Biomedical subjects

C Bredeson

Publications and source records attributed to C Bredeson.

15 recordsLinked to original sources

PubMed2006

Bone marrow transplants from mismatched related and unrelated donors for severe aplastic anemia.

For patients with acquired severe aplastic anemia without a matched sibling donor and not responding to immunosuppressive treatment, bone marrow transplantation from a suitable alternative donor is often attempted. We examined risks of graft failure, graft-versus-host disease and overall survival after 318 alternative donor transplants between 1988 and 1998. Sixty-six patients received allografts from 1-antigen and 20 from >1-antigen mismatched related donors; 181 from matched and 51 from mismatched unrelated donors. Most patients were young, had had multiple red blood cell transfusions and poor performance score at transplantation. We did not observe differences in risks of graft failure and overall mortality by donor type. The probabilities of graft failure at 100 days after 1-antigen mismatched related donor, >1-antigen mismatched related donor, matched unrelated donor and mismatched unrelated donor transplants were 21, 25, 15 and 18%, respectively. Corresponding probabilities of overall survival at 5 years were 49, 30, 39 and 36%, respectively. Although alternative donor transplantation results in long-term survival, mortality rates are high. Poor performance score and older age adversely affect outcomes after transplantation. Therefore, early referral for transplantation should be encouraged for patients who fail immunosuppressive therapy and have a suitable alternative donor.

Adolescent↗

PubMed2005

The implication of follicular lymphoma patients receiving allogeneic stem cell transplantation from donors carrying t(14;18)-positive cells.

We performed real-time quantitative polymerase chain reaction (RQ-PCR) in peripheral blood (PB) and/or bone marrow (BM) samples collected pre- and post transplant from 23 recipient-donor pairs receiving allogeneic stem cell transplantation (allo-SCT) for follicular lymphoma (FL). Of 23 donors, 11 had a PB and/or BM sample positive for t(14;18) (BCL2/IGH fusion) at low levels (<one t(14;18) cell in 10K total cells). Recipients from donors with (n=11) and those without (n=12) detectable t(14:18) cells were similar in age, sex, and disease status pretransplant. No differences in the incidence of graft-versus-host-disease (GVHD), delayed engraftment, relapse rate, disease-free survival and overall survival were identified between the groups. Two recipients without detectable t(14;18) cells pre-transplant showed detectable t(14;18) cells at 2 and 11 years after receiving grafts from donors with t(14:18) cells. Neither patient developed FL 1.5 and 2 years after the emergence of t(14;18) cells. Although the sample size is relatively small, our findings suggest that individuals carrying t(14;18) cells may not be excluded as donors given the lack of an association of t(14;18) detected in donors with adverse clinical outcome. It may be necessary to screen for the donor's t(14;18) status before using t(14;18) for monitoring minimal residual disease by RQ-PCR to exclude the possibility of confounding donor's t(14;18) clone.

Adult↗

PubMed2003

Tumor load in patients with follicular lymphoma post stem cell transplantation may correlate with clinical course.

The purpose of this study was to evaluate if the tumor load, as determined by a real-time quantitative PCR (RQ-PCR) assay, correlated with the clinical course of follicular lymphoma patients after stem cell transplantation (SCT). Cryopreserved bone marrow and/or peripheral blood samples obtained at different time intervals after SCT from 11 patients (seven allogeneic, T-cell depleted/four autologous) were tested for tumor load, as defined by t(14;18) positive cells/total cells, using RQ-PCR. None of the six patients who remained in remission had samples with a tumor load >0.01% after SCT, although fluctuating tumor loads of </=0.01% were observed in three of these patients. In contrast, four of the five patients (three allogeneic/two autologous) with relapsed/progressive disease had increasing tumor loads of >0.01% after SCT (0/6 vs 4/5, P<0.02, Fisher's exact). Our results suggest that RQ-PCR measurable tumor load >0.01% after SCT may correlate with relapsed/progressive disease. Prospective studies with greater numbers of cases are indicated to better determine the critical tumor load that predicts poor outcome after SCT with RQ-PCR.

Adult↗

PubMed2003

Autologous stem cell transplantation in multiple myeloma patients <60 vs >/=60 years of age.

The role of autologous stem cell transplantation (AuSCT) in older multiple myeloma patients is unclear. Using data from the Autologous Blood and Marrow Transplant Registry, we compared the outcome of 110 patients >/=the age of 60 (median 63; range 60-73) years, undergoing AuSCT with that of 382 patients <60 (median 52; range 30-59) years. The two groups were similar except that older patients had a higher beta(2)-microglobulin level at diagnosis (P=0.016) and fewer had lytic lesions (P=0.007). Day 100 mortality was 6% (95% confidence interval 4-9) and 1-year treatment-related mortality (TRM) was 9% (6-13) in patients <60 years, compared with 5% (2-10) and 8% (4-14), respectively, in patients >/=60 years. The relapse rate, progression-free survival (PFS) and overall survival (OS) in the two groups were also similar. Multivariate analysis of all patients identified only an interval from diagnosis to AuSCT >12 months and the use of two prior chemotherapy regimens within 6 months of AuSCT as adverse prognostic factors. Our results indicate that AuSCT can be safely performed in selected older patients: the best results were observed in patients undergoing AuSCT relatively early in their disease course.

Adult↗

PubMed2002

Outpatient total body irradiation as a component of a comprehensive outpatient transplant program.

Outpatient total body irradiation (TBI) as part of a comprehensive outpatient transplant program was delivered to 142 of 167 (85%) consecutive patients receiving TBI-based conditioning therapy. Outpatients received either a single fraction of 500 cGy (110 patients) or 1200 cGy in six fractions over 3 days (32 patients). Patients were assessed daily and were administered oral ondansetron and dexamethasone for prophylaxis of nausea and vomiting as well as i.v. hydration. Accommodation during outpatient TBI-based conditioning was either the patient's home if within 30 min of the hospital, a hotel on the hospital grounds or on a closed hospital ward. None of the 142 patients required admission to the inpatient program during their TBI. There was no difference in 100-day mortality between those receiving TBI as an outpatient (9%) vs as an inpatient (16%). Of four deaths occurring within the first 14 days post transplant, none could be attributed to receiving TBI as an outpatient. Two hundred and six inpatient days were saved through the delivery of outpatient TBI. A comprehensive outpatient program, appropriate patient selection, daily hydration, the use of prophylactic 5HT3 antagonist anti-emetic therapy all contribute to the safe delivery of outpatient TBI.

Adolescent↗

PubMed2001

Factors affecting neutrophil and platelet reconstitution following T cell-depleted bone marrow transplantation: differential effects of growth factor type and role of CD34(+) cell dose.

We have performed univariate and multivariate analysis to determine the factors that affect the kinetics of neutrophil and platelet recovery in 546 recipients of T cell-depleted (TCD) marrow allografts. All patients received marrow depleted of mature CD3(+) T cells by complement-mediated lysis using T(10)B(9)-1A3 (n = 489) or Muromonab-Orthoclone OKT3 (n = 57) monoclonal antibodies. Neutrophil engraftment to 0.5 x 10(9)/1 and platelet engraftment to 20 x 10(9)/l were assessed as endpoints. Factors significantly affecting neutrophil or platelet engraftment in the univariate analysis included patient age, T cell dose, anti-thymocyte globulin use, gender, diagnosis at transplant, CMV serostatus, HLA mismatch, CD34 cell dose (n = 249), and growth factor use and type. These variables were included in the multivariate Cox proportional hazards regression model. The results showed that a faster rate of neutrophil engraftment was independently associated with CD34(+) cell dose > or = 5 x 10(6)/kg and most strongly with growth factor administration. Faster platelet engraftment was associated with transplantation for chronic leukemia, CD34(+) cell dose > or = 2 x 10(6)/kg, an HLA matched related donor, and the absence of growth factor use. G-CSF had a higher relative risk (RR) of enhancing neutrophil engraftment than GM-CSF and significantly delayed platelet engraftment. The combined use of G-CSF + GM-CSF was similar to G-CSF alone. The enhancing effect of G-CSF for neutrophil recovery was most striking for patients who engrafted to 0.5 x 10(9)/1 at or before day 12 (RR = 9.5, P < 0.0001) compared to patients who received no growth factor. Conversely, the delaying effect of G-CSF on platelet engraftment was strongest for patients engrafting on or before day 25 (RR = 0.4, P = 0.0004). Of the independent variables affecting engraftment kinetics in recipients of TCD marrow allografts only growth factor, and to a limited extent, CD34(+) cell dose can be controlled by the clinician. A higher CD34(+) cell dose enhances the rate of both neutrophil and platelet engraftment whereas for G-CSF the benefits of myeloid growth factor use in enhancing neutrophil recovery may be partly offset by a delay in platelet engraftment.

Adolescent↗

PubMed2001

Analysis of risk factors for the development of GVHD after T cell-depleted allogeneic BMT: effect of HLA disparity, ABO incompatibility, and method of T-cell depletion.

Multivariate analysis was performed to determine the independent factors affecting the risk of acute GVHD (aGVHD) grades II to IV and extensive chronic GVHD (cGVHD) and the rate of survival in 481 recipients of T cell-depleted (TCD) marrow allografts who received transplants at a single center between 1991 and 2000. All patients received grafts partially depleted of CD3+ T cells by complement-mediated lysis using 2 narrow-specificity monoclonal antibodies (MoAbs), T10B9.1A-31 (n = 400) or Muromonab-Orthoclone OKT3 (n = 81). Factors considered in the analysis included patient/donor sex, age, cytomegalovirus (CMV) status, and ABO blood group along with T-cell dose, disease, and disease status, donor relationship, HLA antigen (Ag)mismatch (MM), growth-factor use, anti-thymocyte globulin use, year of transplantation, and the MoAb used for TCD. The results showed an association of HLA with an increased relative risk (RR) of aGVHD for recipients of grafts from relateddonors that were > or =2 Ag MM (n = 73, RR = 2.09, P = .005), matched unrelated (UR) donors (n = 130, RR = 1.98, P = .004), and > or =2 Ag MM UR donors (n = 34, RR = 2.68, P = .003) compared with the baseline matched-sibling group (n = 121). No increased risk of aGVHD was seen for 0 to 1 Ag MM family donors (n = 24) or 1 Ag MM UR donors (n = 99). aGVHD risk was increased with minor, but not major or major-minor, ABO disparity (RR = 2.0, P = .003) compared with that of ABO-identical pairs. We found less effective TCD and resultant higher T-cell dose for recipients of grafts that were T cell depleted using OKT3. However, the use of OKT3 and not the T-cell dose was associated with increased aGVH-D risk (RR of 1.84, P = .001). Increased risk of extensive cGVHD was associated with patient age of >20 years (RR = 2.2, P < .0001) and with CMV status (positive patient/negative donor, RR = 1.9, P = .002). Decreased survival was associated with older age (>20 years), a > or =2 Ag MM related donor, a 1 or > or =2 Ag MM UR donor, risk group, and a CMV-positive patient/-negative donor pair. There was no difference in survival for 0 to 1 Ag MM related or matched UR donors compared with the baseline group. These data indicate that there are quantitative as well as potential qualitative differences in outcome depending on the TCD method. Expected and unexpected risk factors for GVHD and survival were associated with partial TCD. Our data support the consideration of ABO match in donor selection, the preferential selection of CMV-positive donors for CMV-positive recipients, and the acceptance of 1 but not > or =2 Ag HLA MM donors.

ABO Blood-Group System↗

PubMed2000

Autologous blood and marrow transplantation in patients 60 years and older.

Although many hematologic malignancies are more common in older patients, autologous blood and marrow transplantation (ABMT) has traditionally been restricted to patients younger than 60 years because of concerns that older patients would be either unable to provide a graft or unable to tolerate the therapy. From June 1995 to May 1998, 30 patients > or = 60 years underwent ABMT at our institution for low-grade lymphoma (4 patients), relapsed intermediate-grade lymphoma (17 patients), or multiple myeloma (9 patients). The median patient age was 62.5 years (range 60-73). Pretransplantation conditioning regimens were CBV (cyclophosphamide, BCNU [carmustine], etoposide) or BEAM (carmustine, etoposide, cytarabine, melphalan) for intermediate-grade lymphoma patients and melphalan 140 mg/m2 + etoposide 60 mg/kg + total body irradiation 500 cGy for the others. The rescue product was bone marrow (BM; 4 patients), peripheral blood stem cells (PBSC; 23 patients), or BM+PBSC (3 patients). The median number of CD34+ cells/kg infused was 3.60 x 10(6) (range 0.53-31.0), by the International Society for Hematotherapy and Graft Engineering method. The treatment-related mortality at day 100 and at 6 months was 10% and 16.7%, respectively. The median days to neutrophil > 0.5 x 10(9)/L was 11 (range 9-25) and platelets > 20 x 10(9)/L was 16 (range 6-70). Three patients died of infection (days 26, 27, and 38), and 1 died of an intracranial hemorrhage related to persistent thrombocytopenia (day 130). Bearman regimen-related toxicity was moderate, with most toxicities < or = grade 2. Seven patients developed significant gut toxicity: 4 patients with Clostridium difficile colitis and 3 patients with neutropenic enterocolitis. Depressive symptoms and signs were noted in 4 patients. Three male patients developed decreased gonadal function after transplantation. These transplantations accounted for 997 patient days, of which 266 days (27%) were in the outpatient BMT program--a smaller percentage than in patients < 60 years (56%, P = .002). Twenty patients are alive 153 to > or = 1224 days after transplantation. ABMT in patients > or = 60 years of age is feasible. Further studies addressing supportive care particular to older patients and comparisons of ABMT with traditional approaches to multiple myeloma and relapsed non-Hodgkin's lymphoma in older patients are needed. Further work to identify elderly patients most likely to benefit from this approach is also required.

Age Factors↗

PubMed1999

Long-term survival and late deaths after allogeneic bone marrow transplantation. Late Effects Working Committee of the International Bone Marrow Transplant Registry.

BACKGROUND AND METHODS: It is uncertain whether mortality rates among patients who have undergone bone marrow transplantation return to the level of the mortality rates of the general population. We analyzed the characteristics of 6691 patients listed in the International Bone Marrow Transplant Registry. All the patients were free of their original disease two years after allogeneic bone marrow transplantation. Mortality rates in this cohort were compared with those of an age-, sex-, and nationality-matched general population. Cox proportional-hazards regression was used to identify risk factors for death more than two years after transplantation (late death). RESULTS: Among patients who were free of disease two years after transplantation, the probability of living for five more years was 89 percent (95 percent confidence interval, 88 to 90 percent). Among patients who underwent transplantation for aplastic anemia, the risk of death by the sixth year after transplantation did not differ significantly from that of a normal population. Mortality remained significantly higher than normal throughout the study among patients who underwent transplantation for acute lymphoblastic leukemia or chronic myelogenous leukemia and through the ninth year among those who underwent transplantation for acute myelogenous leukemia. Recurrent leukemia was the chief cause of death among patients who received a transplant for leukemia, whereas chronic graft-versus-host disease was the chief cause among those who received a transplant for aplastic anemia. Advanced, long-standing disease before transplantation and active chronic graft-versus-host disease were important risk factors for late death. CONCLUSIONS: In patients who receive an allogeneic bone marrow transplant as treatment for acute myelogenous or lymphoblastic leukemia, chronic myelogenous leukemia, or aplastic anemia and who are free of their original disease two years later, the disease is probably cured. However, for many years after transplantation, the mortality among these patients is higher than that in a normal population.

Adolescent↗

PubMed1999

Selection of appropriate venous access for the collection of peripheral blood progenitor cells by experienced apheresis nurses.

Peripheral blood progenitor cells (PBPC) have been extensively used to restore hematopoiesis after myeloablative chemotherapy. While collection regimens designed for optimal mobilization of PBPC are becoming standardized, the ideal venous access option for collection remains unresolved. The purpose of this study was to determine if the venous access of patients could be accurately assessed and appropriate intervention, if necessary, electively undertaken prior to PBPC collection. In this prospective study, 95 consecutive patients about to undergo PBPC collection were evaluated at time of referral to determine the type of venous access necessary for adequate PBPC collection. There were three possible interventions: 1. No access device for patients determined to have an adequate antecubital vein for apheresis access. 2. Insertion of a double lumen Quinton PermCath for those patients with poor antecubital veins. 3. Insertion of a double lumen Hickman catheter for patients with adequate antecubital veins for apheresis but poor peripheral veins for chemotherapy administration. The blood and marrow transplant nurse coordinator evaluated the patients' veins. Of the 95 patients having 192 PBPC collections, 65 were collected using antecubital veins, 21 were collected from PermCaths, and 9 from Hickman catheters. All patients predicted to collect peripherally did so and achieved flow rates equivalent to the PermCath. No patient required urgent line placement at time of PBPC collection. There was no difference in the number of cells collected between the three groups. The result of this study strongly supports a policy of appropriate venous access based on patient vein assessment by experienced nurses.

Adolescent↗

PubMed1998

Cost-effectiveness of low-molecular-weight heparin and unfractionated heparin in treatment of deep vein thrombosis.

BACKGROUND: Acute deep vein thrombosis has traditionally been treated with unfractionated heparin (UFH), administered intravenously, but low-molecular-weight heparins (LMWH), administered subcutaneously, have recently become available. The authors sought to determine which therapy was more cost-effective for inpatient and outpatient treatment of deep vein thrombosis. METHODS: An incremental cost-effectiveness analysis based on a decision tree was performed for 4 treatment strategies for deep vein thrombosis. Rate of major hemorrhage while receiving heparin, rate of recurrence of venous thromboembolism 3 months after treatment and mortality rate 3 months after treatment were determined by meta-analysis. Costs for the UFH therapy were prospectively collected by a case-costing accounting system for 105 patients with deep vein thrombosis treated in fiscal year 1995/96. The costs for LMWH therapy were modelled, and cost-effectiveness was determined by decision analysis. RESULTS: Meta-analysis revealed a mean difference in risk of hemorrhage of -1.1% (95% confidence interval [CI] -2.4% to 0.3%), a mean difference in risk of recurrence of venous thromboembolism of -2.6% (95% CI -4.5% to -0.7%) and a mean difference in risk of death of -1.9% (95% CI -3.6% to -0.4%), all in favour of subcutaneous unmonitored administration of LMWH. The cost to treat one inpatient was $2993 for LMWH and $3048 for UFH. Even more would be saved if LMWH was delivered on an outpatient basis (cost of $1641 per patient). The cost-effectiveness analysis showed that LMWH in any treatment setting is more cost effective than UFH. A sensitivity analysis demonstrated the robustness of this conclusion. INTERPRETATION: Treatment of deep vein thrombosis with LMWH is more cost effective than treatment with UFH in both inpatient and outpatient settings.

Canada↗

PubMed1998

A randomized trial of granulocyte colony-stimulating factor (Neupogen) starting day 1 vs day 7 post-autologous stem cell transplantation.

The purpose of the study was to evaluate the effect of delayed granulocyte colony-stimulating factor (G-CSF) use on hematopoietic recovery post-autologous peripheral blood progenitor cell (PBPC) transplantation. Patients were randomized to begin G-CSF on day +1 or day +7 post transplantation. Thirty-seven patients with lymphoma or myeloma undergoing high-dose therapy and autologous PBPC rescue were randomized to daily subcutaneous G-CSF beginning on day +1 or day +7 post-transplant. Patients < or =70 kg received 300 microg/day and >70 kg 480 microg/day. All patients were reinfused with PBPCs with a CD34+ cell count >2.0 x 10(6)/kg. Baseline characteristics of age, sex and CD34+ cell count were similar between the two arms, the median CD34+ cell count being 5.87 x 10(6)/kg in the day +1 group and 7.70 x 10(6)/kg in the day +7 group (P=0.7). The median time to reach a neutrophil count of >0.5 x 10(9)/l was 9 days in the day +1 arm and 10 days in the day +7 arm, a difference which was not statistically significant (P=0.68). Similarly, there was no difference in median days to platelet recovery >20000 x 10(9)/l, which was 10 days in the day +1 arm and 11 days in the day +7 arm (P=0.83). There was also no significant difference in the median duration of febrile neutropenia (4 vs 6 days; P=0.7), intravenous antibiotic use (7 vs 8 days; P=0.54) or median number of red blood cell transfusions (4 vs 7 units; P=0.82) between the two arms. Median length of hospital stay was 11 days post-PBPC reinfusion in both groups. The median number of G-CSF injections used was 8 in the day +1 group and 3 in the day +7 group (P < 0.0001). There is no significant difference in time to neutrophil or platelet recovery when G-CSF is initiated on day +7 compared to day +1 post-autologous PBPC transplantation. There is also no difference in number of febrile neutropenic or antibiotic days, number of red blood cell transfusions or length of hospital stay. The number of doses of G-CSF used per transplant is significantly reduced with delayed initiation, resulting in a significant reduction in drug costs. For patients with an adequately mobilized PBPC graft, the initiation of G-CSF can be delayed until day +7 post-PBPC reinfusion.

Adult↗

PubMed1997

Cost analysis of the introduction of PBPC for autologous transplantation: effect of switching from bone marrow (BM) to peripheral blood progenitor cells (PBPC).

Increasingly, PBPC instead of BM are used for autologous transplantation. Limited data exist on the economic effects of this change. Using a resource-based utilization model we prospectively determined the costs of 48 autologous transplants (eight BM, 17 BM + PBPC, 23 PBPC), isolating the post-reinfusion period (day 0 to discharge) to better determine the effect of the rescue product. Length of stay post-reinfusion was significantly shorter in patients receiving PBPC (median 13 days) or BM + PBPC (median 14 days) vs BM alone (median 20 days) (P < 0.01). Accordingly, transplant admission costs were less in the PBPC groups (PBPC $22089, BM + PBPC $23179) vs the BM alone group ($32289) (P < 0.05). Rescue product acquisition costs were higher for PBPC (range $3439-$5157) vs BM ($2766) but these costs were offset by the more rapid recovery of patients receiving PBPC. Overall transplant costs depend on the conditioning regimen with a 10-fold cost variation among regimens. Modeled costs for autologus transplantation using various approaches to rescue product acquisition are given. The introduction of PBPC for autologus transplantation has resulted in cost savings at our institution. Although the acquisition costs of PBPC rescue product are greater than for BM, this incremental expense is more than offset by a less expensive post-reinfusion period.

Adolescent↗

PubMed1995

2-Chloro-deoxyadenosine therapy for giant lymph node hyperplasia.

Giant lymph node hyperplasia (GLNH) or Castleman disease is a heterogenous group of atypical lymphoproliferative disorders. Two main histologic variants, the hyaline vascular variant and the plasma cell variant, have been recognized. Although localized GLNH can often be managed successfully with surgery, optimal therapy for multifocal disease has yet to be identified. We report two cases of GLNH treated with 2-chloro-deoxyadenosine (2-CDA), a synthetic purine analogue. 2-CDA was utilized based on its relative lymphocytic toxicity and the putative pathophysiologic process in GLNH being either hamartomatous overgrowth (hyaline-vascular variant) or immune dysfunction and lymphoproliferation (plasma cell variant). One patient with unresectable localized hyaline-vascular GLNH has had a 9-month continuous complete remission following two courses of 2-CDA therapy followed by radiation therapy. The second patient with disseminated plasma cell type had a partial response to two cycles of 2-CDA therapy; however, further cycles were not given due to development of possible early neurotoxicity. Although the optimal management of non-resectable GLNH is yet to be determined, 2-CDA appears to be a viable therapeutic option for patients with this disease process.

Adult↗

PubMedDate not supplied

Dead space ventilation parallels changes in scintigraphic vascular obstruction at recurrence of pulmonary embolism and after thrombolytic therapy: a case report.

Physiological and alveolar dead space ventilation both increase in pulmonary embolism (PE) in proportion to the severity of vascular obstruction. The case of a patient with recurrent PE while on heparin therapy is presented. The recurrence was characterized clinically by severe pulmonary vascular obstruction and right heart dysfunction. The patient was treated with thrombolytic therapy, with excellent clinical and scintigraphic resolution. Dead space ventilation measurements at baseline, at the time of recurrence and after thrombolytic therapy are presented. The potential utility of dead space ventilation measurements for PE diagnosis and management are discussed.

Fibrinolytic Agents↗