Skip to main content

Advertisement

SpringerLink
Log in

Comparison of central nervous system relapse outcomes following haploidentical vs identical-sibling transplant for acute lymphoblastic leukemia

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

Abstract

To explore the incidence, risk factors, and outcomes of central nervous system (CNS) relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukemia (ALL) and to compare the differences in CNS relapse between haploidentical donor HSCT (HID-HSCT) and HLA-identical sibling donor HSCT (ISD-HSCT). We performed a retrospective nested case-control study on patients with CNS relapse after allo-HSCT. The cumulative incidence of CNS relapse was 4.06% after allo-HSCT in ALL, with a significantly poor prognosis. The incidence was 3.91% and 5.36% in HID-HSCT and ISD-HSCT, respectively (p = .227). Among the patients with CNS relapse, the overall survival (OS) at 3 years was 56.2 ± 6.8% in the HID-HSCT subgroup and 76.9 ± 10.2% in the ISD-HSCT subgroup (p = .176). The 3-year cumulative incidence of systemic relapse was also comparable between the two subgroups (HID-HSCT, 40.6 ± 7.4%; ISD-HSCT, 13.3 ± 8.7%, respectively, p = .085). Younger age (p = .045), T-ALL (p = .035), hyperleukocytosis at diagnosis (p < .001), advanced disease stage at transplant (p < .001), pre-HSCT CNS involvement (p < .001), and absence of chronic graft vs host disease (cGVHD) (p < .001) were independent risk factors for CNS relapse after allo-HSCT. In conclusion, CNS relapse was a significant complication after allo-HSCT in ALL and was associated with poor prognosis. The incidences and outcomes were comparable between HID-HSCT and ISD-HSCT.

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. Barredo J, Ritchey AK (2010) Controversies in the management of central nervous system leukemia. Pediatr Hematol Oncol 27(5):329–332. https://doi.org/10.3109/08880011003758422

    Article  PubMed  Google Scholar 

  2. Hardisty RM, Norman PM (1967) Meningeal leukaemia. Arch Dis Child 42(224):441–447. https://doi.org/10.1136/adc.42.224.441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Cortes J, O’Brien SM, Pierce S, Keating MJ, Freireich EJ, Kantarjian HM (1995) The value of high-dose systemic chemotherapy and intrathecal therapy for central nervous system prophylaxis in different risk groups of adult acute lymphoblastic leukemia. Blood 86(6):2091–2097

    Article  CAS  Google Scholar 

  4. Omura GA, Moffitt S, Vogler WR, Salter MM (1980) Combination chemotherapy of adult acute lymphoblastic leukemia with randomized central nervous system prophylaxis. Blood 55(2):199–204

    Article  CAS  Google Scholar 

  5. Fielding AK, Richards SM, Chopra R, Lazarus HM, Litzow MR, Buck G et al (2007) Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study. Blood 109(3):944–950. https://doi.org/10.1182/blood-2006-05-018192

    Article  CAS  PubMed  Google Scholar 

  6. Thomas X, Boiron JM, Huguet F, Dombret H, Bradstock K, Vey N et al (2004) Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol 22(20):4075–4086. https://doi.org/10.1200/jco.2004.10.050

    Article  CAS  PubMed  Google Scholar 

  7. Poon LM, Hamdi A, Saliba R, Rondon G, Ledesma C, Kendrick M, Qazilbash M, Hosing C, Jones RB, Popat UR, Nieto Y, Alousi A, Ciurea S, Shpall EJ, Champlin RE, Kebriaei P (2013) Outcomes of adults with acute lymphoblastic leukemia relapsing after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 19(7):1059–1064. https://doi.org/10.1016/j.bbmt.2013.04.014

    Article  PubMed  Google Scholar 

  8. Mortimer J, Blinder MA, Schulman S, Appelbaum FR, Buckner CD, Clift RA, Sanders JE, Storb R, Thomas ED (1989) Relapse of acute leukemia after marrow transplantation: natural history and results of subsequent therapy. J Clin Oncol 7(1):50–57

    Article  CAS  Google Scholar 

  9. Thompson CB, Sanders JE, Flournoy N, Buckner CD, Thomas ED (1986) The risks of central nervous system relapse and leukoencephalopathy in patients receiving marrow transplants for acute leukemia. Blood 67(1):195–199

    Article  CAS  Google Scholar 

  10. Ganem G, Kuentz M, Bernaudin F, Gharbi A, Cordonnier C, Lemerle S, Karianakis G, Vinci G, Rochant H, Lebourgeois JP, Vernant JP (1989) Central nervous system relapses after bone marrow transplantation for acute lymphoblastic leukemia in remission. Cancer 64(9):1796–1804

    Article  CAS  Google Scholar 

  11. Oshima K, Kanda Y, Yamashita T, Takahashi S, Mori T, Nakaseko C, Fujimaki K, Yokota A, Fujisawa S, Matsushima T, Fujita H, Sakura T, Okamoto S, Maruta A, Sakamaki H, Kanto Study Group for Cell Therapy (2008) Central nervous system relapse of leukemia after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 14(10):1100–1107

    Article  Google Scholar 

  12. Wang Y, Liu QF, Xu LP, Liu KY, Zhang XH, Ma X, Fan ZP, Wu DP, Huang XJ (2015) Haploidentical vs identical-sibling transplant for AML in remission: a multicenter, prospective study. Blood 125(25):3956–3962. https://doi.org/10.1182/blood-2015-02-627786

    Article  CAS  PubMed  Google Scholar 

  13. Wang Y, Wang HX, Lai YR, Sun ZM, Wu DP, Jiang M, Liu DH, Xu KL, Liu QF, Liu L, Wang JB, Gao F, Ou-Yang J, Gao SJ, Xu LP, Huang XJ (2016) Haploidentical transplant for myelodysplastic syndrome: registry-based comparison with identical sibling transplant. Leukemia 30(10):2055–2063. https://doi.org/10.1038/leu.2016.110

    Article  CAS  PubMed  Google Scholar 

  14. Huang XJ, Zhu HH, Chang YJ, Xu LP, Liu DH, Zhang XH, Jiang B, Jiang Q, Jiang H, Chen YH, Chen H, Han W, Liu KY, Wang Y (2012) The superiority of haploidentical related stem cell transplantation over chemotherapy alone as postremission treatment for patients with intermediate- or high-risk acute myeloid leukemia in first complete remission. Blood 119(23):5584–5590. https://doi.org/10.1182/blood-2011-11-389809

    Article  CAS  PubMed  Google Scholar 

  15. Lorentino F, Labopin M, Bernardi M, Ciceri F, Socié G, Cornelissen JJ, Esteve J, Ruggeri A, Volin L, Yacoub-Agha I, Craddock C, Passweg J, Blaise D, Gedde-Dahl T, Poiani M, Fegueux N, Mohty M, Nagler A, On Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (2018) Comparable outcomes of haploidentical, 10/10 and 9/10 unrelated donor transplantation in adverse karyotype AML in first complete remission. Am J Hematol 93(10):1236–1244. https://doi.org/10.1002/ajh.25231

    Article  PubMed  Google Scholar 

  16. Kobayashi S, Kikuta A, Ito M, Sano H, Mochizuki K, Akaihata M, Waragai T, Ohara Y, Ogawa C, Ono S, Ohto H, Hosoya M (2014) Loss of mismatched HLA in myeloid/NK cell precursor acute leukemia relapse after T cell-replete haploidentical hematopoietic stem cell transplantation. Pediatr Blood Cancer 61(10):1880–1882. https://doi.org/10.1002/pbc.24962

    Article  CAS  PubMed  Google Scholar 

  17. Vago L, Perna SK, Zanussi M, Mazzi B, Barlassina C, Stanghellini MT et al (2009) Loss of mismatched HLA in leukemia after stem-cell transplantation. N Engl J Med 361(5):478–488. https://doi.org/10.1056/NEJMoa0811036

    Article  CAS  PubMed  Google Scholar 

  18. Singhal S, Powles R, Treleaven J, Horton C, Tait D, Meller S, Pinkerton CR, Mehta J (1996) Central nervous system relapse after bone marrow transplantation for acute leukemia in first remission. Bone Marrow Transplant 17(4):637–641

    CAS  PubMed  Google Scholar 

  19. Rubin J, Vettenranta K, Vettenranta J, Bierings M, Abrahamsson J, Bekassy AN, Håkansson Y, Frost BM, Arvidson J, Spendilow C, Winiarski J, Gustafsson B (2011) Use of intrathecal chemoprophylaxis in children after SCT and the risk of central nervous system relapse. Bone Marrow Transplant 46(3):372–378. https://doi.org/10.1038/bmt.2010.121

    Article  CAS  PubMed  Google Scholar 

  20. Hamdi A, Mawad R, Bassett R, di Stasi A, Ferro R, Afrough A, Ram R, Dabaja B, Rondon G, Champlin R, Sandmaier BM, Doney K, Bar M, Kebriaei P (2014) Central nervous system relapse in adults with acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 20(11):1767–1771. https://doi.org/10.1016/j.bbmt.2014.07.005

    Article  PubMed  PubMed Central  Google Scholar 

  21. Shi JM, Meng XJ, Luo Y, Tan YM, Zhu XL, Zheng GF et al (2013) Clinical characteristics and outcome of isolated extramedullary relapse in acute leukemia after allogeneic stem cell transplantation: a single-center analysis. Leuk Res 37(4):372–377. https://doi.org/10.1016/j.leukres.2012.12.002

    Article  PubMed  Google Scholar 

  22. Zheng C, Zhu X, Tang B, Yao W, Song K, Tong J, Geng L, Liu H, Sun Z (2015) Comparative analysis of unrelated cord blood transplantation and HLA-matched sibling hematopoietic stem cell transplantation in children with high-risk or advanced acute leukemia. Ann Hematol 94(3):473–480. https://doi.org/10.1007/s00277-014-2213-y

    Article  CAS  PubMed  Google Scholar 

  23. Duval M, Klein JP, He W, Cahn J-Y, Cairo M, Camitta BM, Kamble R, Copelan E, de Lima M, Gupta V, Keating A, Lazarus HM, Litzow MR, Marks DI, Maziarz RT, Rizzieri DA, Schiller G, Schultz KR, Tallman MS, Weisdorf D (2010) Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure. J Clin Oncol 28(23):3730–3738. https://doi.org/10.1200/JCO.2010.28.8852

    Article  PubMed  PubMed Central  Google Scholar 

  24. Wang Y, Liu DH, Xu LP, Liu KY, Chen H, Zhang XH, Chen YH, Han W, Wang FR, Wang JZ, Yan CH, Huang XJ (2012) Prevention of relapse using granulocyte CSF-primed PBPCs following HLA-mismatched/haploidentical, T-cell-replete hematopoietic SCT in patients with advanced-stage acute leukemia: a retrospective risk-factor analysis. Bone Marrow Transplant 47(8):1099–1104. https://doi.org/10.1038/bmt.2011.213

    Article  CAS  PubMed  Google Scholar 

  25. Kantarjian H, Stein A, Gökbuget N, Fielding AK, Schuh AC, Ribera J-M, Wei A, Dombret H, Foà R, Bassan R, Arslan Ö, Sanz MA, Bergeron J, Demirkan F, Lech-Maranda E, Rambaldi A, Thomas X, Horst HA, Brüggemann M, Klapper W, Wood BL, Fleishman A, Nagorsen D, Holland C, Zimmerman Z, Topp MS (2017) Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med 376(9):836–847. https://doi.org/10.1056/NEJMoa1609783

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Piemontese S, Ciceri F, Labopin M, Bacigalupo A, Huang H, Santarone S et al (2015) A survey on unmanipulated haploidentical hematopoietic stem cell transplantation in adults with acute leukemia. Leukemia 29(5):1069–1075. https://doi.org/10.1038/leu.2014.336

    Article  CAS  PubMed  Google Scholar 

  27. Ruggeri A, Labopin M, Sanz G, Piemontese S, Arcese W, Bacigalupo A et al (2015) Comparison of outcomes after unrelated cord blood and unmanipulated haploidentical stem cell transplantation in adults with acute leukemia. Leukemia 29(9):1891–1900. https://doi.org/10.1038/leu.2015.98

    Article  CAS  PubMed  Google Scholar 

  28. Ciurea SO, Zhang MJ, Bacigalupo AA, Bashey A, Appelbaum FR, Aljitawi OS et al (2015) Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia. Blood 126(8):1033–1040. https://doi.org/10.1182/blood-2015-04-639831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Wang Y, Liu DH, Xu LP, Liu KY, Chen H, Chen YH et al (2011) Superior graft-versus-leukemia effect associated with transplantation of haploidentical compared with HLA-identical sibling donor grafts for high-risk acute leukemia: an historic comparison. Biol Blood Marrow Transplant 17(6):821–830. https://doi.org/10.1016/j.bbmt.2010.08.023

    Article  PubMed  Google Scholar 

  30. Yu S, Huang F, Wang Y, Xu Y, Yang T, Fan Z et al (2019) Haploidentical transplantation might have superior graft-versus-leukemia effect than HLA-matched sibling transplantation for high-risk acute myeloid leukemia in first complete remission: a prospective multicentre cohort study. Leukemia. https://doi.org/10.1038/s41375-019-0686-3

  31. Barrett AJ, Battiwalla M (2010) Relapse after allogeneic stem cell transplantation. Expert Rev Hematol 3(4):429–441. https://doi.org/10.1586/ehm.10.32

    Article  PubMed  PubMed Central  Google Scholar 

  32. Ma YR, Xu LP, Zhang XH, Yan CH, Wang Y, Wang FR et al (2017) Comparable post-relapse outcomes between haploidentical and matched related donor allogeneic stem cell transplantation. Bone Marrow Transplant 52(3):409–414. https://doi.org/10.1038/bmt.2016.283

    Article  CAS  PubMed  Google Scholar 

  33. Aldoss I, Al Malki MM, Stiller T, Cao T, Sanchez JF, Palmer J et al (2016) Implications and management of central nervous system involvement before allogeneic hematopoietic cell transplantation in acute lymphoblastic leukemia. Biol Blood Marrow Transplant 22(3):575–578. https://doi.org/10.1016/j.bbmt.2015.10.016

    Article  CAS  PubMed  Google Scholar 

  34. Ikegawa S, Doki N, Kaito S, Kurosawa S, Sakaguchi M, Harada K et al (2017) Central nervous system involvement at the time of allogeneic hematopoietic stem cell transplantation is associated with a poor outcome in patients with acute myeloid leukemia. Pathol Oncol Res 23(2):433–437. https://doi.org/10.1007/s12253-016-0162-6

    Article  CAS  PubMed  Google Scholar 

  35. Prem S, Atenafu EG, Avena J, Bautista R, Law A, Lam W et al (2019) Impact of central nervous system involvement in AML on outcomes after allotransplant and utility of pretransplant cerebrospinal fluid assessment. Eur J Haematol 103(5):483–490. https://doi.org/10.1111/ejh.13314

    Article  PubMed  Google Scholar 

  36. Ostronoff M, Domingues MC, Ostronoff F, Matias C, Florencio R, Matias K et al (2006) Reduced intensity conditioning allogeneic bone marrow transplantation following central nervous system (CNS) relapse of acute promyelocytic leukemia: evidence for a graft-versus-leukemia effect in the CNS. Am J Hematol 81(5):387–388. https://doi.org/10.1002/ajh.20616

    Article  CAS  PubMed  Google Scholar 

  37. Pinkel D, Woo S (1994) Prevention and treatment of meningeal leukemia in children. Blood 84(2):355–366

    Article  CAS  Google Scholar 

  38. Johnston DL, Alonzo TA, Gerbing RB, Lange BJ, Woods WG (2005) Risk factors and therapy for isolated central nervous system relapse of pediatric acute myeloid leukemia. J Clin Oncol 23(36):9172–9178. https://doi.org/10.1200/jco.2005.02.7482

    Article  PubMed  Google Scholar 

  39. Harris AC, Kitko CL, Couriel DR, Braun TM, Choi SW, Magenau J et al (2013) Extramedullary relapse of acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation: incidence, risk factors and outcomes. Haematologica 98(2):179–184. https://doi.org/10.3324/haematol.2012.073189

    Article  PubMed  PubMed Central  Google Scholar 

  40. Mo XD, Kong J, Zhao T, Xu LP, Zhang XH, Liu DH et al (2014) Extramedullary relapse of acute leukemia after haploidentical hematopoietic stem cell transplantation: incidence, risk factors, treatment, and clinical outcomes. Biol Blood Marrow Transplant 20(12):2023–2028. https://doi.org/10.1016/j.bbmt.2014.08.023

    Article  PubMed  Google Scholar 

  41. Wang Y, Chen H, Chen J, Han M, Hu J, Jiong H et al (2018) The consensus on the monitoring, treatment, and prevention of leukemia relapse after allogeneic hematopoietic stem cell transplantation in China. Cancer Lett 438:63–75. https://doi.org/10.1016/j.canlet.2018.08.030

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

The work was supported by the Beijing Natural Science Foundation (H2018206423), the Key Program of the National Natural Science Foundation of China (No. 81730004), the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (81621001), National Natural Science Foundation of China (No. 81670116), the Beijing Natural Science Foundation (No. 7171013), the Beijing Municipal Science and Technology Commission (No. Z171100001017084), and the National Key Research and Development Program of China (No. 2017YFA0105500, No. 2017YFA0105503).

Author information

Author notes

  1. Xin Zhao contributed equally to this work.

Authors and Affiliations

  1. Peking University People’s Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, China

    Qi Chen, Xin Zhao, Hai-xia Fu, Yu-hong Chen, Yuan-yuan Zhang, Jing-zhi Wang, Yu Wang, Chen-hua Yan, Feng-rong Wang, Xiao-dong Mo, Wei Han, Huan Chen, Ying-jun Chang, Lan-ping Xu, Kai-yan Liu, Xiao-jun Huang & Xiao-hui Zhang

  2. Peking University Institute of Hematology, Beijing, China

    Qi Chen, Xin Zhao, Hai-xia Fu, Yu-hong Chen, Yuan-yuan Zhang, Jing-zhi Wang, Yu Wang, Chen-hua Yan, Feng-rong Wang, Xiao-dong Mo, Wei Han, Huan Chen, Ying-jun Chang, Lan-ping Xu, Kai-yan Liu, Xiao-jun Huang & Xiao-hui Zhang

  3. National Clinical Research Center for Hematologic Disease, Beijing, China

    Qi Chen, Xin Zhao, Hai-xia Fu, Yu-hong Chen, Yuan-yuan Zhang, Jing-zhi Wang, Yu Wang, Chen-hua Yan, Feng-rong Wang, Xiao-dong Mo, Wei Han, Huan Chen, Ying-jun Chang, Lan-ping Xu, Kai-yan Liu, Xiao-jun Huang & Xiao-hui Zhang

  4. Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China

    Qi Chen, Xin Zhao, Hai-xia Fu, Yu-hong Chen, Yuan-yuan Zhang, Jing-zhi Wang, Yu Wang, Chen-hua Yan, Feng-rong Wang, Xiao-dong Mo, Wei Han, Huan Chen, Ying-jun Chang, Lan-ping Xu, Kai-yan Liu, Xiao-jun Huang & Xiao-hui Zhang

Authors
  1. Qi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xin Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hai-xia Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yu-hong Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuan-yuan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jing-zhi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Chen-hua Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Feng-rong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Xiao-dong Mo
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Wei Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Huan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Ying-jun Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Lan-ping Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Kai-yan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Xiao-jun Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Xiao-hui Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiao-hui Zhang.

Ethics declarations

Competing interests

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, Q., Zhao, X., Fu, Hx. et al. Comparison of central nervous system relapse outcomes following haploidentical vs identical-sibling transplant for acute lymphoblastic leukemia. Ann Hematol 99, 1643–1653 (2020). https://doi.org/10.1007/s00277-020-04080-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-020-04080-9

Keywords

Search

Navigation