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  • 1
    Online Resource
    Online Resource
    The Use of Reduced Intensity Allogeneic Stem Cell Transplantation (alloSCT) for Recurrence after Autologous Stem Cell Transplantation (ASCT) in Hodgkin’s Disease (HD).
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 5115-5115
    Details
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 5115-5115
    Abstract: Autologous stem cell transplantation(ASCT) can cure up to 50% of patients with relapsed or refractory HD. However, for patients who relapse post ASCT or develop post transplant myelodsyplasia (t-MDS), standard chemotherapy options offer little chance of long-term disease free survival (DFS). The use of allogeneic stem cell (alloSCT) may provide a means of control of the HD through the immune mediated effects of an allogeneic approach and also be curative for concomitant t-MDS. While traditional alloSCT in HD patients was fraught with high treatment related mortality, a reduced intensity conditioning regimen may reduce upfront mortality while still providing long term DFS. Between 11/00 and 1/04, fourteen patients underwent reduced intensity alloSCT at the City of Hope Cancer Center. Median age at alloSCT was 31years (range18–47). Median time from HD diagnosis to alloSCT was 36mos (range 3–123). Eleven patients had relapsed post ASCT and one post syngeneic transplant. One of the pts also had t- MDS. The median time from ASCT to alloSCT was 20 mos(range1–45). Ten pts received sibling alloSCT and four unrelated donor. The conditioning regimen consisted of Fludarabine 125mg/m2+ Melphalan 140mg/m2. All patients received a Cyclosporin(CSA) based graft versus host disease (GVHD) prophylaxis regimen; nine in conjunction with Mycophenolate Mofetil and three in conjunction with Methotrexate. Seven developed acute GVHD (3-GrIII-IV). Two patients died of GVHD. There was no other significant regimen related toxicity. Median length of followup for surviving patients is 55 mos. For eleven evaluable pts, one year OS and DFS are 77% (95%CI 49–100) and 58% (95%CI 25–91) respectively (figure 1). The pt with concomitant t-MDS also achieved a hematologic remission. In conclusion, reduced intensity alloSCT may provide a salvage for heavily pretreated patients with HD that have failed ASCT and who otherwise have a poor prognosis, and it can also provide a treatment for late secondary complications of transplantation such as t-MDS.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V104.11.5115.5115
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    Online Resource
    Online Resource
    Evaluating the Clinical Efficacy of Increased Granulocyte Colony-Stimulation Factor (GCSF) in Patients Who Fail a Standard Dose Regimen during Peripheral Blood Stem Cell Collection.
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 2926-2926
    Details
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 2926-2926
    Abstract: Granulocyte Colony-Stimulating Factor (GCSF) at 10 microg/kg (with or without chemotherapy) is the standard dose commonly administered to patients undergoing Peripheral Blood Stem Cell (PBSC) mobilization and collection. Due to various host and disease factors, 10–20% of our patients failed to mobilize sufficient PBSC at this standard dose. At our institution it is common practice to increase GCSF from 10 microg/kg to 16–20 microg/kg during the initial or second mobilization attempt if the patient is able to tolerate the increased dose. To assess the clinical efficacy of increased GCSF administration among patients who fail to mobilize at the standard dose, we performed a retrospective chart review of 112 patients who underwent stem cell mobilization and collection between 01/31/2000 and 11/6/2003. The median age at the start of collection was 51.2 (range: 1.3–72.2); the case-series was made up of 52 men and 60 women. The majority of the cases were Lymphoma patients (Non-Hodgkin’s Lymphoma=52; Hodgkins Disease=15) with the remaining patients classified as Acute Myeloid Leukemia (AML=12), Multiple Myeloma (MM=13), or ‘Other’ (N=20). Initially all 112 patients received 4–10 days of GCSF at 10 microg/kg per day before the first day of PBSC collection. Because these patients failed to collect sufficient daily CD34 cells, the GCSF dose was increased to 16–20 microg/kg. Before increasing the GCSF dose, the median CD34 daily yield was 0.19 (range: 0.03–0.90), and the median peripheral WBC was 27.6 (range: 1.3–61.8). The median number of collection at 10 microg/kg was 4 (range 2–15), and the median number of days from the end of collection at 10 microg/kg to the start of 16–20 microg/kg was 1 (range: 0–53). After increasing the GCSF dose the median peripheral WBC was 37.1 (range: 3.1–70.2), and the median CD34 daily yield was 0.28 (range: 0.03–3.43). The median CD34 total yield was 3.1 (range 0.6–12.3). Ultimately 90 patients (80%) reached a CD34 cell target of 2*10–6/kg (range: 2.0–12.3), and 22 patients (20%) did not reach this target. The overall difference in CD34 counts pre-post increased GCSF administration was statistically significant (Wilcoxon p 〈 0.01). The difference in CD34 counts (pre-post increase GCSF dose) was explained by age only; the patient’s diagnosis and gender had no statistically significant explanatory value. Patients less than 40 years of age were more likely to have successful PBSC collection with an increase dose of GCSF (p=0.02). The mean difference in daily CD34 yield for patients 〈 40 years was 0.38; for patients ≥40 years was 0.11. Based on this analysis we recommend to increase GCSF dose to 16microg to 20 microgram/kg among the younger ( 〈 40 years) patients who failed a standard dose regimen at 10microg/kg, while other re-mobilization regimens should be considered for older patients irrespective of their gender or underlying diagnosis.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V104.11.2926.2926
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    Online Resource
    Online Resource
    Concentration-dependent dual effect of thrombin on impaired growth/apoptosis or mitogenesis in tumor cells
    American Society of Hematology ; 2000
    In:  Blood Vol. 95, No. 10 ( 2000-05-15), p. 3133-3138
    Details
    In: Blood, American Society of Hematology, Vol. 95, No. 10 ( 2000-05-15), p. 3133-3138
    Abstract: Because thrombin-treated tumor cell-induced metastasis increases tumor nodule volume12 greater than nodule number, we studied the effect of thrombin on tumor cell growth in vitro and in vivo (murine B16F10 melanoma, human HCT8 colon carcinoma, DU145 prostate carcinoma). Tumor cell growth was measured after 3 to 7 days in 1% fetal calf serum (FCS) + RPMI 1640. We found that, whereas relatively low concentrations of thrombin, 0.1 to 0.5 U/mL (1-5 nmol/L) enhance tumor cell growth in vitro approximately 2- to 3-fold, higher concentrations, 0.5 to 1 U/mL (5-10 nmol/L) impaired cell growth approximately 2- to 4-fold. Impaired cell growth was associated with cell cycle arrest at G2M and increased pre-GoDNA, as well as apoptosis, measured by tumor cell binding to Annexin V and propidium iodide. Apoptosis was reversed with the general caspase inhibitor, FK-011. The enhancing and inhibiting effects were specific for thrombin (reversed with inactive diisopropyl-fluorophosphate [DFP] -thrombin) and mediated via the protease-activated receptor 1 (PAR-1). PAR-1 activation was demonstrated by (1) use of a cell line, B16F10, devoid of the 3 other thrombin receptors, PAR-3, PAR-4, and GPIb; and (2) greater sensitivity of PAR-1 transfected B16F10 and HCT8 cells to impaired cell growth/apoptosis, 3- and 14-fold, respectively. Thus, thrombin has a bimodal effect on PAR-1 in tumor cells: enhanced growth at low concentration, impaired growth/apoptosis at higher concentration.
    Type of Medium: Online Resource
    ISSN: 1528-0020 , 0006-4971
    URL: Article
    DOI: 10.1182/blood.V95.10.3133.010k31_3133_3138
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2000
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
    Online Resource
    Online Resource
    Dose Intensity and Risk of Relapse for NHL after Allogeneic Transplant.
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 2311-2311
    Details
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 2311-2311
    Abstract: Reduced intensity regimens (RIR) have largely replaced conventional myeloablative regimens (CMR) for patients with NHL undergoing allogeneic transplant. However, the impact of dose reduction on relapse has not been extensively studied. We performed a retrospective analysis of 88 patients conditioned with CMR (n=48) and a RIR (n=40) of fludarabine 125mg/m2 and melphalan 140mg/m2. GVHD prophylaxis was with cyclosporine + MTX +/− prednisone for CMR and cyclosporine + MMF +/− MTX for the RIR. CMR RIR P Value N 48 40 Low grade B-cell 18 16 NS Intermediate grade B-cell 16 12 NS Mantle cell 10 5 NS T cell 4 7 NS Age (years, median, range) 44 (18–54) 51 (20–67) 0.0002 No of prior regimens (median) 3 2 0.02 Previous autologous transplant 5 16 0.002 Chemosensitivity at transplant 24 31 0.007 FTBI regimen 41 0 〈 0.0001 MUD 8 17 0.009 PBSC 16 36 0.0001 Median follow-up (months,range) 65 (33-95) 20 (6-42) CMR were significantly associated with a lower rate of relapse (RR) of 15% versus 38% after RIR (p=0.017). The 1-year TRM was 38% for CMR and 24% for RIR (p=NS). Kaplan-Meier 2-year OS/PFS for CMR is 52%/48% versus 57%/48% for RIR (p=NS). When analyzed by diagnosis, CMR were significantly associated with decreased RR (10% vs 60%, p=0.004) for intermediate grade B-cell (figure 1). Univariate analysis of patient and treatment-related prognostic factors showed improved survival with chemosensitive disease; treatment intensity was the single predictor of relapse for the entire group, but, when stratified by diagnosis, for intermediate grade B-cell only. In conclusion, CMR provide better disease control for intermediate grade B-cell NHL. Figure Figure
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V104.11.2311.2311
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
    Online Resource
    Online Resource
    Autologous vs Allogeneic Cell Transplantation for Mantle Cell Lymphoma (MCL): Outcomes over a 10-Year Period at City of Hope.
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 894-894
    Details
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 894-894
    Abstract: Mantle cell lymphoma (MCL) carries a poor prognosis with standard therapy. Both allogeneic (ALLO) and autologous stem cell transplant (ASCT) approaches have been used to intensify therapy in an attempt to achieve lasting remissions. 77 patients were transplanted at City of Hope over a 10-year period (1994–2003), including 13 ALLO and 64 ASCT. Demographics: The majority of patients were male (92% ALLO, and 73% ASCT). Median age was significantly younger for the ALLO, 47 years vs. 55 years for ASCT (p=0.003). ALLO patients had received more prior regimens than ASCTs-- avg 3 in ALLO and 1 in ASCT (p-value 0.0031). Median time from diagnosis to transplantation was 1.3 years for ALLO, 0.81 for ASCT. For ALLO patients, 8% were in first complete remission (CR1), 62% in second or subsequent remission, 23% in relapse, and 8% in unknown status. For ASCT patients, 47% were in CR1, 31% in second or subsequent remission, 14% in relapse, 2% in unknown status. Methods: Conditioning regimens for ASCT include FTBI/VP16/CTX (36), BCNU/VP16/CY (14), BEAM (2), Zevalin/BEAM (4), and other (8). One patient received an ASCT transplant, then received a reduced intensity ALLO transplant at the time of second relapse. Conditioning for ALLO included FTBI/CTX (9), Flu/Mel (3), or BU/CY (1), Results: Median follow-up was 57 months for ALLO, and 26 months for ASCT. 3-year Overall Survival (OS), progression free survival (PFS), and relapse rate was 51%, 53%, and 14% , respectively, for ALLO, and 66%, 57%, and 27% for ASCT. Patients transplanted in 1st CR had a significantly higher 3-year OS (85% vs. 52%, p = 0.0153) and PFS (78% vs. 44%, p = 0.027) a trend to a lower RR than patients transplanted in more advanced disease status. Conclusions: MCL patients transplanted in CR1 fared better than those transplanted with more advanced disease status, regardless of transplant approach. While relapse rates were lower in ALLO patients, this did not translate into improvement in OS or PFS, possibly due to a higher transplant related mortality (TRM). Analysis of PFS curves suggests no plateau on the ASCT curve, while late relapses were uncommon in ALLO patients.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V104.11.894.894
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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  • 6
    Online Resource
    Online Resource
    Concentration-dependent dual effect of thrombin on impaired growth/apoptosis or mitogenesis in tumor cells
    American Society of Hematology ; 2000
    In:  Blood Vol. 95, No. 10 ( 2000-05-15), p. 3133-3138
    Details
    In: Blood, American Society of Hematology, Vol. 95, No. 10 ( 2000-05-15), p. 3133-3138
    Abstract: Because thrombin-treated tumor cell-induced metastasis increases tumor nodule volume12 greater than nodule number, we studied the effect of thrombin on tumor cell growth in vitro and in vivo (murine B16F10 melanoma, human HCT8 colon carcinoma, DU145 prostate carcinoma). Tumor cell growth was measured after 3 to 7 days in 1% fetal calf serum (FCS) + RPMI 1640. We found that, whereas relatively low concentrations of thrombin, 0.1 to 0.5 U/mL (1-5 nmol/L) enhance tumor cell growth in vitro approximately 2- to 3-fold, higher concentrations, 0.5 to 1 U/mL (5-10 nmol/L) impaired cell growth approximately 2- to 4-fold. Impaired cell growth was associated with cell cycle arrest at G2M and increased pre-GoDNA, as well as apoptosis, measured by tumor cell binding to Annexin V and propidium iodide. Apoptosis was reversed with the general caspase inhibitor, FK-011. The enhancing and inhibiting effects were specific for thrombin (reversed with inactive diisopropyl-fluorophosphate [DFP]-thrombin) and mediated via the protease-activated receptor 1 (PAR-1). PAR-1 activation was demonstrated by (1) use of a cell line, B16F10, devoid of the 3 other thrombin receptors, PAR-3, PAR-4, and GPIb; and (2) greater sensitivity of PAR-1 transfected B16F10 and HCT8 cells to impaired cell growth/apoptosis, 3- and 14-fold, respectively. Thus, thrombin has a bimodal effect on PAR-1 in tumor cells: enhanced growth at low concentration, impaired growth/apoptosis at higher concentration.
    Type of Medium: Online Resource
    ISSN: 1528-0020 , 0006-4971
    URL: Article
    DOI: 10.1182/blood.V95.10.3133
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2000
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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