title: CD56-enriched donor cell infusion after post-transplantation cyclophosphamide for haploidentical transplantation of advanced myeloid malignancies is associated with prompt reconstitution of mature natural killer cells and regulatory T cells with reduced incidence of acute graft versus host disease: A pilot study.
abstract: We conducted a pilot study on the feasibility of CD56-enriched donor cell infusion after post-transplantation cyclophosphamide (PTCy) for 10 patients with advanced myeloid malignancies undergoing haploidentical peripheral blood stem cell transplantation with cyclosporine alone as graft-versus-host disease (GVHD) prophylaxis and compared the outcome and immune reconstitution with a control group of 20 patients undergoing the same without CD56-enriched donor cell infusion. An early and rapid surge of mature NK cells as well as CD4+T cells and regulatory T cells (Tregs) was noted compared with the control group. KIR of donor phenotype reconstituted as early as day 30 with expression of CD56dimCD16+NKG2A-KIR+phenotype. None experienced viral or fungal infections, and non-relapse mortality was 10% only. The incidence of grade 2-4 acute GVHD was 50% in the control group with none in the CD56 group (P = 0.01). Only two had de novo chronic GVHD in each group. Relapse occurred in five patients in CD56 group with a median follow-up of 12 months, similar to the control group. Our preliminary data show that CD56+donor cell infusion after PTCy and short-course cyclosporine is feasible with prompt engraftment, rapid reconstitution of CD4+T cells, Tregs and NK cells and reduced incidence of acute GVHD.
authors.affiliation: Manashi Chakrabarti Foundation, Kolkata, India; Department of Blood and Marrow Transplantation, Dharamshila Hospital and Research Centre, New Delhi, India. Electronic address: drsaritaranij@gmail.com.
authors.forename: Sarita Rani
authors.initials: SR
authors.lastname: Jaiswal
authors.affiliation: Department of Blood and Marrow Transplantation, Dharamshila Hospital and Research Centre, New Delhi, India.
authors.forename: Shamsur
authors.initials: S
authors.lastname: Zaman
authors.affiliation: Manashi Chakrabarti Foundation, Kolkata, India.
authors.forename: Murugaiyan
authors.initials: M
authors.lastname: Nedunchezhian
authors.affiliation: Manashi Chakrabarti Foundation, Kolkata, India.
authors.forename: Aditi
authors.initials: A
authors.lastname: Chakrabarti
authors.affiliation: Department of Blood and Marrow Transplantation, Dharamshila Hospital and Research Centre, New Delhi, India.
authors.forename: Prakash
authors.initials: P
authors.lastname: Bhakuni
authors.affiliation: Department of Blood and Marrow Transplantation, Dharamshila Hospital and Research Centre, New Delhi, India.
authors.forename: Margoob
authors.initials: M
authors.lastname: Ahmed
authors.affiliation: Department of Blood and Marrow Transplantation, Dharamshila Hospital and Research Centre, New Delhi, India.
authors.forename: Kanika
authors.initials: K
authors.lastname: Sharma
authors.affiliation: Department of Blood and Marrow Transplantation, Dharamshila Hospital and Research Centre, New Delhi, India.
authors.forename: Sheh
authors.initials: S
authors.lastname: Rawat
authors.affiliation: Fred Hutchinson Cancer Research Centre, Seattle, Washington, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: O'donnell
authors.affiliation: Manashi Chakrabarti Foundation, Kolkata, India; Department of Blood and Marrow Transplantation, Dharamshila Hospital and Research Centre, New Delhi, India.
authors.forename: Suparno
authors.initials: S
authors.lastname: Chakrabarti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019002:CD56 Antigen / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage*; D018450:Disease Progression; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control*; D006239:Haplotypes; D019337:Hematologic Neoplasms / Q000453:epidemiology / Q000628:therapy*; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D015994:Incidence; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D010865:Pilot Projects; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism / Q000637:transplantation*; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous / Q000009:adverse effects; D055815:Young Adult
chemical_list: D019002:CD56 Antigen; C522918:NCAM1 protein, human; D003520:Cyclophosphamide
keywords: AML; DLI; NK cell; acute myeloid leukemia; donor lymphocyte infusion; haploidentical; post-transplantation cyclophosphamide