title: Long-term follow-up of a pilot study using a chemotherapy-alone protocol for killer Ig-like receptor-ligand-mismatched haploidentical haematopoietic SCT.
abstract: Advanced haematological malignancies are incurable without allogeneic haematopoietic SCT (HSCT). Many patients do not have a human leukocyte Ag (HLA)-matched donor; hence, haploidentical HSCT has been explored for some 20 years. Previous poor outcomes have improved recently with modifications, including the use of killer Ig-like receptor (KIR)-ligand-mismatched donors and highly T-cell-depleted megadose CD34+ stem cell infusions. Haploidentical HSCT was undertaken in 10 patients with heavily pretreated and advanced myeloid malignancies. Patient/donor pairs were KIR-ligand mismatched (GVL direction). Conditioning regimen was ATG, melphalan, fludarabine and thiotepa. G-CSF-mobilized PBSCs were CD34+ cell selected. No post transplant immunosuppression was given. Two patients died early; all others had sustained engraftment. Natural killer cell recovery, often to supranormal levels, occurred early, whereas CD4+ T-cell recovery was delayed. Acute GVHD occurred in three of eight (30%) patients, and chronic GVHD occurred in three of six (50%) evaluable patients. No infections with Candida or Aspergillus developed in seven patients receiving caspofungin prophylaxis. Three of 10 (30%) patients were alive and disease free at 10.1, 6 and 5.4 years post transplant (Karnovsky scores of 100%). In this heavily pretreated cohort with very advanced myeloid malignancies, KIR-ligand-mismatched haploidentical HSCT cured a significant proportion of patients.
authors.affiliation: Bone Marrow Transplant Programme, Alfred Hospital, Melbourne, Victoria, Australia. a.schwarer@alfred.org.au
authors.forename: A P
authors.initials: AP
authors.lastname: Schwarer
authors.forename: G
authors.initials: G
authors.lastname: Bollard
authors.forename: M
authors.initials: M
authors.lastname: Kapuscinski
authors.forename: J
authors.initials: J
authors.lastname: Muirhead
authors.forename: M
authors.initials: M
authors.lastname: Diviney
authors.forename: C
authors.initials: C
authors.lastname: Hart
authors.forename: K
authors.initials: K
authors.lastname: Dunster
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006239:Haplotypes; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000601:surgery*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D054340:Receptors, KIR / Q000276:immunology*; D014019:Tissue Donors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D054340:Receptors, KIR