Pathology > Basic Hematology > White Cell Disorders >Leukemia: Clinical Aspects

Leukemia: Clinical Aspects

Signs and Symptoms: Acute leukemia frequently presents with weakness, fatigue, fever, pallor, shortness of breath, weight loss, bone pain, night sweats and recurrent infections. The symptoms are often like the flu. Bruising, nosebleeds, unusally heavy menstrual periods, and swollen gums are commonly encountered in leukemia. Physical examination and laboratory studies may reveal anemia, splenomegaly, hepatomegaly and lymphadenopathy.

The chronic leukemias are often asymptomatic, but may present with relatively nonspecific and mild symptoms and signs. At later stages the signs and symptoms may be more like those of acute leukemia.

Many of the nonspecific symptoms are secondary to anemia. Fever is most likely due to infection, but may be due to tumor necrosis factor or other factors released by the leukemic cells.

What is the cause of the bruising?

Cytopenia may be due to decreased marrow production (leukemic infiltration or suppression of the marrow) and splenic sequestration. What might cause the shortness of breath?

High leukocyte counts (>50 x109/L) are seen in about 20% of cases and may lead to leukostasis with plugging of capillaries and small vessels, leukocytosis is almost always seen in myeloid rather than lymphoid leukemias despite the high WBC counts >100 x109/L, more often encountered in CLL.

What are possible causes of infection in acute leukemia? in CLL?

Dagnosis and Prognosis:

  1. Distinguish acute leukemia from chronic leukemia as the prognosis and treatment approach differ greatly. Acute leukemias are generally treated aggressively with intensive chemotherapy while chronic leukemias are often watched or "followed" reserving chemotherapy for later stages when organ infiltration becomes a problem.

  2. Distinguish myeloid from lymphoid for the type of chemotherapy used against acute lymphoblastic leukemia (vincristine, prednisone and anthracycline ± aspiraginase) is very different from the more highly toxic chemotherapy used for acute myeloid leukemia (cytosine arabinoside, anthracycline ± 6-thioguanine).

  3. Currently, the distinction between the various FAB myeloid leukemias does not significantly affect therapy.

4. Among the acute lymphoid leukemias the choice of treatment is influenced by the ALL immunophenotypic subtype.

The above figure shows the different responses to chemotherapy of the four ALL subtypes. The T and B ALLs were treated more aggressively than the Pro-B and pre-B ALLs. Today the pre-B ALLs would get more aggressive therapy.

*Modified Pediatric Oncology Group data, W Crist, 1985

5. Adverse prognostic factors in acute leukemia include:

  1. Drug and/or radiation induced leukemia
  2. Prior MDS "preleukemic" phase3
  3. Cytogenetic abnormalities-
  4. Expression of T-cell markers on myeloid leukemias
  5. Decreased metaphases in culture
  6. Large tumor burden
  7. Miscellaneous, e.g. fever, age, morphology, immunology
  8. Elevated LDH


  1. Therapy begins with induction of remission by intensive chemotherapy requiring intensive medical support, ie. transfusion of blood products, prevention and treatment of infection (isolation, prophylactic antibiotics, etc.), and nutritional support (e.g. hyperalimentation).

  2. Following remission induction, therapy may involve consolidation, intensification, maintenance, and possible central nervous system prophylaxis (mainly in ALL).

  3.  For acute nonlymphocytic leukemia complete remission (CR) is acheived with chemotherapy in 70-80% of cases, but median survival is <2 years and disease-free survival (DFS at 5 yrs) is only 10-15%. As a result bone marrow transplantation (syngeneic, allogeneic, autologous) must be considered after CR is acheived.

  4. In acute lymphoblastic leukemia chemotherapy* allows a CR for children (<15 yrs of age) of 95% with median survival >3 years and long term DFS (cure) of approximately 50%. For adults (same drugs*) the CR is 75-80%, but median survival is <2 years and long term DSF is < 20%.

    Note the differences in results between children and adults. Bone marrow transplantation is becoming an increasingly important mode of therapy and is at times the only curative option.

  5. The most common causes of death are: infection - 60% and hemorrhage - 30%.

*vincristine + prednisone ± asparginase or anthracycline with CNS prophylaxis and maintenance for 2-3 years




A 55-year-old man complains of dizziness, headaches and pruritis after showering. He notes early satiety and smokes ‰ 1 pack of cigarettes/day x 30 years.

On physical examination you find a middle aged man with a ruddy complexion, mild hypertension, and mild spenomegaly.

Clinically you suspect polycythemia and order an erythropoietin level. Based on the above clinical information you expect the following:

A. Polycythemia vera and normal erythropoietin
B. Polycythemia vera and increased erythropoietin
C. Secondary polycythemia and normal erythropoietin
D. Secondary polycythemia and increased erythropoietin


Leukostasis is a complication most commonly associated with:

A. Polycythemia vera
B. Chronic lymphocytic leukemia
C. Acute myeloid leukemia
D. Aplastic anemia
E. Essential thrombocytosis


A 67-year-old man comes to your community practice complaining of weakness and fatigue. His WBC count is 3.5 x109/L with a left shift and 1% blasts. The bone marrow has 15% blasts and you see dyserythropoiesis, dysgranulopoiesis and many large vacuolated platelets. The hematopathologist makes a diagnosis of refractory anemia with excess blasts.

You tell the man that he has a myelodysplastic syndrome. What does that mean Doc ???? You respond:

A. nothing to worry about, most patients get better in ‰ 6 months
B. this is a serious disorder of the bone marrow closely related to 1°myelofibrosis
C. this is a serious disorder of the bone marrow that often, but not always leads to acute myeloid leukemia
D. you have a "preleukemia" and will certainly get acute myeloid leukemia in about 2 months, so get all your affairs settled
E. this is really an early form of acute myeloid leukemia and we will need to begin chemotherapy immediately


You are explaining to the parents of a 6-year-old boy that you must wait for the immunologic testing to be completed before beginning therapy. They want to know what difference it makes if the leukemia is a pro-B, a pre-B, T-cell or Burkitt's leukemia?

You tell them the survival is:

A. greater for T-cell than pro-B
B. greater for Burkitt's than pro-B
C. greater for pro-B than pre-B
D. greater for Burkitt's than pro-B
E. greater for Burkitt's than pre-B

A 61-year-old man has a platelet count of 360 x10 /L, a WBC count of 36 x 10 /L with 35% lymphocytes and an autoimmune hemolytic anemia most likely has:

A. a clonal rearrangement of the JH region of the lymphocytes
B. an relative lymphocytosis
C. a T-gamma lymphocytosis
D. Sezary syndrome
E. Adult T-cell leukemia/lymphoma

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