Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

Successful engraftment of the second reduced-intensity conditioning cord blood transplantation (CBT) for a patient who developed graft rejection and infectious complications after the first CBT for AML

Bone Marrow Transplantation volume 40, pages 395–396 (2007)Cite this article

The effectiveness of cord blood transplantation (CBT) has recently been explored in an increasing number of adult patients.1 However, there are limited data on the management of graft rejection that may follow CBT. Here, we report the case of a patient with graft rejection following CBT; the patient was successfully treated with a second reduced-intensity conditioning (RIC) CBT, despite the fact that he was suffering from serious infectious complications.

A 44-year-old Japanese man was diagnosed with AML (M6). He achieved CR with the first course of induction chemotherapy. However, his condition showed a relapse and the patient achieved a second CR after the second course of chemotherapy. Because of the absence of a suitable donor among family members and unrelated donors, CBT was planned and he was referred to our hospital. The conditioning regimen comprised 12 Gy TBI and 120 mg/kg CY. He received an infusion of serologically two HLA-loci mismatched unrelated cord blood containing 2.20 × 107 nucleated cells/kg. Tacrolimus and short-term MTX were administered for GVHD prophylaxis. Treatment with G-CSF was initiated on day +5. Neutrophil count increased temporarily but decreased subsequently; therefore, on day +19, we performed PCR for amplifying the informative short tandem repeat regions, which demonstrated complete donor chimerism in the PBMC. G-CSF treatment was continued; however, hematological recovery was not observed. On day +28, the BM sample revealed a severely hypocellular marrow, PCR analysis indicated complete recipient chimerism in the PBMC, and graft rejection was diagnosed. Simultaneously, CMV and human herpesvirus 6 (HHV6) DNA were detected in the PBMC by real-time PCR; therefore, treatment using 60 mg/kg foscarnet per day was started. On day +34, bacteremia due to Stenotrophomonas maltophilia and endotoxemia developed. Immediate treatment was started with ciprofloxacin and minocycline, and the central venous catheter was removed. To treat graft rejection, a second CBT was scheduled with the continuous administration of antimicrobial agents. The conditioning regimen comprised administration of 30 mg/m2 fludarabine per day for 6 days and 70 mg/m2 melphalan per day for 1 day. The patient received an infusion of serologically two HLA-loci mismatched unrelated cord blood containing 2.26 × 107 nucleated cells/kg at an interval of 45 days from the first CBT. Continuous intravenous infusion of 0.02 mg/kg tacrolimus per day was started on day −1 and 500 mg mycophenolate mofetil (MMF) was orally administered twice daily on day +1 for GVHD prophylaxis. G-CSF was administered from day +1. He tolerated the procedure well with minimal regimen-related toxicity (RRT). Engraftment was achieved with an ANC above 0.5 × 109/l on day +23 and a platelet count above 20 × 109/l was observed on day +58 after the second CBT. The PBMC sample obtained on day +26 showed complete second-donor chimerism. Along with recovery of the neutrophil count, bacteremia and endotoxemia improved. However, CMV antigenemia developed again despite continuous administration of foscarnet. Moreover, on day +23, HHV6 encephalitis developed. The dosage of foscarnet was increased to 120 mg/kg/day; however, foscarnet was substituted with ganciclovir (5 mg/kg/day) due to development of flatulence as a side effect. CMV antigen-positive cells disappeared and HHV6 encephalitis improved. The patient then developed acute GVHD (skin stage 1, grade I) and bronchiolitis obliterans with organizing pneumonia, which was controlled by steroid administration. The patient’s CR has since been maintained with a Karnofsky performance status of 100%, 5 months after the second CBT.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Chao NJ, Emerson SG, Weinberg KI . Stem cell transplantation (cord blood transplants). Hematol Am Soc Hematol Educ Program 2004, 354–371.

    Article  Google Scholar 

  2. Georges G, Storb R . Failure of sustained engraftment: clinical manifestations and treatment. In: Atkinson K (eds). Clinical Bone Marrow and Blood Stem Cell Transplantation, 3rd edn. Cambridge University Press: Cambridge, UK, 2000. pp 1088–1188.

    Google Scholar 

  3. Tomonari A, Iseki T, Ooi J, Takahashi S, Shindo M, Ishii K et al. Cytomegalovirus infection following unrelated cord blood transplantation for adult patients: a single institute experience in Japan. Br J Haematol 2003; 121: 304–311.

    Article  Google Scholar 

  4. Yoshikawa T . Human herpesvirus 6 infection in hematopoietic stem cell transplant patients. Br J Haematol 2004; 124: 421–432.

    Article  Google Scholar 

  5. Guardiola P, Kuentz M, Garban F, Blaise D, Reiffers J, Attal M et al. Second early allogeneic stem cell transplantations for graft failure in acute leukaemia, chronic myeloid leukemia and aplastic anaemia. French Society of Bone Marrow Transplantation. Br J Haematol 2000; 111: 292–302.

    Article  CAS  Google Scholar 

  6. Platzbecker U, Thiede C, Freiberg-Richter J, Helwig A, Mohr B, Prange G et al. Treatment of relapsing leukemia after allogeneic blood stem cell transplantation by using dose-reduced conditioning followed by donor blood stem cells and GM-CSF. Ann Hematol 2001; 80: 144–149.

    Article  CAS  Google Scholar 

  7. Bolwell B, Sobecks R, Pohlman B, Andresen S, Rybicki L, Kuczkowski E et al. A prospective randomized trial comparing cyclosporine and short course methotrexate with cyclosporine and mycophenolate mofetil for GVHD prophylaxis in myeloablative allogeneic bone marrow transplantation. Bone Marrow Transplant 2004; 34: 621–625.

    Article  CAS  Google Scholar 

  8. Denton M, Kerr KG . Microbiological and clinical aspects of infection associated with Stenotrophomonas maltophilia. Clin Microbiol Rev 1998; 11: 57–80.

    Article  CAS  Google Scholar 

  9. Ohwada C, Nakaseko C, Ozawa S, Takeuchi M, Shono K, Koizumi M et al. Second cord blood transplantation (CBT) with reduced-intensity conditioning for graft failure after the first CBT for AML. Bone Marrow Transplant 2004; 34: 999–1000.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Third Department of Internal Medicine, Yamaguchi University School of Medicine, Yamaguchi, Japan

    Y Nakamura, Y Tanaka, T Ando, Y Sato, T Yujiri & Y Tanizawa

Authors
  1. Y Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T Ando
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Y Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T Yujiri
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Y Tanizawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Y Nakamura.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nakamura, Y., Tanaka, Y., Ando, T. et al. Successful engraftment of the second reduced-intensity conditioning cord blood transplantation (CBT) for a patient who developed graft rejection and infectious complications after the first CBT for AML. Bone Marrow Transplant 40, 395–396 (2007). https://doi.org/10.1038/sj.bmt.1705732

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705732

This article is cited by

Search

Advanced search

Quick links