Acute Lymphoblastic Leukemia: Drug Therapy

Therapeutic targets

  • Destruction of the majority of leukemia cells
  • Achievement of remission (disappearance of disease symptoms; percentage of leukemia cells < 5%, return to normal hematopoiesis), possibly also partial remission or full remission (in blood and bone marrow are no longer detectable leukemia cells).

Therapy recommendations

  • Polychemotherapy with intrathecal (“into the cerebrospinal fluid (CSF) space” (nerve fluid) chemotherapy, plus radiotherapy (radiatio) of the head if necessary (multiple cycles of therapy, each lasting several weeks) [total duration up to 2.5 years]:
    • Induction therapy, consisting of a preliminary phase that serves to initiate treatment (induction phase I): approximately one week of chemotherapy with one to two drugs; this preliminary phase is followed by the actual induction therapy (induction phase II) (including the preliminary phase, this phase lasts approximately five to eight weeks); remission is achieved in approximately 98% of children and adolescents with ALL Caveat (Warning)! In the induction phase the most dangerous infections are seen under glucocorticoid therapy. Fever may be absent! In case of doubt, quickly antibiosis (antibiotic therapy).
    • Consolidation or intensification therapy (chemotherapy two to four months) to destroy further leukemia cells and maintain remission; in addition, CNS therapy (intrathecal chemotherapy with methotrexate, MTX); if necessary, also radiotherapy (Radiatio) of the head (CNS Radiatio: 24 Gy; children: 12 Gy, depending on age up to 18 Gy), if there is evidence of infestation of the CNS.
    • Reinduction therapy (chemotherapy several weeks to months) serves to ensure the complete destruction of all leukemia cells.
    • Maintenance or continuous therapy (chemotherapy over a longer period; usually up to a total therapy duration of two years) serves to prevent a relapse (recurrence of the disease).
  • Recurrence of acute lymphoblastic leukemia: high-dose chemotherapy, possibly total body irradiation for bone marrow destruction (disturbance of the entire bone marrow) followed by stem cell transplantation.
  • See also under “Further therapy”.

Active substances

Cytostatic agents

The following agents are used in the chemotherapy of ALL:

Depending on the exact course, initial leukocyte count (white blood cell count) and age of the patient, therapy regimens differ. No information on dosages is given here, because there are often changes in the respective regimens during chemotherapy. Other agents

New therapy regimens include:

    • Tyrosine kinase inhibitors (TKi).
      • Desatinib for induction plus blinatumomab for consolidation achieved remarkable success in adults with Philadelphia chromosome-positive ALL, with 95% of patients alive and 88% disease-free at 18 months.
      • Imatinib
      • Ponatinib, a third-generation BCR-ABL tyrosine kinase inhibitor (TKi). This appears to be more effective than other TKi and also targets the T315I mutation.
    • Rituximab (anti-CD20 antibody).
    • Blinatumomab, a bispecific antibody that simultaneously targets the CD3 receptor of T cells and the surface protein CD19 of B cells

Further notes

  • Childhood patients with precursor B-cell ALL (5% of cases) – without unfavorable genetic features – can often still be placed in long-term remission after inadequate induction therapy with re-chemotherapy.
  • Patients with acute lymphoblastic leukemia (ALL) often have minimal residual disease (MRD) after successful initial therapy. According to a study, this can be successfully treated by immunotherapy with blinatumomab: In 78 percent of the 113 patients, the minimal residual disease disappeared completely. In 98 percent of cases, this response was achieved in the first cycle.Blinatumomab has been approved since 2019 as monotherapy in adults with Philadelphia chromosome-negative, CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease (MRD) of at least 0.1%.
  • For patients with T-cell ALL (20% of cases), allogeneic stem cell transplantation is required after induction failure.
  • CAR T-cell therapy against CD 19: Long-term remissions were achieved in 7 of 20 children with B-ALL relapses. For this purpose, they received the usual lymphocyte-depleting chemotherapy as a preparation, followed by an infusion with CAR-T cells against CD 19. After about 18 months, 17 children were still in remission.CAR-T cell therapy: for this purpose, the patient’s own T cells are equipped ex vivo, i.e. outside the body, with chimeric antigen receptors (“chimeric antigen receptor”, CAR) at the genetic level. The T cells modified by CAR gene transfer are expanded and reimplanted into the patient after conditioning. By means of the antigen receptor, the CAR T cells can recognize malignant (malignant) cells (without the presentation by B cells). They bind to the surface antigen present on the malignant cell and destroy it.Side effect: cytokine release syndrome (CRS) and neurological side effects.