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Donetsk National Medical University after M.Gorky

Technique Guidelines


the students’ individual preparation for

Practice activities

SUBJECT: Acute leukaemias

INTENDED AUDIENCE: 5-year students

of International Medical Faculty

Donetsk – 2010


PhD, prof. ass. Sklyanna O.V.

PhD, prof. ass. Kalinkina N.V.


Parhomenko Т.А., prof. ass. of department of internal medicine №2

Basiy R.V., prof. ass. of department of humen anatomy, head of methodical room of Donetsk national medical university

I. Importance of the Subject.

Acute leukaemia (AL) is one of the most widespread diseases of blood. Before the appearing modern chemotherapeutical courses of treatment AL was quickly progressive and mortality was high.

There are two types of AL: acute myeloblastic leukaemia (AML) and acute lymphoblastic leukaemia (ALL). AML is the commonest disease in adults (3 per 100,000 annually). The frequency increases with age. It’s unfrequent in children under 15 years. ALL is the commonest malignancy in childhood with the majority of cases in the 2-10 age group. This leukaemia is rare in adults (0,7 to 1,8/100,000 annually). In adults there is a peak at 15-24 years and a further peak in old age (2,3/100,000 >80 years).

Aetiology of AL is unclear. There is an association with pre-existing myelodysplasia, previous cytotoxic chemotherapy (particularly alkylating agents and epipodophyllotoxins), ionizing radiations, benzene exposure, constitutional chromosomal abnormalities, pollution, viruses, chemicals, urban/rural population movements, father’s radiation exposure, radon level and others. Clinical features are: symptoms of anaemia, infection, haemorrhage, signs of leucostasis, hepatomegaly, splenomegaly, lymphadenopathy.

As AL is a multisymptomatic disease each specialist can meet it in his practice. It makes this problem significant not only for haematologists but for doctors of other specialities as well.

II. Key Objective

^ Purpose (общая): to differentiate AL from other diseases with similar symptoms, to determine a tactic of treating and giving emergency medical service the patient with AL.

^ Specific Goals

To develop skills in :

Prior-to- Practice Level of Knowledge and Skills

Possessing a knowledge of and skills in:

1. Picking out of a patient’s complaints, anamnesis and physical neurological examination the most important symptoms typical of AL.

1. Selecting the data from the complaints and case history findings showing the presence of AL (Covered by Propaedeutics and Therapy Course).

2. Identifying the main syndromes of AL.

2. Determining the necessary amount and sequence of investigative methods (Covered by Physiology and Pathophysiology Course, Propaedeutics and Therapy Courses).

3. Prescribing and assessing results of additional methods of study on the basis of diagnostics algorithms. Determining the type and degree of the disease due to the classification.

3. Determining a volume of necessary methods of study:

Physical and laboratory’s findings: FBC and blood film, bone marrow aspirate ± biopsy, bone marrow cytogenetics, (Covered by the courses of physiology and pathophysiology);

X-ray and CT of chest, abdomen, ultrasound investigation of internal organs (Covered by the course of Radiology)

  1. Differentiating AL from other diseases with hyperplastic, haemorrhagic, anemic and intoxicational syndromes.

4. Distinguishing syndromes in case of emergency in the patients affected by AL (Explained in the Propaedeutics and Therapy Course).

5. Determining a tactic of treating a patient and tactic of giving emergency medical service.

5. Applying medications of pathogenetic and symptomatic therapy (Explained in the Pharmacology Course).

The all necessary information you can find in such sources:

  1. Arthur C. Guyton, John E. Textbook of Medical Physiology (Textbook Binding). - Hall W.B. Saunders Company; 10th edition. – 2000.

  2. Aaron B. Caughey, Nancy Palmer, Christie Del Castillo, and Dana Tuttle. Pathophysiology: Hematology and Oncology. -Blueprints Notes & Cases Series. - 2003.

  3. Propedeutics of internal diseases. Edited by V.H.Vasilenko, and A. Grebenev.-Moscow: medicine, 2006.

  4. Drew Provan, Charles R.J. Singer, Trevor Baglin, John Lilleyman. Oxford Handbook of Clinical Hematology. New York, 2004.

Test Questions for Pre-Practice Self-Assessment Purposes.

To assess your Pre-Practice level of knowledge and skills carry out the following tasks. Check your answers with the Key.

Q 1. The patient complains of general weakness, dizziness, low-grade fever during the week. He was treated by himself with vit. C, resolvents without effect. On examination of the patient physician revealed paleness, tachycardia, systolic noise above the apex of heart.

Which of the following syndromes is the one described in this case?

А. hemorrhagic,

B. hyperplastic;

C. uraemic;

D. anemic;

E. intoxicatic.

Q 2. The general blood count of a 29-year-old patient showed the following data: erythrocytes were 3.5×1012, Нb was 110 g/l, color index was 0.9, thrombocytes were 45‰, leucocytes were 15×109, 20% blasts, 40% segmented neutrophils, 32% lymphocytes, 8% monocytes, and ESR was 28 mm/h.

Which of the following cells must be absent in normal general blood count?

А. monocytes;

B. eosinophils;

C. blasts;

D. segmented neutrophils;

E. lymphocytes.

Q 3. On examination of the patient affected by acute lymphoblastic leukaemia physician revealed the enlargement of lymph nodes, both the liver and the spleen, tonsils, hyperplasia of gums. There were acute pains during throbbing on bones, leukemids.

Which of the following syndromes is the one described in this case?

А. hyperplastic;

B. hemorrhagic;

C. anemic;

D. intoxicatic;

E. uraemic.

Q 4. The general blood count of a 42-year-old patient showed the following data: erythrocytes were 4,0×1012, Нb was 130g/l, color index was 0.9, thrombocytes were 20‰, leucocytes were 7.0 ×109, 5 band neutrophils, 55 segmented neutrophils, 32 lymphocytes, 8 monocytes, and ESR was 14 mm/h.

Which of the following drugs could be the reason of such changes?

А. ambroxol;

D. aminocaproic acid;

C. acetylsalicylic acid;

D. sorbifer;

E. efedrin.

Q 5. The white blood cell count of a 34-year-old patient affected by pneumonia showed the following changes: 3% eosinophils, 17% band neutrophils, 56% segmented neutrophils, 20% lymphocytes, and 4% monocytes.

Percentage of which cells in the white blood cell count were high?

А. Segmented neutrophils;

B. Eosinophils;

C. Lymphocytes;

D. Monocytes;

E. Band neutrophils.

Q 6. The patient H., 25 years old, affected by acute myelomonocytic leukaemia complains of fever, hard infections (Herpes, fungal infections).

Which of the following syndromes is the one described in this case?

А. hyperplastic;

B. hemorrhagic;

C. anemic;

D. intoxical ;

E. syndrome of immunodeficiency.

Key Answer 2.

Correct answer is B. These cells are blasts.

Key Answer 3.

Correct answer is A. The hyperplastic syndrome is described in this question. Its main symptoms are lymphadenopathy, the enlargement of spleen, liver, tonsils, hyperplasia of gums. Often there is the pain during knocking the ribs.

If you have made sure that your pre-practice level of knowledge and skills meets the requirements of the starting level, pass on to mastering the subject material.

IV. Subject Material

Theory Topics on the Subject:

  1. Clinical features, anamnesis and examination of the patient.

  2. Methods of clinical, laboratory and instrumental diagnostics of AL.

  3. Differential diagnostics of AL.

  4. Clinical classification of AL.

  5. Aetiology and pathogenesis of AL.

  6. Tactic of treatment of a patient affected by AL.


The information necessary for mastering the theory issues may be found in the following references:

  1. Hematology 2001 American Society of Hematology. Education Program Book. 2001 -

  2. Michael Harvey. Haematology Handbook. Haematology Unit, Liverpool Hospital. 2001.

  3. Alan Rosenwald. Practical Diagnosis of Hematologic Disorders, Fourth Edition. – 2006. - P.168-197.

  4. Chris Cheson Clinical Laboratory Hematology.- Delphi Publishers. – 2007. –P. 54-109.

  5. Cytochemical reference of different hemoblastoses. (appendix 1).

  6. A Flow Chart “Acute Leukaemia” (appendix 3);

  7. Classification of Leukaemias (appendix 2);

Target Activity Questions on the Subject:

Then, proceed to solving some test questions and checking test question 5 with the key answer.

Q 1. A 40-year-old patient complains of a general weakness, dizziness, spots on his trunk and extremities, fever during the two weeks, lymphadenophathy.

The blood count shows the following: erythrocytes 2,3×1012, Hb is 85 g/l, color index is 0.9, thrombocytes are 50 ‰, leucocytes are 20 g/l, 50% blasts, 24% segmented neutrophils, 18% lymphocytes, 8% monocyte. In the myelogram there are 58% of blasts.

Which of the following is the most probable diagnosis?

А. Acute leukaemia;

B. Leukaemoid reaction;

C. Chronic lymphoid leukaemia;

D. Chronic myeloid leukaemia;

E. Polycythemia vera.

Q 2. The patient K. 22 years old, affected by Acute Leukemia the physician suspected syndrome “lysis of blasts”.

Which of the following changes can confirm this syndrome?

А. High level of urinary acid in the blood;

B. High level of direct reacting bilirubini;

C. High level of indirect reacting bilirubini;

D. High level of creatininase;

E. High level of fibrinogen.

Q 3. The patient Р. 27 years old, during last month complains of weakness, fever, sweating, headache, anorexia, losing, pains in bones. Often hemorrhages hurt her. The blood count shows the following: erythrocytes 2,5×1012, Hb is 90 g/l, color index is 0.9, thrombocytes are 60 g/l, leucocytes are 50 g/l, 4% band neutrophils, 40% segmented neutrophils, 10% lymphocytes, 2% monocyte, 35% blasts, and ESR is 25 mm/h. In the myelogram there were 35% of blasts. The results of cytochemistry are peroxidase is negative, lipids are negative, PAS-reaction is positive.

Which of the following is the most probable diagnosis?

А. Acute lymphoblastic leukaemia ;

B Acute monoblastic leukaemia;

C Multiple myeloma

D Chronic lymphoid leukaemia;

E Chronic myeloleukamia

Q 4. For refining the diagnosis the patient was made sternal puncture. In the myelogram there were blasts 77%, myelocytes 0,5%, band neutrophils 3%, segmented neutrophils 2%, lymphocytes 17%, normoblasts 1,5%.

Which of the following is the most probable diagnosis?

А. Polycythemia Vera;

B. Chronic myeloleukamia

C. Chronic lymphoid leukaemia;

D. Multiple myeloma

E. Acute lymphoblastic leukaemia.

Q 5. The patient 19 years old complains of painful swallowing, pain and swelling of neck on the left, fever. These complaints appered a week ago. On examination there were hyperemia of mucous membrane of pharynx, hypertrophy of palatine tonsils without raids. Frontal and back cervical lymph nodes were enlarged with severe pain during palpation. The respiration above lungs was vesicular. Heart sounds were clear. His pulse rate was 87/min, regular in time and force, BP was 120/80. His spleen and liver were enlarged. There was no peripheral oedema. The blood count shows the following: erythrocytes 3,1×1012, Hb is 110 g/l, color index is 0.9, thrombocytes are 190g/l, leucocytes are 12,5 g/l, 14% band neutrophils, 46% segmented neutrophils, 12% lymphocytes, 2% monocyte, atypical mononuclear cells 20% , and ESR is 25 mm/h. 70% of neutrophils have toxical granularity, 30% of neutrophils have hypersegmented nucleus.

Which of the following is the most probable diagnosis?

А. Acute leukaemia

B. Leukaemoid reaction;

C. Chronic leukaemia ;

D. Infectious mononucleosis;

E. Polycythemia Vera.

Key Answer 5

The correct answer is D – Infectious mononucleosis. In this question typical clinical and laboratory findings of this disease are presented. They are fever, enlargement of lymph nodes, spleen and liver, 20% atypical mononuclear cells in the blood analyse.

^ Summary of procedures for the practice on the subject:

Acute Leukaemia

At the beginning of the practice prior-to-practice level of knowledge and skills is assessed. Each student gets a patient for curation, examines patients in the ward, and takes part in additional methods of examination.

After fulfilling the tasks, students and the teacher perform the analysis of each student’s independent work where all the students take part.

At the end of the class final testing on the subject and summing up the results of the lesson are performed.

Appendix 1

break-down chart on the SUBJECT:

break-down chart on the SUBJECT

Acute Leukaemia”


Acute Leukaemia

Main symptoms and syndromes


purpura, menorrhagia and epistaxis, bleeding gums, rectal, retina


lymphadenopathy, hepatomegaly, splenomegaly, gum hypertrophy, skin infiltration.


weakness, fever, sweats, headache, anorexia weight loss, muscle atrophy, ossalg, nausea, vomiting, infections (particularly chest, mouth, perianal, skin).

symptoms of anaemia

weakness, lethargy, breathlessness, lightheadedness and palpitations

Clinical features of


Investigations and diagnosis


  • FBC and blood film (anaemia, thrombocytopenia, blasts, Bone marrow (BM) aspirate (blasts >30%);

  • Immunophenotyping

  • Cytogenetic analysis


differential diagnostics algorithm on the subject :

Chronic leukaemia (Chronic myeloid leukaemia, chronic lymphocytic leukaemia), aplastic anaemia, neutropenia, Hodgkin’s lymphoma


Clinical classification of AL

FAB- classification of AL

(Appendix 2)




(Appendix 4)


  • RBC transfusion

  • platelet transfusion

  • colony-stimulation factor

  • Antibiotic and antifungal drugs

Appendix 2

Clinical classification of AL

^ Acute leukaemia

Chronic leukaemia

FАВ- classification


М0 — AML with minimal differentiation; 3% of cases

m1AML without maturation 20% of cases

М2 — AML with maturation ;

30% of cases

М3 — Acute promyelocytic leukaemia; 10%

М3v – Microgranular variant of APL (high WBC count; minimal granulation)

М4 — Acute myelomonocytic leukaemia; 20%.

М4Eo - М4 variant with 5-30% eosinophils; 5%

^ M5a - Acute monoblastic leukaemia; 10-15%cases are M5a or M5b

M5b- Acute monocytic leukaemia

M6 - Acute erythroleukaemia; 305% of cases but 10-20% of secondary leukaemias.

M7 – Acute megakariooblastic leukaemia (difficult to diagnose morphologically; often dry tap due to fibrosis; requires immunophenotyping with anyi-platelet antibodies or electron microscope analysis of platelet peroxidase) rare

Myeloid forms.

  1. Myeloleukemia.

  2. Osler's disease (erythremia).

  3. Idiopathic myelofibrosis.


l1 — small monomorphic type – small homogeneous blasts, single inconspicuous nucleolus, regular nuclear outline; commonest subtype.

l2 — Large heterogeneous type – larger blasts, more pleomorphic and multinucleonate, irregular frequently clefted nuclei with conspicuous nucleoli.

L3 —Burkitt cell type – large homogeneous blasts, abundant strongly basophilic cytoplasm with vacuoles; associated with B-cell phenotype.

Lymphoid forms.

  • Chronic lymphoid leucosis.

  • Paraproteinemic hemoblastoses (multiple myeloma, and Waldenstrom’s


Appendix 3.

Cytochemical reference of different hemoblastoses.

Form of acute leukaemia




Non-specific esterase


Sour Phosphatase




Positive with big granules

Negative or Weak positive


In separate cells




Positive, diffuse

Weak positive




Myeloblastic cells type;

Monoblastic cells type


Weak positive


Weak positive

Positive, diffuse

Positive with small granules

Weak positive

Expressed positive (inhibite by NaF)




Expressed positive


Weak positive or negative

Weak positive or negative

Positive with small granules

Expressed positive

Expressed positive


Expressed positive


Strong positive

Strong positive

Expressed positive, diffuse

Expressed positive

Expressed positive

Expressed positive


Blastic cells;






Positive, diffuse

Positive, diffuse with big granules

Weak positive













Appendix 4

Normal Blood Indices

General Blood Count (WHO, 1999).


Women 3.7-4.7×1012

Men 4.0-5.1×1012


Women 115-145 g/l

Men 130-164 g/l

Color index(Hb/erythrocytes х 30)



4.0-9.0 g/l





Band neutrophils


Segmented neutrophils









170-360 g/l


Women 36-42%

Men 40-48%


Women 4-16 mm/h

Men 2-10 mm/h

differential diagnostical algorithm on the subject

Appendix 5

List of Nosological Units

  1. Hodgkin’s lymphoma;

  2. Chronic lymphocytic leukaemia;

  3. Chronic myeloid leukaemia;

  4. Aplastic anaemia;

  5. Acute leukaemia.

Syndrome of toxication

Hyperleukocytosis, intermediate lymphoid cells in the blood


Biopsy of lymph node: Reed-Sternberg cells there, character changes there






Hyperleukocytosis with neutrophilia, presence of immature myeloid cells in the blood







Bone marrow aplasy with prevalence of adipose tissue at trepan biopsy



≥30% blast cells in myelogram


^ At the end of the practice class, you shall take a final test, and with this aim in mind, pay attention to the following example tests.

Final Test Questions

Q 1. The patient S., 32 years old, suffering from an Acute leukaemia, is treated with Helcer plot. During the last week was complaining of sleeplessness, severe headache, then he noticed paresis of muscles and speech. He had been made trial spinal puncture, in it there were a lot of blasts.

What complications were there in this case?

А. Meningitis;

B. Neuroleukaemia;

C. Astrocytoma;

D. Cerebral hemorrhage;

E. Arachnoiditis.

Q 2. The patient S., 32 years old, suffering from Acute lymphoblastic leukaemia, on the background of polychemotherapy the temperature is normal, there is no hemorrhages. In a month before the next course of treatment the general blood count showed the following data: erythrocytes were 3.7×1012, Нb was 126g/l, color index was 0.9, thrombocytes were 125*109, leucocytes were 5,2×109, band neutrophils 5%, segmented neutrophils 55%, lymphocytes 34%, 6% monocytes, and ESR was 15 mm/h, there were no blasts. In myelogram were 2% of blasts.

This patient has:

А. Complete remission;

B. Uncomplete remission;

C. Blast crisis;

D. Terminal phase of AL;

E. Myelofibros.

Q 3. 56-year-old patient, has her cervical and axillary lymph nodes palpated that are as big as 2 cm in diameter, dizziness, fever sweating , anorexia, weight loss ( 9 kg during 3 month). On examination: gum hyperplasia, enlargement of lymph nodes. Blood count is: erythrocytes are 3.6×1012, Нb is 125 g/l, color index is 0.9, thrombocytes are 120*109, leucocytes are 9/109 g/l, 5 band neutrophils, 61 segmented lymphocytes, 22 lymphocytes, 12 monocyte.

Which additional method of examination is necessary to use to exclude hemoblastosis?

А. Sternal puncture;

B. spleen biopsy;

C. liver biopsy;

D. USE of spleen;

E. CT of chest.

Q 4. 26-year-old patient, during the last month complains of frequent nosebleeds, profuse mensis, sweating, fever 38,5º, headache, loss weight. The blood count presents the following evidence: erythrocytes are 2.7×1012, Нb is 92 g/l, color index is 0.85, thrombocytes are 55/109,leucocytes are 30/109, 5 band neutrophils, 40 segmented neutrophils, 14 lymphocytes, 8 monocyte, 35 blasts, ESR is 25 mm/h. In myelogram there are 45% blasts.

Results of cytochemical analysis are myeloperoxidase is positive, lipids is positive, PAS-reaction – negative.

Which of the following can be a correct diagnosis?

А. Chronic myeloid leukaemia;

B. Acute lymphoblastic leukaemia;

C. Myelodisplasia;

D. Chronic lymphoid leukaemia;

E. Acute myeloblastic leukaemia.

Q 5. 32-year-old patient, affected by AL, complains of anhydrosis, severe headache, sometimes convulsions. Neurologist has found showings lesions of cranial nerves, paresis of mimic muscles. Neuroleukaemia is under suspicion.

What method of investigations can help in adjustment of diagnosis?

А. CТ of brain;

B. МRТ of brain;

C. Scull X-Ray ;

D. Lumbal puncture;

E. Sternal puncture.

Q 6. The patient, 30 years old, is affected by AL. On the background of polychemotherapy syndrome of blasts lysys has formed.

What drug should be prescribed for prophylaxis of this complication?

А. Alopurinol;

B. Propranolol;

C. Dimedrol;

D. Diazepam;

E. Lasix.


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