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.

  • Original Article
  • Published:

Transplant Toxicities

Long term renal survival in patients undergoing T-Cell depleted versus conventional hematopoietic stem cell transplants

Abstract

Calcineurin inhibitor (CNI)-sparing T-cell depleted (TCD) hematopoietic stem cell transplants (HSCTs) are presumed to be less nephrotoxic than conventional HSCTs. We evaluated incidence and risk factors for kidney failure and chronic kidney disease (CKD) in 231 TCD and 212 conventional HSCT recipients. Kidney failure required a median glomerular filtration rate (GFR) <60 ml/min/1.73 m2 for 100 days anytime after 180-days post-HSCT. Two-year cumulative incidence (CI) of kidney failure was 42% in the conventional versus 31% in the TCD group (P=0.005). TCD, age, acute kidney injury and number of toxic CNI levels all impacted on kidney failure, which was associated with increased all-cause mortality (hazard ratio 2.86 (95% CI: 1.88–4.36), P<0.001). Renal recovery occurred in 28% of kidney failure patients whereas the remaining patients were defined to have CKD. In those with baseline GFR>60 ml/min/1.73 m2, only exposure to nephrotoxic medications was associated with CKD (P=0.033). In the myeloablative-conditioning subgroup only total body irradiation was associated with CKD (P=0.013). Of all patients, five (1.13%) required dialysis. These results confirm an impact of TCD on kidney failure but not CKD for which other risk factors such as radiation or nephrotoxic drug exposure may have a role.

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

Access options

Buy this article

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

Figure 1

Similar content being viewed by others

References

  1. Hingorani S . Renal complications of hematopoietic-cell transplantation. N Engl J Med 2016; 374: 2256–2267.

    Article  Google Scholar 

  2. Socie G, Stone JV, Wingard JR, Weisdorf D, Henslee-Downey PJ, Bredeson C et al. Long-term survival and late deaths after allogeneic bone marrow transplantation. Late Effects Working Committee of the International Bone Marrow Transplant Registry. N Engl J Med 1999; 341: 14–21.

    Article  CAS  Google Scholar 

  3. Ferry C, Gemayel G, Rocha V, Labopin M, Esperou H, Robin M et al. Long-term outcomes after allogeneic stem cell transplantation for children with hematological malignancies. Bone Marrow Transplant 2007; 40: 219–224.

    Article  CAS  Google Scholar 

  4. Al-Hazzouri A, Cao Q, Burns LJ, Weisdorf DJ, Majhail NS . Similar risks for chronic kidney disease in long-term survivors of myeloablative and reduced-intensity allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2008; 14: 658–663.

    Article  Google Scholar 

  5. Kersting S, Hene RJ, Koomans HA, Verdonck LF . Chronic kidney disease after myeloablative allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2007; 13: 1169–1175.

    Article  Google Scholar 

  6. Delgado J, Cooper N, Thomson K, Duarte R, Jarmulowicz M, Cassoni A et al. The importance of age, fludarabine, and total body irradiation in the incidence and severity of chronic renal failure after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2006; 12: 75–83.

    Article  Google Scholar 

  7. Miralbell R, Bieri S, Mermillod B, Helg C, Sancho G, Pastoors B et al. Renal toxicity after allogeneic bone marrow transplantation: the combined effects of total-body irradiation and graft-versus-host disease. J Clin Oncol 1996; 14: 579–585.

    Article  CAS  Google Scholar 

  8. Glezerman IG, Jhaveri KD, Watson TH, Edwards AM, Papadopoulos EB, Young JW et al. Chronic kidney disease, thrombotic microangiopathy, and hypertension following T cell-depleted hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2010; 16: 976–984.

    Article  Google Scholar 

  9. Singh N, McNeely J, Parikh S, Bhinder A, Rovin BH, Shidham G . Kidney complications of hematopoietic stem cell transplantation. Am J Kidney Dis 2013; 61: 809–821.

    Article  CAS  Google Scholar 

  10. Jakubowski AA, Small TN, Kernan NA, Castro-Malaspina H, Collins N, Koehne G et al. T cell-depleted unrelated donor stem cell transplantation provides favorable disease-free survival for adults with hematologic malignancies. Biol Blood Marrow Transplant 2011; 17: 1335–1342.

    Article  Google Scholar 

  11. Hobbs GS, Hamdi A, Hilden PD, Goldberg JD, Poon ML, Ledesma C et al. Comparison of outcomes at two institutions of patients with ALL receiving ex vivo T-cell-depleted or unmodified allografts. Bone Marrow Transplant 2015; 50: 493–498.

    Article  CAS  Google Scholar 

  12. Bayraktar UD, de Lima M, Saliba RM, Maloy M, Castro-Malaspina HR, Chen J et al. Ex vivo T cell-depleted versus unmodified allografts in patients with acute myeloid leukemia in first complete remission. Biol Blood Marrow Transplant 2013; 19: 898–903.

    Article  CAS  Google Scholar 

  13. Naesens M, Kuypers DR, Sarwal M . Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol 2009; 4: 481–508.

    Article  CAS  Google Scholar 

  14. Weiss AS, Sandmaier BM, Storer B, Storb R, McSweeney PA, Parikh CR . Chronic kidney disease following non-myeloablative hematopoietic cell transplantation. Am J Transplant 2006; 6: 89–94.

    Article  CAS  Google Scholar 

  15. Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S et al. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 2006; 145: 247–254.

    Article  CAS  Google Scholar 

  16. KDIGO Working Group. Chapter 1: Definition and Classification of CKD. In: Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl 2013; 3: 19–62.

    Article  Google Scholar 

  17. Parikh CR, Coca SG . Acute renal failure in hematopoietic cell transplantation. Kidney Int 2006; 69: 430–435.

    Article  CAS  Google Scholar 

  18. KDIGO Working Group. Section 2: AKI Definition. In: Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl 2012; 2: 19–22.

    Article  Google Scholar 

  19. Boulad F, Jakubowski A, Papadopoulos EB, Hsu KC, Perales MA, van den Brink M et al. Phase II trial of a chemotherapy-only regimen of busulfan, melphalan, fludarabine and R-ATG followed by allogeneic T-cell depleted hematopoietic stem cell transplants for the treatment of myeloid malignancies. Blood 2007; 110: 2991a.

    Article  Google Scholar 

  20. Devine SM, Carter S, Soiffer RJ, Pasquini MC, Hari PN, Stein A et al. Low risk of chronic graft-versus-host disease and relapse associated with T cell-depleted peripheral blood stem cell transplantation for acute myelogenous leukemia in first remission: results of the blood and marrow transplant clinical trials network protocol 0303. Biol Blood Marrow Transplant 2011; 17: 1343–1351.

    Article  Google Scholar 

  21. Jakubowski AA, Small TN, Young JW, Kernan NA, Castro-Malaspina H, Hsu KC et al. T cell depleted stem-cell transplantation for adults with hematologic malignancies: sustained engraftment of HLA-matched related donor grafts without the use of antithymocyte globulin. Blood 2007; 110: 4552–4559.

    Article  CAS  Google Scholar 

  22. Collins NH, Fernandez J, Bleau S, Smith K, Cordero D, Alpdogan O et al. Comparison of bone marrow and G-CSF mobilized peripheral blood progenitor cells from single normal donors before and after T cell depletion. Cytotherapy 1999; 1: 223.

    Article  Google Scholar 

  23. Collins NH, Bleau SA, Kernan NA, O'Reilly RJ T-cell depletion of bone marrow by treatment with soybean agglutinin and sheep red blood cell rosetting. In: Areman E, Deeg HJ, Sacher RA(eds). Bone Marrow and Stem Cell Processing: Manual of Current Techniques. Davis: Philadelphia, PA, USA, 1992, pp171.

    Google Scholar 

  24. Barker JN, Byam C, Scaradavou A . How I treat: the selection and acquisition of unrelated cord blood grafts. Blood 2011; 117: 2332–2339.

    Article  CAS  Google Scholar 

  25. Humes HD . Aminoglycoside nephrotoxicity. Kidney Int 1988; 33: 900–911.

    Article  CAS  Google Scholar 

  26. Vittecoq D, Dumitrescu L, Beaufils H, Deray G . Fanconi syndrome associated with cidofovir therapy. Antimicrob Agents Chemother 1997; 41: 1846.

    Article  CAS  Google Scholar 

  27. Deray G, Martinez F, Katlama C, Levaltier B, Beaufils H, Danis M et al. Foscarnet nephrotoxicity: mechanism, incidence and prevention. Am J Nephrol 1989; 9: 316–321.

    Article  CAS  Google Scholar 

  28. Harbarth S, Pestotnik SL, Lloyd JF, Burke JP, Samore MH . The epidemiology of nephrotoxicity associated with conventional amphotericin B therapy. Am J Med 2001; 111: 528–534.

    Article  CAS  Google Scholar 

  29. Sorror ML, Martin PJ, Storb RF, Bhatia S, Maziarz RT, Pulsipher MA et al. Pretransplant comorbidities predict severity of acute graft-versus-host disease and subsequent mortality. Blood 2014; 124: 287–295.

    Article  CAS  Google Scholar 

  30. Touzot M, Elie C, van Massenhove J, Maillard N, Buzyn A, Fakhouri F . Long-term renal function after allogenic haematopoietic stem cell transplantation in adult patients: a single-centre study. Nephrol Dial Transplant 2010; 25: 624–627.

    Article  Google Scholar 

  31. Foley RN, Murray AM, Li S, Herzog CA, McBean AM, Eggers PW et al. Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the United States Medicare population, 1998 to 1999. J Am Soc Nephrol 2005; 16: 489–495.

    Article  Google Scholar 

  32. Ellis MJ, Parikh CR, Inrig JK, Kanbay M, Patel UD . Chronic kidney disease after hematopoietic cell transplantation: a systematic review. Am J Transplant 2008; 8: 2378–2390.

    Article  CAS  Google Scholar 

  33. Cohen EP, Drobyski WR, Moulder JE . Significant increase in end-stage renal disease after hematopoietic stem cell transplantation. Bone Marrow Transplant 2007; 39: 571–572.

    Article  CAS  Google Scholar 

  34. Kogon A, Hingorani S . Acute kidney injury in hematopoietic cell transplantation. Semin Nephrol 2010; 30: 615–626.

    Article  Google Scholar 

Download references

Acknowledgements

This work is supported in part by MSK Cancer Center Support Grant/Core Grant (P30 CA008748).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to I G Glezerman.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Glezerman, I., Devlin, S., Maloy, M. et al. Long term renal survival in patients undergoing T-Cell depleted versus conventional hematopoietic stem cell transplants. Bone Marrow Transplant 52, 733–738 (2017). https://doi.org/10.1038/bmt.2016.343

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2016.343

This article is cited by

Search

Quick links