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Chronic lymphocytic leukemia (CLL) is a malignant tumor characterized by the accumulation of mature small lymphocytes in peripheral blood, bone marrow, lymph nodes and secondary lymphoid tissues.
The main cause of death in CLL patients is immune dysfunction and infection
.
Although the application of chemoimmunotherapy and targeted therapies (BTK inhibitors and BCL-2 inhibitors) has improved the prognosis of CLL patients and can extend the overall survival (OS), in the past forty years, deaths caused by infections The rate has not decreased
.
Therefore, infection is the main cause of death in CLL patients
.
In the precursor state of monoclonal B lymphocytosis (MBL) (Figure 1), the watchful waiting period of newly diagnosed patients, or during chemoimmunotherapy or targeted therapy, the occurrence of infection can adversely affect the prognosis of patients
.
Figure 1: Chronic lymphocytic leukemia (CLL) gradually develops from the precursor state of monoclonal B lymphocytosis (MBL)
.
Before the diagnosis and after treatment, the immune function of the newly diagnosed patients is low, so the risk of infection is increased (red arrow).
The treatment of CLL infection is due to the higher risk of death after infection in CLL patients.
When the clinical symptoms of Lang-positive bacteria infection appear, early empiric antibiotic treatment is started immediately
.
Before the use of antibiotics, a comprehensive microbiological examination should be carried out to guide the follow-up targeted antibacterial treatment
.
Patients with CLL should pay attention to invasive fungal infections, especially those who are being treated with BTK inhibitors and corticosteroids
.
However, the routine preventive use of antifungal drugs is not recommended because the incidence of systemic fungal infections is low and there is an interaction between antifungal drugs and CLL treatment drugs
.
Vaccination and prevention of infection CLL patients have a higher risk of invasive pneumococcal infection, so it is recommended to receive pneumococcal vaccine at the same time as seasonal influenza vaccine
.
Generally speaking, the serological vaccine immune response of CLL patients may disappear, especially in patients who have recently been treated with CD20 monoclonal antibodies or immunosuppressants (such as corticosteroids or BTK inhibitors)
.
Therefore, patients with CLL may still be infected with this microorganism after being vaccinated
.
Immunoglobulin replacement therapy is only recommended for patients with recurrent severe infections and severe hypogammaglobulinemia, because the positive impact of replacement therapy on OS has not been confirmed, and the data supporting immunoglobulin replacement therapy are also very limited
.
In general, prophylactic antibiotics are not recommended for patients with CLL
.
However, for patients treated with purine analogs or PI3Kδ inhibitors, drugs such as compound trimethoprim should be considered to prevent pneumocystis, and for patients with a history of herpes, drugs such as acyclovir should be considered to prevent herpes
.
In addition, before any treatment, the infection status of chronic hepatitis B virus should be tested, because the reactivation of hepatitis B virus can significantly affect the prognosis of CLL patients
.
For patients with neutropenia during chemotherapy and targeted therapy, the use of granulocyte colony stimulating factor (G-CSF) should be considered
.
Prediction of infection risk in CLL patients In order to identify high-risk CLL patients with severe infections, researchers developed a machine learning algorithm CLL-TIM.
org to identify these patients at high risk of infection
.
A phase II, randomized, investigator-initiated clinical trial of PreVent-ACaLL (NCT03868722) has a high risk of infection (>65%) and/or CLL patients who need treatment within 2 years of diagnosis (using the CLL-TIM algorithm), the primary endpoint After 24 weeks (12 weeks after the end of treatment), the survival period of the treatment group and the observation group without ≥ grade 3 infection
.
The purpose of this trial is to observe whether short-term (12 weeks) treatment with the BTK inhibitor acatinib and the BCL-2 inhibitor Veneclair can improve the immune function of patients with CLL and reduce the risk of infection
.
It is reported that the PreVent-ACaLL trial is the first clinical trial aimed at improving the immune function of CLL patients, and we look forward to its excellent clinical results
.
A similar algorithm for predicting the risk of infection after CLL treatment has not yet been developed
.
Recent studies have shown that some recurrent mutations in CLL may be related to fatal infections after chemoimmunotherapy
.
Researchers are currently studying the method of combining OMICs data with the CLL-TIM algorithm to assess the risk of infection in different stages of newly diagnosed and treated CLL patients
.
Reference source: Carsten Utoft Niemann.
2021 SOHO.
EXABS-192-CLL.
Stamp "read the original text", we make progress together
The main cause of death in CLL patients is immune dysfunction and infection
.
Although the application of chemoimmunotherapy and targeted therapies (BTK inhibitors and BCL-2 inhibitors) has improved the prognosis of CLL patients and can extend the overall survival (OS), in the past forty years, deaths caused by infections The rate has not decreased
.
Therefore, infection is the main cause of death in CLL patients
.
In the precursor state of monoclonal B lymphocytosis (MBL) (Figure 1), the watchful waiting period of newly diagnosed patients, or during chemoimmunotherapy or targeted therapy, the occurrence of infection can adversely affect the prognosis of patients
.
Figure 1: Chronic lymphocytic leukemia (CLL) gradually develops from the precursor state of monoclonal B lymphocytosis (MBL)
.
Before the diagnosis and after treatment, the immune function of the newly diagnosed patients is low, so the risk of infection is increased (red arrow).
The treatment of CLL infection is due to the higher risk of death after infection in CLL patients.
When the clinical symptoms of Lang-positive bacteria infection appear, early empiric antibiotic treatment is started immediately
.
Before the use of antibiotics, a comprehensive microbiological examination should be carried out to guide the follow-up targeted antibacterial treatment
.
Patients with CLL should pay attention to invasive fungal infections, especially those who are being treated with BTK inhibitors and corticosteroids
.
However, the routine preventive use of antifungal drugs is not recommended because the incidence of systemic fungal infections is low and there is an interaction between antifungal drugs and CLL treatment drugs
.
Vaccination and prevention of infection CLL patients have a higher risk of invasive pneumococcal infection, so it is recommended to receive pneumococcal vaccine at the same time as seasonal influenza vaccine
.
Generally speaking, the serological vaccine immune response of CLL patients may disappear, especially in patients who have recently been treated with CD20 monoclonal antibodies or immunosuppressants (such as corticosteroids or BTK inhibitors)
.
Therefore, patients with CLL may still be infected with this microorganism after being vaccinated
.
Immunoglobulin replacement therapy is only recommended for patients with recurrent severe infections and severe hypogammaglobulinemia, because the positive impact of replacement therapy on OS has not been confirmed, and the data supporting immunoglobulin replacement therapy are also very limited
.
In general, prophylactic antibiotics are not recommended for patients with CLL
.
However, for patients treated with purine analogs or PI3Kδ inhibitors, drugs such as compound trimethoprim should be considered to prevent pneumocystis, and for patients with a history of herpes, drugs such as acyclovir should be considered to prevent herpes
.
In addition, before any treatment, the infection status of chronic hepatitis B virus should be tested, because the reactivation of hepatitis B virus can significantly affect the prognosis of CLL patients
.
For patients with neutropenia during chemotherapy and targeted therapy, the use of granulocyte colony stimulating factor (G-CSF) should be considered
.
Prediction of infection risk in CLL patients In order to identify high-risk CLL patients with severe infections, researchers developed a machine learning algorithm CLL-TIM.
org to identify these patients at high risk of infection
.
A phase II, randomized, investigator-initiated clinical trial of PreVent-ACaLL (NCT03868722) has a high risk of infection (>65%) and/or CLL patients who need treatment within 2 years of diagnosis (using the CLL-TIM algorithm), the primary endpoint After 24 weeks (12 weeks after the end of treatment), the survival period of the treatment group and the observation group without ≥ grade 3 infection
.
The purpose of this trial is to observe whether short-term (12 weeks) treatment with the BTK inhibitor acatinib and the BCL-2 inhibitor Veneclair can improve the immune function of patients with CLL and reduce the risk of infection
.
It is reported that the PreVent-ACaLL trial is the first clinical trial aimed at improving the immune function of CLL patients, and we look forward to its excellent clinical results
.
A similar algorithm for predicting the risk of infection after CLL treatment has not yet been developed
.
Recent studies have shown that some recurrent mutations in CLL may be related to fatal infections after chemoimmunotherapy
.
Researchers are currently studying the method of combining OMICs data with the CLL-TIM algorithm to assess the risk of infection in different stages of newly diagnosed and treated CLL patients
.
Reference source: Carsten Utoft Niemann.
2021 SOHO.
EXABS-192-CLL.
Stamp "read the original text", we make progress together
