scholarly journals Acute hypertensive crisis during infusion of hematopoietic progenitor cell from matched unrelated donors: Identification of predictive factors and optimal treatment

2006 ◽  
Vol 12 (2) ◽  
pp. 156
Author(s):  
R.K. Blackburn ◽  
S.A. Giralt ◽  
R.M. Saliba ◽  
G. Rondon ◽  
J.N. Fenwick
Keyword(s):  
Predictive Factors ◽  
Progenitor Cell ◽  
Hypertensive Crisis ◽  
Optimal Treatment ◽  
Hematopoietic Progenitor Cell ◽  
Hematopoietic Progenitor ◽  
Unrelated Donors

Intravenous Compared to Oral Busulfan with Cyclophophamide for Allogeneic Hematopoietic Progenitor Cell Transplant Conditioning for AML and MDS.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3475-3475
Author(s):  
Ronald Sobecks ◽  
Lisa Rybicki ◽  
Matt Kalaycio ◽  
Robert Dean ◽  
Steven Andresen ◽  
...  
Keyword(s):  
Progenitor Cell ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hematopoietic Progenitor Cell ◽  
Sinusoidal Obstruction Syndrome ◽  
Cell Transplant ◽  
Hematopoietic Progenitor ◽  
Cell Dose ◽  
Unrelated Donors

Abstract Abstract 3475 Busulfan (Bu) is commonly used with cyclophosphamide (Cy) as a conditioning regimen for allogeneic hematopoietic progenitor cell transplantation (HPCT). Recently, intravenous (IV) Bu has often replaced oral Bu for conditioning. We have previously reported that substituting IV for oral Bu was associated with a lower rate of relapse, and superior relapse-free and overall survivals for relapsed or refractory non-Hodgkin lymphoma patients undergoing autologous HPCT (Dean et al. Br J Haematol 2010 Jan;148(2):226-34). We retrospectively compared the outcomes of 135 consecutively treated AML and MDS patients who underwent allogeneic HPCT at our institution from 5/2001 through 10/2009 with BuCy using oral (n = 93) or IV (n = 42) Bu, without dose adjustment. The analysis included matched related (n=97) and 8/8 HLA matched unrelated donors (n=38). Oral Bu was administered as 1 mg/kg every 6 hours for 16 doses while IV Bu was administered as 0.8 mg/kg every 6 hours for 16 doses (days –8 through -4) followed by Cy 60 mg/kg/day × 2 (days –3 and –2). The IV Bu patients were older (median age 49 vs. 47 yrs, respectively, p=0.037), more commonly had unrelated donors and peripheral blood stem cells for their HPCT cell source than those treated with oral Bu. There were no significant differences between the groups with regards to patient gender, race, CIBMTR comorbidity index score, number of prior chemotherapy regimens, pre-transplant disease status (each group had 45% of patients in CR1 or CR2), donor-recipient gender relationships or nucleated cell dose infused. The IV Bu group had a higher median CD34+ cell dose infused than those who received oral Bu (3.34 vs. 2.19 ×106/kg, respectively, p=0.028). The IV Bu patients experienced a significantly lower incidence of mucositis (3% vs. 55%, p<0.001) and less severe mucositis (median OMAS scores 0 vs.0.08, respectively, p<0.001). However, there were no significant differences between the IV and oral Bu groups in days until neutrophil and platelet count engraftment, length of transplant hospitalization, incidence of acute or chronic GVHD, sinusoidal obstruction syndrome, and 100 day mortality. At this time 26 (62%) of the IV Bu patients and 33 (36%) of the oral Bu patients are alive, however, the median follow-up was substantially longer for the oral Bu group (50 vs. 13 months, p<0.001). Disease relapse was the most common cause of death for both the IV and oral Bu patients accounting for approximately 50% of deaths in each group. The 1 and 2 year transplant-related mortality for the IV Bu patients was 21% for both, while that for the oral Bu group was 23% and 29%, respectively. The 1 and 2 year relapse mortality for the IV Bu patients was 21% for both, while that for the oral Bu group was 24% and 29%, respectively. Substituting IV for oral Bu reduces variability in drug exposure and potentially improves safety as suggested from our finding of significantly less severe oral mucositis in the IV Bu group. Further follow-up of the IV Bu group is required to adequately assess for a survival benefit. Whether pharmacokinetic-based Bu dosing can improve outcomes after allogeneic HPCT in this setting is worthy of further study. Disclosures: Sobecks: Otsuka Pharm.: Research Funding.

Amifostine Inhibits Hematopoietic Progenitor Cell Apoptosis by Activating NF-κB/Rel Transcription Factors

Blood ◽  
1999 ◽  
Vol 94 (12) ◽  
pp. 4060-4066 ◽  
Author(s):  
Maria Fiammetta Romano ◽  
Annalisa Lamberti ◽  
Rita Bisogni ◽  
Corrado Garbi ◽  
Antonio M. Pagnano ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Apoptosis ◽  
Progenitor Cell ◽  
Cell Types ◽  
Hematopoietic Progenitor Cell ◽  
Hematopoietic Progenitor ◽  
Mobility Shift ◽  
Human Cord Blood ◽  
Mobility Shift Assay ◽  
Induced Apoptosis

Abstract We investigated the involvement of NF-κB/Rel transcription factors that reportedly can inhibit apoptosis in various cell types in the antiapoptotic mechanism of the cytoprotectant amifostine. In the nontumorigenic murine myeloid progenitor 32D cells incubated with amifostine, we detected a reduction of the IκB cytoplasmic levels by Western blotting and a raising of nuclear NF-κB/Rel complexes by electrophoretic mobility shift assay. Amifostine inhibited by more than 30% the growth factor deprivation-induced apoptosis, whereas its effect failed when we blocked the NF-κB/Rel activity with an NF-κB/Rel-binding phosphorothioate decoy oligodeoxynucleotide. In human cord blood CD34+ cells, the NF-κB/Rel p65 subunit was detectable (using immunofluorescence analysis) mainly in the cytoplasm in the absence of amifostine, whereas its presence was appreciable in the nuclei of cells incubated with the cytoprotectant. In 4 CD34+ samples incubated for 3 days in cytokine-deficient conditions, cell apoptosis was reduced by more than 30% in the presence of amifostine (or amifostine plus a control oligo); the effect of amifostine was abolished in cultures with the decoy oligo. These findings indicate that the inhibition of hematopoietic progenitor cell apoptosis by amifostine requires the induction of NF-κB/Rel factors and that the latter can therefore exert an antiapoptotic activity in the hematopoietic progenitor cell compartment. Furthermore, the identification of this specific mechanism underlying the survival-promoting activity of amifostine lends support to the possible use of this agent in apoptosis-related pathologies, such as myelodysplasias.

Expression of p210 increases hematopoietic progenitor cell radiosensitivity

1993 ◽  
Vol 26 (5) ◽  
pp. 831-836 ◽  
Author(s):  
Maria A. Santucci ◽  
Pervin Anklesaria ◽  
Pierre Laneuville ◽  
Indra J. Das ◽  
Mary Ann Sakakeeny ◽  
...  
Keyword(s):  
Progenitor Cell ◽  
Hematopoietic Progenitor Cell ◽  
Hematopoietic Progenitor
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