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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 -
Haematologica Oct 2019Minimal (or 'measurable') residual disease in acute lymphoblastic leukemia appears to be a prognostic indicator, with potential value in informing individualized... (Meta-Analysis)
Meta-Analysis
Minimal (or 'measurable') residual disease in acute lymphoblastic leukemia appears to be a prognostic indicator, with potential value in informing individualized treatment decisions. Complete understanding of the strength of the association between minimal residual disease and long-term outcomes is, however, lacking. A systematic literature review and meta-analysis were performed to elucidate the clinical significance of minimal residual disease with respect to relapse-free survival and overall survival in precursor B-cell acute lymphoblastic leukemia. A total of 23 articles and abstracts, most published between 2012 and 2016, were identified for inclusion in the primary meta-analysis. Typically, patients were in their first complete remission at the time of minimal residual disease assessment; in two studies, all patients were in their second, or later, complete remission. The primary analysis revealed improved relapse-free survival across all studies for patients who achieved minimal residual disease negativity (random effects hazard ratio, 2.34; 95% confidence interval, 1.91-2.86). Improved overall survival for patients who achieved minimal residual disease negativity was also observed (hazard ratio, 2.19; 95% confidence interval, 1.63-2.94). There was no observed difference in the impact of minimal residual disease status in subgroups based on disease stage, minimal residual disease sensitivity threshold level, Philadelphia chromosome status, histological phenotype, risk group, minimal residual disease testing location, minimal residual disease timing after induction, or minimal residual disease detection method. Despite heterogeneity in study design and patient populations between the contributing studies, these data provide a compelling argument for minimal residual disease as a clinical tool for assessing prognosis and guiding treatment decisions in precursor B-cell acute lymphoblastic leukemia.
Topics: Adult; Humans; Neoplasm, Residual; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Remission Induction
PubMed: 30890593
DOI: 10.3324/haematol.2018.201053 -
Acta Bio-medica : Atenei Parmensis Jan 2022Myasthenia Gravis (MG) is a rare neurological condition characterized by muscle weakness that worsens after use. Myeloproliferative Neoplasms (MPNs) are disorders due to...
Myasthenia Gravis (MG) is a rare neurological condition characterized by muscle weakness that worsens after use. Myeloproliferative Neoplasms (MPNs) are disorders due to stem-cell hyperplasia characterized by an increased peripheral blood cell count, overactive bone marrow, and proliferation of mature hematopoietic cells. MPNs may be Philadelphia (Ph) chromosome-positive or Negative .A systematic review of case reports was conducted by searching PubMed, Scopus, and Google scholar to identify case reports in which there is an association between MG and MPN and know whether MG can be considered a possible neurological paraneoplastic syndrome in patients with MPNs. A total of 13 cases of MPNs associated with MG were identified. The most common type of MPN associated with MG was chronic myeloid leukemia (CML) (10 out of 13 patients). In most of the patients, MG symptoms appeared after a diagnosis of MPN was made. Considering that 10 out of the 13 patients in our cohort had positive auto-antibodies though only 4 of them had thymic hyperplasia, we hypothesize that bone marrow proliferation was responsible for the production of autoantibodies in these patients.As the clonal cell population cannot be eliminated entirely in the bone marrow even after treatment with tyrosine kinase inhibitors (TKI) in Ph +ve MPNs and JAK2 inhibitors in Ph -ve MPNS, MG can occur even in patients who are treated with these agents. A high index of suspicion is needed to diagnose it early, and treatment should be initiated immediately with steroids and anticholinergic agents.
Topics: Bone Marrow; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myasthenia Gravis; Myeloproliferative Disorders; Paraneoplastic Syndromes, Nervous System
PubMed: 35075066
DOI: 10.23750/abm.v92i6.12180 -
Medicine Nov 2022Philadelphia chromosome (Ph) positive myelodysplastic syndrome (MDS) is a very rare disease. At present, the specific role of Ph in MDS is not clear, but such patients...
INTRODUCTION
Philadelphia chromosome (Ph) positive myelodysplastic syndrome (MDS) is a very rare disease. At present, the specific role of Ph in MDS is not clear, but such patients seem to have a poor prognosis, so the disease deserves attention. Here, we describe the history of a woman with Ph-positive MDS and perform a systematic review of related literature.
PATIENT CONCERNS AND DIAGNOSIS
We report a 38-year-old woman with Ph-positive MDS.
INTERVENTIONS AND OUTCOMES
She received chemotherapy with decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor (DCAG) combined with imatinib mesylate and achieved a bone marrow remission. She then underwent an allogeneic hematopoietic stem cell transplant. The condition is good and no recurrence of the disease has been observed.
CONCLUSION
Ph-positive MDS is a very rare disease. Ph may aid in the malignant progression of MDS leaving such patients with a very poor prognosis. Tyrosine kinase inhibitors (TKIs) plus chemotherapy followed by allogeneic hematopoietic stem cell transplantation has provided these patients with satisfactory outcomes.
Topics: Humans; Female; Adult; Philadelphia Chromosome; Transplantation, Homologous; Rare Diseases; Myelodysplastic Syndromes; Hematopoietic Stem Cell Transplantation
PubMed: 36401464
DOI: 10.1097/MD.0000000000031874 -
The Cochrane Database of Systematic... Dec 2019Spinal muscular atrophy (SMA) is caused by a homozygous deletion of the survival motor neuron 1 (SMN1) gene on chromosome 5, or a heterozygous deletion in combination... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Spinal muscular atrophy (SMA) is caused by a homozygous deletion of the survival motor neuron 1 (SMN1) gene on chromosome 5, or a heterozygous deletion in combination with a point mutation in the second SMN1 allele. This results in degeneration of anterior horn cells, which leads to progressive muscle weakness. By definition, children with SMA type I are never able to sit without support and usually die or become ventilator dependent before the age of two years. There have until very recently been no drug treatments to influence the course of SMA. We undertook this updated review to evaluate new evidence on emerging treatments for SMA type I. The review was first published in 2009 and previously updated in 2011.
OBJECTIVES
To assess the efficacy and safety of any drug therapy designed to slow or arrest progression of spinal muscular atrophy (SMA) type I.
SEARCH METHODS
We searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and ISI Web of Science conference proceedings in October 2018. We also searched two trials registries to identify unpublished trials (October 2018).
SELECTION CRITERIA
We sought all randomised controlled trials (RCTs) or quasi-RCTs that examined the efficacy of drug treatment for SMA type I. Included participants had to fulfil clinical criteria and have a genetically confirmed deletion or mutation of the SMN1 gene (5q11.2-13.2). The primary outcome measure was age at death or full-time ventilation. Secondary outcome measures were acquisition of motor milestones, i.e. head control, rolling, sitting or standing, motor milestone response on disability scores within one year after the onset of treatment, and adverse events and serious adverse events attributable to treatment during the trial period. Treatment strategies involving SMN1 gene replacement with viral vectors are out of the scope of this review.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology.
MAIN RESULTS
We identified two RCTs: one trial of intrathecal nusinersen in comparison to a sham (control) procedure in 121 randomised infants with SMA type I, which was newly included at this update, and one small trial comparing riluzole treatment to placebo in 10 children with SMA type I. The RCT of intrathecally-injected nusinersen was stopped early for efficacy (based on a predefined Hammersmith Infant Neurological Examination-Section 2 (HINE-2) response). At the interim analyses after 183 days of treatment, 41% (21/51) of nusinersen-treated infants showed a predefined improvement on HINE-2, compared to 0% (0/27) of participants in the control group. This trial was largely at low risk of bias. Final analyses (ranging from 6 months to 13 months of treatment), showed that fewer participants died or required full-time ventilation (defined as more than 16 hours daily for 21 days or more) in the nusinersen-treated group than the control group (hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.32 to 0.89; N = 121; a 47% lower risk; moderate-certainty evidence). A proportion of infants in the nusinersen group and none of 37 infants in the control group achieved motor milestones: 37/73 nusinersen-treated infants (51%) achieved a motor milestone response on HINE-2 (risk ratio (RR) 38.51, 95% CI 2.43 to 610.14; N = 110; moderate-certainty evidence); 16/73 achieved head control (RR 16.95, 95% CI 1.04 to 274.84; moderate-certainty evidence); 6/73 achieved independent sitting (RR 6.68, 95% CI 0.39 to 115.38; moderate-certainty evidence); 7/73 achieved rolling over (RR 7.70, 95% CI 0.45 to 131.29); and 1/73 achieved standing (RR 1.54, 95% CI 0.06 to 36.92; moderate-certainty evidence). Seventy-one per cent of nusinersen-treated infants versus 3% of infants in the control group were responders on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) measure of motor disability (RR 26.36, 95% CI 3.79 to 183.18; N = 110; moderate-certainty evidence). Adverse events and serious adverse events occurred in the majority of infants but were no more frequent in the nusinersen-treated group than the control group (RR 0.99, 95% CI 0.92 to 1.05 and RR 0.70, 95% CI 0.55 to 0.89, respectively; N = 121; moderate-certainty evidence). In the riluzole trial, three of seven children treated with riluzole were still alive at the ages of 30, 48, and 64 months, whereas all three children in the placebo group died. None of the children in the riluzole or placebo group developed the ability to sit, which was the only milestone reported. There were no adverse effects. The certainty of the evidence for all measured outcomes from this study was very low, because the study was too small to detect or rule out an effect, and had serious limitations, including baseline differences. This trial was stopped prematurely because the pharmaceutical company withdrew funding. Various trials and studies investigating treatment strategies other than nusinersen, such as SMN2 augmentation by small molecules, are ongoing.
AUTHORS' CONCLUSIONS
Based on the very limited evidence currently available regarding drug treatments for SMA type 1, intrathecal nusinersen probably prolongs ventilation-free and overall survival in infants with SMA type I. It is also probable that a greater proportion of infants treated with nusinersen than with a sham procedure achieve motor milestones and can be classed as responders to treatment on clinical assessments (HINE-2 and CHOP INTEND). The proportion of children experiencing adverse events and serious adverse events on nusinersen is no higher with nusinersen treatment than with a sham procedure, based on evidence of moderate certainty. It is uncertain whether riluzole has any effect in patients with SMA type I, based on the limited available evidence. Future trials could provide more high-certainty, longer-term evidence to confirm this result, or focus on comparing new treatments to nusinersen or evaluate them as an add-on therapy to nusinersen.
Topics: Child, Preschool; Humans; Infant; Neuroprotective Agents; Oligonucleotides; Randomized Controlled Trials as Topic; Spinal Muscular Atrophies of Childhood
PubMed: 31825542
DOI: 10.1002/14651858.CD006281.pub5 -
Annals of Diagnostic Pathology Aug 2024Philadelphia (Ph) chromosome (9;22)(q34;q11) comprises 90-95 % of chronic myeloid leukemia (CML), while 5-10 % of CML have translocations involving three or more... (Review)
Review
Does presence of complex translocations involving BCR::ABL1 in chronic myeloid leukemia affect the response rate to tyrosine kinase inhibitors? A systematic review of the literature.
Philadelphia (Ph) chromosome (9;22)(q34;q11) comprises 90-95 % of chronic myeloid leukemia (CML), while 5-10 % of CML have translocations involving three or more chromosomes. The outcome of treating patients harbouring complex Ph-positive cytogenetics with tyrosine kinase inhibitors (TKI) is unclear. In the present systematic review, we aim to summarise the response of patients with complex Ph-positive cytogenetics to treatment with TKI therapy. We collated all available literature from databases such as PubMed, Google Scholar, Web of Science database, Cochrane library, Scopus and Embase (up until January 31st, 2024), which describe cases of patients with CML, harbouring complex Ph-positive variations (three and four-way translocations), and summarised their response to TKI therapy. The studies were screened for the following criteria: documented TKI intervention and outcome (whether CR was achieved). Studies that did not report the same, were excluded. Additionally, we report a case from our center of a 55-year-old patient with CML, positive for the Ph-chromosome, harbouring a three-way translocation involving chromosome 15 i.e. 46XX, t(9;15;22) (q34;p11;q11). Identification of BCR::ABL and involvement of chromosome 15 was carried out using conventional cytogenetics, fluorescence in situ hybridization (FISH), and quantitative PCR (qPCR). Based on the inclusion criteria, a total of 15 studies were included from which a total of 87 cases were covered. Overall, we identified 38 unique complex three- and four-way translocations across 87 Ph-positive cases and found that 85 patients with complex Ph-positive cytogenetics achieved complete remission upon treatment and did not appear to have a lesser response to TKI therapy.
Topics: Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Translocation, Genetic; Protein Kinase Inhibitors; Fusion Proteins, bcr-abl; Middle Aged; Philadelphia Chromosome; Treatment Outcome; Male; Female; Tyrosine Kinase Inhibitors
PubMed: 38636337
DOI: 10.1016/j.anndiagpath.2024.152303