Acute Lymphoblastic Leukemia (ALL)

Acute leukemia-ALL[1]

Acute lymphocytic leukemia (ALL), otherwise referred to as acute lymphoblastic leukemia or acute lymphoid leukemia, is a hematopoietic malignancy that involves the overproduction of cancerous white blood cells in the bone marrow.

Acute Lymphoblastic Leukemia emerges due to the following process: neoplastic.

Presentation

Acute lymphoblastic leukemia is a type of malignancy that most commonly affects children. The cancerous cells can either be found in the bone marrow itself, thus disrupting the process of blood cell production and maturation, or in other extramedullary organs.

The immature white blood cells that are produced by the diseased bone marrow initially replace the organ; as a result, it fails to produce the rest of the cellular lines, such as erythrocytes and platelets. Due to the pancytopenia that exists, patients can present with a multitude of symptoms. Specifically, a diminished erythrocyte count leads to anemia, pallor, weakness and fatigue, reduced platelets induce hemorrhagic events such as petechiae or active hemorrhage and the immature white blood cells cause an inadequate immune response to any infection. Although the patient is vulnerable to various microorganisms, they rarely exhibit septic phenomena. Many times, patients report a history of skeletal pain, arthritis and limping as the sole symptoms; as a result, diagnosis may be delayed [8]. Hepatosplenomegaly, fever and lymphadenopathy are also frequently observed.

In addition to the aforementioned symptoms, some types of ALL may lead to the development of masses outside of the borders of the bone marrow. The central nervous system, head and neck are the most common locations for these growths. The infiltration of the central nervous system may lead to papilledema, palsies of the cranial nerves, lethargy or nuchal rigidity; these symptoms rarely constitute the clinical manifestations at the time that ALL is originally diagnosed [9]. Another symptom that may raise suspicion of ALL is testicular edema in male patients that is not accompanied by pain.

Lastly, stridor is an alarming symptom that should indicate a possible mediastinal mass, which, in turn, may threaten the respiratory function. Corticosteroids should promptly be administered in order to prevent respiratory failure and close monitoring is also considered mandatory.

Workup

The first step towards diagnosing acute lymphocytic leukemia includes blood tests. Laboratory tests are expected to reveal anemia and thrombocytopenia, alongside leukocytosis. Lymphoblasts may also be present. A bone marrow biopsy is also required in order for the diagnosis of ALL to be definitive: the bone marrow is aspirated and biopsized, in order to detect an infiltration by precursor cells and to differentiate between a T or B type leukemia.

Furthermore, imaging modalities can illustrate the extent of the malignancy. Plain radiographs or a computerized tomography scan can be used to eliminate or confirm suspicion that the disease has disseminated to the brain or spinal cord. Finally, a lumbar puncture can also detect cancerous precursor cells within the cerebrospinal fluid.

As soon as the diagnosis of ALL is established, HLA-typing is promptly carried out [10] [11].

Treatment

Acute lymphocytic leukemia is a type of malignancy that may affect various organs and is treated pharmacologically, by administrating chemotherapy.

Treatment is individualized depending on the type of all. In general, every therapeutic plan centers around three basic treatment stages:

  • Remission-induction phase
  • Intensification phase
  • Continuation therapy, reserved for those patients who exhibit residual disease

T-cell acute lymphocytic leukemia is treated with the addition of asparaginase and cyclophosphamide and mature B-cell acute leukemia requires a brief but intensive period of chemotherapy with additional methotrexate, cytarabine and cyclophosphamide.

Prognosis

Acute lymphocytic leukemia is considered a curable malignancy, with survival rates being exceptionally high during the past years. Although it progresses rapidly and will threaten the life of the patient, if left untreated, proper therapeutic actions are promising and generally effective.

Specifically, prognosis depends on a number of factors. Pediatric patients exhibit a greater recovery rate in comparison to adult individuals; amongst the adult group, patients that are diagnosed with ALL before the age of 50 also display a better prognosis. Studies have delineated that the remission rate for patients below the age of 30 is 90%, for patients between the ages of 30 and 60 the rate decreases to 80% and reaches its lowest number, 52%, when referring to patients who are older than 60 years of age [7].

Furthermore, patients who have a white blood cell count greater than 50,000 at the time of diagnosis are expected to respond better to treatment. The extent of the disease, including infiltration of other organs, involvement of the central nervous system etc, also affects prognosis in a negative way.

The exact subtype of ALL also makes a difference in the prognosis: patients with a T-cell acute lymphocytic leukemia recover at a bigger rate, compared to individuals with B-cell ALL. Additionally, individuals whose cancer evinces complete remission during the first 5 weeks since the initiation of treatment are seen in a more positive light, in contradistinction to patients whose remission requires longer periods of time or is never achieved.

Etiology

The exact etiologic mechanisms that underlie ALL have yet to be firmly established. There have been, however, observations that lead to the illustration of various factors that are believed to play a role in the causes.

A genetic background has been proposed, especially due to the 25% possibility of a monozygotic twin to develop the disease, once its sibling is diagnosed with it. ALL has been linked to various other pathologies, such as trisomy 21, Bloom syndrome, Klinefelter syndrome and others [1] [2] [3]. Furthermore, the exposure to radiation or energy from a nuclear explosion, the use of tobacco products and hair dyes, as well as jobs related to electricity are all believed to contribute to the onset of acute lymphocytic leukemia [4].

It is also believed that viruses can lead to the development of such a malignancy, even though this hypothesis has not been substantiated scientifically. Various polymorphisms in the metabolism of folate is another potential etiologic factor [5].

Epidemiology

Although ALL can be diagnosed in patients of all ages, children between the age of 0 to 14 are the ones most commonly affected by it. In fact, this type of cancer has been estimated to display a yearly incidence of approximately 4 cases per 100,000 children in the aforementioned age group [6]. This particular incidence is considered to be an average worldwide estimation.

The disease exhibits a predilection for Caucasian male individuals and its frequency peak is between 2 and 5 years old.

Sex distribution
Age distribution

Pathophysiology

Acute lymphocytic leukemia is a malignancy of the hematopoietic system, namely the bone marrow and, subsequently, of the blood. The bone marrow is a vital organ responsible for the production and maturation of all the lines of the blood's components: erythrocytes, white blood cells and platelets.

The bone marrow produces all three types of cells; after a differentiation process is completed within the organ, it releases mature cells in the circulation. In the case of ALL normal white blood cells fail to differentiate properly and immature precursor cells are released into the circulation. This developmental arrest in the life cycle of leukocytes implies that the immune system does not possess cells that are mature enough to fight infection and the patient is therefore severely immunocompromised. Furthermore, the precursor cells known as lymphoblasts infiltrate the bone marrow to such a degree that they replace the organ's elements and, as a result, it is incapable of producing red cells and platelets as well.

Prevention

The exact etiologic factors that underlie acute lymphocytic leukemia have not yet been clarified; it is therefore not possible to provide any strategic plan concerning its avoidance.

Summary

Acute lymphocytic leukemia (ALL) is a malignancy of the bone marrow. It affects the leukocytes, which are produced from the precursor cells, but fail to differentiate into mature white cells, because of an early arrest in their development.

The malignancy is defined as acute, due to the fact that it progresses quickly and, if left without the administration of the proper chemotherapeutic agents, it may threaten the life of the patient. Children are more commonly affected by this type of cancer than adults: a young age is amongst the positive prognostic factors with regard to the efficacy of the treatment.

The causes of acute lymphocytic leukemia are still not definitively established, although a certain genetic substrate has been proposed. Other factors that potentially contribute to the onset of the disease include exposure to chemicals, smoking and folate metabolism disruption.

ALL is diagnosed via a complete blood count and a bone marrow biopsy to definitively confirm the diagnosis. A plain radiograph or magnetic resonance imaging scan can be used to detect sites of potential dissemination, which are usually found in the brain or spinal cord. It is treated with chemotherapy and prognosis is generally positive.

Patient Information

Acute lymphocytic leukemia (ALL) is a type of cancer that affects the bone marrow, and, subsequently, the blood. It can occur at any age, but children are most commonly affected by it.

The bone marrow is a vital organ, that is responsible for the production and maturation of all of the cellular components of the blood: red blood cells, white blood cells and platelets. In cases of ALL, the white blood cells do not develop properly and experience a very early arrest in their maturation process. As a result, they are released into the circulation at an earlier developmental stage and are too immature to fight infections and diseases. Moreover, these immature cells, called lymphoblasts, progressively replace the material that the bone marrow is made of and lead to a decreased production of red blood cells and platelets as well.

Patients with ALL present with a variety of symptoms. Decreased concentrations of red blood cells lead to anemia, fatigue and weakness; less platelets imply a tendency towards hemorrhaging and the presence of immature white blood cells leads to the inability of the organism to protect itself against infections.

Acute lymphocytic leukemia is diagnosed with a complete blood count and a bone marrow biopsy. Radiologic evaluation is necessary to find out whether the malignant cells have infiltrated the brain or spinal cord. The condition is treated with chemotherapy.

Self-assessment

References

  1. De Keersmaecker K, Marynen P, Cools J. Genetic insights in the pathogenesis of T-cell acute lymphoblastic leukemia. Haematologica. 2005; 90:1116-1127.
  2. Machatschek JN, Schrauder A, Helm F, et al. Acute lymphoblastic leukemia and Klinefelter syndrome in children: two cases and review of the literature. Pediatr Hematol Oncol. 2004; 21:621-626.
  3. Greaves MF, Maia AT, Wiemels JL, et al. Leukemia in twins: lessons in natural history. Blood. 2003; 102:2321-2333.
  4. Snyder DS, Stein AS, O'Donnell MR, et al. Philadelphia chromosome-positive acute lymphoblastic leukemia secondary to chemoradiotherapy for Ewing sarcoma. Report of two cases and concise review of the literature. Am J Hematol. 2005; 78:74-78.
  5. Koppen IJ, Hermans FJ, Kaspers GJ. Folate related gene polymorphisms and susceptibility to develop childhood acute lymphoblastic leukaemia. Br J Haematol. 2010; 148:3-14.
  6. Ribera JM, Oriol A. Acute lymphoblastic leukemia in adolescents and young adults. Hematol Oncol Clin North Am. 2009 Oct; 23(5):1033-42, vi. 
  7. Larson RA. Acute lymphoblastic leukemia: older patients and newer drugs. Hematology Am Soc Hematol Educ Program. 2005; 131-136.
  8. Muwakkit S, Al-Aridi C, Samra A, et al. Implementation of an intensive risk-stratified treatment protocol for children and adolescents with acute lymphoblastic leukemia in Lebanon. Am J Hematol. 2012 Jul; 87(7):678-83.
  9. Pui CH, Robison LL, Look AT. Acute lymphoblastic leukaemia. Lancet. 2008 Mar 22; 371(9617):1030-43.
  10. Hoelzer D, Gökbuget N, Ottmann O, et al. Acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program. 2002:162-192.
  11. Jabbour EJ, Faderl S, Kantarjian HM. Adult acute lymphoblastic leukemia. Mayo Clin Proc. 2005; 80:1517-1527.

  • Morphology using in situ hybridization: an analysis of suspicious cells in bone marrow specimens of two patients completing therapy for acute lymphoblastic leukemia - J Anastasi, JW Vardiman, R Rudinsky - , 1991 - bloodjournal.hematologylibrary.org
  • A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811 - RA Larson, RK Dodge, CP Burns, EJ Lee - , 1995 - bloodjournal.hematologylibrary.org


Media References

  1. Acute leukemia-ALL, CC BY-SA 3.0
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