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Technology in Cancer Research &... 2023Central nervous system leukemia (CNSL) is the most common extramedullary relapse site in patients with Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic...
Comparison of the Efficacy and Safety of Ponatinib and Dasatinib in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia With Central Nervous System Relapse: A Retrospective Study.
INTRODUCTION
Central nervous system leukemia (CNSL) is the most common extramedullary relapse site in patients with Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL), with a poor prognosis and high relapse rate.
METHODS
We characterized the clinical data of 21 Ph-positive B-ALL patients to analyze the efficacy and safety of ponatinib for patients with central nervous system relapsed Ph-positive ALL retrospectively.
RESULTS
There were 11 males and 10 females in the cohort, and their median age was 45 (9-58) years old. The total CR (complete remission) rate was 90.5%. All 9 patients achieved CR in the ponatinib group, and 10 patients achieved CR in the dasatinib group (100% vs 83.3%, respectively; = .486) and minimal residual disease-positive CR in the ponatinib group and dasatinib group (88.9% vs 58.3%, = .178). The medium time after achieving CR was 5 and 8 weeks ( = .047). The total median overall survival (OS) was 31.1 months, and the 3-year OS was 49.0%. The median relapse-free survival (RFS) was 31.0 months, and the 3-year RFS was 45.2%. Patients in the ponatinib group showed a significantly longer OS than those patients in the dasatinib group with (medium OS not reached vs 27.6 months, = .045) or without (medium OS not reached vs 27.6 months, = .039) T315I mutations. The median RFS between the ponatinib group and the dasatinib group with T315I was not reached and 16.2 months, = .065. The median RFS between the ponatinib group and the dasatinib group without T315I was not reached and 16.2 months, = .036. No treatment-related deaths were observed during the therapy.
CONCLUSION
(1) Ph-positive CNSL patients seemed to have a high rate of response and postinduction MRD negativity with ponatinib and dasatinib, but ponatinib seemed to show a shorter time to achieve remission than dasatinib. (2) Ponatinib maintenance treatment might show superior survival for Ph-positive CNSL patients with or without the T315I mutation. (3) Ponatinib and dasatinib seemed to be both safe for the clinical application of Ph-positive CNSL.
Topics: Male; Female; Humans; Middle Aged; Child; Adolescent; Young Adult; Adult; Dasatinib; Retrospective Studies; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Fusion Proteins, bcr-abl; Central Nervous System; Protein Kinase Inhibitors
PubMed: 36959735
DOI: 10.1177/15330338231165866 -
Blood Jun 2021
Topics: COVID-19; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Philadelphia Chromosome; SARS-CoV-2; Vaccination
PubMed: 34110406
DOI: 10.1182/blood.2021011935 -
Biology of Blood and Marrow... Jan 2020Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) is a relatively new entity characterized by high cytokine receptor and tyrosine kinase... (Review)
Review
Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) is a relatively new entity characterized by high cytokine receptor and tyrosine kinase signaling resulting in multiple downstream pathway stimulation. The standard diagnostic method, gene expression profiling, is not widely available. Efforts are ongoing to establish easy and clinically applicable diagnostic pathways to facilitate the accurate identification of these patients and thus enable a better understanding of the prognosis and outcomes with different treatment approaches. The rates of complete remission in ALL patients are consistently above 90% with the different induction protocols; however, maintaining remission depends on the risk group of the patient and consolidation therapy. Allogeneic hematopoietic cell transplant (allo-HCT) is particularly beneficial when the risk of relapse is very high and the expected complications with transplant are low. Data on the outcomes of allo-HCT for Ph-like ALL are scarce. In this article we review the published literature on outcomes of Ph-like ALL patients treated using different therapeutic approaches and make recommendations about transplant consideration for these patients.
Topics: Allografts; Hematopoietic Stem Cell Transplantation; Humans; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 31445182
DOI: 10.1016/j.bbmt.2019.08.010 -
American Journal of Hematology May 2007
Topics: Bardet-Biedl Syndrome; Fusion Proteins, bcr-abl; Humans; Philadelphia Chromosome
PubMed: 17177191
DOI: 10.1002/ajh.20835 -
Medicine May 2024The Philadelphia chromosome (Ph) is seen in most patients with chronic myeloid leukemia and some patients with acute lymphoblastic leukemia. However, Ph-positive acute... (Review)
Review
Philadelphia chromosome-positive acute myeloid leukemia successfully treated by allogeneic hematopoietic stem cell transplantation: A case report and review of the literature.
RATIONAL
The Philadelphia chromosome (Ph) is seen in most patients with chronic myeloid leukemia and some patients with acute lymphoblastic leukemia. However, Ph-positive acute myeloid leukemia (Ph + AML) is a rare entity with a poor prognosis and a short median survival period. To date, there have been few clinical reports on this disease. And the treatment regimen of this disease has not been uniformly determined.
PATIENT CONCERNS
We report a case of a Ph + AML. A 32-year-old male who was admitted to our hospital with weakness for 2 months.
DIAGNOSIS
Philadelphia chromosome-positive acute myeloid leukemia.
INTERVENTIONS
The patient achieved complete remission by the administration of a tyrosine kinase inhibitor, combined with low-intensity chemotherapy and a B-cell lymphoma 2 inhibitor. Then, allogeneic hematopoietic stem cell transplantation (allo-HSCT) from his sister was successfully performed.
OUTCOMES
The patient has been in a continuous remission state for 6 months after transplantation.
LESSONS
We reported a rare Ph + AML case, successfully treated with allo-HSCT. This case provided strong support for treating Ph + AML with allo-HSCT.
Topics: Humans; Male; Hematopoietic Stem Cell Transplantation; Adult; Leukemia, Myeloid, Acute; Philadelphia Chromosome; Transplantation, Homologous; Remission Induction
PubMed: 38728478
DOI: 10.1097/MD.0000000000038110 -
The Oncologist Jul 2023Asciminib is an allosteric high-affinity tyrosine kinase inhibitor (TKI) of the BCR-ABL1 protein kinase. This kinase is translated from the Philadelphia chromosome in... (Randomized Controlled Trial)
Randomized Controlled Trial
The EMA Assessment of Asciminib for the Treatment of Adult Patients With Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase Who Were Previously Treated With at Least Two Tyrosine Kinase Inhibitors.
Asciminib is an allosteric high-affinity tyrosine kinase inhibitor (TKI) of the BCR-ABL1 protein kinase. This kinase is translated from the Philadelphia chromosome in chronic myeloid leukemia (CML). Marketing authorization for asciminib was granted on August 25, 2022 by the European Commission. The approved indication was for patients with Philadelphia chromosome-positive CML in the chronic phase which have previously been treated with at least 2 TKIs. Clinical efficacy and safety of asciminib were evaluated in the open-label, randomized, phase III ASCEMBL study. The primary endpoint of this trial was major molecular response (MMR) rate at 24 weeks. A significant difference in MRR rate was shown between the asciminib treated population and the bosutinib control group (25.5% vs. 13.2%, respectively, P = .029). In the asciminib cohort, adverse reactions of at least grade 3 with an incidence ≥ 5% were thrombocytopenia, neutropenia, increased pancreatic enzymes, hypertension, and anemia. The aim of this article is to summarize the scientific review of the application which led to the positive opinion by the European Medicines Agency's Committee for Medicinal Products for Human Use.
Topics: Adult; Humans; Antineoplastic Agents; Drug Resistance, Neoplasm; Fusion Proteins, bcr-abl; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors
PubMed: 37141403
DOI: 10.1093/oncolo/oyad119 -
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 -
Cancer Aug 2021Dasatinib monotherapy has demonstrated modest clinical activity in chronic myeloid leukemia in lymphoid blastic phase (CML-LBP). The outcome of Philadelphia chromosome...
Outcome of patients with chronic myeloid leukemia in lymphoid blastic phase and Philadelphia chromosome-positive acute lymphoblastic leukemia treated with hyper-CVAD and dasatinib.
BACKGROUND
Dasatinib monotherapy has demonstrated modest clinical activity in chronic myeloid leukemia in lymphoid blastic phase (CML-LBP). The outcome of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) has dramatically improved with hyperfractionated cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone (hyper-CVAD) in combination with tyrosine kinase inhibitors (TKIs).
METHODS
The authors reviewed 85 patients (23 with CML-LBP and 62 with newly diagnosed Ph-positive ALL) who received hyper-CVAD plus dasatinib.
RESULTS
In the CML-LBP cohort, 19 had prior chronic myeloid leukemia as chronic phase (n = 17; 74%), accelerated phase (n = 1; 4%), or myeloid blastic phase (n = 1; 4%); 4 (17%) presented with de novo CML-LBP. The BCR-ABL1 transcript was p210 in 22 patients (96%) and p190 in 1 patient (4%). In the Ph-positive ALL cohort, p210 and p190 transcripts were detected in 13 patients (21%) and 48 patients (77%), respectively. Patients with CML-LBP were less likely to achieve deep molecular remission than patients with Ph-positive ALL: the major molecular response (MMR) rates were 70% and 95%, respectively (P = .007), and the complete molecular response (CMR) rates were 55% and 74%, respectively (P = .16). Survival outcomes were similar for CML-LBP and Ph-positive ALL: the 5-year overall survival (OS) rates were 59% and 48%, respectively (P = .97). Allogeneic stem cell transplantation was associated with a better outcome in CML-LBP (5-year OS rate, 88% vs 57%; P = .04). In Ph-positive ALL, the outcome was driven by deeper molecular remission: the 5-year OS rates were 63% and 25% with CMR and MMR, respectively (P = .002).
CONCLUSIONS
The outcome of CML-LBP has improved with hyper-CVAD plus dasatinib therapy with survival comparable to that of Ph-positive ALL. Further improvement may be achieved with the use of novel TKIs and targeted agents.
Topics: Antineoplastic Combined Chemotherapy Protocols; Dasatinib; Dexamethasone; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 33823073
DOI: 10.1002/cncr.33539 -
Hematology. American Society of... Nov 2018Acute lymphoblastic leukemia (ALL) is characterized by genetic alterations that block differentiation, promote proliferation of lymphoid precursor cells, and are... (Review)
Review
Acute lymphoblastic leukemia (ALL) is characterized by genetic alterations that block differentiation, promote proliferation of lymphoid precursor cells, and are important for risk stratification. Although ALL is less common in adolescents and young adults (AYAs) and adults than children, survival rates are inferior, and long-term prognosis for adults is poor. Thus, ALL remains a challenging disease to treat in the AYA and adult populations. A major contributing factor that influences prognosis in this population is the reduced prevalence of genetic subtypes associated with favorable outcome and a concomitant increase in subtypes associated with poor outcome. Recent advances in genomic profiling across the age spectrum continue to enhance our knowledge of the differences in disease biology between children and adults and are providing important insights into novel therapeutic targets. Philadelphia chromosome-like (Ph-like) ALL is one such subtype characterized by alterations that deregulate cytokine receptor or tyrosine kinase signaling and are amenable to inhibition with approved tyrosine kinase inhibitors. One of the greatest challenges now remaining is determining how to implement this breadth of genomic information into rapid and accurate diagnostic testing to facilitate the development of novel clinical trials that improve the outcome of AYAs and adults with ALL.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Infant; Male; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis
PubMed: 30504302
DOI: 10.1182/asheducation-2018.1.137