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Precursor-Cell Lymphoblastic Leukemia

Pre-ALL

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.

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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.

Easy Bruising
  • Disrupted hematopoiesis leads to the most common presenting symptoms (anemia, infection, easy bruising and bleeding).[web.archive.org]
  • Symptoms of ALL include: Weakness or feeling tired Fever Easy bruising or bleeding Bleeding under the skin Shortness of breath Weight loss or loss of appetite Pain in the bones or stomach Pain or a feeling of fullness below the ribs Painless lumps in[medlineplus.gov]
  • bruising or bleeding Petechiae (flat, pinpoint spots under the skin caused by bleeding) Shortness of breath Weight loss Loss of appetite Bone or joint pain Stomach pain Pain or a feeling of fullness below the ribs Painless lumps in the neck, underarms[uvahealth.com]
Fever
  • Fever is one of the most common symptoms of ALL, and patients with ALL often have fever without any other evidence of infection.[emedicine.medscape.com]
  • A 6-year-old girl presented with pancytopenia, fever, and myelodysplasia. Following transient remission pre-B ALL was diagnosed 14 months later. Clonal B-lineage blasts at the period of pancytopenia were identified retrospectively.[ncbi.nlm.nih.gov]
  • It carries a boxed warning for cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR T-cells causing high fever and flu-like symptoms, and for neurological events.[fda.gov]
Anemia
  • Learn about this topic in these articles: blood disease In blood disease: Leukemia In acute lymphocytic anemia (ALL), most frequently seen in children, the cells are immature forms of the lymphatic series of cells.[britannica.com]
  • Although rarely observed in children affected by acute lymphoblastic leukemia, TTP is a potentially fatal illness that should be considered in the differential diagnosis of thrombocytopenia with hemolytic anemia.[ncbi.nlm.nih.gov]
  • Disrupted hematopoiesis leads to the most common presenting symptoms (anemia, infection, easy bruising and bleeding).[web.archive.org]
Fatigue
  • A 21-year-old woman who presented fatigue had a new diagnosis of acute lymphoblastic leukemia underwent FDG PET/CT. The images demonstrated extramedullary infiltration in multiple organs, including the liver, pancreas, kidney and the bone.[ncbi.nlm.nih.gov]
  • Low levels of other blood cells can cause a variety of symptoms such as bleeding problems, fatigue and shortness of breath. White Blood Cells Copyright Nucleus Medical Media, Inc. Causes The cause of ALL is unknown.[web.archive.org]
  • (including ‘weakness’, ‘fatigue’, ‘weakness/fatigue’), malaise/fatigue (including ‘malaise’ and ‘malaise/fatigue’) and infections (including ‘infection’ and ‘recurrent infections’).[adc.bmj.com]
Weakness
  • She developed VCR toxicity that included tubulopathy, high blood pressure, neuropathic pain, difficulty walking, diffuse muscular weakness, constipation, abdominal pain. There are limited data in children with ALL for posaconazole prophylaxis.[ncbi.nlm.nih.gov]
  • 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[symptoma.com]
Weight Loss
  • These were petechiae/purpura (category derived from ‘petechiae’, ‘purpura’ and ‘petechiae/purpura’), mucosal bleeding (including ‘mucosal bleeding’ and ‘bleeding gums’), anorexia/weight loss (including ‘anorexia’, ‘weight loss’ and ‘anorexia/weight loss[adc.bmj.com]
  • The B symptoms, such as fever, night sweats, and weight loss, are frequent. White blood cell (WBC) count at presentation varies widely, and circulating blasts are generally noted.[accessmedicine.mhmedical.com]
  • Weight Loss Surgery is a Big Decision Our specialists provide the expertise and support you need to reach your weight loss goals.[uhhospitals.org]
  • Symptoms of ALL include: Weakness or feeling tired Fever Easy bruising or bleeding Bleeding under the skin Shortness of breath Weight loss or loss of appetite Pain in the bones or stomach Pain or a feeling of fullness below the ribs Painless lumps in[medlineplus.gov]
Splenomegaly
  • Splenomegaly and thrombocytopenia were frequently observed more in CD200 patients. Increased frequency of CD34 was associated with CD200 and CD56 patients.[ncbi.nlm.nih.gov]
  • Five features were present in 50% of children: hepatomegaly (64%), splenomegaly (61%), pallor (54%), fever (53%) and bruising (52%).[adc.bmj.com]
  • […] lymphoblasts Many myeloblasts Small lymphocytes Entire myeloid series Anemia Severe in 90% Severe in 90% Mild in about 50% Mild in 80% Platelets Low in 80% Low in 90% Low in 20 to 30% High in 60% Low in 10% Lymphadenopathy Common Occasional Common Infrequent Splenomegaly[merckmanuals.com]
  • CT, MRI, or abdominal ultrasonography may help assess splenomegaly or leukemic infiltration of other organs. Prognosis Cure is a realistic goal for both ALL and AML, especially in younger patients.[web.archive.org]
Dyspnea
  • CASE REPORT A 20-year-old man began to experience cough, chest pain, and mild exertional dyspnea. He was admitted to the hospital at 23 years of age with respiratory failure. Chest imaging showed pleural thickening and platythorax.[ncbi.nlm.nih.gov]
  • Symptoms of anemia are common and include fatigue, dizziness, palpitations, and dyspnea upon even mild exertion. Other patients present with signs of bleeding. Bleeding can be the result of thrombocytopenia due to marrow replacement.[emedicine.medscape.com]
  • […] day for the remaining 3 weeks of cycle 1 and for subsequent cycles (up to five cycles total) [35, 36] Supportive care Leukapheresis : Patients with a markedly elevated WBC count, especially 100,000/mm 3, are at risk for leukostasis Symptoms include dyspnea[web.archive.org]
Cough
  • CASE REPORT A 20-year-old man began to experience cough, chest pain, and mild exertional dyspnea. He was admitted to the hospital at 23 years of age with respiratory failure. Chest imaging showed pleural thickening and platythorax.[ncbi.nlm.nih.gov]
  • Wheezing, coughing and/or painful breathing requires immediate medical attention. ALL can cause a variety of symptoms in children based on their age and their disease type.[danafarberbostonchildrens.org]
  • Any wheezing, coughing and/or labored or painful breathing requires immediate medical attention.[chop.edu]
Loss of Appetite
  • Symptoms of ALL include: Weakness or feeling tired Fever Easy bruising or bleeding Bleeding under the skin Shortness of breath Weight loss or loss of appetite Pain in the bones or stomach Pain or a feeling of fullness below the ribs Painless lumps in[medlineplus.gov]
  • […] of appetite Enlarged lymph nodes The signs and symptoms of ALL can be the same as more common children’s illnesses and some children are treated for those other illnesses before leukemia is diagnosed.[curesearch.org]
  • […] of appetite Bone or joint pain Stomach pain Pain or a feeling of fullness below the ribs Painless lumps in the neck, underarms, stomach, or groin Swelling of the liver and/or spleen Diagnosis Your doctor will ask about your symptoms and medical history[web.archive.org]
  • […] of appetite Bone or joint pain Stomach pain Pain or a feeling of fullness below the ribs Painless lumps in the neck, underarms, stomach, or groin Swelling of the liver and/or spleen Diagnosis Your doctor will check for swelling of the liver, spleen or[uvahealth.com]
Vomiting
  • We report a case of a 3 years old boy who presented with prolonged fever, nausea, vomiting and increasing lower limbs pain. Skeletal X-rays and CT scan showed severe osteolytic lesions of the skull and extremities.[ncbi.nlm.nih.gov]
  • They include: nausea vomiting swelling in the face and lower legs muscle cramps rash diarrhoea Depending on how well you respond to treatment, the induction phase can last from two weeks to several months.[hse.ie]
  • Acute lymphocytic leukemia symptoms ALL symptoms are often similar to those of the flu and can include the following: Fever Weakness Fatigue Headaches Loss of appetite Pale skin Vomiting Body aches Other potential signs and symptoms of ALL may include[cancercenter.com]
  • If this happens, the patient may have neurological symptoms, such as dizziness, vomiting, blurred vision, fits (seizures), and headaches. Causes and risk factors The causes of ALL are mostly not yet known, but there are some common risk factors.[medicalnewstoday.com]
Bleeding Gums
  • gums Frequent infections Nosebleeds Easy bruising Swollen lymph nodes around the neck, underarm, stomach or groin Shortness of breath Weight loss Acute lymphocytic leukemia treatment options Treatment for ALL may include chemotherapy, chemotherapy with[cancercenter.com]
  • Symptoms include: Bone and joint pain Easy bruising and bleeding (such as bleeding gums, skin bleeding, nosebleeds, abnormal periods) Feeling weak or tired Fever Loss of appetite and weight loss Paleness Pain or feeling of fullness below the ribs from[medlineplus.gov]
  • Signs and symptoms may include: excessive sweating fatigue frequent unexplained bleeding, such as nosebleeds or bleeding gums high fever painful joints and/or bones panting several infections over a short period swollen glands (lymph nodes) swollen liver[medicalnewstoday.com]
Hepatosplenomegaly
  • Massive hepatosplenomegaly as a presentation of ALL has not been described previously in any patient population.[ncbi.nlm.nih.gov]
  • Lymphadenopathy and hepatosplenomegaly, although rarely symptomatic, are noted in approximately 20% of patients ( 9 ).[accessmedicine.mhmedical.com]
  • The most frequent signs are lymphadenopathies, hepatosplenomegaly, fever, signs of haemorrhage, and bone pain.[orpha.net]
Hepatomegaly
  • We emphasize the importance of being aware of this condition when a patient with ALL in complete remission presents with unexplained hepatomegaly, cytopenia, and fever. Early diagnosis and treatment may be lifesaving.[ncbi.nlm.nih.gov]
  • Five features were present in 50% of children: hepatomegaly (64%), splenomegaly (61%), pallor (54%), fever (53%) and bruising (52%).[adc.bmj.com]
  • Extramedullary infiltration by leukemic cells may cause lymphadenopathy, splenomegaly, hepatomegaly, and leukemia cutis (a raised, nonpruritic rash). Gum hyperplasia may be prominent, particularly in AML.[web.archive.org]
  • Bone pain/tenderness, hepatomegaly, and splenomegaly may be present. About 7% of children have CNS involvement at the time of diagnosis.[lecturio.com]
Palpitations
  • Symptoms of anemia are common and include fatigue, dizziness, palpitations, and dyspnea upon even mild exertion. Other patients present with signs of bleeding. Bleeding can be the result of thrombocytopenia due to marrow replacement.[emedicine.medscape.com]
  • Symptoms Fatigue, dizziness and palpitations. Severe and unusual bone and joint pain. Recurrent and severe infections (oral, throat, skin, perianal infections commonly). Fever without obvious infection (but infection should be assumed).[patient.info]
  • Signs and symptoms Signs and symptoms of ALL include the following: Fever Signs and symptoms of anemia, such as pallor, fatigue, dizziness, palpitations, cardiac flow murmur, and dyspnea with even mild exertion Bleeding Blood clots Palpable lymphadenopathy[emedicine.com]
Tachycardia
  • Other presenting symptoms and signs are usually nonspecific (eg, pallor, fatigue, fever, malaise, weight loss, tachycardia, chest pain) and are attributable to anemia and a hypermetabolic state.[web.archive.org]
  • The pallor, shortness of breath, tachycardia, and fatigue are due to anemia. Image : “Immature Large Blast Cells in Acute Lymphoblastic Leukemia.” by VashiDonsk.[lecturio.com]
  • Tachycardia and a flow murmur. Nonspecific signs of infection. Petechiae (due to thrombocytopenia), may progress into purpura or ecchymoses. Abdominal distention due to hepatomegaly and splenomegaly. Lymphadenopathy. Testicular enlargement.[patient.info]
  • The initial presentation includes manifestations of the underlying anemia – pallor, fatigue, exercise intolerance, tachycardia, dyspnea, and sometimes congestive heart failure; thrombocytopenia – petechiae, purpura, easy bruising, bleeding from mucous[intechopen.com]
Chest Pain
  • CASE REPORT A 20-year-old man began to experience cough, chest pain, and mild exertional dyspnea. He was admitted to the hospital at 23 years of age with respiratory failure. Chest imaging showed pleural thickening and platythorax.[ncbi.nlm.nih.gov]
  • Other symptoms may include swollen lymph nodes (glands), chest pain and abdominal discomfort due to a swollen spleen or liver. Occasionally people have no symptoms and ALL is diagnosed during a routine blood test.[leukaemia.org.au]
  • Other presenting symptoms and signs are usually nonspecific (eg, pallor, fatigue, fever, malaise, weight loss, tachycardia, chest pain) and are attributable to anemia and a hypermetabolic state.[web.archive.org]
Heart Failure
  • failure more frequently in older patients than in young adults.[hematologyandoncology.net]
  • The anthracycline-induced cardiomyopathy is a progressive disorder that manifests with signs of congestive heart failure. Rapid progression of symptoms may occur with pregnancy, anesthesia, or exercise [ 177 , 178 ].[intechopen.com]
Petechiae
  • Where considered clinically appropriate, features that the authors considered similar were aggregated (eg, ‘petechiae’, ‘purpura’ and ‘petechiae/purpura’ were combined into a single category, ‘petechiae/purpura’).[adc.bmj.com]
  • Exposure to x-rays before birth Exposure to radiation, including X-rays and CT scans Previous chemotherapy or other treatment that weakens the immune system Symptoms ALL may cause: Weakness Fatigue Fever Pale skin Night sweats Easy bruising or bleeding Petechiae[web.archive.org]
  • […] including X-rays and CT scans Previous chemotherapy or other treatment that weakens the immune system Symptoms of ALL You should see a doctor if you or your child is experiencing: Weakness Tiredness Fever Pale skin Night sweats Easy bruising or bleeding Petechiae[uvahealth.com]
  • 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[symptoma.com]
Night Sweats
  • The B symptoms, such as fever, night sweats, and weight loss, are frequent. White blood cell (WBC) count at presentation varies widely, and circulating blasts are generally noted.[accessmedicine.mhmedical.com]
  • ALL symptoms include: Weakness or feeling tired Fever or night sweats Shortness of breath Unusual bleeding or bruising Unexplained loss of appetite or weight loss Night sweats Bone or stomach pain Frequent infections Tiny, dark red spots under the skin[cancer.osu.edu]
  • sweats Easy bruising or bleeding Petechiae (flat, pinpoint spots under the skin caused by bleeding) Shortness of breath Weight loss Loss of appetite Bone or joint pain Stomach pain Pain or a feeling of fullness below the ribs Painless lumps in the neck[web.archive.org]
  • sweats These symptoms can occur with other conditions.[medlineplus.gov]
Purpura
  • Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy caused by deficiency of von Willebrand factor-cleaving protease ADAMTS13.[ncbi.nlm.nih.gov]
  • Where considered clinically appropriate, features that the authors considered similar were aggregated (eg, ‘petechiae’, ‘purpura’ and ‘petechiae/purpura’ were combined into a single category, ‘petechiae/purpura’).[adc.bmj.com]
  • […] bleeding gums or nosebleeds high temperature (fever) of 38C (100.4F) or above night sweats bone and joint pain easily bruised skin swollen lymph nodes (glands) abdominal pain – caused by a swollen liver or spleen unexplained weight loss a purple skin rash (purpura[nhs.uk]
Bone Pain
  • CASE OUTLINE: We report a 28-year-old male with the B-cell ALL who presented with extensive osteolytic lesions, bone pain, hepatosplenomegaly, and pancytopenia without circulating blasts in peripheral blood.[ncbi.nlm.nih.gov]
  • The most frequent signs are lymphadenopathies, hepatosplenomegaly, fever, signs of haemorrhage, and bone pain.[orpha.net]
  • Normally, these cells are relatively rare, but in ALL, they continuously multiply and are overproduced by the bone marrow, causing fatigue, anemia, fever, and bone pain due to the spread of these cells into the bone and joint surfaces.[medcell.med.yale.edu]
  • pain, sometimes associated with swelling of the joints The signs and symptoms of ALL can be the same as more common children’s illnesses and many children are treated for those other illnesses before leukemia is diagnosed.[childrensoncologygroup.org]
Myalgia
  • Her fever was of unknown origin but was suspected to be due to the cytokine-release syndrome ( Figure 1B ); she also had myalgias and 2 days of confusion (grade 3), all of which spontaneously resolved.[doi.org]
Arthralgia
  • Bone pain, arthralgia, and/or arthritis may manifest as decreased activity, general fussiness, irritability, or refusal to walk.[clinicaladvisor.com]
Epistaxis
  • A 30-year-old pregnant woman presented at 16 weeks' gestation with epistaxis, jaundice, diffuse abdominal pain and distension, massive hepatosplenomegaly and peripheral oedema.[ncbi.nlm.nih.gov]
  • Bleeding is usually manifested by petechiae, easy bruising, epistaxis, bleeding gums, or menstrual irregularity. Hematuria and GI bleeding are uncommon.[web.archive.org]
  • Epistaxis, menorrhagia and gingival bleeding may also occur. The pallor, shortness of breath, tachycardia, and fatigue are due to anemia. Image : “Immature Large Blast Cells in Acute Lymphoblastic Leukemia.” by VashiDonsk.[lecturio.com]
Headache
  • Following hospital admission, the patient initially presented with headache-caused nocturnal awakenings, evening fever, and cough, and he also lost approximately 7 kg in weight in a month not associated with sweating or itching.[ncbi.nlm.nih.gov]
  • Acute lymphocytic leukemia symptoms ALL symptoms are often similar to those of the flu and can include the following: Fever Weakness Fatigue Headaches Loss of appetite Pale skin Vomiting Body aches Other potential signs and symptoms of ALL may include[cancercenter.com]
  • […] do their jobs cause the symptoms that people have as the leukemic cells invade: fatigue, significant bruising (not just a few bumps and bruises on the shins), fever, significant swollen lymph nodes throughout the body, and less commonly bone pain or headache[hollywoodlife.com]
  • You should see your pediatrician if your child has any of the following: Unexplained fever and headaches Enlarged lymph nodes in the neck, arm pits, or groin Pain in the arms, legs, or back Easy bruising and bleeding Tiny red spots in the skin Fatigue[childrensnational.org]
  • If this happens, the patient may have neurological symptoms, such as dizziness, vomiting, blurred vision, fits (seizures), and headaches. Causes and risk factors The causes of ALL are mostly not yet known, but there are some common risk factors.[medicalnewstoday.com]
Confusion
  • Some patients present with leukostasis and clinical symptoms of impaired circulation such as a headache, confusion and respiratory distress.[lecturio.com]
  • Her fever was of unknown origin but was suspected to be due to the cytokine-release syndrome ( Figure 1B ); she also had myalgias and 2 days of confusion (grade 3), all of which spontaneously resolved.[doi.org]
  • Tremor, headache, and other mental status changes (eg, confusion) have been reported.[bloodjournal.org]
  • Children often have a more aggressive and dramatic presentation that may result in extreme pain in the extremities and joints and can be confused with arthritis.[cancertherapyadvisor.com]
  • Diagnostic confusion with AML, hairy cell leukemia, and malignant lymphoma is not uncommon. Proper diagnosis is crucial because of the difference in prognosis and treatment of ALL and AML.[cancer.gov]
Intracranial Hemorrhage
  • Terson syndrome, in which intraocular hemorrhage is associated with intracranial hemorrhage, is more commonly reported in adults, although ocular manifestations of leukemia have been reported at presentation and are typically asymptomatic.[ncbi.nlm.nih.gov]

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].

Mediastinal Mass
  • A chest radiograph shows normal results with no mediastinal mass or pulmonary infiltrate.[doi.org]
  • Lastly, stridor is an alarming symptom that should indicate a possible mediastinal mass, which, in turn, may threaten the respiratory function.[symptoma.com]
  • In T-cell ALL, a chest X-ray may sometimes show mediastinal widening or mediastinal mass .[lecturio.com]
  • Radiology CXR may show pneumonia, a mediastinal mass or lytic bone lesions. Testicular ultrasound if the testes are enlarged on examination.[patient.info]
Decreased Platelet Count
  • After 16 months, the results of routine blood tests showed reduced hemoglobin levels and decreased platelet counts. In addition, blast-like cells were found in a peripheral blood smear.[ncbi.nlm.nih.gov]
  • The bleeding in ALL is due to decreased platelet counts and occurs in the skin and mucosal surfaces, manifesting as purpura and ecchymosis . Epistaxis, menorrhagia and gingival bleeding may also occur.[lecturio.com]
Thrombocytosis
  • Myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis The criteria for MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T; previously known as RARS-T) include thrombocytosis ( 450 10 9 /L) associated with refractory[doi.org]

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.

References

Article

  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.

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Last updated: 2019-07-11 20:19