What is the first-line treatment for Acute Lymphocytic Leukemia (ALL)?

From the Guidelines

The first-line treatment for acute lymphocytic leukemia (ALL) typically involves a multi-phase chemotherapy regimen, with the most recent guidelines recommending induction therapy using a combination of vincristine, a corticosteroid (dexamethasone), and an anthracycline (daunorubicin or doxorubicin), often with L-asparaginase and sometimes cyclophosphamide, as outlined in the 2025 NCCN guidelines 1. The treatment approach to ALL represents one of the most complex and intensive programs in cancer therapy, with dramatic improvements in outcomes over the past several decades, primarily among children, due to advances in the understanding of molecular genetics and pathogenesis of the disease, incorporation of minimal residual disease (MRD) testing, refinement of risk-adapted treatment algorithms, advent of new targeted agents, and use of allogeneic hematopoietic cell transplantation (HCT) 1. Some key points to consider in the treatment of ALL include:

• Induction regimens for adults with Ph-negative ALL are generally based on a backbone of vincristine, corticosteroids, and anthracyclines 1
• The use of dexamethasone versus prednisone as part of induction therapy in children with ALL has shown that dexamethasone significantly decreased the risk of isolated CNS relapse and improved EFS outcomes compared with prednisone 1
• Central nervous system prophylaxis is essential and includes intrathecal chemotherapy with methotrexate
• For Philadelphia chromosome-positive ALL, tyrosine kinase inhibitors like imatinib are added to the regimen
• Allogeneic stem cell transplantation is considered for high-risk patients
• Treatment is risk-stratified based on age, white blood cell count, cytogenetics, and early response to therapy, with the NCCN panel advocating for shared decision making and treatment decisions based on additional factors such as comorbid medical conditions, performance status, and end-organ function/reserve 1.

From the FDA Drug Label

Dasatinib tablets are indicated for the treatment of pediatric patients 1 year of age and older with ... newly diagnosed Ph+ ALL in combination with chemotherapy. The recommended dose should be administered orally once daily with or without food. For pediatric patients with Ph+ ALL, begin dasatinib therapy on or before day 15 of induction chemotherapy, when diagnosis is confirmed and continue for 2 years.

The first-line treatment for acute lymphocytic leukemia (ALL), specifically Ph+ ALL, in pediatric patients 1 year of age and older, is dasatinib in combination with chemotherapy.

• The recommended starting dose of dasatinib for pediatric patients with Ph+ ALL is based on body weight, as shown in Table 1 in the dasatinib label.
• Dasatinib should be started on or before day 15 of induction chemotherapy and continued for 2 years 2.

In adult acute lymphocytic leukemia, in contrast to childhood acute lymphocytic leukemia, daunorubicin hydrochloride during induction significantly increases the rate of complete remission, but not remission duration, compared to that obtained with vincristine, prednisone, and L-asparaginase alone The use of daunorubicin hydrochloride in combination with vincristine, prednisone, and L-asparaginase has produced complete remission rates of 83% in contrast to a 47% remission in patients not receiving daunorubicin hydrochloride.

For adult acute lymphocytic leukemia, the use of daunorubicin hydrochloride in combination with vincristine, prednisone, and L-asparaginase has been shown to increase the rate of complete remission 3.

• The combination of daunorubicin hydrochloride with vincristine, prednisone, and L-asparaginase produced a complete remission rate of 83%, compared to 47% without daunorubicin hydrochloride.

From the Research

First-Line Treatment for Acute Lymphocytic Leukemia

• The vincristine, doxorubicin, and dexamethasone regimen has been shown to be effective in achieving complete remission in adults with acute lymphocytic leukemia (ALL) 4.
• The addition of daunorubicin to the induction program has been found to increase the complete response rate in adults with ALL 5.
• Sequential induction chemotherapy with vincristine, daunorubicin, cyclophosphamide, and prednisone has also been shown to be effective in achieving complete remission in adults with ALL 6.
• The hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone regimen has been found to be effective in elderly patients with ALL, with a complete response rate of 84% 7.
• Adults with ALL and translocation (1;19) abnormality have been found to have a favorable outcome with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high-dose cytarabine chemotherapy 8.

Factors Affecting Treatment Outcome

• Older age, hypoalbuminemia, hyperbilirubinemia, L2 or L3 morphology, and myeloid markers on leukemic cells have been found to be associated with worse complete remission rates 4.
• Elevated leukocyte or absolute peripheral blast counts, Philadelphia chromosome-positive or B-cell ALL, L2 morphology, and more than one course to achieve complete remission have been found to be associated with worse remission durations 4.
• The presence of myeloid markers on leukemic cells has not been found to affect long-term prognosis 4.

Treatment Regimens

• The VAD regimen consists of vincristine, doxorubicin, and dexamethasone 4.
• The CVAD regimen consists of cyclophosphamide, vincristine, doxorubicin, and dexamethasone 4.
• The hyper-CVAD regimen consists of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high-dose cytarabine 7, 8.