Skip to main content

Advertisement

SpringerLink
Log in

Risk factors in patients undergoing haploidentical hematopoietic stem cell transplantation for high-risk childhood acute leukemia

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

In the present study, we sought to analyze the risk factors following haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in children with high-risk acute leukemia. We retrospectively reviewed data from 73 children with high-risk leukemia. Univariate and multivariate analyses were performed to evaluate relationships between variables and patient outcomes. The mean time for neutrophil engraftment was significantly shorter in children given a graft with a higher number of nucleated cells (>10.13 × 108/kg vs ≤10.13 × 108/kg: 13.79 ± 2.73 vs 17.71 ± 3.90 days, P < 0.001) and in younger children (≤10 years vs >10 years: 14.21 ± 3.12 vs 17.71 ± 3.90 days, P < 0.001). Time to platelet engraftment was clearly shorter in children given a graft with higher number of nucleated cells (>10.13 × 108/kg vs ≤10.13 × 108/kg: 12.12 ± 8.62 vs 32.1 ± 24.83 days, P < 0.028). Overall survival was 64.6 ± 9.1%, 41.1 ± 10.1%, and 81.6 ± 9.6%, respectively, in children with HR-ALL in CR1, ALL in CR2–4, and AML (P = 0.012). The number of total nucleated cells was significantly associated with transplant-related mortality (TRM). We suggest that outcomes of haplo-HSCT may be improved by increased infusion of nucleated cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Pui CH, Evans WE. Treatment of acute lymphoblastic leukemia. N Engl J Med. 2006;354:166–78.

    Article  CAS  PubMed  Google Scholar 

  2. Conter V, Valsecchi MG, Parasole R, Putti MC, Locatelli F, Barisone E, et al. Childhood high-risk acute lymphoblastic leukemia in first remission: results after chemotherapy or transplant from the AIEOP ALL 2000 study. Blood. 2014;123:1470–8.

    Article  CAS  PubMed  Google Scholar 

  3. Marshall GM, Dalla PL, Sutton R, Ng A, de GrootKruseman HA, Vh VDV, et al. High-risk childhood acute lymphoblastic leukemia in first remission treated with novel intensive chemotherapy and allogeneic transplantation. Leukemia. 2013;27:1497–503.

    Article  CAS  PubMed  Google Scholar 

  4. Pulsipher MA, Peters C, Pui CH. High-risk pediatric acute lymphoblastic leukemia: to transplant or not to transplant? Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2011;17:137–48.

    Article  Google Scholar 

  5. Balduzzi A, Valsecchi MG, Uderzo C, Lorenzo PD, Klingebiel T, Peters C, et al. Chemotherapy versus allogeneic transplantation for very-high-risk childhood acute lymphoblastic leukaemia in first complete remission: comparison by genetic randomisation in an international prospective study. Lancet. 2005;366:635–42.

    Article  PubMed  Google Scholar 

  6. Schrauder A, Reiter A, Gadner H, Niethammer D, Klingebiel T, Kremens B, et al. Superiority of allogeneic hematopoietic stem-cell transplantation compared with chemotherapy alone in high-risk childhood T-cell acute lymphoblastic leukemia: results from ALL-BFM 90 and 95. J Clin Oncol. 2006;24:5742–9.

    Article  PubMed  Google Scholar 

  7. Peters C, Schrauder A, Schrappe M, Stackelberg AV, Stary J, Yaniv I, et al. Allogeneic haematopoietic stem cell transplantation in children with acute lymphoblastic leukaemia: the BFM|[sol]|IBFM|[sol]|EBMT concepts. Bone Marrow Transplant. 2005;35(Suppl 1):S9–11.

    Article  PubMed  Google Scholar 

  8. Lang P, Handgretinger R, Niethammer D, Schlegel PG, Schumm M, Greil J, et al. Transplantation of highly purified CD34+ progenitor cells from unrelated donors in pediatric leukemia. Blood. 2003;101:1630–6.

    Article  CAS  PubMed  Google Scholar 

  9. Klingebiel T, Cornish J, Labopin M, Locatelli F, Darbyshire P, Handgretinger R, et al. Results and factors influencing outcome after fully haploidentical hematopoietic stem cell transplantation in children with very high-risk acute lymphoblastic leukemia: impact of center size: an analysis on behalf of the Acute Leukemia and Pediatric Disease Working Parties of the European Blood and Marrow Transplant group. Blood. 2010;115:3437–46.

    Article  CAS  PubMed  Google Scholar 

  10. Aversa F, Tabilio A, Velardi A, Cunningham I, Terenzi A, Falzetti F, et al. Treatment of high risk acute leukaemia with T-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med. 1998;339:1186–93.

    Article  CAS  PubMed  Google Scholar 

  11. Ciurea SO, de Lima M, Cano P, Korbling M, Giralt S, Shpall EJ, et al. High risk of graft failure in patients with anti-HLA antibodies undergoing haploidentical stem cell transplantation. Transplantation. 2009;88:1019–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Huang XJ. Current status of haploidentical stem cell transplantation for leukemia. J Hematol Oncol. 2008;1:1–9.

    Article  Google Scholar 

  13. Kang Y, Chao NJ, Aversa F. Unmanipulated or CD34 selected haplotype mismatched transplants. Curr Opin Hematol. 2008;15:561–7.

    Article  CAS  PubMed  Google Scholar 

  14. Lu DP, Dong L, Wu T, Huang XJ, Zhang MJ, Han W, et al. Conditioning including antithymocyte globulin followed by un-manipulated HLA-mismatched/haploidentical blood and marrow transplantation can achieve comparable outcomes to HLA-identical sibling transplantation. Blood. 2006;107:3065–73.

    Article  CAS  PubMed  Google Scholar 

  15. Xiaojun H, Lanping X, Kaiyan L, Daihong L, Huan C, Wei H, et al. HLA-mismatched/haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for chronic myeloid leukemia: improved outcomes in patients in accelerated phase and blast crisis phase. Ann Med. 2008;40:444–55.

    Article  Google Scholar 

  16. Huang XJ, Liu DH, Liu KY, Xu LP. Treatment of acute leukemia with unmanipulated HLA-mismatched/haploidentical blood and bone marrow transplantation. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2009;15:257–65.

    Article  CAS  Google Scholar 

  17. Jaffe ES, Harris ES, Stein H, Vardiman JW, editors. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. WHO Classification of Tumours. Lyon: IARC Press; 2001.

  18. Aversa F. Haploidentical haematopoietic stem cell transplantation for acute leukaemia in adults: experience in Europe and the United States. Bone Marrow Transplant. 2008;41:473–81.

    Article  CAS  PubMed  Google Scholar 

  19. Wagner JE, Barker JN, DeFor TE, Baker KS, Blazar BR, Eide C, et al. Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases: influence of CD34 cell dose and HLA disparity on treatment-related mortality and survival. Blood. 2002;100:1611–8.

    CAS  PubMed  Google Scholar 

  20. Page KM, Zhang L, Mendizabal A, Wease S, Carter S, Gentry T, et al. Total colony-forming units are a strong, independent predictor of neutrophil and platelet engraftment after unrelated umbilical cord blood transplantation: a single-center analysis of 435 cord blood transplants. Biol Blood Marrow Transplant. 2011;17:1362–74.

    Article  PubMed  Google Scholar 

  21. Laughlin MJ, Barker J, Bambach B, Koc ON, Rizzieri DA, Wagner JE, et al. Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors. N Engl J Med. 2001;344:1815–22.

    Article  CAS  PubMed  Google Scholar 

  22. Chang YJ, Xu LP, Liu DH, Liu KY. Platelet engraftment in patients with hematologic malignancies following unmanipulated haploidentical blood and marrow transplantation: effects of CD34+ cell dose and disease status. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2009;15:632–8.

    Article  Google Scholar 

  23. Yu W, Liu DH, Liu Kai-Yan, Lan-Ping Xu, Zhang Xiao-Hui, Wei HM, et al. Long-term follow-up of haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for the treatment of leukemia. Cancer. 2013;119:978–85.

    Article  Google Scholar 

  24. Kim HJ, Park SJ, Im HW, Dong WK, Min WS, Kim HK, et al. The association of HLA antigen and GVHD in allogeneic hemopoietic stem cell transplantation with histocompatible sibling donor: a single-center experience in Korea. Int J Hematol. 2002;76:267–71.

    Article  CAS  PubMed  Google Scholar 

  25. Huo MR, Xu LP, Li D, Liu DH, Liu KY, Chen H, et al. The effect of HLA disparity on clinical outcome after HLA-haploidentical blood and marrow transplantation. Clin Transplant. 2012;26:284–91.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Hematology, General Hospital of the Air Force, Beijing, 100142, China

    Dong-mei Han, Xiao-li Zheng, Li Ding, Hong-min Yan, Zhi-dong Wang, Mei Xue, Ling Zhu, Jing Liu & Heng-xiang Wang

Authors
  1. Dong-mei Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiao-li Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Li Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hong-min Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhi-dong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mei Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ling Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jing Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Heng-xiang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Heng-xiang Wang.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Han, Dm., Zheng, Xl., Ding, L. et al. Risk factors in patients undergoing haploidentical hematopoietic stem cell transplantation for high-risk childhood acute leukemia. Int J Hematol 106, 820–831 (2017). https://doi.org/10.1007/s12185-017-2317-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-017-2317-y

Keywords

Search

Navigation