Relationship Between Minimal Residual Disease and Outcome in Adult Acute Lymphoblastic Leukemia
In children with acute lymphoblastic leukemia (ALL), the level of minimal residual disease (MRD) at the end of induction strongly predicts outcome, presumably because it measures both drug sensitivity and the number of leukemic cells requiring elimination. Children with high levels (>10–3 leukemi...
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| Published in: | Blood Vol. 87; no. 12; pp. 5251 - 5256 |
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| Main Authors: | , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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Washington, DC
Elsevier Inc
15-06-1996
The Americain Society of Hematology |
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| Abstract | In children with acute lymphoblastic leukemia (ALL), the level of minimal residual disease (MRD) at the end of induction strongly predicts outcome, presumably because it measures both drug sensitivity and the number of leukemic cells requiring elimination. Children with high levels (>10–3 leukemic cells per marrow cell) nearly always relapse, whereas those with low levels (<2 × 10–5) seldom do. However, the importance of MRD in adult ALL is unclear. We studied 27 patients aged 14 to 74 who were treated with a standard protocol and who attained morphological remission. MRD in the marrow at first remission was quantified by using the polymerase chain reaction (PCR), with the rearranged immunoglobulin heavy chain gene as a molecular marker. Levels of MRD varied from 3 × 10–1 to <7 × 10–7. The probability of long-term relapse-free survival was significantly related to the level of MRD and only one of nine patients with MRD >10 3 did not relapse. For patients who did relapse, there was an inverse relationship between MRD level and the length of remission. Overall, MRD in adults in whom a translocation had not been identified was significantly higher than in comparably-treated children, suggesting that ALL in adults is more drug-resistant than in children. |
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| AbstractList | In children with acute lymphoblastic leukemia (ALL), the level of minimal residual disease (MRD) at the end of induction strongly predicts outcome, presumably because it measures both drug sensitivity and the number of leukemic cells requiring elimination. Children with high levels (> 10(-3) leukemic cells per marrow cell) nearly always relapse, whereas those with low levels (<2 x 10(-5)) seldom do. However, the importance of MRD in adult ALL is unclear. We studied 27 patients aged 14 to 74 who were treated with a standard protocol and who attained morphological remission. MRD in the marrow at first remission was quantified by using the polymerase chain reaction (PCR), with the rearranged immunoglobulin heavy chain gene as a molecular marker. Levels of MRD varied from 3 x 10(-1) to <7 x 10(-7). The probability of long-term relapse-free survival was significantly related to the level of MRD and only one of nine patients with MRD >10(- 3) did not relapse. For patients who did relapse, there was an inverse relationship between MRD level and the length of remission. Overall, MRD in adults in whom a translocation had not been identified was significantly higher than in comparably-treated children, suggesting that ALL in adults is more drug-resistant than in children. In children with acute lymphoblastic leukemia (ALL), the level of minimal residual disease (MRD) at the end of induction strongly predicts outcome, presumably because it measures both drug sensitivity and the number of leukemic cells requiring elimination. Children with high levels (>10–3 leukemic cells per marrow cell) nearly always relapse, whereas those with low levels (<2 × 10–5) seldom do. However, the importance of MRD in adult ALL is unclear. We studied 27 patients aged 14 to 74 who were treated with a standard protocol and who attained morphological remission. MRD in the marrow at first remission was quantified by using the polymerase chain reaction (PCR), with the rearranged immunoglobulin heavy chain gene as a molecular marker. Levels of MRD varied from 3 × 10–1 to <7 × 10–7. The probability of long-term relapse-free survival was significantly related to the level of MRD and only one of nine patients with MRD >10 3 did not relapse. For patients who did relapse, there was an inverse relationship between MRD level and the length of remission. Overall, MRD in adults in whom a translocation had not been identified was significantly higher than in comparably-treated children, suggesting that ALL in adults is more drug-resistant than in children. |
| Author | Morley, Alexander A. Hughes, Elizabeth Brisco, Michael J. McCaul, Kieran Neoh, Sim H. Bradstock, Kenneth Sykes, Pamela J. Szer, Jeffrey Enno, Arno |
| Author_xml | – sequence: 1 givenname: Michael J. surname: Brisco fullname: Brisco, Michael J. – sequence: 2 givenname: Elizabeth surname: Hughes fullname: Hughes, Elizabeth – sequence: 3 givenname: Sim H. surname: Neoh fullname: Neoh, Sim H. – sequence: 4 givenname: Pamela J. surname: Sykes fullname: Sykes, Pamela J. – sequence: 5 givenname: Kenneth surname: Bradstock fullname: Bradstock, Kenneth – sequence: 6 givenname: Arno surname: Enno fullname: Enno, Arno – sequence: 7 givenname: Jeffrey surname: Szer fullname: Szer, Jeffrey – sequence: 8 givenname: Kieran surname: McCaul fullname: McCaul, Kieran – sequence: 9 givenname: Alexander A. surname: Morley fullname: Morley, Alexander A. |
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| ContentType | Journal Article |
| Copyright | 1996 American Society of Hematology 1996 INIST-CNRS |
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| Issue | 12 |
| Keywords | Human Antineoplastic agent Prognosis Acute Minimal residual disease Malignant hemopathy Induction treatment Chemotherapy Lymphoproliferative syndrome Adult Remission Acute lymphocytic leukemia Predictive factor Quantitative analysis |
| Language | English |
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| Snippet | In children with acute lymphoblastic leukemia (ALL), the level of minimal residual disease (MRD) at the end of induction strongly predicts outcome, presumably... |
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| SubjectTerms | Adolescent Adult Age Factors Aged Antineoplastic Combined Chemotherapy Protocols - therapeutic use Asparaginase - administration & dosage Biological and medical sciences Bone Marrow - pathology Bone Marrow Transplantation Combined Modality Therapy Cranial Irradiation Cyclophosphamide - administration & dosage Cytarabine - administration & dosage Daunorubicin - administration & dosage Disease-Free Survival Drug Resistance, Neoplasm Etoposide - administration & dosage Gene Rearrangement, B-Lymphocyte, Heavy Chain Hematologic and hematopoietic diseases Humans Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Medical sciences Mercaptopurine - administration & dosage Methotrexate - administration & dosage Middle Aged Neoplasm, Residual Philadelphia Chromosome Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy Prednisolone - administration & dosage Prognosis Survival Analysis Treatment Outcome Vincristine - administration & dosage |
| Title | Relationship Between Minimal Residual Disease and Outcome in Adult Acute Lymphoblastic Leukemia |
| URI | https://dx.doi.org/10.1182/blood.V87.12.5251.bloodjournal87125251 https://www.ncbi.nlm.nih.gov/pubmed/8652840 |
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