Haploidentical allogeneic hematopoietic cell transplantation in adults using CD3/CD19 depletion and reduced intensity conditioning

TY - JOUR

T1 - Haploidentical allogeneic hematopoietic cell transplantation in adults using CD3/CD19 depletion and reduced intensity conditioning

T2 - a phase II study

AU - Federmann, Birgit

AU - Bornhauser, Martin

AU - Meisner, Christoph

AU - Kordelas, Lambros

AU - Beelen, Dietrich W

AU - Stuhler, Gernot

AU - Stelljes, Matthias

AU - Schwerdtfeger, Rainer

AU - Christopeit, Maximilian

AU - Behre, Gerhard

AU - Faul, Christoph

AU - Vogel, Wichard

AU - Schumm, Michael

AU - Handgretinger, Rupert

AU - Kanz, Lothar

AU - Bethge, Wolfgang A

PY - 2012/10

Y1 - 2012/10

N2 - BACKGROUND: We report a prospective multicenter phase II study of haploidentical hematopoietic stem cell transplantation using CD3/CD19-depleted grafts after reduced intensity conditioning with fludarabine, thiotepa, melphalan and OKT-3.DESIGN AND METHODS: Sixty-one adults with a median age of 46 years (range 19-65 years) have been enrolled. Diagnoses were acute myeloid leukemia (n=38), acute lymphoblastic leukemia (n=8), non-Hodgkin's lymphoma (n=6), myeloma (n=4), chronic myeloid leukemia (n=3), chronic lymphatic leukemia (n=1) and myelodysplastic syndrome (n=1). Patients were considered high risk because of refractory disease (n=18), cytogenetics (n=6), complete remission (≥ 2) (n=9), chemosensitive relapse in partial remission (n=4) or relapse after prior hematopoietic stem cell transplantation (n=15 allogeneic, n=8 autologous, n=1 both). At haploidentical hematopoietic stem cell transplantation, 30 patients were in complete remission and 31 in partial remission. Grafts contained a median of 7.0 × 10(6) (range 3.2-22) CD34(+) cells/kg, 4.2 × 10(4) (range 0.6-44) CD3(+) T cells/kg and 2.7 × 10(7) (range 0.00-37.3) CD56(+) cells/kg.RESULTS: Engraftment was rapid with a median of 12 days to granulocytes more than 0.5 × 10(9)/L (range 9-50 days) and 11 days to platelets more than 20 × 10(9) (range 7-38 days). Incidence of grade IIIV acute graft-versus-host-disease and chronic graft-versus-host-disease was 46% and 18%, respectively. Non-relapse mortality on Day 100 was 23% and 42% at two years. Cumulative incidence of relapse/progression at two years was 31%. Kaplan-Meier estimated 1-year and 2-year overall survival with median follow up of 869 days (range 181-1932) is 41% and 28%, respectively.CONCLUSIONS: This regimen allows successful haploidentical hematopoietic stem cell transplantation with reduced intensity conditioning in high-risk patients lacking a suitable donor. (clinicaltrials.gov identifier:NCT00202917).

AB - BACKGROUND: We report a prospective multicenter phase II study of haploidentical hematopoietic stem cell transplantation using CD3/CD19-depleted grafts after reduced intensity conditioning with fludarabine, thiotepa, melphalan and OKT-3.DESIGN AND METHODS: Sixty-one adults with a median age of 46 years (range 19-65 years) have been enrolled. Diagnoses were acute myeloid leukemia (n=38), acute lymphoblastic leukemia (n=8), non-Hodgkin's lymphoma (n=6), myeloma (n=4), chronic myeloid leukemia (n=3), chronic lymphatic leukemia (n=1) and myelodysplastic syndrome (n=1). Patients were considered high risk because of refractory disease (n=18), cytogenetics (n=6), complete remission (≥ 2) (n=9), chemosensitive relapse in partial remission (n=4) or relapse after prior hematopoietic stem cell transplantation (n=15 allogeneic, n=8 autologous, n=1 both). At haploidentical hematopoietic stem cell transplantation, 30 patients were in complete remission and 31 in partial remission. Grafts contained a median of 7.0 × 10(6) (range 3.2-22) CD34(+) cells/kg, 4.2 × 10(4) (range 0.6-44) CD3(+) T cells/kg and 2.7 × 10(7) (range 0.00-37.3) CD56(+) cells/kg.RESULTS: Engraftment was rapid with a median of 12 days to granulocytes more than 0.5 × 10(9)/L (range 9-50 days) and 11 days to platelets more than 20 × 10(9) (range 7-38 days). Incidence of grade IIIV acute graft-versus-host-disease and chronic graft-versus-host-disease was 46% and 18%, respectively. Non-relapse mortality on Day 100 was 23% and 42% at two years. Cumulative incidence of relapse/progression at two years was 31%. Kaplan-Meier estimated 1-year and 2-year overall survival with median follow up of 869 days (range 181-1932) is 41% and 28%, respectively.CONCLUSIONS: This regimen allows successful haploidentical hematopoietic stem cell transplantation with reduced intensity conditioning in high-risk patients lacking a suitable donor. (clinicaltrials.gov identifier:NCT00202917).

KW - Adult

KW - Aged

KW - Antigens, CD19

KW - Antigens, CD34

KW - CD3 Complex

KW - Chimerism

KW - Female

KW - Graft Survival

KW - Graft vs Host Disease

KW - Haplotypes

KW - Hematologic Diseases

KW - Hematopoietic Stem Cell Transplantation

KW - Hematopoietic Stem Cells

KW - Humans

KW - Leukemia

KW - Lymphocyte Depletion

KW - Lymphoma, Non-Hodgkin

KW - Major Histocompatibility Complex

KW - Male

KW - Middle Aged

KW - Multiple Myeloma

KW - Myelodysplastic Syndromes

KW - Receptors, KIR

KW - Risk Factors

KW - Tissue Donors

KW - Transplantation Conditioning

KW - Transplantation, Homologous

KW - Treatment Outcome

KW - Young Adult

KW - Clinical Trial, Phase II

KW - Journal Article

KW - Multicenter Study

KW - Research Support, Non-U.S. Gov't

U2 - 10.3324/haematol.2011.059378

DO - 10.3324/haematol.2011.059378

M3 - SCORING: Journal article

C2 - 22491731

VL - 97

SP - 1523

EP - 1531

JO - HAEMATOLOGICA

JF - HAEMATOLOGICA

SN - 0390-6078

IS - 10

ER -