title: Minimal Identifiable Disease and the Role of Conditioning Intensity in Hematopoietic Cell Transplantation for Myelodysplastic Syndrome and Acute Myelogenous Leukemia Evolving from Myelodysplastic Syndrome.
abstract: Allogeneic hematopoietic cell transplantation (HCT) is the only known treatment with curative potential for myelodysplastic syndrome, but relapse is a major cause of failure. We studied results in 289 patients transplanted between June 2004 and December 2013. Minimal identifiable disease (MID) markers pre-HCT were determined by multiparameter flow cytometry (MFC) and cytogenetics on marrow aspirates. The impact of MID on outcome after low- and high-intensity conditioning HCT was determined. Among 287 assessable patients, 68 (23.7%) had more than 5% marrow blasts at HCT; 219 patients were in morphologic remission but 154 (53.7%) were MID positive, whereas 65 (22.6%) were MID negative. The impact of MID on outcome was significantly different between patients who received low-intensity conditioning and patients who received a high-intensity regimen. The impact of conditioning intensity differed across the various MID categories. In particular, the risk of overall mortality was higher with low-intensity than with high-intensity regimens for patients who were positive for MID by cytogenetics regardless of positivity by MFC (HR, 1.67 if MFC positive/cytogenetics positive, HR, 7.23 if MFC negative/cytogenetics positive). On the other hand, patients who were MID negative by both MFC and cytogenetics had similar risks of mortality with low- and high-intensity regimens (HR, .99). The main factor responsible for mortality after low-intensity conditioning in MID-positive patients was relapse. The presence of MID should be considered when deciding on conditioning intensity because it identifies subgroups of patients who may benefit from high- or low-intensity conditioning.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Washington Medical Center/Seattle Cancer Care Alliance, Seattle, Washington.
authors.forename: Moreno
authors.initials: M
authors.lastname: Festuccia
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Washington Medical Center/Seattle Cancer Care Alliance, Seattle, Washington.
authors.forename: H Joachim
authors.initials: HJ
authors.lastname: Deeg
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Washington Medical Center/Seattle Cancer Care Alliance, Seattle, Washington.
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Gooley
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Kelsey
authors.initials: K
authors.lastname: Baker
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Washington Medical Center/Seattle Cancer Care Alliance, Seattle, Washington.
authors.forename: Brent L
authors.initials: BL
authors.lastname: Wood
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Washington Medical Center/Seattle Cancer Care Alliance, Seattle, Washington.
authors.forename: Min
authors.initials: M
authors.lastname: Fang
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Washington Medical Center/Seattle Cancer Care Alliance, Seattle, Washington.
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Washington Medical Center/Seattle Cancer Care Alliance, Seattle, Washington. Electronic address: hcrawfor@fhcrc.org.
authors.forename: Bart L
authors.initials: BL
authors.lastname: Scott
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001856:Bone Marrow Examination; D002648:Child; D019937:Diagnostic Techniques and Procedures; D005260:Female; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000209:etiology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications* / Q000401:mortality / Q000628:therapy; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000401:mortality; D011379:Prognosis; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods* / Q000401:mortality; D016896:Treatment Outcome; D055815:Young Adult
keywords: Allogeneic transplantation; Conditioning regimen; MDS; minimal identifiable disease; minimal residual disease