History

Children with acute lymphoblastic leukemia (ALL) often present with signs and symptoms that reflect bone marrow infiltration and/or extramedullary disease. When leukemic blasts replace the bone marrow, patients present with signs of bone marrow failure, including anemia, thrombocytopenia, and neutropenia. In patients with B-precursor ALL, bone pain, arthritis, and limping may be presenting symptoms and in 5% of patients are the only symptoms, leading to delays in diagnosis.^[11]Fevers, whether low- or high-grade, are common at presentation, but despite neutropenia, sepsis is rarely seen. Other common clinical manifestations include fatigue, pallor, petechiae, and bleeding. In addition, leukemic spread may manifest as lymphadenopathy and hepatosplenomegaly.

Mature-B ALL may be associated with extramedullary masses in the abdomen or head and neck and central nervous system (CNS) involvement.

In patients with T-lineage ALL, respiratory distress and stridor secondary to a mediastinal mass may be a presenting symptom.

Symptoms of CNS involvement, such as headache, vomiting, lethargy, and nuchal rigidity are rarely noted at initial diagnosis but are more common in T-lineage and mature B cell ALL.^[1]Cranial nerve deficits are an important sign of CNS involvement. Testicular involvement at diagnosis is also rare; if present, it appears as unilateral painless testicular enlargement.

Physical Examination

Physical findings in children with acute lymphoblastic leukemia (ALL) reflect bone marrow infiltration, as well as extramedullary disease. Patients commonly present with pallor caused by anemia and petechiae and bruising secondary to thrombocytopenia. Leukemic infiltration may manifest as lymphadenopathy and hepatosplenomegaly. If it involves the central nervous system (CNS), papilledema, nuchal rigidity, and cranial nerve palsy is sometimes found. Testicular examination in males is critical; leukemic infiltration usually manifests as unilateral painless testicular enlargement.

The presence of stridor is cause for concern and may signify a mediastinal mass, found in half of patients with T-lineage ALL, with a risk of imminent respiratory arrest. Attempts to lay the patient flat or perform intubation should be avoided, and the patient should commence steroid therapy and be transferred to the pediatric intensive care unit for close observation while workup is underway.

Differential Diagnoses

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Media Gallery

Bone marrow aspirate from a child with B-precursor acute lymphoblastic leukemia. The marrow is replaced primarily with small, immature lymphoblasts that show open chromatin, scant cytoplasm, and a high nuclear-cytoplasmic ratio.
Bone marrow aspirate from a child with T-cell acute lymphoblastic leukemia. The marrow is replaced with lymphoblasts of various sizes. No myeloid or erythroid precursors are seen. Megakaryocytes are absent.
Bone marrow aspirate from a child with B-cell acute lymphoblastic leukemia. The lymphoblasts are large and have basophilic cytoplasm with prominent vacuoles.

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Author

Vikramjit S Kanwar, MBBS, MBA, MRCP(UK) Professor Emeritus of Pediatrics, Albany Medical College; Chief of Pediatric Oncology, Homi Bhabha Cancer Hospital, Varanasi, India

Vikramjit S Kanwar, MBBS, MBA, MRCP(UK) is a member of the following medical societies: Children's Oncology Group, Indian Academy of Pediatrics, International Society of Pediatric Oncology

Disclosure: Nothing to disclose.

Coauthor(s)

Noriko Satake, MD Assistant Professor, Department of Pediatric Hematology/Oncology, University of California, Davis, School of Medicine, UC Davis Medical Center

Disclosure: Nothing to disclose.

Janet M Yoon, MD Assistant Clinical Professor, Department of Pediatric Hematology/Oncology, University of California, Davis, School of Medicine, UC Davis Medical Center

Janet M Yoon, MD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology, Children's Oncology Group

Disclosure: Nothing to disclose.

Chief Editor

Jennifer Reikes Willert, MD Associate Clinical Professor, Department of Pediatrics, Division of Pediatric Hematology/Oncology, Section of Stem Cell Transplantation, Stanford University Medical Center, Lucile Packard Children's Hospital

Jennifer Reikes Willert, MD is a member of the following medical societies: American Academy of Pediatrics, American Society for Blood and Marrow Transplantation, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group

Disclosure: Nothing to disclose.

Acknowledgements

Timothy P Cripe, MD, PhD Professor of Pediatrics, Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center; Clinical Director, Musculoskeletal Tumor Program, Co-Medical Director, Office for Clinical and Translational Research, Cincinnati Children's Hospital Medical Center; Director of Pilot and Collaborative Clinical and Translational Studies Core, Center for Clinical and Translational Science and Training, University of Cincinnati College of Medicine

Timothy P Cripe, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Stephan A Grupp, MD, PhD Director, Stem Cell Biology Program, Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia; Associate Professor of Pediatrics, University of Pennsylvania School of Medicine

Stephan A Grupp, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.