Acute lymphocytic leukemia

Last reviewed: September 2018

Last updated: July 2018

Summary

Enlarged lymph nodes are frequently the initial cause for seeking medical attention by the patient. Over 90% of patients have clinically evident hematologic abnormalities at the time of initial diagnosis.

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.

Definitive diagnosis requires a bone marrow aspiration and trephine biopsy. Presence of 20% or more lymphoblasts in the bone marrow confirms the diagnosis of acute lymphocytic leukemia (ALL). Initial peripheral blood smear may show leukemic lymphoblasts.

Treatment uses multiagent dose-intense chemotherapy regimens in induction, consolidation, and maintenance phases. Early 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 management methods, less than 30% of adults with ALL can be cured. Long-term adverse effects of treatment include heart failure, sterility, secondary malignancies, and neurotoxicity.

Definition

Acute lymphocytic leukemia (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, characterized by early lymphoid precursors replacing the normal hematopoietic cells of the bone marrow and further infiltrating various body organs. [1] [2] [3]

History and exam

Key diagnostic factors

lymphadenopathy
hepatosplenomegaly
pallor, ecchymoses, or petechiae
fever
fatigue, dizziness, palpitations, and dyspnea
epistaxis, menorrhagia

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Other diagnostic factors

papilledema, nuchal rigidity, and meningismus
focal neurologic signs
painless unilateral testicular enlargement
renal enlargement
bony pain
abdominal pain
mediastinal or abdominal mass
pleural effusion
skin infiltrations

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Risk factors

children less than 6 years of age
age in mid to late 30s
age in mid 80s
genetic factors
family history of acute lymphocytic leukemia (ALL)
viruses
environmental factors
history of malignancy
treatment with chemotherapy
male sex
white population

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Diagnostic investigations

1st investigations to order

complete blood count (CBC) with differential
serum electrolytes
peripheral blood smear
renal function
liver function
lactic dehydrogenase
coagulation profile
bone marrow aspiration and trephine biopsy
immunophenotyping (on bone marrow, or peripheral blood if cell count is raised)
thiopurine methyltransferase (TPMT) phenotype
cytogenetics
molecular studies

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Investigations to consider

HLA-typing
chest x-ray
lumbar puncture (LP)
pleural tap
CT/MRI brain
CT
minimal residual disease molecular samples

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Treatment algorithm

ACUTE

newly diagnosed: no central nervous system (CNS) disease

newly diagnosed: central nervous system (CNS) disease

ONGOING

complete remission

relapse, refractory, or residual disease

Contributors

Authors VIEW ALL 

Melissa Ooi, MB BCh, BAO, MRCP(I), FRCPath, PhD

Consultant

Department of Haematology-Oncology

National University Cancer Institute

Singapore

Disclosures

MO declares that she has no competing interests.

Michelle Poon, MBBS, MRCP, FRCPath

Senior Consultant

Department of Haematology-Oncology

National University Cancer Institute

Singapore

Disclosures

None declared.

Esther Chan, MD

Consultant

Department of Haematology-Oncology

National University Cancer Institute

Singapore

Disclosures

EC declares that she has no competing interests.

Chin Hin Ng, MD, MRCP, FRCPath

Consultant

Department of Haematology-Oncology

National University Cancer Institute

Singapore

Disclosures

CHN declares that he has no competing interests.

Acknowledgements

Dr Melissa Ooi, Dr Michelle Poon, Dr Esther Chan, and Dr Chin Hin Ng would like to gratefully acknowledge Dr Arati V. Rao, Dr Matthew Smith, Dr Samer Bleibel, and Dr Robert Leonard, previous contributors to this monograph. AVR, MS, SB, and RL declare that they have no competing interests.

Peer reviewers VIEW ALL 

Olga Kozyreva, MD

Staff Physician

Department of Hematology and Oncology

New England Medical Center

Tufts University

Boston

Disclosures

OK declares that she has no competing interests.

Shankaranarayanan Paneesha, MD, MRCP, FRCPath

Consultant Haematologist

Department of Haematology and Stem Cell Transplantation

Heartlands Hospital

Birmingham

Disclosures

SP declares that he has no competing interests.

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Acute lymphocytic leukemia

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic investigations

1st investigations to order

Investigations to consider

Treatment algorithm

newly diagnosed: no central nervous system (CNS) disease

newly diagnosed: central nervous system (CNS) disease

complete remission

relapse, refractory, or residual disease

Contributors

Authors VIEW ALL 

Melissa Ooi, MB BCh, BAO, MRCP(I), FRCPath, PhD

Disclosures

Michelle Poon, MBBS, MRCP, FRCPath

Disclosures

Esther Chan, MD

Disclosures

Chin Hin Ng, MD, MRCP, FRCPath

Disclosures

Acknowledgements

Peer reviewers VIEW ALL 

Olga Kozyreva, MD

Disclosures

Shankaranarayanan Paneesha, MD, MRCP, FRCPath

Disclosures

Differentials

Guidelines

Procedural videos

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