Stages of Blood Cancer

Executive Summary

The staging system of blood cancer depends on the growth of the abnormal cells in the bloodstream. Different types of blood cancer have different stages, and each stage has its complications. The stages range from stage 0 to stage IV. Acute Lymphocytic Leukemia (ALL) affects kids aged three to five and adults over seventy-five, and it doesn’t form tumors. Its staging is done based on the spread of the disease. B cell staging involves B cell growth and its analysis for the stage. T cell staging is analyzed by estimating the subtypes of the T cells. Acute Myeloid Leukemia(AML) is classified into eight subtypes based on the size, number of healthy cells, number of leukemia cells, changes in chromosomes and genetic abnormalities. Its staging is done through the cellular system. Chronic lymphocytic leukemia (CLL) uses the Rai system and the Binet system (used mainly in the united states of America) to do the staging based on the blood cell count and spreading of cancer through lymph nodes. Chronic Myeloid Leukemia (CML) consist of chronic phase CML, accelerated phase CML and blastic phase CML. The staging of lymphoma in adults ranges from stage 0 to IV. The staging of lymphoma in children also ranges from stage 0 to IV with different staging criteria. The staging of myeloma ranges from stage 0 to III.

Staging System of Blood Cancer

Staging is a process of understanding the severity of cancer, like where it has spread. Different types of blood cancer have different stages, and each stage has its complications. Staging is done after doing a couple of tests on the patient, and usually, it’s as follows for any cancer: 

Stage 0 means there’s zero presence of cancer.

Stage 1 indicates that cancer is minute and hasn’t started spreading 

Stage2 and 3 mean that the cancer is noticeable and has begun spreading to the tissues and lymph nodes 

Stage4 shows that the cancer is spreading to the organs 

Staging is essential because it helps doctors understand cancer, how fast it’s spreading, and what organs it has affected to provide the correct treatment to the patient.

Blood cancer has four stages that give us a clear picture of what’s going on. 

Generally, the 1st stage of blood cancer means physically swollen lymph nodes, which is a sign of many lymphocytes. The risk is shallow in this stage as cancer has not spread to any organs.

2nd stage of blood cancer indicates swollen lymph nodes, liver and spleen, which is a sign of an abnormally large number of lymphocytes. The risk in this stage is that cancer may have spread to the organs. Further testing is required to confirm the situation. 

3rd stage of blood cancer still shows swollen lymph nodes, liver, spleen, and anaemia formation. The risk at this stage is high because cancer has spread to one or many organs.  

4th stage of blood cancer is a high-risk stage. By this stage, the cancer is spread to most organs, and anaemia is acute; cancer cells start affecting the lungs, and the platelet count in the blood decreases rapidly.

The stages mentioned above do not apply to all types of blood cancer. Different types of blood cancer and each has stages. 

Acute Lymphocytic Leukaemia (ALL) and its stages of blood cancer – This is caused due to the excess lymphocytes (white blood cells) in the bone marrow (so it doesn’t form tumors), which crowd the healthy white blood cells. If not treated soon, ALL can spread far too quickly. ALL is generally seen in kids aged three to five and adults over seventy-five. As ALL doesn’t form tumors, the staging is done based on the spread of the disease ​1​. 

B cell staging – these B cells or lymphocytes are produced in the bone marrow and grow there. These cells are responsible for hormonal and immune responses and provide antibodies to fight the diseases. The growth of the B cell is taken into consideration for staging. 

  1. Just about 10 per cent of ALL cases have: Early pre-B ALL 
  2. Almost 50 per cent of the patients have: Common ALL
  3. Approximately 10 per cent of the cases: Pre-B ALL     
  4. Just about 4 per cent of the cases have: Mature B-cell ALL 

T cell staging: T cells or lymphocytes are produced in the bone marrow and left in the thymus where they grow. There are different subtypes of the T cells: Helper, Cytotoxic, memory, regulatory, natural killer, and gamma delta T cells.

  1. Just about 5 to 10 per cent of cases have: Pre T ALL 
  2. Almost 15 to 20 per cent of cases have Mature T cell ALL.

Acute Myeloid Leukemia(AML) – The myeloid cells form white blood cells, Red blood cells and Platelets. People with this condition include far less healthy blood cells of all three types. If not treated, AML can spread quickly. AML is a condition primarily seen in men above the age of 65. Since this condition starts in the bone marrow, instead of using the traditional TNM method, the subtypes of AML are used to stage through a cellular system. Acute myeloid leukemia is classified into eight subtypes based on the size, number of healthy cells, number of leukemia cells, changes in chromosomes and genetic abnormalities ​1​. AML is divided into eight subtypes:

  1. Undifferentiated AML – M0: In this stage of Acute myeloid leukaemia, the cells do not mutate. 
  2. Myeloblastic leukaemia – M1: In this stage, the bone marrow blood cells indicate granulocytic differentiation with or without minimal cell maturation.
  3. Myeloblastic AML – M2: The granulocytic differentiation and maturation are observed in this stage.
  4. Promyelocytic leukaemia – M3: In this stage, most of the bone marrow cells are myelocytes or early stages of granulocytes. These cells contain nucleases with abnormal sizes and shapes. 
  5. Myelomonocytic leukaemia -M4: In this stage, more than 20 per cent of monocytes and promonocytes are found in the bone marrow—both the bone marrow and circulating abnormal blood amounts of monocytes and differentiated granulocytes in them. There is also a chance of increasing the number of granular leukocytes, which frequently have a two-lobed nucleus.
  6. Monocytic leukaemia -M5: This subset is further divided into two. The first category has low monoblasts with frilly appearing genetic material. The second category has vast quantities of monoblasts, promonocytes and monocytes. The monocytes in the bloodstream are higher than those in the bone marrow in this stage.
  7. Erothroleukemia -M6: This stage of Acute myeloid leukaemia has abnormal red blood cells, which make up half the blood cells in the bone marrow. 
  8. Megakaryoblastic leukaemia- M7: The cells at this stage of Acute myeloid leukaemia either become megakaryocytes(giant cells of the bone marrow) or lymphoblasts(lymphocyte forming cells). The megakaryoblastic stage has extensive furious tissue deposits.

Chronic lymphocytic leukaemia (CLL)– Like ALL, this condition starts with the Lymphocytes in the bone marrow. The only difference is that this condition takes time to spread. People suffering from this condition, mostly aged 70 or older, don’t show symptoms for years. This cancer uses the Rai system and the Binet system (used mainly in the united states of America) to do the staging based on the blood cell count and spreading of cancer through lymph nodes ​2​.

The Rai system of staging for Chronic lymphocytic leukemia considers three factors: if the lymph nodes are enlarged, the number of lymphocytes in the blood, and if blood disorders like thrombocytopenia or anemia have developed. A sample of 10,000 lymphocytes is considered too high, and the first stage is called 0. The rai system has five stages 

  1. Stage Rai 0: This has a high level of lymphocytes. Usually, 10,000 per sample and no other symptoms are shown. The cells count of the other blood cells is average. It is a low-risk stage.  
  2. Stage Rai 1: This also has a high level of lymphocytes, and the lymph nodes are enlarged. The cells count of the other blood cells is still average. It is a medium risk stage.
  3. Stage Rai 2: This stage has a high level of lymphocytes, and the liver and spleen may have swollen. It is a medium risk stage. 
  4. Stage Rai 3: This stage has a high level of lymphocytes higher than the red blood cells causing anaemia. The lymph nodes, spleen and liver are still swollen. It is a high-risk stage.
  5. Stage Rai 4: This stage has lower red blood cells and platelets, causing anaemia. The lymph nodes, spleen and liver are still swollen. It is a high-risk stage.

Binet staging system: This system provides information about the areas in which the lymphoid tissues are contacted with cancer.

  1. Clinical stage A– In this stage, the lymph nodes are swollen, and cancer has spread to less than three areas.
  2. Clinical stage B– More than three areas are affected by cancer, and lymphoid tissues are swollen. 
  3. Clinical stage C– Blood disorders like anaemia and thrombocytopenia are developed. 

Chronic Myeloid Leukaemia (CML)- Like AML, this condition starts with Myeloid cells with a slower difference in the spread of the disease. CML is mainly seen in adult men, but children can get it in rare cases. Chronic myeloid leukaemia has three stages:

  1. Chronic phase CML – This is the first stage of the disease, and also most patients get diagnosed during this stage. Patients at this stage show symptoms such as fatigue.
  2. Accelerated phase CML – If the treatment given in the chronic stage does not work and cancer becomes aggressive, which provides us with the accelerated phase. In this stage, the symptoms can be observed.
  3. Blastic phase CML – This is the riskiest stage, with 20 per cent lymphoblasts in the body. The symptoms in this stage are the same as Acute myeloid leukaemia.

Lymphoma: This cancer starts in the lymph system network, including lymph nodes, spleen, and thymus gland. This network of vessels carries white blood cells throughout the system to fight diseases. There are two types of Lymphoma. 

Hodgkin’s Lymphoma: B lymphocytes or B cells are the immune cells that make antibodies to fight off hostile bodies. People with this condition have large lymphocytes called Reed Sternberg cells in their lymph nodes. People suffering from this condition are primarily between 15 to 35 or over 50. 

Non- Hodgkin’s lymphoma-B cells and T cells are the immune cells in this condition. People are more likely to contact Non-Hodgkin’s Lymphoma than Hodgkin’s Lymphoma. People suffering from this condition are primarily between 15 to 35 or over 50.

Staging of Lymphoma:

The exact staging method is used for Hodgkin’s and non-Hodgkin’s Lymphoma in adults. There are four stages of blood cancer. Stages one and two are considered early and stage three and four are considered advanced ​3​.

  • Stage 1– This stage tells us about Lymphoma in the lymph nodes. But only in one place, either above or below the diaphragm.
  • Stage 1E– This means that the Lymphoma spreads to one organ outside the lymphatic system, called extranodal Lymphoma.
  • Stage 2– This means that the Lymphoma is in more than two groups in the lymph nodes. But these should be on the same side, either above the diaphragm or below, to be diagnosed as stage 2. 
  • Stage 2E means that the Lymphoma spreads to an organ outside the lymphatic system and more than two lymphoma groups. All these should be on the same side of the diaphragm.
  • Stage 3– The patient has Lymphoma in the lymph nodes on both sides of the diaphragm. 
  • Stage 4- This is the last stage and the advanced stage. Lymphoma is now spread throughout the lymph nodes and organs outside the lymphatic system.

Staging of Lymphoma in children:

Hodgkin’s Lymphoma is staged the same in adults, but non-Hodgkin lymphoma is staged differently in children and adolescents ​4​.

  • Stage 1– In this stage, one of the following things happens Lymphoma is seen as a group at one part of lymph nodes, with the chest and abdomen as an exception.  

Lymphoma is seen in one organ outside the lymphatic system, with the chest and abdomen as an exception. 

Lymphoma is seen in the spleen or one bone. It is an early stage of Lymphoma.

  • Stage 2– In this stage, one of the following things can happen

Lymphoma is seen as a group at more than two lymph nodes on the same side of the diaphragm. 

Lymphoma can be present in one extranodal organ or the gut. This     

It is an early stage of Lymphoma.

  • Stage 3– In this stage, one of the following things can happen

Lymphoma is found above and below the diaphragm or the gut

Lymphoma can be present in two or more extranodal organs

It is found around the spinal cord or in one bone. It is 

An advanced stage of Lymphoma.

  • Stage 4– In this stage, the advanced stage, Lymphoma can be found in the central nervous system or the bone marrow.

Myeloma:

The bone marrow consists of Plasma cells, a type of blood cell that produces antibodies. Myeloma affects the plasma cells, thus producing antibodies that can’t fight infection and crowd the healthy blood cells. It can damage the bones, and hence it’s also called Multiple Myeloma. People suffering from this condition are mostly men over the age of 50. There are two systems for staging multiple myeloma: The Durie-salmon staging system and the Revised international staging system(RISS) ​5​. RISS is the system that is more recent, advanced and frequently used. This system measures Albumin levels, genetic changes, lactate dehydrogenase(LBH) and Beta-2 microglobulin (B2M) to know cancer and predicts how well the body responds to the treatment. 

  • Stage 1– Albumin, LBH and B2M measure is somewhat normal. If diagnosed, myeloma is treatable at this stage, but the symptoms don’t mainly show due to the nature of the disease.
  • Stage 2– The albumin level is low, and the LBH and B2M are normal or high.
  • Stage 3- The B2M and LDH levels are high, and the DNA of the cells start to change. Patients who are diagnosed at this stage live for about three years.   

These are some of the stages of blood cancer.

References

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    Saultz J, Garzon R. Acute Myeloid Leukemia: A Concise Review. JCM. Published online March 5, 2016:33. doi:10.3390/jcm5030033
  2. 2.
    Zengin N, Kars A, Kansu E, et al. Comparison of Rai and Binet Classifications in Chronic Lymphocytic Leukemia. Hematology. Published online January 1997:125-129. doi:10.1080/10245332.1997.11746327
  3. 3.
    Jaffe ES. Diagnosis and classification of lymphoma: Impact of technical advances. Seminars in Hematology. Published online January 2019:30-36. doi:10.1053/j.seminhematol.2018.05.007
  4. 4.
    Minard-Colin V, Brugières L, Reiter A, et al. Non-Hodgkin Lymphoma in Children and Adolescents: Progress Through Effective Collaboration, Current Knowledge, and Challenges Ahead. JCO. Published online September 20, 2015:2963-2974. doi:10.1200/jco.2014.59.5827
  5. 5.
    Scott EC, Hari P, Kumar S, et al. Staging Systems for Newly Diagnosed Myeloma Patients Undergoing Autologous Hematopoietic Cell Transplantation: The Revised International Staging System Shows the Most Differentiation between Groups. Biology of Blood and Marrow Transplantation. Published online December 2018:2443-2449. doi:10.1016/j.bbmt.2018.08.013