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Successful non-T-cell-depleted HLA-haploidentical stem cell transplantation (SCT) with reduced-intensity conditioning from a second child for late graft failure after the first HLA-haploidentical SCT for MDS/overt leukemia based on feto-maternal microchimerism

Bone Marrow Transplantation volume 35, pages 1031–1032 (2005)Cite this article

Long-term feto-maternal microchimerism suggests that immune tolerance exists between mother and child. Based on this hypothesis, we have previously performed human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplantation (SCT) without T-cell depletion (TCD) between noninherited maternal antigen (NIMA)-mismatched family members after reduced-intensity as well as conventional myeloablative conditionings.1, 2 Here, we reported a patient with MDS/overt leukemia who was successfully treated with the second non-TCD HLA-haploidentical reduced-intensity conditioning stem cell transplantation (RIST) from the older son for late graft failure after the first non-TCD HLA-haploidentical RIST from the younger son.

A 63-year-old woman was diagnosed as having MDS (refractory anemia excess blasts-2) in February 2004. She could not achieve remission with two courses of induction chemotherapy, and subsequently evolved into overt leukemia in May 2004. Owing to the lack of HLA-matched donor candidates, she received a non-TCD HLA-haploidentical RIST from her younger son in June 2004 (Table 1). The conditioning regimen consisted of fludarabine (Flu) 25 mg/m2 once daily i.v. from day −6 to day −2 and melphalan (Mel) once daily i.v. on day −3. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus (FK506) with mini-dose methotrexate (Mtx). Peripheral blood stem cells (PBSC) were harvested from her younger son, and 2.45 × 106/kg CD34+ cells were infused. Granulocyte colony-stimulating factor (G-CSF) was administrated from day 1. Hematopoietic recovery was rapid, and full donor chimerism was observed on day 30. Grade I acute GVHD occurred, but subsided spontaneously. However, she had gradually become pancytopenic, and fluorescent in situ hybridization (FISH) analysis of sex chromosomes showed 74% donor chimerism on day 190. She received donor lymphocyte infusion (DLI) twice on days 254 and 308 with 1.0 and 5.0 × 107/kg CD3+ cells, respectively. However, she had shown sustained pancytopenia, and was dependent on frequent red blood cell and platelet transfusions. Nevertheless, she remained in fairly good condition without either any active infections or organ damage. Therefore, she received the second non-TCD haploidentical RIST from the other donor, her elder son, on day 468 after the first SCT (Table 1). The conditioning regimen consisted of Flu 25 mg/m2 once daily i.v. from day −6 to day −2 together with total body irradiation (TBI) 2 Gy twice on day −1 instead of Mel. GVHD prophylaxis and post transplant G-CSF administration were performed in the same manner as the first SCT. PBSC were harvested from her elder son, and 2.63 × 106/kg CD34+ cells were infused. Hematopoietic recovery was rapid without any signs of acute GVHD. PCR of informative short tandem repeat regions demonstrated 100% donor chimerism on day 30 after the second SCT. So far, she has been in complete remission without recurrence of graft failure for 4 months after the second SCT.

Table 1 Characteristics of the patient and the donors in the first and second SCT
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Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan

    S Fuchida, S Nakano, N Yamada, R Uchida, A Okano, M Okamoto & C Shimazaki

  2. NPO HLA Laboratory, Kyoto, Japan

    E Maruya & H Saji

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  1. S Fuchida
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Fuchida, S., Nakano, S., Yamada, N. et al. Successful non-T-cell-depleted HLA-haploidentical stem cell transplantation (SCT) with reduced-intensity conditioning from a second child for late graft failure after the first HLA-haploidentical SCT for MDS/overt leukemia based on feto-maternal microchimerism. Bone Marrow Transplant 35, 1031–1032 (2005). https://doi.org/10.1038/sj.bmt.1704949

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