title: Cord blood chimerism and relapse after haplo-cord transplantation.
abstract: Haplo-cord stem cell transplantation combines the infusion of CD34 selected hematopoietic progenitors from a haplo-identical donor with an umbilical cord blood (UCB) graft from an unrelated donor and allows faster count recovery, with low rates of disease recurrence and chronic graft-versus-host disease (GVHD). But the contribution of the umbilical cord blood graft to long-term transplant outcome remains unclear. We analyzed 39 recipients of haplo-cord transplants with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), engrafted and in remission at 2 months. Median age was 66 (18-72) and all had intermediate, high, or very-high risk disease. Less than 20% UCB chimerism in the CD33 lineage was associated with an increased rate of disease recurrence (54% versus 11% p < 0.0001) and decrease in one year progression-free (20% versus 55%, p = 0.004) and overall survival (30% versus 62%, p = 0.02). Less than 100% UCB chimerism in the CD3 lineage was associated with increase rate of disease recurrence (46% versus 12%, p = 0.007). Persistent haplo-chimerism in the CD3 lineage was associated with an increased rate of disease recurrence (40% versus 15%, p = 0.009) Chimerism did not predict for treatment related mortality. The cumulative incidence of acute GVHD by day 100 was 43%. The cumulative incidence of moderate/severe chronic GVHD was only 5%. Engraftment of the umbilical cord blood grafts provides powerful graft-versus-leukemia (GVL) effects which protect against disease recurrence and is associated with low risk of chronic GVHD. Engraftment of CD34 selected haplo-identical cells can lead to rapid development of circulating T-cells, but when these cells dominate, GVL-effects are limited and rates of disease recurrence are high.
authors.affiliation: a Division of Hematology/Oncology, Weill Cornell Medical College , NY , USA.
authors.forename: Koen
authors.initials: K
authors.lastname: van Besien
authors.affiliation: a Division of Hematology/Oncology, Weill Cornell Medical College , NY , USA.
authors.forename: Nebu
authors.initials: N
authors.lastname: Koshy
authors.affiliation: a Division of Hematology/Oncology, Weill Cornell Medical College , NY , USA.
authors.forename: Usama
authors.initials: U
authors.lastname: Gergis
authors.affiliation: a Division of Hematology/Oncology, Weill Cornell Medical College , NY , USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Mayer
authors.affiliation: b Department of Pathology, Weill Cornell Medical College , NY , USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Cushing
authors.affiliation: b Department of Pathology, Weill Cornell Medical College , NY , USA.
authors.forename: Hannah
authors.initials: H
authors.lastname: Rennert
authors.affiliation: b Department of Pathology, Weill Cornell Medical College , NY , USA.
authors.forename: Ronit
authors.initials: R
authors.lastname: Reich-Slotky
authors.affiliation: a Division of Hematology/Oncology, Weill Cornell Medical College , NY , USA.
authors.forename: Tomer
authors.initials: T
authors.lastname: Mark
authors.affiliation: a Division of Hematology/Oncology, Weill Cornell Medical College , NY , USA.
authors.forename: Roger
authors.initials: R
authors.lastname: Pearse
authors.affiliation: a Division of Hematology/Oncology, Weill Cornell Medical College , NY , USA.
authors.forename: Adriana
authors.initials: A
authors.lastname: Rossi
authors.affiliation: a Division of Hematology/Oncology, Weill Cornell Medical College , NY , USA.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Phillips
authors.affiliation: b Department of Pathology, Weill Cornell Medical College , NY , USA.
authors.forename: Liljana
authors.initials: L
authors.lastname: Vasovic
authors.affiliation: a Division of Hematology/Oncology, Weill Cornell Medical College , NY , USA.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Ferrante
authors.affiliation: b Department of Pathology, Weill Cornell Medical College , NY , USA.
authors.forename: Yen-Michael
authors.initials: YM
authors.lastname: Hsu
authors.affiliation: a Division of Hematology/Oncology, Weill Cornell Medical College , NY , USA.
authors.forename: Tsiporah
authors.initials: T
authors.lastname: Shore
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D015470:Leukemia, Myeloid, Acute / Q000628:therapy; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D012008:Recurrence; D016019:Survival Analysis; D014019:Tissue Donors; D018183:Transplantation Chimera; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D007166:Immunosuppressive Agents
keywords: Clinical results; leukemias and dysplasias; marrow and stem cell transplantation; myeloid; neoplasia; transplantation; umbilical cord blood