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:

Second cancers early post allogeneic transplant: the case of ‘unrestrained’ malignancy?

Bone Marrow Transplantation volume 48, pages 872–874 (2013)Cite this article

Subjects

The incidence of second malignancies following hematopoietic SCT (HSCT) is low, ∼5%.1 The majority of these are hematological, with epithelial malignancies occurring at an incidence of 1–2% at 10-years post transplant, and increasing over time.1 Allogeneic transplant recipients have a 2–6 times higher risk of developing solid tumors when compared with the general population.1, 2, 3

Previous literature attributes second cancers after HSCT to conditioning radiation therapy, chronic GVHD, immunosuppressive treatments or to underlying disease, for example Fanconi’s anemia.1, 2, 3, 4 Epithelial secondary malignancies typically occur many years after transplant. Reported carcinomas include glioblastoma, squamous cell carcinoma (oral-cavity, skin, vulva), melanoma, basal cell carcinoma, ovarian, gastric and renal carcinomas as well as adenocarcinoma of the lung, liver and rectum.1, 2, 3, 4, 5, 6 New epithelial malignancies within <6 months are, however, exceptionally rare. Upon our review of the literature only eight such cases were identified: lung (2), stomach (2), renal (1), ovarian (1) and colon (2).4, 5, 6, 7, 8 Second cancers after transplant are usually recipient-derived, but there are cases of donor origin. A recent review of donor-derived second malignancies after HSCT reported 11 such cases published, these included cases of invasive breast adenocarcinoma (1), oral squamous cell carcinoma (7), lung squamous cell carcinoma (1), Kaposi’s sarcoma (1) and glioblastoma multiforme (1) occurring at an average of 7.9 (range 1–22) years after HSCT.8 In the current patient, donor origin was excluded by karyotype studies (see Figure 1d), pointing to a preexisting (second) or ‘de-novo’ (secondary) tumor of host origin.1, 2, 3, 4, 7 The timing of epithelial malignancy occurring so early after HSCT as in this case, is very atypical. Radiation therapy was not used for conditioning and cases of second malignancy have not been reported following EPOCH chemotherapy. This unusually early presentation of an aggressive new carcinoma could be related to high-intensity immunosuppression (by anti-CD2 Ab, transplant conditioning and/or GVHD prophylaxis), leading to activation of the immunologically ‘restrained’ cancer cells and acceleration of proliferation and growth. Such instances of early new cancer presentations after HSCT may have implications for studying mechanisms of tumorigenesis and cancer immunosurveillance.9, 10 In summary, although early second cancers post allogeneic HSCT are very rare they should be considered in the differential diagnosis of post-transplant hematologic malignancy relapse in a patient with an unusual clinical presentation. The possibility of very early cancers and the broader significance of this phenomenon should also mandate adherence to details in reporting cases with such clinical presentations.

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

Figure 1
Figure 2

References

  1. Rizzo JD, Curtis RE, Socie G, Sobocinski KA, Gilbert E, Landgren O et al. Solid cancers after allogeneic hematopoietic cell transplantation. Blood 2009; 113: 1175–1183.

    Article  CAS  Google Scholar 

  2. Majhail NS . Secondary cancers following allogeneic haematopoietic cell transplantation in adults. Br J Haematol 2011; 154: 301–310.

    Article  Google Scholar 

  3. Curtis RE, Rowlings PA, Deeg HJ, Shriner DA, Socie G, Travis LB et al. Solid cancers after bone marrow transplantation. N Engl J Med 1997; 336: 897–904.

    Article  CAS  Google Scholar 

  4. Witherspoon RP, Fisher LD, Schoch G, Martin P, Sullivan KM, Sanders J et al. Secondary cancers after bone marrow transplantation for leukemia or aplastic anemia. N Engl J Med 1989; 321: 784–789.

    Article  CAS  Google Scholar 

  5. Au WY, Pang A, Chan EC, Chu KM, Shek TW, Kwong YL . Epstein-barr virus-related gastric adenocarcinoma: an early secondary cancer post hemopoietic stem cell transplantation. Gastroenterology 2005; 129: 2058–2063.

    Article  Google Scholar 

  6. Gallagher G, Forrest DL . Second solid cancers after allogeneic hematopoietic stem cell transplantation. Cancer 2007; 109: 84–92.

    Article  Google Scholar 

  7. Au WY, Chan EC, Pang A, Lie AK, Liang R, Yuen AP et al. Nonhematologic malignancies after allogeneic hematopoietic stem cell transplantation: incidence and molecular monitoring. Bone Marrow Transplant 2004; 34: 981–985.

    Article  Google Scholar 

  8. Hu YX, Cui Q, Liang B, Huang H . Donor-derived solid malignancies after hematopoietic stem cell transplantation. Onkologie 2010; 33: 195–200.

    Article  Google Scholar 

  9. Schreiber RD, Old LJ, Smyth MJ . Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science 2011; 331: 1565–1570.

    Article  CAS  Google Scholar 

  10. Smyth MJ, Dunn GP, Schreiber RD . Cancer immunosurveillance and immunoediting: the roles of immunity in suppressing tumor development and shaping tumor immunogenicity. Adv Immunol 2006; 90: 1–50.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to acknowledge Drs Mark Raffeld and Svetlana Pack (Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892) for their help with TCR rearrangement and fluorescent in situ hybridization studies.

Author information

Authors and Affiliations

  1. Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    J K Davidson-Moncada & A Duffy

  2. Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    S Pittaluga & M Roth

  3. Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    K Dunleavy

  4. Experimental Transplant and Immunology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    S Pavletic

Authors
  1. J K Davidson-Moncada
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S Pittaluga
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Roth
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K Dunleavy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A Duffy
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S Pavletic
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S Pavletic.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Davidson-Moncada, J., Pittaluga, S., Roth, M. et al. Second cancers early post allogeneic transplant: the case of ‘unrestrained’ malignancy?. Bone Marrow Transplant 48, 872–874 (2013). https://doi.org/10.1038/bmt.2012.238

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2012.238

Search

Advanced search

Quick links