Acute Lymphoblastic Leukemia Clinical Presentation

  • Author: Karen Seiter, MD; Chief Editor: Emmanuel C Besa, MD  more...
 
Updated: Apr 22, 2016
 

History

Patients with acute lymphoblastic leukemia (ALL) present with either symptoms relating to direct infiltration of the marrow or other organs by leukemic cells, or symptoms relating to the decreased production of normal marrow elements.

Fever is one of the most common symptoms of ALL, and patients with ALL often have fever without any other evidence of infection. However, in these patients, one must assume that all fevers are from infections until proved otherwise, because a failure to treat infections promptly and aggressively can be fatal. Infections are still the most common cause of death in patients undergoing treatment for ALL.

Patients with ALL often have decreased neutrophil counts, regardless of whether their total white blood cell (WBC) count is low, normal, or elevated. As a result, these individuals are at an increased risk of infection. The prevalence and severity of infections are inversely correlated with the absolute neutrophil count (ANC), which is defined as the number of mature neutrophils plus bands per unit of volume. Infections are common when the absolute neutrophil count is less than 500/µL, and they are especially severe when it is less than 100/µL. See the Absolute Neutrophil Count calculator.

Symptoms of anemia are common and include fatigue, dizziness, palpitations, and dyspnea upon even mild exertion. Other patients present with signs of bleeding. Bleeding can be the result of thrombocytopenia due to marrow replacement. Additionally, approximately 10% of patients with ALL have disseminated intravascular coagulation (DIC) at the time of diagnosis. These patients may present with hemorrhagic or thrombotic complications.

Some patients present with palpable lymphadenopathy. Others, particularly those with T-cell ALL, present with symptoms related to a large mediastinal mass, such as shortness of breath.

Infiltration of the marrow by massive numbers of leukemic cells frequently manifests as bone pain. This pain can be severe and is often atypical in distribution.

About 10-20% of ALL patients may present with left upper quadrant fullness and early satiety due to splenomegaly.

Although patients may present with symptoms of leukostasis (eg, respiratory distress, altered mental status) because of the presence of large numbers of lymphoblasts in the peripheral circulation, leukostasis is much less common in people with ALL than those with acute myelogenous leukemia (AML), and it occurs only in patients with the highest WBC counts (ie, several hundred thousand per μL).

Patients with a high tumor burden, particularly those with severe hyperuricemia, can present in renal failure.

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Physical Examination

Patients with acute lymphoblastic leukemia (ALL) commonly have physical signs of anemia, including pallor and a cardiac flow murmur. Fever and other signs of infection, including lung findings of pneumonia, can also occur. Fever should be interpreted as evidence of infection, even in the absence of other signs.

Patients with thrombocytopenia usually demonstrate petechiae, particularly on the lower extremities. A large number of ecchymoses is usually an indicator of a coexistent coagulation disorder such as disseminated intravascular coagulation (DIC).

Signs relating to organ infiltration with leukemic cells and, to a lesser degree, lymphadenopathy may be present.

Occasionally, patients have rashes that result from infiltration of the skin with leukemic cells.

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Contributor Information and Disclosures
Author

Karen Seiter, MD Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology

Disclosure: Received honoraria from Novartis for speaking and teaching; Received consulting fee from Novartis for speaking and teaching; Received honoraria from Celgene for speaking and teaching.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Ronald A Sacher, MB, BCh, FRCPC, DTM&H Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MB, BCh, FRCPC, DTM&H is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society on Thrombosis and Haemostasis, Royal College of Physicians and Surgeons of Canada, American Clinical and Climatological Association, International Society of Blood Transfusion

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: GSK Pharmaceuticals,Alexion,Johnson & Johnson Talecris,,Grifols<br/>Received honoraria from all the above companies for speaking and teaching.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Clarence Sarkodee Adoo, MD, FACP Consulting Staff, Department of Bone Marrow Transplantation, City of Hope Samaritan BMT Program

Clarence Sarkodee Adoo, MD, FACP is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Society of Hematology, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

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Diagnostic workup of a patient with pre–B-cell acute lymphoblastic leukemia. Bone marrow aspiration revealed French-American-British L2 morphology.
Diagnostic workup of a patient with pre–B-cell acute lymphoblastic leukemia. Flow cytometry shows that the cells were positive for CD10, CD19, CD22, CD34, and terminal deoxynucleotidyl transferase.
Table 1. Effect of Chromosome Number on Prognosis
Chromosome Number 3-Year Event-Free Survival
Near tetraploidy 46-56%
Normal karyotype 34-44%
Hyperdiploidy >50 32-59%
Hyperdiploidy 47-50 21-53%
Pseudodiploidy 12-25%
Hypodiploidy 11%
Table 2. Common Cytogenetic Abnormalities in ALL
Abnormality Genes Involved 3-Year Event-Free Survival
t(10;14)(q24;q11) HOX11/TCRA 75%
6q Unknown 47%
14q11 TCRA/TCRD 42%
11q23 MLL 18-26%
9p Unknown 22%
12 TEL 20%
t(1;19)(q23;p13) PBX1/E2A 20%
t(8;14)(q24;q32)



t(2;8)(p12;q24)



t(8;22)(q24;q11)



c-myc/IGH



IGK/c-myc



c-myc/IGL



17%*



80%



t(9;22)(q34;q11) bcr-abl 5-10%*



66%



t(4;11)(q21;q23) AF4-MLL 0-10%
* Traditional regimens.



Hyper-CVAD (cyclophosphamide, vincristine, doxorubicin [Adriamycin], dexamethasone) with rituxan.



Hyper-CVAD with imatinib.



Table 3. Immunophenotyping of ALL Cells – ALL of B-Cell Lineage (85% of cases of adult ALL)
ALL Cells TdT CD19 CD10 CyIg SIg
Early B-precursor ALL + + - - -
Pre–B-cell ALL + + + + -
B-cell ALL - + +/- +/- +
ALL = acute lymphoblastic leukemia; Cylg = Cytoplasmic immunoglobulin; SIg =Surface immunoglobulin; TdT = terminal deoxynucleotidyl transferase.
Table 4. Immunophenotyping of ALL Cells – ALL of T-Cell Lineage (15% of cases of adult ALL)
ALL Cells TdT Surface CD3 CD4/CD8
Early T-precursor ALL + - +/+ or -/-
T-cell ALL + + +/- or -/+
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