Acute Lymphoblastic Leukemia (ALL): The most common pediatric leukemia, is most commonly seen ages 2-10, and rarely over 14. It is also more commonly seen in males than females.
Acute Myelogenous Leukemia (AML): Typically seen in people over 40 years old, with a median age of 65. Again, it is more common in males than females.
Chronic Lymphocytic Leukemia (CLL): Incidence increases with age and has a median age of diagnosis at 71. It is rarely seen in patients under 40, and it is twice as common in males than in females. CLL represents 30% of all the leukemia cases in the United States.
Chronic Myelogenous Leukemia (CML): It is most commonly diagnosed in patients that are in their 4th decade of life, and rarely presents before 20. Higher possibility in males than females.[1]
Etiology:
ALL: Previous exposure to radiation, genetic predisposition, and Human T-cell lymphotropic virus type 1 in adults are all risk factors of ALL.
AML: Fanconi's anemia, Bloom syndrome, and previous exposure to radiation, benzene, and alkylating agents are all causative factors of AML.
CLL: Risk factors for CLL include hereditary disposition, immunodeficiency syndrome and viruses.
CML: Exposure to radiation and benzene have shown connections with CML.[1]
Signs & Symptoms:
ALL: nonspecific, flu-like symptoms, anemia, thrombocytopenia, and neutropenia, liver, splenic and testicular enlargement, joint swelling, bone pain and tenderness.1 AML: nonspecific flu-like symptoms, anemia, reduced platelet production, neurtopenia, enlarged spleen. CLL: patients are commonly symptom-free at diagnosis, caught as an incidental finding from routine blood tests. Fatigue, fever, night sweats and weight loss may be present. Enlarged spleen and lymphadenopathy are common. CML: fatigue, heat intolerance, sweating, weight loss, easy bruising, abdominal discomfort, enlarged spleen, hepatomegaly and lymphadenopathy.
Diagnostic Procedures:
The initial diagnostic workup includes a complete medical history and a comprehensive physical examination.2 Leukemia is typically detected by a complete blood cell count and bone marrow examinations. The specific type of leukemia is determined by different test results listed below.
ALL: A complete blood cell counts and bone marrow biopsy including flow cytometry and cytogenetic studies. AML: Specific blood tests including complete blood counts, differential leukocyte, platelet counts, and blood smears. A bone marrow aspiration and biopsy detecting auer rods. CML: Diagnosis of CML is difficult. Specific blood tests include complete blood counts, differential leukocyte, and platelet counts revealing abnormality may indicate CML. Presence of the Philadelphia chromosome is the main indicator of CML.
Histology:
ALL is the unregulated over creation of lymphoblast.3 The out of control deceased cells overcrowd health cells and inhibit health cell growth.
AML involves hematopoietic stem cells or pluripotent cells.3 These cells lose the ability to differentiate in response to hormonal signals and cellular interactions leading to an accumulation of undifferentiated cells in marrow and or other organs. In the S and M phase of the cell cycle these cells have a decrease portion of blast cells. Due to the decrease the hematopoietic stem cells and pluripotent cells either do not reach maturity or are defective at maturity.
CML is caused by abnormal hematopoietic stem cells that develop daughter cells that have the Philadelphia chromosome.3 An increase in proliferation of granulocytic and megakaryocytic cells occurs because of the abnormal stem cell pool leading to erythropoiesis.
Lymph node drainage:
Due to leukemia being a disease of the blood there is no direct lymph node dissemination.
Metastatic spread:
Leukemia often starts in the bone marrow and quickly moves to the bone.4 The possible sites of spread include:
Lymph nodes
Spleen
Liver
Central nervous system
Other organs
Grading:
French-American-British system is used in the acute forms of leukemia. The CML is graded by determining if the cells are in the chronic phase, accelerated phase, or the acute phase.3
FAB system5
Staging:
ALL staging6
Early pre-B ALL: Approximately 10 percent of ALL cases
Common ALL: Approximately 50 percent of cases
Pre-B ALL: Approximately 10 percent of cases
Mature B-cell ALL (Burkitt leukemia)
AML staging
Undifferentiated AML - M0: In this stage of acute myelogenous leukemia, the bone marrow cells show no significant signs of differentiation.
Myeloblastic leukemia - M1: Bone marrow cells show some signs of granulocytic differentiation with or without minimal cell maturation.
Myeloblastic leukemia - M2: Maturation of the bone marrow cells is beyond the promyelocyte (early granulocyte) stage. Varying amounts of granulocyte maturation may be observed.
Promyelocytic leukemia - M3: Most of the abnormal cells are early granulocytes, between myeloblasts and myelocytes in their stage of development. The cells contain many small particles and have nucleuses of varying size and shape.
Myelomonocytic leukemia - M4: In this stage of acute myelogenous leukemia, the bone marrow and circulating blood have variable amounts of monocytes and differentiated granulocytes in them. The percentage of monocytes and promonocytes in the bone marrow is greater than 20 percent. There may also be an increased number of granular leukocytes called eosinophils, a type of granulocyte that often has a two-lobed nucleus.
Monocytic leukemia - M5: This subset is further divided into two different categories. The first is characterized by poorly differentiated monoblasts with lacy-appearing genetic material. The second subset is characterized by a large number of monoblasts, promonocytes and monocytes. The proportion of monocytes in the bloodstream may be higher than that in the bone marrow.
Erythroleukemia - M6: This form of leukemia is characterized by abnormal red blood cell-forming cells, which make up over half of the nucleated cells in the bone marrow.
Megakaryoblastic leukemia - M7: The blast cells in this form of leukemia look like immature megakaryocytes (giant cells of the bone marrow) or lymphoblasts (lymphocyte-forming cells). M7 leukemia may be distinguished by extensive fibrous tissue deposits (fibrosis) in the bone marrow.
There are three stages of CML.
Chronic: This is the earliest phase of CML. The majority of CML patients are diagnosed during this phase as a result of mild symptoms, particularly fatigue.
Accelerated: If CML has not responded to treatment well during the chronic phase, it becomes more aggressive, which can lead to the accelerated phase. At this point, symptoms may become more noticeable.
Blastic: This is the most aggressive stage of chronic myeloid leukemia. Blastic refers to having more than 20 percent myeloblasts or lymphoblasts. Symptoms are similar to those of acute myeloid leukemia.
Radiation side effects:
The side effects of radiation therapy for leukemia depend on the treatment dose, the part of the body being radiated, the duration of radiation and other factors. Radiation may cause a drop in white blood cell count, which can increase your risk of infection. Some other potential side effects include fatigue, nausea, diarrhea, loss of appetite and skin irritation.6
Prognosis:
ALL3:
75% of patients can be expected to experience a complete remission
Age 2 - 10 carries a poor prognosis, and infants to age 1 have an even poorer prognosis
Age 50 or greater has a worse prognosis than children
Poor performance status, impared organ function, and low serum albumin levels are unfavorable prognostic indicators
AML:
Unfavorable prognostic variables similar to ALL, including age 50 or greater, myelodysplastic syndrome, poor performance status, impaired organ function, low serum albumin.
Children have a poorer prognosis compared to ALL.
High white blood cell count in unfavorable
CLL:
Prognosis factors include stage, age, doubling time of the peripheral blood lymphocyte count, and bone marrow involvement.
T-cell variety is more aggressive
CML:
Prognosis factors include spleen size, platelet count, hematocrit, gender, and percentage of blood myeloblasts.
Active phase of disease has a median survival time of 2 years.
Treatments:
ALL3:
Radiation therapy, chemotherapy, bone marrow transplant
Several radiation techniques used:
Total body radiation with total dose 1200 centigray (cGy). 200cGy per fraction, twice a day (BID), for three consecutive days. Used in combination with bone marrow transplant.
Helmet field may be used to encompass the meninges, total dose 1800cGy, delivered 200cGy per fraction over 9 consecutive days.
CNS technique is a combination of helmet and spine fields when spinal fluid is positive. Helmet field is treated to 2400cGy with 150cGy per fraction and the spine is treated to 1500cGy at 150cGy per fraction.
The final treatment technique for ALL is a testis field. The field receives 400cGy for a single fraction and is commonly used with TBI
AML:
Radiation therapy, chemotherapy, bone marrow transplant
Total body irradiation (TBI) is given BID for 3 days to a total dose of 1200cGy.
Chemotherapy is then given in two groups: remission induction and postinduction consolidation/maintenance
Bone marrow transplant is the final treatment technique
CLL:
Optimal treatment for CLL is unknown.
Chemotherapy is administered for progressive anemia and thrombocytopenia.
Palliative radiation therapy is used for localized masses of lymphoid tissue or enlarged spleen. Usually anterior-posterior/posterior-anterior (AP/PA) to a dose of 500cGy.1 cm margin around the organ, but limit dose to the kidneys.
Surgery can be done to remove the spleen. The enlarged spleen causes cytopenia, which is the result of accelerated removal or excessive pooling of platelets or red blood cells.
CML:
Treatment techniques include radiation therapy, chemotherapy, and bone marrow transplant
Radiation is delivered to the spleen and total body, similar to CLL
Allogeneic bone marrow transplantation is the only curative treatment for CML
TD 5/5:
Tolerance doses that will cause a minimum 5% complication rate within 5 years3: Bladder: 65 Gray (Gy) Brain: 45 Gray (Gy) Colon: 45 Gy Endocrine glands (Thyroid): 45 Gy Esophagus: 55 Gy Heart: 40 Gy Kidney: 23 Gy Larynx: 70 Gy Liver: 30 Gy Lung: 17.5 Gy for whole lung, 30 Gy for 2/3 of lung, 45 Gy for 1/3 of lung Lens: 10 Gy Optic chiasm: 50 Gy Optic nerve: 50 Gy Retina: 45 Gy Rectum: 60 Gy Salivary glands: 50 Gy Skin: 55 Gy Small intestine: 40 Gy Spinal cord: 45 Gy Stomach: 50 Gy Testis: 1 Gy Ovaries: 2-3 Gy
Additional images:
Reprinted from Principles and Practice of Radiation Oncology, 5th edition.7
The above image is a cranial irradiation field outlining treatment that encompasses the entire cranial subarachnoid space of a leukemia patient. The radio-opaque markers outline the anterior aspect of the bony orbit so as to demarcate inclusion of the posterior aspect of the eye within the treatment fields.7
The following images are for patients treated with total body irradiation: Reprinted from Radiation Oncology Management Decisions, 3rd edition.1
Reprinted from Radiation Oncology Management Decisions, 3rd edition.1
Reprinted from Radiation Oncology Management Decisions, 3rd edition.1
Reprinted from Radiation Oncology Management Decisions, 3rd edition.1
References:
Chao KS, Perez CA, Brady LW. Radiation Oncology Management Decisions. 3rd ed. Philadelphia, PA: Lippincott, Williams, and Wilkins; 2011.
Acute Myelogenous Leukemia (AML): Typically seen in people over 40 years old, with a median age of 65. Again, it is more common in males than females.
Chronic Lymphocytic Leukemia (CLL): Incidence increases with age and has a median age of diagnosis at 71. It is rarely seen in patients under 40, and it is twice as common in males than in females. CLL represents 30% of all the leukemia cases in the United States.
Chronic Myelogenous Leukemia (CML): It is most commonly diagnosed in patients that are in their 4th decade of life, and rarely presents before 20. Higher possibility in males than females.[1]
AML: Fanconi's anemia, Bloom syndrome, and previous exposure to radiation, benzene, and alkylating agents are all causative factors of AML.
CLL: Risk factors for CLL include hereditary disposition, immunodeficiency syndrome and viruses.
CML: Exposure to radiation and benzene have shown connections with CML.[1]
AML: nonspecific flu-like symptoms, anemia, reduced platelet production, neurtopenia, enlarged spleen.
CLL: patients are commonly symptom-free at diagnosis, caught as an incidental finding from routine blood tests. Fatigue, fever, night sweats and weight loss may be present. Enlarged spleen and lymphadenopathy are common.
CML: fatigue, heat intolerance, sweating, weight loss, easy bruising, abdominal discomfort, enlarged spleen, hepatomegaly and lymphadenopathy.
ALL: A complete blood cell counts and bone marrow biopsy including flow cytometry and cytogenetic studies.
AML: Specific blood tests including complete blood counts, differential leukocyte, platelet counts, and blood smears. A bone marrow aspiration and biopsy detecting auer rods.
CML: Diagnosis of CML is difficult. Specific blood tests include complete blood counts, differential leukocyte, and platelet counts revealing abnormality may indicate CML. Presence of the Philadelphia chromosome is the main indicator of CML.
AML involves hematopoietic stem cells or pluripotent cells.3 These cells lose the ability to differentiate in response to hormonal signals and cellular interactions leading to an accumulation of undifferentiated cells in marrow and or other organs. In the S and M phase of the cell cycle these cells have a decrease portion of blast cells. Due to the decrease the hematopoietic stem cells and pluripotent cells either do not reach maturity or are defective at maturity.
CML is caused by abnormal hematopoietic stem cells that develop daughter cells that have the Philadelphia chromosome.3 An increase in proliferation of granulocytic and megakaryocytic cells occurs because of the abnormal stem cell pool leading to erythropoiesis.
FAB system5
- Early pre-B ALL: Approximately 10 percent of ALL cases
- Common ALL: Approximately 50 percent of cases
- Pre-B ALL: Approximately 10 percent of cases
- Mature B-cell ALL (Burkitt leukemia)
AML stagingThere are three stages of CML.
AML:
CLL:
CML:
- Radiation therapy, chemotherapy, bone marrow transplant
- Several radiation techniques used:
- Total body radiation with total dose 1200 centigray (cGy). 200cGy per fraction, twice a day (BID), for three consecutive days. Used in combination with bone marrow transplant.
- Helmet field may be used to encompass the meninges, total dose 1800cGy, delivered 200cGy per fraction over 9 consecutive days.
- CNS technique is a combination of helmet and spine fields when spinal fluid is positive. Helmet field is treated to 2400cGy with 150cGy per fraction and the spine is treated to 1500cGy at 150cGy per fraction.
- The final treatment technique for ALL is a testis field. The field receives 400cGy for a single fraction and is commonly used with TBI
AML:CLL:
CML:
Bladder: 65 Gray (Gy)
Brain: 45 Gray (Gy)
Colon: 45 Gy
Endocrine glands (Thyroid): 45 Gy
Esophagus: 55 Gy
Heart: 40 Gy
Kidney: 23 Gy
Larynx: 70 Gy
Liver: 30 Gy
Lung: 17.5 Gy for whole lung, 30 Gy for 2/3 of lung, 45 Gy for 1/3 of lung
Lens: 10 Gy
Optic chiasm: 50 Gy
Optic nerve: 50 Gy
Retina: 45 Gy
Rectum: 60 Gy
Salivary glands: 50 Gy
Skin: 55 Gy
Small intestine: 40 Gy
Spinal cord: 45 Gy
Stomach: 50 Gy
Testis: 1 Gy
Ovaries: 2-3 Gy
Reprinted from Principles and Practice of Radiation Oncology, 5th edition.7
The above image is a cranial irradiation field outlining treatment that encompasses the entire cranial subarachnoid space of a leukemia patient. The radio-opaque markers outline the anterior aspect of the bony orbit so as to demarcate inclusion of the posterior aspect of the eye within the treatment fields.7
The following images are for patients treated with total body irradiation:
Reprinted from Radiation Oncology Management Decisions, 3rd edition.1
Reprinted from Radiation Oncology Management Decisions, 3rd edition.1
Reprinted from Radiation Oncology Management Decisions, 3rd edition.1
Reprinted from Radiation Oncology Management Decisions, 3rd edition.1