to diepoxibutane (Deb-test). Patients were hospitalized for
the administration of rabbit ATG and discharged when clinically
stable, usually after approximately three weeks. The
local medical ethics committee approved this study, and
data were obtained from written and computerized material
records.
Treatment regimen
An initial intravenous test dose was performed on all
patients to assess for allergic hypersensitivity. Rabbit
ATG (Timoglobulina®, Genzyme, Cambridge, MA, USA) was
administered at a dose of 5 mg/kg/d i.v for five consecutive
days. Serum sickness prophylaxis was with methylprednisolone
at 2 mg/kg/d was given prior to the first dose of
ATG, and was continued for ten days and then tapered over
the subsequent seven days. Cyclosporine was initiated on
day 6 at 10 mg/kg/d p.o in divided doses q12 h. CsA was
administered for at least six months, adjusted to blood levels
(therapeutic range between 150 and 250 ng/mL).
Supportive care
Granulocyte colony stimulating factor (G-CSF) was administered
at a dose of 5 g/kg subcutaneously from day +1 to day
+30 to maintain neutrophils >0.5 x 109/Lto avoid infections.
Itraconazole was used as prophylaxis for fungal infection
at a dose of 100 mg/d for at least one month after rabbit
ATG. Other prophylactic antibiotics were not routinely
administered.
Red blood cells were transfused in patients with symptomatic
anemia or to maintain a hemoglobin level higher
than 9 g/dL. Platelets were transfused prophylactically in
all patients with a platelet count lower than 10 x 109/L.
Platelets were transfused at a higher threshold (20 x 109/L)
in the presence of fever and/or clinical bleeding.
Definitions
Compete response (CR) was defined as transfusion independence
associated with hemoglobin (Hb) > 110 g/L, neutrophil
count > 1.5 x 109/L, and platelet count > 100 x 109/L. Partial
response (PR) was defined as transfusion independence, but
not meeting the blood count criteria for CR. All remissions
had to be confirmed by two blood counts at least four weeks
apart. Response was evaluated at 180 days from treatment.
Relapse was indicated by the requirement of red blood cell
and/or platelet transfusion after transfusion independence
lasting three or more months.
Clonal evolution was defined as the appearance of a new
clonal disorder on cytogenetics or characteristic morphologic
changes on bone marrow examination.
Statistical analysis
Summary statistics, including means, proportions, and their
corresponding standard deviations were used to describe
patients’ age, gender, and other baseline characteristics.
Sample proportions and their 95% confidence intervals (CIs)
were used to describe the six-month response rates for
patients categorized by discrete risk factors. Long-term