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Long-term survival after HLA-haploidentical SCT from noninherited maternal antigen-mismatched family donors: impact of chronic GVHD

Bone Marrow Transplantation volume 44, pages 327–329 (2009)Cite this article

Allo-SCT from an HLA-haploidentical family donor has been the treatment of choice in patients with high-risk hematologic malignancies, who are expected to have a better prognosis with SCT but lack immediate access to a conventional stem cell source.1, 2 With intent to minimize the risk of severe GVHD, most haploidentical SCT protocols employ ex vivo or in vivo T-cell depletion, albeit at the expense of an increased risk of infection or relapse as a result of poor post-transplant immune reconstitution. To develop an alternative strategy to perform haploidentical SCT that confers improved immune recovery and acceptable risk of GVHD, we have explored the feasibility of T-cell-replete SCT from family donors mismatched for noninherited maternal HLA antigens (NIMA); NIMA-mismatched donor selection is based on the hypothesis that the detection of long-term maternal or fetal microchimerism in the donor's peripheral circulation is associated with immunological hyporesponsiveness against NIMA (in the case of NIMA mismatch in the graft-vs-host direction) or against inherited paternal HLA antigens (IPA) (in the case of NIMA mismatch in the host-vs-graft direction).3 According to this scenario, we and other groups showed that T-cell-replete HLA-haploidentical SCT from a NIMA-mismatched family donor is feasible in selected patients with poor-risk hematologic malignancies.3, 4 However, late complications and long-term outcomes in patients undergoing such transplantations have been so far largely unknown. Therefore, we retrospectively studied the severity of chronic GVHD, requirement for immunosupressive treatment, and status of primary disease in long-term survivors who received T-cell-replete NIMA-mismatched haploidentical SCT.

We collected data on 16 consecutive patients who had survived more than 3 years after NIMA-mismatched SCT performed between January 2001 and July 2004 at 11 institutions that participated in our previous nationwide study (Table 1).3 At the time of SCT, they had a median age of 19 years (range, 2–56) and received BM (n=5) or G-CSF-mobilized peripheral blood (n=11) as treatment for acute myeloid leukemia (n=6), acute lymphoblastic leukemia (n=3), chronic myeloid leukemia (n=4) and other B-cell neoplasms (n=3); 6 patients had a chemosensitive disease and 10 had a refractory disease. Early outcomes of 14 of these transplantations have been described elsewhere.3, 4, 5 All patients received tacrolimus-based GVHD prophylaxis after myeloablative (n=10) or reduced-intensity conditioning (n=6). The type of donor was NIMA-mismatched sibling in 9 cases, mother in 6 and daughter in 1; all patient-donor pairs had two or three serologic mismatches at HLA-A, HLA-B and HLA-DR antigens in the graft-versus-host direction. The presence of long-term maternal or fetal microchimerism was detected in all donors through NIMA- or IPA-specific nested PCR as described earlier.3 Karnofsky score was employed to record the performance status for patients who were 16 years or older, whereas Lansky score was applied for those who were younger than 16 years of age. Organ-specific symptoms related to chronic GVHD and their severity were diagnosed and evaluated by consensus criteria proposed by the National Institutes of Health Chronic GVHD Diagnosis and Staging Working Group.6

Table 1 Characteristics of long-term survivors after NIMA-mismatched haploidentical SCT
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Authors and Affiliations

  1. Department of Hematology and Oncology, Kyoto University Hospital, Kyoto, Japan

    J Kanda, T Ichinohe & T Uchiyama

  2. Kyoto Prefectural University of Medicine, Kyoto, Japan

    C Shimazaki & A Morimoto

  3. Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan

    M Hamaguchi

  4. Nakadoori General Hospital, Akita, Japan

    A Watanabe

  5. Matsushita Memorial Hospital, Moriguchi, Japan

    H Ishida, T Yoshihara & N Uoshima

  6. Department of Pediatrics, Kyoto University Hospital, Kyoto, Japan

    S Adachi

  7. University of Yamanashi School of Medicine, Yamanashi, Japan

    T Inukai

  8. Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Japan

    A Sawada

  9. Suzuka Kaisei Hospital, Suzuka, Japan

    K Oka

  10. Kawasaki Medical School, Kurashiki, Japan

    M Itoh

  11. Osaka City University Graduate School of Medicine, Osaka, Japan

    M Hino

  12. Non-profit Organization HLA Laboratory, Kyoto, Japan

    E Maruya & H Saji

  13. Aichi Medical University, Nagakute, Japan

    Y Kodera

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Correspondence to T Ichinohe.

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Kanda, J., Ichinohe, T., Shimazaki, C. et al. Long-term survival after HLA-haploidentical SCT from noninherited maternal antigen-mismatched family donors: impact of chronic GVHD. Bone Marrow Transplant 44, 327–329 (2009). https://doi.org/10.1038/bmt.2009.18

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