Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer; it also strikes adults of all ages. Malignant transformation and uncontrolled proliferation of an abnormally differentiated, long-lived hematopoietic progenitor cell results in a high circulating number of blasts, replacement of normal marrow by malignant cells, and the potential for leukemic infiltration of the central nervous system (CNS) and testes. Symptoms include fatigue, pallor, infection, bone pain, CNS symptoms (eg, headache), easy bruising, and bleeding. Examination of peripheral blood smear and bone marrow is usually diagnostic. Treatment typically includes combination chemotherapy to achieve remission, intrathecal and systemic chemotherapy and/or corticosteroids for CNS prophylaxis, and sometimes cerebral irradiation for intracerebral leukemic infiltration, consolidation chemotherapy with or without stem cell transplantation, and maintenance chemotherapy for up to 3 years to avoid relapse. Show The American Cancer Society estimates that in the United States in 2022 there will be over 6600 new cases of acute lymphoblastic leukemia (ALL) and almost 1600 deaths will have occurred. Sixty percent of all ALL cases occur in children, with a peak incidence at age 2 to 5 years; a second peak occurs after age 50. ALL is the most common cancer in children, and represents about 75% of leukemias among children < 15 years of age. It is the 2nd most common cause of death in children < 15 years. The risk declines slowly until the mid-20s and then begins to rise again slowly after age 50. ALL accounts for about 20% of adult acute leukemias. The average lifetime risk of ALL in both sexes is about 0.1% (1 in 1000 Americans). Hispanic populations have a higher incidence of ALL than other racial/ethnic populations due in part to polymorphisms in the ARID5B gene. Similar to acute myeloid leukemia, acute lymphoblastic leukemia is caused by a series of acquired genetic aberrations. Malignant transformation usually occurs at the pluripotent stem cell level, although it sometimes involves a committed stem cell with more limited capacity for self-renewal. Abnormal proliferation, clonal expansion, aberrant differentiation, and diminished apoptosis (programmed cell death) lead to replacement of normal blood elements with malignant cells. In acute lymphoblastic leukemia, the precursor lymphoid neoplasms are broadly categorized based on their lineage into
The 2016 World Health Organization (WHO) classification of lymphoid neoplasms incorporates genetic data, clinical features, cell morphology, and immunophenotype, all of which have important implications for disease prognosis and management. Symptoms and signs of acute lymphoblastic leukemia may be present for only days to weeks before diagnosis. The most common presenting symptoms are due to disrupted hematopoiesis with ensuing
Anemia can manifest with fatigue, weakness, pallor, malaise, dyspnea on exertion, tachycardia, and exertional chest pain. Thrombocytopenia can cause mucosal bleeding, easy bruising, petechiae/purpura, epistaxis, bleeding gums, and heavy menstrual bleeding. Hematuria and gastrointestinal bleeding are uncommon. Patients can present with spontaneous hemorrhage, including intracranial or intra-abdominal hematomas. Granulocytopenia or neutropenia can lead to a high risk of infections, including those of bacterial, fungal, and viral etiologies. Patients may present with fevers and a severe and/or recurrent infection. Organ infiltration by leukemic cells results in enlargement of the liver, spleen, and lymph nodes. Bone marrow and periosteal infiltration may cause bone and joint pain, especially in children with ALL. CNS penetration and meningeal infiltration are common and can result in cranial nerve palsies, headache, visual or auditory symptoms, altered mental status, and transient ischemic attack/stroke.
A diagnosis of acute lymphoblastic leukemia is made when blast cells of lymphoid origin are ≥ 20% of marrow nucleated cells or ≥ 20% of non-erythroid cells when the erythroid component is > 50%. If marrow cells are insufficient or unavailable, diagnosis can be made by the same criteria using a peripheral blood sample. CBC and peripheral smear are the first tests done; pancytopenia and peripheral blasts suggest acute leukemia. Blast cells in the peripheral smear may approach 90% of the white blood cell (WBC) count.
Aplastic anemia
Aplastic Anemia Aplastic anemia is a disorder of the hematopoietic stem cell that results in a loss of blood cell precursors, hypoplasia or aplasia of bone marrow, and cytopenias in two or more cell lines ... read more
Bone marrow examination (aspiration and needle biopsy) is routinely done. Blast cells in the bone marrow are typically between 25 and 95% in patients with ALL. Histochemical studies, cytogenetics, and immunophenotyping studies help distinguish the blasts of ALL from those of AML or other disease processes.
Histochemical studies include staining for terminal deoxynucleotidyl transferase (TdT), which is positive in cells of lymphoid origin. Detection of specific immunophenotypic markers such as CD3 (for lymphoid cells of T cell origin) and CD19, CD20, and CD22 (for lymphoid cells of B cell origin) is essential in classifying the acute leukemias. Common cytogenetic abnormalities in ALL include t(9;22) in adults and t(12;21) and high hyperdiploidy in children (see table
Common Cytogenetic Abnormalities in ALL
Common Cytogenetic Abnormalities in ALL  Less common cytogenetic abnormalities include the following:
BCR-ABL-like acute lymphoblastic leukemia overlaps genetically with ALL in which the Philadelphia chromosome [a reciprocal balanced translocation between chromosomes 9 and 22, t(9;22)] is present (Ph+ ALL). Other laboratory findings may include hyperuricemia, hyperphosphatemia Hyperphosphatemia Hyperphosphatemia is a serum phosphate concentration > 4.5 mg/dL (> 1.46 mmol/L). Causes include chronic kidney disease, hypoparathyroidism, and metabolic or respiratory acidosis. Clinical... read more , hyperkalemia Hyperkalemia Hyperkalemia is a serum potassium concentration > 5.5 mEq/L (> 5.5 mmol/L), usually resulting from decreased renal potassium excretion or abnormal movement of potassium out of cells. There... read more , hypocalcemia Hypocalcemia Hypocalcemia is a total serum calcium concentration < 8.8 mg/dL (< 2.20 mmol/L) in the presence of normal plasma protein concentrations or a serum ionized calcium concentration < 4... read more , and elevated lactate dehydrogenase (LDH), which indicate a tumor lysis syndrome Tumor Lysis and Cytokine Release Syndromes Adverse effects are common in patients receiving any cancer therapy, particularly cytopenias, gastrointestinal effects, and tumor lysis and cytokine release syndromes. Patients may also have... read more . Elevated serum levels of hepatic transaminases or creatinine, and hypoglycemia may also be present. Patients with Ph+ ALL and patients with t(v;11q23) involving MLL rearrangements often present with hyperleukocytosis. CT of the head is done in patients with CNS symptoms. CT of the chest and abdomen should be done to detect mediastinal masses and lymphadenopathy and may also detect hepatosplenomegaly. Echocardiography or multi-gated acquisition (MUGA) scanning is typically done to assess baseline cardiac function (prior to administration of anthracyclines, which are cardiotoxic). Prognostic factors help determine treatment protocol and intensity. Favorable prognostic factors are
Unfavorable factors include
Regardless of prognostic factors, the likelihood of initial remission is ≥ 95% in children and 70 to 90% in adults. Of children, > 80% have continuous disease-free survival for 5 years and appear to be cured. Of adults, < 50% have long-term survival. Factors contributing to poorer clinical outcomes in adults compared with children include the following:
Most investigatory protocols select patients with poor prognostic factors for more intense therapy because the increased risk of and toxicity from treatment are outweighed by the greater risk of treatment failure leading to death.
Treatment for newly diagnosed acute lymphoblastic leukemia generally consists of 3 to 4 cycles of chemotherapy blocks of non–cross-resistant chemotherapy for the first 9 to 12 months, followed by 2.5 to 3 years of maintenance chemotherapy. The 4 general phases of chemotherapy for acute lymphoblastic leukemia include
The goal of induction treatment is complete remission, defined as < 5% blast cells in the bone marrow, an absolute neutrophil count > 1000/mcL (> 1 × 109/L), a platelet count > 100,000/mcL (> 100 × 109/L), and no need for blood transfusion. In patients with complete remission, a low measurable residual
disease (also known as minimal residual disease or MRD) is the most important prognostic factor (1
Treatment references Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer; it also strikes adults of all ages. Malignant transformation and uncontrolled proliferation of an abnormally differentiated... read more
Components of induction therapy include
Some regimens use a corticosteroid to reduce disease burden prior to intensive induction. In younger adults, a regimen that includes asparaginase and/or cyclophosphamide for induction, similar to treatment protocols used in children, may increase rates of response and achievement of undetectable minimal residual disease. If complete remission is not achieved after induction, some regimens recommend a second induction course to try to get more patients to complete remission before consolidation. For patients with Philadelphia chromosome–positive (Ph+) ALL, a tyrosine kinase inhibitor (eg, imatinib, dasatinib) can be added to the drug regimen. For patients with CD20 positive B-lymphoblastic leukemia, rituximab can be added. Interim maintenance and late/delayed intensification therapy are used after consolidation therapy. These phases of therapy incorporate a variety of chemotherapeutic agents with different doses and schedules that are less intense than induction and consolidation. Most regimens include maintenance therapy with monthly vincristine, weekly methotrexate, daily mercaptopurine, and 5 days/month corticosteroid. Therapy duration is usually 2½ to 3 years. CNS prophylaxis starts during induction and continues throughout all phases of treatment. Because lymphoblasts often infiltrate the spinal fluid and meninges, all regimens include CNS prophylaxis and treatment with intrathecal methotrexate, cytarabine, and hydrocortisone in combination or as monotherapy. High doses of systemic methotrexate and/or cytarabine penetrate the CNS, providing extra CNS prophylaxis if regimens include these drugs. Cranial nerve or whole-brain irradiation was previously often done for patients at high risk of CNS disease (eg, high WBC count, high serum lactate dehydrogenase, B-cell phenotype), but its use has been decreasing in recent years. About one third of patients with acute lymphoblastic leukemia are older adults (> 65). Older ALL patients are more likely to have precursor B-cell ALL and have higher risk and more complex cytogenetics, including Philadelphia chromosome positive (Ph+) or t(v;11q23) MLL (KMT2A) rearranged disease. Some, but not all, older patients can tolerate standard induction therapy. Subsequent treatment regimens (CNS prophylaxis, postremission consolidation or intensification, and maintenance) depend on the individual patient's comorbidities and performance status. For example, older patients with several comorbidities and poor performance status may undergo gentler induction therapy without consolidation or maintenance. In older patients with Ph+ ALL, tyrosine kinase inhibitors (eg, imatinib, dasatinib) plus corticosteroids given with either low-intensity or no chemotherapy have resulted in 95 to 100% complete remission rate, with a 45 to 50% 2-year relapse free survival and about 70% 2-year overall survival. For older patients with ALL who are in their first complete remission, nonmyeloablative or reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation Hematopoietic Stem Cell Transplantation Hematopoietic stem cell (HSC) transplantation is a rapidly evolving technique that offers a potential cure for hematologic cancers ( leukemias, lymphomas, myeloma) and other hematologic disorders... read more is an option. Targeted immunotherapy drugs that are available for treatment of relapsed or refractory ALL are increasingly used for treatment of older patients with ALL in clinical trials or clinical practice. Older patients with ALL probably tolerate asparaginase more poorly than younger patients do. Leukemic cells may reappear in the bone marrow, CNS, testes, or other sites. Bone marrow relapse is particularly ominous. Although a new round of chemotherapy may induce a second remission in the majority of children and about one third of adults, subsequent remissions tend to be brief. Chemotherapy causes only a few patients with early bone marrow relapse to achieve long disease-free second remissions or cure. Available immunotherapies for relapsed or refractory ALL include
Blinatumomab, a biospecific CD19-directed CD3 T-cell engager, prolongs overall survival for children and adults with relapsed or refractory B-cell precursor ALL, whether Ph+ or Ph-. Life-threatening toxicities may include
cytokine release syndrome
Cytokine release syndrome Adverse effects are common in patients receiving any cancer therapy, particularly cytopenias, gastrointestinal effects, and tumor lysis and cytokine release syndromes. Patients may also have... read more and neurologic toxicities (eg,
seizures, encephalopathy with altered consciousness, and disordered speech, coordination, and/or balance). Interruption or stopping blinatumomab with or without use of high-dose dexamethasone may be necessary. The most common neurologic symptoms after blinatumomab use are headache and tremor
(3
Treatment references Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer; it also strikes adults of all ages. Malignant transformation and uncontrolled proliferation of an abnormally differentiated... read more Other agents that have been available, but for which clinically meaningful outcomes have not been convincingly demonstrated (ie, the approvals were based upon response rate but there were no trials verifying an improvement in disease-related symptoms or increased survival). Examples include
CNS relapse treatment includes intrathecal methotrexate (with or without cytarabine or corticosteroids) twice weekly until all signs disappear. The role of continued intrathecal drug use or CNS irradiation is unclear. Testicular relapse may be evidenced clinically by painless firm swelling of a testis or may be identified on biopsy. If unilateral testicular involvement is clinically evident, the apparently uninvolved testis should undergo biopsy. Treatment is radiation therapy of the involved testis and administration of systemic reinduction therapy. Supportive care is similar in the acute leukemias and may include
Transfusions of red blood cells and sometimes platelets are administered as needed to patients with bleeding or anemia. Prophylactic platelet transfusion is done when platelets fall to < 10,000/mcL (< 10 × 109/L). Anemia (hemoglobin < 7 or 8 g/dL [< 70 to 80 g/L]) is treated with transfusions of packed red blood cells. Granulocyte transfusions are not routinely used. Antimicrobials are often needed
for prophylaxis and treatment because patients are immunosuppressed; in such patients, infections can progress quickly with little clinical prodrome. After appropriate studies and cultures have been done, febrile patients with neutrophil counts < 500/mcL (< 0.5 × 109/L) should begin treatment with a broad-spectrum bactericidal antibiotic that is effective against gram-positive and gram-negative organisms (eg, ceftazidime, piperacillin and
tazobactam, meropenem). Fungal infections, especially pneumonias, may develop and are difficult to diagnose, so chest CT to detect fungal pneumonia should be done early (ie, within 72 hours of presentation with neutropenic fever, depending on the degree of suspicion). Empiric antifungal therapy should be given if antibacterial therapy is not effective within 72 hours. There is a significant drug-drug interaction between vincristine, which is commonly used in all ALL
treatment regimens, and azole antifungals. In patients with refractory pneumonitis, Pneumocystis jirovecii infection
Pneumocystis jirovecii Pneumonia Pneumocystis jirovecii is a common cause of pneumonia in immunosuppressed patients, especially in those infected with human immunodeficiency virus (HIV) and in those receiving systemic... read more
Posaconazole, a 2nd-generation triazole antifungal drug, is indicated for primary prophylaxis in patients age > 13 years who are at high risk of developing invasive Aspergillus and Candida infections because of immunosuppression (eg, hematopoietic stem cell transplant recipients with graft-versus-host disease). In patients with drug-induced immunosuppression (eg, prolonged use of corticosteroids for ALL treatment), trimethoprim/sulfamethoxazole (TMP/SMX), dapsone, atovaquone, or pentamidine is indicated to prevent P. jirovecii pneumonia. Acyclovir or valacyclovir prophylaxis is generally recommended for all patients. Hydration, urine alkalinization with IV sodium bicarbonate, and allopurinol or rasburicase can prevent and treat the hyperuricemia, hyperphosphatemia, hypocalcemia, and hyperkalemia (ie,
tumor lysis syndrome
Tumor Lysis and Cytokine Release Syndromes Adverse effects are common in patients receiving any cancer therapy, particularly cytopenias, gastrointestinal effects, and tumor lysis and cytokine release syndromes. Patients may also have... read more ) caused by the
rapid lysis of leukemic cells during initial therapy in ALL. Hyperuricemia is minimized by reducing the conversion of xanthine to uric acid by giving allopurinol (a xanthine oxidase inhibitor) or rasburicase (a recombinant urate-oxidase enzyme) before starting chemotherapy. Patients with
G6PD deficiency
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymatic defect common in people with African ancestry that can result in hemolysis after acute illnesses or intake of oxidant... read more
Psychologic support may help patients and their families with the shock of illness and the rigors of treatment for a potentially life-threatening condition.
The following is an English-language resource that may be useful. Please note that THE MANUAL is not responsible for the content of this resource. Click here for Patient Education What is the nursing diagnosis with acute lymphocytic leukemia and thrombocytopenia?Based on the assessment data, major nursing diagnoses for the patient with ALL may include: Risk for infection related to overproduction of immature WBCs. Risk for impaired skin integrity related to toxic effects of chemotherapy, alteration in nutrition, and impaired immobility.
What are some nursing diagnosis for leukemia?Here are five (5) nursing care plans (NCP) and nursing diagnosis for patients with leukemia:. Risk for Infection.. Risk for Deficient Fluid Volume.. Acute Pain.. Activity Intolerance.. Deficient Knowledge.. Other Possible Nursing Care Plans.. What is the diagnosis of acute lymphocytic leukemia?To confirm a diagnosis of acute lymphoblastic leukaemia, the haematologist will take a small sample of your bone marrow to examine under a microscope. The haematologist will use a local anaesthetic to numb the skin over a bone – usually the hip bone – before removing a sample of bone marrow using a needle.
What are three differential diagnoses for acute lymphocytic leukemia?The following are possible differential diagnosis for ALL: Acute myelocytic leukemia. Acute anemia. Juvenile Rheumatoid Arthritis.
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