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Leukemia

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Overview of Leukemia

Blood cancer or leukemia is a cancer of the cells in the bone marrow that form the white blood cells (WBCs). They produce huge number of altered WBCs which occupy more space and do not leave place for the RBCs or the platelets to grow. Thus, WBCs function is impaired, and anemia and bleeding tendencies developed. These abnormal WBCs ultimately spill into the circulating blood from the bone marrow and later infiltrate important organs like the liver, spleen and even the brain.1,2

Leukemia must be treated, if left untreated it will lead to mortality.

Classification of Leukemia

Leukemia is best classified on the basis of the type of cell involved and the maturity of the leukemic cells. There are two types of leukemias such as acute leukemias and chronic leukemias. Further, acute and chronic leukemias can be classified as myelogenous (myelocytic) and lymphogenous (lymphocytic).1,2

The types of leukemias:

Acute Leukemias    

  • Acute myelogenous leukemia (AML)    
  • Acute lymphoblastic leukemia (ALL)    

Chronic Leukemias

  • Chronic myelogenous leukemia (CML)
  • Chronic lymphocytic leukemia (CLL)

Acute leukemias are characterized by the presence of immature cells called ‘blasts’ and a very rapid clinical course, which is fatal unless treated. On the other hand, chronic leukemias are characterized by the presence of mature cells at least in the initial course of the disease, and an indolent course.

Genisis of Leukemia

The process of differentiation of the stem cells (primitive cells that develop into the mature and normal blood cells) within the bone marrow is blocked resulting into accumulation of immature cells in the morrow. These cells overfill the space in the morrow and do not allow other cells like RBCs and platelets to grow properly.1,2

Causes of Leukemia

Leukemia may develop due to many different causes.1–4 Some of the causes associated with the disease are briefly given as follows.

  • Radiation
  • Chemicals
  • Viruses
  • Genetic and chromosomal factors

Occurrence of Leukemia

The incidence of various types of leukemias varies with age. The most common type of anemia in children below 10 years of age is the ALL.5 The peak incidence of ALL is between the ages of 3 and 5 years. Acute myeloid leukemia is the most common leukemia in the adult age group. In general, acute leukemia is more common in men than women.

Chronic myeloid leukemia affects people after the 4th decade of their lives though childhood CML is also seen occasionally. Chronic lymphocytic leukemia is seen in the elderly.

Signs and symptoms of Leukemia

Anemia and bone pain are common symptoms.

Acute leukemias are characterized by abrupt onset with most individuals presenting within 3 months of onset of symptoms. The predominant features may be a single or a combination of paleness of the skin and eyes (pallor) and fatigue because of anemia; easy bruisability, bleeding gums or nose bleeds. Fever and infective lesions of the throat or mouth may also be seen.1,6–8

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Acute promyelocytic leukemia may present with severe bleeding tendency especially in adults while acute myelomonocytic leukemia may present with typical features like gum hypertrophy.7,8

In ALL, The onset of enlargement of lymph nodes is a common presentation and the liver and spleen more commonly involved than with AML.

The onset of CML can be insidious. Enlargement of the spleen is a very common feature of this disease and hence many a times, the affected individual presents with a dragging pain in the abdomen. Anemia is a common feature and fatigue, weakness and pallor are frequent signs. Bleeding into the skin and features of easy bruising are also noted. However, in CML, the platelet counts may be normal or even increased. The bleeding tendency in CML is attributed to an abnormality in the function of the platelets.9

Most frequent presentation of CLL is an enlargement in the size of superficial lymph nodes. Like other leukemias, pallor, tiredness, weakness and weight loss may be present. However, these symptoms usually occur in the later stages of the disease. At times, the disease may be accidentally diagnosed when a routine blood test is done.

Diagnosis of Leukemia

Diagnosis is made based on detailed history, clinical feature together with laboratory tests.1,2,9 Complete blood counts show a typical picture depending on the type of leukemia. In AML, the ‘myeloblast’ is increased in number. In ALL, the pathological cell is the ‘lymphoblast’. Chronic myeloid leukemia is characterized by the presence of ‘myelocyte’ whereas in CLL, the dominant cell is the ‘lymphocyte.’

Some times bone marrow testing is also needed for the diagnosis. Newer tests like flow cytometry are available in the advanced centers which ensure accurate diagnosis.

Treatment of Leukemia

General Considerations

The objectives of the treatment are as follows:

  • To eradicate the leukemic cells from the blood and the bone marrow.
  • To avoid the complications due to inadequate production of normal blood cells.

The age of onset of leukemias and the type of leukemias are considered before starting the treatment.

Stages of Treatment

First Stage: Remission Induction

It aims at eradicating the disease from the blood, bone marrow and organs. Attainment of complete remission entails loss of all abnormal clinical and laboratory findings attributable to leukemia.

Second Stage: Maintenance treatment

Such remission inducing treatments entail a high degree of morbidity but once in remission the quality of life of the patient certainly improves.

Along these stages, it is important to have a supportive treatment to avoid complications arising from the chemotherapy and the disease.10

Specific Therapy

Chemotherapy is the mainstay of any leukemia treatment, as it destroys the leukemic cells.1 Chemotherapeutic agents include drugs like cytosine arabinoside, daunorubicin, doxorubicin, prednisolone, methotrexate etc. Newer regimes are continuously being tried out and debated.11

Response to the treatment varies from person to person and with the type of the leukemia. Complete remissions are obtained in more than 90% of patients with ALL.

Supportive Therapy

Supportive therapy includes treatment of infections with antibiotics and transfusions to increase the hemoglobin and platelet counts. Psychological and social support goes a long way in helping these patients.1

Newer Therapies

Newer modalities of therapy include the bone marrow transplantation, a type of stem-cell therapy and monoclonal antibody therapy.

References

1.Firkin F, Chesterman C, Pennington D, Rush B (eds). The leukemias. In: De Gruchy’s Clinical Haematology in Medical Practice. .5th edn. Blackwell Publishing, pp 236–277.

2.In: Cotran, Kumar, Robbins, (eds). Disease of white cells, lymph nodes, and spleen. In: Pathologic Basis of Disease. 4th edn. WB Saunders Company, 1989, pp 703–753.

3.Bizzozero OJ, Johnson KG, Ciocco A. Radiation related leukemia in Hiroshima and Nagasaki. 1946-1964. Distribution, incidence and appearance time. New Engl J Med. 1966; 274: 1905–1105.

4.Kurzrock R, et al. The molecular genetics of Philadelphia chromosome-positive leukemias. New Engl J Med. 1988; 319: 990.

5.Richard AL. Acute leukemia: Epidemology 12 Oncology, xvi Acute Leukemia, ACP Medicine Online. In: Dale DC, Federman DD (eds). WebMD Inc.,New York, 2000. http:// www.acpmedicine.com/. Assessed on: 19 Feb 2008.

6.D’Costa GF, Dua SR, Patil YV. A spectrum of pediatric bone marrow and trephine biopsies. BHJ. 2007, 453–463.

7.Blood diseases in infancy and childhood. In: Miller DR, Bachner RL (eds). 6th edn. St Louis, The CV Mosby Company, 1990.

8.Acute myelogenous leukemia. In: Karp JE (ed.). Contemporary Hematology. Vol 357(21), 2007. p 2208.

9.David GS, Richard MS, Goldman J. Clinical features at diagnosis in 430 patients with chronic myeloid leukemia seen at a referral centre over a 16-year period. Br J Hematol. 1997; 96(1): 111–116.

10.Von Hoff DD, Rozencweig M, Piccart M. The cardiotoxity of anticancer agents. Semin Oncol. 1982; 9: 23–33.

11.Zwiebel JA,. New agents for Acute myelogenous leukemia. Leukemia. 2000; 14: 488–490.