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Prepublished online as a Blood First Edition Paper on May 17, 2002; DOI 10.1182/blood-2001-11-0059.
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Blood, 15 August 2002, Vol. 100, No. 4, pp. 1192-1200
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
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 on behalf of the AIEOP-BMT
Group
From Oncoematologia Pediatrica, Università di
Pavia, IRCCS Policlinico San Matteo, Pavia, Italy; Clinica Pediatrica,
Università di Bologna, Policlinico Sant'Orsola, Bologna, Italy;
Oncoematologia Pediatrica, Ospedale G. Gaslini, Genova, Italy; Clinica
Pediatrica, Università di Milano Bicocca, Ospedale San Gerardo,
Monza, Italy; Oncoematologia Pediatrica, Dipartimento di Pediatria,
Università di Padova, Padova, Italy; Clinica Pediatrica, Ospedale
Regina Margherita, Università di Torino, Torino, Italy; Clinica
Pediatrica, Spedali Civili, Università di Brescia, Brescia,
Italy; Clinica Pediatrica, Università di Pisa, Pisa, Italy.
Chronic graft-versus-host disease (cGVHD) remains the
major cause of late morbidity and mortality after allogeneic
hematopoietic stem cell transplantation (HSCT). However, only a few
studies specifically focused on children, and little information is
available on the antileukemic effect of cGVHD and its impact on
disease-free survival (DFS) in children. We retrospectively analyzed
696 children given allogeneic HSCT for malignant (n = 450) or
nonmalignant (n = 246) diseases. The donor was an HLA-identical
sibling in 461 cases and an alternative donor in 235. Bone marrow was
the stem cell source in 647 cases, peripheral blood in 17, and cord blood (CB) in 32. cGVHD developed in 173 children (25%) at a median of
116 days after HSCT. Three-year cGVHD probability was 27%. In
multivariate analysis, variables predicting cGVHD were donor and
recipient age, grade II to IV acute GVHD, female donor for male
recipient, diagnosis of malignancy, and use of total body irradiation;
CB transplants had a very low risk of cGVHD (RR = 0.07,
P = .0001). cGVHD occurrence increased transplant-related mortality (P < .05). Nevertheless, in hematologic
malignancies, patients with cGVHD had a reduced relapse probability
compared with children without cGVHD (16% ± 3% versus
39% ± 3%, P = .0001) and a better DFS (68% ± 4%
versus 54% ± 3%, P = .01). The antileukemic effect
of cGVHD was observed mainly in patients with acute lymphoblastic leukemia (ALL). This study provides novel data on cGVHD in childhood. Use of CB stem cells and preparative regimens without radiotherapy may
prevent its development. In patients affected by ALL, cGVHD was
associated with a strong graft-versus-leukemia effect, improving DFS.
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