Acute Lymphoblastic Leukemia
Epidemiology and Etiology
Acute lymphoblastic leukemia (ALL) is the most common childhood leukemia with an estimated 6150 new cases in the US in 2020.1 The median age at presentation is 35 years with a bimodal distribution including a peak at 4-5 years and a second gradual peak after the age of 50.
Pathology
ALL can arise from B- or T-lymphocyte progenitors, with B cell ALL comprising more than two-thirds of cases. The WHO classifies ALL into three categories: B cell with recurrent genetic abnormalities (see Table 22-6), T cell, and B cell NOS.
Clinical Presentation
Symptoms may include fatigue, fever, and bleeding. Leukostasis is uncommon, even with high white blood cell counts. Lymphadenopathy and splenomegaly are present in approximately 20% of cases. CNS may be involved at presentation, manifesting as headache or cranial nerve palsies.
Diagnostic Testing
Basic workup is similar to that required in AML. Immunophenotyping by flow cytometry is often necessary to distinguish ALL from AML. CSF sampling for CNS involvement should be assessed.
TREATMENT
Several complex regimens such as the Berlin-Frankfurt-Munster; hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD); Cancer and Leukemia Group B 8811; and the German Multicenter ALL regimen have been used for the treatment of ALL. Treatment is subdivided into induction, consolidation, and maintenance phases, usually administered over a course of 2-3 years. Due to the high risk of CNS relapse, prophylactic intrathecal therapy is administered during the induction and consolidation phases. Adolescents and young adults (AYA) may benefit from pediatric-inspired treatment regimens similar to those used for the treatment of pediatric ALL, which often contain more CNS prophylaxis and asparaginase.35
Additional therapies may include the following:
• Rituximab added to the regimen in those with CD20+ ALL.
• A BCR-ABLl TKI (imatinib, dasatinib, etc.) to the regimen for those with BCR-ABLl+ ALL.
• Blinatumomab (CD3 ? CD19 BiTE) for patients in an MRD positive remission or those with CD19 positive relapsed/refractory disease.
• Inotuzumab ozogamicin (CD22 ADC) for CD22 positive relapsed/refractory disease.
• Tisagenlecleucel (CD19 CAR-T therapy) for patients up to age 25 years with B-cell precursor ALL that is refractory or in second or later relapse.
• Allogeneic stem cell transplantation may be considered in relapsed ALL and for those with high-risk disease. High-risk genetic features include hypodiploidy, t(9;22) BCR-ABLl, KMT2A (MLL) rearrangement, and BCR-ABLl-like genotype based on gene expression profiling. Age #8804;1 year or #8805;10 years old and WBC #8805;50 ? 109#8725;L are also poor prognostic factors.35