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» Home » CAD » Oncology » Hematology » Acute lymphoblastic leukemia(All)
Background
Acute Lymphoblastic leukemia (ALL) is also known as acute lymphocytic leukemia based on B or T lymphocyte proliferation. ALL is cancer where the bone marrow makes many lymphocytes (a category of white blood cells), which develops both in children and adults.
Neoplasms usually spread through the blood, but they can also invade lymph nodes, the liver, the CNS, and the testicles. This disease accounts for 2% of lymphoid cancer cases in the United States. The frequency of disease occurring in males is greater than in females.
Patients with acute lymphoblastic leukemia present with symptoms like anemia, neutropenia, and thrombocytopenia, and these are related to bone marrow replacement disorders that occur due to ALL tumors. B-lymphocyte’s symptoms include fever, night sweats, and weight loss.
Epidemiology
In the USA, every year 4000 people (which majority below the age of 18) suffered from ALL. Children under 3 years with Down syndrome (Trisomy 21), neurofibromatosis type 1, blood syndrome, and ataxia-telangiectasia are the most affected group.
Overall, the incidence of acute lymphoblastic leukemia is low in overall population studies; however, it occurs in 3.3 cases in 100,000 children. Since the 1980s, survival rates for ALL have increased significantly, with a recent five-year gross survival rate calculated at > 85%.
Anatomy
Pathophysiology
Acute lymphoblastic leukemia can develop when DNA damage causes uncontrolled growth in lymphoid cells, causing them to spread throughout the body.
Conditions like splenomegaly and hepatomegaly are raised due to the sequestration of platelets and lymphocytes in the spleen and liver. The migration of WBC to the spleen is not common. It reacts by trying to wash away the WBC from the blood.
Etiology
The etiology of acute lymphoblastic leukemia is idiopathic. Even though, some environmental factors bear some of the reasons for the etiology of ALL, such as sufficient exposure to X-rays or gamma rays, which cause ionization in the body, or medication history with chemotherapy or radiotherapy.
Some genetic studies revealed that somatic, polymorphic variants of ARD5B, IKZFI (the gene encoding Ikaros), and CDKN2A also play a part in an increased risk of neoplasm. Nevertheless, rare germline mutations in PAX5, ETV6, and p53 are powerful factors for leukemia development.
Genetics
Prognostic Factors
In adults, only 30% with ALL are restored to health today. Better prognosis criteria include:
A list of poor prognostic factors is:
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
50
mg/m^2
Intravenous (IV)
once in a 21- or 28-day course in combination with cyclophosphamide, vincristine, and dexamethasone.
30 mg/m2 IV on days 1, 8, and 15 of the 8-week cycle in combination with cyclophosphamide, thioguanine, vincristine, and cytarabine.
MRD-positive lymphoblastic leukemia:
Premedication of prednisone:
100
mg
Intravenous (IV)
every hour
prior to the first dose of each 6-week cycle of blinatumomab
Premedication of dexamethasone: 16 mg IV once an hour prior to the first dose of each 6-week cycle of blinatumomab
>45 kg: 28 mcg IV once a day with continuous infusion on the day 1 to 28 of a 6-week cycle for 4 cycles (fixed dose)
<45 kg: 15 mcg/m2 IV once a day with continuous infusion on the day 1 to 28 of a 6-week cycle for 4 cycles (fixed dose)
Relapsed/refractory acute lymphoblastic leukemia:
Premedication of dexamethasone: 20 mg IV once an hour prior to the first dose of each 6-week cycle of blinatumomab for 8 consecutive cycles
>45 kg: 9 mcg IV once a day with continuous infusion on days 1 to 7 and 28 mcg IV once a day on days 8 to 28 of cycle-1 of 6-weeks
28 mcg IV once a day with continuous infusion on days 1 to 28 of cycles 2 to 5 of 6-weeks
28 mcg IV once a day with continuous infusion on days 1 to 28 of cycles 6 to 9 of the 12-weeks cycle
<45 kg: 5 mcg/m2 IV once a day with continuous infusion on days 1 to 7 and 15 mcg/m2 IV once a day on days 8 to 28 of cycle-1 of 6-weeks (do not exceed 28 mcg/day)
15 mcg/m2 IV once a day with continuous infusion on days 1 to 28 of cycles 2 to 5 of 6-weeks (do not exceed 28 mcg/day)
15 mcg/m2 IV once a day with continuous infusion on days 1 to 28 of cycles 6 to 9 of the 12-weeks cycle (do not exceed 28 mcg/day)
Dose Adjustments
Terminate the therapy temporarily if transaminases > 5 times ULN and/or bilirubin > 3 times ULN (hepatotoxicity)
600
mg
Orally
once a day
; continue the treatment until there is no progressive disease or unacceptable toxicity occurs
Cycle 1 -total dose include 1.8 mg per m2 per cycle
Day-1 0.8 mg per m2 IV
Day-8 0.5 mg per m2 IV
Day-15: 0.5 mg per m2 IV
The maximum duration of therapy for Cycle 1 is 21 days or can be continued to 28 days and 7-day treatment on Day 21.
for Subsequent Cycles:
patients who achieve a CR or CRi, a dose of 1.5 mg per m2 per cycle is recommended:
Day-1, 0.5 mg per m2 given IV
Day-8, 0.5 mg per m2 given IV
Day-15, 0.5 mg per m2 given IV
The maximum duration of therapy is 28 days, and seven days of treatment given on the 21st day
For patients who didn't succeed in CR or CRi, a dose of 1.8 mg per m2 per cycle is recommended:
-On day 1, 0.8 mg per m2 IV
-On day 8, 0.5 mg per m2 IV
-On day 15, 0.5 mg per m2 IV
The maximum duration of therapy is 28 days and seven days of treatment on Day 21
patients who didn't succeed in CR or CRi within three cycles should discontinue therapy
12
mg/m^2
Intravenous (IV)
per day IV for 3 days in combination with cytarabine
Induce the dose of 2.5 mg/kg orally daily
Usually, it is 100-200 mg orally each day in an average adult
May increase the dose by 5 mg/kg after every 4 weeks
The maintenance dose is 1.5-2.5 mg/kg orally each day
ponatinib is indicated in patients who have acute lymphoblastic leukemia (Philadelphia chromosome-positive)
A dose of 45 mg, four times daily, is administered four times daily
The medication is continued until the disease is reduced to acceptable toxicity
Dose Adjustments
In case of adverse reactions, the dose is modified or reduced
The pattern of dose reduction goes like this
First dose reduction: 30 mg four times daily
Second dose reduction: 15 mg four times daily
Third dose reduction: 10 mg four times daily
In case of more reduction of dose, discontinue the treatment
1500 mg/m2 Intravenous over 2 hrs on days 1, 3, and 5; start repeating every 21 days
Neurologic status should be monitored
It is indicated in the treatment of Philadelphia chromosome-negative acute lymphoblastic leukemia
The adults with 2nd or more relapse of the disease who has passed 2 or more therapies for leukemia
2.25 mg/m2 for 1 hour every 7 days
Dose Modifications
For grade 3 or continuing grade 2, interrupt the therapy
Discontinue if the symptoms don’t clear
Reduce the dose to 2 mg/m2 later, the improvement of grade 1 or 2
Interrupt the therapy for a week, and discontinue the therapy if symptoms degrade to grade 3 or 4
After 1st grade improvement, reduce the dose to 1.5 mg/m2
asparaginase Erwinia chrysanthemi recombinant
Indicated for Acute Lymphoblastic Leukemia
25 mg/m2 Intramuscularly every 48 hours
Or
Administer on Monday, Wednesday, and Friday plan:
25 mg/m2 Intramuscularly on every Monday morning and Wednesday morning; and then 50 mg/m2 Intramuscularly on Friday afternoon, and the dose should administer 53-58 hours following the Wednesday morning dose
Lymphoblastic Lymphoma
25 mg/m2 Intramuscularly every 48 hours
Or
Administer on Monday, Wednesday, and Friday plan:
25 mg/m2 Intramuscularly on every Monday morning and Wednesday morning; and then 50 mg/m2 Intramuscularly on Friday afternoon, and the dose should administer 53-58 hours following the Wednesday morning dose
Indicated for Refractory or Relapsed Acute Lymphoblastic Leukemia
For individuals below 21 years old
The recommended dosage is 52 mg/m² administered intravenously over a period of 2 hours every day for 5 successive days
The treatment cycles should be repeated every two to six weeks after the patient has recovered or their organ function has returned to baseline
lymphodepleting chemotherapy
every day for four days, intravenous fludarabine 30 mg/m2
commencing with the first dosage of fludarabine, 500 mg/m2 of cyclophosphamide was administered intravenously every day for two days
tisagenlecleucel intravenous infusion
Administer 2 to 14 days after completion of lymphodepleting chemotherapy
Do not use a leukocyte-depleting filter
30
mg/m^2
Intravenous (IV)
per day on days 0 and 1 of a 4-week cycle in combination with dexrazoxane, vincristine, methotrexate, cytarabine.
CNS therapy for high-risk patients: 30 mg/m2 per day of a 3-week cycle in combination with dexrazoxane, vincristine, mercaptopurine, and cytarabine.
MRD-positive Acute lymphoblastic leukemia:
Premedication of prednisone:
100
mg
Intravenous (IV)
every hour
prior to the first dose of each 6-week cycle of blinatumomab
Premedication of dexamethasone: 16 mg IV once an hour prior to the first dose of each 6-week cycle of blinatumomab
<45 kg: 15 mcg/m2 IV once a day with continuous infusion on the day 1 to 28 of a 6-week cycle for 4 cycles (fixed dose)
Relapsed/refractory acute lymphoblastic leukemia:
<45 kg: 5 mcg/m2 IV once a day with continuous infusion on days 1 to 7 and 15 mcg/m2 IV once a day on days 8 to 28 of cycle-1 of 6-weeks (do not exceed 28 mcg/day)
15 mcg/m2 IV once a day with continuous infusion on days 1 to 28 of cycles 2 to 5 of 6-weeks (do not exceed 28 mcg/day)
15 mcg/m2 IV once a day with continuous infusion on days 1 to 28 of cycles 6 to 9 of the 12-weeks cycle (do not exceed 28 mcg/day)
Dose Adjustments
Terminate the therapy temporarily if transaminases > 5 times ULN and/or bilirubin > 3 times ULN (hepatotoxicity)
MRD-positive Acute lymphoblastic leukemia:
Premedication of prednisone:
100
mg
Intravenous (IV)
every hour
prior to the first dose of each 6-week cycle of blinatumomab
Premedication of dexamethasone: 16 mg IV once an hour prior to the first dose of each 6-week cycle of blinatumomab
Premedication of dexamethasone: 16 mg IV once an hour prior to the first dose of each 6-week cycle of blinatumomab
<45 kg: 15 mcg/m2 IV once a day with continuous infusion on the day 1 to 28 of a 6-week cycle for 4 cycles (fixed dose)
Relapsed/refractory acute lymphoblastic leukemia:
<45 kg: 5 mcg/m2 IV once a day with continuous infusion on days 1 to 7 and 15 mcg/m2 IV once a day on days 8 to 28 of cycle-1 of 6-weeks (do not exceed 28 mcg/day)
15 mcg/m2 IV once a day with continuous infusion on days 1 to 28 of cycles 2 to 5 of 6-weeks (do not exceed 28 mcg/day)
15 mcg/m2 IV once a day with continuous infusion on days 1 to 28 of cycles 6 to 9 of the 12-weeks cycle (do not exceed 28 mcg/day)
Dose Adjustments
Terminate the therapy temporarily if transaminases > 5 times ULN and/or bilirubin > 3 times ULN (hepatotoxicity)
Age:>1 year
340 mg per m2 given orally per day or 170 mg per m2 given orally twice a day
The maximum dose given is 600 mg daily
continue the treatment until there is no progressive disease or unacceptable toxicity occurs
Age: <1year <
Safety and efficacy not established
5
mg/m^2
per day IV for 3 days in combination with cytarabine
The induction dose is 1.25-2.5 mg/kg (50-75 mg/m²) orally each day
The maintenance dose is 1.5-2.5 mg/kg orally each day in combination with methotrexate
Reduce the dose by 75% if there is concomitant administration of allopurinol
Reduce dose in case of renal impairment
650 mg/m2 Intravenous over 1-hr 5 times consecutive days, start repeating cycle every 21 days
asparaginase Erwinia chrysanthemi recombinant
Indicated for Acute Lymphoblastic Leukemia
Age >1 month
25 mg/m2 Intramuscularly every 48 hours
Or
Administer on Monday, Wednesday, and Friday plan:
25 mg/m2 Intramuscularly on every Monday morning and Wednesday morning; and then 50 mg/m2 Intramuscularly on Friday afternoon, and the dose should administer 53-58 hours following the Wednesday morning dose
Age <1 month
Safety and efficacy not established
Lymphoblastic Lymphoma
Age >1 month
25 mg/m2 Intramuscularly every 48 hours
Or
Administer on Monday, Wednesday, and Friday plan:
25 mg/m2 Intramuscularly on every Monday morning and Wednesday morning; and then 50 mg/m2 Intramuscularly on Friday afternoon, and the dose should administer 53-58 hours following the Wednesday morning dose
Age <1 month
Safety and efficacy not established
Indicated for Refractory or Relapsed Acute Lymphoblastic Leukemia
For Age ≥1 year
The recommended dosage is 52 mg/m² administered intravenously over a period of 2 hours every day for 5 successive days
The treatment cycles should be repeated every two to six weeks after the patient has recovered or their organ function has returned to baseline
Lymphodepleting chemotherapy
Cyclophosphamide 500 mg/m² intravenous every day for 2 days starting with the first dose of fludarabine
Fludarabine 30 mg/m² intravenous every day for 4 days
tisagenlecleucel intravenous infusion
Administer 2 to 14 days after completing lymphodepleting chemotherapy
Dosage Modifications
Cytokine release syndrome (CRS) management
Symptoms: Fatigue, anorexia, low-grade fever
CRS requiring mild intervention
Administer antipyretics, intravenous fluids, oxygen, and low-dose vasopressors as required
CRS requiring moderate to aggressive intervention
Administer oxygen, high-dose, mechanical ventilation, and other supportive care as required
Repeat tocilizumab as required at a minimum interval of 8 hour if there is no clinical progression
Dosing Considerations
only for autologous use
For < 60 years: 12 mg/m2 per day IV on days 2, 4, 6, and 8 in combination with tretinoin
For age 61 to 70: 9 mg/m2 per day IV on days 2, 4, 6, and 8 in combination with tretinoin
For age 61 to 70: 9 mg/m2 per day IV on days 2, 4, 6, and 8 in combination with tretinoin
For age >70: 6 mg/m2 per day IV on days 2, 4, 6, and 8 in combination with tretinoin
Future Trends
References
https://www.ncbi.nlm.nih.gov/books/NBK459149/
https://www.cancer.org/cancer/acute-lymphocytic-leukemia
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» Home » CAD » Oncology » Hematology » Acute lymphoblastic leukemia(All)
Acute Lymphoblastic leukemia (ALL) is also known as acute lymphocytic leukemia based on B or T lymphocyte proliferation. ALL is cancer where the bone marrow makes many lymphocytes (a category of white blood cells), which develops both in children and adults.
Neoplasms usually spread through the blood, but they can also invade lymph nodes, the liver, the CNS, and the testicles. This disease accounts for 2% of lymphoid cancer cases in the United States. The frequency of disease occurring in males is greater than in females.
Patients with acute lymphoblastic leukemia present with symptoms like anemia, neutropenia, and thrombocytopenia, and these are related to bone marrow replacement disorders that occur due to ALL tumors. B-lymphocyte’s symptoms include fever, night sweats, and weight loss.
In the USA, every year 4000 people (which majority below the age of 18) suffered from ALL. Children under 3 years with Down syndrome (Trisomy 21), neurofibromatosis type 1, blood syndrome, and ataxia-telangiectasia are the most affected group.
Overall, the incidence of acute lymphoblastic leukemia is low in overall population studies; however, it occurs in 3.3 cases in 100,000 children. Since the 1980s, survival rates for ALL have increased significantly, with a recent five-year gross survival rate calculated at > 85%.
Acute lymphoblastic leukemia can develop when DNA damage causes uncontrolled growth in lymphoid cells, causing them to spread throughout the body.
Conditions like splenomegaly and hepatomegaly are raised due to the sequestration of platelets and lymphocytes in the spleen and liver. The migration of WBC to the spleen is not common. It reacts by trying to wash away the WBC from the blood.
The etiology of acute lymphoblastic leukemia is idiopathic. Even though, some environmental factors bear some of the reasons for the etiology of ALL, such as sufficient exposure to X-rays or gamma rays, which cause ionization in the body, or medication history with chemotherapy or radiotherapy.
Some genetic studies revealed that somatic, polymorphic variants of ARD5B, IKZFI (the gene encoding Ikaros), and CDKN2A also play a part in an increased risk of neoplasm. Nevertheless, rare germline mutations in PAX5, ETV6, and p53 are powerful factors for leukemia development.
In adults, only 30% with ALL are restored to health today. Better prognosis criteria include:
A list of poor prognostic factors is:
50
mg/m^2
Intravenous (IV)
once in a 21- or 28-day course in combination with cyclophosphamide, vincristine, and dexamethasone.
30 mg/m2 IV on days 1, 8, and 15 of the 8-week cycle in combination with cyclophosphamide, thioguanine, vincristine, and cytarabine.
MRD-positive lymphoblastic leukemia:
Premedication of prednisone:
100
mg
Intravenous (IV)
every hour
prior to the first dose of each 6-week cycle of blinatumomab
Premedication of dexamethasone: 16 mg IV once an hour prior to the first dose of each 6-week cycle of blinatumomab
>45 kg: 28 mcg IV once a day with continuous infusion on the day 1 to 28 of a 6-week cycle for 4 cycles (fixed dose)
<45 kg: 15 mcg/m2 IV once a day with continuous infusion on the day 1 to 28 of a 6-week cycle for 4 cycles (fixed dose)
Relapsed/refractory acute lymphoblastic leukemia:
Premedication of dexamethasone: 20 mg IV once an hour prior to the first dose of each 6-week cycle of blinatumomab for 8 consecutive cycles
>45 kg: 9 mcg IV once a day with continuous infusion on days 1 to 7 and 28 mcg IV once a day on days 8 to 28 of cycle-1 of 6-weeks
28 mcg IV once a day with continuous infusion on days 1 to 28 of cycles 2 to 5 of 6-weeks
28 mcg IV once a day with continuous infusion on days 1 to 28 of cycles 6 to 9 of the 12-weeks cycle
<45 kg: 5 mcg/m2 IV once a day with continuous infusion on days 1 to 7 and 15 mcg/m2 IV once a day on days 8 to 28 of cycle-1 of 6-weeks (do not exceed 28 mcg/day)
15 mcg/m2 IV once a day with continuous infusion on days 1 to 28 of cycles 2 to 5 of 6-weeks (do not exceed 28 mcg/day)
15 mcg/m2 IV once a day with continuous infusion on days 1 to 28 of cycles 6 to 9 of the 12-weeks cycle (do not exceed 28 mcg/day)
Dose Adjustments
Terminate the therapy temporarily if transaminases > 5 times ULN and/or bilirubin > 3 times ULN (hepatotoxicity)
600
mg
Orally
once a day
; continue the treatment until there is no progressive disease or unacceptable toxicity occurs
Cycle 1 -total dose include 1.8 mg per m2 per cycle
Day-1 0.8 mg per m2 IV
Day-8 0.5 mg per m2 IV
Day-15: 0.5 mg per m2 IV
The maximum duration of therapy for Cycle 1 is 21 days or can be continued to 28 days and 7-day treatment on Day 21.
for Subsequent Cycles:
patients who achieve a CR or CRi, a dose of 1.5 mg per m2 per cycle is recommended:
Day-1, 0.5 mg per m2 given IV
Day-8, 0.5 mg per m2 given IV
Day-15, 0.5 mg per m2 given IV
The maximum duration of therapy is 28 days, and seven days of treatment given on the 21st day
For patients who didn't succeed in CR or CRi, a dose of 1.8 mg per m2 per cycle is recommended:
-On day 1, 0.8 mg per m2 IV
-On day 8, 0.5 mg per m2 IV
-On day 15, 0.5 mg per m2 IV
The maximum duration of therapy is 28 days and seven days of treatment on Day 21
patients who didn't succeed in CR or CRi within three cycles should discontinue therapy
12
mg/m^2
Intravenous (IV)
per day IV for 3 days in combination with cytarabine
Induce the dose of 2.5 mg/kg orally daily
Usually, it is 100-200 mg orally each day in an average adult
May increase the dose by 5 mg/kg after every 4 weeks
The maintenance dose is 1.5-2.5 mg/kg orally each day
ponatinib is indicated in patients who have acute lymphoblastic leukemia (Philadelphia chromosome-positive)
A dose of 45 mg, four times daily, is administered four times daily
The medication is continued until the disease is reduced to acceptable toxicity
Dose Adjustments
In case of adverse reactions, the dose is modified or reduced
The pattern of dose reduction goes like this
First dose reduction: 30 mg four times daily
Second dose reduction: 15 mg four times daily
Third dose reduction: 10 mg four times daily
In case of more reduction of dose, discontinue the treatment
1500 mg/m2 Intravenous over 2 hrs on days 1, 3, and 5; start repeating every 21 days
Neurologic status should be monitored
It is indicated in the treatment of Philadelphia chromosome-negative acute lymphoblastic leukemia
The adults with 2nd or more relapse of the disease who has passed 2 or more therapies for leukemia
2.25 mg/m2 for 1 hour every 7 days
Dose Modifications
For grade 3 or continuing grade 2, interrupt the therapy
Discontinue if the symptoms don’t clear
Reduce the dose to 2 mg/m2 later, the improvement of grade 1 or 2
Interrupt the therapy for a week, and discontinue the therapy if symptoms degrade to grade 3 or 4
After 1st grade improvement, reduce the dose to 1.5 mg/m2
asparaginase Erwinia chrysanthemi recombinant
Indicated for Acute Lymphoblastic Leukemia
25 mg/m2 Intramuscularly every 48 hours
Or
Administer on Monday, Wednesday, and Friday plan:
25 mg/m2 Intramuscularly on every Monday morning and Wednesday morning; and then 50 mg/m2 Intramuscularly on Friday afternoon, and the dose should administer 53-58 hours following the Wednesday morning dose
Lymphoblastic Lymphoma
25 mg/m2 Intramuscularly every 48 hours
Or
Administer on Monday, Wednesday, and Friday plan:
25 mg/m2 Intramuscularly on every Monday morning and Wednesday morning; and then 50 mg/m2 Intramuscularly on Friday afternoon, and the dose should administer 53-58 hours following the Wednesday morning dose
Indicated for Refractory or Relapsed Acute Lymphoblastic Leukemia
For individuals below 21 years old
The recommended dosage is 52 mg/m² administered intravenously over a period of 2 hours every day for 5 successive days
The treatment cycles should be repeated every two to six weeks after the patient has recovered or their organ function has returned to baseline
lymphodepleting chemotherapy
every day for four days, intravenous fludarabine 30 mg/m2
commencing with the first dosage of fludarabine, 500 mg/m2 of cyclophosphamide was administered intravenously every day for two days
tisagenlecleucel intravenous infusion
Administer 2 to 14 days after completion of lymphodepleting chemotherapy
Do not use a leukocyte-depleting filter
30
mg/m^2
Intravenous (IV)
per day on days 0 and 1 of a 4-week cycle in combination with dexrazoxane, vincristine, methotrexate, cytarabine.
CNS therapy for high-risk patients: 30 mg/m2 per day of a 3-week cycle in combination with dexrazoxane, vincristine, mercaptopurine, and cytarabine.
MRD-positive Acute lymphoblastic leukemia:
Premedication of prednisone:
100
mg
Intravenous (IV)
every hour
prior to the first dose of each 6-week cycle of blinatumomab
Premedication of dexamethasone: 16 mg IV once an hour prior to the first dose of each 6-week cycle of blinatumomab
<45 kg: 15 mcg/m2 IV once a day with continuous infusion on the day 1 to 28 of a 6-week cycle for 4 cycles (fixed dose)
Relapsed/refractory acute lymphoblastic leukemia:
<45 kg: 5 mcg/m2 IV once a day with continuous infusion on days 1 to 7 and 15 mcg/m2 IV once a day on days 8 to 28 of cycle-1 of 6-weeks (do not exceed 28 mcg/day)
15 mcg/m2 IV once a day with continuous infusion on days 1 to 28 of cycles 2 to 5 of 6-weeks (do not exceed 28 mcg/day)
15 mcg/m2 IV once a day with continuous infusion on days 1 to 28 of cycles 6 to 9 of the 12-weeks cycle (do not exceed 28 mcg/day)
Dose Adjustments
Terminate the therapy temporarily if transaminases > 5 times ULN and/or bilirubin > 3 times ULN (hepatotoxicity)
MRD-positive Acute lymphoblastic leukemia:
Premedication of prednisone:
100
mg
Intravenous (IV)
every hour
prior to the first dose of each 6-week cycle of blinatumomab
Premedication of dexamethasone: 16 mg IV once an hour prior to the first dose of each 6-week cycle of blinatumomab
Premedication of dexamethasone: 16 mg IV once an hour prior to the first dose of each 6-week cycle of blinatumomab
<45 kg: 15 mcg/m2 IV once a day with continuous infusion on the day 1 to 28 of a 6-week cycle for 4 cycles (fixed dose)
Relapsed/refractory acute lymphoblastic leukemia:
<45 kg: 5 mcg/m2 IV once a day with continuous infusion on days 1 to 7 and 15 mcg/m2 IV once a day on days 8 to 28 of cycle-1 of 6-weeks (do not exceed 28 mcg/day)
15 mcg/m2 IV once a day with continuous infusion on days 1 to 28 of cycles 2 to 5 of 6-weeks (do not exceed 28 mcg/day)
15 mcg/m2 IV once a day with continuous infusion on days 1 to 28 of cycles 6 to 9 of the 12-weeks cycle (do not exceed 28 mcg/day)
Dose Adjustments
Terminate the therapy temporarily if transaminases > 5 times ULN and/or bilirubin > 3 times ULN (hepatotoxicity)
Age:>1 year
340 mg per m2 given orally per day or 170 mg per m2 given orally twice a day
The maximum dose given is 600 mg daily
continue the treatment until there is no progressive disease or unacceptable toxicity occurs
Age: <1year <
Safety and efficacy not established
5
mg/m^2
per day IV for 3 days in combination with cytarabine
The induction dose is 1.25-2.5 mg/kg (50-75 mg/m²) orally each day
The maintenance dose is 1.5-2.5 mg/kg orally each day in combination with methotrexate
Reduce the dose by 75% if there is concomitant administration of allopurinol
Reduce dose in case of renal impairment
650 mg/m2 Intravenous over 1-hr 5 times consecutive days, start repeating cycle every 21 days
asparaginase Erwinia chrysanthemi recombinant
Indicated for Acute Lymphoblastic Leukemia
Age >1 month
25 mg/m2 Intramuscularly every 48 hours
Or
Administer on Monday, Wednesday, and Friday plan:
25 mg/m2 Intramuscularly on every Monday morning and Wednesday morning; and then 50 mg/m2 Intramuscularly on Friday afternoon, and the dose should administer 53-58 hours following the Wednesday morning dose
Age <1 month
Safety and efficacy not established
Lymphoblastic Lymphoma
Age >1 month
25 mg/m2 Intramuscularly every 48 hours
Or
Administer on Monday, Wednesday, and Friday plan:
25 mg/m2 Intramuscularly on every Monday morning and Wednesday morning; and then 50 mg/m2 Intramuscularly on Friday afternoon, and the dose should administer 53-58 hours following the Wednesday morning dose
Age <1 month
Safety and efficacy not established
Indicated for Refractory or Relapsed Acute Lymphoblastic Leukemia
For Age ≥1 year
The recommended dosage is 52 mg/m² administered intravenously over a period of 2 hours every day for 5 successive days
The treatment cycles should be repeated every two to six weeks after the patient has recovered or their organ function has returned to baseline
Lymphodepleting chemotherapy
Cyclophosphamide 500 mg/m² intravenous every day for 2 days starting with the first dose of fludarabine
Fludarabine 30 mg/m² intravenous every day for 4 days
tisagenlecleucel intravenous infusion
Administer 2 to 14 days after completing lymphodepleting chemotherapy
Dosage Modifications
Cytokine release syndrome (CRS) management
Symptoms: Fatigue, anorexia, low-grade fever
CRS requiring mild intervention
Administer antipyretics, intravenous fluids, oxygen, and low-dose vasopressors as required
CRS requiring moderate to aggressive intervention
Administer oxygen, high-dose, mechanical ventilation, and other supportive care as required
Repeat tocilizumab as required at a minimum interval of 8 hour if there is no clinical progression
Dosing Considerations
only for autologous use
For < 60 years: 12 mg/m2 per day IV on days 2, 4, 6, and 8 in combination with tretinoin
For age 61 to 70: 9 mg/m2 per day IV on days 2, 4, 6, and 8 in combination with tretinoin
For age 61 to 70: 9 mg/m2 per day IV on days 2, 4, 6, and 8 in combination with tretinoin
For age >70: 6 mg/m2 per day IV on days 2, 4, 6, and 8 in combination with tretinoin
https://www.ncbi.nlm.nih.gov/books/NBK459149/
https://www.cancer.org/cancer/acute-lymphocytic-leukemia
Acute Lymphoblastic leukemia (ALL) is also known as acute lymphocytic leukemia based on B or T lymphocyte proliferation. ALL is cancer where the bone marrow makes many lymphocytes (a category of white blood cells), which develops both in children and adults.
Neoplasms usually spread through the blood, but they can also invade lymph nodes, the liver, the CNS, and the testicles. This disease accounts for 2% of lymphoid cancer cases in the United States. The frequency of disease occurring in males is greater than in females.
Patients with acute lymphoblastic leukemia present with symptoms like anemia, neutropenia, and thrombocytopenia, and these are related to bone marrow replacement disorders that occur due to ALL tumors. B-lymphocyte’s symptoms include fever, night sweats, and weight loss.
In the USA, every year 4000 people (which majority below the age of 18) suffered from ALL. Children under 3 years with Down syndrome (Trisomy 21), neurofibromatosis type 1, blood syndrome, and ataxia-telangiectasia are the most affected group.
Overall, the incidence of acute lymphoblastic leukemia is low in overall population studies; however, it occurs in 3.3 cases in 100,000 children. Since the 1980s, survival rates for ALL have increased significantly, with a recent five-year gross survival rate calculated at > 85%.
Acute lymphoblastic leukemia can develop when DNA damage causes uncontrolled growth in lymphoid cells, causing them to spread throughout the body.
Conditions like splenomegaly and hepatomegaly are raised due to the sequestration of platelets and lymphocytes in the spleen and liver. The migration of WBC to the spleen is not common. It reacts by trying to wash away the WBC from the blood.
The etiology of acute lymphoblastic leukemia is idiopathic. Even though, some environmental factors bear some of the reasons for the etiology of ALL, such as sufficient exposure to X-rays or gamma rays, which cause ionization in the body, or medication history with chemotherapy or radiotherapy.
Some genetic studies revealed that somatic, polymorphic variants of ARD5B, IKZFI (the gene encoding Ikaros), and CDKN2A also play a part in an increased risk of neoplasm. Nevertheless, rare germline mutations in PAX5, ETV6, and p53 are powerful factors for leukemia development.
In adults, only 30% with ALL are restored to health today. Better prognosis criteria include:
A list of poor prognostic factors is:
https://www.ncbi.nlm.nih.gov/books/NBK459149/
https://www.cancer.org/cancer/acute-lymphocytic-leukemia
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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.
MASSACHUSETTS – USA
60 Roberts Drive, Suite 313,
North Adams, MA 01247
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Opp Kiosk Koffee,
Shirole Lane, Off FC Road,
Pune 411004, Maharashtra
