Abstract
Myeloablative T cell depleted (CD34-selected) hematopoietic cell transplantation (HCT) is associated with less acute and chronic graft versus host disease (GVHD). We aimed to examine vaccine responses in relation to immune reconstitution and post HCT rituximab administration in this population. This single center retrospective study included 251 patients with hematological malignancies who received a first CD34-selected HCT between 2012 and 2015. Of 251 patients, 190 were alive 1 year after HCT. Among the entire population, 77 (30.7%) patients were vaccinated. After vaccine administration, 35/44 (80%), 30/75 (40%), 27/36 (75%), 33/65 (51%), 34/51 (51%), 22/28 (79%) and 20/34 (59%) of evaluable patients had protective antibody titers for haemophilus influenzae type B (Hib), Pneumococcus, Tetanus, Diphtheria, Pertussis, hepatitis A (HAV), and hepatitis B (HBV) respectively. Responders to the pneumococcal vaccine had a higher CD45RA T cell count than non responders, with 12/18 patients (66.7%) vs 11/32 (34.4%) p = 0.04. For pneumococcal vaccine, there was also a trend to higher total lymphocyte B cell count in responders vs non responders p = 0.06. Rituximab post HCT was given to 59/251 (23.5%) patients. No difference was found in immune reconstitution patterns for rituximab use between vaccine responders and not. Recipients of CD34-selected HCT may respond to vaccination, and T and B cell subsets could be useful to predict vaccine response.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Data availability
The dataset generated for the current study is not publicly available due to confidentiality reasons, but is available from the corresponding author on reasonable request.
References
Styczyński J, Tridello G, Koster L, Iacobelli S, van Biezen A, van der Werf S, et al. Death after hematopoietic stem cell transplantation: changes over calendar year time, infections and associated factors. Bone Marrow Transpl. 2020;55:126–36.
Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis Publ Infect Dis Soc Am. 2014;58:309–18.
Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J, et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transpl J Am Soc Blood Marrow Transpl. 2009;15:1143–238.
Bryant AR, Perales MA. Advances in Ex Vivo T Cell Depletion - Where Do We Stand? Adv Cell Gene Ther. 2019;2:e29.
Wagner JE, Donnenberg AD, Noga SJ, Cremo CA, Gao IK, Yin HJ, et al. Lymphocyte depletion of donor bone marrow by counterflow centrifugal elutriation: results of a phase I clinical trial. Blood. 1988;72:1168–76.
Sao H, Kitaori K, Kasai M, Shimokawa T, Kato C, Yamanishi H, et al. A new marrow T cell depletion method using anti-CD6 monoclonal antibody-conjugated magnetic beads and its clinical application for prevention of acute graft-vs.-host disease in allogeneic bone marrow transplantation: results of a phase I-II trial. Int J Hematol. 1999;69:27–35.
Dykes JH, Toporski J, Juliusson G, Békássy AN, Lenhoff S, Lindmark A, et al. Rapid and effective CD3 T-cell depletion with a magnetic cell sorting program to produce peripheral blood progenitor cell products for haploidentical transplantation in children and adults. Transfus. 2007;47:2134–42.
Goldberg JD, Linker A, Kuk D, Ratan R, Jurcic J, Barker JN, et al. T cell-depleted stem cell transplantation for adults with high-risk acute lymphoblastic leukemia: long-term survival for patients in first complete remission with a decreased risk of graft-versus-host disease. Biol Blood Marrow Transpl J Am Soc Blood Marrow Transpl. 2013;19:208–13.
Tamari R, Chung SS, Papadopoulos EB, Jakubowski AA, Hilden P, Devlin SM, et al. CD34-Selected Hematopoietic Stem Cell Transplants Conditioned with Myeloablative Regimens and Antithymocyte Globulin for Advanced Myelodysplastic Syndrome: Limited Graft-versus-Host Disease without Increased Relapse. Biol Blood Marrow Transpl J Am Soc Blood Marrow Transpl. 2015;21:2106–14.
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 Transpl. 2015;50:493–8.
Perales MA, Jenq R, Goldberg JD, Wilton AS, Lee SSE, Castro-Malaspina HR, et al. Second-line age-adjusted International Prognostic Index in patients with advanced non-Hodgkin lymphoma after T-cell depleted allogeneic hematopoietic SCT. Bone Marrow Transpl. 2010;45:1408–16.
Barba P, Martino R, Zhou Q, Cho C, Castro-Malaspina H, Devlin S, et al. CD34+ Cell Selection versus Reduced-Intensity Conditioning and Unmodified Grafts for Allogeneic Hematopoietic Cell Transplantation in Patients Age >50 Years with Acute Myelogenous Leukemia and Myelodysplastic Syndrome. Biol Blood Marrow Transpl J Am Soc Blood Marrow Transpl. 2018;24:64–72.
Pasquini MC, Devine S, Mendizabal A, Baden LR, Wingard JR, Lazarus HM, et al. Comparative outcomes of donor graft CD34+ selection and immune suppressive therapy as graft-versus-host disease prophylaxis for patients with acute myeloid leukemia in complete remission undergoing HLA-matched sibling allogeneic hematopoietic cell transplantation. J Clin Oncol J Am Soc Clin Oncol. 2012;30:3194–201.
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 Transpl J Am Soc Blood Marrow Transpl. 2013;19:898–903.
Tamari R, Oran B, Hilden P, Maloy M, Kongtim P, Papadopoulos EB, et al. Allogeneic Stem Cell Transplantation for Advanced Myelodysplastic Syndrome: Comparison of Outcomes between CD34+ Selected and Unmodified Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transpl J Am Soc Blood Marrow Transpl. 2018;24:1079–87.
Luznik L, Pasquini MC, Logan B, Soiffer RJ, Wu J, Devine SM, et al. Randomized Phase III BMT CTN Trial of Calcineurin Inhibitor-Free Chronic Graft-Versus-Host Disease Interventions in Myeloablative Hematopoietic Cell Transplantation for Hematologic Malignancies. J Clin Oncol J Am Soc Clin Oncol. 2022;40:356–68.
Nash RA, Dansey R, Storek J, Georges GE, Bowen JD, Holmberg LA, et al. Epstein-Barr virus-associated posttransplantation lymphoproliferative disorder after high-dose immunosuppressive therapy and autologous CD34-selected hematopoietic stem cell transplantation for severe autoimmune diseases. Biol Blood Marrow Transpl J Am Soc Blood Marrow Transpl. 2003;9:583–91.
Lee YJ, Huang YT, Kim SJ, Maloy M, Tamari R, Giralt SA, et al. Adenovirus Viremia in Adult CD34(+) Selected Hematopoietic Cell Transplant Recipients: Low Incidence and High Clinical Impact. Biol Blood Marrow Transpl J Am Soc Blood Marrow Transpl. 2016;22:174–8.
Huang YT, Kim SJ, Lee YJ, Burack D, Nichols P, Maloy M, et al. Co-Infections by Double-Stranded DNA Viruses after Ex Vivo T Cell-Depleted, CD34+ Selected Hematopoietic Cell Transplantation. Biol Blood Marrow Transpl J Am Soc Blood Marrow Transpl. 2017;23:1759–66.
Huang YT, Neofytos D, Foldi J, Kim SJ, Maloy M, Chung D, et al. Cytomegalovirus Infection after CD34(+)-Selected Hematopoietic Cell Transplantation. Biol Blood Marrow Transpl J Am Soc Blood Marrow Transpl. 2016;22:1480–6.
Goldberg JD, Zheng J, Ratan R, Small TN, Lai KC, Boulad F, et al. Early recovery of T-cell function predicts improved survival after T-cell depleted allogeneic transplant. Leuk Lymphoma. 2017 Aug;58:1859–71.
Palazzo M, Shah GL, Copelan O, Seier K, Devlin SM, Maloy M, et al. Revaccination after Autologous Hematopoietic Stem Cell Transplantation Is Safe and Effective in Patients with Multiple Myeloma Receiving Lenalidomide Maintenance. Biol Blood Marrow Transpl J Am Soc Blood Marrow Transpl. 2018;24:871–6.
Styczynski J, Tridello G, Koster L, Knelange N, Wendel L, van Biezen A, et al. Decrease of lethal infectious complications in the context of causes of death (COD) after hematopoietic cell transplantation: COD-2 and COD-1 study of the Infectious Diseases Working Party EBMT. Bone Marrow Transpl. 2023;58:881–92.
Gouveia-Alves F, Gouveia R, Ginani VC, Seber A, Kuramoto DA, Murad GFA, et al. Adherence and immune response to revaccination following hematopoietic stem cell transplantation at a pediatric onco-hematology reference center. Transpl Infect Dis J Transpl Soc. 2018;20:e12903.
Conrad A, Perry M, Langlois ME, Labussière-Wallet H, Barraco F, Ducastelle-Leprêtre S, et al. Efficacy and Safety of Revaccination against Tetanus, Diphtheria, Haemophilus influenzae Type b and Hepatitis B Virus in a Prospective Cohort of Adult Recipients of Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transpl J Am Soc Blood Marrow Transpl. 2020;26:1729–37.
Sattler C, Hoffmann P, Herzberg PY, Weber D, Holler B, Fehn U, et al. Primary vaccination in adult patients after allogeneic hematopoietic stem cell transplantation - A single center retrospective efficacy analysis. Vaccine. 2021;39:4742–50.
Small TN, Avigan D, Dupont B, Smith K, Black P, Heller G, et al. Immune reconstitution following T-cell depleted bone marrow transplantation: effect of age and posttransplant graft rejection prophylaxis. Biol Blood Marrow Transpl J Am Soc Blood Marrow Transpl. 1997;3:65–75.
Small TN, Papadopoulos EB, Boulad F, Black P, Castro-Malaspina H, Childs BH, et al. Comparison of immune reconstitution after unrelated and related T-cell-depleted bone marrow transplantation: effect of patient age and donor leukocyte infusions. Blood. 1999;93:467–80.
Lewin SR, Heller G, Zhang L, Rodrigues E, Skulsky E, van den Brink MRM, et al. Direct evidence for new T-cell generation by patients after either T-cell-depleted or unmodified allogeneic hematopoietic stem cell transplantations. Blood. 2002;100:2235–42.
Cordonnier C, Ljungman P, Juergens C, Maertens J, Selleslag D, Sundaraiyer V, et al. Immunogenicity, safety, and tolerability of 13-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine in recipients of allogeneic hematopoietic stem cell transplant aged ≥2 years: an open-label study. Clin Infect Dis Publ Infect Dis Soc Am. 2015;61:313–23.
Mond JJ, Lees A, Snapper CM. T cell-independent antigens type 2. Annu Rev Immunol. 1995;13:655–92.
Black S, Shinefield H, Fireman B, Lewis E, Ray P, Hansen JR, et al. Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Northern California Kaiser Permanente Vaccine Study Center Group. Pediatr Infect Dis J. 2000;19:187–95.
Gurion R, Rozovski U, Itchaki G, Gafter-Gvili A, Leibovitch C, Raanani P, et al. Humoral serological response to the BNT162b2 vaccine is abrogated in lymphoma patients within the first 12 months following treatment with anti-CD2O antibodies. Haematologica. 2022;107:715–20.
Haggenburg S, Hofsink Q, Lissenberg-Witte BI, Broers AEC, van Doesum JA, van Binnendijk RS, et al. Antibody Response in Immunocompromised Patients With Hematologic Cancers Who Received a 3-Dose mRNA-1273 Vaccination Schedule for COVID-19. JAMA Oncol. 2022;8:1477–83.
Tvito A, Ronson A, Ghosheh R, Kharit M, Ashkenazi J, Magen S, et al. Anti-CD20 monoclonal antibodies inhibit seropositive response to Covid-19 vaccination in non-Hodgkin lymphoma patients within 6 months after treatment. Exp Hematol. 2022;107:20–3.
Acknowledgements
We are grateful to the patients who participated in the study for their consideration in providing the blood specimens.
Funding
Financial Support This research was supported in part by National Institutes of Health award number P01 CA23766 and National Institutes of Health/National Cancer Institute Cancer Center Support grant P30 CA008748. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Author information
Authors and Affiliations
Contributions
Miguel A Perales, Gunjan L Shah, Giovanna Melica, and Elaina Preston conceived the study, performed the interpretation of the data, made critical revisions for intellectual content, and provided final approval of the version to be published. Kenneth Seier and Sean M Devlin performed the statistical analysis and interpretation of the data. All authors contributed to the study design and critical revisions for intellectual content. All authors contributed to the revision of the manuscript and approved the final version.
Corresponding author
Ethics declarations
Competing interests
MAP: honoraria from Adicet, Allogene, Allovir, Caribou Biosciences, Celgene, Bristol-Myers Squibb, Equilium, Exevir, ImmPACT Bio, Incyte, Karyopharm, Kite/Gilead, Merck, Miltenyi Biotec, MorphoSys, Nektar Therapeutics, Novartis, Omeros, OrcaBio, Syncopation, VectivBio AG, and Vor Biopharma. He serves on DSMBs for Cidara Therapeutics, Medigene, and Sellas Life Sciences, and the scientific advisory board of NexImmune. He has ownership interests in NexImmune, Omeros and OrcaBio. He has received institutional research support for clinical trials from Allogene, Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis. GM: honoraria and institutional research support from Gilead, Janssen and MSD. GLS: Research funding from Janssen, Amgen, Beyond Spring, GPCR, and BMS. DSMB for ArcellX. No financial disclosure were reported by any other authors.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Melica, G., Preston, E., Palazzo, M. et al. Immune reconstitution, vaccine responses, and rituximab use after ex-vivo CD34-selected myeloablative allogenic hematopoietic cell transplantation. Bone Marrow Transplant 59, 625–629 (2024). https://doi.org/10.1038/s41409-024-02232-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41409-024-02232-3