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  • 1
    Publication Date: 1989-02-15
    Description: Based on the recent reports that recombinant human granulocyte/macrophage colony-stimulating factor (rhGM-CSF) accelerates the rate of engraftment in a variety of autologous bone marrow transplantation settings, we have investigated its effects on hematopoietic recovery of patients with acute lymphoblastic leukemia (ALL) undergoing autologous bone marrow transplantation. Our studies, which involved 25 autologous ALL recipients who received rhGM-CSF and 27 controls similar for disease status (remission or relapse) and disease type (B- or T-lineage) differed from previous studies in one important aspect: the bone marrows were purged with 4- hydroperoxcyclophosphamide (4HC) and anti-T or anti-B-cell lineage- specific antibodies before transplantation. Such treatments frequently lead to a reduction in the CFU-GM content of the transplanted marrow. Eighteen of 25 patients completed the entire course of rhGM-CSF. Of the 16 patients who received greater than or equal to 64 micrograms/M2/d for at least eight days, there were five patients who had an apparent rhGM-CSF response and 11 patients who did not respond. Of the parameters analyzed, only the number of CFU-GM progenitor cells infused per kilogram was significantly associated with an rhGM-CSF response. All patients receiving greater than or equal to 1.2 x 10(4) CFU-GM progenitors per kilogram achieved an absolute neutrophil count (ANC) greater than or equal to 1,000/microL by day 21 and had a greater than 50% decrement in ANC within 48 to 72 hours of discontinuing rhGM-CSF, as contrasted to none of the patients receiving less than or equal to 7.2 x 10(3) CFU-GM progenitors per kilogram.(ABSTRACT TRUNCATED AT 250 WORDS)
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 2
    Publication Date: 1989-02-15
    Description: Based on the recent reports that recombinant human granulocyte/macrophage colony-stimulating factor (rhGM-CSF) accelerates the rate of engraftment in a variety of autologous bone marrow transplantation settings, we have investigated its effects on hematopoietic recovery of patients with acute lymphoblastic leukemia (ALL) undergoing autologous bone marrow transplantation. Our studies, which involved 25 autologous ALL recipients who received rhGM-CSF and 27 controls similar for disease status (remission or relapse) and disease type (B- or T-lineage) differed from previous studies in one important aspect: the bone marrows were purged with 4- hydroperoxcyclophosphamide (4HC) and anti-T or anti-B-cell lineage- specific antibodies before transplantation. Such treatments frequently lead to a reduction in the CFU-GM content of the transplanted marrow. Eighteen of 25 patients completed the entire course of rhGM-CSF. Of the 16 patients who received greater than or equal to 64 micrograms/M2/d for at least eight days, there were five patients who had an apparent rhGM-CSF response and 11 patients who did not respond. Of the parameters analyzed, only the number of CFU-GM progenitor cells infused per kilogram was significantly associated with an rhGM-CSF response. All patients receiving greater than or equal to 1.2 x 10(4) CFU-GM progenitors per kilogram achieved an absolute neutrophil count (ANC) greater than or equal to 1,000/microL by day 21 and had a greater than 50% decrement in ANC within 48 to 72 hours of discontinuing rhGM-CSF, as contrasted to none of the patients receiving less than or equal to 7.2 x 10(3) CFU-GM progenitors per kilogram.(ABSTRACT TRUNCATED AT 250 WORDS)
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 3
    Publication Date: 1986-06-01
    Description: A 12-year-old male with acute lymphocytic leukemia received donor bone marrow from his histocompatible father whose marrow was harvested 40 minutes postmortem after he suffered a myocardial infarction. The marrow was stored in liquid nitrogen for 17 days prior to infusion into the recipient. Trypan blue viability was greater than 99% for the fresh marrow. Progenitor cell assays revealed that 20% of the CFU-MIX, 16% of the BFU-E, 10% of the CFU-E, and 17% of the CFU-GM were spared during the cryopreservation period. Posttransplantation, the recipient had a leukocyte count greater than 10(3)/microL by day 26. Southern blotting analysis documented the donor origin of the peripheral blood mononuclear cells and granulocytes isolated 46 days posttransplantation. Unfortunately, the patient died of complications relating to graft-v-host disease 67 days following transplantation. This case demonstrates the feasibility of cadaveric marrow as a source of donor cells and is the first reported case of documented leukocyte engraftment in a recipient of cadaveric marrow.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 4
    Publication Date: 1982-04-01
    Description: Successful complete hematopoietic reconstitution (CHR) using nonleukemic peripheral stem cells (PSC) after marrow ablation has been reported in animals but not man. Previous studies of cytapheresis products from humans, as a prelude to use for CHR, have documented the presence of committed myeloid (CFU-GM) and erythroid (BFU-E) precursors. We have examined mononuclear cell (MNC) products collected on the Fenwal CS3000 Blood Cell Separator for these plus the more primitive mixed (granulo-, erythro-, mono-, and megakaryocytic) cell colony-forming units (CFU-GEMM) and for various lymphocytic subpopulations (LSP). One to two-hour products contained 36 +/- 7 CFU- GEMM/10(6) MNC (mean +/- SE, n = 8) or 490 +/- 131/ml product. This compared favorably with blood (23 +/- .4/10(6) MNC or 46 +/- 8/ml, n = 14) and bone marrow (146 +/- 58/10(6) MNC, n = 12). Collection efficiency for E-rosette-positive cells approximated that for total lymphocytes and was variable for other LSP. Recovery of CFU-GEMM after freezing in 10% dimethylsulfoxide at a controlled rate and storage in liquid N2 was 54% +/- 8% (n = 8). Cytapheresis collection of large numbers of pluripotent hematopoietic precursors and demonstration of adequate recovery of these after cryopreservation, both previously unreported, are significant steps toward eventual CHR using nonleukemic PSC.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 5
    Publication Date: 1990-11-01
    Description: Peripheral blood stem cells (PBSC) are being used as one alternative to autologous marrow rescue for patients with neuroblastoma and other solid malignancies. Some physicians prefer use of PBSC because less risk of tumor contamination is believed to exist. This hypothesis was evaluated by immunocytologic analysis of blood samples and concurrently drawn bone marrow (BM) samples and of PBSC harvests obtained from 31 patients with disseminated neuroblastoma. We found circulating neoplastic cells in 75% of specimens analyzed at diagnosis, in 36% during therapy, and in 14% of PBSC harvests. Tumor cells in blood obtained during therapy did not appear until 3 months after the time of diagnosis. Clearance of circulating neuroblastoma cells was documented after two courses of induction chemotherapy. Six of 13 patients with minimal or no BM disease had positive blood specimens. We conclude that substantial risk of tumor contamination of PB harvests exists and recommend that induction chemotherapy be administered before hematopoietic progenitor cells are collected from blood.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 6
    Publication Date: 1986-06-01
    Description: A 12-year-old male with acute lymphocytic leukemia received donor bone marrow from his histocompatible father whose marrow was harvested 40 minutes postmortem after he suffered a myocardial infarction. The marrow was stored in liquid nitrogen for 17 days prior to infusion into the recipient. Trypan blue viability was greater than 99% for the fresh marrow. Progenitor cell assays revealed that 20% of the CFU-MIX, 16% of the BFU-E, 10% of the CFU-E, and 17% of the CFU-GM were spared during the cryopreservation period. Posttransplantation, the recipient had a leukocyte count greater than 10(3)/microL by day 26. Southern blotting analysis documented the donor origin of the peripheral blood mononuclear cells and granulocytes isolated 46 days posttransplantation. Unfortunately, the patient died of complications relating to graft-v-host disease 67 days following transplantation. This case demonstrates the feasibility of cadaveric marrow as a source of donor cells and is the first reported case of documented leukocyte engraftment in a recipient of cadaveric marrow.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 7
    Publication Date: 1982-04-01
    Description: Successful complete hematopoietic reconstitution (CHR) using nonleukemic peripheral stem cells (PSC) after marrow ablation has been reported in animals but not man. Previous studies of cytapheresis products from humans, as a prelude to use for CHR, have documented the presence of committed myeloid (CFU-GM) and erythroid (BFU-E) precursors. We have examined mononuclear cell (MNC) products collected on the Fenwal CS3000 Blood Cell Separator for these plus the more primitive mixed (granulo-, erythro-, mono-, and megakaryocytic) cell colony-forming units (CFU-GEMM) and for various lymphocytic subpopulations (LSP). One to two-hour products contained 36 +/- 7 CFU- GEMM/10(6) MNC (mean +/- SE, n = 8) or 490 +/- 131/ml product. This compared favorably with blood (23 +/- .4/10(6) MNC or 46 +/- 8/ml, n = 14) and bone marrow (146 +/- 58/10(6) MNC, n = 12). Collection efficiency for E-rosette-positive cells approximated that for total lymphocytes and was variable for other LSP. Recovery of CFU-GEMM after freezing in 10% dimethylsulfoxide at a controlled rate and storage in liquid N2 was 54% +/- 8% (n = 8). Cytapheresis collection of large numbers of pluripotent hematopoietic precursors and demonstration of adequate recovery of these after cryopreservation, both previously unreported, are significant steps toward eventual CHR using nonleukemic PSC.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 8
    Publication Date: 1990-11-01
    Description: Peripheral blood stem cells (PBSC) are being used as one alternative to autologous marrow rescue for patients with neuroblastoma and other solid malignancies. Some physicians prefer use of PBSC because less risk of tumor contamination is believed to exist. This hypothesis was evaluated by immunocytologic analysis of blood samples and concurrently drawn bone marrow (BM) samples and of PBSC harvests obtained from 31 patients with disseminated neuroblastoma. We found circulating neoplastic cells in 75% of specimens analyzed at diagnosis, in 36% during therapy, and in 14% of PBSC harvests. Tumor cells in blood obtained during therapy did not appear until 3 months after the time of diagnosis. Clearance of circulating neuroblastoma cells was documented after two courses of induction chemotherapy. Six of 13 patients with minimal or no BM disease had positive blood specimens. We conclude that substantial risk of tumor contamination of PB harvests exists and recommend that induction chemotherapy be administered before hematopoietic progenitor cells are collected from blood.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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