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Thiotepa cyclophosphamide followed by granulocyte colony-stimulating factor mobilized allogeneic peripheral blood cells in adults with advanced leukemia.
- Source :
-
Blood [Blood] 1996 Jul 01; Vol. 88 (1), pp. 353-7. - Publication Year :
- 1996
-
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.
- Subjects :
- Actuarial Analysis
Adult
Aged
Bone Marrow Diseases chemically induced
Bone Marrow Transplantation
CD4 Lymphocyte Count
Cause of Death
Combined Modality Therapy
Cyclophosphamide administration & dosage
Cyclophosphamide pharmacology
Feasibility Studies
Female
Follow-Up Studies
Graft Survival
Graft vs Host Disease etiology
Graft vs Host Disease mortality
Granulocyte Colony-Stimulating Factor adverse effects
Humans
Infections etiology
Infections mortality
Leukapheresis adverse effects
Leukemia blood
Leukemia mortality
Leukemia therapy
Lymphoma blood
Lymphoma drug therapy
Lymphoma therapy
Male
Middle Aged
Multiple Myeloma blood
Multiple Myeloma drug therapy
Multiple Myeloma therapy
Multiple Organ Failure etiology
Multiple Organ Failure mortality
Myelodysplastic Syndromes blood
Myelodysplastic Syndromes drug therapy
Myelodysplastic Syndromes therapy
Pilot Projects
Primary Myelofibrosis blood
Primary Myelofibrosis drug therapy
Primary Myelofibrosis therapy
Salvage Therapy
Survival Analysis
Survival Rate
Thiotepa administration & dosage
Tissue Donors
Transplantation, Homologous
Treatment Outcome
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Bone Marrow drug effects
Bone Marrow Diseases prevention & control
Granulocyte Colony-Stimulating Factor pharmacology
Hematopoietic Stem Cell Transplantation adverse effects
Hematopoietic Stem Cell Transplantation mortality
Hematopoietic Stem Cells drug effects
Leukemia drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 88
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 8704195