LEUKEMIA

Moore than a disease

Done by:
-Francisco Javier Fuentes Montijano
-Berta Domínguez Hurtado
-Teresa Hernández Iglesias
Group: T-13
LEUKEMIA’S HISTORY

First described this disease was Velpeau in 1827, which saw a 63 year old patient with fever,
weakness and a huge growth of the abdomen. He found at autopsy liver and spleen a huge
(spleen weighed 4 kilos), and "blood was like a porridge consistency and remembered the color
of red wine yeasts" (Velpeau 1827).

Moreover, Barth (1856) studied in 1839 a patient whose blood was analyzed by Donne (1844),
who observed microscopically at autopsy, a "much like mucous cells pus cells. "According
to this sequence, Donne would have been the first person to describe microscopically the
leukemic cells.
Initial studies of patients living with leukemia were made in 1845 by three researchers of the
time: Virchow (1845) in Germany, which called white blood disease and was the first to
propose that the problem was not infectious but a different pathology affecting certain
organs, and Bennett (1845) and Craigie (1845) in Scotland, which also recognized theentity as a
problem of white blood cells. Virchow (1856), who would become one of the great men in
the world condition, introduced two years after the word leukemia, which has lasted until today,
as the name proposed by Bennett leucocitemia (1852) prevailedonly short time. Differed in their
work Virchow leukemia, leukocytosis, while describing two types of leukemia: the spleen
associated with splenomegaly, and lymph, which had enlarged lymph nodes. Years later,
in 1857, there were other new contributions. Friedreich (1857) first described a form
of leukemia called acute, and Neumann (1878) established the existence of myelogenous
leukemia, novel concepts for the time.
It is important to appraise the work of these pioneers in the discovery of leukemia, especially
because scientifically, the classification and study of leukemia could not be
displayed until the stain is met Erlich (1891) in 1891, which allowed the differentiation
different maturational stages of leukocytes and identify the different variants of leukemic
cells. It is also interesting to note that since 1903 the classified into acute leukemia
(lymphocytic, myelocytic, monocytic or erythroleukemia) and chronic (lymphocytic
ormyelogenous) (Schilling-Torgau Reschad and 1913). However, it was not until 1930, when
beginning to take place in Europe bone marrow aspirates, which began to understand better the
morphological alterations of stem cells that produce the disease (Clemmensen 1974).

In the second half of the twentieth century, important advances were made in the treatment of
acute leukemias, which changed in a remarkable way the prevailing concept that the
word leukemia was synonymous with death in the short term. These advances are
currently able to cure almost all children and about a third of adults with the lymphoblastic.
DEFINITION
Leukemia, like other cancers, results from mutations in the DNA. Certain mutations can trigger
leukemia by activating oncogenes or deactivating tumor suppressor genes, and thereby
disrupting the regulation of cell death, differentiation or division. These mutations may occur
spontaneously or as a result of exposure to radiation or carcinogenic substances.
Among adults, the known causes are natural and artificial ionizing radiation, a few viruses such
as Human T-lymphotropic virus, and some chemicals, notably benzene and
alkylating chemotherapy agents for previous malignancies. Use of tobacco is associated with a
small increase in the risk of developing acute myeloid leukemia in adults. Cohort and case-
control studies have linked exposure to some petrochemicals and hair dyes to the development
of some forms of leukemia. A few cases of maternal-fetal transmission have been reported. Diet
has very limited or no effect, although eating more vegetables may confer a small protective
benefit.
Viruses have also been linked to some forms of leukemia. Experiments on mice and other
mammals have demonstrated the relevance of retroviruses in leukemia, and human retroviruses
have also been identified. The first human retrovirus identified was Human T-lymphotropic
virus, or HTLV-1, which is known to cause adult T-cell leukemia.
Some people have a genetic predisposition towards developing leukemia. This predisposition is
demonstrated by family histories and twin studies. The affected people may have a single gene
or multiple genes in common. In some cases, families tend to develop the same kind of
leukemia as other members; in other families, affected people may develop different forms
of leukemia or related blood cancers.

TYPES OF LEUKEMIA

Acute Lymphocytic Leukemia (ALL) - This is the most common type of leukemia
among young children, although adults can get it as well, especially those over the age
of 65.
Chronic Lymphocytic Leukemia (CLL) - This is most common among adults over 55,
although younger adults can get it as well.
Acute Myelogenous Leukemia (AML) - AML is more common among adults than
children, and affects males significantly more often than females
Chronic Myelogenous Leukemia (CML) - The vast majority of patients are adults.

DISEASES RELATED TO LEUKEMIA

The association of Down's syndrome and leukemia has been documented for over 50 years.
Multiple studies have established the incidence of leukemia in Down's syndrome patients to be
10- to 20- fold higher than that in the general population. The age of onset for leukemia in these
children is bimodal, peaking first in the newborn period and again at 3-6 years. This increased
risk extends into adulthood. All cytogenetic types of Down's syndrome apparently predispose to
leukemia. There are case reports in which leukemia, Down's syndrome, and other chromosomal
aberrations cluster within a family. In these kind reds, there may be a familial tendency toward
nondisjunction. Congenital leukemia also occurs with increased frequency in Down's syndrome
patients, and is characterized by a preponderance of acute non lymphoblastic leukemia.
SYMPTOMS OF LEUKEMIA
• Fever, chills and other symptoms similar to those of a flu-like feeling.
• Weakness and fatigue
• Frequent infections
• Loss of appetite and / or weight
• Enlarged lymph nodes, liver or spleen
• Ecchymosis, petechiae and mucosal bleeding.
• Gums swollen or bleeding
• sweating, especially at night
• bone or joint
In acute leukemia, abnormal cells can be grouped into the brain or spinal cord
(collectively the central nervous system or CNS), causing headaches, vomiting, loss of
muscle control, confusion and seizures. If the cells are concentrated in the testicular
areacan cause pain and inflammation. Some patients may experience skin or eye
infiltration.Leukemia can also affect the digestive system, liver, spleen, lungs and other
body parts.
In chronic leukemia, the abnormal blood cells may gradually concentrate in different
parts of the body, such as central nervous system, lymph nodes, liver, spleen,
gastrointestinal tract, skin and testes.

DIAGNOSIS
The elements are used to diagnose bone marrow peripheral blood and lymph nodes.The
technique used is the cytogenetic diagnosis investigating chromosomal alterations
during the controlled phase.The type found in adults in the translocation 9 to 22 and its
exponent Philadelphia chromosome expression of the anomaly in children is
characterized by monosomy of chromosome 7, absent the PH.
Hematological traits investigated in chronic phase adults presenting leukocytosis
constant, the decrease in alkaline phosphatase, and bone marrow fibrosis, being
pathognomonic of blood hiperbasofilia.

The haematological manifestation in children is normoblastemia anemia, increased

Hb.fetal ineffective erythropoiesis in bone marrow megaloblastosis, being the hallmark
pattern of fetal erythropoiesis. Shows reduction of Hb. A2. The clinic is expressed by
progressive malnutrition, increased viseromegalia, and respiratory infections
The advanced stage is characterized by abdominal boluminoso, multiple hemorrhages,
fevers, increased anemia, thrombocytopenia and leukocytosis blastosis (Myeloblastic
myelomonocytic or erythroid leukemia).
In the terminal phase occurs marrow hypoplasia and dissemination of leukemic
infiltrate.

Differential diagnosis.
Sometimes diagnosing CML is sufficient when the patient presents with significant
leukocytosis and significant splenomegaly. But sometimes when the patient has a
moderate leukocytosis is important to make the differential diagnosis of CML with
other myeloproliferative disorders with reactive leukocytes, infection, steroids, with
metastatic tumors in bone marrow, states of shock or acute bleeding and hemolysis
reaction medullary of agranulocytosis.
It is important to note that bone biopsy is used to assess the degree of expansion by
medullary myeloid elements having significant reduction in fat gaps.
TREATMENT
Some CML patients may survive today, in the absence of treatment, from a few months
of diagnosis up to and including 10 years, a situation which indicates the complexity
and uncertainty in the time to predict the lifetime of the patient.
With regard to therapy can be said that progress has been made in the quality of life of
the patient, but regrettably not been able to get a lot of time to prolong the survival of
those affected. The most promising advance in this respect has been the bone marrow
transplant (BMT) as the only potentially curative really matter. However obtain a donor
arises in most cases serious problems because, as is well known, the need to preserve
the antigenic pattern of an individual.
It must be considered the indestructible impulse of those icons of science, we constantly
extend the boundaries of discovery. These exponent, despite the existence of the
transplant does not neglect the patient waiting for a donor, and try to slow the disease
progression refine chemotherapeutic maneuvers.

The preferred chemotherapy is the use of alkylating agents such as busulfan, of course,
under strict medical supervision because of the prolonged action featuring these drugs,
which may include a bone marrow aplasia even if so it may not.These agents what they
do is slow the benign stage disease and lower the astronomical value of the leukocyte
makes approximately 16% of the initial total. The same is true of hydroxyurea used in
the process of metamorphosis.
During the blastic phase of therapeutic the choice is chemotherapy, as in acute
leukemia, 6-mercaptopurine monotherapy. In the statement above is added in a slightly
more recent discovery, and INF is the use as therapeutic alternative.
The results measured are the same as those obtained with hydroxyurea and alkylating
agents, with the difference that the INF in chronic phase, and the combination of
hydroxyurea in INF but the accelerated phase, extending about four times venigna phase
of the disease and leukocyte formula refers to percentage of initial in lower even than
that achieved with alkylating agents and hydroxyurea for themselves. It has even been
observed in some patients, the Ph chromosome negativity.
The negatives of the use of IFN is the depression of the number of platelets with
subsequent thrombocytopenia due to depressing effect on protein synthesis in the CFU-
ME, and the blocking of certain growth factors required for plaquetogenesis. It has also
been reported digestive problems and flu-like paintings, but a smaller percentage than
the last.
Due to the adverse impact of drug therapy patients receive hemotherapeutic support
with red cells and platelets concentrates.
Another measure would consist in the car offensive stem cell transplantation of bone
marrow obtained from the same patient in the chronic state of disease, and preserved in
a suitable medium. From this therapy would involve injecting stem cells after treatment
chemoteherapeutic chronic phase to the point of aplastic anemia, and the intended
purpose would be to recreate a new "CHRONIC PHASE" of the disease outbreak in a
patient blasts.
Death usually occurs as a result of bleeding or infection; sequel to the LMC, either in its
chronic stage or phase of acceleration, and occur more frequently in the disease
progression to blastic phase.