ABSTRACT
The clinical results, cellular immune reconstitution, and hematopoietic chimerism obtained after transplantation of recombinant human granulocyte colony-stimulating factor mobilized allogeneic peripheral blood stem cells (PBSCs) from genotypically human leukocyte antigen (HLA)-identical sibling (n = 36) or alternative family donors (n = 24) were prospectively compared in patients with hematologic malignancies. Thirty-two of 34 evaluable patients with HLA-identical sibling donors and all patients with alternative family donors achieved trilineage engraftment. The median time intervals to reach peripheral neutrophil counts <500/microL (13 v 17 days) or <1,000/microL (16 v 19 days) and unsupported platelet counts <20,000/microL (11 v 15 days) or <50, 000/microL (19 v 24 days) as well as red blood cell and platelet transfusion requirements were not significantly different between both patient subsets. The cumulative probability of grades II through IV acute graft-versus-host disease (GVHD) for the 60 study patients was 48% +/- 10% but ranged between 86% +/- 12% in patients whose donors had at least one HLA-A,B,DR,DQ,DP antigen disparity in direction to acute GVHD, and 25% +/- 9% in recipients of GVHD-matched transplants (P < .003). The 2-year survival estimates were 54% +/- 10% for patients with alternative family donors and 65% +/- 9% for patients with HLA-identical sibling donors. Multivariate analysis identified the pretransplantation disease stage, patient age, and acute GVHD as independent predictors of overall and disease-free survival, whereas alternative family donors alone had no adverse effect on these clinical endpoints. Monthly monitoring of peripheral blood T-helper cell subsets, B cells, and monocytes during the first year posttransplantation showed a nearly identical course of immune cell reconstitution in both patient subsets. In addition, no differences in the proportions of complete chimeric patients were detectable between the two patient subsets by sex chromosome and variable number of tandem repeats analysis up to 12 months posttransplantation. In conclusion, PBSCs from alternative family donors represent an attractive source for allogeneic transplantation in patients lacking HLA-identical sibling donors and should be further evaluated in comparison with marrow transplants from alternative family donors.
Subject(s)
Granulocyte Colony-Stimulating Factor/pharmacology , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Mobilization , Hematopoietic Stem Cell Transplantation , Transplantation, Homologous , Adolescent , Adult , Aged , Child , Child, Preschool , Chimera , Female , Filgrastim , Graft vs Host Disease/etiology , Hematologic Neoplasms/immunology , Hematologic Neoplasms/mortality , Histocompatibility Testing , Humans , Male , Middle Aged , Polymerase Chain Reaction , Prospective Studies , Recombinant Proteins , Survival RateSubject(s)
Pneumatosis Cystoides Intestinalis/diagnostic imaging , Pneumoperitoneum/etiology , Tomography, X-Ray Computed , Adult , Combined Modality Therapy , Diagnosis, Differential , Fatal Outcome , Female , Graft vs Host Disease/complications , Graft vs Host Disease/diagnostic imaging , Graft vs Host Disease/therapy , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/complications , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnostic imaging , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Leukemia, Myeloid, Chronic-Phase/complications , Leukemia, Myeloid, Chronic-Phase/diagnostic imaging , Leukemia, Myeloid, Chronic-Phase/therapy , Pneumoperitoneum/diagnostic imagingABSTRACT
Clinical studies are evaluating possible advantages of allogeneic peripheral blood stem cell transplantation (PBSCT) over bone marrow transplantation (BMT). We compared immune reconstitution after PBSCT (n = 20) and BMT (n = 20) in terms of lymphocyte subset counts and proliferative in vitro responses to mitogens and recall antigens (follow-up: 5 to 11 months posttransplant). Additionally, 10 PBSC harvests and 10 marrow harvests were analyzed for their composition of immunocompetent cells. Compared with BMT patients, PBSCT recipients had PB counts of naive (CD4+CD45RA+) and memory (CD4+CD45RO+) helper T cells and of B cells (CD19+) that were elevated (P < .003, P < .001, and P < .004, respectively) and proliferative responses to phytohemagglutinin (P < .0001), pokeweed mitogen (P < .02), Tetanus toxoid (P < .0005), and Candida (P < .004) that were increased. PBSCT recipients received a mean of 188 (range, 44 to 280) x 10(6) naive helper T cells and 169 (range, 18 to 296) x 10(5) memory helper T cells per kilogram; the corresponding numbers for BMT recipients were 11 (range, 4 to 24) and 10 (range, 1 to 22) x 10(5) cells per kilogram, respectively. The question of whether the documented improved in vitro immune competence after PBSCT is associated with a lower incidence of infectious complications in vivo still needs further study.
Subject(s)
Bone Marrow Transplantation , Hematopoietic Stem Cell Transplantation , Lymphocyte Count , Lymphocyte Subsets , Adult , Anemia, Aplastic/therapy , Candida/immunology , Female , Graft Survival , Hematologic Neoplasms/therapy , Humans , Immunocompetence , Immunologic Memory , Immunophenotyping , Lymphocyte Activation , Male , Middle Aged , Mitogens/pharmacology , Prospective Studies , Simplexvirus/immunology , Tetanus Toxoid/immunology , Time FactorsABSTRACT
The determination of oral turinabol (4-chloro-17 alpha-methyl-17 beta-hydroxy-1,4-androstadien-3-one) [1] in the 'free' fraction of human urine samples by gas chromatography and capillary column gas chromatography/mass spectrometry was studied. After administration to man, three major metabolites are formed whose structures were identified as 6 beta-hydroxy-turinabol [2], 6 beta, 12-dihydroxy-turinabol [4], and 6 beta, 16-dihydroxy-turinabol [5], respectively. In much smaller quantities at least another three metabolites are excreted, one of which could be identified as 17 epi-turinabol [6]. No measurable amounts of 1 itself were detected in any of the urine samples investigated. The rate of metabolism and urinary excretion is reasonably fast. The total amount of recovered material, in the form of the three main metabolites, is on the order of 15%. Clean-up procedures and chromatographic conditions are presented in detail.
Subject(s)
Testosterone/analogs & derivatives , Adult , Chemical Phenomena , Chemistry , Chromatography, Gas/methods , Gas Chromatography-Mass Spectrometry , Humans , Male , Middle Aged , Testosterone/urineABSTRACT
The determination of methandienone (I) (17 alpha-methyl-17 beta-hydroxyandrosta-1,4-dien-3-one) in human urine by gas chromatography and capillary column gas chromatography--mass spectrometry has been studied. After oral administration to man two major metabolites were detected, the structures of which have been identified as 17-epi-methandienone (II) and 6 beta-hydroxy-17-epi-methandienone (III). These metabolites are exclusively excreted in the unconjugated form. At least two more metabolites are extractable from the free fraction of the urine but no measurable amounts of I itself were found. The rate of metabolism and urinary excretion seems to be reasonably fast. The total amount of recovered I in the form of the metabolites II and III is about 5%. Extraction and clean-up procedures and chromatographic details are presented.
