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» Home » CAD » Oncology » Hematology » Acute Myeloid Leukemia (AML)
Background
Acute myeloid leukemia (AML) is the most prevalent type of leukemia in adults, accounting for over 80% of all occurrences.
Clonal growth of immature blast cells in the peripheral blood, and bone marrow results in inefficient erythropoiesis and bone marrow failure.
It usually begins in the bone marrow but rapidly spreads to the blood. It can spread to the lymph nodes, liver, testicles, spleen, and central nervous system.
Epidemiology
In the United States, there are around 20,000 instances every year.
The typical age upon diagnosis is around 65 years. It is more common in non-Hispanic whites. Males outnumber females by a factor of five, with a ratio of 5:3.
Anatomy
Pathophysiology
AML is defined as mutations in hematopoiesis-related genes. These mutations cause clonal growth of undifferentiated myeloid precursors in the peripheral blood and bone marrow, which leads to inadequate erythropoiesis and bone marrow failure.
Although the specific source of genetic abnormalities is unknown, a few risk factors include radiation, chemotherapeutic drugs, and smoking. Myelodysplastic syndrome, myeloproliferative diseases, aplastic anemia, and paroxysmal nocturnal hemoglobinuria can all lead to AML.
It is vital to investigate familial causes of genetic alterations. Nucleophosmin 1 mutations are seen in 25%-30% of AML patients. This is the most prevalent mutation detected in AML and is more common in women.
Clinically, the mutation has a monocytic appearance and predicts a good outcome without FMS-like tyrosine kinase three or FLT3-ITD. In young and old individuals, NPM1 mutations are chemosensitive to rigorous chemotherapy.
Etiology
Several congenital abnormalities, including Bloom syndrome and Down syndrome, increase the risk of AML, which often manifests in the early twenties. Cigarette smoke, radiation, and benzene are all environmental risk factors for AML. Lastly, prior chemotherapeutic drug exposure is a risk factor for AML.
Genetics
Prognostic Factors
Chromosome abnormalities and genetic mutations are prognostic factors (FLT3 gene has unfavorable prognosis while NPM1 gene has a favorable prognosis).
Elderly individuals, white blood cell count larger than 100,000 at the time of diagnosis, and the detection of leukemic cells in the central nervous system have all been linked to poorer outcomes.
Clinical History
Physical Examination
Age group
Associated comorbidity
Associated activity
Acuity of presentation
Differential Diagnoses
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
by Stage
by Modality
Chemotherapy
Radiation Therapy
Surgical Interventions
Hormone Therapy
Immunotherapy
Hyperthermia
Photodynamic Therapy
Stem Cell Transplant
Targeted Therapy
Palliative Care
Medication
5
mg/m^2
Intravenous (IV)
5
days
daily infused over 3 hours, generally given in combination with daunorubicin and cytarabine
CLAG regimen:
5
mg/m^2
Intravenous (IV)
Over 2 hr
5
days
given in combination with cytarabine, filgrastim and mitoxantrone
300
mg
Orally
once a day
14
days
for 28 days cycle
100
mg
Tablet
Oral
once a day
Continue the treatment until disease progression or unacceptable toxicity occurs Patients without disease progression or unacceptable severe effects continue the treatment for six months to achieve clinical response
20
mg/m^2
Intravenous (IV)
over 1 hr
once daily for 5 days at 28-day cycle
For AML with TP53 mutation:
20 mg/m2 IV infused over 1 hour for 10 days for 28-day cycle
20 mg/m2 IV infused over 1 hour for 5 days for 28-days cycle in combination with venetoclax
Dose Adjustments
Require dose adjustment in case of renal dysfunction or hemodialysis
Terminate the use of docetaxel if total bilirubin > 2.5 times ULN
Administer 80% of the dose: AST/ALT > 2.5 to 5 times ULN
Discontinue the therapy with docetaxel: AST/ALT >5 times
Delay the treatment for 6 to 8 weeks: hematologic toxicity (ANC<1000/µl and platelets < 50,000/µl)
500
mg
Orally
once a day
continue the treatment until disease progression or unacceptable toxicity occurs
patients without disease progression or unacceptable toxicity, given the treatment for up to a minimum of 6 months for clinical response
Newly diagnosed CD33-positive acute myeloid leukemia (AML):
COMBINATION REGIMEN
Induction: 3 mg per m2 IV over 2hrs for Days 1, 4, and 7 given in combination with daunorubicin and cytarabine
the drug gemtuzumab during the second induction cycle gemtuzumab isn't encouraged for patients who require a second induction cycle
Consolidation: 3 mg per m2 IV over 2hrs on Day 1 in combination with daunorubicin and cytarabine
Newly diagnosed CD33-positive acute myeloid leukemia (AML):
SINGLE-AGENT REGIMEN:
Induction: 6 mg per m2 IV over 2hrs on Day 1 and 3 mg/m2 IV on Day 8
Continuation: 2 mg per m2 IV over 2hrs on Day 1 every four weeks
Relapsed or Refractory CD33-positive AML:
SINGLE-AGENT REGIMEN:
3 mg per m2 IV over 2hrs on Days 1, 4, and 7
a single course of gemtuzumab given for treatment in the relapsed or refractory setting
150
mg
Capsules
Orally
twice a day
until the disease progresses
Dose Adjustments
Differentiation syndrome
Withhold REZLIDHIA if differentiation syndrome is suspected until signs and symptoms become improved
Systemic corticosteroids should be given; hemodynamic monitoring should start and continue for at least three days after symptom remission
Restart REZLIDHIA at 150 mg twice daily once the differentiation syndrome has subsided.
Indicated for Acute myeloid leukemia following induction therapy:
• This is a treatment regimen for administering medication (likely a form of chemotherapy) intravenously at a dose of 250 mcg/m2/day over 4 hours
• The treatment is to begin on or around day 11 of the treatment cycle, or four days after the completion of induction chemotherapy provided that the patient's bone marrow is hypoplastic (meaning that it has a reduced number of cells) and that the number of blasts (immature blood cells) is less than 5%. Suppose a second cycle of induction chemotherapy is needed
• In that case, the treatment is to be administered approximately four days after the completion of the chemotherapy, again provided that the bone marrow is hypoplastic with less than 5% blasts
• The treatment is to continue until the patient's absolute neutrophil count (ANC) is more significant than 1500 cells/mm3 for three consecutive days or a maximum of 42 days
100 mg orally four times daily on 1-28 days of 28 days cycle. It is given in combination with 20 mg of cytarabine subcutaneously, twice daily, for 1-10 days of the cycle
Dose Adjustments
In case of QT prolongation (separate ECGs ≥2)
QTc >480 to 500 milliseconds
Check the electrolyte levels and provide supplements as indicated
Review & adjust concomitant medications with QTc interval-prolonging effects
Weekly monitor the ECGs for 2 weeks after the QTc prolongation resolution ≤480 milliseconds
QT >500 milliseconds
Check the electrolyte levels and provide supplements as indicated
Review & adjust concomitant medications with QTc interval-prolonging effects
Check on glasdegib dosing; restart at a reduced dose of 50 mg per day when QTc interval returns to 30 milliseconds
Weekly monitor the ECGs for 2 weeks after the QTc prolongation resolution
Consider re-starting glasdegib dose to 100 mg per day if other causes are identified for QTc prolongation
If QTc prolongation occurs with life-threatening arrhythmia, discontinue the dosing permanently
In case of hematologic toxicity
If platelets are less than 10 Gi/L or neutrophil count is less than 0.5 Gi/L for more than 42 days in the absence of disease, discontinue cytarabine and glasdegib permanently.
In case of non-hematologic toxicity
Interrupt glasdegib until symptoms are reduced
Start glasdegib at the same dose or reduce the dose to 50 mg
In high-grade, non-hematologic toxicity, discontinue glasdegib permanently
In case of renal impairment
No dosage modifications are recommended if eGFR 15-89 mL/min (mild-to-severe)
Monitor the patients with severe renal impairment (when eGFR is 15-29 mL/min); there is an increased risk of adverse effects
No studies are performed in the case of hepatic impairment
120 mg orally each day, the response may get delayed Continue the dose for at least 6 months until the unacceptable toxicity or disease progression
Dose Adjustments
In case of adverse reactions
For PRES (posterior reversible encephalopathy syndrome), discontinue the treatment
If the QTc interval >500 milliseconds interrupt the treatment; start over at 80 mg when the QTc interval gets backs within 30 milliseconds
For pancreatitis, interrupt the treatment if the condition persists; start over the dose at 80 mg
Differentiation Syndrome
If differentiation syndrome is suspected, administer systemic corticosteroids, and start hemodynamic monitoring
Continue this process until symptoms are resolved for minimum 3 days
Interrupt dose if severe symptoms and signs persist for over 48 hours after initiating corticosteroids
Start over the previous dose if the symptoms improve
Hepatic or renal impairment
In the case of mild to moderate hepatic or renal impairment, the effect of meaningful pharmacokinetics is unknown
In case of severe hepatic or renal impairment, the effect of the drug is unknown
50 mg orally twice daily from the 8th to the 21st day of the cycle
Use the drug in combination with standard daunorubicin and cytarabine
The dose should be taken with food
Induction therapy: On days 1 through 3, administer 12 mg/m2 once a day (in addition to 100 mg/m2 of cytarabine given as a continuous intravenous infusion on days 1 through 7)
Second Induction Therapy: On days 1 and 2, inject 12 mg/m2 (combined with a continuous 24-hour intravenous infusion of cytarabine on days 1 through 5)
Consolidation: Day 1 and Day 2 IV administration of 12 mg/m2. The first course is typically delivered six weeks after the last introductory course, while the second is delivered four weeks later.
Indicated for Acute Nonlymphocytic Leukaemia:
2 mg/kg orally everyday
If there is no improvement after four weeks, gradually increase to 3 mg/kg/day
Consume on an empty stomach to avoid nausea and vomiting
cytarabine/daunorubicin liposomal
Induction
First cycle: Administering liposomal daunorubicin at a dosage of 44 mg/m2 along with cytarabine at a dosage of 100 mg/m2 via intravenous infusion on days first third and fifth recommended
Second cycle: Exclusively intended for patients who do not experience a favorable outcome following the initial induction cycle
If there were no unacceptable toxicity, the second cycle can be administered within a time frame of 2-5 weeks following the initial cycle
If necessary, It involves the intravenous (IV) administration of liposomal daunorubicin at a dosage of 44 mg/m2 and cytarabine at a dosage of 100 mg/m2
This administration should be performed on the first and third days
Consolidation
Consolidation: intravenous liposomal (daunorubicin 29 mg/m2/cytarabine 65 mg/m2) on days 1 and 3
begin the initial consolidation phase approximately 5-8 weeks following the commencement of the preceding induction phase
quizartinib (Pending FDA Approval)
FDA approval pending for relapsed or resistant acute myeloid leukemia (AML).
Children and adolescents:
8.9
mg/m^2
Intravenous (IV)
once a day
5
days
Children > 2 years and adolescents:
75
mg/m^2
Subcutaneous (SC)
once a day
7
days
Or
300 mg/m^2 IV once a day for 2 days.
Children > 2 years and adolescents:
75
mg/m^2
Subcutaneous (SC)
once a day
7
days
Or
300 mg/m^2 IV once a day for 2 days.
off-label: If the child is less than three years, a dose :
3.3
mg/kg
once a day
IV given continuous infusion for four days If the child is more than three years, a dose of 100 mg per m² per day IV given continuous infusion for four days
Safety and efficacy are not studied
Newly Diagnosed De Novo CD33-positive AML:
Combination Regimen:
age: >1year
BSA< 0.6 m2: 0.1 mg per kg IV over 2hrs
BSA>0.6 m2: 0.3 mg per m2 IV over 2hrs
INDUCTION 1:
gemtuzumab is given for Induction 1 once in combination with standard chemotherapy
In the second induction cycle, gemtuzumab isn't encouraged
INTENSIFICATION:
in the first or third intensification cycles, gemtuzumab isn't encouraged
gemtuzumab is given for Intensification 2 once in combination with standard chemotherapy
During Intensification 2, check for risks and potential benefits before giving gemtuzumab
Relapsed or Refractory CD33-positive AML:
SINGLE-AGENT REGIMEN:
age: > 2years
3 mg per m2 given IV over 2hrs on Days 1, 4, and 7
a single course of gemtuzumab for treatment in the relapsed or refractory setting
Indicated for Acute Nonlymphocytic Leukaemia:
2 mg/kg orally everyday
If there is no improvement after four weeks, gradually increase to 3 mg/kg/day
Consume on an empty stomach to avoid nausea and vomiting
cytarabine/daunorubicin liposomal
Induction
First cycle: Intravenous administration of liposomal daunorubicin at a dosage of 44 mg/m2 in combination with cytarabine at a dosage of 100 mg/m2 on days first third and fifth
Second cycle: This is exclusively intended for patients who do not experience a response during their initial induction cycle
If there were no instances of unacceptable toxicity, the second cycle may be scheduled within a timeframe of 2-5 weeks following the initial cycle
In case it is required, the liposomal formulation of daunorubicin should be administered intravenously at a dose of 44 mg/m2, along with intravenous administration of cytarabine at a dose of 100 mg/m2 on the first and third days
Consolidation
Consolidation: intravenous liposomal (daunorubicin at a dosage of 29 mg/m2 and cytarabine at a dosage of 65 mg/m2) on days 1 and 3
begin the initial consolidation phase approximately 5-8 weeks following the commencement of the preceding induction phase
Refer adult dosing
20
mg/m^2
Intravenous (IV)
over 1 hr
for 5 days for a 28-day cycle in combination with venetoclax
Terminate the therapy as soon as unacceptable adverse effects appear
Future Trends
References
https://www.ncbi.nlm.nih.gov/books/NBK507875/
ADVERTISEMENT
» Home » CAD » Oncology » Hematology » Acute Myeloid Leukemia (AML)
Acute myeloid leukemia (AML) is the most prevalent type of leukemia in adults, accounting for over 80% of all occurrences.
Clonal growth of immature blast cells in the peripheral blood, and bone marrow results in inefficient erythropoiesis and bone marrow failure.
It usually begins in the bone marrow but rapidly spreads to the blood. It can spread to the lymph nodes, liver, testicles, spleen, and central nervous system.
In the United States, there are around 20,000 instances every year.
The typical age upon diagnosis is around 65 years. It is more common in non-Hispanic whites. Males outnumber females by a factor of five, with a ratio of 5:3.
AML is defined as mutations in hematopoiesis-related genes. These mutations cause clonal growth of undifferentiated myeloid precursors in the peripheral blood and bone marrow, which leads to inadequate erythropoiesis and bone marrow failure.
Although the specific source of genetic abnormalities is unknown, a few risk factors include radiation, chemotherapeutic drugs, and smoking. Myelodysplastic syndrome, myeloproliferative diseases, aplastic anemia, and paroxysmal nocturnal hemoglobinuria can all lead to AML.
It is vital to investigate familial causes of genetic alterations. Nucleophosmin 1 mutations are seen in 25%-30% of AML patients. This is the most prevalent mutation detected in AML and is more common in women.
Clinically, the mutation has a monocytic appearance and predicts a good outcome without FMS-like tyrosine kinase three or FLT3-ITD. In young and old individuals, NPM1 mutations are chemosensitive to rigorous chemotherapy.
Several congenital abnormalities, including Bloom syndrome and Down syndrome, increase the risk of AML, which often manifests in the early twenties. Cigarette smoke, radiation, and benzene are all environmental risk factors for AML. Lastly, prior chemotherapeutic drug exposure is a risk factor for AML.
Chromosome abnormalities and genetic mutations are prognostic factors (FLT3 gene has unfavorable prognosis while NPM1 gene has a favorable prognosis).
Elderly individuals, white blood cell count larger than 100,000 at the time of diagnosis, and the detection of leukemic cells in the central nervous system have all been linked to poorer outcomes.
5
mg/m^2
Intravenous (IV)
5
days
daily infused over 3 hours, generally given in combination with daunorubicin and cytarabine
CLAG regimen:
5
mg/m^2
Intravenous (IV)
Over 2 hr
5
days
given in combination with cytarabine, filgrastim and mitoxantrone
300
mg
Orally
once a day
14
days
for 28 days cycle
100
mg
Tablet
Oral
once a day
Continue the treatment until disease progression or unacceptable toxicity occurs Patients without disease progression or unacceptable severe effects continue the treatment for six months to achieve clinical response
20
mg/m^2
Intravenous (IV)
over 1 hr
once daily for 5 days at 28-day cycle
For AML with TP53 mutation:
20 mg/m2 IV infused over 1 hour for 10 days for 28-day cycle
20 mg/m2 IV infused over 1 hour for 5 days for 28-days cycle in combination with venetoclax
Dose Adjustments
Require dose adjustment in case of renal dysfunction or hemodialysis
Terminate the use of docetaxel if total bilirubin > 2.5 times ULN
Administer 80% of the dose: AST/ALT > 2.5 to 5 times ULN
Discontinue the therapy with docetaxel: AST/ALT >5 times
Delay the treatment for 6 to 8 weeks: hematologic toxicity (ANC<1000/µl and platelets < 50,000/µl)
500
mg
Orally
once a day
continue the treatment until disease progression or unacceptable toxicity occurs
patients without disease progression or unacceptable toxicity, given the treatment for up to a minimum of 6 months for clinical response
Newly diagnosed CD33-positive acute myeloid leukemia (AML):
COMBINATION REGIMEN
Induction: 3 mg per m2 IV over 2hrs for Days 1, 4, and 7 given in combination with daunorubicin and cytarabine
the drug gemtuzumab during the second induction cycle gemtuzumab isn't encouraged for patients who require a second induction cycle
Consolidation: 3 mg per m2 IV over 2hrs on Day 1 in combination with daunorubicin and cytarabine
Newly diagnosed CD33-positive acute myeloid leukemia (AML):
SINGLE-AGENT REGIMEN:
Induction: 6 mg per m2 IV over 2hrs on Day 1 and 3 mg/m2 IV on Day 8
Continuation: 2 mg per m2 IV over 2hrs on Day 1 every four weeks
Relapsed or Refractory CD33-positive AML:
SINGLE-AGENT REGIMEN:
3 mg per m2 IV over 2hrs on Days 1, 4, and 7
a single course of gemtuzumab given for treatment in the relapsed or refractory setting
150
mg
Capsules
Orally
twice a day
until the disease progresses
Dose Adjustments
Differentiation syndrome
Withhold REZLIDHIA if differentiation syndrome is suspected until signs and symptoms become improved
Systemic corticosteroids should be given; hemodynamic monitoring should start and continue for at least three days after symptom remission
Restart REZLIDHIA at 150 mg twice daily once the differentiation syndrome has subsided.
Indicated for Acute myeloid leukemia following induction therapy:
• This is a treatment regimen for administering medication (likely a form of chemotherapy) intravenously at a dose of 250 mcg/m2/day over 4 hours
• The treatment is to begin on or around day 11 of the treatment cycle, or four days after the completion of induction chemotherapy provided that the patient's bone marrow is hypoplastic (meaning that it has a reduced number of cells) and that the number of blasts (immature blood cells) is less than 5%. Suppose a second cycle of induction chemotherapy is needed
• In that case, the treatment is to be administered approximately four days after the completion of the chemotherapy, again provided that the bone marrow is hypoplastic with less than 5% blasts
• The treatment is to continue until the patient's absolute neutrophil count (ANC) is more significant than 1500 cells/mm3 for three consecutive days or a maximum of 42 days
100 mg orally four times daily on 1-28 days of 28 days cycle. It is given in combination with 20 mg of cytarabine subcutaneously, twice daily, for 1-10 days of the cycle
Dose Adjustments
In case of QT prolongation (separate ECGs ≥2)
QTc >480 to 500 milliseconds
Check the electrolyte levels and provide supplements as indicated
Review & adjust concomitant medications with QTc interval-prolonging effects
Weekly monitor the ECGs for 2 weeks after the QTc prolongation resolution ≤480 milliseconds
QT >500 milliseconds
Check the electrolyte levels and provide supplements as indicated
Review & adjust concomitant medications with QTc interval-prolonging effects
Check on glasdegib dosing; restart at a reduced dose of 50 mg per day when QTc interval returns to 30 milliseconds
Weekly monitor the ECGs for 2 weeks after the QTc prolongation resolution
Consider re-starting glasdegib dose to 100 mg per day if other causes are identified for QTc prolongation
If QTc prolongation occurs with life-threatening arrhythmia, discontinue the dosing permanently
In case of hematologic toxicity
If platelets are less than 10 Gi/L or neutrophil count is less than 0.5 Gi/L for more than 42 days in the absence of disease, discontinue cytarabine and glasdegib permanently.
In case of non-hematologic toxicity
Interrupt glasdegib until symptoms are reduced
Start glasdegib at the same dose or reduce the dose to 50 mg
In high-grade, non-hematologic toxicity, discontinue glasdegib permanently
In case of renal impairment
No dosage modifications are recommended if eGFR 15-89 mL/min (mild-to-severe)
Monitor the patients with severe renal impairment (when eGFR is 15-29 mL/min); there is an increased risk of adverse effects
No studies are performed in the case of hepatic impairment
120 mg orally each day, the response may get delayed Continue the dose for at least 6 months until the unacceptable toxicity or disease progression
Dose Adjustments
In case of adverse reactions
For PRES (posterior reversible encephalopathy syndrome), discontinue the treatment
If the QTc interval >500 milliseconds interrupt the treatment; start over at 80 mg when the QTc interval gets backs within 30 milliseconds
For pancreatitis, interrupt the treatment if the condition persists; start over the dose at 80 mg
Differentiation Syndrome
If differentiation syndrome is suspected, administer systemic corticosteroids, and start hemodynamic monitoring
Continue this process until symptoms are resolved for minimum 3 days
Interrupt dose if severe symptoms and signs persist for over 48 hours after initiating corticosteroids
Start over the previous dose if the symptoms improve
Hepatic or renal impairment
In the case of mild to moderate hepatic or renal impairment, the effect of meaningful pharmacokinetics is unknown
In case of severe hepatic or renal impairment, the effect of the drug is unknown
50 mg orally twice daily from the 8th to the 21st day of the cycle
Use the drug in combination with standard daunorubicin and cytarabine
The dose should be taken with food
Induction therapy: On days 1 through 3, administer 12 mg/m2 once a day (in addition to 100 mg/m2 of cytarabine given as a continuous intravenous infusion on days 1 through 7)
Second Induction Therapy: On days 1 and 2, inject 12 mg/m2 (combined with a continuous 24-hour intravenous infusion of cytarabine on days 1 through 5)
Consolidation: Day 1 and Day 2 IV administration of 12 mg/m2. The first course is typically delivered six weeks after the last introductory course, while the second is delivered four weeks later.
Indicated for Acute Nonlymphocytic Leukaemia:
2 mg/kg orally everyday
If there is no improvement after four weeks, gradually increase to 3 mg/kg/day
Consume on an empty stomach to avoid nausea and vomiting
cytarabine/daunorubicin liposomal
Induction
First cycle: Administering liposomal daunorubicin at a dosage of 44 mg/m2 along with cytarabine at a dosage of 100 mg/m2 via intravenous infusion on days first third and fifth recommended
Second cycle: Exclusively intended for patients who do not experience a favorable outcome following the initial induction cycle
If there were no unacceptable toxicity, the second cycle can be administered within a time frame of 2-5 weeks following the initial cycle
If necessary, It involves the intravenous (IV) administration of liposomal daunorubicin at a dosage of 44 mg/m2 and cytarabine at a dosage of 100 mg/m2
This administration should be performed on the first and third days
Consolidation
Consolidation: intravenous liposomal (daunorubicin 29 mg/m2/cytarabine 65 mg/m2) on days 1 and 3
begin the initial consolidation phase approximately 5-8 weeks following the commencement of the preceding induction phase
quizartinib (Pending FDA Approval)
FDA approval pending for relapsed or resistant acute myeloid leukemia (AML).
Children and adolescents:
8.9
mg/m^2
Intravenous (IV)
once a day
5
days
Children > 2 years and adolescents:
75
mg/m^2
Subcutaneous (SC)
once a day
7
days
Or
300 mg/m^2 IV once a day for 2 days.
Children > 2 years and adolescents:
75
mg/m^2
Subcutaneous (SC)
once a day
7
days
Or
300 mg/m^2 IV once a day for 2 days.
off-label: If the child is less than three years, a dose :
3.3
mg/kg
once a day
IV given continuous infusion for four days If the child is more than three years, a dose of 100 mg per m² per day IV given continuous infusion for four days
Safety and efficacy are not studied
Newly Diagnosed De Novo CD33-positive AML:
Combination Regimen:
age: >1year
BSA< 0.6 m2: 0.1 mg per kg IV over 2hrs
BSA>0.6 m2: 0.3 mg per m2 IV over 2hrs
INDUCTION 1:
gemtuzumab is given for Induction 1 once in combination with standard chemotherapy
In the second induction cycle, gemtuzumab isn't encouraged
INTENSIFICATION:
in the first or third intensification cycles, gemtuzumab isn't encouraged
gemtuzumab is given for Intensification 2 once in combination with standard chemotherapy
During Intensification 2, check for risks and potential benefits before giving gemtuzumab
Relapsed or Refractory CD33-positive AML:
SINGLE-AGENT REGIMEN:
age: > 2years
3 mg per m2 given IV over 2hrs on Days 1, 4, and 7
a single course of gemtuzumab for treatment in the relapsed or refractory setting
Indicated for Acute Nonlymphocytic Leukaemia:
2 mg/kg orally everyday
If there is no improvement after four weeks, gradually increase to 3 mg/kg/day
Consume on an empty stomach to avoid nausea and vomiting
cytarabine/daunorubicin liposomal
Induction
First cycle: Intravenous administration of liposomal daunorubicin at a dosage of 44 mg/m2 in combination with cytarabine at a dosage of 100 mg/m2 on days first third and fifth
Second cycle: This is exclusively intended for patients who do not experience a response during their initial induction cycle
If there were no instances of unacceptable toxicity, the second cycle may be scheduled within a timeframe of 2-5 weeks following the initial cycle
In case it is required, the liposomal formulation of daunorubicin should be administered intravenously at a dose of 44 mg/m2, along with intravenous administration of cytarabine at a dose of 100 mg/m2 on the first and third days
Consolidation
Consolidation: intravenous liposomal (daunorubicin at a dosage of 29 mg/m2 and cytarabine at a dosage of 65 mg/m2) on days 1 and 3
begin the initial consolidation phase approximately 5-8 weeks following the commencement of the preceding induction phase
Refer adult dosing
20
mg/m^2
Intravenous (IV)
over 1 hr
for 5 days for a 28-day cycle in combination with venetoclax
Terminate the therapy as soon as unacceptable adverse effects appear
https://www.ncbi.nlm.nih.gov/books/NBK507875/
Acute myeloid leukemia (AML) is the most prevalent type of leukemia in adults, accounting for over 80% of all occurrences.
Clonal growth of immature blast cells in the peripheral blood, and bone marrow results in inefficient erythropoiesis and bone marrow failure.
It usually begins in the bone marrow but rapidly spreads to the blood. It can spread to the lymph nodes, liver, testicles, spleen, and central nervous system.
In the United States, there are around 20,000 instances every year.
The typical age upon diagnosis is around 65 years. It is more common in non-Hispanic whites. Males outnumber females by a factor of five, with a ratio of 5:3.
AML is defined as mutations in hematopoiesis-related genes. These mutations cause clonal growth of undifferentiated myeloid precursors in the peripheral blood and bone marrow, which leads to inadequate erythropoiesis and bone marrow failure.
Although the specific source of genetic abnormalities is unknown, a few risk factors include radiation, chemotherapeutic drugs, and smoking. Myelodysplastic syndrome, myeloproliferative diseases, aplastic anemia, and paroxysmal nocturnal hemoglobinuria can all lead to AML.
It is vital to investigate familial causes of genetic alterations. Nucleophosmin 1 mutations are seen in 25%-30% of AML patients. This is the most prevalent mutation detected in AML and is more common in women.
Clinically, the mutation has a monocytic appearance and predicts a good outcome without FMS-like tyrosine kinase three or FLT3-ITD. In young and old individuals, NPM1 mutations are chemosensitive to rigorous chemotherapy.
Several congenital abnormalities, including Bloom syndrome and Down syndrome, increase the risk of AML, which often manifests in the early twenties. Cigarette smoke, radiation, and benzene are all environmental risk factors for AML. Lastly, prior chemotherapeutic drug exposure is a risk factor for AML.
Chromosome abnormalities and genetic mutations are prognostic factors (FLT3 gene has unfavorable prognosis while NPM1 gene has a favorable prognosis).
Elderly individuals, white blood cell count larger than 100,000 at the time of diagnosis, and the detection of leukemic cells in the central nervous system have all been linked to poorer outcomes.
https://www.ncbi.nlm.nih.gov/books/NBK507875/
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Founded in 2014, medtigo is committed to providing high-quality, friendly physicians, transparent pricing, and a focus on building relationships and a lifestyle brand for medical professionals nationwide.
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North Adams, MA 01247
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Shirole Lane, Off FC Road,
Pune 411004, Maharashtra
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