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Allografting

Long-term follow-up of a pilot study using a chemotherapy-alone protocol for killer Ig-like receptor-ligand-mismatched haploidentical haematopoietic SCT

Bone Marrow Transplantation volume 46, pages 1331–1338 (2011)Cite this article

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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.

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Acknowledgements

This trial was supported in part by a research grant from the Investigator Initiated Studies Program of Merk and Co. Inc. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merk and Co. Inc.

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Authors and Affiliations

  1. Bone Marrow Transplant Programme, Alfred Hospital, Melbourne, Victoria, Australia

    A P Schwarer, G Bollard, M Kapuscinski & J Muirhead

  2. Victorian Tissue Typing and Immunogenetics Service, Australian Red Cross Blood Service, Melbourne, Victoria, Australia

    M Diviney & C Hart

  3. Pathology Service, Alfred Hospital, Melbourne, Victoria, Australia

    K Dunster

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  1. A P Schwarer
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Correspondence to A P Schwarer.

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Additional information

The data presented in this paper were in part presented at the 2008 Annual Meeting of the Haematology Society of Australia and New Zealand (abstract A196).

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Schwarer, A., Bollard, G., Kapuscinski, M. et al. Long-term follow-up of a pilot study using a chemotherapy-alone protocol for killer Ig-like receptor-ligand-mismatched haploidentical haematopoietic SCT. Bone Marrow Transplant 46, 1331–1338 (2011). https://doi.org/10.1038/bmt.2010.299

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