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Engraftment syndrome after allogeneic stem cell transplantation: a systematic review and meta-analysis

Bone Marrow Transplantation volume 58, pages 1–9 (2023)Cite this article

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Abstract

Engraftment syndrome (ES) is associated with neutrophil recovery after stem cell transplantation (SCT). It is associated with autologous and allogeneic SCT. However, a literature review has shown that allogeneic SCT (allo-SCT) is associated with ES without conclusive data on risk factors or effects on outcomes. This meta-analysis was undertaken to estimate the cumulative incidence of ES following allo-SCT, and to evaluate the risk factors and outcomes among patients with ES following allo-SCT. Current literature was searched using electronic databases, and manually. Studies with ES after allo-SCT were selected, and a meta-analysis of proportion was performed using the Freeman–Tukey Double Arcsine transformation, random-effects model to calculate the cumulative incidence of ES. Donor type, source of haematopoetic stem cells, graft vs. host disease (GvHD) prophylaxes, and conditioning regimens’ intensity were evaluated for risk factors for ES. Association of acute GvHD (aGvHD), chronic GvHD (cGvHD), relapse, nonrelapse mortality (NRM), and overall survival (OS) between the ES and no ES groups were assessed using the odds ratio (OR). Eighteen studies were included comprising 3620 patients receiving allo-SCT and 774 of them had developed ES with a cumulative incidence of 35.4%. The odds of aGvHD (OR 2.5, p < 0.001), cGvHD (OR 4.5, p = 0.021), and NRM (OR 1.8, p = 0.01) were higher among patients who developed ES. The odds of relapse were significantly less (OR = 0.679, p = 0.011) among the ES group. OS (OR = 0.72, p < 0.001) was reduced in the ES group. Myeloablative conditioning was found to be a significant risk factor for ES development. In conclusion, ES after allo-SCT is common with higher odds of developing aGvHD, cGvHD, and NRM and lower odds of OS.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Giralt S, Bishop MR. Principles and overview of allogeneic hematopoietic stem cell transplantation. Cancer Treat Res. 2009;144:1–21.

    Article  Google Scholar 

  2. Sahu KK. Infectious disease in hematopoietic stem cell transplantation. Ther Adv Infect Dis. 2021;8:20499361211005600. https://doi.org/10.1177/20499361211005600.

    Article  Google Scholar 

  3. Spitzer TR. Engraftment syndrome following hematopoietic stem cell transplantation. Bone Marrow Transplant. 2001;27:893–8.

    Article  Google Scholar 

  4. Spitzer TR. Engraftment syndrome: double-edged sword of hematopoietic cell transplants. Bone Marrow Transplant. 2015;50:469–75.

    Article  Google Scholar 

  5. Maiolino A, Biasoli I, Lima J, Portugal AC, Pulcheri W, Nucci M. Engraftment syndrome following autologous hematopoietic stem cell transplantation: definition of diagnostic criteria. Bone Marrow Transplant. 2003;31:393–7.

    Article  Google Scholar 

  6. Schmid I, Stachel D, Pagel P, Albert MH. Incidence, predisposing factors, and outcome of engraftment syndrome in pediatric allogeneic stem cell transplant recipients. Biol Blood Marrow Transplant. 2008;14:438–44.

    Article  Google Scholar 

  7. Patel KJ, Rice RD, Hawke R, Abboud M, Heller G, Scaradavou A, et al. Pre-engraftment syndrome after double-unit cord blood transplantation: a distinct syndrome not associated with acute graft-versus-host disease. Biol Blood Marrow Transplant. 2010;16:435–40.

    Article  Google Scholar 

  8. Chang L, Frame D, Braun T, Gatza E, Hanauer DA, Zhao S, et al. Engraftment syndrome after allogeneic hematopoietic cell transplantation predicts poor outcomes. Biol Blood Marrow Transplant. 2014;20:1407–17.

    Article  Google Scholar 

  9. Nishio N, Yagasaki H, Takahashi Y, Hama A, Muramatsu H, Tanaka M, et al. Engraftment syndrome following allogeneic hematopoietic stem cell transplantation in children. Pediatr Transplant. 2009;13:831–7.

    Article  Google Scholar 

  10. Gorak E, Geller N, Srinivasan R, Espinoza-Delgado I, Donohue T, Barrett AJ, et al. Engraftment syndrome after nonmyeloablative allogeneic hematopoietic stem cell transplantation: incidence and effects on survival. Biol Blood Marrow Transplant. 2005;11:542–50.

    Article  Google Scholar 

  11. Omer AK, Kim HT, Yalamarti B, McAfee SL, Dey BR, Ballen KK, et al. Engraftment syndrome after allogeneic hematopoietic cell transplantation in adults. Am J Hematol. 2014;89:698–705.

    Article  Google Scholar 

  12. Poonsombudlert K, Kewcharoen J, Prueksapraopong C, Limpruttidham N. Engraftment syndrome and acute graft-versus-host disease: a meta-analysis. Hawaii J Health Soc Welf. 2020;79:194–201.

    Google Scholar 

  13. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700. https://doi.org/10.1136/bmj.b270010.

    Article  Google Scholar 

  14. Hong KT, Kang HJ, Kim NH, Kim MS, Lee JW, Kim H, et al. Peri-engraftment syndrome in allogeneic hematopoietic SCT. Bone Marrow Transplant. 2013;48:523–8.

    Article  Google Scholar 

  15. Murad MH, Sultan S, Haffar S, Bazerbachi F. Methodological quality and synthesis of case series and case reports. BMJ Evid Based Med. 2018;23:60–63.

    Article  Google Scholar 

  16. Wells G, Shea B, O’Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analysis. Available from www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 2 July 2021.

  17. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al. Cochrane handbook for systematic reviews of interventions. Version 6.1 (updated September 2020). Cochrane; 2020.

  18. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.

    Article  Google Scholar 

  19. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.

    Article  Google Scholar 

  20. Yanagisawa R, Katsuyama Y, Shigemura T, Saito S, Tanaka M, Nakazawa Y, et al. Engraftment syndrome, but not acute GVHD, younger age, CYP3A5 or MDR1 polymorphisms, increases tacrolimus clearance in pediatric hematopoietic SCT. Bone Marrow Transplant. 2011;46:90–97.

    Article  Google Scholar 

  21. Wang X, Liu H, Li L, Geng L, Ding K, Liu X, et al. Pre-engraftment syndrome after unrelated donor umbilical cord blood transplantation in patients with hematologic malignancies. Eur J Haematol. 2012;88:39–45.

    Article  Google Scholar 

  22. Kanda J, Kaynar L, Kanda Y, Prasad VK, Parikh SH, Lan L, et al. Pre-engraftment syndrome after myeloablative dual umbilical cord blood transplantation: risk factors and response to treatment. Bone Marrow Transplant. 2013;48:926–31.

    Article  Google Scholar 

  23. Park M, Lee SH, Lee YH, Yoo KH, Sung KW, Koo HH, et al. Pre-engraftment syndrome after unrelated cord blood transplantation: a predictor of engraftment and acute graft-versus-host disease. Biol Blood Marrow Transplant. 2013;19:640–6.

    Article  Google Scholar 

  24. Brownback KR, Simpson SQ, McGuirk JP, Tara L, Lin TL, Abhyankar S, et al. Pulmonary manifestations of the pre-engraftment syndrome after umbilical cord blood transplantation. Ann Hematol. 2014;93:847–54.

    Article  Google Scholar 

  25. Chen Y, Huang XJ, Liu KY, Chen H, Chen YH, Zhang XH, et al. Infusion-related febrile reaction after haploidentical stem cell transplantation in children is associated with higher rates of engraftment syndrome and acute graft-versus-host disease. Pediatr Transplant. 2015;19:918–24.

    Article  Google Scholar 

  26. Chen Y, Xu LP, Liu KY, Chen H, Chen YH, Zhang XH, et al. High incidence of engraftment syndrome after haploidentical allogeneic stem cell transplantation. Eur J Haematol. 2015;96:517–26.

    Article  Google Scholar 

  27. İleri T, Ünal İnce E, Çakmaklı H, Uysal Z, Gençtürk Z, Ertem M. Evaluation of engraftment syndrome in children following full-matched related donor hematopoietic stem cell transplantations. Pediatr Transplant. 2016;20:581–9.

    Article  Google Scholar 

  28. Iguchi A, Terashita Y, Sugiyama M, Ohshima J, Sato TZ, Cho Y, et al. Graft-versus-host disease (GVHD) prophylaxis by using methotrexate decreases pre-engraftment syndrome and severe acute GVHD, and accelerates engraftment after cord blood transplantation. Pediatr Transplant. 2016;20:114–9.

    Article  Google Scholar 

  29. Khandelwal P, Mellor-Heineke S, Rehman N, Lane A, Smiley K, Villanueva J, et al. Cytokine profile of engraftment syndrome in pediatric hematopoietic stem cell transplant recipients. Biol Blood Marrow Transplant. 2016;22:690–7.

    Article  Google Scholar 

  30. Konuma T, Kohara C, Watanabe E, Mizukami M, Nagai E, Oiwa-Monna M, et al. Cytokine profiles of pre-engraftment syndrome after single-unit cord blood transplantation for adult patients. Biol Blood Marrow Transplant. 2017;23:1932–8.

    Article  Google Scholar 

  31. Mirgh S, Khattry N. Acute complications in stem cell transplantation. In: Chandy M, Radhakrishnan VS, Sukumaran R, editors. Contemporary bone marrow transplantation. Organ and tissue transplantation. Cham: Springer; 2020. p. 1–35. https://doi.org/10.1007/978-3-319-64938-2_6-1.

  32. Pagliuca S, Michonneau D, Sicre de Fontbrune F, Sutra Del Galy A, Xhaard A, Robin M, et al. Allogeneic reactivity-mediated endothelial cell complications after HSCT: a plea for consensual definitions. Blood Adv. 2019;3:2424–35.

    Article  Google Scholar 

  33. Grant A, Chapman LRM, Mitchell R, O’Brien TA. Engraftment syndrome following hematopoietic stem cell transplant: a review of the literature. Clin Transplant. 2020;34:e13875. https://doi.org/10.1111/ctr.13875.

    Article  Google Scholar 

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Authors and Affiliations

  1. King Khalid University Hospital, Riyadh, Saudi Arabia

    Ghada ElGohary

  2. Faculty of Medicine, Ain Shams University, Cairo, Egypt

    Ghada ElGohary

  3. Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA

    Amir A. Toor

  4. Department of Medical Oncology, Division of Hematological Malignancies, Thomas Jefferson University Hospital, Philadelphia, PA, USA

    Usama Gergis

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  1. Ghada ElGohary
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  2. Amir A. Toor
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  3. Usama Gergis
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GE: editing the manuscript and collecting the data. AAT: reviewing the manuscript. UG: the idea creator and reviewing the manuscript.

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Correspondence to Ghada ElGohary.

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ElGohary, G., Toor, A.A. & Gergis, U. Engraftment syndrome after allogeneic stem cell transplantation: a systematic review and meta-analysis. Bone Marrow Transplant 58, 1–9 (2023). https://doi.org/10.1038/s41409-022-01849-6

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