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Prepublished online as a Blood First Edition Paper on May 17, 2002; DOI 10.1182/blood-2001-11-0059.
Submitted November 28, 2001
Accepted April 3, 2002
Chronic graft-versus-host disease in children: incidence, risk factors and impact on outcome
Marco Zecca*, Arcangelo Prete, Roberto Rondelli, Edoardo Lanino, Adriana Balduzzi, Chiara Messina, Franca Fagioli, Fulvio Porta, Claudio Favre, Andrea Pession, and Franco Locatelli
IRCCS Policlinico San Matteo, Universita di Pavia, Oncoematologia Pediatrica, Pavia, Italy
Universita di Bologna, Policlinico Sant'Orsola, Clinica Pediatrica, Bologna, Italy
Ospedale G. Gaslini, Oncoematologia Pediatrica, Genova, Italy
Universita di Milano Bicocca, Ospedale San Gerardo, Clinica Pediatrica, Monza, Italy
Dipartimento di Pediatria, Universita di Padova, Oncoematologia Pediatrica, Padova, Italy
Ospedale Regina Margherita, Universita di Torino, Clinica Pediatrica, Torino, Italy
Spedale Civili, Universita di Brescia, Clinica Pediatrica, Brescia, Italy
Universita di Pisa, Clinica Pediatrica, Pisa, Italy
* Corresponding author; email: m.zecca{at}smatteo.pv.it.
Introduction. Chronic graft-versus-host disease (C-GVHD) remains the major cause of late morbidity and mortality after allogeneic stem cell transplantation (HSCT). However, no study specifically focused on children and few information is available on the anti-leukemic effect of C-GVHD and on its impact on disease-free survival (DFS) in children.
Patient characteristics. We retrospectively analyzed 696 children given allogeneic HSCT for malignant (450) or non malignant (246) diseases. The donor was an HLA-identical sibling in 461 cases, a partially matched relative in 68 and an unrelated volunteer in 167. Stem cell source was bone marrow in 647 cases, peripheral blood in 17 and cord blood (CB) in 32.
Results. 173 children (25%) developed C-GVHD at a median of 116 days after HSCT. 3-year probability of developing C-GVHD was 27%. C-GVHD was extensive in 64 cases and limited in 109. In multivariate analysis, variables predicting C-GVHD were: grade II-IV acute GVHD, female donor for male recipient, diagnosis of malignancy and use of total-body irradiation, while CB transplants were associated with a very low risk of C-GVHD (RR=0.01, P=0.0001). C-GVHD determined an increased transplant-related mortality (P<0.05). Nevertheless, in hematological malignancies, patients with C-GVHD had a reduced relapse probability as compared to children without C-GVHD (16±3% vs. 39±3%, P=0.0001), and a better DFS (68±4% vs. 54±3%, P=0.01). The anti-leukemic effect of C-GVHD, confirmed in multivariate analysis, was mainly observed in patients with acute lymphoblastic leukemia (ALL).
Conclusions. This study provides novel data on the risk of C-GVHD in childhood. Use of CB stem cells and preparative regimens without radiotherapy may prevent its development. In patients affected by ALL, C-GVHD was associated with a strong graft-versus-leukemia effect, improving DFS.
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