Elsevier

Mayo Clinic Proceedings

Volume 91, Issue 11, November 2016, Pages 1645-1666
Mayo Clinic Proceedings

Symposium on neoplastic hematology and medical oncology
Adult Acute Lymphoblastic Leukemia

https://doi.org/10.1016/j.mayocp.2016.09.010Get rights and content

Abstract

Conventional cytotoxic chemotherapy used to treat acute lymphoblastic leukemia (ALL) results in high cure rates in pediatric patients but is suboptimal in the treatment of adult patients. The 5-year overall survival is approximately 90% in children and 30% to 40% in adults and elderly patients. Adults with ALL tend to have higher risk factors at diagnosis, more comorbidities, and increasing age that often requires dose reductions. Major advancements have been made in redefining the pathologic classification of ALL, identifying new cytogenetic-molecular abnormalities, and developing novel targeted agents in order to improve survival. The addition of new monoclonal antibodies and tyrosine kinase inhibitors to conventional chemotherapy in the frontline setting has resulted in increased rates of complete remission and overall survival. These new developments are changing the treatment of adult ALL from a “one therapy fits all” approach to individualized treatment based on patient’s cytogenetic and molecular profile.

Section snippets

Epidemiology and Etiology

ALL has a bimodal distribution with the first peak occurring in individuals around 5 years of age and the second peak at around 50 years of age. It is mainly considered a pediatric leukemia with 80% of cases occurring in children and 20% occurring in adults.4, 5, 6, 7 The median age at diagnosis is 14 years, and approximately 60% of patients are diagnosed at younger than 20 years of age, 25% at around 45 years of age, and 11% at around 65 years of age.8 ALL is relatively uncommon during late

Clinical Presentation and Laboratory Abnormalities

The clinical presentation of ALL is nonspecific, and thus, patients can present with an array of ailments such as “B symptoms” (ie, fever, unexpected weight loss, night sweats), infection, easy bruising/bleeding, dyspnea, and fatigue due to low blood cell counts.8 Patients may exhibit petechiae, pallor, and ecchymosis on physical examination, but children may present with only joint pain.19

Approximately 20% of patients will have leukemic infiltration in the spleen and/or liver leading to

Diagnostic Evaluation

The diagnosis of ALL requires the presence of 20% or more lymphoblasts in the bone marrow.8 Further assessment by flow cytometry, morphological studies, immunophenotyping, and cytogenetic testing is important. Historically, the diagnosis of ALL was based on the French-American-British morphological criteria that described 3 subtypes of ALL (L1, L2, and L3) based on cell size, cytoplasm, nucleoli vacuolation, and basophilia.21 Because of this system’s lack of prognostic value, a classification

Treatment

The structure of adult ALL treatment is similar to that for pediatric ALL; the chemotherapy consists of induction, consolidation, and long-term maintenance therapy along with CNS prophylaxis interwoven during the first year of treatment. The purpose of this multidrug treatment approach is to eradicate the disease and restore normal hematopoiesis, provide prophylaxis to “sanctuary sites,” and prevent an upsurge of resistant clones that may lead to relapse.19

Treatment Approach

A bone marrow examination must be performed to confirm the diagnosis of ALL. In addition, a complete immunophenotypic, cytogenetic, and molecular panel should be conducted because it is crucial for risk stratification and to determine targetable mutations. This will help determine the most optimal treatment regimen.

Conclusion

Major progress has been made in revising prognostic factors, understanding the impact of MRD, and the development of novel targeted therapies for adult patients with ALL. The addition of rituximab to conventional chemotherapy in the treatment of B-cell ALL has substantially improved survival. The incorporation of TKIs in the treatment of Ph-positive ALL has drastically improved outcomes, but their role after transplant is still to be determined. Blinatumomab and inotuzumab have marked activity

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    Potential Competing Interests: Drs Elias J Jabbour and Hagop M Kantarjian have research grants from Pfizer, Amgen, Ariel, and Bristol-Myers Squibb.

    The Symposium on Neoplastic Hematology and Medical Oncology will continue in an upcoming issue.

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