(See also Overview of Leukemia Overview of Leukemia Leukemia is a malignant condition involving the excess production of immature or abnormal leukocytes, which eventually suppresses the production of normal blood cells and results in symptoms... read more .)
The American Cancer Society estimates that in the United States in 2020 there will be about 6,150 new cases of acute lymphoblastic leukemia (ALL) and about 1,520 deaths. 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, and 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.
Pathophysiology of ALL
Similar to acute myeloid leukemia Acute Myeloid Leukemia (AML) In acute myeloid leukemia (AML), malignant transformation and uncontrolled proliferation of an abnormally differentiated, long-lived myeloid progenitor cell results in high circulating numbers... read more (AML), 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.
Classification of ALL
In acute lymphoblastic leukemia, the precursor lymphoid neoplasms are broadly categorized based on their lineage into
B-lymphoblastic leukemia/lymphoma (B-ALL/LBL)
T-lymphoblastic leukemia/lymphoma (T-ALL/LBL)
Disease can manifest as leukemia when neoplastic cells (lymphoblasts) involve blood and bone marrow (defined as > 20% bone marrow blasts) or as lymphoma Overview of Lymphoma Lymphomas are a heterogeneous group of tumors arising in the reticuloendothelial and lymphatic systems. The major types are Hodgkin lymphoma and non-Hodgkin lymphoma (see table Comparison of... read more when blasts infiltrate mainly extramedullary tissue.
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 ALL
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.
Diagnosis of ALL
Complete blood count (CBC) and peripheral blood smear
Bone marrow examination
Histochemical studies, cytogenetics and immunophenotyping
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 , viral infections such as infectious mononucleosis Infectious Mononucleosis Infectious mononucleosis is caused by Epstein-Barr virus (EBV, human herpesvirus type 4) and is characterized by fatigue, fever, pharyngitis, and lymphadenopathy. Fatigue may persist weeks or... read more , and vitamin B12 deficiency Vitamin B12 Deficiency Dietary vitamin B12 deficiency usually results from inadequate absorption, but deficiency can develop in vegans who do not take vitamin supplements. Deficiency causes megaloblastic anemia, damage... read more , and folate deficiency Folate Deficiency Folate deficiency is common. It may result from inadequate intake, malabsorption, or use of various drugs. Deficiency causes megaloblastic anemia (indistinguishable from that due to vitamin... read more should be considered in the differential diagnosis of severe pancytopenia. Leukemoid reactions (marked granulocytic leukocytosis [ie, WBC > 50,000/mcL, > 50 × 109/L] produced by normal bone marrow) to infectious disease never manifest with high blast counts. Unlike in AML, Auer rods (linear azurophilic inclusions in the cytoplasm of blast cells) are never present in acute lymphoblastic leukemia.
Bone marrow examination (aspiration and needle biopsy) is routinely done. Blast cells in the bone marrow are classically between 25 and 95%.
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 immunophenotypical 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 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 ).
Less common cytogenetic abnormalities include the following:
t(v;11q23) /MLL or KMT2A rearranged, including t(4;11)/KMT2A-AF4
t(8;14), t(8;22), t(2;8)/C-MYC rearranged
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 features... 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 are... 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 4.7 mg/dL ( 1.17... 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. Patients may also have adverse effects resulting from their cancer. Successfully managing these adverse effects is important... read more . Elevated serum 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).
Prognosis for ALL
Prognostic factors help determine treatment protocol and intensity.
Favorable prognostic factors are
Age 3 to 9 years
WBC count < 25,000/mcL (< 25 × 109/L) or < 50,000/mcL (< 50 × 109/L) in children
Leukemic cell karyotype with high hyperdiploidy (51 to 65 chromosomes), t(1;19), and t(12;21)
No CNS disease at diagnosis
Unfavorable factors include
Leukemic cell karyotype with 23 chromosomes (haploidy), with < 46 chromosomes (hypodiploidy), or with 66 to 68 chromosomes (near triploidy)
Leukemic cell karyotype with t(v;11q23) MLL (KMT2A) rearranged, including t(4;11)/KMT2A-AF4
Leukemic cell karyotype t(5;14)/IL3-IG
Leukemic cell karyotype t(8;14), t(8;22), t(2;8) C-MYC rearranged
Presence of the Philadelphia (Ph) chromosome t(9;22) BCR-ABL1
Increased age in adults
BCR/ABL-like molecular signature
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:
Less ability to tolerate intensive chemotherapy
More frequent and severe comorbidities
Higher risk ALL genetics that confer chemotherapy resistance
Poorer adherence to ALL treatment regimens, which include frequent (often daily or weekly) out-patient chemotherapy and doctor visits
Less frequent use of pediatric-inspired treatment regimens
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 of ALL
Prophylactic CNS chemotherapy and sometimes CNS radiation
For Ph+ ALL, also a tyrosine kinase inhibitor
Sometimes immunotherapy, targeted therapy, 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 , and/or radiation therapy
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
Interim maintenance and intensification
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 ). Measurable or minimal residual disease is microscopic disease that is not detected by standard assays but can be measured by more sensitive assays. A low measurable residual disease (MRD negativity) is defined variably (based on the assay used) as < 0.01 to 0.1% leukemic cells in bone marrow
Components of induction therapy include
A high-dose corticosteroid (eg, dexamethasone, prednisone)
An anthracycline (eg, daunorubicin, doxorubicin, idarubicin)
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.
The goal of consolidation is to prevent leukemic regrowth. Consolidation therapy usually lasts a few months and combines regimen-specific courses of non–cross-resistant drugs that have different mechanisms of action. For adults with Ph+ ALL, allogeneic 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 recommended as consolidation therapy.
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.
Medically frail patients with ALL
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 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.
Relapsed or refractory ALL
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.
New immunotherapy approaches show impressive results in relapsed/refractory ALL. Antibodies, such as blinatumomab, that bring T cells into close proximity to leukemic blasts demonstrate activity in relapsed ALL. Chimeric antigen receptor T (CAR-T) cells, engineered and generated from the patient's T cells, induce remission in patients with relapsed ALL with remarkable efficacy, albeit with significant toxicity (2 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 ).
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. Patients may also have adverse effects resulting from their cancer. Successfully managing these adverse effects is important... 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 ).
Inotuzumab ozogamicin, a CD22-directed antibody-drug conjugate with calicheamicin, is also available for adults with relapsed or refractory B-cell precursor ALL. One study found significantly higher remission rates after 1 to 2 cycles of therapy with inotuzumab ozogamicin than with standard chemotherapy (4 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 ). Inotuzumab may cause hepatotoxicity, including fatal and life-threatening veno-occlusive disease and is associated with higher post-transplant non-relapse mortality.
Tisagenlecleucel, a CD19-directed genetically modified autologous T-cell immunotherapy, is available for the treatment of patients up to 25 years of age with B-cell precursor ALL that is refractory or in a 2nd or later relapse. Cytokine release syndrome Cytokine release syndrome Adverse effects are common in patients receiving any cancer therapy. Patients may also have adverse effects resulting from their cancer. Successfully managing these adverse effects is important... read more and life-threatening or fatal neurologic toxicities may occur (5 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 are available, but for which clinically meaningful outcomes have not been convincingly demonstrated, include
Liposomal vincristine (a vinca alkaloid): For adults with Ph- ALL in at least 2nd relapse or that has progressed despite ≥ 2 antileukemia therapies
Clofarabine (a purine nucleoside analog): For patients age 1 to 21 years with relapsed or refractory ALL after ≥ 2 prior regimens
Nelarabine (a purine nucleoside) analog prodrug of guanosine arabinoside: For T-cell ALL that has not responded to or has relapsed after ≥ 2 prior regimens
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 following reinduction chemotherapy or immunotherapy offers the greatest hope of long-term remission or cure if an HLA-matched sibling is available. Cells from other relatives or from matched, unrelated donors are sometimes used. Transplantation is rarely used for patients > 65 years because it is much less likely to be successful and because adverse effects are much more likely to be fatal.
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
Hydration and urine alkalinization
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, are becoming more common; these infections 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 corticosteroids... read more or a viral infection should be suspected and confirmed by bronchoscopy and bronchoalveolar lavage and treated appropriately. 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. Patients may also have adverse effects resulting from their cancer. Successfully managing these adverse effects is important... 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.
Psychologic support may help patients and their families with the shock of illness and the rigors of treatment for a potentially life-threatening condition.
1. Berry DA, Zhou S, Higley H, et al: Association of minimal residual disease with clinical outcome in pediatric and adult acute lymphoblastic leukemia: A meta-analysis. JAMA Oncol 3(7): e170580, 2017. doi:10.1001/jamaoncol.2017.0580
2. Lee DW, Kochenderfer JN, Stetler-Stevenson M, et al: T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet385(9967) :517–528, 2015.
3. Kantarjian H, Stein A, Gökbuget N, et al: Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med 376(9):836–847, 2017.
4. Kantarjian HM, DeAngelo DJ, Stelljes M, et al: Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med 375(8):740–753, 2016.
5. Maude SL, Laetsch TW, Buechner J, et al: Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med 378(5):439–448, 2018.
Acute lymphoblastic leukemia (ALL) is the most common cancer in children but also occurs in adults.
Central nervous system (CNS) involvement is common; most patients receive intrathecal chemotherapy and corticosteroids and sometimes CNS radiation therapy.
Response to treatment is good in children, with cure possible in > 80% of children but in < 50% of adults.
Repeat induction chemotherapy, immunotherapy, and stem cell transplantation may be helpful for relapse.
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.