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Nature Reviews. Disease Primers Jun 2024Acute lymphoblastic leukaemia (ALL) is a haematological malignancy characterized by the uncontrolled proliferation of immature lymphoid cells. Over past decades,... (Review)
Review
Acute lymphoblastic leukaemia (ALL) is a haematological malignancy characterized by the uncontrolled proliferation of immature lymphoid cells. Over past decades, significant progress has been made in understanding the biology of ALL, resulting in remarkable improvements in its diagnosis, treatment and monitoring. Since the advent of chemotherapy, ALL has been the platform to test for innovative approaches applicable to cancer in general. For example, the advent of omics medicine has led to a deeper understanding of the molecular and genetic features that underpin ALL. Innovations in genomic profiling techniques have identified specific genetic alterations and mutations that drive ALL, inspiring new therapies. Targeted agents, such as tyrosine kinase inhibitors and immunotherapies, have shown promising results in subgroups of patients while minimizing adverse effects. Furthermore, the development of chimeric antigen receptor T cell therapy represents a breakthrough in ALL treatment, resulting in remarkable responses and potential long-term remissions. Advances are not limited to treatment modalities alone. Measurable residual disease monitoring and ex vivo drug response profiling screening have provided earlier detection of disease relapse and identification of exceptional responders, enabling clinicians to adjust treatment strategies for individual patients. Decades of supportive and prophylactic care have improved the management of treatment-related complications, enhancing the quality of life for patients with ALL.
Topics: Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 38871740
DOI: 10.1038/s41572-024-00525-x -
Nature Reviews. Disease Primers Jun 2024
Topics: Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 38871713
DOI: 10.1038/s41572-024-00531-z -
Blood Cancer Journal Jun 2024Childhood acute lymphoblastic leukemia (cALL) survivors suffer early-onset chronic diseases classically associated with aging. Normal aging is accompanied by organ...
Childhood acute lymphoblastic leukemia (cALL) survivors suffer early-onset chronic diseases classically associated with aging. Normal aging is accompanied by organ dysfunctions, including immunological ones. We hypothesize that thymic immunosenescence occurs in cALL survivors and that its severity may correlate with early-onset chronic diseases. The PETALE study is a cALL survivor cohort with an extensive cardiovascular and metabolic evaluation. The thymic immunosenescence biomarker, signal joint T-cell receptor excision circles (TREC), was evaluated and was highly correlated with age in healthy participants (n = 281) and cALL survivors (n = 248). We observed a systematic thymic immunoage accentuation in each cALL survivor compared to controls ranging from 5.9 to 88.3 years. The immunoage gain was independent of age at diagnosis and treatment modalities and was more severe for females. Thymic aging was associated with several pathophysiological parameters, was greater in survivors suffering from metabolic syndrome, but there was no significant association with global physical condition. The decrease in TREC was independent from blood cell counts, which were normal, suggesting a segmental aging of the thymic compartment. Indeed, increased plasmatic T cell regulatory cytokines IL-6, IL-7 and GM-CSF accompanied high immunoage gain. Our data reveal that cALL or its treatment trigger a rapid immunoage gain followed by further gradual thymic immunosenescence, similar to normal aging. This leads to an enduring shift in accentuated immunoage compared to chronological age. Thus, accentuated thymic immunosenescence is a hallmark of cALL survivorship and TREC levels could be useful immunosenescence biomarkers to help monitoring the health of cancer survivors.
Topics: Humans; Female; Male; Child; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Adolescent; Adult; Thymus Gland; Child, Preschool; Young Adult; Aged; Middle Aged; Aged, 80 and over; Cancer Survivors; Immunosenescence; Survivorship
PubMed: 38871704
DOI: 10.1038/s41408-024-01071-1 -
Journal of Investigative Medicine : the... Jun 2024Forty-one families with multiple cases of de novo acute myeloid leukemia (AML), B-cell acute lymphocytic leukemia (B-ALL) or both are presented. The families were...
Forty-one families with multiple cases of de novo acute myeloid leukemia (AML), B-cell acute lymphocytic leukemia (B-ALL) or both are presented. The families were randomly collected from physicians, genetic counselors and other sources. Medical records were collected and reviewed for all families. In 17 of the families a parent and child with acute leukemia were identified and in 15 of the pairs the parent and child were of the same sex. Nine grandparent-grandchild affected pairs with AML-AML were identified, occurring in 6 families, and 6 of those pairs were also of the same sex. Anticipation was a common feature of these multigenerational pairs. Twenty families were identified with multiple siblings (none twins) with acute leukemia. This includes 16 sibling pairs and 4 sibling triples. The members of each sibling pair in the AML-AML group and in the B-ALL-B-ALL group were generally of roughly the same age. Curiously, this is not true of those in the AML-B-ALL group. Four of the 41 families had contributions to more than 1 family relationship category. Although inheritance in familial acute leukemia has usually been consistent with an autosomal dominant pattern, these data suggest that an X chromosome gene may be involved in some cases, perhaps in the pseudoautosomal region of the X chromosome as we have reported in familial Hodgkin lymphoma.
PubMed: 38869159
DOI: 10.1177/10815589241262735 -
Clinical Laboratory Jun 2024
Topics: Humans; Male; E1A-Associated p300 Protein; Oncogene Proteins, Fusion; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Trans-Activators; Middle Aged
PubMed: 38868890
DOI: 10.7754/Clin.Lab.2023.231226 -
BMC Infectious Diseases Jun 2024The impact of COVID-19 infection on the blood system remains to be investigated, especially with those encountering hematological malignancies. It was found that a high... (Comparative Study)
Comparative Study
BACKGROUND
The impact of COVID-19 infection on the blood system remains to be investigated, especially with those encountering hematological malignancies. It was found that a high proportion of cancer patients are at an elevated risk of encountering COVID-19 infection. Leukemic patients are often suppressed and immunocompromised, which would impact the pathology following COVID-19 infection. Therefore, this research aims to bring valuable insight into the mechanism by which COVID-19 infection influences the hematological and biochemical parameters of patients with acute leukemia.
METHODS
This retrospective investigation uses repeated measures to examine changes in hematological and biochemical parameters among patients with acute leukemia before and after COVID-19 infection at a major Saudi tertiary center. The investigation was conducted at the Ministry of National Guard-Health Affairs in Riyadh, Saudi Arabia, on 24 acute leukemia patients with COVID-19 between April 2020 and July 2023. The impact of COVID-19 on clinical parameters, comorbidities, and laboratory values was evaluated using data obtained from the electronic health records at four designated time intervals. The relative importance of comorbidities, testing preferences, and significant predictors of survival was ascertained.
RESULTS
The majority of leukemic COVID-19-infected patients, primarily detected through PCR tests, were diagnosed with acute lymphoblastic leukemia (70.8%). The hematological and biochemical parameters exhibited stability, except for a brief increase in ALT and a sustained rise in AST. These changes were not statistically significant, and parameters remained normal at all time points. Additionally, an increase in monocyte count was shown at time point-3, as well as platelet counts at time point 2.
CONCLUSION
While this study did not detect statistically significant effects of COVID-19 on biochemical and hematological parameters in acute leukemia patients, further investigation is needed to fully understand the potential adverse reactions and modifications following COVID-19 infection.
Topics: Humans; COVID-19; Male; Female; Retrospective Studies; Adult; Middle Aged; Saudi Arabia; SARS-CoV-2; Young Adult; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Aged; Leukemia, Myeloid, Acute; Adolescent; Comorbidity
PubMed: 38862891
DOI: 10.1186/s12879-024-09485-9 -
Cirugia Y Cirujanos 2024To evaluate if the comorbidity and coinfections presented by SARS-CoV-2 infection vs. COVID-19 impact our Mexican children. (Observational Study)
Observational Study
OBJECTIVE
To evaluate if the comorbidity and coinfections presented by SARS-CoV-2 infection vs. COVID-19 impact our Mexican children.
METHOD
Prospective and observational study that included the 2020-2021 peak influenza season. All patients with a diagnosis of infection by SARS-CoV-2 vs. COVID-19 who were admitted to the Hospital Infantil de Mexico were analyzed. Real-time RT-PCR for SARS-CoV-2 was performed in all patients, determining E, RdRp and RP genes and protein N, as well as RT-PCR for detection of respiratory viruses.
RESULTS
The inclusion criteria were met by 163 patients. The group with the highest risk of becoming ill was adolescents (40.4%), followed by schoolchildren and preschoolers (21.4% and 19.6% of the cases, respectively). There were three cases with viral coinfection: two (1.2%) with parvovirus B-19 and one (0.6%) with herpes type I; another two (1.2%) showed bacterial coinfection. The main comorbidity were obesity, acute lymphoblastic leukemia and arterial hypertension. Regarding mortality, we only had four cases (2.4%).
CONCLUSIONS
Obesity, cancer, hypertension, heart disease and diabetes are comorbidity present in our patients, as referred to in literature, but not coinfections. In our study, we did not have any associated mortality related to comorbidity.
Topics: Humans; COVID-19; Coinfection; Child; Child, Preschool; Comorbidity; Male; Prospective Studies; Female; Adolescent; Mexico; Influenza, Human; Hypertension; Infant; Seasons; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Bacterial Infections
PubMed: 38862113
DOI: 10.24875/CIRU.23000080 -
Biochimica Et Biophysica Acta.... Jun 2024Cytokine receptor-like factor 2 (CRLF2) and interleukin-7 receptor α (IL-7Rα) form a receptor for thymic stromal lymphopoietin (TSLP). A somatic mutation consisting of...
Identification of amino acids in transmembrane domains of mutated cytokine receptor-like factor 2 and interleukin-7 receptor α required for constitutive signal transduction.
Cytokine receptor-like factor 2 (CRLF2) and interleukin-7 receptor α (IL-7Rα) form a receptor for thymic stromal lymphopoietin (TSLP). A somatic mutation consisting of the substitution of five amino acids (SLLLL) in the transmembrane domain of CRLF2 with three amino acids, including glutamic acid, isoleucine, and methionine (insEIM), which has been identified in acute lymphocytic leukemia, causes the TSLP-independent dimerization with IL-7Rα and activation. However, the dimerization mechanism remains unclear. In this study, we examined the involvement of the amino acids in the transmembrane domains of EIM CRLF2 and IL-7Rα in TSLP-independent activation. HEK293 cells were transfected with vectors encoding CRLF2 and IL-7Rα, or their mutants, in which the amino acid of the transmembrane domain was replaced with alanine. STAT5 phosphorylation was detected using western blotting, and receptor dimerization was analyzed using the NanoBiT assay. The substitution of glutamic acid within the insEIM mutation for alanine failed to cause the STAT5 phosphorylation in the absence of TSLP. Moreover, the alanine substation of the specific leucine residues in the transmembrane domains of both CRLF2 and IL-7Rα abrogated the TSLP-independent signal transduction and dimerization. The mutation of IL-7Rα W264 partially reduced the phosphorylation of STAT5 without affecting receptor dimerization. These results suggest that the amino acids in the transmembrane domains of EIM CRLF2 and IL-7Rα play at least three possible functions: interaction through hydrogen bonds, hydrophobic interaction, and signal transduction. Our findings contribute to a better understanding of the function of the transmembrane domains of cytokine receptors in their dimerization and signal transduction.
PubMed: 38862034
DOI: 10.1016/j.bbamem.2024.184359 -
Acta Haematologica Jun 2024Introduction Promotion of self-efficacy can enhance engagement with healthcare and treatment adherence in patients with cancer. We report the outcomes of a pilot trial...
Effect of Digital Health Coaching on Self-Efficacy and Patient Reported Outcomes in Individuals with Acute Myeloid and Chronic Lymphocytic Leukemia: A Pilot Randomized Controlled Trial.
Introduction Promotion of self-efficacy can enhance engagement with healthcare and treatment adherence in patients with cancer. We report the outcomes of a pilot trial of a digital health coach intervention in patients with leukemia with the aim of improving self-efficacy. Methods Adult patients with newly diagnosed acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) were randomized 1:1 to a digital health coach intervention or standard of care. The primary outcome of self-efficacy was measured by the Cancer Behavior Inventory (CBI) score. Results One-hundred and forty-seven patients (37 AML, 110 CLL) were enrolled from July 2020 to December 2022. In the AML cohort, there was a mean increase in CBI score of 7.03 in the digital health coaching arm compared to a mean decrease of -3.57 in the control arm at 30 days (p=0.219). There were no significant associations between the intervention and other patient reported outcomes for patients with CLL. Conclusion There were numerical, but not statistically significant increases in self-efficacy metrics in AML patients who received digital health coaching. Although this trial was underpowered due to enrollment limitations during a pandemic, digital health coaching may provide benefit to patients with hematologic malignancy and warrants further investigation.
PubMed: 38861934
DOI: 10.1159/000539756 -
Infection Prevention in Practice Sep 2024Gastroenteritis accounts for about 10% of the deaths among children, especially in immunocompromised children. Few studies on the prevalence of gastrointestinal...
BACKGROUND
Gastroenteritis accounts for about 10% of the deaths among children, especially in immunocompromised children. Few studies on the prevalence of gastrointestinal infections caused by RNA viruses have been done in Iran. The aim of the study was to evaluate the detection of RNA viruses causing diarrhoea using a multiplex PCR.
METHODS
Stool samples were collected from 130 paediatric patients with diarrhoea who had acute lymphocytic leukaemia, non-Hodgkin lymphoma, and retinoblastoma. After RNA extraction and synthesis of cDNA, multiplex PCR was done to evaluate the presence of rotavirus, norovirus, astrovirus, and enterovirus.
RESULTS
There were 9 (6.9%), 7 (5.4%), 3 (2.3%), and 6 (4.6%) cases of rotavirus, norovirus, astrovirus, and enterovirus detected, respectively. One case of co-infection with astrovirus and norovirus was observed.
CONCLUSIONS
This is the first report from Iran which identified the presence of common RNA viruses causing diarrhoea in immunocompromised children. Increased awareness of these viruses will enable healthcare professionals to improve strategies and policies to control spread and infection caused by these viruses.
PubMed: 38855735
DOI: 10.1016/j.infpip.2024.100370