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PubMed1993

Impairment of bronchial mucociliary clearance in long-term survivors of heart/lung and double-lung transplantation. The Paris-Sud Lung Transplant Group.

The study objective was to investigate bronchial mucociliary clearance after heart/lung and double lung transplantation. Bronchial mucociliary clearance was measured using a noninvasive radioaerosol technique: 99mTc-labeled albumin was aerosolized using a spinning-top generator (mass median aerodynamic diameter, 7.5 mu; geometric standard deviation, 1.5 mu). Radioactivity counts were acquired during 60 min with a gamma camera. A region of interest was drawn over the right lung delineated by a 133Xe lung ventilation image. Bronchial mucociliary clearance was assessed as the percentage of decrease in radioactivity per hour calculated on time-activity curves fitted by a monoexponential model. To exclude patients with acute lung rejection, opportunistic lung infection, and obliterative bronchiolitis, all patients with transplants underwent pulmonary function tests and bronchoscopic examination before clearance measurement. Eight heart/lung and five double-lung nonsmoking transplant patients with normal lung histology were studied 19.3 +/- 4.0 mo after surgery and compared to nine normal nonsmokers. A similar proximal deposition of the aerosol was obtained in patients with transplants and normal subjects; skew values of distribution histograms of aerosol radioactivity counts were 2.1 +/- 0.2 and 1.8 +/- 0.1, respectively, and the ratios between central and peripheral 99mTc radioactivity counts were 2.4 +/- 0.1 and 2.3 +/- 0.2, respectively. No significant difference was observed in bronchial clearance values between patients with heart/lung and double-lung transplants (26.4 +/- 3.0 percent/h vs 35.9 +/- 3.5 percent/h). Conversely, bronchial clearance was significantly lower in transplant recipients (30.0 +/- 2.5 percent/h) than in normal controls (58.7 +/- 6.2 percent/h; p < 0.001). This decreased bronchial clearance can be expected to increase the risk of lung infection in long-term survivors of heart/lung and double-lung transplantation.

Adult↗
PubMed1978

Syngeneic transplantation of fetal rat pancreas. II. Effect of insulin treatment on the growth and differentiation of pancreatic implants fifteen days after transplantation.

Eight 18-days-postcoitum fetal pancreases were transplanted to isogenic alloxan-diabetic male rats. Some recipients were treated with insulin for seven days immediately after transplantation. Eight animals in both the insulin-treated group and control group were killed 15days after transplantation for morphologic and hormonal studies of the transplanted tissue. Using the morphometric technique of linear scanning, the insulin, glucagon, and somatostatin immunocytochemically positive, cell masses of the fetal pancreatic implants were quantitated. The beta cell mass of the implants from the control animals increased roughly eightfold from the time of transplant; insulin treatment resulted in a further two- to threefold increase. The insulin content of the implants increased more than did the beta cell mass, resulting in the fivefold increase in insulin per beta cell. The alpha cell and delta cell masses did not change during the transplant site, the mass of functional beta cells, and the cell-to-cell content of the implanted tissue. These results are discussed in relation to previous quantitative studies of pancreatic islet cell growth. The relationships of the transplant site, the mass of functional beta cell, and the cell-to-cell interaction within the islet to the maintenance of glucose homeostasis are also discussed.

Animals↗
PubMed1988

Pancreatic transplantation as treatment for IDDM. Proposed candidate criteria before end-stage diabetic nephropathy. The University of Michigan Pancreas Transplant Evaluation Committee.

Most candidates for pancreatic transplantation have end-stage diabetic nephropathy (ESDN) and receive a pancreas transplant either sequential to or simultaneous with a renal transplant. Because ESDN is often associated with severe irreversible neurovascular complications, the selection of these candidates may defeat the intent of pancreatic transplantation, i.e., the reversal, stabilization, or retardation of neurovascular complications. Also, advanced neurovascular complications in these candidates may result in serious morbidity and mortality after pancreatic transplantation. Our multidisciplinary Pancreas Transplant Evaluation Committee has developed tentative candidate criteria for insulin-dependent diabetic patients before ESDN. With the proposed criteria, candidates are selected who have predictors of future morbidity and mortality but who do not yet demonstrate irreversible neurovascular complications and an inexorable general course of deterioration. As pancreatic transplantation becomes more successful, candidate criteria must be continually reassessed to better identify those who may obtain maximal benefit.

Adult↗
PubMed2004

Megadose CD34+ hemopoietic stem cell transplantation for patients with high risk acute myeloid leukemia who have no HLA matched donor--a pilot study of a full haplotype mismatch transplantation.

BACKGROUND: Haploidentical transplantation has become a popular modality of treatment for acute myeloid leukemia (AML) patients lacking donors with matching HLA. We attempted to assess the success rate and ramifications of full haplotype mismatch transplantation. METHODS: Four patients received stem cell transplantation from their full haplotype mismatched family donors. The conditioning regimen included total-body irradiation, intravenous busulfan, antithymocyte globulin, and fludarabine. Megadose CD34+ stem cell transplants were performed, in a dosage range between 10.9 x 10(6)/kg and 20.6 x10(6)/kg. Neither GvHD prophylaxis nor post-transplant G-CSF were administered. We monitored patients' bone marrow cellularity and peripheral blood chimerism using real-time PCR. RESULTS: All patients evidenced stable engraftment. The most frequent side effect was severe mucositis, but all patients recovered successfully, without early death. No patients exhibited acute GvHD. Two refractory patients relapsed soon after transplantation. The other 2 patients have remained in good clinical condition, with a follow-up duration of 1-4 months. CONCLUSION: Using a newly-developed conditioning regimen, we were able to circumvent GvHD and graft failure, which are the main limitations associated with full haplotype mismatch transplantation. According to our analysis of the relevant literature, it appears that this is the first report of such a conditioning regimen.

Adolescent↗
PubMed1997

Health and functional status of long-term survivors of bone marrow transplantation. EBMT Working Party on Late Effects and EULEP Study Group on Late Effects. European Group for Blood and Marrow Transplantation.

BACKGROUND: Although many patients now survive the short-term complications of bone marrow transplantation for life-threatening hematologic disease, information on the health and activity of long-term survivors is sparse. OBJECTIVE: To evaluate the morbidity and mortality of patients surviving more than 5 years after allogeneic bone marrow transplantation. DESIGN: Retrospective, multicenter study. PATIENTS: 798 recipients of bone marrow transplants (477 adults, 321 children) from 43 European centers. Patients had received transplants before December 1985 and had survived at least 5 years. Patients had received allogeneic or syngeneic bone marrow for leukemia, lymphoma, inborn diseases of the hematopoietic and immune systems, and severe aplastic anemia. MEASUREMENTS: Survival, clinical performance according to Karnofsky score (in increments of 10%), and social reintegration were assessed as outcomes. Patient age and sex, primary disease and status at transplantation, histocompatibility of the donor, conditioning regimen, type of prophylaxis of graft-versus-host disease, and acute and chronic graft-versus-host disease were evaluated as variables. RESULTS: For the 55 5-year survivors, actuarial mortality was 8% at 10 years and 14% at 15 years. The leading causes of death were disease recurrence (21 patients), chronic graft-versus-host disease with complicating infections and lung disease (11 patients), secondary cancer (8 patients), and the acquired immunodeficiency syndrome (AIDS) (5 patients). When patients with recurrent disease were excluded, late death was associated with chronic graft-versus-host disease (P < 0.001), occurrence of secondary cancer (P < 0.001), male sex of the patient (P = 0.05), and female sex of the donor (P = 0.002). Clinical performance was normal (Karnofsky score, 100%) or minimally reduced (Karnofsky score, 90%) in 93% of patients; 89% of patients resumed full-time work or school. Reduced performance status and incomplete resumption of social activity were associated with chronic graft-versus-host disease, recurrent leukemia, AIDS, secondary cancer, organ dysfunction, and neurologic or psychological problems. Other risk factors for incomplete resumption of social activity were female sex (P = 0.002) and older age at transplantation (P = 0.001). CONCLUSIONS: More than 5 years after bone marrow transplantation, most patients were in good health (93%) and had returned to full-time work or school (89%). Recurrence of the primary disease, secondary cancer, and chronic graft-versus-host disease and its sequelae remain problems for some patients.

Adult↗
PubMed2000

High-dose chemotherapy and autologous stem-cell transplantation for ovarian cancer: an autologous blood and marrow transplant registry report.

BACKGROUND: Autologous transplantation is increasingly used to treat epithelial ovarian cancer. However, it is not clear which patients may benefit. OBJECTIVE: To determine overall and progression-free survival and factors associated with favorable outcome after autotransplantation for ovarian cancer. DESIGN: Observational cohort study. SETTING: 57 centers reporting to the Autologous Blood and Marrow Transplant Registry (ABMTR). PATIENTS: 421 women who received transplants between 1989 and 1996. INTERVENTIONS: High-dose chemotherapy using diverse regimens with hematopoietic stem-cell rescue. MEASUREMENTS: Primary outcomes were progression-free survival and overall survival. Multivariate analyses using Cox proportional hazards regression considered the following factors: age, Karnofsky performance score, initial stage, histologic characteristics, previous therapy, remission status, extent of disease, graft source, transplant regimen, and year of transplantation. RESULTS: Most patients had extensive previous chemotherapy. Forty-one percent had platinum-resistant tumors, and 38% had tumors at least 1 cm in diameter. Only 34 patients (8%) received transplants as part of initial therapy. The probability of death within 100 days was 11% (95% CI, 8% to 14%). Two-year progression-free survival was 12% (CI, 9% to 16%), and 2-year overall survival was 35% (CI, 30% to 41%). Younger age, Karnofsky performance score of at least 90%, non-clear-cell disease, remission at transplantation, and platinum sensitivity were associated with better outcomes. Progression-free and overall survival were 22% (CI, 12% to 33%) and 55% (CI, 42% to 66%), respectively, for women with a high Karnofsky performance score and non-clear-cell, platinum-sensitive tumors. CONCLUSIONS: Some subgroups of patients with ovarian cancer seem to have good outcomes after autotransplantation, although several biases may have affected these observations. Phase III trials are needed to compare such outcomes with outcomes of conventional chemotherapy.

Age Factors↗
PubMed1998

[Recent advances in living-related liver transplantation and in liver transplantation for patients with liver cirrhosis and hepatocellular carcinoma].

Living-related-donor liver transplantation has been performed in more than 700 patients in Japan. This article deals with recent advances in living-related-donor liver transplantation and the strategy for liver transplantation for patients with liver cirrhosis and hepatocellular carcinoma. The indication for living-related-donor liver transplantation has gradually widened to include urgent cases as well as adult patients. In living-related-donor liver transplantation for adults, limitation of graft volume has led to the use of left hepatic lobe grafts including the caudate lobe, or right hepatic lobe grafts. The results of liver transplantation for patients with hepatitis B cirrhosis, hepatitis C cirrhosis and hepatocellular carcinoma have improved, due mainly to advances in patient selection and perioperative medical Care. The widespread use of liver transplants from both living and cadaveric donors is necessary in Japan, where adult patients with viral hepatitis and hepatocellular carcinoma account for the majority of patients with end-stage liver disease.

Adult↗
PubMed2003

Immune mechanisms contributing to spontaneous acceptance of liver transplants in rodents and their potential for clinical transplantation.

The fate of organ transplants between unrelated individuals of the same species is almost always rejection unless the recipient receives immunosuppressive drugs. Liver transplants are an exception, as in a number of animal models they are often accepted without requiring any treatment. Several mechanisms have been proposed for liver transplant acceptance, including: the vascular structure of the liver, which allows interaction between naïve T cells and liver parenchymal cells; the atypical leukocyte populations of the liver-particularly immature dendritic cells; neutralization of rejection by donor soluble MHC antigen; establishment of microchimerism by donor hematopoietic stem cells; and death by "neglect" of recipient T cells in response to inappropriate activation by donor liver leukocytes. Although all these mechanisms may contribute to liver acceptance to some degree, an important finding is that liver acceptance appears to be mainly due to donor leukocytes transplanted with the liver. In combination with the observation of rapid T cell activation followed by their death after liver transplantation, these findings have identified a prominent role for donor leukocyte-induced deletion of liver-reactive T cells. These findings suggest novel ways to explore improved treatment for transplant patients, including the administration of donor leukocytes at the time of transplantation and the delay of some components of immunosuppressive-drug induction therapy.

Animals↗
PubMed2006

Secondary kidney transplantation in a patient 16 years after simultaneous pancreas and kidney transplantation--a case report.

Simultaneous pancreas and kidney transplantation (spktx) is currently the most effective method of treatment of type 1 diabetes complicated by renal insufficiency. The first successful spktx in Poland was performed in the Department of General, Vascular and Transplant Surgery of the Warsaw Medical University on the 4th of February 1988. Since then 70 spktx were performed in our Department. We present a 44-year-old patient who after 16 years of good function of both transplanted organs presented with elevated creatinine levels (>4 mg/dl) as a result of chronic rejection of the kidney allograft. On the 22nd of January 2005 the patient underwent secondary kidney transplantation. The immunosuppresive protocol consisted of MMF, CsA and steroids. Humanized anti-lL-2 monoclonal antibodies (daclizumab) were used as pre-procedure induction. Using a mid-line incision the new kidney graft was anastomosed to the recipient left external iliac vessels. The ureter was anastomosed with the bladder without anti reflux procedures and the allograft was placed in the retroperitoneum below the previously transplanted kidney. Graftectomy of the first kidney allograft was not performed. After surgery, normal creatinine parameters were restored to a level of 1, 1 mg/dl and an increase in urine output was noted from 1 to 4 liters per day. Oral intake of foods was resumed on the 4th postoperative day and no early complications were observed. 12 months observation period confirmed stabile function of both transplanted organs. Secondary kidney transplantation in patients after spktx is technically possible and may be considered an option in patients with diminishing function of the first kidney allograft.

Adult↗
PubMed1990

Graft-versus-leukaemia activity associated with CMV-seropositive donor, post-transplant CMV infection, young donor age and chronic graft-versus-host disease in bone marrow allograft recipients. The Nordic Bone Marrow Transplantation Group.

Risk factors for post-transplant relapse were analysed retrospectively in 163 patients treated with allogenic bone marrow transplantation for acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL) or lymphoblastic lymphoma in first to fourth remission or during relapse. Multifactorial analysis was performed according to Cox with fixed pretransplant covariates and post-transplant cytomegalovirus (CMV) infection and graft-versus-host (GVHD) as time-dependent covariates. Advanced stage of leukemia at the time of transplantation was an important risk factor for subsequent relapse. Furthermore, the study confirmed a graft-versus-leukaemia (GVL) activity associated with chronic GVHD, including de novo chronic GVHD (intensity factor 0.08, p = 0.004). In a model excluding chronic GVHD, female donor-to-male recipient (a risk factor for GVHD), was associated with decreased post-transplant relapse risk (intensity factor 0.3, p = 0.008), suggesting that an allo-reaction against a minor transplantation antigen (Hy) may mediate antileukaemic activity. A decrease of the relapse risk by a factor 0.18 was observed in recipients with AML as well as ALL when the donor was CMV seropositive (p = 0.0002). This effect was restricted to patients who had laboratory evidence of post-transplant CMV infection. When CMV infection occurred and donor was seropositive the relapse risk was reduced by a factor 0.035. The effect was not mediated through an increased occurrence of grade 2-4 acute or chronic GVHD and could not be explained by a statistical bias due to censoring of patients who died in remission. Rather, donor CMV immunity was associated with GVHD independent GVL activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1978

Hepatocellular transplantation --morphological study on hepatocytes transplanted into rat spleen--.

Hepatocellular transplantation into the spleen was investigated as a new attempt in utilizing isolated hepatocytes to compensate for impaired liver function. Present study was undertaken to evaluate morphological and histochemical alterations up to 6 weeks following transplantation in hepatocytes transplanted into the splenic parenchyma. Light microscopic studies revealed viable hepatocellular islets in the splenic parenchyma up to 6 weeks, although minimal cytoplasmic changes were observed. Electron microscopic studies demonstrated moderate changes in organelles, which developed gradually as the time after transplantation proceeded. Distortion and fragmentation of the membranes around the cytoplasm and organelles were not recognized. Moreover, newly formed bile canaliculi and tight junctions which indicate reconstruction of hepatic plates were observed between adjacent cell membranes, and enzyme activities were detected by cytochemical determination of glucose-6-phosphatase in the hepatocytes even 6 weeks after transplantation. The transplanted hepatocytes preserved their characteristic enzyme and fine structures as hepatocytes up to 6 weeks. Our present study based on the persistence of cellular viability suggests that inoculated hepatocytes do maintain their hepatocellular functions after transplantation.

Animals↗
PubMed1986

[Study on heterotransplantation of human malignant urogenital tumors in nude mice: results of transplantation and the characteristics of the transplanted tumors].

Between July, 1981 and June, 1984, 40 malignant urogenital neoplasms were heterotransplanted into nude mice to clarify the biological characteristics of malignancies and screen the effective anticancer drugs against them. The primary tumor take was confirmed in 7 tumors (17.5%), including 4 of 14 renal cell carcinomas (28.6%) and 3 of 13 bladder cancers (23.1%). No primary take was recognized in renal pelvic, ureteral, prostatic and testicular cancers. Three of the 7 tumors (43%) with primary take (7.5% in total) have been serially transplanted for more than a year. These three established tumors were all renal cell carcinomas and were designated as AM-RC-1, AM-RC-6 or AM-RC-11. The take rate of tumor tissues obtained from primary and metastatic lesions was 18.2% (6/33) and 14.3% (1/7), respectively. The duration from tumor inoculation to take was examined in seven transplantable tumors. The shortest was 12 days in renal cell carcinoma, the longest was 36 days in bladder cancer and the average was 24.4 days. The correlation between the time from tumor extraction to inoculation and transplantability was investigated. The take rate was 29.4% within 3 hours, and 18.2% beyond 3 hours. The obvious effect of anti-asialo GM1 antibody on tumor take, which inhibits the natural killer activity of mice or rats selectively, was not demonstrated owing to the small number of cases. The histopathological features of seven original tumors with primary take were examined. All of the 4 renal cell carcinomas were shown to be histologically high grade and advanced. Two of the 3 bladder cancers were poorly differentiated. Therefore, the differentiation or growth rate of the tumor was suggested to be closely correlated with transplantability. The three strains of renal cell carcinomas transplanted serially for a long-term period, AM-RC-1, AM-RC-6 and AM-RC-11 disclosed a constant growth after the 7th, 9th and 10th inoculation respectively. The renal cell carcinomas serially transplantable to nude mice maintained the basic histologic findings of the original tumor even after long-term serial transplantation.

Animals↗
PubMed1981

[Does the number of treated rejection episodes in the first transplantation influence the survival of the patient with kidney re-transplantation?].

The records of 77 patients who received a second kidney transplant at the Surgery Department of Addenbrooke's Hospital, Cambridge, have been re-examined to assess the influence of the number of rejection episodes treated during the first transplant on the survival of the second. 61 of the 77 retransplanted patients lost their first kidney for immunological reasons. 6 did not present any treated episode of rejection, 45 one episode only and in 10 greater than 1 episode was treated during the first transplant. P less than 0.05 from 1 to 5 years as regards survival of the second transplants in patients whose first kidney did not present treated rejection episodes by comparison with those presenting 1 or greater than 1. No significant difference was noted in patient survival in the various groups under examination. On the basis of the results obtained, it is concluded that, in addition to the cause of failure and duration of the first transplant, the number of treated rejection episodes during the first transplant should be considered as a critical parameter for better selection of the most suitable candidates for receiving a second transplant.

Graft Rejection↗
PubMed1995

Comparison of autologous bone marrow transplantation and peripheral blood stem cell transplantation after first remission induction treatment in multiple myeloma.

The optimal source of stem cells is a controversial issue in the field of autologous stem cell transplantation. A comparison of autologous bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) after first remission induction treatment in multiple myeloma was made by a retrospective analysis of 132 transplants performed in 18 French Centers from 1984 to 1991 (81 autologous BMT, 51 PBSCT). The two groups differed in the median age (PBSCT 49 years; autologous BMT 55 years, P < 0.001), the duration of chemotherapy prior to transplantation, the interval between stem cell collection and transplantation, and in the conditioning regimen (more total body irradiation and higher doses of irradiation in the PBSCT group). The median time to neutrophil recovery was shorter in the PBSCT group (13 days vs. 20 days, P < 0.001), but the median time to platelet recovery did not differ significantly between PBSCT (26 days) and autologous BMT (22 days). There was no significant difference between the two groups regarding overall response rate (PBSCT 84%, autologous BMT 82%) and complete remission rate (PBSCT 37%, autologous BMT 36%). The actuarial relapse-free survival, time to treatment failure and overall survival were not significantly different. A case controlled study comparing 43 autologous BMT and 43 PBSCT matched for age and status at the time of transplantation did not show any advantage of PBSCT over autologous BMT in terms of immediate outcome, relapse-free survival, overall survival and time to treatment failure. Thus, in this retrospective analysis, the only significant benefit for PBSCT was reduced time to neutrophil recovery.

Adult↗
PubMed1995

Pancreas transplantation in the United States as reported to the United Network for Organ Sharing (UNOS) and analyzed by the International Pancreas Transplant Registry.

As of 1995, more than 7,500 pancreas transplants had been reported to the International Pancreas Transplant Registry. More than 5,300 were performed in the United States, including more than 4,000 since the inception of the UNOS Registry in October, 1987. The bladder drainage (BD) technique has been the most widely used duct management technique since 1987 with 93% of all cases. In the overall analysis of US BID cadaveric pancreas transplants reported to the registry, patient survival and pancreas functional graft survival rates were 91% and 75% respectively, at one year, 88% and 72% at 2 years, and 85% and 67% at 3 years. When the 1987-95 US data for primary BID cases was analyzed according to the three major recipient categories [simultaneous pancreas/kidney transplants (SPK) (n=3,539); pancreas after kidney transplants (PAK) (n=238); and pancreas transplants alone (PTA) (n=175)], patient survival rates were no different (91%, 92% and 91% at one year, respectively), but pancreas graft survival rates were significantly higher in the SPK than in the PAK and PTA categories (78%, 56%, and 55%, at one year, respectively). In the SPK group, kidney graft survival rates at one year were 86%. An improvement of the graft survival could be shown over the analyzed time period for all categories. Outcomes were also compared according to whether induction immunotherapy in recipients included ALG/ATG/ATS, OKT3 or neither. In the primary SPK category, patients who received OKT3 (n=1,416) showed the best outcome with one-year graft survival rates of 83% followed by ALG/ATG/ATS (n=1,559) with 78%. Patients that received neither (n=410) had a significantly lower graft survival rate. In the primary PAK category, the use of OKT3 (n=49) was associated with lower graft survival rates than when ALG/ATG/ATS (n=143) or neither (n=40) were given, 51%, 66%, and 55% at one-year, respectively. In the PTA category, the use of ALG/ATG/ATS (n=93) was associated with significantly higher graft survival rates than when OKT3 (n=62) or neither (n=9) were used, being 63%, 58%, and none, respectively, at one-year. No negative impact of longer preservation time could be found in the univariate analysis. The effect of HLA-A, B and DR mismatching on outcome for primary US cases was also determined. Again the results differed according to recipient category. For SPK cases, there was only a beneficial effect of a perfect 6 antigen match (n=21) compared to 1 and 2-6 mismatches being 85%, 73% and 78% at one-year. In the primary PAK category, graft survival rates were significantly higher in those mismatched for 0 (n=6) and one (n=25) than for 2-6 (n=195) HLA antigens, being 100%, 76% and 58% at one year. In the primary PTA category there were no zero mismatch, technically successful cases. One-year graft survival rates were 70% (n=10) for the category with one mismatch and 55% (n=157) in the 2-6 antigen mismatch group. Cox multivariate analyses of the US data base showed that, overall, recipient category was the most significant factor (relative risk for graft loss being significantly lower for SPK than for PAK and PTA cases). Other variables also had an impact on results depending on the recipient category. Recipient age has an impact on patient survival as well as graft survival. It was most influential in the SPK and PAK category, but an effect was not seen in the PTA category. In both the PAK and PTA categories, minimizing HLA mismatches was associated with a significantly lower risk for graft loss. In the SPK and PTA category, anti-T-cell therapy significantly lowered the risk of graft loss. In the PAK and SPK category the transplant outcome improved significantly over the analyzed time period. Patient survival also improved overtime.

Adult↗
PubMed1996

Pancreas transplantation in the United States (US) and non-US as reported to the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry (IPTR).

As of November 1996, more than 8,800 pancreas transplants had been reported to the IPTR. There were 6,500 performed in the US, including more than 5,800 since the inception of the UNOS Registry in October 1987, and more than 1,000 in 1995. In Europe, more than 2,100 cases were reported to the IPTR, while fewer than 200 have been done in other locations. This report analyzes cases reported since 1987. In the US, BD has been used for the majority (92%). However, ED has recently increased in popularity, and for 1995, 15% of US cases were done by this method. In the SPK category results for 1994-1996 BD (n = 1,510) and ED (n = 221) were comparable, with one-year GSRs of 62% and 77%, respectively. When the 1987-1996 US data for BD cases were analyzed according to the 3 major recipient categories, SPK transplants (n = 3,989); PAK transplants (n = 375) and PAK transplants (n = 229), patient survival rates were no different (92%, 92% and 91%, respectively at one year). But one-year pancreas GSRs were significantly higher (p = 0.0001) in the SPK than in the PAK and PTA categories (79%, 60% and 57%, respectively). In the SPK group, the one-year kidney GSR was 88%. Retransplants and primary transplants fared similarly in the SPK category, with one-year GSRs of 79% (n = 3,947) and 77% (n = 42), respectively. But in the PAK category, primary transplants did better, 62% (n = 275) versus 47% (n = 100) functioning at one year. The PTA category outcome was also better for primary than retransplants, with GSRs of 57% (n = 191) and 51% (n = 38) at one year. An improvement in GSRs could be shown over the analyzed time period for all categories; for 1994-1996 cases in the SPK (n = 1,516), PAK (n = 141) and PTA (n = 64) categories, one-year pancreas GSRs were 81%, 71% and 64%, respectively (p = 0.004). The kidney GSR for 1994-96 SPK cases was 88% at one year. Preservation had minimal impact on outcome. In the SPK category, one-year GSRs for pancreases stored less than 12 (n = 1,400), 12-24 (n = 2,256) and more than 24 (n = 195) hours were 78%, 80% and 76%, respectively. The impact of FK506 immunosuppression on pancreas transplant survival was also analyzed for 1994-1996 cases. The results were comparable to those with CsA. For SPK cases, one-year GSRs were 82% with CsA (n = 1,247) and 81% with FK506 (n = 257). The one-year immunological loss rates were 2% and 3%, respectively. For PAK cases, one-year GSRs were 84% for FK506- (n = 42) and 65% for CsA- (n = 97) treated recipients (p < 0.04), and the immunological loss rates at one year were 11% and 7%, respectively. In PTA cases, the one-year GSRs were 66% with CsA (n = 37) and 64% with FK506 (n = 26) with immunological loss rates of 9% and 0%, respectively (p > 0.2). Outcomes were also compared according to whether recipients underwent induction immunotherapy with ALG/ATG/ATS, OKT3, or neither. In the SPK category, GSRs were 81% with OKT3 (n = 1,600), 75% with ALG/ATG/ATS (n = 1,715) and 75% with neither (n = 45) (p < 0.001). In the PAK category, the use of OKT3 (n = 81) was associated with lower graft survival rates than when ALG/ATG/ATS (n = 220) or neither (n = 49) was given (43%, 62%, and 54% at one year, respectively). In the PTA category the use of ALG/ ATG/ATS (n = 132) or OKT3 (n = 76) was associated with significantly higher graft survival (59% and 57%, respectively) than when neither (n = 13) was used (26% at one year). The effect of HLA-A,-B and -DR mismatching on outcome for US cases was determined on both overall graft survival rates and on risks for immunological loss. For SPK cases, the pancreas GSRs were significantly higher (p < 0.04) with zero-mismatched grafts (n = 30) than with higher degrees of mismatches (85% at one year versus 69%, 76% and 79% with one [n = 67], 2-3 [n = 925] and 4-6 [n = 2,836] mismatches, respectively). For PAK cases GSRs were progressively higher with decreasing numbers of mismatches (100%, 75%, 58% and 53% at one year with zero [n = 7], one [n = 35], 2-3 [

Adult↗
PubMed1999

Heterotopic sternum transplant in rats: A new model of a vascularized bone marrow transplantation.

We introduced the heterotopic vascularized sternum transplant as a more simple and pure alternative to allogeneic hind limb transplantation for the study of bone marrow transplantation. We report the clinical and histopathological manifestations after transplantation of syngeneic and allogeneic sternal grafts with and without immunosuppression with FK-506. Syngeneic grafts maintained normal histology, whereas allografts showed rejection, which was prevented by FK-506. FK-506-treated allografts developed chimerism that was present throughout the observation period. Transplantation of the sternum may be a valuable model to study vascularized bone marrow transplantation and its effects on repopulation of bone marrow of the host, chimerism, and tolerance.

Animals↗
PubMed2006

Long-term outcomes of myeloablation and autologous transplantation of relapsed acute myeloid leukemia in second remission: a British Society of Blood and Marrow Transplantation registry study.

Relapsed acute myeloid leukemia (AML) in adults has a poor prognosis if treated with chemotherapy alone. Case series have previously supported the role of myeloablation and autologous transplantation as a potentially curative treatment. This study aimed to use the large numbers and extended follow-up data in the British Society of Blood and Marrow Transplantation (BSBMT) registry database to establish long-term outcomes and relate these to biological and procedural factors. The BSBMT registry database was used to retrospectively identify 152 adult patients (age, 16-69 years) with AML in second remission treated with autologous transplantation in 1982-2003. Cytogenetic data were available for 68% of the patients; of these, at diagnosis, 42% had good risk features, 57% had standard risk features, and 1% had poor risk features. Conditioning regimens varied; autologous rescue was provided with bone marrow (BM) (71%), peripheral blood stem cells (PBSCs) (18%), or both (11%), which were harvested during first complete remission (CR1) and/or second CR (CR2). Median follow-up was 84 months (range, 2-200 months). At 10 years, actuarial overall survival (OS) was 32%, progression-free survival (PFS) was 28%, and relapse rate (RR) was 57%. The 100-day nonrelapse mortality (NRM) was 7%, rising to 11% at 1 year and to 14% at 10 years. OS was significantly related to M3 subtype (5-year OS, 66%; P = .005), patient age at diagnosis (P = .005) and transplantation (P = .026), and length of CR1, with greatest significance if the patient was dichotomized at CR1 duration of < 8 months or > or = 8 months (P = .0001). There was no difference in OS between regimens containing total body irradiation (TBI) and chemotherapy alone (P = .7). In relation to the nature of autologous graft material, there was improved OS (P = .025) and PFS (P = .009) with the use of cells harvested entirely in CR1 compared with cells harvested in CR2 or in both CR1 and CR2. Engraftment times were significantly shortened with the use of PBSCs alone or in combination with BM compared with BM alone (P = .0001), but there was no significant long-term impact on OS, PFS, RR, or NRM. This study provides long-term follow-up data in one of the largest series of patients with standard-risk and good-risk AML in CR2 treated with autologous transplantation and supports earlier observations that long-term survival is achievable in about 1/3 of patients overall and in about 2/3 of patients with M3 with a relatively low NRM. Outcomes are better in patients with CR1 > or = 8 months by use of grafts obtained entirely in CR1 and use of PBSCs. TBI conditioning did not confer an advantage. Randomized studies against unrelated donor transplantation are warranted.

Acute Disease↗