title: Cytogenetic Evolution in Myeloid Neoplasms at Relapse after Allogeneic Hematopoietic Cell Transplantation: Association with Previous Chemotherapy and Effect on Survival.
abstract: Cytogenetic evolution (CGE) in patients with myeloid neoplasms who relapsed after an allogeneic (allo) hematopoietic cell transplantation (HCT) has been evaluated by only few studies. The effect of the CGE on survival of relapsed allo-HCT recipients is not clear. The effect of previously received chemotherapy to induce CGE in this patient population has not been studied. The aims of our study are to (1) characterize the patterns of cytogenetic change in patients with myeloid neoplasms who relapsed after an allo-HCT, (2) evaluate the effect of CGE on survival, and (3) explore the association of CGE with previous chemotherapy (including the lines of salvage therapy, type of induction, and conditioning therapy). Of 49 patients with a myeloid malignancy (27 acute myeloid leukemia [AML], 19 myelodysplastic syndrome [MDS]/myeloproliferative neoplasm [MPN], and 3 chronic myelogenous leukemia) who relapsed after an allo-HCT, CGE was observed in 25 (51%), whereas 24 patients had unchanged cytogenetic findings at relapse. The CGE group carried more cytogenetic abnormalities at original diagnosis. The most frequent cytogenetic change was the acquisition of 3 or more new chromosomal abnormalities followed by acquisition of unbalanced abnormalities, aneuploidy, and emergence of apparently new clones unrelated to the original clone. The CGE cohort had higher proportion of MDS and MPN and fewer patients with de novo AML. Disease risk assessment category showed a trend to higher frequency of high-risk patients in the CGE group, though the difference was not statistically significant. Time from diagnosis to transplantation and time from transplantation to relapse were not different between the CGE and non-CGE groups. CGE and non-CGE cohorts had similar exposures to salvage therapy and to induction chemotherapy, as well as similar conditioning regimens; thus, no particular type of chemotherapy emerged as a predisposing factor to CGE. CGE was associated with significantly shortened post-transplantation and postrelapse survival when compared with those of the non-CGE group (P = .004 and P < .001, respectively). Our results underscore the significance of CGE in progression of myeloid malignancies after an allo-HCT.
authors.affiliation: Department of Internal Medicine, Mayo Clinic Arizona, Phoenix, Arizona.
authors.forename: Natalie
authors.initials: N
authors.lastname: Ertz-Archambault
authors.affiliation: Division of Health Sciences Research, Mayo Clinic Arizona, Phoenix, Arizona.
authors.forename: Heidi
authors.initials: H
authors.lastname: Kosiorek
authors.affiliation: Department of Hematology and Oncology, Mayo Clinic Arizona, Phoenix, Arizona.
authors.forename: James L
authors.initials: JL
authors.lastname: Slack
authors.affiliation: Division of Laboratory Genetics, Mayo Clinic, Rochester, Minnesota.
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Lonzo
authors.affiliation: Division of Laboratory Genetics, Mayo Clinic, Rochester, Minnesota.
authors.forename: Patricia T
authors.initials: PT
authors.lastname: Greipp
authors.affiliation: Department of Hematology and Oncology, Mayo Clinic Arizona, Phoenix, Arizona.
authors.forename: Nandita
authors.initials: N
authors.lastname: Khera
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Phoenix, Arizona. Electronic address: Kelemen.katalin@mayo.edu.
authors.forename: Katalin
authors.initials: K
authors.lastname: Kelemen
mesh_terms: D000328:Adult; D000368:Aged; D000782:Aneuploidy; D000970:Antineoplastic Agents / Q000494:pharmacology; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics*; D002869:Chromosome Aberrations; D002999:Clone Cells; D003582:Cytogenetics; D018450:Disease Progression; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors; D014184:Transplantation, Homologous / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents
keywords: Chemotherapy; Cytogenetics; Hematopoietic cell transplantation (HCT); Myeloid neoplasm; Relapse