Thirty-one patients (median age, 44 years) with advanced
hematologic malignancies were given
thiotepa 15 mg/kg, and
cyclophosphamide 120 (n = 14) or 150 (n = 17) mg/kg followed by unfractionated peripheral blood stem cell transplants (PBSCT) from genotypically identical siblings (n = 28) or one
antigen mismatched family donor (n = 3). Donors were mobilized with
granulocyte colony-stimulating factor 5 to 10 microgram/kg/d for 6 days and underwent two to three leukapheresis on days +5, +6, +7. The median cell yield per donor expressed/kg of recipients
body weight was as follows: nucleated cells 13 x 10(8)/kg; CD34+ cells 6 x 10(6)/kg; colony-forming unit-granulocyte macrophage 38 x 10(4)/kg, and CD3+ cells 449 x 10(6)/kg. The diagnoses were
chronic myeloid leukemia (n = 4), acute myeloid (n = 9) or
lymphoid leukemia (n = 2), acute
myelofibrosis (n = 2),
multiple myeloma (n = 1),
lymphoma (n = 6),
chronic lymphocytic leukemia (n = 1) myelodysplasia (n = 6). Twenty-eight patients had advanced disease, 29 patients were first grafts, and 2 were second transplants 3 and 9 years after the first. Neutrophil counts of 0.5 x 10(9)/L and platelet counts of 30 x 10(9)/L platelets were both achieved on day +14 (median). Engraftment could be proven by sex markers or
DNA polymorphism in 29 of 31 patients: one had early
leukemia relapse and one patient was unevaluable because of early death. Acute
graft-versus-host disease (GVHD) was scored as minimal or absent (grade 0 to 1) in 14 patients, moderate (grade II) in 13, and severe (grade III to IV) in four. Causes of death were
leukemia (n = 4), acute GVHD (n = 4, with associated
cytomegalovirus infections in three),
sepsis (n = 1),
liver failure (n = 1), multiorgan failure (n = 1), and
hemorrhage (n = 1). The actuarial transplant mortality is 29%, the actuarial relapse rate 22%. Nineteen patients survive with a median follow up of 288 days (100-690). The actuarial 2-year survival is 57%. Three patients received PBSCT from family donors mismatched for one
class II antigen: all engrafted, one developed grade I aGVHD; one died of
leukemia on day +155; two are alive disease free 267 to 290 days postgraft. This study suggests that
thiotepa cyclophosphamide followed by unfractionated PBSC allograft may be an alternative form of transplant for adults with advanced
leukemia, also in the setting of one
antigen mismatched donor. The engraftment is rapid with acceptable GVHD and relatively low transplant-related mortality.