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Hematology/oncology and Stem Cell... Apr 2023Matched donor (MD) allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the preferred choice of treatment for Philadelphia chromosome-positive... (Meta-Analysis)
Meta-Analysis
Effects of different types of allogeneic hematopoietic stem cell transplantation donors on Philadelphia chromosome-positive acute lymphoblastic leukemia during the tyrosine kinase inhibitor era: A systematic review and meta-analysis.
BACKGROUND
Matched donor (MD) allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the preferred choice of treatment for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph ALL) patients who have achieved complete remission. This systematic review and meta-analysis was conducted to investigate the effects of allo-HSCTs from different donor types for Ph ALL patients who received tyrosine kinase inhibitors (TKIs).
METHODS
Studies in EMBASE and MEDLINE between inception and December 2020 were identified using search terms related to "Ph ALL" and "HSCT." Eligible studies were studies with Ph ALL patients who received a TKI and allo-HSCT. The primary outcomes of interest-the overall survival (OS) or relapse-free survival (RFS)-needed to be reported. The Mantel-Haenszel method was used to combine the effect estimates and associated 95% confidence intervals (CIs) of each donor type.
RESULTS
Fourteen cohort studies were identified for the meta-analysis. Haploidentical (HID)-HSCT for Ph ALL patients resulted in a superior RFS to MD-HSCT, with a pooled odds ratio (OR) of 1.57 (95% CI, 1.05-2.32; I = 0%). However, HID-HSCT and MD-HSCT had comparable OS. Furthermore, HID-HSCT group had a significantly lower relapse rate than MD-HSCT group. On the other hand, the risks of graft-versus-host disease (GvHD) were higher for HID-HSCT and pooled OR of chronic GvHD rate. The OS and RFS of matched sibling-HSCT, matched unrelated-HSCT, and cord blood-HSCT were comparable with those of HID-HSCT.
CONCLUSION
This systematic review and meta-analysis showed that HID-HSCT is as effective as MD-HSCT in Ph ALL patients.
Topics: Humans; Philadelphia Chromosome; Tyrosine Kinase Inhibitors; Protein Kinase Inhibitors; Hematopoietic Stem Cell Transplantation; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Graft vs Host Disease; Acute Disease; Recurrence; Retrospective Studies
PubMed: 34743893
DOI: 10.1016/j.hemonc.2021.09.007 -
Cancer Control : Journal of the Moffitt... 2021Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by the overproduction of mature myeloid cells and are often associated...
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by the overproduction of mature myeloid cells and are often associated with an acquired genetic mutation of . Various epidemiological studies have indicated associations between environmental factors, lifestyle factors, and host characteristics with developing MPNs. This review aims to collect and summarize the existing information on these risk factors and establish their association with pathogenesis MPNs. Medline, Embase, PubMed, and grey literature were systematically searched using key terms for MPNs, and epidemiological study designs, that is, cross-sectional studies, case-control, and cohort, that investigated the risk factors for MPNs published were identified. Out of the 4621 articles identified, 20 met the selection criteria and were included in this review. Heterogeneity, study reliability, and bias were assessed. A significant association was found between smoking and the development of MPNs. This relationship has been explained by the substantial increase in several proinflammatory mediators and systematic oxidative stress causing hyperstimulation of myeloid compartments leading to the development of MPNs. Obesity was modestly linked with an increased risk of MPNs. The underlying mechanisms have been linked to changes in endocrine, metabolic, and inflammatory systems. No strong association was found between exposure to hazardous substances, that is, benzene and MPNs, but further investigation on the effects of increased levels and duration of exposure on hematopoietic stem cells will be beneficial. Unique individual and host variations have been determined as a modifier of disease pathogenesis and phenotype variations. There is a higher incidence rate of females developing MPNs, specifically ET, than males with higher PV incidence. Therefore, gender contributes to the heterogeneity in myeloproliferative neoplasm. Studies identified as part of this review are very diverse. Thus, further in-depth assessment to explore the role of these etiological factors associated with MPNs is warranted.
Topics: Cigarette Smoking; Environment; Environmental Exposure; Female; Humans; Inflammation Mediators; Life Style; Male; Myeloproliferative Disorders; Obesity; Oxidative Stress; Philadelphia Chromosome; Risk Factors; Sex Distribution; Sociodemographic Factors
PubMed: 34645293
DOI: 10.1177/10732748211046802 -
Cureus Aug 2021Hydroxyurea (HU) or hydroxycarbamide is a cytotoxic antimetabolite widely used to treat Philadelphia chromosome-negative Myeloproliferative Neoplasms (Ph-MPN) like... (Review)
Review
Hydroxyurea (HU) or hydroxycarbamide is a cytotoxic antimetabolite widely used to treat Philadelphia chromosome-negative Myeloproliferative Neoplasms (Ph-MPN) like Polycythemia Vera (PV), Essential Thrombocythemia (ET), and Primary Myelofibrosis (PMF). Patients with Ph-MPN are at an increased risk of Non-melanoma skin cancers (NMSC). The cause of this finding remains uncertain. In this systematic review, we would like to know if chronic use of HU in this population is responsible for the sudden onset of NMSC. The results obtained will help the patients and clinicians with early diagnosis of cutaneous lesions and in optimizing the current treatment options for MPN. We conducted a multi-database literature search, applied eligibility criteria and quality assessment tools to the studies extracted, with an intention to include only fair to high-quality articles. We analyzed six observational studies and four traditional reviews. Two out of 10 studies concluded that no relationship exists between the incidence of NMSC and HU. The remaining eight studies indicated the association. According to these studies, the possible risk factors include old age, excessive exposure to sunlight, higher doses, and prolonged HU therapy duration. Ultraviolet (UV) radiation and HU play a combined role in carcinogenesis. Periodic dermatologic screening is essential in these patients. Prompt biopsy and accurate diagnosis can prevent the progression of cancer and decrease the associated morbidity and mortality. True incidence and causation cannot be ascertained due to the scarcity of research on this topic. Multi-center prospective studies in large groups of Ph-MPN patients are recommended to determine the temporal relationship between NMSC and HU treatment.
PubMed: 34527458
DOI: 10.7759/cureus.16978 -
PloS One 2021Minimal residual disease (MRD) appeared to be a potent prognostic indicator in patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL),... (Meta-Analysis)
Meta-Analysis
Association of minimal residual disease with clinical outcomes in Philadelphia chromosome positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era: A systemic literature review and meta-analysis.
Minimal residual disease (MRD) appeared to be a potent prognostic indicator in patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL), with potential value in informing individualized treatment decisions. Hence, we performed herein a systemic literature review and meta-analysis to comprehensively address the prognostic value of MRD in Ph+ ALL. Systematic literature review was conducted in PubMed, Embase, and Cochrane databases with the data access date up to September 23, 2020. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated with fixed-effects or random-effects models. Furthermore, subgroup analyses were performed to assess the robustness of the associations. 27 studies with a total number of 3289 patients were eligible for this meta-analysis. Combined HRs suggested that MRD positivity was associated with inferior event-free survival (EFS) (HR = 2.00, 95% CI 1.77-2.26) and overall survival (OS) (HR = 2.34, 95% CI 1.86-2.95). The associations remained statistically significant in subgroup analyses including age group, MRD timing, disease status at MRD, MRD cutoff level, et al. Our findings suggested MRD as a potent clinical tool for assessing the prognosis of Ph+ ALL. Further studies using MRD-based risk stratification might help optimize individualized treatment strategies for Ph+ ALL patients.
Topics: Humans; Immunotherapy; Neoplasm, Residual; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Progression-Free Survival; Protein Kinase Inhibitors
PubMed: 34437635
DOI: 10.1371/journal.pone.0256801 -
PloS One 2021Hematopoietic stem cell transplantation (HSCT) is the current mainstay treatment for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). However,... (Meta-Analysis)
Meta-Analysis
Is stem cell transplantation still needed for adult Philadelphia chromosome-positive acute lymphoblastic leukemia receiving tyrosine kinase inhibitors therapy?: A systematic review and meta-analysis.
BACKGROUND
Hematopoietic stem cell transplantation (HSCT) is the current mainstay treatment for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). However, tyrosine kinase inhibitors (TKI) also play a significant role in the treatment of these patients. We conducted this systematic review and meta-analysis to compare the efficacy of allogeneic (allo-) HSCT, autologous (auto-) HSCT, and chemotherapy (CMT) alone-all in combination with TKIs in adult Ph+ ALL patients.
MATERIALS AND METHODS
This systematic review identified studies from the EMBASE and MEDLINE databases from inception to April 2021 using search terms related to "ALL" and "HSCT." Eligible studies could be randomized controlled trials or cohort studies that included adult Ph+ ALL patients who received a TKI and either allo-HSCT, auto-HSCT, or CMT alone, and that reported the number of patients in each group for each of our primary outcomes of interest: overall survival (OS) or disease-free survival (DFS). Point estimates and associated 95% confidence intervals (CI) from each study were combined using the Hantel-Maenszel method.
RESULTS
After two rounds of review, 26 cohort studies were determined to be eligible for the meta-analysis. Adult Ph+ ALL patients who received HSCT had better survival outcomes than those who did not receive any HSCT (pooled odds ratio [OR] for OS of 1.61, 95%CI: 1.08-2.40; I2 = 59%, and for DFS of 3.23, 95%CI: 2.00-5.23; I2 = 62% for allo-HSCT; and, pooled OR for OS of 7.04, 95%CI: 1.97-25.15; I2 = 0%, and for DFS of 5.78, 95%CI: 1.04-32.19; I2 = 42% for auto-HSCT). Allo-HSCT recipients had comparable OS and DFS, but lower relapse rate compared to auto-HSCT recipients. Funnel plot generally demonstrated no presence of publication bias.
CONCLUSIONS
This systematic review and meta-analysis demonstrated superior results of HSCT in Ph+ ALL patients compared to CMT alone. Moreover, auto-HSCT could be implemented with comparable survival outcomes to allo-HSCT in patients with no available donor or when haploidentical HSCT is not feasible.
Topics: Allografts; Disease-Free Survival; Hematopoietic Stem Cell Transplantation; Humans; Molecular Targeted Therapy; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Protein Kinase Inhibitors
PubMed: 34181696
DOI: 10.1371/journal.pone.0253896 -
Clinical Lymphoma, Myeloma & Leukemia Jan 2021Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) is a subgroup of B-cell precursor ALL (BCP-ALL) with a gene expression profile analogous to... (Review)
Review
Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) is a subgroup of B-cell precursor ALL (BCP-ALL) with a gene expression profile analogous to Philadelphia-positive ALL and recurrent IKAROS Family Zinc Finger 1 (IKZF1) gene deletion despite lacking BCR-ABL1 (Breakpoint cluster region-ABL protooncogene) translocation. Although recognized to occur at all ages, the proportion of cases among BCP-ALL varies (< 10% in children and up to 30% in adolescents). In all age groups, males are more commonly affected. Generally, Ph-like ALL is associated with adverse clinical features and an increased risk of treatment failure with conventional approaches. Genetic alterations such as aberrant expression, point mutations, or fusion translocations lead to activation of cytokine receptors and signaling kinases, which affect the ABL1 (ABL class fusion) or Janus Kinase (JAK) signaling pathways. Several clinical trials are being conducted to understand whether specific tyrosine kinase inhibitor therapy can improve cure rates. This review summarizes the current literature available about this entity.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Young Adult
PubMed: 33485429
DOI: 10.1016/j.clml.2020.08.011 -
BMJ Open Jan 2021To investigate the effectiveness and safety of tyrosine kinase inhibitors (TKIs) in the management of paediatric Philadelphia chromosome-positive acute lymphoblastic... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To investigate the effectiveness and safety of tyrosine kinase inhibitors (TKIs) in the management of paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ALL).
DESIGN
A systematic review and meta-analysis.
DATA SOURCES
Electronic searches were conducted on CENTRAL, MEDLINE, EMBASE, SIOP, ASPHO, ASCO, ASH and four Chinese databases from inception to 8 March 2020. Language of publications was restricted in English and Chinese.
ELIGIBILITY CRITERIA
Prospective and retrospective comparative studies were included.
DATA EXTRACTION AND SYNTHESIS
Two authors independently assessed and extracted data. Quality of studies was assessed by the Cochrane Collaboration's tool and Newcastle-Ottawa Scale. Subgroup analysis was performed by comparing different types of TKIs. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.
RESULTS
Two randomised controlled trials (RCTs) and four cohort studies enrolling 536 patients were included. For RCTs, the pooled HR was 0.68 (95% CI 0.26 to 1.78) in overall survival (OS), 0.63 (95% CI 0.28 to 1.42) in event-free survival (EFS), respectively, comparing TKI arm with non-TKI arm for treatment of paediatric Ph+ALL. There was significant difference in OS and EFS between imatinib arm and dasatinib arm (HR 2.26, 95% CI 1.02 to 5.01; HR 2.36; 95% CI 1.27 to 4.39, respectively). For cohort studies, the pooled HR was 0.25 (95% CI 0.14 to 0.47) in OS, 0.25 (95% CI 0.12 to 0.56) in EFS, respectively, comparing TKI arm with non-TKI arm. There was no significance difference in adverse drug reaction between TKI group and without TKI group (risk ratio (RR) 0.82, 95% CI 0.63 to 1.08 in RCT; RR 1.01, 95% CI 0.64 to 1.59 in cohort studies; respectively), and imatinib versus dasatinib (RR 0.97, 95% CI 0.77 to 1.23). The quality of evidence was rated as low for OS, EFS and adverse drug reaction (ADR).
CONCLUSIONS
The combination of TKIs with chemotherapy is likely to improve the OS and EFS rates in paediatric Ph+ALL, and dasatinib is superior than imatinib. Large sample size and prospective controlled studies are warranted.
PROSPERO REGISTRATION NUMBER
CRD42018104107.
Topics: Child; Disease-Free Survival; Humans; Imatinib Mesylate; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Protein Kinase Inhibitors; Randomized Controlled Trials as Topic
PubMed: 33468532
DOI: 10.1136/bmjopen-2020-042814 -
The Annals of Pharmacotherapy Oct 2021To assess the current literature for blinatumomab in the treatment of adult and pediatric B-cell acute lymphoblastic leukemia (ALL).
OBJECTIVE
To assess the current literature for blinatumomab in the treatment of adult and pediatric B-cell acute lymphoblastic leukemia (ALL).
DATA SOURCES
We conducted a PubMed (inception to December 11, 2020) and ClinicalTrials.gov systematic literature search using the following terms: , and .
STUDY SELECTION AND DATA EXTRACTION
All relevant published articles, package inserts, and meeting abstracts evaluating the use of blinatumomab in ALL were considered for inclusion.
DATA SYNTHESIS
Blinatumomab, a first-in-class bispecific T-cell engager monoclonal antibody, facilitates cytotoxic T-cell activation and subsequent eradication of CD19-positive B cells. The confirmatory phase III TOWER trial demonstrated superior overall survival (OS) with blinatumomab compared with standard chemotherapy (7.7 months vs 4.0 months) in relapsed and refractory (R/R) B-cell ALL. In the phase II BLAST trial, blinatumomab achieved a complete measurable residual disease (MRD) response in 78% of evaluable patients, with a median OS of 36.5 months. Potentially life-threatening cytokine release syndrome and neurotoxicity occurred in approximately 15% and 65% of patients, respectively.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
Following initial Food and Drug Administration approval in 2014, blinatumomab gained expanded approval in pediatric patients and in Philadelphia chromosome-positive R/R ALL. In 2018, blinatumomab became the first and only drug approved for the treatment of persistent MRD in any hematologic malignancy. Emerging data demonstrate promising efficacy with blinatumomab in specific ALL settings, including frontline therapy, as a bridge to transplantation, and in "chemotherapy-free" combination regimens.
CONCLUSIONS
Blinatumomab provides a paradigm-shifting treatment option; however, many questions surrounding optimal patient selection, sequencing, and cost-effectiveness remain.
Topics: Antibodies, Bispecific; Antineoplastic Agents; Child; Humans; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction
PubMed: 33435716
DOI: 10.1177/1060028020988411 -
American Journal of Medical Genetics.... Jan 2021This objective of this systematic review was to estimate live birth rate and explore prognostic indicators in fetuses with 45,X karyotype and a posterior cystic hygroma...
This objective of this systematic review was to estimate live birth rate and explore prognostic indicators in fetuses with 45,X karyotype and a posterior cystic hygroma (CH). Electronic databases were searched and studies reporting pregnancy outcomes (termination, spontaneous abortion, demise, or live birth) for fetuses with 45,X karyotype and a CH diagnosed on ultrasound were included. For cases of survival, CH characteristics, presence of hydrops fetalis, or concomitant anomalies, delivery details, and postnatal outcomes were summarized. A total of 95 studies, including 535 cases, met inclusion criteria: 285 (53.3%) pregnancies were terminated, 72 (13.5%) had spontaneous abortion or demise, 164 (30.7%) had unspecified pregnancy failure, and 14 (2.6%) were live births. Among live births with data available, all CH measured 2-7 cm, more than half were septate, and almost all regressed in size or eventually disappeared. Hydrops fetalis was noted in five cases. Of the eight live births with neonatal outcomes available, three neonates died shortly after birth and five survived past the neonatal period. This review suggests that diagnosis of CH in a 45,X fetus is associated with an estimated live birth rate of 2.6%, but only 1% survive to infancy. Prognosis appears to improve with CH regression.
Topics: Chromosome Aberrations; Female; Fetus; Humans; Infant, Newborn; Karyotype; Karyotyping; Lymphangioma, Cystic; Pregnancy; Pregnancy Outcome; Prognosis; Ultrasonography, Prenatal
PubMed: 33026168
DOI: 10.1002/ajmg.a.61902 -
Annals of Hematology Nov 2020In the era of tyrosine kinase inhibitors (TKIs), allogeneic hematopoietic stem cell transplantation (allo-HSCT) is recommended as a standard approach for Philadelphia... (Comparative Study)
Comparative Study Meta-Analysis
Comparative study on allogeneic with autologous hematopoietic stem cell transplantation in adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia in the era of TKIs: a systematic review and meta-analysis.
In the era of tyrosine kinase inhibitors (TKIs), allogeneic hematopoietic stem cell transplantation (allo-HSCT) is recommended as a standard approach for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) achieving complete remission (CR). However, the role of autologous hematopoietic stem cell transplantation (auto-HSCT) in adult patients achieving complete molecular remission (CMR) is an alternative, less toxic treatment options, especially for the patients who lack suitable donors and are unfit for allo-HSCT. Thus, we conducted a systematic review and meta-analysis to compare the efficacy of allo-HSCT and auto-HSCT for the treatment of adult patients with Ph+ ALL. We searched the PubMed, Embase, Scopus, and Cochrane Library for studies published before June 2019 without language restriction. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for overall survival (OS) and relapse-free survival (RFS) and odds ratios (ORs) and 95% CIs for relapse rate (RR) and treatment-related mortality (TRM). Four prospective studies and one retrospective study were included with a total of 810 patients. We found auto-HSCT was superior to allo-HSCT in OS (HR = 1.42, 95% CI: 1.06-1.91, P = 0.02), and there was no difference between allo-HSCT and auto-HSCT for RFS (HR = 1.10, 95% CI: 0.86-1.40, P = 0.44) and RR (OR = 0.53, 95% CI: 0.22-1.26, P = 0.15). The risk of TRM for patients undergoing allo-HSCT was significantly higher than that of the patients who received auto-HSCT (OR = 5.06, 95% CI: 1.03-24.75, P = 0.05). Our meta-analysis shows that auto-HSCT may be an attractive and alternative treatment option for adult Ph+ ALL patients achieving CMR, with similar or better outcomes than allo-HSCT in the era of TKIs.
Topics: Adult; Allografts; Autografts; Disease-Free Survival; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Survival Rate
PubMed: 32960314
DOI: 10.1007/s00277-020-04258-1