-
Expert Review of Respiratory Medicine Aug 2022
Dasatinib-related pleural effusion and lymphocytosis rates are different between adult and pediatric patients with Philadelphia chromosome-positive leukemias: are age and comorbidities only to blame?
Topics: Adult; Antineoplastic Agents; Child; Dasatinib; Humans; Leukemia; Lymphocytosis; Philadelphia Chromosome; Pleural Effusion; Protein Kinase Inhibitors
PubMed: 36069271
DOI: 10.1080/17476348.2022.2122445 -
Annals of Hematology Jun 2023Philadelphia chromosome-like (Ph-like) ALL is a recent subtype of acute lymphoblastic leukemia. Although it does not express the BCR-ABL fusion gene, it has a behavior... (Review)
Review
Philadelphia chromosome-like (Ph-like) ALL is a recent subtype of acute lymphoblastic leukemia. Although it does not express the BCR-ABL fusion gene, it has a behavior like true BCR/ABL1-positive cases. This subtype harbors different molecular alterations most commonly CRLF2 rearrangements. Most cases of Ph-like ALL are associated with high white blood cell count, high minimal residual disease level after induction therapy, and high relapse rate. Efforts should be encouraged for early recognition of Ph-like ALL to enhance therapeutic strategies. Recently, many trials are investigating the possibility of adding the tyrosine kinase inhibitor (TKI) to chemotherapy to improve clinical outcomes. The role and best timing of allogeneic bone marrow transplant in those cases are still unclear. Precision medicine should be implemented in the treatment of such cases. Here in this review, we summarize the available data on Ph-like ALL.
Topics: Humans; Fusion Proteins, bcr-abl; Bone Marrow Transplantation; Philadelphia Chromosome; Protein Kinase Inhibitors; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 37129698
DOI: 10.1007/s00277-023-05241-2 -
Annals of Hematology Mar 2024Survival rates of patients with Philadelphia chromosome-positive ALL (Ph+ALL) have improved considerably with the introduction of tyrosine kinase inhibitors (TKI);...
Survival rates of patients with Philadelphia chromosome-positive ALL (Ph+ALL) have improved considerably with the introduction of tyrosine kinase inhibitors (TKI); however, hematopoietic stem cell transplantation (HSCT) continues to play an important role. Reduced-intensity conditioning (RIC) regimens have been widely applied particularly for older patients, but their validity for children and adolescents with Ph+ALL has not been investigated. In this study, data from patients receiving HSCT for de novo Ph+ALL in first or second remission at ages younger than 25 years and with a history of pre-HSCT TKI therapy were retrospectively collected through the nationwide registry in Japan. In 265 patients who received myeloablative conditioning (MAC) and 33 patients receiving RIC, 5-year leukemia-free survival (LFS) rates were 67.3% and 79.8%, respectively (p = 0.142). Multivariate analysis of LFS, focusing on patients with good performance status, identified RIC as a significant prognostic factor for LFS (hazard ratio 0.32, p = 0.032), as well as older age, higher leukocyte count at diagnosis, and disease with additional chromosomal abnormalities. These trends were similar when we focused on patients who received prophylactic post-HSCT TKI treatment, as 5-year LFS was 81.0% for MAC and 84.4% for RIC (p = 0.748). In summary, HSCT with RIC regimen showed at least comparable LFS to HSCT with MAC regimen, and RIC was an independent favorable prognostic factor on multivariate analysis adjusting potential prognostic factors. While patient numbers were limited, our data suggest that RIC may be safely applied in this group, particularly combined with prophylactic post-HSCT TKI maintenance therapy.
Topics: Child; Humans; Adolescent; Retrospective Studies; Philadelphia Chromosome; Hematopoietic Stem Cell Transplantation; Acute Disease; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Transplantation Conditioning
PubMed: 38006571
DOI: 10.1007/s00277-023-05557-z -
International Journal of Molecular... Sep 2021Philadelphia chromosome negative myeloproliferative neoplasms (MPN) are composed of polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis... (Review)
Review
Philadelphia chromosome negative myeloproliferative neoplasms (MPN) are composed of polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF). The clinical picture is determined by constitutional symptoms and complications, including arterial and venous thromboembolic or hemorrhagic events. MPNs are characterized by mutations in , , or , with additional mutations leading to an expansion of myeloid cell lineages and, in PMF, to marrow fibrosis and cytopenias. Chronic inflammation impacting the initiation and expansion of disease in a major way has been described. Neutrophilic granulocytes play a major role in the pathogenesis of thromboembolic events via the secretion of inflammatory markers, as well as via interaction with thrombocytes and the endothelium. In this review, we discuss the molecular biology underlying myeloproliferative neoplasms and point out the central role of leukocytosis and, specifically, neutrophilic granulocytes in this group of disorders.
Topics: Hematologic Neoplasms; Humans; Myeloproliferative Disorders; Neoplasm Proteins; Neutrophils; Philadelphia Chromosome
PubMed: 34502471
DOI: 10.3390/ijms22179555 -
Current Hematologic Malignancy Reports Dec 2020The treatment of acute lymphoblastic leukemia (ALL) in adolescent and young adult (AYA) patients has markedly improved with the adoption of pediatric-inspired protocols.... (Review)
Review
PURPOSE OF REVIEW
The treatment of acute lymphoblastic leukemia (ALL) in adolescent and young adult (AYA) patients has markedly improved with the adoption of pediatric-inspired protocols. However, there remain several subtypes of ALL that represent significant therapeutic challenges. Here, we review the current evidence guiding treatment of Philadelphia chromosome-positive (Ph+), Philadelphia chromosome-like (Ph-L), and early T-precursor (ETP) ALL in the AYA population.
RECENT FINDINGS
Clinical trials in Ph + ALL have demonstrated the superior efficacy of second- and third-generation tyrosine kinase inhibitors (TKIs) to induce and maintain remission. Current efforts now focus on determining the durability of these remissions and which patients will benefit from transplant. For Ph-like and ETP ALL, recent studies are investigating the addition of novel agents to standard treatment. The treatment of Ph + ALL has significantly improved with the addition of potent TKIs. However, the treatment of Ph-like and ETP ALL remains a challenge. At this time, the judicious use of allogenic transplant is the only current approach to modify this increased risk.
Topics: Adolescent; Biomarkers, Tumor; Clinical Decision-Making; Clinical Trials as Topic; Combined Modality Therapy; Disease Management; Disease Susceptibility; Drug Evaluation, Preclinical; Humans; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Treatment Outcome; Young Adult
PubMed: 32920736
DOI: 10.1007/s11899-020-00597-y -
Current Oncology Reports Jun 2021Over the past two decades, tyrosine kinase inhibitors (TKIs) have changed the management of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic... (Review)
Review
PURPOSE OF REVIEW
Over the past two decades, tyrosine kinase inhibitors (TKIs) have changed the management of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), and this has led to significant improvement in their outcome. In this review, we will provide an overview of the current understanding of treatment of Ph+ ALL focusing on TKIs, alloHSCT, and novel therapies.
RECENT FINDINGS
The advent of more potent TKIs and the novel therapeutic options including blinatumomab, inotuzumab ozogamicin, and CD19 CAR-T therapy has changed the role of allogeneic hematopoietic stem cell transplant (alloHSCT) and intensive chemotherapy. To avoid toxicity from the historical treatment strategies, a more individualized, targeted approach to therapy including detection and monitoring of measurable residual disease (MRD) has become of interest. The treatment of patients with Ph+ ALL has been rapidly evolving with a more individualized, targeted treatment and use of TKIs and novel therapy.
Topics: Antineoplastic Agents; Hematopoietic Stem Cell Transplantation; Humans; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Protein Kinase Inhibitors
PubMed: 34125415
DOI: 10.1007/s11912-021-01086-y -
Hematology (Amsterdam, Netherlands) Dec 2022To compare the outcomes of tyrosine kinase inhibitors (TKIs) in combination with reduced-dose chemotherapy with those of standard induction chemotherapy, as well as the...
To compare the outcomes of tyrosine kinase inhibitors (TKIs) in combination with reduced-dose chemotherapy with those of standard induction chemotherapy, as well as the outcomes between chemotherapy and transplantation, in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). We retrospectively reviewed cases of Ph+ ALL treated with TKIs and combination chemotherapy. The patients were allocated to either the TKIs with reduced-dose chemotherapy group or the TKIs with standard chemotherapy group. In additions, patients were further stratified into either the transplant group or the non-transplant group. The complete remission rate (88.7% vs. 83.9%, = 0.372), major molecular response (58.9% vs. 56.0%, = 0.750), molecular complete response (20.5% vs. 22.0%, = 0.891), and early mortality rate (3.2% vs. 3.5%, = 0.922) were similar between the TKIs with reduced-dose chemotherapy group and the TKIs with standard chemotherapy group. The proportions of lung infections, bloodstream infections, patients with >21 days of hospitalization, the total costs, transfusion costs, and antimicrobial costs were higher in the standard chemotherapy group than in the TKIs with reduced-dose chemotherapy group. The 3-year overall survival rates (59.0% [95% CI, 46.6-74.7%] vs. 38.4% [95% CI, 29.9-49.4%]) and disease-free survival rates (48.6% [95% CI, 34.2-69.1%] vs. 32.0% [95% CI, 23.5-43.7%]) were significantly better in the transplant group than in the non-transplant group. An induction regimen combining TKIs with reduced-dose chemotherapy and transplantation during the first complete remission remains a suitable and effective option for patients with Ph+ ALL.
Topics: Adult; Hematopoietic Stem Cell Transplantation; Humans; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Protein Kinase Inhibitors; Retrospective Studies
PubMed: 36083141
DOI: 10.1080/16078454.2022.2119344 -
Haematologica Jul 2021
Topics: Humans; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Vincristine
PubMed: 33538156
DOI: 10.3324/haematol.2020.278077 -
British Journal of Haematology Sep 2023Chemotherapy-free regimens are reshaping the treatment landscape of Philadelphia chromosome-positive acute lymphoblastic leukaemia. The report by Xie et al. suggests...
Chemotherapy-free regimens are reshaping the treatment landscape of Philadelphia chromosome-positive acute lymphoblastic leukaemia. The report by Xie et al. suggests that the combination of dasatinib and prednisone is effective as induction and early consolidation. Survival was improved in patients who subsequently underwent allogeneic stem cell transplantation. Commentary on: Xie et al. Dasatinib plus prednisone as induction and consolidation for adults with Ph-positive acute lymphoblastic leukaemia: A single-arm, multicentre, phase 2 trial. Br J Haematol 2023;202:1119-1126.
Topics: Adult; Humans; Dasatinib; Philadelphia Chromosome; Prednisone; Antineoplastic Combined Chemotherapy Protocols; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Protein Kinase Inhibitors
PubMed: 37525325
DOI: 10.1111/bjh.19012 -
Hematology. American Society of... Dec 2022Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) carried a very poor prognosis prior to the advent of tyrosine kinase inhibitors (TKIs) that...
Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) carried a very poor prognosis prior to the advent of tyrosine kinase inhibitors (TKIs) that block the activity of the BCR-ABL1 oncoprotein. With improvements in TKI efficacy and allogeneic hematopoietic cell transplantation (HCT), survival has improved over the past 3 decades, and the role of chemotherapy and allogeneic HCT is now changing. Better risk stratification, the application of the third-generation TKI ponatinib, and the use of immunotherapy with the CD19-CD3 bifunctional T-cell engaging antibody blinatumomab in place of chemotherapy has made therapy for Ph+ ALL more tolerable and arguably more efficacious, especially for older patients who comprise most patients with Ph+ ALL.
Topics: Humans; Protein Kinase Inhibitors; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Hematopoietic Stem Cell Transplantation; Philadelphia Chromosome
PubMed: 36485090
DOI: 10.1182/hematology.2022000338