PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Transplantation Conditioning”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1984

[Transplant conditioning and transplant size in heterotopic autologous spleen transplantation].

In an experimental study we compared two methods of preparing transplants in rabbits (n = 66): 4-5 splenic fragments with a thickness of 1 mm and graduated weight (5-800 mg) were attached onto the peritoneal peritoneum. Splenic homogenates with increasing weight (5-800 mg) were placed in 4-5 preformed pockets in the parietal peritoneum. At different postoperative intervals (maximum 42 days), a relaparotomy was performed. The regenerated splenic tissue was dissected, weighted and histologically examined. We found a linear correlation between pre- and postoperative weight. However, this correlation applies only to the homogenates with a weight of maximal 200 mg and to the fragments with a weight of maximal 300 mg. We have come to the conclusion that homogenates regenerate better than fragments.

Animals↗
PubMed2002

Intracellular Ca2+ regulation in hepatocytes under experimental transplantation conditions.

Under transplant conditions excessive accumulation of intracellular calcium ([Ca2+](i)) is considered to be a mediator of cell injury during ischaemia and re-oxygenation. To clarify this consideration as well as the necessity of calcium-free preservation solutions, we used a well-known in-vitro model. Furthermore, a new application to mimic clinical situation was established, and we evaluated the correlation between [Ca2+](i) change and cell survival in monolayers of isolated rat hepatocytes undergoing cold hypoxia in defined solutions and during re-oxygenation. [Ca2+](i) was measured in single cells by ratio imaging of Fura-2 fluorescence after various periods of cold hypoxia (ischaemia phase) in different preservation solutions [UW, HTK, EC and Krebs-Henseleit buffer (KH)] and following warm normoxic reperfusion (re-oxygenation phase) with KH. Cell survival was measured simultaneously by trypan-blue exclusion. Cell survival decreased, depending on preservation solution and preservation time. The partially tremendous [Ca2+](i) change under cold hypoxia did not correlate with the change in cell survival. For example, UW-stored cells showed a [Ca2+](i) loss from 280 nM to 56 nM, compared with KH-stored cells with a [Ca2+](i) increase of up to 445 nM. Our results indicate that [Ca2+](i) plays only a minor role in the pathomechanisms of hypoxic and re-oxygenation hepatocellular injury.

Animals↗
PubMed1996

A more immunosuppressive pre-transplant conditioning may be required for Chinese patients with thalassaemia.

Bone marrow transplantation was performed on 14 Chinese patients with transfusion dependent thalassaemia major (n = 13) and haemoglobin H disease (n = 1). The donors were HLA identical siblings. The source of haematopoietic stem cells were from bone marrow (n = 13) and umbilical cord blood (n = 1). The pre-transplant conditioning regimens were (1) busulphan 14 mg/kg and cyclophosphamide 200 mg/kg in two patients; (2) busulphan 16 mg/kg, cyclophosphamide 200 mg/kg and anti-thymocyte globulin 110 mg/kg in five patients; (3) busulphan 16 mg/kg, cyclophosphamide 150 mg/kg and anti-thymocyte globulin 110 mg/kg in seven patients. Graft-versus-host disease prophylaxis was cyclosporin A and methotrexate. All patients engrafted and achieved stable haematopoiesis except the one who underwent the umbilical cord blood transplant, who had autologous marrow recovery. One patient who had stable engraftment rejected the marrow graft and developed aplastic anaemia 4 months after BMT. This patient had a second BMT but rejection recurred again. She eventually died of septicaemia. The other 12 patients were transfusion independent and disease free. The majority have gone back to school or work. Disease-free and actuarial survival probability were 85 and 93%, respectively with a median follow-up time of 30 months (13 to 42 months). Our data suggest that BMT from HLA identical siblings for transfusion dependent thalassaemia gives a high chance of cure with acceptable mortality and morbidity, and that a more immunosuppressive pre-transplant conditioning schedule may be required to prevent rejection.

Adolescent↗
PubMed1999

Use of idarubicin in pre-transplant conditioning in children with high-risk acute leukaemia.

The major cause of treatment failure following allogeneic bone marrow transplantation for acute leukaemia is disease relapse. In an attempt to reduce post- transplant relapse in 33 children with high-risk acute leukaemia who received a related or unrelated bone marrow transplant, the pre-transplant conditioning regimen was intensified by the addition of idarubicin. Its toxicity and effects on survival were evaluated over a 57-month period. Toxicity, largely gastrointestinal, was increased but acceptable, and there was no specific regimen-related toxicity. Relapse rates were low (24%) in this high risk group, but mortality was increased in those receiving unrelated donor grafts, largely due to sepsis. Idarubicin does appear to have a role to play in the conditioning regimen of patients with high-risk acute leukaemia undergoing BMT, and may reduce relapse rates without increasing transplant-related mortality.

Acute Disease↗
PubMed1991

Influence of nephrotoxic drugs on the late renal toxicity associated with bone marrow transplant conditioning regimens.

The total body irradiation that is given as part of bone marrow transplant conditioning regimens is a factor in the renal toxicity that is observed after bone marrow transplant, but it may not be the only factor. We hypothesize that nephrotoxic drugs used in prior chemotherapy can precipitate renal radiation damage. Studies were designed to determine if nephrotoxic antineoplastic drugs could shorten the latent period for the development of radiation nephritis. Rats were given bilateral renal irradiation using a radiation schedule that produced moderate nephritis. Cisplatinum, BCNU, or mitomycin were given before, during, or after irradiation at doses that produced only mild nephrotoxicity. All cisplatinum-radiation sequences resulted in decreased renal function, with radiation prior to cisplatinum producing the greatest dysfunction. BCNU increased renal dysfunction equally in all schedules, but mitomycin had only minimal effects. Most drug schedules, including those with mitomycin, produced earlier development of morbidity after fractionated renal irradiation. In a second set of studies, rats were given single doses of the same nephrotoxic drugs, followed 3 months later by total body irradiation plus bone marrow transplant. The drugs had no effect on the marrow ablation dose, but BCNU and cisplatinum decreased gastrointestinal tolerance. Four months after total body irradiation, rats which received drugs alone or total body irradiation alone have essentially normal renal function, but rats which received cisplatinum plus total body irradiation or BCNU plus total body irradiation show a dose-dependent decrease in renal function. These studies show that radiation nephritis can be precipitated by low doses of nephrotoxic drugs, and may help to explain the incidence of early radiation nephritis in bone marrow transplant patients conditioned with total body irradiation.

Animals↗
PubMed1981

[Effect of different transplant conditions on lipid peroxidation in the transplant and the recipient's tissues].

This work analyses the change of LPO intensity in transplanted skin and in recipient tissue: in blood and skin adjoining the transplants during 27 days after auto- and homotransplantation. A conclusion is made that primary LPO strengthening of autotransplants and skin, adjoining the transplant during 9-14 days after transplantation, growing lesser, reaches the level of intact skin. Under homotransplantation the primary LPO strengthening not only reaches the initial level 9-14 days of the transplantation, but continues to increase. It was shown that the first maximum of LPO strengthening in the transplants (2-5 days after transplantation) were caused by ischemic lesions and the second maximum - by immunologic shifts.

Animals↗
PubMed1984

Investigations on the instability of drug sensitivity in dependence on culture and transplantation conditions in case of a human lung carcinoma.

Changes of biological properties, DNA-distribution patterns and drug sensitivity testing in vivo and in vitro after different culture and transplantation conditions in case of a human lung carcinoma are described. While DNA-distribution patterns of cells before any culture (OSC, TC 0) showing two clearly different aneuploid cell populations (DNA-index DI: 3.9 and 4.9), cells after 8 passages (TC 8) in vitro demonstrate only one cell population. These cells do not differ from double value (4C) of diploid cells (2C). DNA-distribution patterns of cells of solid tumors grown in nude mice (nu/nu 2089-1) show a cell population with DI 6.3. In line with these results, cells and tissues after different culture and transplantation conditions exhibit variable drug sensitivities. The lung carcinoma (OSC) shows clear reactions measured either by 3H-thymidine or 3H-deoxyuridine in the presence of Cyclophosphamide and Methotrexate. Adriblastin and 5-Fluorouracil did not show any effects after 48 hours treatment. Cultivated cells (TC 8) were sensitive against all antineoplastic drugs tested. Tumor tissue grown in nude mice (nu/nu 2089-1) shows the strongest effect after 5-Fluorouracil treatment both in vitro and in vivo. Selection of different cell population were discussed with regard to these findings.

Adenocarcinoma↗
PubMed2000

Melphalan/TBI is not more carcinogeneic than cyclophosphamide/TBI for transplant conditioning: follow-up of 725 patients from a single centre over a period of 26 years.

As there is concern regarding the high carcinogenic potential of melphalan (Mel), 725 patients with haematological malignancies who received allogeneic (n = 714) or syngeneic (n = 11) transplants over the last 26 years were followed-up to evaluate if melphalan was more likely to result in secondary malignant neoplasms (SMNs) than cyclophosphamide (Cy). Three hundred and ninety-five were treated with Cy/TBI and 330 with Mel/TBI. Twelve patients developed non-haematological SMN. Median time to develop a SMN was 7 years (range 2-17 years). Age-adjusted rate was significantly higher than in the general population (observed 12 expected 1.2, risk 10; P < 0.0001). The cumulative overall risk of developing a SMN at 2, 5, 10 and 15 years post transplant was 0.4% (95% CI 0.1-2.6%), 1.7% (95% CI 0.6-4.4%), 6.4% (95% CI 2.8-10.8%) and 6.6% (95% CI 3.4-12.4%), respectively. Even though age-adjusted rates were higher than the general population melphalan/TBI was not associated with higher age-adjusted risk than Cy/TBI (increased risk 7.9 vs 11.4; P = NS). The cumulative overall risk of SMNs was not different with CY/TBI or Mel/TBI (8/393 vs 4/363; 10 year risk 4.4%, 95% CI 1.8-10.6 vs 8.4%, 95% CI 2.9-22.9; P = NS). The risk was significantly higher with use of additional cranial or cranio-spinal irradiation (17.5% vs 2.7% at 10 years; P = 0.0241). Transplants for acute lymphatic leukaemia resulted in a higher incidence of SMNs than did transplants for other diseases (ALL: 17.4%, 95% CI 6.3-42.6%; other diseases: 3.4% (95% 1.3-8.5%, P = 0.0469). The risk of SMN for patients with chronic GVHD was 8.4% (95% CI 3.7-18.7%) as compared to 3.5% (95% CI 1-11.1%) for patients without chronic GVHD (P = NS). No factor was associated with independently increased risk in multivariate analysis. Use of melphalan and TBI for transplant conditioning does not appear to be associated with higher risk of second malignant neoplasms than cyclophosphamide and TBI.

Adolescent↗
PubMed1995

TNF alpha levels are increased during bone marrow transplantation conditioning in patients who develop acute GVHD.

TNF alpha levels were determined by ELISA in serum from 112 BMT patients during pre-transplant conditioning. Patients who developed post-transplant complications had significantly higher TNF alpha levels than those without complications (mean 620 pg/ml vs 440 pg/ml, P = 0.04). In particular this effect is associated with patients who developed grade II-IV acute GVHD (mean 960 pg/ml, P < 0.001) and chronic GVHD (mean 724 pg/ml, P = 0.001). High TNF alpha levels were the only statistically significant risk factor for acute GVHD. IL-1 beta and IL-6 levels were not correlated with TNF alpha levels or posttransplantation complications. In multivariate analysis of chronic GVHD, patient age > 17 years and CMV disease were the only statistically significant risk factors. Relapse was associated with low levels of TNF alpha during conditioning (mean 318 pg/ml, P = 0.02). In multivariate analysis, high risk disease was the only factor that correlated with relapse. Low risk patients had significantly higher levels than high risk patients (551 vs 377, P= 0.04). CML and MDS patients had higher TNF alpha levels than acute leukemia patients. There was no difference in TNF alpha levels between patients conditioned with BU/CY and CY/TBI. We conclude that determination of TNF alpha levels during conditioning may be useful in the prediction of acute GVHD.

Acute Disease↗
PubMed1998

Allogeneic peripheral blood progenitor cell transplantation conditioned with anti-thymocyte globulin for treatment of graft failure after allogeneic bone marrow transplantation.

A 43-year-old female with AML-M1 developed late graft failure 4 months after her first allogeneic bone marrow transplant. The patient then underwent a second transplant with peripheral blood progenitor cells obtained from the same HLA-identical brother. The donor peripheral blood progenitor cells were mobilized with granulocyte colony-stimulating factor (10 micrograms/kg daily s.c. for 6 days). The patient received horse anti-thymocyte globulin alone (15 mg/kg per day for 5 days) as the conditioning regimen. Rapid hematopoietic recovery followed a sustained engraftment. The time to reach 0.5 x 10(9)/l neutrophils and 25 x 10(9)/l platelets was 10 and 12 days, respectively. Cytogenetic analysis of bone marrow performed on day +20 demonstrated a 46XY karyotype of donor origin. There was no acute graft-versus-host disease. The patient remains in complete remission with a karnofsky score of 90% 5 months after peripheral blood progenitor cell transplantation. To treat graft failure after allogeneic bone marrow transplantation, allogeneic peripheral blood progenitor cell transplantation conditioned with anti-thymocyte globulin alone should be considered as a feasible alternative to marrow transplant.

Adult↗
PubMed2001

Bone marrow transplant conditioning intensified with liposomal clodronate to eliminate residual host antigen presenting cells fails to ameliorate GVHD and increases PERI-BMT mortality.

BACKGROUND: Graft versus host disease (GVHD) mediated by allogeneic donor T cells may be initiated and/or exacerbated by residual host antigen presenting cells (APC) which survive the transplant conditioning regimen. We examined whether the depletion of hepatic and splenic APC could reduce the severity of hepatic GVHD after bone marrow transplantation (BMT). METHODS: Recipient mice were depleted for hepatic and splenic phagocytic APCs by i.v. injection of clodronate- (dichloromethylene diphosphonate) containing liposomes before fully allogeneic or MHC-matched, minor Ag-mismatched BMT. Severity of hepatic GVHD was scored on histological sections 2, 3, 4, or 9 weeks after BMT. RESULTS: No differences in the severity of GVHD were observed between APC-depleted mice and control mice. APC-depleted mice had increased peritransplant mortality due to sepsis. Bacterial clearance assays showed that APC-depleted mice were unable to efficiently clear bacteria, although nondepleted, transplanted mice were able to clear bacteria as quickly as naive control mice. CONCLUSIONS: Residual host phagocytic APC do not appear to play a role in the induction of GVHD after BMT. They are, however, essential for prevention of sepsis in the transplant host.

Animals↗
PubMed2002

Increasing use of reduced intensity conditioning transplants: report of the 2001 EBMT activity survey.

Since 1990, the EBMT has annually collected numbers of HSCT by disease indication, donor type and stem cell source. The 2001 survey concentrates on the use of reduced intensity conditioning (RIC) transplants and its dissemination in Europe. In 2001, there were 19576 HSCT for new patients, 6413 with allogeneic HSCT (33%), 13163 with autologous HSCT (67%) and 3256 additional re- or multiple transplants, 868 (667/201) allogeneic and 2658 (537/2121) autologous, collected from 596 centers in 35 European countries. The main indications in 2001 were leukemias (32%; 73% of them allogeneic); lymphomas (53%; 92% of them autologous); solid tumors (11%; 93% of them autologous) and non-malignant disorders (4%; 90% of them allogeneic). Compared to 2000, there was a drop in allogeneic HSCT of over 20% for chronic myeloid leukemia and an increase of 2% in autologous HSCT. A total of 1759 or 27% of allogeneic transplants were reported as RIC HSCT. These have risen in number in 3 years from <1% in 1998. There are wide variations from 0 to 71% RIC HSCT in European countries with no obvious explanation. These data document the current status of blood and marrow transplantation in Europe and indicate a marked change towards RIC HSCT in allogeneic transplantation.

Bone Marrow Transplantation↗
PubMed2001

CD34+-selected autologous peripheral blood stem cell transplantation conditioned with total body irradiation for malignant lymphoma: increased risk of infectious complications.

Although high-dose chemotherapy with autologous peripheral blood stem cell transplantation (autoPBSCT) has been shown or confirmed to be an effective treatment for high-risk and relapsed non-Hodgkin's lymphoma (NHL), relapse after autoPBSCT remains a serious problem. In a clinical trial to overcome relapse, we adopted a treatment plan in which PBSCs purified in vitro to CD34+ cells to deplete tumor cells (CD34+ autoPBSCT), total body irradiation (TBI) of 1200 cGy, and melphalan, 180 mg/m2, were used as a preconditioning regimen. Eighteen patients with relapsed or high-risk NHL participated in the study. This study compared the incidence of complications following CD34+ autoPBSCT preconditioned with the TBI regimen (n = 10): the TBI group; CD34+ autoPBSCT with the non-TBI regimen (n = 8): the non-TBI group; and unselected autoPBSCT with the non-TBI regimen (n = 19): the unselected autoPBSCT control group. After day 30 posttransplantation, 6 of 10 patients treated with the TBI regimen developed 11 infectious complications in total, compared with only 1 of 8 patients treated with the non-TBI regimen and 4 of 19 patients given unselected autoPBSCT. Two fatal complications occurred in the TBI group, but none occurred in the other 2 groups. The CD4+ lymphocyte count at 1 month posttransplantation was significantly lower in the TBI group than in the unselected autoPBSCT group. These findings suggest that the addition of TBI to the preconditioning regimen for CD34+ autoPBSCT is associated with an increased incidence of severe infectious complications after transplantation.

Adult↗
PubMed2001

Modulation of platelet aggregation in baboons: implications for mixed chimerism in xenotransplantation. I. The roles of individual components of a transplantation conditioning regimen and of pig peripheral blood progenitor cells.

BACKGROUND: The induction of tolerance to pig antigens in primates may facilitate the development of successful clinical xenotransplantation protocols. The infusion of mobilized porcine peripheral blood leukocytes (PBPCs, comprised of approximately 2% peripheral blood progenitor cells) into splenectomized preconditioned baboons, intended to induce mixed hematopoietic cell chimerism, however, results in a severe thrombotic microangiopathy (TM) that includes pronounced thrombocytopenia. Because the mechanisms responsible for this phenomenon are unclear, we have explored the effects of individual components of the conditioning regimen, of therapeutic adjuncts, and of PBPCs on platelet aggregation. METHODS: Groups of splenectomized baboons (n = at least 2 in each group) were treated with single components of the conditioning regimen--whole body irradiation (WBI), antithymocyte globulin (ATG), extracorporeal immunoadsorption (EI), mycophenolate mofetil (MMF), anti-CD40L monoclonal antibody (mAb), cobra venom factor (CVF), pig hematopoietic growth factors (interleukin-3 (pIL3) and stem cell factor (pSCF))--or with potential adjuncts, prostacyclin (PGI2), heparin, methylprednisolone, and eptifibatide (a GPIIb/IIIa antagonist). Blood samples were collected and platelet-rich plasma (PRP) was prepared. Using light transmission aggregometry, the extent of aggregation induced by platelet agonists (thrombin, adenosine diphosphate (ADP), collagen, ristocetin, and arachidonic acid) was determined in vitro. PRP was also prepared from untreated baboons, PBPCs were added, and platelet aggregation was measured in the absence of exogenous platelet agonists. RESULTS: WBI, ATG, MMF, anti-CD40L mAb, CVF, pIL3, pSCF, and PGI2 had no effect on purified baboon platelet aggregation profiles in vitro. Eptifibatide markedly inhibited platelet aggregation induced by all standard agonists. EI or heparin inhibited thrombin-induced platelet aggregation, and methylprednisolone inhibited ADP-induced aggregation to some extent. In vitro addition of PBPCs to PRP stimulated platelet aggregation in the absence of any agonists. Prior treatment of baboons with eptifibatide, however, inhibited this effect by 70% to 80%. CONCLUSIONS: Aggregation of baboon platelets and TM is directly induced by PBPCs, but not by individual components of the conditioning regimen. GPIIb/IIIa antagonists, such as eptifibatide, interfere directly with xenogeneic PBPC-platelet interactions and may further ameliorate TM in the pig-to-primate model.

Animals↗
PubMed2000

Is there a best transplant conditioning regimen for acute myeloid leukemia?

The outcome of marrow transplantation is largely determined by the effectiveness of the transplant preparative regimen. Nonetheless, there have been startlingly few randomized trials attempting to identify optimal regimens for specific conditions and, at present, no single approach has emerged as superior for the treatment of acute myeloid leukemia (AML) in the few trials that have been performed. Newer approaches that appear encouraging in phase II studies include substituting etoposide for cyclophosphamide, adding thiotepa to the traditional cyclophosphamide plus total body irradiation combination in the setting of T cell depletion, and using antibody-based targeted radiotherapy as part of the transplant regimen. The ability to obtain allogeneic engraftment with nonablative regimens may open the door to additional innovative approaches, combining very specific antileukemia therapy with relatively nontoxic measures to ensure engraftment.

Acute Disease↗
PubMed1996

Interstitial pneumonitis following autologous bone-marrow transplantation conditioned with cyclophosphamide and total-body irradiation.

PURPOSE: To assess the influence of different total-body irradiation (TBI) regimens on interstitial pneumonitis (IP), we retrospectively analyzed our clinical data concerning an homogeneous group of patients conditioned with cyclophosphamide (CY) alone and single-dose or fractionated TBI before autologous bone-marrow transplantation (ABMT). METHODS AND MATERIALS: One hundred eighty-six patients with acute nonlymphoblastic leukemia (n = 101), acute lymphoblastic leukemia (n = 62), chronic myeloid leukemia (n = 11), non-Hodgkin's lymphoma (n = 10), and multiple myeloma (n = 2) referred to our department between May 13, 1981 and September 16, 1992, underwent TBI before ABMT. The male-to-female ratio was 123:63 (1.95), and mean and median age was 33 +/- 12 (6-63 years) and 35 years, respectively. Cyclophosphamide alone (60 mg/kg/day on each of 2 successive days) was used as conditioning chemotherapy in all patients. Patients were irradiated according to two techniques: either with single-dose (STBI) (n = 124; 10 Gy administered to the midplane at the level of L4, and 8 Gy to the lungs) or with fractionated (FTBI) (n = 62; 12 Gy in 6 fractions over 3 consecutive days to the midplane at the level of L4, and 9 Gy to the lungs) TBI. The mean instantaneous dose rate was 0.057 +/- 0.0246 Gy/min (0.0264-0.1692 Gy/min). It was < or = 0.048 Gy/min in 48 patients (LOW group), > 0.048 and < or = 0.09 Gy/min in 129 patients (MEDIUM group), and > 0.09 Gy/min in 9 patients (HIGH group). The median follow-up period was 5 years (24-120 months). RESULTS: In January 1994, the 5-year overall (including all causes of death) and disease-free survival (DFS) rates were 50 and 48%, respectively. The 5-year DFS was 47.9% in the STBI group, and 47.8% in the FTBI group (p = 0.77). It was 44% in the HIGH group, 53% in the MEDIUM group, and 34% in the LOW group (LOW vs. MEDIUM, p = 0.009). The 5-year IP incidence was 17% in all patients, 16% in the STBI group and 18% in the FTBI group (p = 0.37), but it was significantly higher in patients receiving high instantaneous dose rate TBI (56% in the HIGH, 13% in the MEDIUM, 20% in the LOW groups; HIGH vs. MEDIUM, p = 0.002). However, sex (p = 0.37), age (18% for > 20 vs. 10% for < or = 20 years, p = 0.37), and body weight (> 60 kg vs. < or = 60 kg, p = 0.09) did not influence the IP incidence in univariate analyses. Multivariate analysis (Cox model) revealed that the instantaneous dose rate (p = 0.05), and the age (p = 0.04) were the two independent factors influencing the incidence of IP. CONCLUSION: This retrospective study including only the patients transplanted with ABMT conditioned with CY alone and STBI or FTBI concluded that instantaneous dose rate and age significantly influenced the incidence of IP, whereas sex, body weight, and fractionation did not.

Adolescent↗