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American Journal of Hematology Jun 2022
Dismal outcomes of patients with relapsed/refractory Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia after failure of both inotuzumab ozogamicin and blinatumomab.
Topics: Antibodies, Bispecific; Humans; Inotuzumab Ozogamicin; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 35266566
DOI: 10.1002/ajh.26526 -
British Journal of Haematology Nov 2017The BCR-ABL1 fusion gene is caused by a translocation between chromosomes 9 and 22, resulting in an abnormal chromosome 22 (Philadelphia chromosome; Ph). Prior to the...
The presence of Philadelphia chromosome does not confer poor prognosis in adult pre-B acute lymphoblastic leukaemia in the tyrosine kinase inhibitor era - a surveillance, epidemiology, and end results database analysis.
The BCR-ABL1 fusion gene is caused by a translocation between chromosomes 9 and 22, resulting in an abnormal chromosome 22 (Philadelphia chromosome; Ph). Prior to the introduction of tyrosine kinase inhibitors (TKI), the presence of BCR-ABL1 conferred a poor prognosis in patients with acute lymphoblastic leukaemia (ALL). We compared the survival of Ph+ and Ph-ALL during the period when TKIs were universally available in the US for Ph+ALL, using a Surveillance, Epidemiology, and End Results (SEER) Database analysis. A total of 2694 patients with pre-B ALL (206 Ph+ALL; 2488 Ph-ALL) aged ≥18 years, who were diagnosed between 2010 and 2014, were identified in SEER registries. The median overall survival (OS) was 32 months in Ph+ALL (95% confidence interval [CI] 18 months-not reached) and 27 months (95% CI 24-30 months) in Ph-ALL (Log-rank test P-value 0·34). Older age was associated with worse prognosis in both Ph+ALL and Ph-ALL. Age-adjusted OS was inferior in Hispanics and African-Americans compared to non-Hispanic whites. Survival of pre-B ALL shows continued improvement with time. Philadelphia chromosome status does not confer poor prognosis in pre-B ALL in the TKI era: prognostic factors in pre-B ALL should be re-evaluated in the light of this finding.
Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Ethnicity; Humans; Middle Aged; Philadelphia Chromosome; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Registries; Survival Analysis; Young Adult
PubMed: 29047122
DOI: 10.1111/bjh.14953 -
Blood Cancer Journal Jan 2023This retrospective observational study (NEUF) included adult patients with B-cell acute lymphoblastic leukemia (B-cell ALL) who had received blinatumomab for the... (Observational Study)
Observational Study
This retrospective observational study (NEUF) included adult patients with B-cell acute lymphoblastic leukemia (B-cell ALL) who had received blinatumomab for the treatment of minimal residual disease-positive (MRD+) or relapsed/refractory (R/R) B-cell ALL via an expanded access program (EAP). Patients were eligible if blinatumomab was initiated via the EAP between January 2014 and June 2017. Patients were followed from blinatumomab initiation until death, entry into a clinical trial, the end of follow-up, or the end of the study period (December 31, 2017), whichever occurred first. Of the 249 adult patients included, 109 were MRD+ (83 Philadelphia chromosome-negative [Ph-] and 26 Philadelphia chromosome-positive [Ph+]) and 140 had a diagnosis of R/R B-cell ALL (106 Ph- and 34 Ph+). In the MRD+ group, within the first cycle of blinatumomab treatment, 93% (n = 49/53) of Ph- and 64% (n = 7/11) of Ph+ patients with evaluable MRD achieved an MRD response (MRD <0.01%). Median overall survival (OS) was not reached over a median follow-up time of 18.5 months (Ph-, 18.8 [range: 5.1-34.8] months; Ph+, 16.5 [range: 1.8-31.6] months). In the R/R group, within two cycles of blinatumomab, 51% of Ph- and 41% of Ph+ patients achieved complete hematologic remission (CR/CRh/CRi), and 83% of Ph- and 67% of Ph+ MRD-evaluable patients in CR/CRh/CRi achieved an MRD response. Median (95% confidence interval) OS was 12.2 (7.3-24.2) months in the R/R Ph- subgroup and 16.3 (5.3-not estimated) months in the R/R Ph+ subgroup. This large, real-world data set of adults with B-cell ALL treated with blinatumomab confirms efficacy outcomes from published studies.
Topics: Adult; Humans; Antibodies, Bispecific; Burkitt Lymphoma; Lymphoma, B-Cell; Philadelphia Chromosome; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Antineoplastic Agents, Immunological
PubMed: 36599847
DOI: 10.1038/s41408-022-00766-7 -
Zhonghua Xue Ye Xue Za Zhi = Zhonghua... Jul 2019To compare the clinical features between the 2 cohorts developing myelodysplastic syndrome or acute myeIogenous Ieukemia in Philadelphia chromosome-negative cells...
To compare the clinical features between the 2 cohorts developing myelodysplastic syndrome or acute myeIogenous Ieukemia in Philadelphia chromosome-negative cells (Ph(-) MDS/AML) and maintaining disease stable in the patients with Philadelphia chromosome-positive chronic myeloid Ieukemia (Ph(+) CML) who had clonal chromosomal abnormalities in Philadelphia chromosome-negative metaphases (CCA/Ph(-)) during tyrosine kinase inhibtor (TKI) - therapy. We retrospectively analyzed Ph(+) CML patients who developed CCA/Ph(-) during TKI-therapy from May 2001 to December 2017. Data of CCA/Ph(-) 63 patients, including 7 progressing to Ph(-) MDS/AML and 56 remaining disease stable were collected. Compared with those with stable disease, patients with Ph(-)MDS/AML had lower hemoglobin (=0.007) and platelet (=0.006) counts, and higher proportion of peripheral blasts (<0.001) when the first time CCA/Ph(-) was detected, and more mosonomy 7 abnormality (5/7, 71.4%) when MDS or AML was diagnosed; meanwhile, trisomy 8 (32/56, 57.1%) was more common in those with stable disease. Outcome of the patients with Ph(-) MDS/AML were poor. However, most of those with CCA/Ph(-) and stable disease had optimal response on TKI-therapy. A few patients with Ph(+) CML developed CCA/Ph(-) during TKI-therapy, most of them had stable disease, but very few patients developed Ph(-) MDS/AML with more common occurrence of monosomy 7 or unknown cytopenia. Our data suggested the significance of monitoring of peripheral blood smear, bone marrow morphology and cytogenetic analysis once monosomy 7 or unknown cytopenia occurred.
Topics: Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Philadelphia Chromosome; Protein-Tyrosine Kinases; Retrospective Studies
PubMed: 32397016
DOI: 10.3760/cma.j.issn.0253-2727.2019.07.003 -
The Korean Journal of Internal Medicine Sep 2023We performed a prospective study to determine the efficacy and safety of rituximab including chemotherapy in CD20-positive acute lymphoblastic leukemia (ALL).
BACKGROUND/AIMS
We performed a prospective study to determine the efficacy and safety of rituximab including chemotherapy in CD20-positive acute lymphoblastic leukemia (ALL).
METHODS
Patients with newly diagnosed ALL, aged ≥ 15 years, were eligible for the study if their leukemic blast cells in bone marrow expressed CD20 ≥ 20% at the time of diagnosis. Patients received multiagent chemotherapy with rituximab. After achieving complete remission (CR), patients received five cycles of consolidation with concomitant rituximab. Rituximab was administered monthly from day 90 of transplantation for patients who received allogeneic hematopoietic cell transplantation.
RESULTS
In patients with Philadelphia (Ph)-negative ALL, 39 of 41 achieved CR (95.1%), the 2- and 4-year relapse-free survival (RFS) rates were 50.4% and 35.7%, and the 2- and 4-year overall survival (OS) rates were 51.5% and 43.2%, respectively. In the group with Ph-positive ALL, all 32 patients achieved CR, the 2- and 4-year RFS rates were 60.7% and 52.1%, and the 2- and 4-year OS rates were 73.3% and 52.3%, respectively. In the Ph-negative ALL group, patients with higher CD20 positivity experienced more favorable RFS (p < 0.001) and OS (p = 0.06) than those with lower CD20 positivity. Patients who received ≥ 2 cycles of rituximab after transplantation had significantly improved RFS (hazard ratio [HR], 0.31; p = 0.049) and OS (HR, 0.29; p = 0.021) compared with those who received < 2 cycles.
CONCLUSION
The addition of rituximab to conventional chemotherapy for CD20-positive ALL is effective and tolerable (Clinicaltrials. gov NCT01429610).
Topics: Humans; Rituximab; Prospective Studies; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Antineoplastic Combined Chemotherapy Protocols; Hematopoietic Stem Cell Transplantation
PubMed: 37334511
DOI: 10.3904/kjim.2022.401 -
The Journal of Clinical Investigation Aug 2007Peter Nowell and David Hungerford's discovery of the Philadelphia chromosome facilitated many critical studies that have led to a paradigm shift in our understanding of... (Review)
Review
Peter Nowell and David Hungerford's discovery of the Philadelphia chromosome facilitated many critical studies that have led to a paradigm shift in our understanding of cancer as a disease of stem cells. This Review focuses on the application of these concepts to investigation of the role of stem cells in prostate cancer initiation and progression. Major strides in the development of in vitro and in vivo assays have enabled identification and characterization of prostate stem cells as well as functional evaluation of the tumorigenic effects of prostate cancer-related genetic alterations.
Topics: Animals; Cell Transformation, Neoplastic; Humans; Male; Neoplastic Stem Cells; Philadelphia Chromosome; Prostatic Neoplasms; Stem Cells
PubMed: 17671638
DOI: 10.1172/JCI32810 -
Hematology/oncology Clinics of North... Oct 2009The Philadelphia (Ph) chromosome, a short chromosome 22, is the most frequent cytogenetic abnormality in adult patients with acute lymphoblastic leukemia (ALL). It... (Review)
Review
The Philadelphia (Ph) chromosome, a short chromosome 22, is the most frequent cytogenetic abnormality in adult patients with acute lymphoblastic leukemia (ALL). It occurs in approximately 20% to 30% of adults and in about 5% of children with this disease. The incidence rises with age and occurs in approximately 50% of patients older than 50 years. This article reviews the treatment regimens for Ph+ ALL, including imatinib and second generation tyrosine kinase inhibitors (TKIs). The introduction of effective TKIs in the treatment of Ph+ ALL has introduced several avenues of research in a disease that was hitherto difficult to treat.
Topics: Adult; Humans; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 19825452
DOI: 10.1016/j.hoc.2009.07.007 -
American Journal of Hematology Mar 2023
Topics: Adult; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Cyclophosphamide; Longitudinal Studies; Philadelphia Chromosome
PubMed: 36540957
DOI: 10.1002/ajh.26813 -
Blood Oct 1987Of 366 children with acute lymphoblastic leukemia (ALL) in whose bone marrow cells complete G-banding of chromosomes was successful, translocations were present at... (Comparative Study)
Comparative Study
Of 366 children with acute lymphoblastic leukemia (ALL) in whose bone marrow cells complete G-banding of chromosomes was successful, translocations were present at diagnosis in 141 (38.5%). The Philadelphia (Ph) chromosome was identified in 18 of these cases (4.9%). Features closely associated with the presence of the Ph chromosome were older age (median, 7.9 years), high leukocyte count (median, 47.3 X 10(9)/L), French-American-British L1 blast cell morphology, high incidence of CNS leukemia at diagnosis, and the common ALL immunophenotype. All patients were treated according to modern chemotherapeutic regimens for ALL used at our institution. Complete remissions were successfully induced in only 13 (72%) of the 18 patients with Ph + ALL, and only six remain free of leukemia for periods of 7+, 9+, 10+, 13+, 49+, and 70+ months. Our findings confirm the association of the Ph chromosome with classic high-risk features of ALL in children and suggest that this abnormality confers a very poor prognosis that has not yet been improved by modifications in established therapeutic regimens.
Topics: Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Chromosome Aberrations; Follow-Up Studies; Humans; Immunologic Techniques; Karyotyping; Leukemia, Lymphoid; Phenotype; Philadelphia Chromosome
PubMed: 3307953
DOI: No ID Found -
The Journal of Molecular Diagnostics :... Nov 2022Identification of specific leukemia subtypes is a key to successful risk-directed therapy in childhood acute lymphoblastic leukemia (ALL). Although RNA sequencing...
Identification of specific leukemia subtypes is a key to successful risk-directed therapy in childhood acute lymphoblastic leukemia (ALL). Although RNA sequencing (RNA-seq) is the best approach to identify virtually all specific leukemia subtypes, the routine use of this method is too costly for patients in resource-limited countries. This study enrolled 295 patients with pediatric ALL from 2010 to 2020. Routine screening could identify major cytogenetic alterations in approximately 69% of B-cell ALL (B-ALL) cases by RT-PCR, DNA index, and multiplex ligation-dependent probe amplification. STIL-TAL1 was present in 33% of T-cell ALL (T-ALL) cases. The remaining samples were submitted for RNA-seq. More than 96% of B-ALL cases and 74% of T-ALL cases could be identified based on the current molecular classification using this sequential approach. Patients with Philadelphia chromosome-like ALL constituted only 2.4% of the entire cohort, a rate even lower than those with ZNF384-rearranged (4.8%), DUX4-rearranged (6%), and Philadelphia chromosome-positive (4.4%) ALL. Patients with ETV6-RUNX1, high hyperdiploidy, PAX5 alteration, and DUX4 rearrangement had favorable prognosis, whereas those with hypodiploid and KMT2A and MEF2D rearrangement ALL had unfavorable outcomes. With the use of multiplex ligation-dependent probe amplification, DNA index, and RT-PCR in B-ALL and RT-PCR in T-ALL followed by RNA-seq, childhood ALL can be better classified to improve clinical assessments.
Topics: Child; Humans; Oncogene Proteins, Fusion; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Aneuploidy; DNA
PubMed: 35963521
DOI: 10.1016/j.jmoldx.2022.08.001