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Blood, 1 January 2002, Vol. 99, No. 1, pp. 75-82
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Reduced-intensity conditioning followed by allografting of
hematopoietic cells can produce clinical and molecular remissions in
patients with poor-risk hematologic malignancies
Paolo Corradini,
Corrado Tarella,
Attilio Olivieri,
Alessandro M. Gianni,
Claudia Voena,
Francesco Zallio,
Marco Ladetto,
Michele Falda,
Moira Lucesole,
Anna Dodero,
Fabio Ciceri,
Fabio Benedetti,
Alessandro Rambaldi,
Maria R. Sajeva,
Moreno Tresoldi,
Alessandro Pileri,
Claudio Bordignon, and
Marco Bregni
From the Department of Hematology, Istituto Scientifico
HS Raffaele, Milano; Department of Hematology, University of Torino;
Division of Hematology, University of Ancona; Medical Oncology/BMT
Unit, Istituto Nazionale Tumori, University of Milano; Department of
Hematology, University of Verona; Department of Hematology, Ospedali
Riuniti, Bergamo; Department of Hematology, S Camillo Hospital, Rome,
Italy.
A reduced-intensity conditioning regimen was investigated in 45 patients with hematologic malignancies who were considered poor
candidates for conventional myeloablative regimens. Median patient age
was 49 years. Twenty-six patients previously failed autologous
transplantation, and 18 patients had a refractory disease at the time
of transplantation. In order to decrease nonrelapse mortality, and
enhance the graft-versus-tumor effect, a program was designed in which
a reduced conditioning with thiotepa, fludarabine, and cyclophosphamide
was associated with programmed reinfusions of donor lymphocytes for
patients without graft-versus-host disease (GVHD), not achieving
clinical and molecular remission after transplantation. GVHD
prophylaxis consisted of cyclosporine A and methotrexate. Seventeen
patients received marrow cells and 28 received mobilized hematopoietic
cells. All patients engrafted. The probability of grades II-IV and
III-IV acute GVHD were 47% and 13%, respectively. The probability of
nonrelapse mortality, progression-free survival, and overall survival
were 13%, 57%, and 53%, respectively. Thirteen patients in complete
remission had a polymerase chain reaction marker for minimal disease
monitoring; 10 achieved molecular remission after transplantation. Nine
patients received donor lymphocytes: one patient with mantle cell
lymphoma had a minimal response, one patient with refractory anemia
with excess of blasts in transformation achieved complete remission,
and 7 patients did not respond. At a median follow-up of 385 days
(range, 24 to 820 days), 25 patients (55%) were alive in complete
remission. Although longer follow-up is needed to evaluate the
long-term outcome, the study shows that this regimen is associated with
a durable engraftment, has a low nonrelapse mortality rate, and can
induce clinical and molecular remissions.
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