Summary
Definition
History and exam
Key diagnostic factors
- lymphadenopathy
- hepatosplenomegaly
- pallor, ecchymoses, or petechiae
- constitutional symptoms (fevers, night sweats, weight loss)
- recurrent infections
- fatigue, palpitations, light-headedness, and dyspnea
- easy bruising, epistaxis, excessive bleeding
Other diagnostic factors
- mental status changes, focal neurologic signs/deficits, headache, papilledema, nuchal rigidity, and meningismus
- bone pain
- painless unilateral testicular enlargement
- mediastinal mass
- abdominal mass
- pleural/pericardial effusion
- skin infiltrations (skin nodules)
- eosinophilia
- bone marrow necrosis
- joint pain/swelling
Risk factors
- children <5 years of age
- genetic disorders
- having an identical (monochorionic) twin with ALL
- family history of ALL
- viral infections
- environmental factors
- history of malignancy
- treatment with chemotherapy
- male sex
- Hispanic populations
- folate metabolism polymorphisms
- poor maternal diet
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 (cytomorphology)
- immunophenotyping
- cytogenetic analysis (karyotyping; fluorescence in situ hybridization [FISH])
- molecular testing (reverse transcriptase polymerase chain reaction [RT-PCR])
- multigene panel testing (MGPT)
- blood group and antibody screening
- viral antibody test
- counseling and fertility preservation
Tests to consider
- chromosomal microarray analysis (CMA)
- lumbar puncture
- chest x-ray
- pleural/pericardial tap
- CT/MRI of head
- CT neck, thorax, abdomen, pelvis
- PET/CT scan (whole-body)
- 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
Treatment algorithm
adolescents and adults: newly diagnosed Ph+ B-ALL
adolescents and adults: newly diagnosed Ph-negative B-ALL
adolescents and adults: newly diagnosed T-ALL
complete remission
relapsed or refractory disease
Contributors
Authors
Ryan D. Cassaday, MD
Professor
Division of Hematology and Oncology, University of Washington School of Medicine
Clinical Research Division, Fred Hutchinson Cancer Center
Seattle, WA
Disclosures
RDC has received research funding from Amgen, Jazz Pharmaceuticals, Incyte, Kite/Gilead, Merck, Pfizer, Servier, Takeda, and Vanda Pharmaceuticals; honoraria/consulting from Amgen, AstraZeneca, Autolus, Clear Pharmaceuticals, Jazz, Kite/Gilead, Merck, Pfizer, Sana Biotechnologies, Servier, and Takeda; served on a board/review committee for Autolus and PeproMene Bio; and his spouse has been employed by and owned stock (sold 3 years ago) in Seagen.
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
MA
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
UK
Disclosures
SP declares that he has no competing interests.
Peer reviewer acknowledgements
BMJ Best Practice topics are updated on a rolling basis in line with developments in evidence and guidance. The peer reviewers listed here have reviewed the content at least once during the history of the topic.
Disclosures
Peer reviewer affiliations and disclosures pertain to the time of the review.
References
Key articles
National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: acute lymphoblastic leukemia [internet publication].Full text
Gökbuget N, Boissel N, Chiaretti S, et al. Diagnosis, prognostic factors, and assessment of ALL in adults: 2024 ELN recommendations from a European expert panel. Blood. 2024 May 9;143(19):1891-902.Full text Abstract
DuVall AS, McNeer J, Cheung MC, et al. ASH 2026 guidelines for frontline management of acute lymphoblastic leukemia in adolescents and young adults. Blood Adv. 2026 Feb 11:bloodadvances.2021006469.Full text Abstract
Gökbuget N, Boissel N, Chiaretti S, et al. Management of ALL in adults: 2024 ELN recommendations from a European expert panel. Blood. 2024 May 9;143(19):1903-30.Full text Abstract
O'Dwyer KM, Winestone LE, Cheung MC, et al. ASH 2026 guidelines for management of relapsed/refractory disease in adolescents and young adults with ALL. Blood Adv. 11 Feb 2026 [Epub ahead of print]. Abstract
Reference articles
A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.
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