Leukemia Treatment Regimens: Acute Lymphoblastic Leukemia (ALL)

Share this content:
SEE BELOW THE CHART TO SEE DRUG MONOGRAPHS FOR LEUKEMIAS, LYMPHOMAS, AND OTHER HEMATOLOGIC CANCERS.


<

LEUKEMIA TREATMENT REGIMENS:

Acute Lymphoblastic Leukemia (ALL)

Note: The NCCN guidelines for Acute Lymphoblastic Leukemia (ALL) should be consulted for the management of patients with lymphoblastic lymphoma.

Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment.

Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are only provided to supplement the latest treatment strategies.

The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available. They are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient's care or treatment. The NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

(Revised 5/2017)

© 2017 by Haymarket Media, Inc.

Ph(+) AYA (Age 15–39 years) 1,a,b,c

Note: All recommendations are Category 2A unless otherwise indicated.

PROTOCOL

REGIMEN AND DOSING

Children's Oncology Group (COG) AALL-00312

Induction

4 weeks of standard induction chemotherapy

Consolidation

Block 1 (3 weeks)

Day 1: Methotrexate (MTX) intrathecally (IT), etoposide 100mg/m2/day intravenously (IV), ifosfamide 3.4g/m2/day IV

Days 1–21: Imatinib 340mg/m2/day orally

Days 6–15: Filgrastim 5g/kg/day subcutaneously (SC) ± imatinib

Days 8 and 15: CNS leukemia only: MTX IT, hydrocortisone IT, cytarabine IT.

Block 2 (3 weeks)

Day 1: Age adjusted: MTX IT, hydrocortisone IT, cytarabine IT + MTX 5g/m2 IV over 24 hours

Days 1–21: Imatinib 340mg/m2/day orally (hold imatinib if patient does not achieve count recovery within 2 weeks of last dose of previous course)

Days 2–3: Leucovorin 75mg/m2 36 hours after MTX, followed by 15mg/m2 IV or orally every 6 hours for 6 doses + cytarabine 3g/m2/dose IV every 12 hours for 4 doses

Days 4–13: Filgrastim 5g/kg/day SC ± imatinib.

Reinduction

Day 1: Vincristine 1.5mg/m2 IV + age adjusted: MTX IT, hydrocortisone IT, cytarabine IT

Days 1–2: Daunorubicin 45mg/m2/day IV bolus

Days 1–21: Dexamethasone 6mg/m2/day orally ± imatinib 340mg/m2/day orally (hold imatinib if patient does not achieve count recovery within 2 weeks of last dose of previous course)

Days 3–4: Cyclophosphamide 250mg/m2/dose IV every 12 hours for 4 doses + mesna 125mg/m2/dose IV every 12 hours for 4 doses

Days 4, 6, 8, 10, 12, 15, 17, 19, and 21: L-asparaginase 6,000 IU/m2 intramuscularly (IM)

Days 5–14: Filgrastim 5g/kg/day SC

Days 8 and 15: Vincristine 1.5mg/m2 IV

Day 15: Age adjusted: MTX IT, hydrocortisone IT, cytarabine IT.

Intensification

Day 1: Age adjusted: MTX IT, hydrocortisone IT, cytarabine IT + MTX 5g/m2 IV over 24 hours

Days 1–63: Imatinib 340mg/m2/day orally (hold imatinib if patient does not achieve count recovery within 2 weeks of last dose of previous course)

Days 2–3: Leucovorin 75mg/m2 36 hours after MTX, followed by 15mg/m2 IV or orally every 6 hours for 6 doses

Day 8: MTX 5g/m2 IV over 24 hours

Days 9–10: Leucovorin 75mg/m2 36 hours after MTX, followed by 15mg/m2 IV or orally every 6 hours for 6 doses

Day 15: Age adjusted: MTX IT, hydrocortisone IT, cytarabine IT

Days 15–19: Etoposide 100mg/m2/day IV + cyclophosphamide 300mg/m2/day IV + mesna 150mg/m2/day IV

Days 20–29: Filgrastim 5mcg/kg/day SC

Days 36–37: Cytarabine 3g/m2 IV

Day 37: L-asparaginase 6,000 IU/m2 IM ± imatinib (hold imatinib if patient does not achieve count recovery within 2 weeks of last dose of previous course)

Days 43–44: Cytarabine 3g/m2 IV

Day 44: L-asparaginase 6,000 IU/m2 IM ± imatinib (hold imatinib if patient does not achieve count recovery within 2 weeks of last dose of previous course).

Repeat reinduction block 2 (3 weeks) and intensification block 2 (9 weeks) sequentially.

Maintenance

Cycles 1–4 (8 weeks)

Day 1: Age adjusted: MTX IT, hydrocortisone IT, cytarabine IT + vincristine 1.5mg/m2 IV + MTX 5g/m2 IV over 24 hours

Days 1–5: Dexamethasone 6mg/m2/day orally

Days 1–56: Imatinib 340mg/m2/day orally (hold imatinib if patient does not achieve count recovery within 2 weeks of last dose of previous course)

Days 2–3: Leucovorin 75mg/m2 36 hours after MTX, followed by 15mg/m2 IV or orally every 6 hours for 6 doses

Days 8, 15, and 22: MTX 20mg/m2/week orally

Days 8–28: 6-mercaptopurine (MP) 75mg/m2/day

Day 29: Age adjusted: MTX IT, hydrocortisone IT, cytarabine IT + vincristine 1.5mg/m2 IV

Days 29–33: Dexamethasone 6mg/m2/day orally

Days 29–40: Imatinib 340mg/m2/day orally (hold imatinib if patient does not achieve count recovery within 2 weeks of last dose of previous course)

Days 36–40: Etoposide 100mg/m2 IV + cyclophosphamide 300mg/m2 IV

Days 41–50: Filgrastim 5g/kg/day SC.

Cycles 5–12 (8 weeks)

Cycle 5 only: Cranial irradiation 12 Gy

Day 1: Vincristine 1.5mg/m2 IV

Days 1–5: Dexamethasone 6mg/m2/day orally

Days 1–14: Imatinib 340mg/m2/day orally (hold imatinib if patient does not achieve count recovery within 2 weeks of last dose of previous course)

Days 8, 15, and 22: MTX 20mg/m2/week orally

Days 8–28: 6-MP 75mg/m2/day

Day 29: Vincristine 1.5mg/m2 IV

Days 29–33: Dexamethasone 6mg/m2/day orally

Days 29–42: Imatinib 340mg/m2/day orally (hold imatinib if patient does not achieve count recovery within 2 weeks of last dose of previous course)

Day 36: MTX 20mg/m2/week orally

Days 36–56: 6-MP 75mg/m2/day

Days 43 and 50: MTX 20mg/m2/week orally.

EsPhALL regimen (imatinib + backbone of Berlin-Frankford-Munster regimen)3

Induction

Standard induction protocols per national guidelines.

Post-Induction Block 1

Days 1–28: 6-MP 60mg/m2 orally + imatinib 300mg/m2

Days 1 and 28: Cyclophosphamide 1000mg/m2 IV

Days 3–6, 10–13, 17–20, and 24–27: Cytosine arabinoside (ARA-C) 75mg/m2 SC

Days 3 and 7: Age adjusted: MTX IT (dosages: ≥1 year <2 years = 8mg; ≥2 years <3 years = 10mg; ≥3 years = 12mg).

Post-Induction Block 2

Day 1: MTX 5,000mg/m2 IV + Age adjusted: MTX IT + ARA-C IT + prednisone (PRED) IT (dosages: ≥1 year <2 years = MTX 8mg, ARA-C 20mg, PRED 6mg; ≥2 years <3 years = MTX 10mg, ARA-C 26mg, PRED 8mg; ≥3 years = MTX 12mg, ARA-C 30mg, PRED 10mg)

Days 1–5: Dexamethasone 20mg/m2 orally or IV

Days 1 and 6: Vincristine 1.5mg/m2 IV

Days 2–4: Cyclophosphamide 200mg/m2 IV

Day 5: ARA-C 2,000mg/m2 IV

Day 6: L-Asparaginase 25,000IU/m2 intramuscular (IM)

Days 6–20: Imatinib 300mg/m2 orally.

Post-Induction Block 3

Day 1: MTX 5,000mg/m2 IV + Age adjusted: MTX IT + ARA-C IT + PRED IT (dosages: ≥1 year <2 years = MTX 8mg, ARA-C 20mg, PRED 6mg; ≥2 years <3 years = MTX 10mg, ARA-C 26mg, PRED 8mg; ≥3 years = MTX 12mg, ARA-C 30mg, PRED 10mg)

Days 1–5: Dexamethasone 20mg/m2 orally or IV

Days 1 and 6: Vindesine 3mg/m2 IV

Days 2–4: Ifosfamide 800mg/m2 IV

Day 5: Daunorubicin 30mg/m2 IV

Day 6: L-Asparaginase 25,000IU/m2 IM

Days 6–20: Imatinib 300mg/m2 orally.

Post-Induction Block 4

Days 1–2: ARA-C 2,000mg/m2 IV

Days 1–5: Dexamethasone 20mg/m2 orally or IV

Day 1: Age adjusted: MTX IT + ARA-C IT + PRED IT (dosages: ≥1 year <2 years = MTX 8mg, ARA-C 20mg, PRED 6mg; ≥2 years <3 years = MTX 10mg, ARA-C 26mg, PRED 8mg; ≥3 years = MTX 12mg, ARA-C 30mg, PRED 10mg)

Days 3–5: Vepeside 100mg/m2 IV

Day 6: L-Asparaginase 25,000IU/m2 IM

Days 6–20: Imatinib 300mg/m2 orally.

Reinduction

Days 1–21 + tapering: Dexamethasone 10mg/m2 orally

Days 8, 15, 22, and 29: Vincristine 1.5mg/m2 IV + doxorubicin 25mg/m2 IV

Days 8, 11, 15, and 18: L-Asparaginase 10,000IU/m2 IM

Day 36: Cyclophosphamide 1000mg/m2 IV

Days 36–49: 6-Thioguanine 60mg/m2 orally

Days 38–41 and 45–48: ARA-C 75mg/m2 SC

Days 38–45: Age adjusted: MTX IT (dosages: ≥1 year <2 years = 8mg; ≥2 years <3 years = 10mg; ≥3 years = 12mg)

Days 36–63: Imatinib 300mg/m2 orally.

Administer reinduction twice, once before and once after interim maintenance. Omit IT therapy from second administration due to previous cranial irradiation.

Interim Maintenance

Days 1–29: 6-MP 50mg/m2 orally

Days 8, 15, 22, and 29: MTX 20mg/m2 orally

Cranial irradiation 1.4–1.7Gy (total dose per phase: standard = 18Gy; if <2 years = 12Gy; if CNS invasive = 24Gy).

Continuation Therapy (Maintenance)

6-MP 50mg/m2 orally daily until day +728 from diagnosis

MTX 20mg/m2 orally weekly till day +728 from diagnosis.

Hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) + Tyrosine Kinase Inhibitors (TKIs)4-7

Induction

4 cycles Hyper-CVAD alternating with 4 cycles of high dose cytarabine and MTX.

Days 1–14 of each cycle: Dasatinib 50mg orally twice daily (or 100mg daily) OR imatinib 400mg orally daily.

OR

Day 1: Cyclophosphamide 1,200mg/m2 IV over 3 hours

Days 1–3: Daunorubicin 60mg/m2 IV over 1 hour

Days 1–21: Prednisolone 60mg/m2 orally

Days 1, 8, 15, and 22: Vincristine 1.3mg/m2 IV bolus

Days 8–63: Imatinib 600mg orally

Day 29: MTX 15mg IT, cytarabine 40mg IT, dexamethasone 4mg IT.

OR

Pretreatment for 7 days: Prednisone at increasing doses from 10–40mg/m2/day.

Days 1–45: Imatinib 800mg orally daily + prednisone 40mg/m2 daily (patients >60 years).

OR

Pretreatment for 7 days: Prednisone at increasing doses from 10–60mg/m2/day

Days 1–48: Dasatinib 70mg orally twice daily

Days 1–24: Prednisone 60mg/m2 daily (max 120mg daily)

Days 22 and 43: MTX IT

Days 25–32: Prednisone taper.

Consolidation

Allogeneic hematopoietic cell transplant (HCT), if a donor is available and consider post-HCT TKI.

OR

Continue multiagent chemotherapy + TKI.

Maintenance

MTX weekly + 6-MP daily + vincristine pulse monthly + prednisone pulse monthly for 2 to 3 years.

Multiagent Chemotherapy + TKIs8,9

Induction

Day 1: Cyclophosphamide 1,200mg/m2 IV over 3 hours

Days 1–3: Daunorubicin 60mg/m2 IV over 1 hour

Days 1, 8, 15, and 22: Vincristine 1.3mg/m2 IV bolus

Days 1–21: Prednisolone 60mg/m2 orally daily

Days 8–63: Imatinib 600mg orally daily

Day 29: MTX 15mg IT + cytarabine 40mg IT + dexamethasone 4mg IT.

Consolidation 1

Day 1: MTX 1g/m2 IV over 24 hours + MTX 15mg IT + cytarabine 40mg IT + dexamethasone 4mg IT

Days 1–3: Methylprednisolone 50mg IV over 1 hour × 2 doses

Days 2 and 3: Cytarabine 2g/m2 IV over 3 hours.

Repeat for 4 cycles.

Consolidation 2

Day 1: MTX 15mg IT + cytarabine 40mg IT + dexamethasone 4mg IT.

Repeat for 4 cycles.

Day 1–28: Imatinib 600mg orally daily.

Maintenance

Day 1: Vincristine 1.3mg/m2 IV bolus

Days 1–5: Prednisolone 60mg/m2 orally daily

Day 1–28: Imatinib 600mg orally daily

Repeat every 4 weeks up to 2 years from the date of complete remission.

Hyper-CVAD + TKIs4-7

Induction

4 cycles Hyper-CVAD alternating with 4 cycles of high dose cytarabine and MTX.

Days 1–14 of each cycle: Dasatinib 50mg orally twice daily (or 100mg daily)3 OR imatinib 400mg orally daily.

OR

Day 1: Cyclophosphamide 1,200mg/m2 IV over 3 hours

Days 1–3: Daunorubicin 60mg/m2 IV over 1 hour

Days 1–21: Prednisolone 60mg/m2 orally

Days 1, 8, 15, and 22: Vincristine 1.3mg/m2 IV bolus

Days 8–63: Imatinib 600mg orally

Day 29: MTX 15mg IT, cytarabine 40mg IT, dexamethasone 4mg IT.

OR

Pretreatment for 7 days: Prednisone at increasing doses from 10–40mg/m2/day

Days 1–45: Imatinib 800mg orally daily + prednisone 40mg/m2 daily (patients >60 years).

OR

Pretreatment for 7 days: Prednisone at increasing doses from 10–60mg/m2/day

Days 1–24: Prednisone 60mg/m2 daily (max 120mg daily)

Days 1–48: Dasatinib 70mg orally twice daily

Days 22 and 43: MTX IT

Days 25–32: Prednisone taper.

Consolidation

Allogeneic hematopoietic cell transplant (HCT), if a donor is available and consider post-HSCT TKI.

OR

Continue multiagent chemotherapy + TKI.

Maintenance

MTX weekly + 6-MP daily + vincristine pulse monthly + prednisone pulse monthly for 2 to 3 years.

Multiagent Chemotherapy + TKIs8,9

Induction

Day 1: Cyclophosphamide 1,200mg/m2 IV over 3 hours

Days 1–3: Daunorubicin 60mg/m2 IV over 1 hour

Days 1, 8, 15, and 22: Vincristine 1.3mg/m2 IV bolus

Days 1–21: Prednisolone 60mg/m2 orally daily

Days 8–63: Imatinib 600mg orally daily

Day 29: MTX 15mg IT + cytarabine 40mg IT + dexamethasone 4mg IT.

Consolidation 1

Day 1: MTX 1g/m2 IV over 24 hours + MTX 15mg IT + cytarabine 40mg IT + dexamethasone 4mg IT

Days 1–3: Methylprednisolone 50mg IV over 1 hour × 2

Days 2 and 3: Cytarabine 2g/m2 IV over 3 hours.

Repeat for 4 cycles.

Consolidation 2

Day 1: MTX 15mg IT + cytarabine 40mg IT + dexamethasone 4mg IT.

Repeat for 4 cycles.

Days 1–28: Imatinib 600mg orally daily

Maintenance

Day 1: Vincristine 1.3mg/m2 IV bolus

Days 1–5: Prednisolone 60mg/m2 orally daily

Day 1–28: Imatinib 600mg orally daily.

Repeat every 4 weeks up to 2 years from the date of complete remission.

Ph(+) Adult (Age ≥40 years)1,a,b,c

Corticosteroids + TKIs10-12

Pretreatment

Days 1–7: Prednisone at increasing doses from 10–40mg/m2 orally daily.

Induction

Days 1–45: Imatinib 800mg orally daily + prednisone 40mg/m2 orally daily.

OR

Pretreatment

Days 1–7: Prednisone at increasing doses from 10–60mg/m2 orally daily.

Induction

Days 1–84: Dasatinib 70mg orally twice daily

Days 1–32: Prednisone 60mg/m2 orally daily (maximum 120mg daily) until day 24, then tapered and stopped at day 32

Days 22 and 43: MTX 15mg IT.

Vincristine + Dexamethasone + TKIs13,14

Pretreatment

Days 1–7: Prednisone at increasing doses from 10–40mg/m2 orally daily.

Induction

Cycle 1:

Days 1–28: Imatinib 800mg orally daily

Days 1, 8, 15, and 22: Vincristine 2mg IV

Days 1–2, 8–9, 15–16, and 22–23: Dexamethasone 40mg orally daily.

Cycle 2:

Day 1: MTX 1g/m2 IV

Days 2 and 3: Cytarabine 3g/m2 IV every 12 hours

Days 1–14: Imatinib 800mg orally daily.

OR

Pretreatment

Days 1–7: Prednisone at increasing doses from 10–40mg/m2 orally daily.

Induction

Cycle 1:

Days 1–28: Dasatinib 140mg orally once daily (100mg if patient >70 years)

Days 1, 8, 15, and 22: Vincristine 1mg IV

Days 1–2, 8–9, 15–16, and 22–23: Dexamethasone 40mg orally daily (20mg if patient >70 years).

Consolidation

Cycles 1, 3, and 5:

Days 1–28: Dasatinib 100mg orally daily

Day 1: MTX 1g/m2 IV (500mg/m² if patient >70 years)

Day 2: Asparaginase 10,000IU/m2 IM (5,000IU/m² if patient >70 years)

Cycles 2, 4, and 6:

Days 1–28: Dasatinib 100mg orally daily

Day 1, 3, and 5: Cytarabine 1,000mg/m2 every 12 hours IV (500mg/m² if patient >70 years).

Maintenance

Dasatinib sequentially with 6-MP and MTX orally one every other month, plus dexamethasone and vincristine every 2 months up to 24 months, followed by dasatinib alone until relapse or death.

Ph(−) AYA (Age 15–39 years) 1,a,b,c

GRAALL-200315

Corticosteroid Pre-Phase

1–7 days before induction therapy: Prednisone 60mg/m2/day

4–7 days before induction therapy: MTX 15mg IT.

Induction

Day 1: Cyclophosphamide 750mg/m2/day + vincristine 2mg IV

Days 1–3: Daunorubicin 50mg/m2/day

Days 1–14: Prednisone 60mg/m2/day

Day 8: Vincristine 2mg IV + L-asparaginase 6,000IU/m2/day

Days 10 and 12: L-asparaginase 6,000IU/m2/day

Day 15: Vincristine 2mg IV

Day 15: For Good Early Responders: Cyclophosphamide 750mg/m2/day.

OR

Days 15 and 16: For Poor Early Responders: Cyclophosphamide 500mg/m2/12 hours

Days 15 and 16: Daunorubicin 30mg/m2/day

Day 17: Lenograstim 150mcg/m2/day to myeloid recovery

Days 20 and 22: L-asparaginase 6,000IU/m2/day

Day 22: Vincristine 2mg IV

Days 24, 26, and 28: L-asparaginase 6,000IU/m2/day.

Salvage

Days 1–3: Idarubicin 12mg/m2/day

Days 1–4: Cytarabine 2g/m2/12 hours

Day 9: Filgrastim to myeloid recovery.

Consolidation

Blocks 1, 4, and 7:

Days 1 and 2: Cytarabine 2g/m2/12 hours + dexamethasone 10mg/12 hours

Day 3: L-asparaginase 10,000IU/m2/day

Days 7–13: Filgrastim to myeloid recovery.

Blocks 2, 5, and 8:

Day 15: MTX 3g/m2 continuous infusion + vincristine 2mg IV + 6-MP 60mg/m2/day

Day 16: L-asparaginase 10,000IU/m2/day

Days 16–21: 6-MP 60mg/m2/day

Days 22–27: Filgrastim to myeloid recovery.

Blocks 3, 6, and 9:

Day 29: MTX 25mg/m2/day

Days 29 and 30: Cyclophosphamide 500mg/m2/day + etoposide 75mg/m2/day

Day 31: Filgrastim to myeloid recovery.

Late intensification between consolidation blocks 6 and 7 (for patients in complete remission [CR] after the first induction course)

Day 1: Vincristine 2mg IV

Days 1–3: Daunorubicin 30mg/m2/day

Days 1–14: Prednisone 60mg/m2/day

Day 8: Vincristine 2mg IV

Days 8, 10, and 12: L-asparaginase 6,000IU/m2/day

Day 15: Vincristine 2mg IV + cyclophosphamide 500mg/m2/12 hours

Days 18, 20, and 22: L-asparaginase 6,000IU/m2/day.

Late intensification between consolidation blocks 6 and 7 (for patients in CR after salvage course)

Days 1–3: Idarubicin 9mg/m2/day

Days 1–4: Cytarabine 2g/m2/12 hours

Day 9: Filgrastim to myeloid recovery.

Maintenance

Months 1–12

Day 1: Vincristine 2mg IV

Days 1–7: Prednisone 40mg/m2/day.

Months 1–24

Daily: 6-MP 60mg/m2/day

Weekly: MTX 25mg/m2/week.

CNS Therapy—Prophylaxis

Triple IT Injection

1 IT injection at Days 1 and 8 of induction; 1 IT injection at Day 29 of each series of consolidation blocks; 1 IT injection at Day 1 of late intensification.

Cranial Irradiation

18Gy before maintenance therapy initiation. 6-MP 60mg/m2/day during irradiation.

CNS Therapy—Treatment of patients with initial CNS involvement:

Triple IT Injection

8 IT injections starting from 7 days before induction to Day 21 of induction; 4 IT injections during the first 2 consolidation blocks; 1 IT injection at Day 29 of consolidation blocks 3 and 6.

Cranial Irradiation

15Gy before HCT or 24Gy before maintenance therapy initiation

6-MP 60mg/m2/day during irradiation.

COG AALL-043416

Induction (4 weeks)

Day 1: Cytarabine IT

Days 1, 8, 15, and 22: Vincristine IV + daunorubicin IV

Days 1–28: Prednisone IV or orally twice daily

Day 4, 5, or 6: Pegaspargase IM or IV over 1–2 hours

Days 8 and 29: MTX IT.

Consolidation

Days 1–5 and 43–47: Nelarabine IV over 60 minutes

Days 15, 22, 57, and 64: MTX IT

Days 8 and 50: Cyclophosphamide IV over 30 minutes

Days 8–11, 15–18, 50–53, and 57–60: Cytarabine IV over 15–30 minutes or SC

Days 8–21 and 50–63: Mercaptopurine orally

Days 22, 29, 64, and 71: Vincristine sulfate IV

Days 22 and 64: Pegaspargase IM or IV over 1–2 hours.

COG AALL023217,18

Induction

Days 1–28: Prednisone oral or IV twice daily

Day 1: Cytarabine IT

Days 1, 8, 15, and 22: Vincristine IV + daunorubicin IV

Days 4, 5, or 6: Pegaspargase IM

Days 8 and 29: MTX IT

Days 15 and 22: Only patients with CNS3 disease: MTX IT.

Extended Induction

Only for patients with M2 disease of M1 disease with >1% MRD

Days 1–14: Prednisone oral of IV twice daily

Days 1 and 8: Vincristine IV

Day 1: Daunorubicin IV

Days 4, 5, or 6: Pegaspargase IM.

Consolidation (7–8 weeks)

Days 1 and 29: Cyclophosphamide IV over 30 min

Days 2–5, 9–12, 30–33, and 37–40: Cytarabine IV or SC

Days 1–14 and 29–42: Mercaptopurine orally

Days 15, 22, 43, and 50: Vincristine IV

Days 15 and 43: Pegaspargase IM

Days 1, 8, 15, and 22: MTX IT (patients with CNS3 disease receive MTX on Days 1 and 8 only).

Interim Maintenance I

Days 1, 11, 21, 31, and 41: Vincristine IV + escalating dose MTX IV

Days 1 and 21: MTX IT

Days 2 and 22: Pegaspargase IM.

OR

Days 1, 15, 29, and 43: Vincristine IV and high-dose MTX IV over 24 hours

Days 1–56: Mercaptopurine orally

Days 1 and 29: MTX IT.

Delayed Intensification I

Days 1, 8, 15, 43, and 50: Vincristine IV

Days 1–21: Only patients aged 1–12: Dexamethasone orally or IV twice daily

Days 1–7 and 15–21: Only patients aged ≥13 years: Dexamethasone orally or IV twice daily

Days 1, 8, and 15: Doxorubicin IV

Days 4, 5, or 6 and day 43: Pegaspargase IM

Day 29: Cyclophosphamide IV

Days 30–33 and 37–40: Cytarabine IV or SC

Days 29–42: Oral thioguanine

Days 1, 29, and 36: MTX IT.

Interim Maintenance II

Days 1, 11, 21, 31, and 41: Vincristine IV + MTX IV

Days 2 and 22: Pegaspargase IM

Days 1 and 21: MTX IT.

Delayed Intensification II

Same regimen as delayed intensification I

Day 29: CNS3 patients only: Start radiotherapy for 3–10 days; All other slow early response patients: Start prophylactic cranial radiotherapy for 8 days.

Maintenance Therapy

Day 1: MTX IT

Days 1, 29, and 57: Vincristine IV

Days 1–5, 29–33, and 57–61: Dexamethasone orally twice daily

Days 1–84: Mercaptopurine orally

Days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78: MTX orally.

DFCI ALL Regimen per DFCI Protocol 00-0119,20

Induction (4 weeks)

Days 0, 7, 14, and 21: Vincristine 1.5mg/m2 weekly (maximum, 2mg)

Days 0–28: Prednisone 40mg/m2/day

Days 0 and 1: Doxorubicin 30mg/m2/dose (high-risk patients: with dexrazoxane 300mg/m2/dose) + MTX 4g/m2 (8–24 hours after doxorubicin) with leucovorin rescue

1 dose: L-asparaginase 25,000IU/m2 IM

Day 0: Cytarabine IT

Day 14 (1 dose): MTX IT + cytarabine IT + hydrocortisone IT

CNS Therapy (3 weeks)

Day 1: Vincristine 2mg/m2

14 days: 6-Mercaptopurine (6-MP) 50mg/m2/day orally at bedtime

Standard-risk patients: MTX IT + cytarabine IT + hydrocortisone IT twice weekly × 4 doses

High-risk patients: MTX IT + cytarabine IT twice weekly × 4 doses + doxorubicin 30mg/m2 + dexrazoxane 300mg/m2 + cranial radiation

Intensification (30 weeks)

Cycle every 3 weeks

Day 1: Vincristine 2mg/m2

14 doses: 6-MP 50mg/m2/day orally at bedtime

Once Weekly: MTX 30mg/m2 (1mg/kg if <0.6 m2) IV or IM

Days 1–5: Prednisone 40mg/m2/day orally ÷ twice daily (20mg/m2 per dose)

Weekly: L-asparaginase 25,000IU/m2 IM, weekly × 30 weeks OR 12,500IU/m2 IM (starting dose) weekly, with dose adjusted every 3 weeks to maintain nadir serum asparaginase activity between 0.1–0.14IU/mL

Start of a cycle every 9 weeks: MTX IT + cytarabine IT + hydrocortisone IT × 6 doses, then every 18 weeks through completion of therapy (at start of a cycle).

High-risk patients: Same as above, except higher corticosteroid dose

Days 1–5: Prednisone 120mg/m2/day)

Day 1 of each cycle: Doxorubicin 30mg/m2 (cumulative dose 300mg/m2) + dexrazoxane 300mg/m2/dose [NOTE: No weekly MTX IV/IM until doxorubicin completed, and IT therapy of MTX/cytarabine every 18 weeks]

Continuation (74 weeks)

Cycle every 3 weeks

Standard-risk patients: Same as intensification, except no L-asparaginase

High-risk patients: Same as SR patients, including lower corticosteroid dose of dexamethasone 6mg/m2 per day and prednisone 40mg/m2 per day on days 1 to 5.

USC ALL Regimen per CCG-188221

Induction Phase I

Days 1–3: Daunorubicin 60mg/m2 IV

Days 1, 8, 15, and 22: Vincristine 1.4mg/m2 IV (maximum, 2mg)

Day 15: Pegaspargase 2,000IU/m2 IV

Days 1–28: Prednisone 60mg/m2 orally

Days 8 and 15: MTX 12mg IT.

Induction Phase II

Days 1 and 29: Cyclophosphamide 1g/m2 IV

Days 1–4, 8–11, 29–32, and 36–39: Cytarabine 75mg/m2 IV

Days 15, 22, 43, and 50: Vincristine 1.4mg/m2 IV (maximum, 2mg)

Day 15: Pegaspargase 2,000IU/m2 IV

Days 15–29: Prednisone 20mg/m2 orally

Days 1– 14 and 29–43: Mercaptopurine 60mg/m2 orally

Days 1, 8, 15, and 22: MTX 12mg IT.

Intensification

Days 1 and 15: MTX 1g/m2 IV (T-cell ALL, 2.5g/m2 IV) +

leucovorin 15mg every 6 hours IV starting 36 hours from start of MTX

Day 16: Pegaspargase 2,000IU/m2 IV

Days 16–30: Prednisone 20mg/m2 orally

Consolidation

Days 1–5: Cytarabine 75mg/m2 IV + teniposide 60mg/m2 IV.

Delayed Reinduction

Days 1, 8, and 15: Daunorubicin 25mg/m2 IV

Days 1, 8, 15, 43, and 50: Vincristine 1.4mg/m2 IV (maximum, 2mg)

Days 15–22 and 43–50: Dexamethasone 10mg/m2 orally

Day 15: Pegaspargase 2,000IU/m2 IV

Day 29: Cyclophosphamide 1g/m2

Days 29–32 and 36–39: Cytarabine 75mg/m2 IV

Days 26–42: Thioguanine 60mg/m2 orally

Days 1, 29, and 36: MTX 12mg IT.

Maintenance

Monthly for 24 months from end of all consolidations

Days 1–5: Prednisone 60mg/m2 orally (year 1, monthly; year 2, every 2 months)

Day 1: Vincristine 1.4mg/m2 (maximum, 2mg) IV (year 1, monthly; year 2, every 2 months)

Days 1–28: Mercaptopurine 60mg/m2 orally

Days 1, 8, 15, and 22: MTX 20mg/m2 orally + MTX 12mg IT (year 1, once every 3 months).

Imatinib 600mg once daily from induction until end of standard maintenance regimen added for Philadelphia chromosome–positive patients.

PETHEMA ALL-9622

Induction

Days 1, 8, 15, and 22: Vincristine 2mg IV + daunorubicin 30mg/m2 IV

Days 1–27: Prednisone 60mg/m2 IV or orally

Days 1 and 29: MTX 15mg IT + cytarabine 30mg IT + hydrocortisone 20mg IT

Days 10–12, 17–19, and 24–26: Asparaginase 10,000U/m2

Days 28–35: Prednisone 30mg/m2 IV or orally

Day 36: Cyclophosphamide 1,000mg/m2 IV.

Consolidation

Days 1–7: Mercaptopurine 50mg/m2 orally

Days 1, 28, and 56: MTX 3g/m2 IV over 24 hours

Days 14 and 42: Teniposide 150mg/m2 IV every 12 hours

Days 14, 15, 42, and 43: Cytarabine 500mg/m2 IV every 12 hours

Days 1, 28, and 56: MTX 15mg IT + cytarabine 30mg IT + hydrocortisone 20mg IT.

Consolidation-2/Reinduction

Days 1–14: Dexamethasone 10mg/m2 orally or IV daily

Days 1, 2, 8, and 9: Daunorubicin 30mg/m2 IV

Days 1–3 and 15–17: Asparaginase 10,000U/m2 IM or IV

Days 1, 8, and 15: Vincristine 1.5mg/m2 IV

Days 1 and 15: Cyclophosphamide 600mg/v IV + MTX 15mg IT + cytarabine

30mg IT + hydrocortisone 20mg IT

Days 15–21: Dexamethasone 5mg/m2 orally or IV daily.

Maintenance-1

MTX 20mg/m2 IM weekly until week 52

Mercaptopurine 50mg/m2 orally daily until week 52.

CALGB 1040323

Induction

Day 1: Cytarabine IT

Days 8 and 29: MTX IT

Days 1, 8, 15, and 22: Daunorubicin IV + Vincristine IV

Day 4: PEG-asparaginase.

Consolidation

Days 1, 8, 15, and 22: MTX IT

Days 1 and 29: Cyclophosphamide IV

Days 1–4, 8–11, 29–32, and 36–39: Cytarabine

Days 1–14 and 29–42: 6-Mercaptopurine orally

Days 15, 22, 43, and 50: Vincristine IV

Day 15 and 43: PEG-asparaginase.

Interim Maintenance

Days 1 and 31: MTX IT

Days 1, 11, 21, 31, and 41: Vincristine IV + MTX

Days 2 and 22: PEG-asparaginase.

Delayed Intensification

Days 1, 29, and 36: MTX IT

Days 1–7 and 15–21: Dexamethasone orally

Days 1, 8, and 15: Doxorubicin IV

Days 4 and 43: PEG-asparaginase

Day 29: Cyclophosphamide IV

Days 29–32 and 36–39: Cytarabine IV

Days 29–42: 6-Thioguanine orally.

Maintenance

Days 15 and 29: MTX IT of first 4 courses of maintenance

Days 1, 29, and 57: Vincristine IV

For Females: Days 1–5, 29–33, and 57–61: Dexamethasone orally for 2 years from interim maintenance

For Males: Days 1–84: 6-Mercaptopurine orally for 3 years from interim maintenance

Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78: MTX; held on Day 29 of first 4 courses of maintenance when methotrexate IT is given.

CALGB 8811 (Larson Regimen)24

Induction

Day 1: Cyclophosphamide 1, 200mg/m2 IV

Days 1–3: Daunorubicin 45mg/m2 IV

Days 1, 8, 15, and 22: Vincristine 2mg IV

Days 1–21: Prednisone 60mg/m2/day orally

Days 5, 8, 11, 15, 18, and 22: L-asparaginase 6,000IU/m2 SC.

Consolidation

Day 1: MTX 15mg IT + cyclophosphamide 1,000mg/m2 IV

Days 1–14: 6-Mercaptopurine 60mg/m2/day orally

Days 1–4 and 8–11: Cytarabine 75mg/m2/day SC

Days 15 and 22: Vincristine 2mg IV

Days 15, 18, 22, and 25: L-asparaginase 6,000IU/m2 SC.

Repeat cycle every 4 weeks for 2 cycles, followed by:

Days 1–12: Cranial irradiation 2,400cGy

Days 1, 8, 15, 22, and 29: MTX 15mg IT

Days 1–70: 6-Mercaptopurine 60mg/m2/day orally

Days 36, 43, 50, 57, and 64: MTX 20mg/m2 orally, followed by:

Days 1, 8, and 15: Doxorubicin 30mg/m2 IV

Days 1, 8, and 15: Vincristine 2mg IV

Days 1–14: Dexamethasone 10mg/m2/day orally

Day 29: Cyclophosphamide 1,000mg/m2 IV

Days 29–42: 6-Thioguanine 60mg/m2/day orally

Days 29–32 and 36–39: Cytarabine 75mg/m2/day SC, followed by:

Day 1: Vincristine 2mg IV

Days 1–5: Prednisone 60mg/m2/day orally

Days 1, 8, 15, and 22: MTX 20mg/m2 orally

Days 1–28: 6-Mercaptopurine 60mg/m2/day orally.

Repeat cycle every 4 weeks until 24 months from diagnosis.

Linker 4-Drug Regimen25

Induction

Days 1–3: Daunorubicin 50mg/m2/day IV

Days 1, 8, 15, and 22: Vincristine 2mg IV

Days 1–28: Prednisone 60mg/m2/day orally

Days 17–28: L-asparaginase 6,000IU/m2/day IM.

If bone marrow on Day 14 has residual leukemia:

Day 15: Daunorubicin 50mg/m2 IV.

If bone marrow on Day 28 has residual leukemia:

Day 29 and 30: Daunorubicin 50mg/m2 IV

Days 29–35: L-asparaginase 6,000IU/m2/day IM.

Days 29–42: Prednisone 60mg/m2/day orally.

Consolidation

Cycles 1, 3, 5, and 7:

Days 1 and 2: Daunorubicin 50mg/m2/day IV

Days 1 and 8: Vincristine 2mg IV

Days 1–14: Prednisone 60mg/m2/day orally

Days 4, 7, 9, 11, and 14: L-asparaginase 12,000IU/m2/day IM.

Cycles 2, 4, 6, and 8:

Days 1, 4, 8, and 11: Teniposide 165mg/m2 IV + cytarabine 300mg/m2 IV.

Cycle 9:

MTX 690mg/m2 IV over 42 hours, followed by leucovorin 15mg/m2 IV every 6 hours x 12 doses, followed by:

MTX 20mg/m2 orally weekly + 6-Mercaptopurine 75mg/m2 orally daily for 30 months.

Hyper-CVAD ± Rituximab26,27

Cycles 1, 3, 5, and 7

Days 1–3: Cyclophosphamide 300mg/m2 IV every 12 hours + mesna 600mg/m2/day continuous IV infusion starting 1 hour before cyclophosphamide until 12 hours after completion of cyclophosphamide

Days 1–4 and 11–14: Dexamethasone 40mg orally daily, ±

Days 1 and 8: Rituximab 375mg/m2 IV

Day 4: Doxorubicin 50mg/m2 IV over 24 hours

Days 4 and 11: Vincristine 2mg IV.

Cycles 2, 4, 6, and 8

Day 1: MTX 200mg/m2 IV over 2 hours followed by 800mg/m2 continuous IV infusion over 22 hours followed by leucovorin 50mg IV every 6 hours starting 12 hours after completion of MTX until MTX level <0.05uM

Days 2–3: Cytarabine 3g/m2 (1g/m2 for patients >60 years old) IV over 2 hours every 12 hours, ±

Days 1 and 8: Rituximab 375mg/m2 IV.

CNS Prophylaxis

Day 2: MTX 12mg IT

Day 8: Cytarabine 100mg IT.

MRC UKALLXII/ECOG299328

Induction

Phase 1 (Weeks 1–4):

Days 1, 8, 15, and 22: Daunorubicin 60mg/m2 IV + vincristine 1.4mg/m2 IV

Days 1–28: Prednisone 60mg/m2 orally daily

Day 15: MTX 12.5mg IT

Days 17–28: L-asparaginase 10,000IU IV or IM.

Phase 2 (Weeks 5–8):

Days 1, 15, and 29: Cyclophosphamide 650mg/m2 IV

Days 1–4, 8–11, 15–18, and 22–25: Cytarabine 75mg/m2 IV

Days 1–28: 6-Mercaptopurine 6mg/m2 orally daily

Days 1, 8, 15, and 22: MTX 12.5mg IT.

Intensification

Days 1, 8, and 22: MTX 3g/m2 IV

Days 2, 9, and 23: L-asparaginase 10,000IU IM or IV + standard leucovorin rescue.

Consolidation

Cycle 1:

Days 1–5: Etoposide 100mg/m2 IV + cytarabine 75mg/m2 IV

Days 1, 8, 15, and 22: Vincristine 1.4mg/m2 IV

Days 1–28: Dexamethasone 10mg/m2 orally daily.

Cycle 2 (4 Weeks After Cycle 1):

Days 1–5: Cytarabine 75mg/m2 IV + etoposide 100mg/m2 IV.

Cycle 3 (4 Weeks After Cycle 2):

Days 1, 8, 15, and 22: Daunorubicin 25mg/m2 IV

Day 29: Cyclophosphamide 650mg/m2 IV

Days 31–34 and 38–41: Cytarabine 75mg/m2 IV

Days 29–42: Thioguanine 60mg/m2 orally daily.

Maintenance:

Vincristine 1.4mg/m2 IV every 3 months

Prednisone 60mg/m2 orally for 5 days every 3 months

6-Mercaptopurine 75mg/m2 orally daily

MTX 20mg/m2 orally or IV once weekly.

Continue for 2.5 years from start of intensification therapy.

Relapsed or Refractory ALL1a

Ph(+) ALL

Dasatinib (preferred)29,30,d

Dasatinib 140mg orally daily.

Continue until disease progression or unacceptable toxicity.

Nilotinib31,e

Nilotinib 400mg orally twice daily.

Continue until disease progression or unacceptable toxicity.

Imatinib (preferred)32

Imatinib 600mg orally daily.

Continue until disease progression or unacceptable toxicity.

Ponatinib (preferred)33, f

Ponatinib 45mg orally daily.

Continue until disease progression or unacceptable toxicity.

Ph(−) ALL

Clofarabine-Containing Regimens (for B-ALL)34,35

Induction

Days 1–5: Clofarabine 40mg/m2 IV over 2 hours + etoposide 100mg/m2 IV over 2 hours + cyclophosphamide 440mg/m2 IV over 1 hours.

Consolidation

Days 1–4: Clofarabine 40mg/m2 IV over 2 hours + etoposide 100mg/m2 IV over 2 hours + cyclophosphamide 440mg/m2 IV over 1 hours.

Cytarabine-Containing Regimens36

Days 1–5: Cytarabine 3g/m2 IV over 3 hours

Day 3: Idarubicin 40mg/m2.

Alkylator-Containing Regimens37

Days 1–3: Mitoxantrone 8mg/m2 IV daily

Days 1–5: Etoposide 100mg/m2 IV daily + ifosfamide 1.5g/m2 IV daily.

Nelarabine (for T-ALL)38

Days 1, 3, and 5: Nelarabine 1.5g/m2/day IV over 2 hours.

Repeat cycle every 21 days.

Augmented Hyper-CVAD39

Cycles 1, 3, 5, and 7

Day 1: Pegaspargase 2,500units/m2 IV

Days 1–3: Cyclophosphamide 300mg/m2 IV every 12 hours for 6 doses + MESNA 600mg/m2 continuous IV infusion over 24 hours daily

Day 4: Doxorubicin 50mg/m2 IV over 24 hours

Days 1, 8, and 15: Vincristine 2mg IV

Days 1–4 and 15–18: Dexamethasone 80mg IV or orally.

Cycles 2, 4, 6, and 8

Day 1: MTX 1g/m2 IV over 24 hours with leucovorin 50mg IV given 12 hours after completion of MTX, followed by leucovorin 15mg IV every 6 hours for 8 doses

Days 2–3: Cytarabine 3g/m2 IV every 12 hours for 4 doses

Day 5: Pegaspargase 2,500units/m2 IV.

Maintenance

Mercaptopurine 50mg orally 3 times daily + MTX 20mg/m2 orally weekly + vincristine 2mg IV every 28–35 days + prednisone 200mg orally daily on days 1–5.

Vincristine Sulfate Liposome Injection40,41

Liposomal vincristine sulfate 2.25mg/m2 IV over 1 hour once weekly until response, progression, toxicity, or pursuit of HCT.

Blinatumomab (for B-ALL; preferred)42–44,g

Cycle 1

Days 1–7: Blinatumomab 9mcg/day continuous IV infusion

Days 8–28: Blinatumomab 28mcg/day continuous IV infusion.

Subsequent Cycles

Days 1–28: Blinatumomab 28mcg/day continuous IV infusion.

Repeat cycle every 42 days.

a All regimens include CNS prophylaxis with systemic therapy (eg, methotrexate, cytarabine, 6-MP) and/or IT therapy (eg, IT methotrexate, IT cytarabine; triple IT therapy with methotrexate, cytarabine, corticosteroid).

b For patients receiving 6-MP, consider testing for TPMT gene polymorphisms, particularly in patients who develop severe neutropenia after starting 6-MP.

c Dose modifications for antimetabolites in maintenance should be consistent with the chosen treatment regimen. It may be necessary to reduce dose/eliminate antimetabolite in the setting of myelosuppression and/or hepatotoxicity.

d For patients with mutations Y253H, E255K/V or F359V/C/I.

e For patients with mutations F317L/V/I/C, T315A or V299L.

f Ponatinib has activity against T315I mutations and is effective in treating patients with resistant or progressive disease on multiple TKIs, but is associated with a high frequency of serious vascular events. The FDA indications are for the treatment of adult patients with T3151-positive PH+ ALL and for the treatment of adult patients with PH+ ALL for whom no other TKI therapy is indicated.

g Blinatumuomab may cause severe, life-threatening, or fatal adverse events, including cytokine release syndrome and neurologic toxicities. Understanding the REMS programs and/or experience in the use of the drug as well as resources to monitor the patient closely are essential. It is important that the instruction for blinatumomab product preparation (including admixing) and administration are strictly followed to minimize medication errors, including underdose and overdose.

References

1. NCCN Clinical Practice Guidelines in Oncology®. Acute Lymphoblastic Leukemia. v 2.2016. Available at: http://www.nccn.org/ professionals/physician_gls/pdf/all.pdf. Accessed May 10, 2017.

2. Schultz KR, Bowman WP, Aledo A, et al. Improved early event-free survival with imatinib in Philadelphia chromosome-positive ALL: A Children's Oncology Group Study. J Clin Oncol. 2009;27(31):5175–5181.

3. Biondi A, Schrappe M, De Lorenzo P, et al. Imatinib after induction for treatment of children and adolescents with Philadelphia-chromosome- positive acute lymphoblastic leukaemia (EsPhALL): a randomised, open-label, intergroup study. Lancet Oncol. 2012;13(9):936-945.

4. Ravandi F, O'Brien S, Thomas D, et al. First report of phase 2 study of dasatinib with hyper-CVAD for the frontline treatment of patients with Philadelphia chromosome-positive ALL. Blood. 2010;116(12):2070–2077.

5. Thomas DA, Faderl S, Cortes J, et al. Treatment of Philadelphia chromosome-positive ALL with hyper-CVAD and imatinib mesylate. Blood. 2004;103(12):4396–4407.

6. Thomas DA, Kantarjian HM, Cortes J, et al. Outcome after frontline therapy with the hyper-CVAD and imatinib mesylate regimen for adults with de novo or minimally treated Philadelphia chromosome-positive ALL [abstract]. Blood. 2008;112 (Supple 11):Abstract 2931.

7. Thomas DA, O'Brien SM, Faderl S, et al. Long-term outcome after hyper-CVAD and imatinib for de novo or minimally treated Philadelphia chromosome-positive ALL [abstract]. J Clin Oncol. 2010;28:Abstract 6506.

8. Mizuta S, Matsuo K, Yagasaki F, et al. Pre-transplant imatinib-based therapy improves the outcome of allogenic hematopoietic stem cell transplantation for BCR-ABL-positive ALL. Leukemia. 2011;25(1):41–47.

9. Yanada M, Takeuchi J, Sugiura I, et al. High complete remission rate and promising outcome by combination of imatinib and chemotherapy for newly diagnosed BCR-ABL-positive ALL: a phase II study by the Japan Adult Leukemia Study Group. J Clin Oncol. 2006;24(3):460–466.

10. Vignetti M, Fazi P, Cimino G, et al. Imatinib plus steroids induces complete remissions and prolonged survival in elderly Philadelphia chromosome-positive patients with ALL without additional chemotherapy: results of the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) LAL0201-B protocol. Blood. 2007;109(9):3676–3678.

11. Foa R, Vitale A, Guarini A, et al. Dasatinib monotherapy effective and feasible as first-line treatment of adult Ph+ ALL patients. Final results of the GIMEMA LAL1205 study [abstract]. Blood. 2008;112(Supple 11):Abstract 305.

12. Foa R, Vitale A, Vignetti M, et al. Dasatinib as first-line treatment for adult patients with Ph+ ALL. Blood. 2011;118(25):6521–6528.

13. Chalandon Y, Thomas X, Hayette S, et al. Is less chemotherapy detrimental in adults with Ph+ ALL treated with high-dose imatinib? Results of the prospective randomized Graaph-2005 study [abstract]. Blood. 2012;120:Abstract 138.

14. Rousselot P, Coude MM, Huguet F, et al. Dasatinib and low intensity chemotherapy for first-line treatment in patients with de novo Ph+ ALL aged 55 and over: final results of the EWALL-Ph-01 study [abstract]. Blood. 2012;120:Abstract 666.

15. Huguet F, Leguay T, Raffoux E, et al. Pediatric-inspired therapy in adults with Ph- ALL: the GRAALL-2003 study. J Clin Oncol. 2009;27(6):911–918.

16. Winter SS, Devidas M, Wood B, et al. Nelarabine may be safely incorporated into a phase III study for newly diagnosed T-lineage ALL: a report from the Children's Oncology Group [abstract]. Blood. 2010;116:Abstract 865.

17. Borowitz MJ, Wood BL, Devidas M, et al. Prognostic significance of minimal residual disease in high risk B-ALL: a report from Children's Oncology Group study AALL0232. Blood. 2015;126(8):964–971.

18. COG-AALL0232. http://www.ped-onc.org/diseases/ALLtrials/COG0232.html. Accessed May 20, 2017.

19. Waber DP, McCabe M, Sebree M, et al. Neuropsychological outcomes of a randomized trial of prednisone versus dexamethasone in acute lymphoblastic leukemia: findings from Dana-Farber Cancer Institute ALL Consortium Protocol 00-01. Pediatr Blood Cancer. 2013;60:1785–1791.

20. Vrooman LM, Stevenson KE, Supko JG, et al. Postinduction dexamethasone and individualized dosing of Escherichia coli L-asparaginase each improve outcome of children and adolescents with newly diagnosed acute lymphoblastic leukemia: results from a randomized study—Dana-Farber Cancer Institute ALL Consortium Protocol 00-01. J Clin Oncol. 2013;31(9):1202–1210.

21. Douer D, Aldoss I, Lunning MA, et al. Pharmacokinetics-based integration of multiple doses of intravenous pegaspargase in a pediatric regimen for adults with newly diagnosed acute lymphoblastic leukemia. J Clin Oncol. 2014;32(9):905–911.

22. Ribera JM, Oriol A, Sanz MA, et al. Comparison of the results of the treatment of adolescents and young adults with standard-risk ALL with the Programa Espanol de Tratamiento en Hematologia pediatric-based protocol ALL-96. J Clin Oncol. 2008;26(11):1843–1849.

23. Stock W, Luger SM, Advani AS, et al. Favorable outcomes for older adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL): early results of U.S. Intergroup Trial C10403 [abstract]. Blood. 2014;124:Abstract 796.

24. Larson RA, Dodge RK, Burns CP, et al. A five-drug remission induction regimen with intensive consolidation for adults with ALL: a cancer and leukemia group B study 8811. Blood. 1995;85(8):2025–2037.

25. Linker C, Damon L, Ries C, Navarro W. Intensified and shortened cyclical chemotherapy for adult ALL. J Clin Oncol. 2002;20:2464–2471.

26. Kantarjian H, Thomas D, O'Brien S, et al. Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult ALL. Cancer. 2004;101(12):2788–2801.

27. Thomas DA, O'Brien S, Faderl S, et al. Chemoimmunotherapy with a modified hyper-CVAD and rituximab regimen improves outcome in de novo Ph- precursor B-lineage ALL. J Clin Oncol. 2010;28(24):3880–3889.

28. Rowe JM, Buck G, Burnett AK, et al. Induction therapy for adults with ALL: results of more than 1500 patients from the international ALL trial: MRC XII/ECOG E2993. Blood. 2005;106(12):3760–3767.

29. Lilly MB, Ottmann OG, Shah NP, et al. Dasatinib 140 mg once daily versus 70 mg twice daily in patients with Ph+ ALL who failed imatinib: results from a phase 3 study. Am J Hematol. 2010;85(3):164–170.

30. Ottmann O, Dombret H, Martinelli G, et al. Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Ph+ ALL with resistance or intolerance to imatinib: interim results of a phase 2 study. Blood. 2007;110(7):2309–2315.

31. Kantarjian H, Giles F, Wunderle L, et al. Nilotinib in imatinib-resistant CML and Ph+ ALL. N Engl J Med. 2006;354(24):2542–2551.

32. Ottmann OG, Druker BJ, Sawyers CL, et al. A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoid leukemias. Blood. 2002;100(6):1965-1971.

33. Cortes JE, Kim DW, Pinilla-Ibarz J, et al. A phase 2 trial of ponatinib in Ph+ leukemias. N Engl J Med. 2013;369(19):1783–1796.

34. Jeha S, Gaynon PS, Razzouk BI, et al. Phase II study of clofaribine in pediatric patients with refractory or relapsed ALL. J Clin Oncol. 2006;24(12):1917–1923.

35. Miano M, Pistorio A, Putti MC, et al. Clofarabine, cyclophosphamide and etoposide for the treatment of relapsed or resistant ALL in pediatric patients. Leuk Lymphoma. 2012;53(9): 1693–1698.

36. Weiss MA, Aliff TB, Tallman MS, et al. A single, high dose of idarubicin combined with cytarabine as induction therapy for adult patients with recurrent or refractory ALL. Cancer. 2002; 95(3):581–587.

37. Schiller G, Lee M, Territo M, Gajewski J, Nimer S. Phase II study of etoposide, ifosfamide, and mitoxantrone for the treatment of resistant adult ALL. Am J Hematol. 1993;43(3):195–199.

38. DeAngelo DJ, Yu D, Johnson JL, et al. Nelarabine induces complete remissions in adults with relapsed or refractory T-lineage ALL or lymphoblastic lymphoma: Cancer and Leukemia Group B study 19801. Blood. 2007;109(12):5136–5142.

39. Faderl S, Thomas DA, O'Brien S, et al. Augmented hyper-CVAD based on dose-intensified vincristine, dexamethasone, and asparaginase in adult ALL salvage therapy. Clin Lymphoma Myeloma Leuk. 2011;11(1):54–59.

40. Deitcher OR, O'Brien S, Deitcher SR, et al. Single-agent vincristine sulfate liposomes injection compared to historical single-agent therapy for adults with advanced, relapsed and/or refractory Ph- ALL [abstract]. Blood. 2011;118:Abstract 2592.

41. O'Brien S, Schiller G, Lister J, et al. High-dose vincristine sulfate liposome injection for advanced, relapsed, and refractory adult Ph-ALL. J Clin Oncol. 2013;31(6):676–683.

42. Topp MS, Gokbuget N, Zugmaier G, et al. Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL. Blood. 2012;120(26):5185–5187.

43. Topp MS, Kufer P, Gokbuget N, et al. Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy- refractory minimal residual disease in B-lineage ALL patients results in high response rate and prolonged leukemia-free survival. J Clin Oncol. 2011;29(18):2493–2498.

44. Topp MS, Goekbuget N, Stein AS, et al. Confirmatory open-label, single-arm, multicenter phase 2 study of the BiTE antibody blinatumomab in patients with relapsed/refractory B-precursor ALL [abstract]. J Clin Oncol. 2014;32:Abstract 7005.


Hematologic Cancer Drug Monographs

Leukemias, Lymphomas, And Other Hematologic Cancers

ADCETRIS ALKERAN ALKERAN FOR INJECTION
ARRANON ARZERRA BELEODAQ
BENDEKA BEXXAR BICNU
BLEOMYCIN BLINCYTO BOSULIF
BUSULFEX CAMPATH CERUBIDINE
CLADRIBINE CLOLAR CYCLOPHOSPHAMIDE
CYTARABINE CYTOXAN INJECTION DACOGEN
DARZALEX DEPOCYT DOXIL
DOXORUBICIN HCL DOXORUBICIN HCL SOLUTION DTIC-DOME
EMPLICITI ERWINAZE EVOMELA
FARYDAK FLUDARA FOLOTYN
GAZYVA GLEEVEC GLEOSTINE
HYDREA ICLUSIG IDAMYCIN
IDAMYCIN PFS IMBRUVICA INTRON A
INTRON A SOLN ISTODAX JAKAFI
KEYTRUDA KYPROLIS LEUKERAN
MARQIBO MATULANE METHOTREXATE FOR INJECTION
METHOTREXATE INJECTION MITOXANTRONE HCL MUSTARGEN
MYLERAN NINLARO ONCASPAR
ONTAK OPDIVO PAMIDRONATE DISODIUM INJECTION
PENTOSTATIN POMALYST PURINETHOL
PURIXAN REVLIMID RITUXAN
SPRYCEL SYNRIBO TABLOID
TARGRETIN TARGRETIN GEL TASIGNA
THALOMID TREANDA TREXALL
TRISENOX UVADEX VALCHLOR
VELCADE VENCLEXTA VESANOID
VIDAZA VINBLASTINE FOR INJECTION VINBLASTINE INJECTION
VINCASAR PFS VUMON ZEVALIN
ZOLINZA ZOMETA ZYDELIG

Data provided by the Monthly Prescribing Reference (MPR) Hematology/Oncology Edition.

Related Resources

You must be a registered member of Cancer Therapy Advisor to post a comment.

Regimen and Drug Listings

GET FULL LISTINGS OF TREATMENT Regimens and Drug INFORMATION

Bone Cancer Regimens Drugs
Brain Cancer Regimens Drugs
Breast Cancer Regimens Drugs
Endocrine Cancer Regimens Drugs
Gastrointestinal Cancer Regimens Drugs
Gynecologic Cancer Regimens Drugs
Head and Neck Cancer Regimens Drugs
Hematologic Cancer Regimens Drugs
Lung Cancer Regimens Drugs
Other Cancers Regimens
Prostate Cancer Regimens Drugs
Rare Cancers Regimens
Renal Cell Carcinoma Regimens Drugs
Skin Cancer Regimens Drugs
Urologic Cancers Regimens Drugs

Sign Up for Free e-newsletters