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Cytotherapy Sep 2022An intensified conditioning regimen incorporating medium-dose etoposide (VP16) is an option for patients with acute lymphoblastic leukemia (ALL). However, the prognostic...
Overcoming minimal residual disease using intensified conditioning with medium-dose etoposide, cyclophosphamide and total body irradiation in allogeneic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in adults.
BACKGROUND AIMS
An intensified conditioning regimen incorporating medium-dose etoposide (VP16) is an option for patients with acute lymphoblastic leukemia (ALL). However, the prognostic impacts of the addition of VP16 to cyclophosphamide (CY) and total body irradiation (TBI) in patients with Philadelphia chromosome-positive (Ph+) ALL with regard to minimal residual disease (MRD) status have not been elucidated.
METHODS
The authors retrospectively compared the outcomes of patients with Ph+ ALL who underwent allogeneic transplantation following VP16/CY/TBI (n = 101) and CY/TBI (n = 563).
RESULTS
At 4 years, the VP16/CY/TBI group exhibited significantly better disease-free survival (DFS) (72.6% versus 61.7%, P = 0.027) and relapse rate (11.5% versus 21.1%, P = 0.020) and similar non-relapse mortality (16.0% versus 17.2%, P = 0.70). In subgroup analyses, the beneficial effects of the addition of VP16 on DFS were more evident in patients with positive MRD status (71.2% versus 48.4% at 4 years, P = 0.022) than those with negative MRD status (72.8% versus 66.7% at 4 years, P = 0.24). Although MRD positivity was significantly associated with worse DFS in patients who received CY/TBI (48.4% versus 66.7%, P < 0.001), this was not the case in those who received VP16/CY/TBI (71.2% versus 72.8%, P = 0.86).
CONCLUSIONS
This study demonstrated the benefits of the addition of VP16 in Ph+ ALL patients, especially those with positive MRD status. VP16/CY/TBI could be a potential strategy to overcome the survival risk of MRD positivity.
Topics: Acute Disease; Adult; Cyclophosphamide; Etoposide; Hematopoietic Stem Cell Transplantation; Humans; Neoplasm, Residual; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Transplantation Conditioning; Whole-Body Irradiation
PubMed: 35534419
DOI: 10.1016/j.jcyt.2022.03.004 -
Hematology/oncology and Stem Cell... Dec 2020Lymphoblastic lymphomas (LBLs) are neoplasms of precursor B and T cells; they are considered in the same spectrum as precursor B and T cell acute lymphoblastic leukemia... (Review)
Review
Lymphoblastic lymphomas (LBLs) are neoplasms of precursor B and T cells; they are considered in the same spectrum as precursor B and T cell acute lymphoblastic leukemia (ALL). The World Health Organization classification classifies both LBL and ALL as one disease entity. While chromosome abnormalities are well defined with all of their therapeutic and prognostic implications in ALL, these are not well studied in LBL. Here, we describe a case of Philadelphia chromosome-positive LBL and review the available literature regarding this entity.
Topics: Adult; Female; Humans; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 29913129
DOI: 10.1016/j.hemonc.2018.05.007 -
Medicine Sep 2021Chronic myelogenous leukemia (CML) with thrombocytosis and complex chromosomal translocation is extremely rare in clinical setting. Here, we reported the clinical and...
RATIONALE
Chronic myelogenous leukemia (CML) with thrombocytosis and complex chromosomal translocation is extremely rare in clinical setting. Here, we reported the clinical and pathological characteristics of CML patients, which were characterized by thrombocytosis and complex Philadelphia chromosome translocation. Moreover, we also introduced our therapeutic schedule for this patient as well as review relative literature.
PATIENT CONCERNS
A 24-year-old female presented with night sweating, fatigue, and intermittent fever for 1 month.
DIAGNOSIS
Fluorescence in situ hybridization results revealed that breakpoint cluster region (BCR)-Abelson (ABL) gene fusion in 62% of the cells and karyotyping showed a complex 3-way 46, XY, t(9;22;11) (q34;q11;q13) [19/20] translocation. This patient was diagnosed with CML complicated with thrombocytosis and complex Philadelphia chromosome translocation.
INTERVENTIONS
The patients received continuously oral imatinib mesylate tablets (400 mg) once a day.
OUTCOMES
After treatment with imatinib for 3 months, the BCR/ABLIS was less than 0.1% and achieved major molecular response. Moreover, the BCR/ABLIS of this patient achieved major molecular response. The BCR/ABLIS values at 6 months and 12 months were less than 0.01% and 0.0032%, respectively. And no BCR/ABL fusion was detected in the next 2 years follow-up period.
LESSONS
Imatinib might represent a preferred therapeutic option for CML patients with rare thrombocytosis and complex chromosomal translocation. In addition, BCR/ABL fusion gene examination in patients with thrombocytosis might represent an effective strategy to avoid the misdiagnosis of this specific CML population.
Topics: Antineoplastic Agents; Female; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome; Thrombocytosis; Young Adult
PubMed: 34477162
DOI: 10.1097/MD.0000000000027134 -
Philadelphia chromosome-negative B-cell acute lymphoblastic leukaemia with kinase fusions in Taiwan.Scientific Reports Mar 2021Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukaemia (ALL), a high-risk subtype characterised by genomic alterations that activate cytokine receptor and...
Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukaemia (ALL), a high-risk subtype characterised by genomic alterations that activate cytokine receptor and kinase signalling, is associated with inferior outcomes in most childhood ALL clinical trials. Half of the patients with Ph-like ALL have kinase rearrangements or fusions. We examined the frequency and spectrum of these fusions using a retrospective cohort of 212 newly diagnosed patients with childhood B-cell ALL. Samples without known chromosomal alterations were subject to multiplex reverse transcription polymerase chain reaction to identify known Ph-like kinase fusions. Immunoglobulin heavy chain locus (IGH) capture and kinase capture were applied to samples without known kinase fusions. We detected known kinase fusions in five of 212 patients, comprising EBF1-PDGFRB, ETV6-ABL1, ZC3HAV1-ABL2, EPOR-IGH, and CNTRL-ABL1. Two patients with P2RY8-CRLF2 were identified. Patients with non-Ph kinase fusions had inferior 5-year event-free survival and overall survival compared with patients with other common genetic alterations. The prevalence of non-Ph kinase fusions in our Taiwanese cohort was lower than that reported in Caucasian populations. Future clinical trials with tyrosine kinase inhibitors may be indicated in Taiwan because of the inferior outcomes for B-cell ALL with kinase fusions.
Topics: Base Sequence; Child; Child, Preschool; Cohort Studies; Female; Gene Deletion; Gene Rearrangement; Humans; Immunoglobulin Heavy Chains; Infant; Male; Neoplasm Proteins; Oncogene Proteins, Fusion; Philadelphia Chromosome; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Progression-Free Survival; Protein Kinases; Taiwan
PubMed: 33707599
DOI: 10.1038/s41598-021-85213-6 -
Journal of Hematology & Oncology Apr 2024The chemo-free concept represents a new direction for managing adult patients with Ph-positive acute lymphoblastic leukemia (Ph + ALL). The tyrosine kinase... (Review)
Review
The chemo-free concept represents a new direction for managing adult patients with Ph-positive acute lymphoblastic leukemia (Ph + ALL). The tyrosine kinase inhibitors (TKIs), blinatumomab and venetoclax serve as the backbone of chemo-free regimens; several prospective studies involving these drugs have demonstrated high remission rates and promising, albeit short, survival outcomes. This review summarizes the latest updates on chemo-free regimens in the treatment of adult patients with Ph + ALL, presented at the 2023 ASH annual meeting.
Topics: Adult; Humans; Antineoplastic Combined Chemotherapy Protocols; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Protein Kinase Inhibitors; Congresses as Topic
PubMed: 38627786
DOI: 10.1186/s13045-024-01539-4 -
Journal of Medical Case Reports May 2021Chronic myeloid leukemia is a hematologic malignancy associated with the fusion of two genes: BCR and ABL1. This fusion results from a translocation between chromosomes... (Review)
Review
A unique three-way Philadelphia chromosome variant t(4;9;22)(q21;q34;q11.2) in a newly diagnosed patient with chronic phase chronic myeloid leukemia: a case report and review of the literature.
BACKGROUND
Chronic myeloid leukemia is a hematologic malignancy associated with the fusion of two genes: BCR and ABL1. This fusion results from a translocation between chromosomes 9 and 22, which is called the Philadelphia chromosome. Although the Philadelphia chromosome is present in more than 90% of patients with chronic myeloid leukemia, 5-8% of patients with chronic myeloid leukemia show complex variant translocations. Herein, we report a unique case of a three-way translocation variant in chronic phase chronic myeloid leukemia.
CASE PRESENTATION
A 40-year-old Asian male who presented with leukocytosis was diagnosed with chronic phase chronic myeloid leukemia. Cytogenetic karyotyping analysis showed 46,XY,t(4;9;22)(q21;q34;q11.2). He was treated with bosutinib and then changed to dasatinib because of intolerance, and MR4.5 (BCR-ABL/ABL ≦ 0.0032%, international scale) was achieved after 17 months of continuous treatment.
CONCLUSION
This was the 14th case of t(4;9;22), in particular, a new variant Ph translocation involved in chromosome 4q21 and the first successful case treated with tyrosine kinase inhibitors in the world. We summarize previous case reports regarding three-way variant chromosome translocation, t(4;9;22) and discuss how this rare translocation is linked to prognosis.
Topics: Adult; Fusion Proteins, bcr-abl; Humans; Karyotyping; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Philadelphia Chromosome; Translocation, Genetic
PubMed: 34030730
DOI: 10.1186/s13256-021-02885-4 -
Cancer Aug 2015Significant advances have been made in the last decade toward a better understanding of the disease pathogenesis and the development of novel therapies that target... (Review)
Review
Significant advances have been made in the last decade toward a better understanding of the disease pathogenesis and the development of novel therapies that target specific subsets of adult acute lymphoblastic leukemia (ALL). Risk-adapted strategies are transforming the disease treatment and prognosis. With current treatment regimens, long-term survival is achieved by approximately 50% of patients with B-cell ALL, 50% to 60% of patients with Philadelphia chromosome-positive ALL, and approximately 80% of patients with Burkitt's leukemia. Genomic profiling in ALL has identified new prognostic markers, new therapeutic targets, and novel ALL subtypes. These may be amenable to future targeted therapies that can further improve outcomes. The early recognition of early precursor T-cell ALL, a distinct pathobiological entity with a poor prognosis, is essential for the development of an effective clinical management strategy. The role of monoclonal antibodies and cytotoxic T-cell therapies continues to be defined. Many of the approaches are currently being evaluated for ALL salvage. Their incorporation into frontline adult ALL therapy, in concomitant or sequential strategies, may increase the cure rates to levels achieved in pediatric ALL and may reduce the need for prolonged intensive and maintenance chemotherapy.
Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Allografts; Antigens, CD20; Genes, Neoplasm; Hematopoietic Stem Cell Transplantation; Humans; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Young Adult
PubMed: 25891003
DOI: 10.1002/cncr.29383 -
Leukemia Oct 2009Ph-positive chronic myeloid leukemia (CML) and Ph-negative chronic myeloproliferative diseases (MPDs), characterized in many cases by the presence of the JAK2(V617F)... (Review)
Review
Ph-positive chronic myeloid leukemia (CML) and Ph-negative chronic myeloproliferative diseases (MPDs), characterized in many cases by the presence of the JAK2(V617F) mutation, have many features in common and yet also show fundamental differences. In this review, we pose five discrete and related questions relevant to both categories of hematological malignancy, namely: What are the mechanisms that underlie disease progression from a relatively benign or chronic phase? By what therapeutic methods might one target residual leukemia stem cells in CML? Is JAK2(V617F) the original molecular event in MPD? What epigenetic events must have a role in dictating disease phenotype in MPDs? And finally, Will the benefits conferred by current or future JAK2(V617F) inhibitors equal or even surpass the clinical success that has resulted from the use of tyrosine kinase inhibitors in CML? These and others questions must be addressed and in some cases should be answered in the foreseeable future.
Topics: Chronic Disease; Humans; Janus Kinase 2; Leukemia, Myeloid, Chronic-Phase; Myeloproliferative Disorders; Philadelphia Chromosome
PubMed: 19641523
DOI: 10.1038/leu.2009.142 -
Acta Medica Indonesiana Jan 2011Although presently known as an environmentally-related disease and appears mostly sporadic, cancer is regarded as a genetic disease based on the presence of gene... (Review)
Review
Although presently known as an environmentally-related disease and appears mostly sporadic, cancer is regarded as a genetic disease based on the presence of gene mutation as a consistent factor. The "Philadelphia Chromosome" found consistently among chronic myeloid leukemia (CML) patients was the first significant finding of a chromosomal abnormality specifically related to a particular disease. Starting from this point, cytogenetics as the study of chromosomes has become a valuable tool in the assessment of cancer - as an aid in diagnosis, thus guiding therapy, and as a prognostic marker. As is the nature of the proliferating marrow, chromosomal abnormalities were found mostly in hematologic malignancies, and the findings more pathognomonic. The situation is different in solid tumors, which when visible to the naked eye already will have complex chromosomal changes and thus pose technical difficulties to the cytogeneticist. However, scientists believe that the shift in chromosomal studies from conventional cytogenetics to molecular cytogenetics will provide further information regarding solid tumors.
Topics: Biomarkers, Tumor; Chromosome Disorders; Cytogenetics; Gene Deletion; Hematologic Neoplasms; Humans; Karyotyping; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome; Prognosis; Translocation, Genetic
PubMed: 21339549
DOI: No ID Found -
Haematologica Oct 2021
Topics: Humans; Imidazoles; Nitriles; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pyrazoles; Pyridazines; Pyrimidines
PubMed: 34196168
DOI: 10.3324/haematol.2021.278697