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PubMed1990

Cardiac innervation after double lung transplantation. Toronto Lung Transplant Group.

Double lung transplantation has been successfully introduced for patients with end-stage pulmonary disease and preserved cardiac function. An advantage of this operation compared with heart-lung transplantation is retention of the recipient's heart. The operative dissection, however, may lead to interruption of sympathetic and parasympathetic pathways to the heart and consequent denervation of the native heart. The cardiac innervation of seven double lung transplant recipients was investigated by the heart rate response to carotid sinus massage, the Valsalva maneuver, intravenous injection of atropine, and exercise. Five single lung and two heart-lung transplant recipients were studied for comparison. Of the seven double lung transplant recipients, three had abnormal responses to carotid sinus massage, six to the strain phase of the Valsalva maneuver, and five to the release phase of the Valsalva maneuver. Three of six double lung transplant recipients tested had no response to intravenous injection of atropine, and five of seven patients had an abnormal recovery of heart rate after maximal exercise. No patient had a normal response to all interventions, and three patients had responses compatible with complete cardiac denervation. It is concluded that cardiac denervation may occur after double lung transplantation, most likely caused by surgical interruption of sympathetic and parasympathetic pathways during dissection of the recipient's trachea.

Adult↗
PubMed1990

Allogeneic bone marrow transplantation for leukemia in Europe: regional differences. Report from the Leukemia Working party of the European Group for Bone Marrow Transplantation.

The results of 1904 allogeneic HLA identical sibling donor bone marrow transplants performed in 52 European centers between 1979 and 1986 and reported to the EBMT leukemia registry were analysed by geographical location of the transplant. Patients were grouped into six regions: United Kingdom, Nordic Group, Benelux, France, Central Europe and Southern Europe. There were significant differences between these regions with respect to patient population and outcome. The relative proportion of the three major disease categories, stage and subtype of the diseases, graft-versus-host disease prevention methods, donor recipient sex combinations, age of the patient, year of the transplant and the time intervals from diagnosis to transplant, from diagnosis to first complete remission for acute leukemia and the time from first complete remission to the transplant varied from region to region. The analysis of outcome parameters showed a significant difference in relapse incidence from region to region. This influence of region was confirmed in a multivariate analysis and was independent of the other factors known to affect outcome. Leukemia-free survival and transplant-related mortality were not different. The reasons for these differences could not be explained by the data in the registry. We conclude that regional factors must be considered when bone marrow transplant data are compared and we postulate that pretransplant factors probably affect outcome more than was previously realized.

Adolescent↗
PubMed1994

Liver transplantation in the United States: results from the National Pitt-UNOS Liver Transplant Registry. United Network for Organ Sharing.

The growth in liver transplantations recorded by the Pitt-UNOS Liver Transplant Registry since October 1987 continues, and in 1993 the rate of increase was greater than it had been in recent years. This is in spite of the fact that the net growth of new centers was smaller in 1993 than in any previous year examined. Pediatric recipients in 1993 were compared with those in previous years, and no significant differences were found for sex, race, or age. In contrast to prior years, the majority of pediatric recipients in 1993 awaited transplantation at home. The most common indication for liver transplantation in children was biliary atresia, although the proportion of recipients with this primary liver disease decreased slightly in 1993. Significant increases were noted in the proportions of pediatric recipients with fulminant liver failure, and hepatoblastoma. Significantly fewer children received ABO-incompatible livers in 1993 compared with prior years, part of which may be a function of the increasing use of living-related donors. Many of the characteristics examined for adult recipients had different distributions in 1993 than in prior years. The proportion of White recipients declined in 1993, due to increases among Black and Hispanic recipients. The mean and median ages of adult recipients continued to increase because of the increasing proportion of recipients aged 60 and over. The proportion of adult recipients awaiting transplantation outside of the hospital continued to increase in 1993. The increase in the proportion of recipients with positive CMV serology is likely due to the increasing age of the recipients in 1993. A smaller proportion of multiorgan transplantations was performed in 1993, due to the elimination of procedures involving only the liver and pancreas. Alcoholic cirrhosis was replaced by hepatitis non-A, non-B, or C as the most common reason for LTX. The proportions of recipients with fulminant liver failure and malignancies, indications for poorest survival, declined significantly in 1993. The cumulative probability of surviving for 6 years after initial transplantation was 0.70 (without retransplantation = 0.58) for pediatric recipients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1995

[The duration of action of vecuronium in five patients after kidney transplantation--comparison with that during kidney transplantation].

We compared the duration of vecuronium action in five patients after the kidney transplantation with that during kidney transplantation. After the transplantation, three patients required no hemodialysis therapy but two patients underwent hemodialysis therapy again. In all these five patients, including patients who were back to hemodialysis therapy, the durations of vecuronium action after receiving transplanted kidney were shorter than those during kidney transplantation. These shortened durations are speculated to be mainly due to excretion of vecuronium by the transplanted kidney and the effect of long term steroid therapy. However in this study the durations of vecuronium action in patients who required further hemodialysis therapy were also shorter than those during kidney transplantation. To determine whether this is a common or exceptional phenomenon, further evaluation should be needed.

Adult↗
PubMedDate not supplied

Cytomegalovirus after heart transplantation. Risk factors for infection and death: a multiinstitutional study. The Cardiac Transplant Research Database Group.

Cytomegalovirus infection is a major cause of morbidity and rehospitalization after heart transplantation. To assess its incidence and risk factors in the current era of heart transplantation, we analyzed cytomegalovirus infection data in 1553 patients from 26 institutions (Cardiac Transplant Research Database Group) undergoing primary heart transplantation between Jan. 1, 1990, and June 30, 1992. There were 230 treated cytomegalovirus infections in 200 patients, of which 16 were fatal (6%; 70% confidence limits 5% to 9%). Actuarial freedom from cytomegalovirus infection was 98% 1 month, 88% 3 months, and 83% 24 months after transplantation, with a peak incidence of initial infection at 2 months. Twenty-five (12%) of 200 patients with cytomegalovirus infection had recurrent cytomegalovirus infection during a mean follow-up of 13.9 months. The primary location of cytomegalovirus infection was blood in 100 infections (43%), lung in 69 (30%), gastrointestinal tract in 54 (23%), and other sites in seven patients (3%). Cytomegalovirus pneumonia exhibited the highest mortality rate (13%). Risk factors by multivariate analysis for earlier development of cytomegalovirus infection included pretransplantation cytomegalovirus serology (positive donor, negative recipient [p < 0.0001]; positive donor, positive recipient [p = 0.0002]; and negative donor, positive recipient [p = 0.02]) and cytolytic induction therapy (p = 0.05). A cytomegalovirus-positive recipient with a cytomegalovirus-positive donor had a 15% chance of having cytomegalovirus infection, whereas a cytomegalovirus-negative recipient with a cytomegalovirus-positive donor had a 24% chance. Ganciclovir treatment was administered in 227 (99%) of 230 infections. By multivariable analysis, the likelihood of a fatal cytomegalovirus infection was increased with a higher number of infections of any type during the first post transplantation month (p < 0.0001). There was no increased mortality rate in cytomegalovirus infections associated with cytomegalovirus-positive donor and cytomegalovirus-negative recipient (6% mortality rate) versus all other cytomegalovirus infections (6% mortality rate) (p = 0.9) or with OKT3 induction therapy (0% mortality rate) versus all others (noninduction and induction with other than OKT3) (1.4%) (p = 0.03). In conclusion, the biggest determinant of cytomegalovirus infection is donor and recipient pretransplantation cytomegalovirus serologic results with cytolytic induction therapy adding a small additional risk. The overall mortality rate from cytomegalovirus infections is low (7%) in the current era with rapid culture techniques and ganciclovir therapy. Cytomegalovirus infections are more likely to be fatal if there are more frequent preceding infections of any type, but mortality rates are not increased by OKT3 induction or with a cytomegalovirus-positive donor organ transplanted into a cytomegalovirus-negative recipient.

Adolescent↗
PubMed1993

Alternative donor transplants for leukemia. Scientific Advisory Committee of the International Bone Marrow Transplant Registry.

We analyzed transplant outcome in more than 2,500 recipients of alternative donor and HLA-identical sibling transplants. These data indicate: (1) results of alternative donor transplants are inferior to HLA-identical sibling transplants; (2) zero HLA-antigen disparate unrelated and one HLA-antigen disparate related donors have comparable results; (3) amongst unrelated donors, zero and one HLA-antigen disparity has comparable results; and (4), amongst related transplants, two HLA-antigen disparate transplants fare worse than one HLA-antigen disparate transplants. These data should be useful in deciding when to use an alternative donor and selecting the best donor.

Bone Marrow Transplantation↗
PubMed1996

[Organ transplantation. 4. Renal transplantation].

Renal transplantation is well recognized as a better modality for improving quality of life (QOL) in patients with end stage renal disease as compared with hemodialysis. The better QOL attained by renal transplantation can be maintained as far as a renal allograft functions. The results of renal transplantation have been markedly improved mainly by introducing cyclosporine (CsA), especially using regimens in which a more decreased dose of CsA is used in combination with other immunosuppressive drugs, including azathiopurine and ALG to avoid nephrotoxicity of CsA. Mortality due to a variety of complications such as infections, hepatic failure, malignancy and cardiovascular diseases aggravates the results of renal transplantation. Although the result of Kidney transplantation in Japan is as good as that observed in European countries ane the United States, a number of transplantation performed in Japan is extremely small compared with these countries. In order to increase a number of renal transplantation in Japan, all efforts aiming at promoting cadaveric kidney donation should be performed as a first priority.

Humans↗
PubMed1997

The incremental risk of female sex in heart transplantation: a multiinstitutional study of peripartum cardiomyopathy and pregnancy. Cardiac Transplant Research Database Group.

BACKGROUND: Controversy remains regarding the reason females seem to be at increased risk for rejection after heart transplantation. Therefore this study was performed to define the effect of a pretransplantation diagnosis of peripartum cardiomyopathy and the effect of previous pregnancy on the outcome (incidence of rejection and death) of females after heart transplantation. METHODS: In this multiinstitutional study of 3244 adult (greater than 13 years of age) heart transplant recipients, (a) the outcome of 40 females who underwent transplantation for peripartum cardiomyopathy was compared with that of 200 females of childbearing age (13 to 45 years) who underwent transplantation for other indications and (b) the posttransplantation outcome of 543 females with a history of pregnancy was compared with that of 101 nulliparous adult females and 2562 adult males. RESULTS: The posttransplantation outcome of females with a history of peripartum cardiomyopathy was similar to that of females of childbearing age who underwent transplantation for other indications. However, parous females had a significantly shorter time to first rejection (p < 0.0001) and greater cumulative rejection than nulliparous females or males. By multivariable analysis, the risk factors for cumulative rejection at 1 year were a history of pregnancy (p < 0.0001), younger recipient age (p < 0.0001), induction therapy (p < 0.0001), and the number of human leukocyte antigen-DR mismatches (p = 0.007). CONCLUSION: Our data suggest that it is previous pregnancy, and not sex per se, that is associated with an increased frequency of rejection in females after heart transplantation.

Actuarial Analysis↗
PubMed1997

[Diagnostic imaging in the selection of candidates to orthotopic transplantation of the liver. Experience at a hospital lacking a transplantation department].

We report the experience of our general hospital in selecting the patients for orthotopic liver transplantation (OLT). Fifty-one patients with cirrhosis were examined and 20 of them submitted to OLT from August, 1992, to November, 1995. For liver studies, the 20 transplant recipients were examined with US and plain and dynamic CT; 15/20 were submitted to CTAP, 10/20 to Lipiodol CT and 17/20 to angiography. The accuracy of these techniques in HCC detection was assessed by correlation with resected whole livers. The accuracy of duplex Doppler and color flow Doppler for portal and/or mesenteric vein thrombosis was evaluated by correlation with resected livers, CT and angiographic findings. Pathologic examinations diagnosed HCC in 5/20 transplant recipients: 2 lesions (1.5 cm and 2 cm; 2 cm and 3.5 cm) were found in 2 resected specimens (total hepatectomy) and 1 lesion was found in 3 cases (2.5 cm, 1.5 cm, 1 cm). The sensitivity of US, plain and dynamic CT in identifying HCC patients was 20%; US and CT specificity rates were 100% and 87%, respectively. CTAP sensitivity was 75% and the sensitivity of Lipiodol CT and angiography was 100%. Therefore, in our series, US was poorly sensitive in the detection of liver cancers, which may depend on the small number of patients, lesion size (< or = 3.5 cm) and the radiologists ignoring clinical and laboratory data on purpose. Nevertheless, the patients with a single HCC not exceeding 5 cm phi or with no more than 3 tumors, none of them exceeding 3 cm phi, are generally considered eligible for transplantation: therefore, our patients chosen for OLT on the basis of US and CT findings were actually eligible for transplantation in spite of US and CT false negative results. At US, the portal vein had an average caliber of 13.5 +/- 2.5 mm in 21/51 patients; the average caliber of the common hepatic artery was 6 +/- 1.5 mm in 49/51 patients; average spleen length was 174 +/- 38 mm. US showed ascites in 28/51 cases. In conclusion, considering also the long stand-by list for OLT, the first selection of transplant candidates could be performed with US and color flow Doppler, plain and dynamic CT. The patients who are ruled out as candidates for OLT on the basis of the findings of these imaging techniques and of clinical and laboratory findings are submitted to no further examination and referred to the transplantation unit. Otherwise, if conventional and color flow Doppler US and conventional CT are not enough to exclude a patient from OLT, the subject is submitted to more invasive (angiography, CTAP, Lipiodol CT) or less widespread (spiral CT, MRI) techniques.

Adult↗
PubMed2002

[Amniotic membrane transplantation with limbal stem cell transplantation as a combined procedure for corneal surface reconstruction after severe thermal or chemical burns].

BACKGROUND: Severe thermal and chemical burns may result in limbal deficiency leading to persistent epithelial defects, complete conjunctival epithelial ingrowth and vascularisation of the cornea. If sufficiently severe, these burns may lead to very significant visual impairment. Amniotic membrane transplantation with limbal transplantation has recently been proposed as a new method for corneal surface reconstruction. PATIENTS AND METHODS: A total of 14 patients (age 18-62 years, mean age 42 years) with limbal deficiency resulting from thermal ( n=1) or chemical burns ( n=13) underwent surgery. The corneal pannus was completely removed and the amniotic membrane was grafted onto the cornea. Limbal transplantation using autografts obtained from contralateral eyes was performed simultaneously in seven cases. Allografts from a donor were transplanted in seven cases with bilateral involvement. These patients received oral cyclosporin A postoperatively. The mean follow-up time was 18 months. RESULTS: In all cases of limbal autografts the corneal surface showed a complete and stable epithelialisation within a few weeks. Out of seven patients with limbal allografts three displayed recurrent epithelial defects in the long term. The initially semitransparent amniotic membrane became more translucent and biomicroscopically invisible within several months after surgery. There was an increase in visual acuity in most cases, limited mostly by irregular astigmatism due to the initial stromal loss. CONCLUSIONS: Amniotic membrane transplantation with limbal transplantation allows reconstruction ocular surfaces severely damaged by chemical or thermal burns. In most cases, however, additional surgical procedures such as lamellar or penetrating keratoplasty are required for adequate visual rehabilitation.

Administration, Oral↗
PubMed2006

Results of the cord blood transplantation study (COBLT): outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with lysosomal and peroxisomal storage diseases.

The Cord Blood Transplantation Study (COBLT), sponsored by the National Heart, Lung, and Blood Institute, is a phase II multicenter study designed to evaluate the use of cord blood in allogeneic transplantation. In this report, we evaluated the outcomes of cord blood transplantation in 69 patients with lysosomal and peroxisomal storage diseases. Patients with mucopolysaccharidoses I to III, mucolipidoses (ML) II (n = 36), adrenoleukodystrophy (n = 8), metachromatic leukodystrophy (n = 6), Krabbe disease (n = 16), and Tay-Sachs disease (n = 3) were enrolled between August 1999 and June 2004. All patients received the same preparative regimen, graft-versus-host disease (GVHD) prophylaxis, and supportive care. End points included survival, engraftment, GVHD, and toxicity. Sixty-nine patients (64% men; 81% white) with a median age of 1.8 years underwent transplantation with a median cell dose of 8.7 x 10(7)/kg. One-year survival was 72% (95% confidence interval, 61%-83%). The cumulative incidence of neutrophil engraftment by day 42 was 78% (95% confidence interval, 67%-87%) at a median of 25 days. Grade II to IV acute GVHD occurred in 36% of patients. Cord blood donors are readily available for rapid transplantation. Cord blood transplantation should be considered as frontline therapy for young patients with lysosomal and peroxisomal storage diseases.

Child↗
PubMed2006

Improving outcome of allogeneic stem cell transplantation by immunomodulation of the early post-transplant environment.

There has been great progress in understanding the alloresponse and the process of immune recovery after stem cell transplantation. Here, we highlight ways in which transplant outcome is determined by unique immunological features of the early post-transplant period that modulate the growth and function of the grafted donor T cells and stem cells. Better understanding of these early events and more detailed knowledge of the phenotype and function of transplanted donor cells facilitate strategies to optimize immune recovery, prevent graft-versus-host disease (GVHD) and boost immunity to viruses and leukemia. Approaches that optimize CD34 cell dose, techniques to remove GVHD-reacting T cells by T cell subset selection, suicide gene insertion or selective allodepletion, and the adoptive transfer of antigen-specific T cells have reached the stage of clinical trials. Furthermore, murine transplant experiments indicate ways to prevent GVHD while preserving immune function by depletion of naïve cells, T cytotoxic 1 and T helper 1 cells, or by enrichment of regulatory T cells. Many of these approaches appear feasible in clinical transplantation and have yielded promising initial results, but proof that the goal of controlled selective immune reconstitution can be achieved is still awaited.

Animals↗
PubMed2001

Accelerated telomere shortening following allogeneic transplantation is independent of the cell source and occurs within the first year post transplant.

Telomere shortening has been documented in the blood cells of recipients of allogeneic bone marrow transplants compared with their donors. Allogeneic peripheral blood progenitor cells (PBPCs) have been increasingly used as an alternative to bone marrow. Their advantages include earlier engraftment and immune reconstitution following transplantation. We have measured telomere length of neutrophils and T cells in fully engrafted recipients of allogeneic bone marrow (n = 19) and allogeneic PBPC (n = 17) and also measured sequential telomere length in four patients after transplantation. Overall, significant telomere shortening occurred in recipients in neutrophils (0.3 kb, P < 0.001) and T cells (0.2 kb, P = 0.045). The data demonstrate that first, the degree of shortening was the same for BM and PBPC transplants and was not related to the time taken to engraft neutrophils and platelets and second, telomere shortening occurs in the first year post transplant without further shortening during the period of observation. These data suggest that the superiority of engraftment seen in PBPC transplants is independent of telomere shortening and other mechanisms such as homing or seeding may be more important.

Adolescent↗
PubMed2002

Transplant-related toxicity and mortality: an AIEOP prospective study in 636 pediatric patients transplanted for acute leukemia.

Hematopoietic stem cell transplantation can cure high-risk acute leukemia (AL), but the occurrence of non-leukemic death is still high. The AIEOP conducted a prospective study in order to assess incidence and relationships of early toxicity and transplant-related mortality (TRM) in a pediatric population. Between 1990 and 1997 toxicities reported in eight organs (central nervous system, heart, lungs, liver, gut, kidneys, bladder, mucosa) were classified into three grades (mild, moderate, severe) and prospectively registered for 636 consecutive children who underwent autologous (216) or allogeneic (420) transplantation, either from an HLA compatible related (294), or alternative (126) donor in 13 AIEOP transplant centers. Overall, 47% of the patients are alive in CR (3-year EFS: 45.2%, s.e.: 2.1), 19% died in CR at a median of 60 days (90-day TRM: 14.3%, s.e.: 1.4), 34% relapsed. Toxicity of any organ, but mucosa and gut, was positively correlated with early death; moderate and severe toxicity to heart, lungs, liver and kidneys significantly increased early TRM, with estimated relative risks of 9.1, 5.5, 2.7 and 2.8, respectively, as compared to absent or mild toxicity. Patients with grade III-IV aGVHD experienced more than double (56% vs. 19%) TRM than patients with grade 0-II aGVHD. A higher cumulative toxicity score, estimating the impact of toxicity on TRM, was significantly associated with transplantation from an alternative donor. Quantitative assessment allowed us to describe the extent to which 'grade' of toxicity and 'type' of involved organs were related to mortality and pre-transplant characteristics and yielded a prognostic score potentially useful to compare different conditioning regimens and predict probability of early death.

Adolescent↗
PubMed2003

Autologous stem cell transplantation in multiple myeloma: improved survival in nonsecretory multiple myeloma but lack of influence of age, status at transplant, previous treatment and conditioning regimen. A single-centre experience in 127 patients.

High-dose therapy with autologous stem cell transplantation (ASCT) has become the treatment of choice for symptomatic eligible patients with multiple myeloma (MM). We report our centre experience and analyse retrospectively the prognostic influence of pretransplant characteristics and transplant modalities on response and survival. A total of 127 MM patients (median age: 55.2 years) were transplanted between 1994 and 2001. In all, 69 patients had IgG, 28 IgA, 23 light chain, one IgD and six non secretory MM. At the time of autograft, 6% of patients were in complete remission (CR), 73% in partial remission (PR), 12% showed minor response to previous treatment and 9% had stable or refractory disease. Prior to autograft, 79% of cases had received only one line of chemotherapy and 21% two or more lines. All patients received PBSC support after conditioning with 200 mg/m(2) melphalan alone (100 patients) or melphalan and TBI (27 patients). We evaluated the influence of age (using as cutoff value the ages of 55, 60 and 65 years), type of MM, status pre- and post-ASCT, number of lines of previous regimens, time of ASCT from diagnosis, year of autograft, dose of reinfused CD34+ cells, plasma cell infiltration and beta(2)-microglobulin at diagnosis on overall (OS) and progression-free survivals (PFS) to define patients with better prognosis. Following ASCT, 15% of patients were in CR and 81% in PR, while only two patients progressed. Median OS and PFS from transplantation were 50.4 and 23.5 months, respectively. Median OS from diagnosis was 79.7 months. Transplant-related mortality was 2.3%. Low levels of beta(2)-microglobulin and the achievement of CR post-transplant correlated with longer PFS (P<0.03 and P<0.01, respectively). The median PFS was 36.1, 23.9, 21.1 and 16.4 months for nonsecretory, IgG, IgA and light chain subtypes, respectively. Age was not an important prognostic factor at a cutoff value of 55 or 60 years. We conclude that ASCT is a safe and effective procedure even in resistant cases. The outcome was independent of age, time from diagnosis, previous treatment and conditioning regimen, but there was a tendency for better survival in the nonsecretory patients.

Age Factors↗
PubMed1996

A comparison of busulphan versus total body irradiation combined with cyclophosphamide as conditioning for autograft or allograft bone marrow transplantation in patients with acute leukaemia. Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT).

We retrospectively compared the outcome in patients in the EBMT database transplanted for acute leukaemia from January 1987 to January 1994 who received busulphan and cyclophosphamide (BU/CY) as a pretransplant regimen versus those who received cyclophosphamide and total-body irradiation (CY/TBI). The patients were matched for type of transplant (autologous bone marrow transplantation (ABMT) versus allogeneic (BMT)), diagnosis (acute lymphoblastic leukaemia (ALL) or acute myeloid leukaemia (AML)), status (early (first complete remission, CR-1) versus intermediate (second or later remission, first relapse)), age, FAB classification for AML, prevention of graft-versus-host disease and year of transplantation. In ABMT recipients (matched paired 530 x 2) with ALL CR-1, AML CR-1 and AML intermediate disease, transplant-related mortalities (TRM) relapse incidence (RI) and leukaemia-free survival (LFS) did not differ significantly in patients treated with BU/CY or CY/TBI. However, in ABMT recipients with ALL intermediate disease, the probability of relapse was 82 +/- 5% (+/- 95% confidence interval) in the BU/CY group compared to 62 +/- 6% in the CY/TBI group (P = 0.002) and the 2-year leukaemia-free survival 14 +/- 4% and 34 +/- 6%, respectively (P = 0.002). In BMT recipients of bone marrow from HLA-identical siblings (matched paired 391 x 2), the TRM, RI and LFS did not differ significantly between the two treatments in all groups. In particular, the 2-year LFS in patients with AML CR-1 was 64 +/- 3% in those treated with BU/CY (n = 237) compared to 66 +/- 3% in those given CY/TBI (n = 237). In all groups the findings were confirmed in a multivariate analysis of prognostic factors. Veno-occlusive disease (VOD) of the liver (P < 0.05) and haemorrhagic cystitis (P < 0.001) was more common in the BU/CY group compared to the CY/TBI group for ABMT and BMT patients. In conclusion, BU/CY and CY/TBI as pretransplant regimens gave similar results in all situations, except ABMT for ALL intermediate stages with more than 2 years from diagnosis to transplantation, where a lower RI and a higher LFS were associated with CY/TBI.

Acute Disease↗
PubMed1997

Clinical presentation and outcome of tuberculosis in kidney, liver, and heart transplant recipients in Spain. Spanish Transplantation Infection Study Group, GESITRA.

BACKGROUND: Tuberculosis is unusual in transplant recipients. The incidence, clinical manifestations, and optimal treatment of this disease in this population has not been adequately defined. The present study was undertaken to assess the incidence, clinical features, and response to therapy of Mycobacterium tuberculosis infection in solid-organ transplant recipients. METHODS: We evaluated retrospectively the incidence, clinical characteristics, diagnostic procedures, antituberculous treatment, clinical course, and factors influencing mortality in 51 solid-organ transplant recipients who developed tuberculosis after transplantation. We also reviewed the world literature on tuberculosis in solid-organ transplantation. RESULTS: The overall incidence of tuberculosis was 0.8%. The localization was pulmonary in 63% of the cases, disseminated in 25%, and extrapulmonary in 12%. Tuberculosis developed from 15 days to 13 years after surgery (mean, 23 months). In one third of the cases, diagnosis was not suspected initially, and in three cases, diagnosis was made at necropsy. Fever was the most frequent symptom, followed by constitutional symptoms, cough, respiratory insufficiency, and pleuritic pain. Fifteen patients (33%) developed hepatotoxicity during treatment; hepatotoxicity was severe in seven cases. Hepatotoxicity was higher in patients receiving four or more antituberculous drugs (50%) than in patients receiving three drugs (21%; P=0.03). Serum levels of cyclosporine decreased in the 26 patients under the simultaneous use of rifampin. Nine of them (35%) developed acute rejection, and five (56%) died, in comparison with 3 of 17 patients (18%) who did not develop rejection after the use of cyclosporine and rifampin (P=0.03). Although microbiological response was favorable in 94% of the 35 patients who completed 6 or more months of treatment, 16 other patients (31%) died before diagnosis or in the course of treatment. None of the patients treated for more than 9 months died as a consequence of tuberculosis, whereas the mortality rate was 33% among those treated for 6 to 9 months (P=0.03). Use of antilymphocyte antibodies or high doses of steroids for acute rejection before tuberculosis was associated with a higher mortality rate. CONCLUSIONS: M tuberculosis causes serious and potentially life-threatening disease in solid-organ transplant recipients. Treatment with at least three drugs during 9 months or more, avoiding the use of rifampin, appears to be appropriate.

Adult↗
PubMed1997

Transplantation of CD95 ligand-expressing grafts: influence of transplantation site and difficulty in protecting allo- and xenografts.

BACKGROUND: CD95 and its ligand (CD95L) have been implicated in the regulation of immune responses. Recently, it was reported that CD95L expression prevented rejection of allogeneic grafts transplanted under the kidney capsule. In contrast, we reported that enforced CD95L expression in subcutaneously grafted cells induced acute rejection even in the syngeneic or immunodeficient hosts. In this study, we investigated whether the CD95L-expressing cells could be protected from rejection when transplanted under the kidney capsule. METHODS: CD95-negative cells (baby hamster kidney and L5178Y lymphoma cells) were transfected with CD95L cDNA to express functional CD95L. The cells were transplanted into skin or renal subcapsular space of immunocompetent or T cell-deficient nu/nu mice. RESULTS: The parental cells grew well in nu/nu or syngeneic mice but were rejected in allogeneic or xenogeneic immunocompetent mice. The CD95L transfectants were rejected when transplanted subcutaneously in all types of mice studied. However, when transplanted under the kidney capsule, they survived in nu/nu or syngeneic mice but were rejected in allogeneic or xenogeneic immunocompetent mice. CONCLUSIONS: These results imply that CD95L expression may not be sufficient to protect the grafts from rejection, and the survival of CD95L-bearing grafts is substantially influenced by the site of transplantation.

Animals↗