Background
Acute lymphoblastic leukemia (ALL) is a malignant (clonal) disease of the bone marrow in which early lymphoid precursors proliferate and replace the normal hematopoietic cells of the marrow. ALL may be distinguished from other malignant lymphoid disorders by the immunophenotype of the cells, which is similar to B- or T-precursor cells. Immunochemistry, cytochemistry, and cytogenetic markers may also aid in categorizing the malignant lymphoid clone.
The image below shows pre–B-cell ALL.
Diagnostic workup of a patient with pre–B-cell acute lymphoblastic leukemia. Bone marrow aspiration revealed French-American-British L2 morphology. See also Pediatric Acute Lymphoblastic Leukemia and Acute Myelogenous Leukemia.
Pathophysiology
The malignant cells of acute lymphoblastic leukemia (ALL) are lymphoid precursor cells (ie, lymphoblasts) that are arrested in an early stage of development. This arrest is caused by an abnormal expression of genes, often as a result of chromosomal translocations. The lymphoblasts replace the normal marrow elements, resulting in a marked decrease in the production of normal blood cells. Consequently, anemia, thrombocytopenia, and neutropenia occur to varying degrees. The lymphoblasts also proliferate in organs other than the marrow, particularly the liver, spleen, and lymph nodes.
Etiology
Less is known about the etiology of acute lymphoblastic leukemia (ALL) in adults compared with acute myelogenous leukemia (AML). Most adults with ALL have no identifiable risk factors.
Although most leukemias occurring after exposure to radiation are AML rather than ALL, an increased prevalence of ALL was noted in survivors of the Hiroshima atomic bomb but not in those who survived the Nagasaki atomic bomb.
Rare patients have an antecedent hematologic disorder (AHD) such as myelodysplastic syndrome (MDS) that evolves to ALL. However, most patients with MDS that evolves to acute leukemia develop AML rather than ALL.
Increasingly, cases of ALL with abnormalities of chromosome band 11q23 following treatment with topoisomerase II inhibitors for another malignancy have been described. However, most patients who develop secondary acute leukemia after chemotherapy for another cancer develop AML rather than ALL.
Epidemiology
Acute lymphoblastic leukemia (ALL) is the most common type of cancer and leukemia in children in the United States. In adults, this disease is less common than acute myelogenous leukemia (AML). Approximately 1000 new cases of ALL occur in adults each year. However, due to the fact that there are more adults than children, the number of cases seen in adults is comparable to that seen in children.
Worldwide, the highest incidence of ALL occurs in Italy, the United States, Switzerland, and Costa Rica, and this disease is slightly more common in men than in women.
Prognosis
Only 20-40% of adults with acute lymphoblastic leukemia (ALL) are cured with current treatment regimens.
Patients with acute lymphoblastic leukemia (ALL) are divided into 3 prognostic groups: good risk, intermediate risk, and poor risk.
Good risk includes the following:
- No adverse cytogenetics
- Age younger than 30 years
- White blood cell (WBC) count of less than 30,000/μL
- Complete remission within 4 weeks
Intermediate risk includes those whose condition does not meet the criteria for either good risk or poor risk.
Poor risk includes the following:
- Adverse cytogenetics [(t9;22), (4;11)]
- Age older than 60 years
- Precursor B-cell WBCs with WBC count greater than 100,000/μL
- Failure to achieve complete remission within 4 weeks
Patients with precursor B-cell ALL have an extremely poor prognosis. Essentially, following standard chemotherapy or autologous transplantation, long-term survival is not achieved. Several reports have indicated that some patients with precursor B-cell ALL and t(4;11) may have prolonged survival following allogeneic transplantation; therefore, this is the treatment of choice.
Immunophenotype effects on prognosis
Czuczman et al studied 259 patients treated with several Cancer and Leukemia Group B (CALGB) protocols for newly diagnosed acute lymphoblastic leukemia (ALL) and found no significant difference in response rates, remission duration, or survival for patients expressing myeloid antigens versus those not expressing myeloid antigens.[1] B-lineage phenotype was expressed in 79% of patients; one third of these coexpressed myeloid antigens. Seventeen percent of patients demonstrated T-lineage ALL; one quarter of these coexpressed myeloid antigens.[1]
T-lineage ALL was associated with younger age, male sex, presence of a mediastinal mass, higher WBC count and hemoglobin level, longer survival, and longer disease-free survival. The number of T markers expressed also had prognostic significance. Patients expressing 6 or more markers had longer disease-free and overall survival compared with patients expressing 3 or fewer markers.
In a report by Preti et al, 64 of 162 patients with newly diagnosed ALL coexpressed myeloid markers.[2] Patients coexpressing myeloid markers were significantly older, had a higher prevalence of CD34 expression, and had a lower prevalence of common ALL antigen expression than patients without myeloid expression. A trend toward a decreased remission rate was observed for patients coexpressing myeloid markers (64%) relative to those who did not coexpress such markers (78%).[2] However, no significant effect on remission duration or overall survival was observed.
Chromosome number and prognosis
The effect of chromosome number on prognosis is displayed in Table 1, below.
Table 1. Effect of Chromosome Number on Prognosis (Open Table in a new window)
| Chromosome Number | 3-Year Event-Free Survival |
| Near tetraploidy | 46-56% |
| Normal karyotype | 34-44% |
| Hyperdiploidy >50 | 32-59% |
| Hyperdiploidy 47-50 | 21-53% |
| Pseudodiploidy | 12-25% |
| Hypodiploidy | 11% |
Complications and prognosis
The most common complication is failure of the leukemia to respond to chemotherapy. These patients do poorly, because they usually do not respond to other chemotherapy regimens.
Death in those with ALL may occur as a result of uncontrolled infection or hemorrhage. This may occur even after the use of appropriate blood product and antibiotic support.
Patient Education
Patients with acute lymphoblastic leukemia (ALL) should be instructed to immediately seek medical attention if they are febrile or have signs of bleeding. Furthermore, while receiving chemotherapy, patients with leukemia should avoid exposure to crowds and people with contagious illnesses, especially children with viral infections.
Although activity may occur as tolerated, patients with ALL may not participate in strenuous activities such as lifting or exercise. In addition, a neutropenic diet is recommended in these individuals, as follows:
- No fresh fruits or vegetables may be eaten.
- All foods must be cooked.
- Meats are to be cooked until well done.
For patient education information, see Blood and Lymphatic System Center and Cancer and Tumors Center, as well as Leukemia.
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| Chromosome Number | 3-Year Event-Free Survival |
| Near tetraploidy | 46-56% |
| Normal karyotype | 34-44% |
| Hyperdiploidy >50 | 32-59% |
| Hyperdiploidy 47-50 | 21-53% |
| Pseudodiploidy | 12-25% |
| Hypodiploidy | 11% |
| Abnormality | Genes Involved | 3-Year Event-Free Survival |
| t(10;14)(q24;q11) | HOX11/TCRA | 75% |
| 6q | Unknown | 47% |
| 14q11 | TCRA/TCRD | 42% |
| 11q23 | MLL | 18-26% |
| 9p | Unknown | 22% |
| 12 | TEL | 20% |
| t(1;19)(q23;p13) | PBX1/E2A | 20% |
| t(8;14)(q24;q32) t(2;8)(p12;q24) t(8;22)(q24;q11) | c-myc/IGH IGK/c-myc c-myc/IGL | 17%* 80%† |
| t(9;22)(q34;q11) | bcr-abl | 5-10%* 66%‡ |
| t(4;11)(q21;q23) | AF4-MLL | 0-10% |
| * Traditional regimens. † Hyper-CVAD (cyclophosphamide, vincristine, doxorubicin [Adriamycin], dexamethasone) with rituxan. ‡ Hyper-CVAD with imatinib. | ||
| ALL Cells | TdT | CD19 | CD10 | CyIg | SIg |
| Early B-precursor ALL | + | + | - | - | - |
| Pre–B-cell ALL (see the image below) | + | + | + | + | - |
| B-cell ALL | - | + | +/- | +/- | + |
| ALL = acute lymphoblastic leukemia; Cylg = Cytoplasmic immunoglobulin; SIg =Surface immunoglobulin; TdT = terminal deoxynucleotidyl transferase. | |||||
| ALL Cells | TdT | Surface CD3 | CD4/CD8 |
| Early T-precursor ALL | + | - | +/+ or -/- |
| T-cell ALL | + | + | +/- or -/+ |
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