Early reconstitution of lymphocytes after allogenic hematopoietic stem cell transplantation affects chronic graft-versus-host disease.
LD-index
allogeneic-HSCT
chronic GVHD
lymphopenia
Journal
Pediatrics international : official journal of the Japan Pediatric Society
ISSN: 1442-200X
Titre abrégé: Pediatr Int
Pays: Australia
ID NLM: 100886002
Informations de publication
Date de publication:
Jan 2022
Jan 2022
Historique:
revised:
05
04
2022
received:
29
11
2021
accepted:
15
04
2022
pubmed:
6
7
2022
medline:
6
1
2023
entrez:
5
7
2022
Statut:
ppublish
Résumé
Lymphocyte reconstitution after hematopoietic stem cell transplantation (HSCT) is important for the prevention of infections, as well as for the reduction of recurrence, by its graft versus tumor effect. However, these lymphocytes may also play a role in the development of graft-versus-host disease (GVHD). Few studies have investigated the association between lymphocyte reconstitution and clinical outcomes after HSCT. This issue was investigated by retrospectively analyzing pediatric patients who received their first allogeneic-HSCT using a newly developed parameter, the LD-index, which evaluates both the intensity and duration of lymphopenia. A total of 101 patients underwent allo-HSCT from April 2007 to August 2019 in our hospital. Excluding patients who died before lymphocyte recovery or underwent multiple HSCT, 78 patients were analyzed for associations between the LD-index with various factors relating to HSCT. A significantly high association was observed between a low LD-index and the incidence of chronic GVHD (P = 0.0019). Analysis of predictive factors for chronic GVHD was carried out using univariate analysis. Lower LD-index, donor source and duration of lymphopenia were found to be significant factors associated with chronic GVHD. Multivariate analysis, however, only identified an association between a lower LD-index and an increased incidence of chronic GVHD (P = 0.00081). Early reconstitution of lymphocytes after allo-HSCT is associated with a higher incidence of chronic GVHD.
Sections du résumé
BACKGROUND
BACKGROUND
Lymphocyte reconstitution after hematopoietic stem cell transplantation (HSCT) is important for the prevention of infections, as well as for the reduction of recurrence, by its graft versus tumor effect. However, these lymphocytes may also play a role in the development of graft-versus-host disease (GVHD). Few studies have investigated the association between lymphocyte reconstitution and clinical outcomes after HSCT.
METHODS
METHODS
This issue was investigated by retrospectively analyzing pediatric patients who received their first allogeneic-HSCT using a newly developed parameter, the LD-index, which evaluates both the intensity and duration of lymphopenia. A total of 101 patients underwent allo-HSCT from April 2007 to August 2019 in our hospital. Excluding patients who died before lymphocyte recovery or underwent multiple HSCT, 78 patients were analyzed for associations between the LD-index with various factors relating to HSCT.
RESULTS
RESULTS
A significantly high association was observed between a low LD-index and the incidence of chronic GVHD (P = 0.0019). Analysis of predictive factors for chronic GVHD was carried out using univariate analysis. Lower LD-index, donor source and duration of lymphopenia were found to be significant factors associated with chronic GVHD. Multivariate analysis, however, only identified an association between a lower LD-index and an increased incidence of chronic GVHD (P = 0.00081).
CONCLUSIONS
CONCLUSIONS
Early reconstitution of lymphocytes after allo-HSCT is associated with a higher incidence of chronic GVHD.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e15222Informations de copyright
© 2022 Japan Pediatric Society.
Références
Savani BN, Mielke S, Rezvani K et al. Absolute lymphocyte count on day 30 is a surrogate for robust hematopoietic recovery and strongly predicts outcome after T cell-depleted allogeneic stem cell transplantation. Biol. Blood Marrow Transplant. 2007; 13: 1216-23.
Le Blanc K, Barrett AJ, Schaffer M et al. Lymphocyte recovery is a major determinant of outcome after matched unrelated myeloablative transplantation for myelogenous malignancies. Biol. Blood Marrow Transplant. 2009; 15: 1108-15.
Auletta JJ, Lazarus HM. Immune restoration following hematopoietic stem cell transplantation: an evolving target. Bone Marrow Transplant. 2005; 35: 835-57.
Michelis FV, Messner HA, Loach J et al. Early lymphocyte recovery at 28 d post-transplant is predictive of reduced risk of relapse in patients with acute myeloid leukemia transplanted with peripheral blood stem cell grafts. Eur. J. Haematol. 2014; 93: 273-80.
Niederwieser D, Gastl G, Rumpold H, Marth CH, Kraft D, Huber H. Rapid reappearance of large granular lymphocytes with concomitant reconstitution of natural killer activity after human bone marrow transplantation. Br. J. Haematol. 1987; 65: 301-5.
Jiang YZ, Barrett AJ, Goldman JM, Mavroudis DA. Association of natural killer cell immune recovery with a graft-versus-leukemia effect independent of graft-versus-host-disease following allogeneic bone marrow transplantation. Ann. Hematol. 1997; 74: 1-6.
Powels R, Singhal S, Treleaven J, Kulkarni S, Horton C, Mehta J. Identification of patients who may benefit from prophylactic immunotherapy after bone marrow transplantation for acute myeloid leukemia on the basis of lymphocyte recovery early after transplantation. Blood 1998; 91: 3481-6.
Kumar S, Chen MG, Gastineau DA et al. Effect of slow lymphocyte recovery and type of graft-versus-host disease prophylaxis on relapse after allogeneic bone marrow transplantation for acute myeloid leukemia. Bone Marrow Transplant. 2001; 28: 951-6.
Ishaqi MK, Afzal S, Dupuis A, Doyle J, Gassas A. Early lymphocyte recovery post-allogeneic hematopoietic stem cell transplantation is associated with significant graft-versus-leukemia effect without increase in graft-versus-host disease in pediatric acute lymphoblastic leukemia. Bone Marrow Transplant. 2008; 41: 245-52.
Kim DH, Sohn SK, Won DI, Lee NY, Suh JS, Lee KB. Rapid helper T-cell recovery above 200×106/l at 3 months correlates to successful transplant outcomes after allogeneic stem cell transplantation. Bone Marrow Transplant. 2006; 37: 1119-28.
Kim DH, Kim JG, Sohn SK et al. Clinical impact of early absolute lymphocyte count after allogeneic stem cell transplantation. Br. J. Haematol. 2004; 125: 217-24.
Einsele H, Ehninger G, Steidle M et al. Lymphocytopenia as an unfavorable prognostic factor in patients with cytomegalovirus infection after bone marrow transplantation. Blood 1993; 82: 1672-8.
Bacigalupo A, Ballen K, Rizzo D et al. Defining the intensity of conditioning regimens: working definitions. Biol. Blood Marrow Transplant. 2009; 15: 1628-33.
Pauw BD, Walsh TJ, Donnelly JP et al. Revised definitions of invasive fungal disease from the European organization for research and treatment of cancer / invasive fungal infections cooperative group and the national institute of allergy and infectious diseases mycoses study group (EORTC/MSG) Consensus Group. Clin. Infect. Dis. 2008; 46: 1813-21.
Harris AC, Young R, Devine S et al. International, multicenter standardization of acute graft-versus-host disease clinical data collection: a report from the Mount Sinai Acute GVHD International Consortium. Biol. Blood Marrow Transplant. 2016; 22: 4-10.
Jagasia MH, Greinix HT, Arora M et al. National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: Ⅰ. The 2014 diagnosis and staging working group report. Biol. Blood Marrow Transplant. 2015; 21: 389-401.
Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013; 48: 452-8.
Portugal RD, Garnica M, Nucci M. Index to predict invasive mold infection in high-risk neutropenic patients based on the area over the neutrophil curve. J. Clin. Oncol. 2009; 27: 3849-54.
Sano H, Kobayashi R, Suzuki D, Hori D, Kishimoto K, Kobayashi K. Impact of the D-index deduced from the duration and intensity of neutropenia following chemotherapy on the risk of invasive fungal infection in pediatric acute myeloid leukemia. Int. J. Hematol. 2018; 108: 85-90.
Afzal S, Ishaqi MK, Dupuis A, Doyle J, Gassas A. Early lymphocyte recovery after allogeneic hematopoietic SCT is associated with significant GVL effect in pediatric ALL but not acute myelogenous leukemia - Update study. Bone Marrow Transplant. 2009; 44: 799-804.
Kimura S, Wada K, Sakamoto M et al. L-index as a novel index to evaluate both the intensity and duration of lymphopenia after allogeneic hematopoietic stem cell transplantation. Transpl. Infect. Dis. 2012; 14: 364-73.
Kimura S, Sato M, Misaki Y et al. Prospective validation of the L-index reflecting both the intensity and duration of lymphopenia and its detailed evaluation using a lymphocyte subset analysis after allogeneic hematopoietic stem cell transplantation. Transpl. Immunol. 2020; 58: 101262.
Shearer WT, Rosenblatt HM, Gelman RS et al. Lymphocyte subsets in healthy children from birth through 18 years of age: the pediatric AIDS clinical trials group P1009 study. J. Allergy Clin. Immunol. 2003; 112: 973-80.
Filipovich AH, Weisdorf D, Pavletic S et al. National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol. Blood Marrow Transplant. 2005; 11: 945-56.
Lee SJ. Have we made progress in the management of chronic graft-vs-host disease? Best Pract. Res. Clin. Haematol. 2010; 23: 529-35.
Cooke KR, Luznik L, Sarantopoulos S et al. The biology of chronic graft-versus-host disease: a task force report from the national institutes of health consensus development project on criteria for clinical trials in chronic graft-versus host disease. Biol. Blood Marrow Transplant. 2017; 23: 211-34.
Schultz KR, Kariminia A, Ng B et al. Immune profile differences between chronic GVHD and late acute GVHD: results of the ABLE/PBMTC 1202 studies. Blood 2020; 135: 1287-98.
Flowers ME, Inamoto Y, Carpenter PA et al. Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria. Blood 2011; 117: 3214-9.
Ozawa S, Nakaseko C, Nishimura M et al. Chronic graft-versus-host disease after allogeneic bone marrow transplantation from an unrelated donor: incidence, risk factors and association with relapse. A report from the Japan Marrow Donor Program. Br. J. Haematol. 2007; 137: 142-51.
Anasetti C, Logan BR, Lee SJ et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. N. Engl. J. Med. 2012; 367: 1487-96.
Bejanyan N, Brunstein CG, Cao Q et al. Delayed immune reconstitution after allogeneic transplantation increases the risks of mortality and chronic GVHD. Blood Adv. 2018; 2 (8): 909-22.
Renard C, Barlogis V, Mialou V et al. Lymphocyte subset reconstitution after unrelated cord blood or bone marrow transplantation in children. Br. J. Haematol. 2011; 152 (3): 322-30.