Cancer, Acute Lymphocytic Leukemia (ALL)


Article Author:
Yana Puckett


Article Editor:
Onyee Chan


Editors In Chief:
Rhonda Coffman
Lindsay Iverson
Heather Templin


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
3/31/2019 10:28:49 PM

Introduction

Acute Lymphocytic Leukemia (ALL) is a malignancy of B or T lymphoblasts characterized by uncontrolled proliferation of abnormal, immature lymphocytes and their progenitors which ultimately leads to the replacement of bone marrow elements and other lymphoid organs resulting in a typical disease pattern characteristic of Acute Lymphocytic Leukemia. ALL accounts for approximately 2 percent of the lymphoid neoplasms diagnosed in the United States. Acute Lymphocytic Leukemia occurs slightly more frequently in males than females, and three times as frequently in Whites as in Blacks. Patients with Acute Lymphocytic Leukemia typically present with symptoms related to anemia, thrombocytopenia, and neutropenia due to the replacement of the bone marrow with tumor. Symptoms can include fatigue, easy or spontaneous bruising/bleeding, and infections. B-symptoms, such as fever, night sweats, and unintentional weight loss are often present, but may be mild. Hepatomegaly, splenomegaly, and lymphadenopathy can be seen in up to half of adults on presentation. Central nervous system (CNS) involvement is common and can be accompanied by cranial neuropathies or symptoms, predominantly meningeal, related to increased intracranial pressure.[1][2][3]

Etiology

The etiology of Acute Lymphocytic Leukemia is unknown. However, certain environmental factors have been implicated in the etiology of Acute Lymphocytic Leukemia such as exposure to benzene, ionizing radiation, or previous exposure to chemotherapy or radiotherapy.

Genomic studies have noted that somatic, polymorphic variants of ARD5B, IKZF1 (the gene encoding Ikaros) and CDKN2A are associated with an increased risk of ALL (odds ratio 1.3 to 1.9). Other rare germline mutations in PAX5, ETV6, and particularly p53 can also strongly predispose to the development of leukemia.

Acute lymphoblastic Leukemia is not considered a familial disease and no screening programs have been developed to test for it in childhood. 

Epidemiology

It is diagnosed in about 4000 people in the United States each year with the majority being under the age of 18. It is the most common malignancy of childhood. The peak age of diagnosis is between two and ten years of age. Acute Lymphocytic Leukemia is more common in children with Trisomy 21 (Down syndrome), neurofibromatosis type 1, Bloom syndrome, and ataxia telangiectasia. All are common in children between two and three years of age. Prognosis is diminished in children when diagnosed in infants less than one year of age and in adults. It is more favorable in children. Association of the MLL gene in children at 11q23 chromosome is associated with poor prognosis. Acute Lymphocytic Leukemia is a disease with low incidence overall in population studies. The incidence of Acute Lymphocytic Leukemia is about 3.3 cases per 100,000 children. Survival rates for ALL have improved dramatically since the 1980s, with a current five-year overall survival rate estimated at greater than 85 percent.

Pathophysiology

Acute Lymphocytic Leukemia is thought to occur after damage to DNA causes lymphoid cells to undergo uncontrolled growth and spread throughout the body. Splenomegaly and hepatomegaly occur due to sequestration of platelets and lymphocytes in the spleen and liver as the white blood cells are not typical the spleen reacts to them by trying to remove them from the blood. [4][5][6]

Histopathology

On peripheral blood smears of Acute Lymphocytic Leukemia patients, lymphoblasts vary in size. Various CD cytokines must be tested to evaluate for what kind of Acute Lymphocytic Leukemia the patient has.

History and Physical

The most common presenting symptoms of Acute Lymphocytic Leukemia are nonspecific and may be difficult to distinguish from common, self-limited diseases of childhood. In a meta-analysis, more than half of children with childhood leukemia had at least one of the following five features on presentation: palpable liver, palpable spleen, pallor, fever, or bruising. ALL patients typically present with symptoms of night sweats, easy bruising, skin pallor, unexplained lymphadenopathy, weakness, weight loss, hepatosplenomegaly, or difficulty breathing. Some patients may present with Superior Vena Cava Syndrome. Bone pain, mental changes, and oliguria may also be present. ALL can also present with testicular enlargement, musculoskeletal pain, mediastinal mass, and incidentally found peripheral blood cell abnormalities. 

Evaluation

Acute Lymphocytic Leukemia diagnosis should be explored initially with a laboratory evaluation consisting of a CBC, electrolyte and renal panel, LDH level. Additionally, imaging such as a chest x-ray for symptoms of shortness of breath may be obtained. If abdominal fullness, tenderness or abdominal mass are symptoms, then a CT scan of the abdomen and pelvis should be obtained. This can also help with staging of the disease.

Treatment / Management

Children who are suspected of having Acute Lymphocytic Leukemia should be referred to a pediatric center that specializes in cancer for evaluation and treatment. For children with Acute Lymphocytic Leukemia, induction therapy consists of anthracycline, vincristine, 1-asparaginase, and a corticosteroid. Maintenance therapy utilizes oral 6-mercaptopurine or methotrexate delivered once weekly or once monthly.  Successful treatment of children with Acute Lymphocytic Leukemia involves administration of a multidrug regimen that is divided into several phases (i.e., induction, consolidation, and maintenance) and includes therapy directed to the central nervous system (CNS). Most treatment protocols take two to three years to complete. Stem cell transplantation can sometimes be used as a treatment in which patient's normal source of blood cells (bone marrow) is replaced by healthy young blood cells (stem cells) from a healthy well-matched donor. Splenectomy is rarely required for Acute Lymphocytic Leukemia. Splenectomy can help boost platelet count, but does not affect the outcome of leukemia itself. Splenectomy can be performed for severe symptoms that are not amenable to chemotherapy treatment such as abdominal pain. Radiation can also be used in cases of enlarged spleen to try and reduce the size of the spleen in most cases. [7][8][9]

Pearls and Other Issues

Despite improvements in supportive care, death resulting from treatment toxicity remains a challenge. It is important to watch out for Tumor Lysis Syndrome which occurs when chemotherapy causes cancer cells to lyse releasing certain intracellular elements such as potassium, calcium, uric acid, and phosphorus. These elements, in large numbers, resulting in toxicity that can often lead to renal failure. Pretreatment with fluids and steroids typically prevents Tumor Lysis Syndrome. However, if it occurs, aggressive fluid therapy is the treatment. 

Even after treatment, Acute Lymphocytic Leukemia can come back (relapse). Relapses can occur as far back as 21 years. IT is important to address other issues associated with cancer treatment in a young child including providing psychological support to child, parents, and family. 

Enhancing Healthcare Team Outcomes

The management of acute leukemia is by a multidisciplinary team that includes an oncologist, internist, infectious disease expert, and a hematologist. The primary care provider and nurse practitioner may be responsible for follow up after treatment and report back to the interdisciplinary team. Despite improvements in supportive care, death resulting from treatment toxicity remains a challenge. It is important to watch out for Tumor Lysis Syndrome which occurs when chemotherapy causes cancer cells to lyse releasing certain intracellular elements such as potassium, calcium, uric acid, and phosphorus. These elements, in large numbers, resulting in toxicity that can often lead to renal failure. Pretreatment with fluids and steroids typically prevents Tumor Lysis Syndrome. However, if it occurs, aggressive fluid therapy is the treatment. 

Even after treatment, Acute Lymphocytic Leukemia can come back (relapse). Relapses can occur as far back as 21 years. IT is important to address other issues associated with cancer treatment in a young child including providing psychological support to child, parents, and family. 


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Cancer, Acute Lymphocytic Leukemia (ALL) - Questions

Take a quiz of the questions on this article.

Take Quiz
Which of the following is not part of induction therapy for acute lymphoblastic leukemia?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is associated with the CD10 antigen?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which is true regarding childhood leukemias?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 49-year-old male with fatigue and easy bruising is found to have terminal deoxynucleotidyl transferase (TdT) positive cells in the blood. He may have which of the following conditions?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 6-year-old child is brought in by for recurrent fevers, extreme fatigue, and bruising on her legs. She was previously well with no past medical history. She was noted by her parents to be "very tired" starting about 1 week ago. She also began having daily fevers 3 days ago. Yesterday was noted to have large bruises on her legs bilaterally, despite no history of trauma. Prior to the past week she had been going to school and doing well. On physical exam, the child is pale and tired-appearing. Her temperature is 102 degrees F (38.9 degrees C) orally. She has a few petechiae in her oropharynx and diffuse cervical lymphadenopathy. She has a 2/6 systolic ejection murmur. Her liver and spleen are both palpable 1 cm below the costal margin. Her legs have multiple large ecchymoses. Her complete blood count revealed a white blood cell count of 65,000/microliter, a hemoglobin of 6.4 g/dL, and a platelet count of 18,000. What is the diagnosis?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 6-year-old child is brought in by her parents for recurrent fevers, extreme fatigue, and bruising on her legs. She was a previously well child with no past medical history but was noted by her parents to be "very tired" starting about 1 week ago. She also began having daily fevers 3 days ago, and yesterday was noted to have large bruises on her legs bilaterally, despite no history of trauma. Prior to the past week she had been going to school and doing well. On physical exam, the child is pale and tired-appearing. Her temperature is 102 degrees F (38.9 C) orally. She has a few petechiae in her oropharynx and diffuse cervical lymphadenopathy. She has a 2/6 systolic ejection murmur. Her liver and spleen are both palpable 1 cm below the costal margin. Her legs have multiple large ecchymoses. Her complete blood count revealed a white blood cell count of 65,000/microL, a hemoglobin of 6.4 g/dL, and a platelet count of 18,000. The differential has 84% large white blood cells with minimal agranular pale blue cytoplasm and large nuclei with very fine chromatin and large nucleoli. Which of the fallowing studies is NOT indicated for this patient at this time?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 6-year-old child is brought in by her parents for recurrent fevers, extreme fatigue, and bruising on her legs. She was a previously well child with no past medical history but was noted by her parents to be "very tired" starting about 1 week ago. She also began having daily fevers 3 days ago, and yesterday was noted to have large bruises on her legs bilaterally, despite no history of trauma. Prior to the past week she had been going to school and doing well. On physical exam, the child is pale and tired-appearing. Her temperature is 102 degrees F (38.9 C) orally. She has a few petechiae in her oropharynx and diffuse cervical lymphadenopathy. She has a 2/6 systolic ejection murmur. Her liver and spleen are both palpable 1 cm below the costal margin. Her legs have multiple large ecchymoses. Her complete blood count revealed a white blood cell count of 65,000/microL, a hemoglobin of 6.4 g/dL, and a platelet count of 18,000. The differential has 84% large white blood cells with minimal agranular pale blue cytoplasm and large nuclei with very fine chromatin and large nucleoli. Which of the following interventions is indicated for this patient at this time?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 6-year-old child is brought to your clinic by her parents for recurrent fevers, extreme fatigue, and bruising on her legs. She was a previously well child with no past medical history but was noted by her parents to be "very tired" starting about 1 week ago. She also began having daily fevers 3 days ago, and yesterday was noted to have large bruises on her legs bilaterally, despite no history of trauma. Prior to the past week she had been going to school and doing well. On physical exam, the child is pale and tired-appearing. Her temperature is 102 degrees F (38.9 C) orally. She has a few petechiae in her oropharynx and diffuse cervical lymphadenopathy. She has a 2/6 systolic ejection murmur. Her liver and spleen are both palpable 1 cm below the costal margin. Her legs have multiple large ecchymoses. Her complete blood count revealed a white blood cell count of 65,000/mL, a hemoglobin of 6.4 g/dL, and a platelet count of 18,000. The differential has 84% large white blood cells with minimal agranular pale blue cytoplasm and large nuclei with very fine chromatin and large nucleoli. Which of the following features of this patient's presentation places her at highest risk for treatment failure?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What is the likelihood of a child with standard-risk, acute lymphoblastic leukemia entering remission after the first month of induction therapy?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Anti-cancer therapy is initiated in a patient with acute lymphocytic leukemia. Side effects of this treatment can be decreased by inhibition of which enzyme?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Acute lymphoblastic leukemia does not present with which of the following?

(Move Mouse on Image to Enlarge)
  • Image 4443 Not availableImage 4443 Not available
    Contributed by Wikimedia Commons,"Medical gallery of Mikael Häggström 2014" (Public Domain)
Attributed To: Contributed by Wikimedia Commons,"Medical gallery of Mikael Häggström 2014" (Public Domain)



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 65-year-old male with acute lymphocytic leukemia is admitted for thrombocytopenia. What is the appropriate room assignment?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 4-year-old is brought to the emergency department with complaints of fatigue and undocumented fevers for a few days. He has previously been healthy, but his mother is worried that he looks pale. There have been no gastrointestinal symptoms, but he has woken several times in the past week with leg pain. His gums have been bleeding after brushing his teeth. The child is pale, has diffuse lymphadenopathy, splenomegaly, and scattered petechiae. There is no hepatomegaly or other findings. CBC shows WBC of 9,000/microliter, hemoglobin 8.7 g/dL, hematocrit of 24%, and platelets 8,000/microliter. An automated differential shows many atypical lymphocytes. What is the next best step in management?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A nurse is caring for a 4-year-old with acute lymphoblastic leukemia (ALL). Which of the following is true regarding ALL? Select all that apply.



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Cancer, Acute Lymphocytic Leukemia (ALL) - References

References

Roberts KG, Genetics and prognosis of ALL in children vs adults. Hematology. American Society of Hematology. Education Program. 2018 Nov 30;     [PubMed]
Jain T,Litzow MR, No free rides: management of toxicities of novel immunotherapies in ALL, including financial. Hematology. American Society of Hematology. Education Program. 2018 Nov 30;     [PubMed]
Dinner S,Liedtke M, Antibody-based therapies in patients with acute lymphoblastic leukemia. Hematology. American Society of Hematology. Education Program. 2018 Nov 30;     [PubMed]
DeRenzo C,Krenciute G,Gottschalk S, The Landscape of CAR T Cells Beyond Acute Lymphoblastic Leukemia for Pediatric Solid Tumors. American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting. 2018 May 23;     [PubMed]
Ramos KN,Ramos IN,Zeng Y,Ramos KS, Genetics and epigenetics of pediatric leukemia in the era of precision medicine. F1000Research. 2018;     [PubMed]
Valentin R,Grabow S,Davids MS, The rise of apoptosis: targeting apoptosis in hematologic malignancies. Blood. 2018 Sep 20;     [PubMed]
Brown PA,Shah B,Fathi A,Wieduwilt M,Advani A,Aoun P,Barta SK,Boyer MW,Bryan T,Burke PW,Cassaday R,Coccia PF,Coutre SE,Damon LE,DeAngelo DJ,Frankfurt O,Greer JP,Kantarjian HM,Klisovic RB,Kupfer G,Litzow M,Liu A,Mattison R,Park J,Rubnitz J,Saad A,Uy GL,Wang ES,Gregory KM,Ogba N, NCCN Guidelines Insights: Acute Lymphoblastic Leukemia, Version 1.2017. Journal of the National Comprehensive Cancer Network : JNCCN. 2017 Sep;     [PubMed]
Radich JP,Zelenetz AD,Chan WC,Croce CM,Czuczman MS,Erba HP,Horning SJ,Houldsworth J,Smith BD,Snyder DS,Sundar HM,Wetzler M,Winter JN, NCCN task force report: molecular markers in leukemias and lymphomas. Journal of the National Comprehensive Cancer Network : JNCCN. 2009 Jul;     [PubMed]
Alvarnas JC,Brown PA,Aoun P,Ballen KK,Barta SK,Borate U,Boyer MW,Burke PW,Cassaday R,Castro JE,Coccia PF,Coutre SE,Damon LE,DeAngelo DJ,Douer D,Frankfurt O,Greer JP,Johnson RA,Kantarjian HM,Klisovic RB,Kupfer G,Litzow M,Liu A,Rao AV,Shah B,Uy GL,Wang ES,Zelenetz AD,Gregory K,Smith C, Acute Lymphoblastic Leukemia, Version 2.2015. Journal of the National Comprehensive Cancer Network : JNCCN. 2015 Oct;     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of NP-Adult Acute Gerontology. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for NP-Adult Acute Gerontology, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in NP-Adult Acute Gerontology, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of NP-Adult Acute Gerontology. When it is time for the NP-Adult Acute Gerontology board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study NP-Adult Acute Gerontology.