Chromosomal abnormalities in women with breast cancer after autologous stem cell transplantation are infrequent and may not predict development of therapy-related leukemia or myelodysplastic syndrome

Ja, Martínez-Climent; Am, Comes; Vizcarra, E; Benet, Isabel; Arbona, Cristina; Prósper, Felipe; Solano, Carlos; B, García Clavel; Marugán, Isabel; Lluch, Aña; Garcı́a-Conde, J

doi:10.1038/sj.bmt.1702416

Cited by 18 publications

(8 citation statements)

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“…17 In a Spanish trial involving 229 patients after a median followup of 36 months, no single case of secondary MDS/AML was observed. 19 In that trial, cytogenetic aberrations were found in some patients (5%), after HDCT, but these aberrations were only transient and disappeared without developing into MDS or AML. Recently, in a retrospective EBMT study, only one case of treatment-related AML with 11q23 translocation was observed in 364 patients with primary breast cancer after HDCT.…”

Section: Discussionmentioning

confidence: 99%

“…Few studies investigated the risk of secondary MDS/AML after highdose chemotherapy (HDCT) in breast cancer patients, suggesting a similar incidence as conventional chemotherapy. [16][17][18][19] Mitoxantrone is part of several high-dose chemotherapy regimens followed by autologous stem cell transplantation in breast cancer patients. [20][21][22][23] In the present study, we evaluate the incidence of secondary MDS/AML in 305 breast cancer patients after mitoxantrone-based high-dose conditioning regimens, followed by autologous stem cell transplantation in a joint analysis of the Solid Tumor Working Party of the European Group for Blood and Marrow Transplantation (EBMT), the German Adjuvant Breast Cancer Study Group (GABG), and the University of California, San Francisco (UCSF).…”

Section: Discussionmentioning

confidence: 99%

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Secondary acute leukemia following mitoxantrone-based high-dose chemotherapy for primary breast cancer patients

Kröger

Damon

Zander

et al. 2003

Bone Marrow Transplant

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Summary:The incidence of secondary myelodysplasia/acute myeloid leukemia (AML) was retrospectively assessed in an international joint study in 305 node-positive breast cancer patients, who received mitoxantrone-based high-dose chemotherapy (HDCT) followed by autologous stem cell support as adjuvant therapy. The median age of the patients was 57 years (range 22-67). In all, 268 patients received peripheral blood stem cells, and 47 patients received autologous bone marrow. After a median followup of 57 months (range 10-125), three cases of secondary AML (sAML) were observed, resulting in a cumulative incidence of 0.94%. One case of sAML developed 18 months after HDCT (FAB M3) The karyotype was translocation 15;17 and, after induction therapy, the patient underwent autologous stem cell transplantation, and is in complete remission (CR) of both breast cancer and AML. The second patient developed AML (FAB M4eo with inversion 16) 5 months after HDCT. This patient achieved CR after induction therapy, but died of infectious complication. A third patient developed AML (FAB M4) 6 months after HDCT. She achieved CR after induction therapy, but relapsed and expired 28 months after diagnosis of AML. sAML after mitoxantrone-based HDCT is a possible, but rare complication in breast cancer patients. Bone Marrow Transplantation (2003) 32, 1153-1157. doi:10.1038/sj.bmt.1704291 Keywords: high-dose chemotherapy; adjuvant therapy; breast cancer; mitoxantrone; secondary AML Secondary myelodysplasia (MDS) or acute myeloid leukemia (AML) in breast cancer patients is a rare but wellknown long-term complication of prior chemotherapy or radiation therapy as adjuvant therapy. 1-3 Specific risk factors are the combinations of chemotherapy and radiation therapy, the cumulative dose of alkylating agents and the duration of therapy. 2 Two different types of treatmentrelated leukemia can be distinguished. The first type results from prior therapy with alkylating agents or radiation therapy, and occurs after a latency period of 5-7 years. This type of AML is often preceded by a preleukemic period of MDS. Nearly 90% of the patients with alkylating agentrelated MDS or AML show clonal chromosome aberrations including monosomy or deletions on chromosomes 5 and/or 7 or complex aberrations involving chromosomes 3, 12, 17, and 21. 4 The second type of therapy-related leukemia is induced by topoisomerase II-targeted drugs like etoposide, anthracyclines or, recently, anthracenediones. [5][6][7] This type of AML usually occurs after a median of 2 years and is not preceded by a myelodysplastic syndrome. According to the French-American-British (FAB) classification, more frequently, M4 or M5 subtype is observed and cytogenetic analysis showed a high frequency of rearrangements of the chromosome band as 11q23, translocation (t)(8;21), t(15;17), inversion 16 (inv(16)) or t(8;16), as in de novo AML. 5,8 Recently, several studies indicated that adjuvant chemotherapy consisting of the anthracenedione mitoxantrone, a topoisomerase II-targeted drug, may induce sec...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Secondary acute leukemia following mitoxantrone-based high-dose chemotherapy for primary breast cancer patients

Kröger

Damon

Zander

et al. 2003

Bone Marrow Transplant

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“…[1011] Except MDS, aberrations of 5q generally occur as a part of the complex karyotype in de novo AML. [61112] Post-chemotherapy remission marrow showed the persistence of a dic(5q) clone along with a major normal diploid clone. Later on, successive follow-up cytogenetic studies after PBSCT revealed a normal diploid karyotype, indicating successful peripheral stem cell transplantation with rejuvenation of normal hematopoiesis, which was supported by VNTR analysis that revealed donor genotype.…”

Section: Discussionmentioning

confidence: 99%

“…[4–7] The therapy-related malignancies like post-BMT or post-chemotherapy/radiation-induced leukemia frequently show aberrations of chromosomes 5, 7, 11q23, and 21q22 at early stages, probably due to genetic damage to the residual malignant cells. [6–9]…”

Section: Introductionmentioning

confidence: 99%

Emergence of an unrelated highly aberrant clone in an AML patient at relapse four months after peripheral blood stem cell transplantation

et al. 2007

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We report a case of AML-M1 with 5q aberration at diagnosis. The patient was treated with high-dose chemotherapy (HDCT). After remission induction, he received allogenic peripheral blood stem cell transplantation (PBSCT) from an HLA-match donor brother. The successive follow-up conventional cytogenetics investigations in remission after HDCT and PBSCT revealed cytogenetic remission. The most interesting observation in this case is that relapsed marrow revealed the emergence of an entirely new, highly aberrant, unrelated clone with unusual translocations t(6;17)(p23;p11.2),+8,der(8)dup inv(8)(q23qter), t(10;19)(q26;q13.3) 4½ months after PBSCT. Our findings suggest the possibility of a mutagenic effect of HDCT and myeloablative intense chemotherapy before PBSCT that could have induced a genetic lesion in the recipient's genetically unstable stem cells in an environment of immunosuppression. The highly complex nature of the clone and the rapid clonal evolution indicates the possibility of selective pressure with proliferative advantage.

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“…Some CCA can be a transient finding, especially when the CCA emerges during or immediately following cytotoxic therapies (including chemotherapy and SCT); these transient CCAs are unlikely associated with t‐MDS/AML In a case series of acquired isolated del(7q) following cytotoxic therapies, among 27 patients who had at least 1 follow‐up cytogenetics study, del(7q) was persistent in 15 patients and was transient in 12 patients. Of note, 13 of 15 (87%) patients with persistent del(7q) were either diagnosed with t‐MDS at the time of del(7q) detection or developed t‐MDS during the follow‐up.…”

Section: Ccaus Emerging After Cytotoxic Therapiesmentioning

confidence: 99%

How I investigate Clonal cytogenetic abnormalities of undetermined significance

Tang

Medeiros

Wang

2018

Int J Lab Hematology

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Myelodysplastic syndromes are a group of hematopoietic stem cell diseases characterized by cytopenia(s), morphological dysplasia, and clonal hematopoiesis. In some patients, the cause of cytopenia(s) is uncertain, even after thorough clinical and laboratory evaluation. Evidence of clonal hematopoiesis has been used to support a diagnosis of myelodysplastic syndrome in this setting. In patients with cytopenia(s), the presence of clonal cytogenetic abnormalities, except for +8, del(20q) and -Y, can serve as presumptive evidence of myelodysplastic syndrome. Recent advances in next-generation sequencing have detected myeloid neoplasm-related mutations in patients who do not meet the diagnostic criteria for myelodysplastic syndrome. Various terms have been adopted to describe these cases, including clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS). Similarly, studies have shown that certain chromosomal abnormalities, including ones commonly detected in myelodysplastic syndrome, may not be associated necessarily with an underlying myelodysplastic syndrome. These clonal cytogenetic abnormalities of undetermined significance (CCAUS) are similar to CHIP and CCUS. Here, we review the features of CCAUS, distinguishing CCAUS from clonal cytogenetic abnormalities associated with myelodysplastic syndrome, and the potential impact of CCAUS on patient management.

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Chromosomal abnormalities in women with breast cancer after autologous stem cell transplantation are infrequent and may not predict development of therapy-related leukemia or myelodysplastic syndrome

Cited by 18 publications

References 27 publications

Secondary acute leukemia following mitoxantrone-based high-dose chemotherapy for primary breast cancer patients

Secondary acute leukemia following mitoxantrone-based high-dose chemotherapy for primary breast cancer patients

Emergence of an unrelated highly aberrant clone in an AML patient at relapse four months after peripheral blood stem cell transplantation

How I investigate Clonal cytogenetic abnormalities of undetermined significance

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