II. History
- Success story of Twentieth Century Oncology
- Previously ALL was 100% fatal in 3 months
- Current Chemotherapy regimens hold >50% cure
III. Epidemiology
- Disease of children and young adults in 80% of cases
- Onset is at under age 20 years old in more than half of patients
- Highest Incidence is between ages 2-3 years (most cases occur in age <5 years)
- However, 20% of Acute Lymphoblastic Leukemia cases occur in age >50 years old
- Most common childhood (25% of cancers diagnosed under age 15 years)
- Ethnicity
- Highest Incidence in hispanic and white children
- Lowest rate among black children
IV. Risk Factors
- Prenatal Radiation Exposure
-
Genetic Syndromes
- Down Syndrome
- Neurofibromatosis
- Ataxia Telangiectasia
- Shwachman syndrome
- Bloom syndrome
V. Symptoms
- See Acute Leukemia
- Asymptomatic in 6% of children at time of diagnosis
- Fever (49 to 57%)
- Unintentional Weight Loss (26 to 31%)
- Lethargy or Fatigue (45 to 64%)
- Pallor (28 to 46%)
- Bleeding or Bruising (10 to 43%)
- Musculoskeletal pain, esp. leg or back pain (21 to 59%)
- Gastrointestinal symptoms from Hepatosplenomegaly
- Nausea
- Abdominal fullness
- Early Satiety
VI. Signs
- See Acute Leukemia
- Hepatomegaly or Splenomegaly (50% to 75% in children, 20% of adults)
- Lymphadenopathy
- Testicular involvement may occur
- Anterior Mediastinal Mass (T-Cell Variant)
- CNS Involvement (Meningeal Irritation, cranial Neuropathy) in 5-8% of adults with Acute Lymphoblastic Leukemia
VII. Labs: Pathology
- Immature Lymphoblasts (blast cells)
- Round or convoluted nuclei
- Express Common ALL Antigen (CALLA) in 60% of cases
- Contrast with Acute Myelogenous Leukemia
- Smaller blast cells with ALL
- No Auer rods in ALL
- Contain deoxynucleotidyl transferase in 90% of cases (rare in AML)
-
Lymphocyte Cell Types
- T-Cell Type (20% of cases)
- B-Cell Type (5%)
- Null Cell Type (15%)
- Other findings and diagnostics
- Lumbar Puncture for CSF
- Philadelphia Chromosome (BCR-ABL1 Fusion Gene) may be present
- Primarily seen in CML (90% of cases)
- However also present in ALL (2-4% of children, 20-40% of adults)
VIII. Diagnosis
- Sources
- Blast cell predominance (both ALL and AML)
- However, blast cell absence on Peripheral Smear does not exclude Acute Leukemia
- Studies to distinguish between ALL and AML
- Lymphoblasts represent >20% of cells in Bone Marrow sample in ALL
- Flow cytometry with immunophenotyping
- Sorts and counts cells by cell surface markers
- Cytogenetic testing
- Chromosome evaluation (karyotype or fluorescence in situ hybridization analysis)
IX. Management: Acute
- Remission-Induction Chemotherapy
- CNS Prophylaxis (prevents Leukemic Meningitis)
- Whole Brain Radiation (18 to 24-Gy)
- Intrathecal Methotrexate
- Maintenance Chemotherapy for 2-3 years
-
Targeted Cancer Therapy (small molecule inhibitors and Biologic Agents, typically in adults)
- Tisagenleucel (Kymriah)
- FDA approved in under age 25 years
- Tyrosine Kinase Inhibitors
- Indicated in Philadelphia Chromosome positive ALL
- Tisagenleucel (Kymriah)
X. Management: Surveillance of survivors treated with Chemotherapy and Radiation
- Initial surveillance
- Year 1
- Monthly Physical Exam and Complete Blood Count (CBC) with differential
- Every 2 month Liver Function Tests until normal
- Bone Marrow Aspirate or Lumbar Puncture as indicated
- Echocardiogram as indicated
- Year 2
- Every 3 month physical exam (with testicular exam) and Complete Blood Count with differential
- Year 3 (and after)
- Every 6 to 12 month physical exam (with testicular exam) and Complete Blood Count with differential
- Year 1
- Routine periodic exams
- Annual physical exam (or more often in first 3 years as above)
- Growth Exam (growth chart plotting in children)
- Annual Eye Examination
- Dental care every 6 months
- Cancer screening
- Complete skin exam
- Testicular exam
- Annual lab testing
- Complete Blood Count with differential
- Obtain for up to 10 years following last treatment
- Obtain more often in first three years as listed above
- Comprehensive metabolic panel
- Includes serum Electrolytes, Serum Creatinine, Blood Urea Nitrogen, Serum Calcium and Liver Function Tests
- Serum Phosphorus
- Serum Magnesium
- Thyroid Stimulating Hormone
- Urinalysis
- If Hematuria, frequency or urgency
- Complete Blood Count with differential
- Communicable Disease Testing (one time screening)
- Hepatitis C Antibody testing (if treated before 1993)
- Hepatitis B Surface Antigen and Hepatitis B Core Antibody (if treated before 1972)
- HIV Test (if treated between 1977 and 1986)
- Other tests as indicated
- Respiratory symptoms
- Hearing changes
- Cardiac symptoms (e.g. CHF)
- Repeat testing every 3-5 years if pretreatment cardiac testing was abnormal
- Echocardiogram
- Electrocardiogram (EKG)
- Obtain baseline and every 2 to 5 years if Anthracycline-based Chemotherapy (Daunorubicin, Doxorubicin)
-
Vaccinations
- See Hematopoietic Stem Cell Transplant for Vaccination precautions
- Do not administer live Vaccinations during Chemotherapy
- Maintain age appropriate Vaccinations if not contraindicated
- Maintain Covid19 Vaccine, Influenza Vaccine, Pneumococcal Vaccine if not contraindicated
XI. Management: Surveillance of survivors miscellaneous
- Treated with cranial or craniospinal radiation
- Neuroimaging is indicated for neurologic symptoms
- Treated with Hematopoietic Stem Cell Transplantation
- See Hematopoietic Stem Cell Transplant for protocol
XII. Prognosis (U.S., 2000 to 2018)
- Child: Cure rates approach 90%
- Age under 20 years: 87% five year survival
- Adults: Cure rates 40 to 50%
- Long term survival <30% (increasing with Targeted Cancer Therapy)
- Age under 50 years: Five-year survival 75%
- Age 50 to 64 years: Five-year survival 30%
- Age over 50 years: Five-year survival 15%
XIII. Complications
- See Acute Leukemia
- Leukemic Meningitis in relapse
-
General Chemotherapy complications
- Lymphocytopenia
- Immunodeficiency (predominantly T-Cells)
- Growth retardation (most attain normal growth)
- Sterility (most resolves)
- Joint osteonecrosis (hips, Shoulders and knees)
- Cummulative 20 year Incidence 2.8% in adolescents treated for ALL
- Cyclophosphamide related
- Anthracycline (Doxorubicin or Daunorubicin) related
- Cranial Radiotherapy related
- CNS tumor
- Papillary Thyroid Carcinoma
- Acute monocytic Leukemia
- Cognitive decline
- Osteoporosis
- Obesity
- Periodontal Disease
- Cataracts
XIV. Resources
- National Cancer Institute
Images: Related links to external sites (from Bing)
Related Studies
Definition (MEDLINEPLUS) |
Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, however, the bone marrow produces abnormal white blood cells. These cells crowd out the healthy blood cells, making it hard for blood to do its work. In acute lymphocytic leukemia (ALL), also called acute lymphoblastic leukemia, there are too many of specific types of white blood cells called lymphocytes or lymphoblasts. ALL is the most common type of cancer in children. Possible risk factors for ALL include being male, being white, previous chemotherapy treatment, exposure to radiation, and for adults, being older than 70. Symptoms of ALL include:
Tests that examine the blood and bone marrow diagnose ALL. Treatments include chemotherapy, radiation therapy, stem cell transplants, and targeted therapy. Targeted therapy uses substances that attack cancer cells without harming normal cells. Once the leukemia is in remission, you need additional treatment to make sure that it does not come back. NIH: National Cancer Institute |
Definition (NCI) | Leukemia with an acute onset, characterized by the presence of lymphoblasts in the bone marrow and the peripheral blood. It includes the acute B lymphoblastic leukemia and acute T lymphoblastic leukemia. |
Definition (NCI_CDISC) | A progressive, proliferative disease of blood cells, originating from immature lymphoid cells. |
Definition (NCI_NCI-GLOSS) | An aggressive (fast-growing) type of leukemia (blood cancer) in which too many lymphoblasts (immature white blood cells) are found in the blood and bone marrow. |
Definition (CSP) | acute leukemia in which lymphoblasts and their progenitor cells predominate; the most common childhood cancer and accounts for 20 percent of adult acute leukemia; common ALL antigen (CALLA) expressed in most cases. |
Concepts | Neoplastic Process (T191) |
ICD9 | 204.0 |
ICD10 | C91.0 , C91.00, M9821/3 |
SnomedCT | 91857003, 90151006, 154588002, 190034000, 128822004 |
English | Lymphoid leukemia, acute, ALL - Acute lymphobl leukaemia, ALL - Acute lymphobl leukemia, LEUKEMIA ACUTE LYMPHOBLASTIC, [M]Acute lymphoid leukaemia, [M]Acute lymphoid leukemia, Acute lymphocytic leukemia, acute lymphatic leukemia, acute lymphogenous leukemia, ALL (acute lymphocytic leukemia), acute lymphocytic leukemia (diagnosis), acute lymphocytic leukemia, Acute lymphoid leukaemia, disease, Acute lymphoid leukemia, disease, Acute lymphoblastic leukaemia -RETIRED-, Lymphoid leukaemia, acute, Leukemia lymphoblastic acute, Acute Lymphoblastic Leukemia, Acute Lymphogenous Leukemia, Precursor Lymphoblastic Leukemia, Acute Lymphocytic Leukemias, acute lymphocytic leukemia (ALL), Acute lymphoblastic leukemia [ALL], Acute lymphoblastic leukaemia NOS, Acute lymphoblastic leukemia NOS, Leukaemia;acute lymphocytic, acute lymphatic leukaemia, leukemia lymphoblastic, leukemia acute lymphoblastic, acute lymphoblastic leukaemia, acute lymphoblastic leukemias, leukemia - acute lymphoblastic, lymphocytic leukemia acute, acute leukaemia lymphoblastic, acute leukemia lymphocytic, acute leukemia lymphoid, acute leukemia lymphoblastic, acute lymphoid leukemia, lymphoblastic leukaemia, lymphoblastic leukemia, Leukaemias acute lymphocytic, Leukemia, Acute Lymphocytic, Acute Lymphocytic Leukemia, [M]Acute lymphoid leukaemia (disorder), Acute lymphoblastic leukemia (morphologic abnormality), [M]Acute lymphoid leukemia (morphologic abnormality), ACUTE LYMPHOCYTIC LEUKAEMIA, LEUKEMIA, LYMPHOBLASTIC, MALIGNANT, PRECURSOR LYMPHOBLASIC LEUKEMIA, ACUTE LYMPHOGENOUS LEUKEMIA, PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA, Acute lymphoblastic leukemia, NOS, LYMPHOBLASTIC LEUKEMIA, ALL, ACUTE LYMPHOCYTIC LEUKEMIAS, acute lymphoblastic leukemia, ACUTE LYMPHOID LEUKEMIA, ALL - ACUTE LYMPHOCYTIC LEUKEMIA, Leukaemia lymphoblastic acute, Acute lymphoid leukemia, Acute lymphatic leukemia, Lymphoblastic leukemia, ALL - Acute lymphoblastic leukaemia, ALL - Acute lymphoblastic leukemia, Acute lymphoblastic leukaemia, Acute lymphoblastic leukemia, Acute lymphoid leukaemia, Acute lymphatic leukaemia, Acute lymphocytic leukaemia, Acute lymphoblastic leukaemia-lymphoma, Acute lymphoblastic leukemia-lymphoma, Acute lymphoid leukemia, disease (disorder), Lymphoblastic leukaemia, leukemia, acute lymphocytic, leukemia; lymphatic, acute, lymphatic; leukemia, acute, Lymphoblastic leukemia, NOS, Acute lymphoblastic leukemia -RETIRED-, Lymphoblastic Leukemia, Acute Lymphocytic Leukaemia, Acute Lymphoid Leukemia, Precursor Cell Lymphoblastic Leukemia, ALL - Acute Lymphocytic Leukemia, Leukemias acute lymphocytic, Leukemia;acute lymphocytic, acute lymphocytic leukaemia |
Spanish | leucemia linfoide aguda, enfermedad, Leucemia linfática aguda, Leucemia linfoide aguda, Leucemia linfoblástica aguda, [M] leucemia linfoide aguda (anomalía morfológica), [M] leucemia linfoide aguda, leucemia linfoide aguda, enfermedad (trastorno), leucemia linfoide aguda, Leucemia aguda linfocítica, Leucemia linfocítica aguda |
Italian | Leucemia linfocitica acuta, Leucemie linfocitiche acute, Leucemia linfoblastica acuta, Leucemia linfatica acuta, ALL, Leucemia linfoide, acuta, Leucemia linfoide acuta |
Dutch | lymfoïde leukemie, acuut, acute lymfatische leukemie, acute lymfoblastische leukemie, acute lymfoïde leukemie, lymfoblastische leukemie acuut, ALL, leukemie; lymfatisch, acuut, lymfatisch; leukemie, acuut, Acute lymfoblastenleukemie, acute lymfocytaire leukemie, lymfocytische leukemieën acuut |
French | Leucémie lymphatique aiguë, Leucémie lymphoblastique aiguë, Leucémie lymphoïde aiguë, LLA, Leucémie lymphoïde, aiguë, Leucémie lymphocytaire aiguë, Leucémie aiguë lymphoblastique, Leucémies lymphocytaires aiguës |
German | akute lymphoblastische Leukaemie, akute Lymphoblastenleukaemie, ALL, akute lymphoide Leukaemie, lymphoide Leukaemie, akut, akute lymphablastische Leukaemie, Leukaemie lymphoblastisch akut, Akute lymphoblastische Leukaemie, Leukaemien akut lymphozytaer, akute lymphatische Leukaemie |
Portuguese | Leucemia linfóide aguda, Leucemia linfática aguda, Leucemia linfoblástica aguda, Leucemia linfocítica aguda, Leucemias linfocítica aguda |
Japanese | 急性リンパ球性白血病, 急性リンパ性白血病, 急性リンパ芽球性白血病, ALL, ALL, キュウセイリンパキュウセイハッケツビョウ, キュウセイリンパセイハッケツビョウ, キュウセイリンパガキュウセイハッケツビョウ |
Czech | Akutní lymfatická leukemie, Akutní lymfoblastické leukemie, Akutní lymfoidní leukemie, Akutní lymfocytická leukemie, Akutní lymfoblastická leukemie, ALL |
Korean | 급성 림프모구성 백혈병 |
Hungarian | Heveny lymphoblastos leukemia, Heveny lymphoid fehérvérűség, Acut lymphatikus leukaemia, Acut lymphatikus leukemia, Acut lymphoblastos leukemia, ALL, Acut lymphoblastos leukaemia, Lymphoid fehérvérűség, heveny, Acut lymphocytás leukemia, Leukemiák, acut lymphocytás, Fehérvérűség limfoblasztos heveny, Lymphoid fehérvérűség, acut, Acut lymphocytás leukaemia, Acut lymphoid leukaemia |