy. The higher imatinib dosing in cohort 5 appears to improve survival by having an impact on the outcome of children with a higher burden of minimal residual disease after induction. Conclusion Imatinib plus intensive chemotherapy improved 3-year EFS in children and adolescents with Ph+ ALL, with no appreciable increase in toxicity. BMT plus imatinib offered no advantage over BMT alone. Additional follow-up is required to determine the impact of this treatment on long-term EFS and determine whether chemotherapy plus imatinib can replace BMT.

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.

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 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.

Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome–positive acute lymphoblastic leukemia: results of the GRAAPH-2003 study

Blood ◽  
2006 ◽  
Vol 109 (4) ◽  
pp. 1408-1413 ◽  
Author(s):  
Adrienne de Labarthe ◽  
Philippe Rousselot ◽  
Françoise Huguet-Rigal ◽  
Eric Delabesse ◽  
Francis Witz ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Quantitative Polymerase Chain Reaction ◽  
Philadelphia Chromosome ◽  
Disease Free Survival ◽  
Free Survival ◽  
Prospective Trials ◽  
Polymerase Chain ◽  
Philadelphia Chromosome Positive

AbstractThe combination of imatinib with chemotherapy has been recently reported as very promising in patients with Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL). During 2004 and 2005, 45 patients with newly diagnosed Ph+ ALL were treated in the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAAPH) 2003 study, in which imatinib was started with HAM (mitoxantrone with intermediate-dose cytarabine) consolidation in good early responders (corticosensitive and chemosensitive ALL) or earlier during the induction course in combination with dexamethasone and vincristine in poor early responders (corticoresistant and/or chemoresistant ALL). Imatinib was then continuously administered until stem cell transplantation (SCT). Overall, complete remission (CR) and BCR-ABL real-time quantitative polymerase chain reaction (RQ-PCR) negativity rates were 96% and 29%, respectively. All of the 22 CR patients (100%) with a donor actually received allogeneic SCT in first CR. At 18 months, the estimated cumulative incidence of relapse, disease-free survival, and overall survival were 30%, 51%, and 65%, respectively. These 3 end points compared very favorably with results obtained in the pre-imatinib LALA-94 trial. This study confirms the value of the combined approach and encourages prospective trials to define the optimal chemotherapy that has to be combined with imatinib and to carefully reevaluate the place of allogeneic SCT in this new context.

Sign in / Sign up

Export Citation Format

Share Document