Acute Lymphoblastic Leukemia Treatment Regimens , Oncology and Hematology

1. ALL
Hamzeh Nusairat PharmD, JUST university
TREATMENT REGIMENS

2. Induction
 vincristine
 glucocorticoid (dexamethasone or prednisone)
 Pegaspargase
+++
 Daunorubicin ((four-drug induction) for high risk)

3. CNS Prophylaxis
 methotrexate + cytarabine + hydrocortisone (Intrathecally)
 methotrexate (Intrathecally)
 cytarabine (Intrathecally)
 dexamethasone
 cranial irradiation

4. CNS T-cell ALL Prophylaxis
 high-dose methotrexate.

5. Consolidation Therapy
 Regimens
1) either non–cross-resistant drugs that are different from the induction.
2)or more dose-intensive use of the same drugs.
 Standard 4 weeks  vincristine, mercaptopurine, and intrathecal methotrexate.
 For high risk [intensified consolidation]  vincristine, mercaptopurine, and
intrathecal methotrexate, pegaspargase, cyclophosphamide, and low-dose
cytarabine

6. Consolidation T-cell ALL
 Nelarabine ++
 vincristine, mercaptopurine, and intrathecal methotrexate, pegaspargase,
cyclophosphamide, and low-dose cytarabine

7. Delayed intensification / Interim
maintenance
 Delayed intensification:
 cyclophosphamide,
 methotrexate,
 limited amounts of doxorubicin.
 Interim maintenance:
 dexamethasone,
 vincristine,
 Weekly methotrexate,
 mercaptopurine,
 Intrathecal methotrexate.

8. Maintenance Therapy
 daily mercaptopurine (in evening)
 weekly methotrexate for 12-week
 monthly “pulses” of vincristine and a steroid
FOR 3 years

9. Philadelphia Chromosome
 four-drug induction regimen + imatinib mesylate (with all regimens)
 Ponatinib  which is effective in imatinib resistant leukemia [ T315I mutations]

10. Down Syndrome ALL
 Same as normal BUT anthracycline Exposure Is limited
 MTX + leucovorin rescue
 Leucovorin = folate

11. ALL in Adults
 Cancer and Leukemia Group B (CALGB) 8,811 (Larson regimen)
 Eastern Cooperative Oncology Group (ECOG) 2,993, or (Linker regimen)
 (hyperCVAD) = high-dose methotrexate
 cytarabine alternating
 fractionated cyclophosphamide
 vincristine, doxorubicin, and dexamethasone

12.  65 years of age orfor those with a poor performance status,
 imatinib +++
 concurrent chemotherapy with a tyrosine kinase inhibitor, either alone or
combined with corticosteroids
 first-line therapy.

13. Adult B-cell ALL
 hyperCVAD and rituximab

14.  Clofarabine  for 2nd relapse and later …..
 Nelarabine  for T Cell Relapse
 liposomal vincristine, moxetumomab pasudotox, inotuzumab ozogamicin, and bortezomib
 Blinatumomab [bi-specific T-cell engager (BiTE) ] relapsed ph(-) B-cell precursor ALL
By
 linking CD19 (B cell) and CD3 (T cell), blinatumomab enables a cascade of events
 resulting in lysis of CD19 cells.

15.  Chimeric antigen receptor (CAR) T-cell therapy  genetically
engineered T cells
 designed to express CARs directed against CD19, resulting in T cells
 targeting leukemic cells that express CD19.

16.  HSCT  the treatment of choice for early bone marrow relapse less than 36
months cr NOT FOR elderly patients
 nonmyeloablative transplant (NMT).  FOR elderly patients

17. References
 1. DeRemer D, & Higgins T (2020). Acute leukemias. DiPiro J.T., & Yee G.C., &
Posey L, & Haines S.T., & Nolin T.D., & Ellingrod V(Eds.), Pharmacotherapy: A
Pathophysiologic Approach, 11e. McGraw-
Hill. https://accesspharmacy.mhmedical.com/content.aspx?bookid=2577&section
id=237233312