title: Thiotepa cyclophosphamide followed by granulocyte colony-stimulating factor mobilized allogeneic peripheral blood cells in adults with advanced leukemia.
abstract: 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.
authors.affiliation: Divisione Ematologia 2, Ospedale San Martino, Genova, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bacigalupo
authors.forename: M T
authors.initials: MT
authors.lastname: Van Lint
authors.forename: M
authors.initials: M
authors.lastname: Valbonesi
authors.forename: G
authors.initials: G
authors.lastname: Lercari
authors.forename: P
authors.initials: P
authors.lastname: Carlier
authors.forename: T
authors.initials: T
authors.lastname: Lamparelli
authors.forename: F
authors.initials: F
authors.lastname: Gualandi
authors.forename: D
authors.initials: D
authors.lastname: Occhini
authors.forename: S
authors.initials: S
authors.lastname: Bregante
authors.forename: A
authors.initials: A
authors.lastname: Valeriani
authors.forename: G
authors.initials: G
authors.lastname: Piaggio
authors.forename: A
authors.initials: A
authors.lastname: Pitto
authors.forename: F
authors.initials: F
authors.lastname: Benvenuto
authors.forename: O
authors.initials: O
authors.lastname: Figari
authors.forename: G
authors.initials: G
authors.lastname: De Stefano
authors.forename: A
authors.initials: A
authors.lastname: Caimo
authors.forename: M
authors.initials: M
authors.lastname: Sessarego
mesh_terms: D000206:Actuarial Analysis; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects*; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000517:prevention & control*; D016026:Bone Marrow Transplantation; D018791:CD4 Lymphocyte Count; D002423:Cause of Death; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000494:pharmacology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007239:Infections / Q000209:etiology / Q000401:mortality; D007937:Leukapheresis / Q000009:adverse effects; D007938:Leukemia / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D008223:Lymphoma / Q000097:blood / Q000188:drug therapy / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy / Q000628:therapy; D009102:Multiple Organ Failure / Q000209:etiology / Q000401:mortality; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000188:drug therapy / Q000628:therapy; D010865:Pilot Projects; D055728:Primary Myelofibrosis / Q000097:blood / Q000188:drug therapy / Q000628:therapy; D016879:Salvage Therapy; D016019:Survival Analysis; D015996:Survival Rate; D013852:Thiotepa / Q000008:administration & dosage; D014019:Tissue Donors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide; D013852:Thiotepa