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.

For >45 kg: Administer a dose of 28 mcg intravenous route one time daily with continuous infusion on the day 1 to day 28 up to 6-week cycle including total 4 cycles
For <45 kg: Administer a dose of 15 mcg/m2 intravenously one time daily with continuous infusion on the day 1 to day 28 up to 6-week cycle including total 4 cycles

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

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

For the Patients on a cytarabine-containing regimen who are not responding to induction therapy:
Administer 165 mg/m2 intravenously at a minimum half-hour to 1-hour duration & administer cytarabine 300 mg/m2 intravenously two times a week in 8-9 doses
For Individuals unresponsive to regimens involving prednisone & vincristine:
Intravenous administration of 250 mg/m2 for a minimum of half-hour to 1-hour duration & administer prednisone in the dose of 40 mg/m2 for the duration of twenty-eight days through oral route with the administration of vincristine 1.5 mg/m2 intravenously in a week for the duration of four to eight weeks

Administer a dose of 3 to 4 mg/m2 intravenously weekly

Approved for adult patients experiencing refractory or relapsed B-cell precursor acute lymphoblastic leukemia (ALL), the treatment regimen involves lymphodepleting chemotherapy with fludarabine and cyclophosphamide, followed by the intravenous infusion of brexucabtagene autoleucel
Before commencing lymphodepleting chemotherapy, ensure the availability of brexucabtagene autoleucel
Lymphodepleting chemotherapy involves the intravenous administration of fludarabine at 25 mg/m2 over 30 minutes on the fourth, third, and second day preceding the infusion of brexucabtagene autoleucel
Additionally, cyclophosphamide is given at 900 mg/m2 intravenously over 60 minutes on the second day before the infusion of brexucabtagene autoleucel Intravenous infusion of brexucabtagene autoleucel is exclusively for autologous use and should be administered post-completion of lymphodepleting chemotherapy
The dosage is determined based on the quantity of chimeric antigen receptor (CAR)-positive viable T cells. The target dose is 1x 106 CAR-positive viable T cells per kilogram of body weight, with a maximum limit of 1x 108 CAR-positive viable T cells

Dose Adjustments

Management of Cytokine release syndrome:
Grade 1
Symptoms: Fever, nausea, fatigue, headache, myalgia, malaise If symptoms persist after 24 hours, administer tocilizumab at a dose of 8 mg/kg intravenously over 1 hour, with a maximum dose not exceeding 800 mg
Grade 2
Moderate intervention is required for symptoms, such as oxygen requirement <40% FiO2 hypotension responsive to fluids, a low dose of one vasopressor, or Grade 2 organ toxicity
Administer tocilizumab at a dose of 8 mg/kg intravenously over 1 hour, with a maximum dose not exceeding 800 mg
Repeat tocilizumab every 8 hours as necessary if there is no response to intravenous fluids or if supplemental oxygen needs to increase; do not exceed three doses within a 24-hour period or a total of 4 doses
If there is improvement, discontinue tocilizumab
If there is no improvement after 24 hours of starting tocilizumab, administer methylprednisolone (1 mg/kg intravenously twice daily) or dexamethasone (10 mg intravenously every 6 hours) until Grade 1, then taper corticosteroids
Grade 3
Symptoms necessitate aggressive intervention, such as oxygen requirement ≥40% FiO2, hypotension requiring high-dose or multiple vasopressors, Grade 3 organ toxicity, or Grade 4 transaminitis
Administer tocilizumab as outlined in Grade 2; discontinue if there is improvement
Prescribe corticosteroid doses as specified for Grade 2; taper if there is improvement or manage as Grade 4 if there is no improvement
Grade 4
Symptoms are posing a risk to life, necessitating ventilator assistance, ongoing venovenous hemodialysis, or organ toxicity of Grade 4 (excluding transaminitis)
Administer Tocilizumab according to Grade 2; if there's an improvement, discontinue
Inject Methylprednisolone 1000 mg intravenously daily for three days; reduce if there's an improvement or contemplate alternative immunosuppressants if no improvement is observed
Grading and management of Neurologic toxicity:
For Grades 2, 3, or 4: Contemplate the use of non-sedating antiseizure medications (such as levetiracetam) as a preventive measure against seizures
Grade 1
In the presence of concurrent Cytokine Release Syndrome (CRS), administer tocilizumab following the guidelines for Grade 1 CRS. If no concurrent CRS is observed, provide supportive care
Grade 2 with concurrent CRS
Administer tocilizumab following the specified doses for CRS Grade 2. If there's no improvement within 24 hours of initiating tocilizumab, administer 10 mg of dexamethasone intravenously every 6 hours if the individual is not already using other corticosteroids. Continue the use of dexamethasone until the event reaches Grade 1 or lower, then gradually taper over a 3-day period
Grade 2 or 3 without concurrent Cytokine Release Syndrome (CRS)
Initiate dexamethasone at 10 mg intravenously every 6 hours if the individual is not already using other corticosteroids. Continue this regimen until the event reaches Grade 1 or lower, then taper over a 3-day period. If the situation is Grade 3 and there is no improvement, handle it as Grade 4, employing intravenous methylprednisolone
Grade 3 with concurrent CRS
Administer tocilizumab following the doses specified for CRS Grade 2. Additionally, initiate dexamethasone at 10 mg intravenously every 6 hours if the person is not already using other corticosteroids. Continue the dexamethasone regimen until the event reaches Grade 1 or lower, then taper over a 3-day period
Grade 4 with concurrent Cytokine Release Syndrome (CRS)
Initiate tocilizumab following the specified doses for CRS Grade 2. Simultaneously, administer methylprednisolone at 1000 mg intravenously per day for three days, starting with the first dose of tocilizumab. If improvement is observed, proceed with the management as outlined above
Grade 4 without concurrent CRS
Administer methylprednisolone at 1000 mg intravenously per day for three days. If improvement occurs, manage the situation as described above. If there is no improvement, consider exploring alternative immunosuppressants

The dose is administered as a quick intravenous infusion lasting less than 30 minutes:

Administer a dose of 45 mg/m2 intravenous route once daily on day no. 1, 2, and 3 of the first course

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)

For <45 kg:
Administer a dose of 15 mcg/m2 intravenous route one time daily with continuous infusion on the day 1 to day 28 of a 6-week cycle including total of 4 cycles

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

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 the Patients on a cytarabine-containing regimen who are not responding to induction therapy (for 14 days & more)
Administer 165 mg/m2 intravenously at a minimum half-hour to 1-hour duration & administer cytarabine 300 mg/m2 intravenously two times a week in 8-9 doses
For Individuals unresponsive to regimens involving prednisone & vincristine: (for 14 days & more)
Intravenous administration of 250 mg/m2 for a minimum of half-hour to 1-hour duration & administer prednisone in the dose of 40 mg/m2 for duration of twenty-eight days through oral route with the administration of vincristine 1.5 mg/m2 intravenously in a week for the duration of four to eight weeks

Administer a dose of 4 to 5 mg/m2 intravenously weekly

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