Acute lymphoblastic leukemia

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Last reviewed: 14 Apr 2025

Last updated: 26 Nov 2024

Acute lymphoblastic leukemia (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 hematopoietic 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 exam 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 multiagent 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.

Definition

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]

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][5] Mixed-phenotype (B-cell and T-cell) ALL may occur, but is exceptionally rare.

History and exam

Key diagnostic factors

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

Full details

Other diagnostic factors

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

Full details

Risk factors

children less than 5 years of age
genetic factors
family history of ALL
viruses
environmental factors
history of malignancy
treatment with chemotherapy
male sex
Hispanic populations
folate metabolism polymorphisms
poor maternal diet

Full details

Diagnostic tests

1st tests to order

CBC with differential
peripheral blood smear
serum electrolytes
serum uric acid
serum lactate dehydrogenase (LDH)
renal function tests
liver function tests
coagulation profile
bone marrow evaluation
immunophenotyping
cytogenetic analysis (karyotyping and fluorescence in situ hybridization [FISH])
molecular studies (reverse transcriptase polymerase chain reaction [RT-PCR])
next-generation sequencing (NGS) assay
blood group and antibody screening
antibody testing for infection

Full details

Tests to consider

chest radiograph
lumbar puncture
pleural tap
CT/MRI brain
CT chest
scrotal ultrasound
baseline measurable residual disease (MRD) testing
thiopurine methyltransferase (TPMT) phenotyping
nudix hydrolase 15 (NUDT15) phenotyping
HLA-typing
echocardiogram or multigated acquisition (MUGA) scan

Full details

Treatment algorithm

ACUTE

adolescents and adults: newly diagnosed Ph+ B-ALL

adolescents and adults: newly diagnosed Ph-negative B-ALL or T-ALL

ONGOING

complete remission: standard-risk Ph-negative B-ALL or T-ALL

complete remission: Ph+ B-ALL and high-risk Ph-negative B-ALL or T-ALL

relapsed or refractory disease

Contributors

Authors

Ryan D. Cassaday, MD

Associate Professor

Division of Hematology and Oncology, University of Washington School of Medicine

Clinical Research Division, Fred Hutchinson Cancer Center

Seattle

Disclosures

RDC has received research funding from Amgen, Jazz Pharmaceuticals, Incyte, Kite/Gilead, Merck, Pfizer, Servier, and Vanda Pharmaceuticals; honoraria/consulting from Amgen, Jazz, Kite/Gilead, and Pfizer; serves on a board/advisory committee for Autolus and PeproMene Bio; and his spouse has been employed by and owned stock in Seagen. RDC is an author of several articles cited in the topic.

Acknowledgements

Dr Ryan D. Cassaday would like to gratefully acknowledge Dr Melissa Ooi, Dr Michelle Poon, Dr Esther Chan, Dr Chin Hin Ng, Dr Arati V. Rao, Dr Matthew Smith, Dr Samer Bleibel, and Dr Robert Leonard, previous contributors to this topic.

Disclosures

MO, MP, EC, CHN, AVR, MS, SB, and RL declare that they have no competing interests.

Peer reviewers

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.

Shankaranarayana 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.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

Alaggio R, Amador C, Anagnostopoulos I, et al. The 5th edition of the World Health Organization classification of haematolymphoid tumours: lymphoid neoplasms. Leukemia. 2022 Jul;36(7):1720-48.Full text Abstract

Arber DA, Orazi A, Hasserjian RP, et al. International consensus classification of myeloid neoplasms and acute leukemias: integrating morphologic, clinical, and genomic data. Blood. 2022 Sep 15;140(11):1200-8.Full text Abstract

National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: acute lymphoblastic leukemia [internet publication].Full text

Hoelzer D, Bassan R, Dombret H, et al. Acute lymphoblastic leukaemia in adult patients: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016 Sep;27(suppl 5):v69-82.Full text Abstract

National Comprehensive Cancer Network. NCCN practice guidelines in oncology: pediatric acute lymphoblastic leukemia [internet publication].Full text

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials
- Acute myeloid leukemias (AML)
- Lymphoblastic lymphoma (LBL)
- Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase fusion genes (MLNE)
More Differentials
Guidelines
- Management of ALL in adults: 2023 ELN recommendations from a European expert panel
- ESMO clinical practice guideline interim update on the use of targeted therapy in acute lymphoblastic leukaemia
More Guidelines
Patient information
Leukemia (acute lymphocytic)
More Patient information
Videos
Diagnostic lumbar puncture in adults: animated demonstration
More videos
Log in or subscribe to access all of BMJ Best Practice

Use of this content is subject to our disclaimer

Acute lymphoblastic leukemia

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic tests

1st tests to order

Tests to consider

Treatment algorithm

adolescents and adults: newly diagnosed Ph+ B-ALL

adolescents and adults: newly diagnosed Ph-negative B-ALL or T-ALL

complete remission: standard-risk Ph-negative B-ALL or T-ALL

complete remission: Ph+ B-ALL and high-risk Ph-negative B-ALL or T-ALL

relapsed or refractory disease

Contributors

Authors

Ryan D. Cassaday, MD

Disclosures

Acknowledgements

Disclosures

Peer reviewers

Olga Kozyreva, MD

Disclosures

Shankaranarayana Paneesha, MD, MRCP, FRCPath

Disclosures

References

Key articles

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials

Guidelines

Patient information

Videos

Log in or subscribe to access all of BMJ Best Practice

Log in or subscribe to access all of BMJ Best Practice

Log in to access all of BMJ Best Practice