PROGNOSIS AND THERAPY WHEN ACUTE PROMYELOCYTIC LEUKEMIA AND OTHER “GOOD RISK” ACUTE MYELOID LEUKEMIAS OCCUR AS A THERAPY-RELATED MYELOID NEOPLASM
Treatment for a pre-existing condition using chemotherapy, radiation therapy, immunosuppressive therapy, or a combination of these modalities may lead to the devastating complication of therapy-related myelodysplastic syndrome or acute myeloid leukemia (t-MDS/t-AML), collectively known as therapy-re...
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| Language: | English |
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PAGEPress Publications
2011-07-01
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| Series: | Mediterranean Journal of Hematology and Infectious Diseases |
| Online Access: | http://www.mjhid.org/index.php/mjhid/article/view/289 |
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| author | Richard A. Larson Michelle Le Beau |
| author_facet | Richard A. Larson Michelle Le Beau |
| author_sort | Richard A. Larson |
| collection | DOAJ |
| description | Treatment for a pre-existing condition using chemotherapy, radiation therapy, immunosuppressive therapy, or a combination of these modalities may lead to the devastating complication of therapy-related myelodysplastic syndrome or acute myeloid leukemia (t-MDS/t-AML), collectively known as therapy-related myeloid neoplasm (t-MN). This disorder arises as a direct consequence of mutational events induced by the primary treatment. The outcomes for these patients have been historically poor compared to people who develop AML de novo. Currently comprising 10-20% of all cases of AML, t-MN is relatively resistant to conventional leukemia therapies, and is associated with short survival times. Median life expectancy from diagnosis is about 8-10 months in most series. Although the spectrum of cytogenetic abnormalities in t-AML is similar to AML de novo, the frequency of unfavorable cytogenetics, such as a complex karyotype or deletion or loss of chromosomes 5 and/or 7, is considerably higher in t-MN. Two distinct groups of patients with t-MN have been described. The more common subtype, seen in about 75% of patients, typically occurs 5-7 years after first exposure to alkylating agents or radiation, is often preceded by a myelodysplastic syndrome, and is frequently accompanied by clonal cytogenetic abnormalities such as the loss of all or part of chromosomes 5 or 7. Mutations of the P53 tumor suppressor gene are also common. The risk is related to total cumulative exposure over time to alkylating agents. In contrast, among individuals who develop t-AML after treatment with topoisomerase II inhibitors, the latency period to the development of t-AML is often only 1-3 years, antecedent MDS is rare, and gene rearrangements involving MLL at 11q23 or RUNX1/AML1 at 21q22 are common. It is now well recognized that acute promyelocytic leukemia (APL) and other subtypes of AML with balanced translocations sometimes occur as a t-MN in patients who have previously received cytotoxic therapy or ionizing radiation therapy. In general, t-MN patients should be encouraged to participate in prospective clinical trials that are appropriately designed for other AML patients with similar cytogenetic abnormalities. Patients who have an HLA-matched donor should be considered for allogeneic hematopoietic cell transplantation, although patients with favorable karyotypes such as t(15;17) and inv(16) may do well with conventional intensive chemotherapy. This review will focus on these “good risk” therapy-related leukemias, i.e. those with APL or inv(16)/t(16;16) or t(8;21). |
| format | Article |
| id | doaj-art-bf7f5d69817c489ab1fe9fd6383855ff |
| institution | DOAJ |
| issn | 2035-3006 |
| language | English |
| publishDate | 2011-07-01 |
| publisher | PAGEPress Publications |
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| series | Mediterranean Journal of Hematology and Infectious Diseases |
| spelling | doaj-art-bf7f5d69817c489ab1fe9fd6383855ff2025-08-20T02:51:02ZengPAGEPress PublicationsMediterranean Journal of Hematology and Infectious Diseases2035-30062011-07-0131e2011032e201103210.4084/mjhid.2011.032181PROGNOSIS AND THERAPY WHEN ACUTE PROMYELOCYTIC LEUKEMIA AND OTHER “GOOD RISK” ACUTE MYELOID LEUKEMIAS OCCUR AS A THERAPY-RELATED MYELOID NEOPLASMRichard A. LarsonMichelle Le BeauTreatment for a pre-existing condition using chemotherapy, radiation therapy, immunosuppressive therapy, or a combination of these modalities may lead to the devastating complication of therapy-related myelodysplastic syndrome or acute myeloid leukemia (t-MDS/t-AML), collectively known as therapy-related myeloid neoplasm (t-MN). This disorder arises as a direct consequence of mutational events induced by the primary treatment. The outcomes for these patients have been historically poor compared to people who develop AML de novo. Currently comprising 10-20% of all cases of AML, t-MN is relatively resistant to conventional leukemia therapies, and is associated with short survival times. Median life expectancy from diagnosis is about 8-10 months in most series. Although the spectrum of cytogenetic abnormalities in t-AML is similar to AML de novo, the frequency of unfavorable cytogenetics, such as a complex karyotype or deletion or loss of chromosomes 5 and/or 7, is considerably higher in t-MN. Two distinct groups of patients with t-MN have been described. The more common subtype, seen in about 75% of patients, typically occurs 5-7 years after first exposure to alkylating agents or radiation, is often preceded by a myelodysplastic syndrome, and is frequently accompanied by clonal cytogenetic abnormalities such as the loss of all or part of chromosomes 5 or 7. Mutations of the P53 tumor suppressor gene are also common. The risk is related to total cumulative exposure over time to alkylating agents. In contrast, among individuals who develop t-AML after treatment with topoisomerase II inhibitors, the latency period to the development of t-AML is often only 1-3 years, antecedent MDS is rare, and gene rearrangements involving MLL at 11q23 or RUNX1/AML1 at 21q22 are common. It is now well recognized that acute promyelocytic leukemia (APL) and other subtypes of AML with balanced translocations sometimes occur as a t-MN in patients who have previously received cytotoxic therapy or ionizing radiation therapy. In general, t-MN patients should be encouraged to participate in prospective clinical trials that are appropriately designed for other AML patients with similar cytogenetic abnormalities. Patients who have an HLA-matched donor should be considered for allogeneic hematopoietic cell transplantation, although patients with favorable karyotypes such as t(15;17) and inv(16) may do well with conventional intensive chemotherapy. This review will focus on these “good risk” therapy-related leukemias, i.e. those with APL or inv(16)/t(16;16) or t(8;21).http://www.mjhid.org/index.php/mjhid/article/view/289 |
| spellingShingle | Richard A. Larson Michelle Le Beau PROGNOSIS AND THERAPY WHEN ACUTE PROMYELOCYTIC LEUKEMIA AND OTHER “GOOD RISK” ACUTE MYELOID LEUKEMIAS OCCUR AS A THERAPY-RELATED MYELOID NEOPLASM Mediterranean Journal of Hematology and Infectious Diseases |
| title | PROGNOSIS AND THERAPY WHEN ACUTE PROMYELOCYTIC LEUKEMIA AND OTHER “GOOD RISK” ACUTE MYELOID LEUKEMIAS OCCUR AS A THERAPY-RELATED MYELOID NEOPLASM |
| title_full | PROGNOSIS AND THERAPY WHEN ACUTE PROMYELOCYTIC LEUKEMIA AND OTHER “GOOD RISK” ACUTE MYELOID LEUKEMIAS OCCUR AS A THERAPY-RELATED MYELOID NEOPLASM |
| title_fullStr | PROGNOSIS AND THERAPY WHEN ACUTE PROMYELOCYTIC LEUKEMIA AND OTHER “GOOD RISK” ACUTE MYELOID LEUKEMIAS OCCUR AS A THERAPY-RELATED MYELOID NEOPLASM |
| title_full_unstemmed | PROGNOSIS AND THERAPY WHEN ACUTE PROMYELOCYTIC LEUKEMIA AND OTHER “GOOD RISK” ACUTE MYELOID LEUKEMIAS OCCUR AS A THERAPY-RELATED MYELOID NEOPLASM |
| title_short | PROGNOSIS AND THERAPY WHEN ACUTE PROMYELOCYTIC LEUKEMIA AND OTHER “GOOD RISK” ACUTE MYELOID LEUKEMIAS OCCUR AS A THERAPY-RELATED MYELOID NEOPLASM |
| title_sort | prognosis and therapy when acute promyelocytic leukemia and other good risk acute myeloid leukemias occur as a therapy related myeloid neoplasm |
| url | http://www.mjhid.org/index.php/mjhid/article/view/289 |
| work_keys_str_mv | AT richardalarson prognosisandtherapywhenacutepromyelocyticleukemiaandothergoodriskacutemyeloidleukemiasoccurasatherapyrelatedmyeloidneoplasm AT michellelebeau prognosisandtherapywhenacutepromyelocyticleukemiaandothergoodriskacutemyeloidleukemiasoccurasatherapyrelatedmyeloidneoplasm |