Acute lymphoblastic leukaemia

Acute lymphoblastic leukaemia (ALL) is a malignant clonal disease that develops when a lymphoid progenitor cell becomes genetically altered and undergoes uncontrolled proliferation. Early lymphoid precursor cells replace the normal haematopoietic cells of the bone marrow and further infiltrate various body organs.

Most patients have signs and symptoms related to cytopenias (e.g., fatigue, easy bruising) at initial presentation and diagnosis. Enlarged lymph nodes can be an initial presenting cause.

Physical examination may reveal pallor, ecchymoses, lymphadenopathy, or hepatosplenomegaly. There may also be evidence of tissue infiltration such as bone pain, testicular enlargement, and cranial nerve palsies.

A definitive diagnosis of ALL requires cytomorphology assessment, immunophenotyping, molecular studies, and cytogenetic analysis of the bone marrow (or peripheral blood if there are sufficient numbers of circulating lymphoblasts).

Treatment uses multi-agent chemotherapy-based regimens in induction, consolidation, and maintenance phases. Allogeneic stem cell transplantation (SCT) is considered in selected patients. Salvage chemotherapy, immunotherapy, and SCT are options for relapsed, refractory, or residual disease.

Despite the aggressive treatment approach, only 40% to 60% of adults with ALL are cured. Long-term adverse effects of treatment include heart failure, sterility, secondary malignancies, and neurotoxicity.

ALL is a malignant clonal disease that develops when a lymphoid progenitor cell becomes genetically altered through somatic changes and undergoes uncontrolled proliferation. This progressive clonal expansion eventually leads to ALL, characterised by early lymphoid precursors replacing the normal haematopoietic cells of the bone marrow and further infiltrating various body organs.[1]Pui CH, Relling MV, Downing JR. Acute lymphoblastic leukemia. N Engl J Med. 2004 Apr 8;350(15):1535-48. http://www.ncbi.nlm.nih.gov/pubmed/15071128?tool=bestpractice.com [2]Hoelzer D, Gökbuget N, Ottmann O, et al. Acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program. 2002 Jan;(1):162-92. https://ashpublications.org/hematology/article/2002/1/162/18610/Acute-Lymphoblastic-Leukemia http://www.ncbi.nlm.nih.gov/pubmed/12446423?tool=bestpractice.com [3]Jabbour EJ, Faderl S, Kantarjian HM. Adult acute lymphoblastic leukemia. Mayo Clin Proc. 2005 Nov;80(11):1517-27. http://www.ncbi.nlm.nih.gov/pubmed/16295033?tool=bestpractice.com

B-ALL (arising from B lymphoid progenitors) accounts for approximately 75% of cases, with the remainder being predominantly T-ALL (arising from T lymphoid progenitors).[4]Bene MC, Castoldi G, Knapp W, et al. Proposals for the immunological classification of acute leukaemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia. 1995 Oct;9(10):1783-6. http://www.ncbi.nlm.nih.gov/pubmed/7564526?tool=bestpractice.com [5]Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J. 2017 Jun 30;7(6):e577. https://www.nature.com/articles/bcj201753 http://www.ncbi.nlm.nih.gov/pubmed/28665419?tool=bestpractice.com ​​ Mixed-phenotype (B-cell and T-cell) ALL may occur, but is exceptionally rare.