Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
-
Biol. Blood Marrow Transplant. · Jan 1999
Comparative StudyA retrospective comparison of allogeneic peripheral blood stem cell and bone marrow transplantation results from a single center: a focus on the incidence of graft-vs.-host disease and relapse.
To detect the effect of the stem cell source, allogeneic peripheral blood stem cell transplantations (alloPBSCTs) performed between 1995 and 1997 from human leukocyte antigen (HLA)-identical siblings in 40 patients with acute and chronic hematological disorders were compared with a historical group of 40 patients with similar variables who had received allogeneic bone marrow transplants (alloBMTs) between 1993 and 1995. Patients in both groups were identical except that both the recipient and the donor ages were, on average, higher in the alloPBSCT group (26 vs. 36 [p = 0.005] and 27 vs. 32 [p = 0.024], respectively). Patients received similar therapy excluding posttransplant granulocyte colony-stimulating factor administration (97% in alloBMT vs. 12.5% in alloPBSCT). ⋯ Although not statistically significant, a relatively higher relapse rate occurred in the alloBMT group (21.4 vs. 10.7%). The estimated disease-free survival in month 24 was 51.3% for alloBMT and 54.6% for alloPBSCT, and the estimated overall survival in month 24 was 56.1% for alloBMT and 64.6% for alloPBSCT. In conclusion, this retrospective comparison suggests that alloPBSCT from HLA-identical donors is associated with faster engraftment, fewer transfusions, and no greater incidence of aGVHD, but a high incidence of cGVHD.
-
Biol. Blood Marrow Transplant. · Jan 1999
Dose rate-dependent marrow toxicity of TBI in dogs and marrow sparing effect at high dose rate by dose fractionation.
We evaluated the marrow toxicity of 200 and 300 cGy total-body irradiation (TBI) delivered at 10 and 60 cGy/min, respectively, in dogs not rescued by marrow transplant. Additionally, we compared toxicities after 300 cGy fractionated TBI (100 cGy fractions) to that after single-dose TBI at 10 and 60 cGy/min. Marrow toxicities were assessed on the basis of peripheral blood cell count changes and mortality from radiation-induced pancytopenia. ⋯ Seventeen dogs were given 300 cGy TBI at 60 cGy/min, administered either as single doses (n=5) or three fractions of 100 cGy each (n=10). Within the limitations of the experimental design, three conclusions were drawn: 1) with 200 and 300 cGy single-dose TBI, an increase of dose rate from 10 to 60 cGy/min, respectively, caused significant increases in marrow toxicity; 2) at 60 cGy/min, dose fractionation resulted in a significant decrease in marrow toxicities, whereas such a protective effect was not seen at 10 cGy/min; and 3) with fractionated TBI, no significant differences in marrow toxicity were seen between dogs irradiated at 60 and 10 cGy/min. The reduced effectiveness of TBI when a dose of 300 cGy was divided into three fractions of 100 cGy or when dose rate was reduced from 60 cGy/min to 10 cGy/min was consistent with models of radiation toxicity that allow for repair of sublethal injury in DNA.
-
Biol. Blood Marrow Transplant. · Jan 1999
Manganese [correction of Magnesium] superoxide dismutase (MnSOD) plasmid/liposome pulmonary radioprotective gene therapy: modulation of irradiation-induced mRNA for IL-I, TNF-alpha, and TGF-beta correlates with delay of organizing alveolitis/fibrosis.
Radiation pneumonitis remains a critical dose-limiting toxicity of total body irradiation (TBI) for use in bone marrow transplantation. The acute and chronic phases of radiation damage in the mouse lung have been shown to correlate with mouse strain genotype and are dependent on fraction size, total dose, and total lung volume. Our prior studies demonstrated effective prevention of irradiation-induced lung damage and improved survival in C57BL/6J mice by MnSOD plasmid/liposome gene therapy. ⋯ Then, in striking contrast to the other two cytokines, an increase in TGF-beta2 mRNA occurred at around 120 days and correlated with the detection of organizing alveolitis/radiation fibrosis and mortality. These results are consistent with a two-phase mechanism in the molecular pathology of irradiation lung injury, in which IL-1 cytokine mRNA levels correlated with the acute pneumonitis phase and delayed elevation of TNF-alpha (80-100 days), TGF-beta1 (100 days), and TGF-beta2 (120 days) were associated with the fibrosis phase. Insight into the cell-specific and tissue-specific molecular mechanisms of ionizing irradiation induction of mRNA for pulmonary cytokines may provide new strategies for treatment of radiation pneumonitis in TBI patients.
-
Biol. Blood Marrow Transplant. · Dec 1997
Clinical TrialFractionated total-body irradiation, etoposide, and cyclophosphamide followed by allogeneic bone marrow transplantation for patients with high-risk or advanced-stage hematological malignancies.
Myeloablative therapy followed by allogeneic bone marrow transplantation (BMT) has proven to be curative therapy in patients with hematologic malignancies. Relapse, however, remains a major cause of treatment failure for patients with advanced disease. During the past 15 years, we have gained considerable experience with the combination of fractionated total-body irradiation (FTBI) and etoposide followed by allogeneic BMT for hematologic malignancies. ⋯ Regimen related mortality occurred in 9 patients (4, veno-occlusive disease of the liver; 2, multi-organ failure; 1, diffuse alveolar hemorrhage; 1, central nervous system (CNS) hemorrhage; 1, adult respiratory distress syndrome (ARDS). The combination of FTBI, etoposide, and cyclophosphamide followed by allogeneic BMT is an effective and relatively well-tolerated regimen for patients with advanced hematologic malignancies. The role for this regimen should be further defined by prospective clinical trials.
-
Biol. Blood Marrow Transplant. · Dec 1997
Clinical TrialDecrease in tumor cell contamination and progenitor cell yield in leukapheresis products after consecutive cycles of chemotherapy for breast cancer treatment.
In this retrospective study, we assessed the impact of each of three consecutive cycles of conventional-dose chemotherapy on CD34+ cells, colony-forming units granulocyte-macrophage (CFU-GM), and contaminating breast cancer cells collected in the leukapheresis products of patients with metastatic breast cancer. The patients subsequently underwent high-dose chemotherapy followed by autologous blood progenitor cell transplantation. We analyzed 172 leukapheresis products from 17 patients and have correlated the long-term clinical outcome with tumor cell contamination. ⋯ The likelihood of contamination by breast cancer cells after cycle I was significantly higher than after subsequent cycles of chemotherapy (p = 0.0052). Simultaneously, there was a significant decrease in quantity of CD34+ cells and CFU-GM (p < 0.0001 for both comparisons). Our study indicated that leukapheresis products collected after the second or third cycles of induction chemotherapy carry a significantly lower likelihood of tumor cell contamination, albeit the quantity of CD34+ cells or CFU-GM collected was also significantly reduced.