Saturday, November 11, 2017

Leukemia is a Type of Cancer

Leukemia is a Type of Cancer- Previously we had discussed 10 types of cancer. Apparently leukemia is a type of cancer. How is the explanation? Leukemia means “white cells in the blood.” The name comes from the  fact that many (but not all) leukemias, or blood cancers, present  with a high white blood cell count. There are four major types of  leukemias and some rarer ones. The major types are acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), chronic  myelogenous leukemia (CML) and chronic lymphocytic leukemia (CLL).  Acute leukemias (AML and ALL) are defined by the proportion of very  immature cells, called “blasts,” in the bone marrow. When the  proportion of blasts is 20% or more, acute leukemia is considered to  be present. Normal bone marrow has less than 5% blasts. An ALL is a  leukemia made of precursors of lymphocytes. An AML is a leukemia  made of precursors for all other blood cell types and their various  subtypes.

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Although ALL is 10 times more frequent than AML in children, AML is 10 times more frequent than ALL in the elderly. The  prognosis of ALL worsens sharply with age. Although the age effect  in ALL is not entirely understood, one contributing factor is that  ALL in older people is more likely to have unfavorable chromosome  mutations associated with resistance to treatment. Treatment of  leukemia is a lengthy chemotherapy regimen combining multiple agents, usually composed of three phases: (a) an induction  chemotherapy using intensive treatments with substantial side  effects, usually lasting 2 to 3 months, with the goal of inducing a  remission (i.e., no visible leukemia cells); (b) a few months of  consolidation therapy, usually still with an intensive treatment  program, with the goal of reinforcing the remission; and (c) a  period of approximately 2 years with a low-dose maintenance therapy, usually with pills. This combination treatment approach has produced  the best results in children, although bone marrow transplantation  can sometimes produce even higher rates of remission. The data are  less extensive in older adults, but the same strategy is applied by
analogy.
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The treatment of AML is structured similarly to that of ALL. Although  modern consolidation regimens usually relieve the need for a maintenance therapy, there is still some debate on the topic. All  subtypes of AML respond to fairly similar treatments with one  exception. The AML M3, or promyelocytic leukemia, has a chromosome  mutation, [t:15;17], that makes it very sensitive to all-trans-retinoic acid (a drug of the same  family as Accutane). When this drug is added to chemotherapy, this leukemia has a much better rate of cure than do the other AMLs. CML is characterized by a very specific mutation, namely the Philadelphia chromosome. This is an  exchange of a piece of an arm between chromosome 9 and chromosome  22 (called atranslocation, written [t:9;22]).  This joins two genes called bcr and abl. CML goes through three  phases over time: thechronicphase, where the  marrow blast count is normal; theaccelerated  phase, where the blast count is increased but does not reach 20%;  and theblasticphase, where the blast count  transforms into an acute leukemia (either AML or ALL). Bone marrow  transplantation is still the only treatment proven to bring a cure  for CML.

However, bone marrow transplantation is not an option for most older patients because it is a very aggressive form of  treatment with a high risk of serious complications. The rate of complications increases, and the ability to withstand them decreases  with age. Research protocols are exploring less toxic regimens. The  treatment strategy is changing rapidly as a new family of  medications targeting the protein made by the bcr/abl mutation  emerges. The paramount drug in this family is imatinib (Gleevec),  which produces a high percentage of complete remissions. People with  chronic phase CML who experience a complete remission with this drug  have very few progressions over 5 years. However, it is not yet  known what happens beyond that period of time. Responses are also  seen in accelerated and blastic phases, but their duration is short, and combinations with chemotherapy are being explored.

CLL is the most frequent leukemia among older adults. Rather than an  excessive production of cells, it is caused by a failure of old  lymphocytes to die when their time comes. These lymphocytes keep  circulating in the blood, and the white blood cell count rises  slowly. The behavior of CLL is variable. Many patients live several years or even decades with it, but it can sometimes have a more aggressive behavior. Unfortunately, no treatment to date has changed the survival rate of patients with CLL. Because the condition often is not lethal and aggressive treatment has not changed life  expectancy, the goal of treatment is primarily to relieve symptoms  rather than to attempt a cure. Many fairly tolerable drugs are  available: chemotherapy drugs (e.g., chlorambucil, fludarabine) and  antibodies (e.g., rituximab, alemtuzumab). There is considerable debate as to the order and combinations in which to use these drugs, and treatment needs to be tailored individually.

Contributors: Martine Extermann
Edited by: Kyriakos S. Markides
Encyclopedia of Health & Aging


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