title: Improved Outcome of Refractory/Relapsed Acute Myeloid Leukemia after Post-Transplantation Cyclophosphamide-Based Haploidentical Transplantation with Myeloablative Conditioning and Early Prophylactic Granulocyte Colony-Stimulating Factor-Mobilized Donor Lymphocyte Infusions.
abstract: We carried out post-transplantation cyclophosphamide (PTCy)-based haploidentical peripheral blood stem cell transplantation in 51 patients with refractory/relapsed acute myeloid leukemia not in remission. The first 10 patients received nonmyeloablative conditioning followed by planned granulocyte colony-stimulating factor (G-CSF)-mobilized donor lymphocyte infusions (DLIs) on days 35, 60, and 90. No patient developed graft-versus-host disease (GVHD), but 90% had disease progression between 3 and 6 months. A subsequent 41 patients received myeloablative conditioning (MAC); the first 20 patients did not receive DLIs (MAC group) and the next 21 patients received G-CSF-mobilized DLIs (G-DLI) on days 21, 35, and 60 (MAC-DLI group). The incidence of disease progression and progression-free survival at 18 months were 66% and 25% in the MAC group compared with 21.4% and 61.9% in the MAC-DLI group (P = .01). Chronic GVHD but not acute GVHD was increased in the MAC-DLI group (41.2% versus 11%, P = .05). Natural killer cell alloreactive donor was associated with lower incidence of disease progression in the MAC but not in MAC-DLI group. The only factor favorably influencing disease progression and progression-free survival was administration of G-DLI after myeloablative conditioning. Our study shows that early administration of G-DLI is feasible after PTCy-based haploidentical hematopoietic stem cell transplantation for refractory/relapsed acute myeloid leukemia and might be associated with improved survival after MAC.
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: Shamsuz
authors.initials: S
authors.lastname: Zaman
authors.affiliation: Manashi Chakrabarti Foundation, Kolkata, India; KPC Medical College and Hospital, Kolkata, India.
authors.forename: Aditi
authors.initials: A
authors.lastname: Chakrabarti
authors.affiliation: Apollo Gleneagles Hospital, Kolkata, India.
authors.forename: Subrata
authors.initials: S
authors.lastname: Sen
authors.affiliation: Apollo Gleneagles Hospital, Kolkata, India.
authors.forename: Shashwata
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Department of Blood and Marrow Transplantation, Dharamshila Hospital and Research Centre, New Delhi, India.
authors.forename: Sneh
authors.initials: S
authors.lastname: Bhargava
authors.affiliation: CSIR-Indian Institute of Chemical Biology, Kolkata, India; Academy of Scientific and Innovative Research, CSIR-CRRI, New Delhi, India.
authors.forename: Kunal
authors.initials: K
authors.lastname: Ray
authors.affiliation: Fred Hutchinson Cancer Research Centre, Seattle, Washington.
authors.forename: Paul V
authors.initials: PV
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; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods* / Q000639:trends; D007694:Killer Cells, Natural / Q000276:immunology / Q000637:transplantation*; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use; D054340:Receptors, KIR / Q000276:immunology; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D019172:Transplantation Conditioning / Q000379:methods; D000075442:Transplantation, Haploidentical / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019653:Myeloablative Agonists; D054340:Receptors, KIR; D016179:Granulocyte Colony-Stimulating Factor
keywords: AML; DLI; Haploidentical; Post-transplantation cyclophosphamide; Refractory