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 Blood, 1 September 2008, Vol. 112, No. 5, pp. 2160-2162.
Prepublished online as a Blood First Edition Paper on July 2, 2008; DOI 10.1182/blood-2008-02-141325.

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TRANSPLANTATION

Brief Report

Expansion of donor-derived hematopoietic stem cells with PIGA mutation associated with late graft failure after allogeneic stem cell transplantation

Kanako Mochizuki1,*, Chiharu Sugimori1,*, Zhirong Qi1, Xuzhang Lu1, Akiyoshi Takami1, Ken Ishiyama1, Yukio Kondo1, Hirohito Yamazaki1, Hirokazu Okumura1, and Shinji Nakao1

1 Cellular Transplantation Biology, Division of Cancer Medicine, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan

A small population of CD55–CD59– blood cells was detected in a patient who developed donor-type late graft failure after allogeneic stem cell transplantation (SCT) for treatment of aplastic anemia (AA). Chimerism and PIGA gene analyses showed the paroxysmal nocturnal hemoglobinuria (PNH)–type granulocytes to be of a donor-derived stem cell with a thymine insertion in PIGA exon 2. A sensitive mutation-specific polymerase chain reaction (PCR)–based analysis detected the mutation exclusively in DNA derived from the donor bone marrow (BM) cells. The patient responded to immunosuppressive therapy and achieved transfusion independence. The small population of PNH-type cells was undetectable in any of the 50 SCT recipients showing stable engraftment. The de novo development of donor cell–derived AA with a small population of PNH-type cells in this patient supports the concept that glycosyl phosphatidylinositol–anchored protein–deficient stem cells have a survival advantage in the setting of immune-mediated BM injury.


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N. S. Young
Paroxysmal nocturnal hemoglobinuria and myelodysplastic sydromes: clonal expansion of PIG-A-mutant hematopoietic cells in bone marrow failure
Haematologica, January 1, 2009; 94(1): 3 - 7.
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