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Long-term outcome and chimerism in patients with Wiskott–Aldrich syndrome treated by hematopoietic cell transplantation: a retrospective nationwide survey

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Abstract

We analyzed the outcomes of allogeneic stem cell transplantation (SCT) and risk factors for chimerism in 108 patients with Wiskott–Aldrich syndrome (WAS) who were registered with The Japan Society for Hematopoietic Cell Transplantation between January 1985 and December 2016. A preparative conditioning regimen consisting of myeloablative conditioning (MAC) was provided to 76 patients, and reduced-intensity conditioning was provided to 30 patients. Fifty-one patients received prophylaxis against graft-versus-host disease (GVHD) with cyclosporine, and 51 patients received tacrolimus (Tac). Chimerism analyses had been performed in 91 patients. Neutrophil engraftment was achieved in 91 patients (84.3%). The engraftment rate was significantly higher in patients who received Tac for GVHD prophylaxis (p = 0.028). Overall survival rate (OS) was significantly higher in patients with complete chimerism than in patients with mixed chimerism (88.2 ± 6.1% and 66.7 ± 9.9%, respectively, p = 0.003). Multivariate analysis showed that the rate of complete chimerism in patients who received MAC including cyclophosphamide (CY) at a dose of 200 mg/kg was significantly higher (p = 0.021) than that in patients who received other conditioning. Thus, MAC including CY at a dose of 200 mg/kg and Tac for GVHD prophylaxis were optimal conditions of SCT for patients with WAS under existing study.

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References

  1. Familiärer WA. angeborener Morbus Werlhofii. Monatsschr Kinderheilkd. 1937;68:212–6 (in German).

    Google Scholar 

  2. Aldrich RA, Steinberg AG, Campbell DC. Pedigree demonstrating a sex-linked recessive condition characterized by draining ears, eczematoid dermatitis and bloody diarrhea. Pediatrics. 1937;13:133–9.

    Google Scholar 

  3. Derry JM, Ochs HD, Francke U. Isolation of a novel gene mutated in Wiskott–Aldrich syndrome. Cell. 1994;78:635–44.

    Article  CAS  PubMed  Google Scholar 

  4. Moratto D, Giliani S, Bonfim C, Mazzolari E, Fischer A, Ochs HD, et al. Long-term outcome and lineage-specific chimerism in 194 patients with Wiskott–Aldrich syndrome treated by hematopoietic cell transplantation in the period 1980–2009: an international collaborative study. Blood. 2011;118:1675–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kobayashi R, Ariga T, Nonoyama S, Kanegane H, Tsuchiya S, Morio T, et al. Outcome in patients with Wiskott–Aldrich syndrome following stem cell transplantation: an analysis of 57 patients in Japan. Br J Haematol. 2006;135:362–6.

    Article  PubMed  Google Scholar 

  6. Wallace WHB, Kelsey TW. Follicle stimulating hormone is an accurate predictor of azoospermia in childhood cancer survivors. PLoS One. 2010;12:e0181377.

    Google Scholar 

  7. Green DM, Sklar CA, Boice JD Jr, Mulvihill JJ, Whitton JA, Stovall M, et al. Ovarian failure and reproductive outcomes after childhood cancer treatment: results from the childhood cancer survivor study. J Clin Oncol. 2009;27:2374–81.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Ishida S, Doki N, Shingai N, Yoshioka K, Kakihana K, Sakamaki H, et al. The clinical features of fatal cyclophosphamide-induced cardiotoxicity in a conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Ann Hematol. 2016;95:1145–50.

    Article  CAS  PubMed  Google Scholar 

  9. Murdych T, Weisdorf DJ. Serious cardiac complications during bone marrow transplantation at the University of Minnesota, 1977–1997. Bone Marrow Transplant. 2001;28:283–7.

    Article  CAS  PubMed  Google Scholar 

  10. Teepen JC, van Leeuwen FE, Tissing WJ, van Dulmen-den Broeder E, van den Heuvel-Eibrink MM, van der Pal HJ, et al. Long-term risk of subsequent malignant neoplasms after treatment of childhood cancer in the DCOG LATER study cohort: role of chemotherapy. J Clin Oncol. 2017;35:2288–98.

    Article  CAS  PubMed  Google Scholar 

  11. Atsuta Y, Hirakawa A, Nakasone H, Kurosawa S, Oshima K, Sakai R, et al. Late mortality and causes of death among long-term survivors after allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2016;22:1702–9.

    Article  PubMed  Google Scholar 

  12. Sakai R, Taguri M, Oshima K, Mori T, Ago H, Adachi S, et al. A comparison of tacrolimus and cyclosporine combined with methotrexate for graft-versus-host disease prophylaxis, stratified by stem cell source: a retrospective nationwide survey. Int J Hematol. 2016;103:322–33.

    Article  CAS  PubMed  Google Scholar 

  13. Nasu R, Nannya Y, Shinohara A, Ichikawa M, Kurokawa M. Favorable outcomes of tacrolimus compared with cyclosporine A for GVHD prophylaxis in HSCT for standard-risk hematological diseases. Ann Hematol. 2014;93:1215–23.

    Article  CAS  PubMed  Google Scholar 

  14. Inamoto Y, Flowers ME, Wang T, Urbano-Ispizua A, Hemmer MT, Cutler CS, et al. Tacrolimus versus cyclosporine after hematopoietic cell transplantation for acquired aplastic anemia. Biol Blood Marrow Transplant. 2015;21:1776–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Storb R, Yu C, Wagner JL, Deeg HJ, Nash RA, Kiem HP, et al. Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before and pharmacological immunosuppression after marrow transplantation. Blood. 1997;89:3048–54.

    CAS  PubMed  Google Scholar 

  16. Iguchi A, Terashita Y, Sugiyama M, Ohshima J, Sato TZ, Cho Y, et al. Graft-versus-host disease (GVHD) prophylaxis by using methotrexate decreases pre-engraftment syndrome and severe acute GVHD, and accelerates engraftment after cord blood transplantation. Pediatr Transplant. 2016;20:114–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Mrs. Yumiko Shinohe and Mrs. Miyuki Yanagida for their excellent assistance in the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Pediatrics, Hokkaido University Hospital, N14W5, Kita-ku, Sapporo, 060-8638, Japan

    Akihiro Iguchi & Yuko Cho

  2. Department of Cell Transplantation and Regenerative Medicine, Tokai University School of Medicine, Tokyo, Japan

    Hiromasa Yabe & Shunichi Kato

  3. Department of Hematology and Oncology, Children’s Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    Koji Kato

  4. Department of Pediatric Hematology/Oncology, Osaka City General Hospital, Osaka, Japan

    Junichi Hara

  5. Department of Hematology/Oncology, Saitama Children’s Medical Center, Saitama, Japan

    Katsuyoshi Koh

  6. Department of Cell Therapy and Transplantation Medicine (Pediatrics), The University of Tokyo Hospital, Tokyo, Japan

    Junko Takita

  7. Department of Pediatrics, Nara Medical University Hospital, Nara, Japan

    Takashi Ishihara

  8. Department of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan

    Masami Inoue

  9. Department of Pediatrics, Medical Hospital, Tokyo Medical and Dental University, Tokyo, Japan

    Kohsuke Imai & Tomohiro Morio

  10. Department of Pediatrics, National Kyushu Cancer Center, Fukuoka, Japan

    Hideki Nakayama

  11. Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Japan

    Yoshiko Hashii

  12. Children’s Medical Center Tochigi, Jichi Medical University, Shimotsuke, Japan

    Akira Morimoto

  13. Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan

    Yoshiko Atsuta

  14. Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Yoshiko Atsuta

Authors
  1. Akihiro Iguchi
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  2. Yuko Cho
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  3. Hiromasa Yabe
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  4. Shunichi Kato
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  5. Koji Kato
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  6. Junichi Hara
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  7. Katsuyoshi Koh
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  8. Junko Takita
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  9. Takashi Ishihara
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  10. Masami Inoue
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  11. Kohsuke Imai
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  12. Hideki Nakayama
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  13. Yoshiko Hashii
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  14. Akira Morimoto
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  15. Yoshiko Atsuta
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  16. Tomohiro Morio
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Consortia

Hereditary disorder Working Group of the Japan Society for Hematopoietic Cell Transplantation

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Correspondence to Akihiro Iguchi.

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Iguchi, A., Cho, Y., Yabe, H. et al. Long-term outcome and chimerism in patients with Wiskott–Aldrich syndrome treated by hematopoietic cell transplantation: a retrospective nationwide survey. Int J Hematol 110, 364–369 (2019). https://doi.org/10.1007/s12185-019-02686-y

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  • DOI: https://doi.org/10.1007/s12185-019-02686-y

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