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PubMed1996

Are heart-lung transplant recipients protected from developing transplant coronary artery disease? A case-matched intracoronary ultrasound study.

BACKGROUND: Accelerated coronary artery disease is a major cause of mortality in heart transplant recipients; however, it does not appear to play a major role in the clinical outcome of heart-lung transplant recipients. The purpose of this study was to determine whether the incidence and severity of transplant coronary artery disease as detected by intracoronary ultrasound in heart-lung transplant recipients are less than those encountered in heart transplant recipients. METHODS AND RESULTS: We studied the left anterior descending coronary artery with the use of intracoronary ultrasound imaging in 22 heart-lung transplant recipients at the time of their routine annual coronary angiogram. Twenty-two heart transplant recipients were case matched for number of years after transplant at ultrasound study, recipient age, donor age, and diagnosis of nonischemic cardiomyopathy. Mean intimal area, intimal index, Stanford class, and incidence of at least moderate disease (Stanford class > or = 3) were measured and calculated in each group and then compared between the two groups. Mean intimal area (1.6 +/- 2.5 versus 3.8 +/- 2.8 mm2), mean intimal index (0.07 +/- 0.10 versus 0.22 +/- 0.14), mean Stanford class (1.7 +/- 1.0 versus 2.7 +/- 1.2), and incidence of Stanford class > or = 3 (14% versus 45%) were significantly lower in the heart-lung transplant recipient group. CONCLUSIONS: The incidence and severity of transplant coronary artery disease are much less in patients receiving heart-lung transplants than in those receiving heart transplants alone.

Adult↗
PubMed1995

Reduced transplant lung volumes after single lung transplantation for chronic obstructive pulmonary disease.

Single lung transplantation is now an extremely successful option for the treatment of end-stage chronic obstructive pulmonary disease (COPD). This procedure involves placing a normal sized lung in a hyperinflated hemithorax. Preliminary observations of these patients suggest that the transplanted lung volume is smaller than expected and often the native (COPD) lung increases in volume. The purpose of this investigation was to quantify the volume contributions of the transplant and native lung to the total lung capacity. In seven patients who underwent single lung transplant for end-stage COPD the transplant and native lung volumes were measured by computer-analyzed planimetry immediately after transplant and the following 6 mo post-transplant. The transplant lung volume was smaller than predicted immediately after transplant at only 33 +/- 5% (mean +/- SD) of predicted TLC. This did not change significantly over the next 6 mo. Native lung volume increased following transplant to 74 +/- 19% predicted TLC at 1 mo and 80 +/- 16% at 6 mo. Five of the seven patients subsequently underwent measurement of pleural pressures at TLC. The mean static pleural pressure at TLC was low at -16 +/- 5.1 cm H2O. In summary, following single lung transplantation for COPD the transplanted lung is significantly restricted. We conclude that the likely mechanism of this restriction is due to low transpulmonary pressure generation.

Female↗
PubMed2002

Is transplant operation important in determining posttransplant risk of bronchiolitis obliterans syndrome in lung transplant recipients?

STUDY OBJECTIVES: Lung transplantation continues to be limited by the development of chronic allograft dysfunction in the form of bronchiolitis obliterans syndrome (BOS). The effect of a transplant operation on patients with BOS has not been well-studied, but patients who undergo double-lung transplantation have better long-term survival. We hypothesized that double-lung transplantation leads to decreased rates of BOS. METHODS: A retrospective review of all lung transplant recipients at our institution, surviving for > 6 months after undergoing their transplant operation. Demographic data, information on other factors leading to the development of BOS, survival information, and data on the presence and timing of BOS were collected. RESULTS: BOS occurred in 41.3% of the recipients (93 of 225 patients) at a median time of 4.2 years. Single-lung transplantation was associated with increased rates of BOS compared to double-lung transplantation (49.3% vs 31.7%, respectively; p = 0.007), at the time of the analysis. Single-lung and double-lung transplant recipients had different baseline characteristics, but after controlling for these factors the type of transplant remained a significant predictor of the length of time to the onset of BOS in a multivariable proportional hazard model. CONCLUSIONS: Double-lung transplantation is associated with a reduced risk for BOS in our study population. A multicenter study with complete BOS information on all patients with a single pretransplant diagnosis would be useful to confirm the above findings. Further research is needed to determine how the type of transplant contributes to the risk for BOS.

Age Distribution↗
PubMed2005

Impact of cadaveric renal transplantation on survival in patients listed for transplantation.

The aim of this study was to assess the magnitude of the survival benefit of renal transplantation compared with dialysis in patients selected for transplantation in Scotland. Longitudinal study of survival and mortality risk in all adult patients (1732) listed for a first transplant between January 1, 1989, and December 31, 1989, in Scotland. A time-dependent Cox regression analysis adjusted for comorbidity, sociodemographic and geographic factors, primary renal disease, time on dialysis, and year of listing compared the risk of death for patients receiving a first cadaveric transplant versus all patients on dialysis listed for transplantation. After adjustment for the covariates, the relative risk (RR) of death during the first 30 days after transplantation was 1.35 (95% confidence interval [CI], 0.63 to 2.86) compared with patients on dialysis (RR = 1). The long-term RR (at 18 mo) for the transplant recipients was 0.18 (95% CI, 0.08 to 0.42) when compared with patients on dialysis (RR = 1). This lower long-term risk of death was present in all patients undergoing transplantation, irrespective of their age group or primary renal disease. Similar results were seen when survival with a transplant was censored for graft failure. The projected life expectancy with a transplant was 17.19 yr compared with only 5.84 yr on dialysis. Despite an initial higher risk of death, long-term survival for patients who undergo transplantation is significantly better compared with patients who are listed but remain on dialysis. A successful transplant triples the life expectancy of a listed renal failure patient.

Adult↗
PubMed1997

Correlation of the arterial resistive index in pancreas transplants of patients with transplant rejection.

OBJECTIVE: This study was undertaken to determine whether arterial resistive indexes (RIs) in pancreas transplants correlate with biopsy-proven transplant rejection. MATERIALS AND METHODS: We retrospectively reviewed arterial RIs in pancreas transplants for all patients who underwent Doppler sonography within 1 week before transcystoscopic or percutaneous biopsy of pancreas transplants. RIs were correlated with type and degree of rejection in the 20 transplants for which biopsies provided sufficient tissue for diagnosis. Three patients were subsequently eliminated from the study because of significant intervening therapy between sonography and biopsy. RESULTS: The nine transplants with no evidence of rejection had a mean arterial RI of 0.64 (range, 0.49-0.80). The six transplants with acute mild or moderate rejection had a mean RI of 0.67 (range, 0.56-0.73). The two transplants with acute severe rejection had a mean RI of 0.85 (range, 0.80-0.90). We found no statistically significant difference between arterial RIs in pancreas transplants of patients with acute mild or acute moderate rejection and those with no evidence of rejection. CONCLUSION: Arterial RIs of pancreas transplants do not differentiate between acute mild or acute moderate rejection and absence of rejection. The higher mean value of arterial RIs in pancreas transplants with acute severe rejection suggests that elevated arterial RIs are sensitive, but not specific, for revealing acute severe rejection of pancreas transplants. However, our study data are limited, and a larger sample size is necessary to draw statistically significant conclusions.

Adult↗
PubMed1997

Psychological and social adjustment after pediatric liver transplantation as a function of age at surgery and of time elapsed since transplantation.

The study assessed psychological and social adjustment to pediatric liver transplantation in 101 patients aged 4-16 years who had undergone transplantation 2-10 years earlier. Each parent completed the Child Behavior Check List (CBCL) independently and answered a transplantation questionnaire assessing psychosocial issues. Most children scored within the normal range for both parts of the CBCL (i.e. Behavioral Problems and Social Competences). The impact of age at transplantation and of time elapsed since transplantation were examined. Earlier transplantation was associated with subsequent higher scores for Aggressive Behavior and Sex Problems, with lower scores for Activities and Competences, and with more parental anxiety concerning their child's health. The longer the time elapsed since transplantation, the more mothers rated high levels on the Somatic complaints, Anxiety/depression, Competence, and Social activity CBCL scales for their child. Parents reported talking more about the transplantation with their children with increasing time following transplantation. This suggests that transplantation remains an important event even after long periods of time from the transplant event. Finally, despite the difficulties encountered, more than 80% of the parents considered the transplantation had been beneficial to their child.

Adaptation, Psychological↗
PubMed1997

Renal transplantation in children from 1987-1996: the 1996 Annual Report of the North American Pediatric Renal Transplant Cooperative Study.

The 1996 Annual Report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) summarizes data voluntarily collected from 130 centers on 4329 children and adolescent patients who received renal transplants on or after January 1, 1987. This report updates information on transplants; data on dialysis and chronic renal insufficiency have, for the first time, been reported separately (in submission). The NAPRTCS registry shows that the majority of pediatric renal transplants are performed in children above 6 years of age (73%). The most frequent diagnoses include obstructive uropathy (16%), aplastic/hypoplastic/dysplastic kidneys (16%), and focal segmental glomerulosclerosis (12%). Pre-emptive transplantation was performed in 24% of patients. Triple drug maintenance therapy with prednisone, cyclosporine and azathioprine was used by >70% of all transplant recipients throughout 7 years of follow-up. Fifty-six per cent of transplant recipients were rehospitalized during months 1-5 (51% live donor (LD), 62% cadaver donor (CD)), with rejection and infection as the main causes. In the period 30-35 months post-transplant, 19-22% of patients (163 LD, 185 CD) were rehospitalized. The median time to the first rejection was 46 days for CD transplants and 377 days for LD grafts (p<.001). Six-year graft survival rates were 73% and 56% for LD grafts and CD grafts, respectively (p<.001). The overall growth deficit was constant over a period of 60 months. However, children transplanted under 5 years of age reduce their height deficit by about one-third compared to an increase in height deficit of up to 22% for older children. The NAPRTCS data analysis also demonstrates a delay in first rejection episodes in LD compared to CD transplants, and a steady improvement in CD graft survival over the past 5 years in pediatric transplant recipients.

Adolescent↗
PubMed2001

The 12th Annual Report of the North American Pediatric Renal Transplant Cooperative Study: renal transplantation from 1987 through 1998.

The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) presents an annual report for all transplants registered from January 1987 onwards. In this report we reviewed 6,534 renal transplants recorded for 5,958 patients who had entered the study by January 1999, and attempted to identify changes in practice patterns that had led to improved graft survival. There has been a steady decline in cadaver source transplants nationally and our accrual for 1996 and 1997 reflected this trend. There has also been a decrease in the number of infants and young children receiving a transplant in recent years. From a peak of 23.3% in the 1987-91 cohort, the current report shows that children under 6 yr of age now account for only 20.4% of all transplants. Changing disease patterns and rates of progression of disease have decreased the percentage of Caucasian children in the transplant registry, from 68.5% in the first 5 yr to 62.9% in the most recent cohort. Changing practice patterns have markedly reduced the use of cadaver donor (CD) kidneys (recovered from donors younger than 10 yr of age) from 35% in 1991 to 22% in the current report. Acute rejection patterns are identical for CD and living donor (LD) grafts for the first 2 weeks post-transplant. The comparative percentages on days 30 and 45 are 36% and 44% for CD, and 26% and 32% for LD recipients respectively. By the end of the first year post-transplant, 45% of LD and 60% CD recipients have had an acute rejection. There has been a marked improvement in our ability to reverse the initial episode of rejection; in 1987, 52% were completely reversed in LD recipients, and in 1997 61% were reversed. Rejection percentages continued to be lower in patients maintained on cyclosporin A (CsA) doses of > 6.4 mg/kg. One-, 3-, and 5-yr graft survival probabilities were 91%, 85%, and 80%, respectively, for LD recipients, and 83%, 73%, and 65% for CD recipients. Comparative 1- and 3-yr figures from 1987 to 1991 were 88% and 81% for LD and 74% and 63% for CD recipients. When short-term graft survival (1 yr) results were compared, a significant improvement was demonstrated from 71.7% in 1987/88 to 92.6% in 1998/1999 for CD transplants. Hence, changing practice patterns have gradually brought the short-term graft survival of CD transplants very close to that of LD transplants. The continuing decrease in the incidence of acute rejections in more recent years should translate into a further delay in the onset of chronic rejection, thus improving graft longevity.

Adolescent↗
PubMed1991

The Washington University-Barnes Hospital experience with lung transplantation. Washington University Lung Transplantation Group.

OBJECTIVE: --To review our experience with lung transplantation, emphasizing recipient selection, choice of procedure, functional results, and outcome. DESIGN: --Retrospective review of patients who received lung transplants at Barnes Hospital, St Louis, Mo, between July 1, 1988, and January 31, 1991. SETTING: --Washington University School of Medicine, St Louis, Mo, and Barnes Hospital, a medical school and its affiliated referral hospital, respectively. PATIENTS: --Sixty-nine lung transplant procedures were performed in 66 recipients. Patients with clinically and physiologically severe lung disease were selected according to predetermined guidelines. Underlying diseases in the recipients included chronic obstructive pulmonary disease, alpha 1-antitrypsin deficiency emphysema, cystic fibrosis, pulmonary fibrosis, primary pulmonary hypertension, Eisenmenger's syndrome associated with an atrial septal defect, bronchiectasis, eosinophilic granuloma, and lymphangiomyomatosis. INTERVENTION: --Double-lung, bilateral sequential, and single-lung transplantations were performed. Eight patients underwent en bloc double-lung transplantations or a modification of this procedure with separate bronchial anastomoses. Thereafter, the bilateral sequential approach to replacement of both lungs was performed in 26 patients. Thirty-two patients underwent single-lung transplantations. MAIN OUTCOME MEASURES: --Pulmonary function tests, arterial blood gas levels, pulmonary artery pressure, pulmonary vascular resistance, and actuarial survival. RESULTS: --Actuarial survival at 1 year for the 66 lung transplant recipients was 79%. Actuarial survival at 1 year was 82% for the bilateral lung transplant recipients and was 90% for the single-lung transplant recipients. In patients with either restrictive or obstructive lung disease, pulmonary function tests and arterial blood gas levels improved markedly after lung transplantation. In patients with primary pulmonary hypertension or Eisenmenger's syndrome, the pulmonary artery pressure decreased and the cardiac index increased into the normal range after single-lung transplantation. CONCLUSIONS: --In carefully selected patients with end-stage lung disease, single-lung and bilateral lung transplantations can significantly improve functional capacity, with promising early actuarial survival statistics after 1 year.

Actuarial Analysis↗
PubMed1996

[Results of 75 lung transplantations performed in Groningen in 1990-1995. Lung Transplantation Group Groningen].

OBJECTIVE: To describe the development of the lung transplantation programme in Groningen, and the results of single and bilateral lung transplantations in the first 75 consecutive patients, up to December 1995. DESIGN: Retrospective. SETTING: Academic Hospital Groningen, the Netherlands. METHODS: The results of the lung transplantation programme were evaluated retrospectively. RESULTS: In November 1990 the first unilateral lung transplantation was performed in Groningen in a patient with pulmonary fibrosis. In February 1991 a national lung transplantation programme for the Netherlands was instituted in Groningen by the government. Of 500 patients referred from all over the Netherlands from 1990 to December 1995, 75 were transplanted, 16 unilaterally and 59 bilaterally. The actuarial survival for all patients was 85% after 1 year and 72% after 2 years. After transplantation 16 patients died (21%) after 15 months follow-up (median). Early mortality (5%) was caused by graft failure, late mortality (16%) by chronic rejection and lymphoproliferative disease. The mean time on the transplantation waiting list was 9.3 months; it increased during the programme. The limiting factor for further expansion of the programme was caused by donor scarcity. The lungs from only 16% of the multiorgan donors reported by Eurotransplant to our centre could be transplanted. CONCLUSION: The results of the lung transplantation programme in Groningen are good but with an increasing number of lung transplantation centres in the Eurotransplant region the further development of lung transplantation in the Netherlands will depend mainly on the availability of lung donors from the Netherlands.

Adolescent↗
PubMed1998

Quality of life 6 months after heart transplantation compared with indicators of illness severity before transplantation.

BACKGROUND: Quality of life is an important healthcare outcome to study. Quality of life after heart transplantation has not been compared with indicators of severity of illness before heart transplantation. OBJECTIVE: To compare differences in quality of life 6 months after heart transplantation with two preoperative indicators of severity of illness: New York Heart Association classification and United Network for Organ Sharing status. METHODS: Data were collected from a nonrandom sample of 219 adult patients who had received a heart transplant 6 months earlier. Patients were divided into groups on the basis of their New York Heart Association classification and United Network for Organ Sharing status immediately before transplantation. Instruments used were the Heart Transplant Symptom Checklist, Heart Transplant Stressor Scale, Rating Question Form, Quality of Life Index, Sickness Impact Profile, and Jalowiec Coping Scale. Data were analyzed with descriptive statistics, chi-square tests, and independent t tests. RESULTS: Quality of life 6 months after receiving a heart transplant varied with severity of illness before transplantation. These differences in quality of life were in the following domains: physical and occupational function, psychological state, and social interaction. Six months after receiving a heart transplant, patients who were more severely ill before transplantation were less satisfied with their lives, perceived that they were not doing as well, experienced more family-related stress, and used more negative coping strategies than did patients who were less severely ill preoperatively. CONCLUSIONS: These findings indicate the need for further study of quality of life in the transplant recipients who are the most critically ill in intensive care settings before surgery, to develop interventions to improve recipients' quality of life, and to evaluate effectiveness of those interventions longitudinally.

Adaptation, Physiological↗
PubMedDate not supplied

Can clamping of splenic vessels prevent abrupt increase of portal vein pressure and migration of transplanted hepatocytes to the liver after intrasplenic hepatocyte transplantation?

BACKGROUND/AIMS: It is well known that hepatocyte transplantation can retain some proper functions, significantly improve the survival rate of rats with different models of acute fulminant hepatic failure, correct some congenital genetic disorders, and improve liver function in cirrhosis. Portal hypertension and hepatic embolization have been described following intrasplenic hepatocyte transplantation. We evaluated the effect of temporary occlusion of splenic vessels on changes in portal vein pressure and on distribution of transplanted hepatocytes after hepatocyte transplantation into the spleen in normal rats. METHODOLOGY: Liver cirrhosis has been induced in rats by 1% dimethylnitrosamine (Sigma, St. Louis, Mo) dissolved in normal saline at the dose of 10 ml of DMN/Kg, i.p., 3 consecutive days a week for 4 weeks. Donor hepatocytes were harvested by in situ ethylenediaminetetraacetic acid (EDTA) perfusion. Changes in portal vein pressures were monitored by a pressure monitor and distribution of transplanted hepatocytes was assayed by measurement of radioactivity of 51Cr-labeled transplanted hepatocytes according to clamping or non-clamping during intrasplenic hepatocyte transplantation. RESULTS: The changes in portal pressure remained significantly high 10 min after hepatocyte transplantation in the nonocclusion groups compared to the occlusion groups. However, the changes in portal vein pressures in cirrhotic rats returned to normal faster than in normal rats after cell transplantation in the nonocclusion groups. The distribution of 51Cr-labeled transplanted hepatocytes into the spleen significantly diminished radioactivity of the liver at 10 min, 2 hours, and 24 hours in the occlusion groups compared to the nonocclusion groups. Also, duration of clamping time of splenic vessels did not influence the initial distribution of transplanted hepatocytes at the time of intrasplenic hepatocyte injection. CONCLUSIONS: These results suggested that temporary occlusion of splenic vessels should be routinely used during intrasplenic hepatocyte transplantation.

Animals↗
PubMed2002

Use of EBV PCR for the diagnosis and monitoring of post-transplant lymphoproliferative disorder in adult solid organ transplant patients.

Epstein-Barr virus (EBV) is known to be involved in the majority of patients who develop post-transplant lymphoproliferative disorder after solid organ transplant. We conducted a retrospective study to determine the utility of qualitative and quantitative Epstein-Barr virus polymerase chain reaction (PCR) for the diagnosis and monitoring of post-transplant lymphoproliferative disorder in adult solid organ transplant patients. Peripheral blood leukocytes obtained from 35 adult solid organ transplant patients consecutively referred for evaluation of possible post-transplant lymphoproliferative disorder, were tested by EBV PCR at the time of initial evaluation and at time points thereafter. Eighteen of 35 (51%) patients were ultimately diagnosed with post-transplant lymphoproliferative disorder by tissue biopsy. Fifteen of 18 (83%) patients were found to have EBER-1 positive tumors by in situ hybridization. EBV PCR was positive in 7 of 15 patients, suggesting a sensitivity of 39%. Seventeen patients without post-transplant lymphoproliferative disorder and three with EBER-1 negative post-transplant lymphoproliferative disorder all had negative EBV PCR tests, suggesting a specificity of 100%. We observed that declines in EBV DNA load were associated with response to therapeutic interventions, such as reduction in immunosuppression, rituximab therapy and chemotherapy. We conclude that peripheral blood EBV PCR may have a role in the diagnosis and monitoring of post-transplant lymphoproliferative disorder in adult solid organ transplant patients.

Adult↗
PubMed2000

Second allogeneic haematopoietic stem cell transplantation in relapsed acute and chronic leukaemias for patients who underwent a first allogeneic bone marrow transplantation: a survey of the Société Française de Greffe de moelle (SFGM).

Although recurrent malignancy is the most frequent indication for second stem cell transplantation (2nd SCT), there are few reports that include sufficiently large numbers of patients to enable prognostic factor analysis. This retrospective study includes 150 patients who underwent a 2nd SCT for relapsed acute myeloblastic leukaemia (n = 61), acute lymphoblastic leukaemia (n = 47) or chronic myeloid leukaemia (n = 42) after a first allogeneic transplant (including 26 T-cell-depleted). The median interval between the first transplant and relapse, and between relapse and second transplant was 17 months and 5 months respectively. After the 2nd SCT, engraftment occurred in 93% of cases, 32% of patients developed acute graft-vs.-host disease (GVHD) >/= grade II and 38% chronic GVHD. The 5-year overall and disease-free survival were 32 +/- 8% and 30 +/- 8%, respectively, with a risk of relapse of 44 +/- 12% and a transplant-related mortality of 45 +/- 9%. In a multivariate analysis, five factors were associated with a better outcome after 2nd SCT: age < 16 years at second transplant; relapse occurring more than 12 months after the first transplant; transplantation from a female donor; absence of acute GVHD; and the occurrence of chronic GVHD. The best candidates for a second transplant are likely to be patients with acute leukaemia in remission before transplant, in whom the HLA-identical donor was female and who relapsed more than 1 year after the first transplant.

Acute Disease↗
PubMed2002

Correlation of time to platelet engraftment with amount of transplanted CD34+CD41+ cells after allogeneic bone marrow transplantation.

A major problem after autologous or allogeneic stem cell transplantation is prolonged thrombocytopenia. There are several studies published about correlations of the composition of the graft and time to platelet engraftment for autologous transplantation but only a few studies for allogeneic transplantation. In our study, we wanted to find out whether the correlation between the time to platelet engraftment and amount of transplanted CD34(+)CD41(+) cells described previously after autologous peripheral blood stem cell transplantation could be reproduced in the allogeneic bone marrow transplantation setting. We found correlations not only for the number of transplanted CD34(+) cells with the time to leukocyte engraftment (r = -0.32, p = 0.045) but also for the number of transplanted CD34(+)CD41(+) cells and time to platelet engraftment (r = -0.34, p = 0.038), which were both statistically significant. A significant correlation between transplanted CD34(+) cells versus platelet engraftment and transplanted CD34(+)CD41(+) cells versus leukocyte engraftment was not found. The finding that the amount of committed megakaryocyte progenitor cells in the graft is an important predictive factor for platelet engraftment after allogeneic bone marrow transplantation might be the base for future studies of ex vivo expansion of clonable megakaryocyte precursors.

Adolescent↗
PubMed2002

Increased presence of anti-HLA antibodies early after allogeneic granulocyte colony-stimulating factor-mobilized peripheral blood hematopoietic stem cell transplantation compared with bone marrow transplantation.

We have recently shown that the use of allogeneic granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood hematopoietic stem cell transplantation (PBHSCT), as compared with bone marrow transplantation (BMT), is associated with increased titers of antibodies (Abs) directed against red blood cell ABO antigens. To further evaluate the influence of a G-CSF-mobilized PBHSCT graft on alloimmune Ab responses, we examined the frequency of anti-HLA Abs after transplantation in the setting of the same randomized study, comparing PBHSCT with BMT in adults. Anti-HLA Ab presence was determined by complement-dependent cytotoxicity assay (CDC) and flow cytometry in the recipient before and 30 days after transplantation as well as in the donor before graft donation. The use of PBHSCT was significantly associated with increased detection of anti-HLA immunoglobulin G (IgG) Abs early after transplantation as evidenced by flow cytometry (11 of 24 versus 4 of 27 transplant recipients, P =.03) and, less so, by CDC (5 of 24 versus 1 of 27 transplant recipients, P =.09). The difference between PBHSCT and BMT was further heightened when analysis was restricted to anti-HLA IgG Ab-negative donor/recipient pairs. In such a setting, early anti-HLA Ab was never detected after BMT but was repeatedly detected after PBHSCT (flow cytometry, 6 of 18 versus 0 of 17 transplant recipients, P =.02; CDC, 4 of 23 versus 0 of 26 transplant recipients, P =.04). Importantly, the PBHSCT-associated increase in anti-HLA Ab detection was observed despite a reduction in the median number of platelet-transfusion episodes per patient in PBHSC transplant versus BM transplant recipients (3 platelet-transfusion episodes [range, 1-21] in PBHSCT group vs 6 platelet-transfusion episodes [range, 3-33] in the BMT group; P =.02). In conclusion, this study strongly suggests that G-CSF-mobilized PBHSCT results in an increased incidence of circulating anti-HLA Abs and further confirms that the use of such a graft alters alloimmune Ab responses.

Adult↗
PubMed2004

Lymphomas after solid organ transplantation: a collaborative transplant study report.

We used the Collaborative Transplant Study database to analyze the incidence, risk, and impact of malignant lymphomas in approximately 200,000 organ transplant recipients. Over a 10-year period, the risk in renal transplant recipients was 11.8-fold higher than that in a matched nontransplanted population (p<0.0001). The majority of lymphomas were diagnosed after the first post-transplant year. Heart-lung transplants showed the highest relative risk (RR 239.5) among different types of organ transplants. In kidney recipients, immunosuppression with cyclosporine did not confer added risk compared with azathioprine/steroid treatment, whereas treatment with FK506 increased the risk approximately twofold. Induction therapy with OKT3 or ATG, but not with anti-IL2 receptor antibodies, increased the risk of lymphoma during the first year. Antirejection therapy with OKT3 or ATG also increased the risk. First-year mortality in renal and heart transplant patients with lymphoma was approximately 40% and 50%, respectively, and showed no improvement in recent years. A pattern of preferential localization to the vicinity of the transplant was noted, and the prognosis of the patient was related to localization. This study highlights the continuing risk for lymphoma with time post-transplantation, the contribution of immunosuppression to increased risk, and continuing poor outcomes in patients with post-transplant lymphoma.

Adolescent↗
PubMed2004

Reducing transplant-related mortality after allogeneic hematopoietic stem cell transplantation.

BACKGROUND AND OBJECTIVES: Transplant-related mortality (TRM) following allogeneic hematopoietic stem cell transplantation (HSCT) has been reported to be related to disease stage, duratiion of disease and type of donor. Furthermore, the outcome of transplants performed in the 1990s appears to be better than that of transplants done in the previous decade. The aims of this study were to determine whether these relationships still hold and whether the outcome of transplants is continuing to improve. DESIGN AND METHODS: We analyzed 1180 consecutive patients with leukemia (n=979) or other hematologic malignancies (n=201) undergoing HSCT in 4 time periods: before 1990, 1991-1995, 1996-2000, and 2001-2002. Changes during these eras include increasing patient age, more unrelated transplants, more patients with advanced disease, different graft-versus-host disease (GvHD) prophylaxis, and different management of infections. RESULTS: The actuarial 2-year transplant-related mortality (TRM) differed significantly between the transplant eras (p<0.001) with a significant interaction with disease phase (p=0.018). In patients in first remission (n=585) TRM was 34%, 25%, 21% and 6% in the four transplant eras. The reduction in TRM was less evident in patients in second remission (n=284) (37%, 35%, 30%, 25%) and absent in relapsed patients (n=311) (TRM=45%, 41%, 29%, 51%). This is a consequence of reductions in GvHD, infections and multiorgan failure among patients in remission but not among those who relapse. The actuarial 2-year survival has improved significantly in patients in first remission (54%, 66%, 72%, 78%) but not in those in second remission (38%, 46%, 52%,45%), or relapsed patients (31%, 25%, 36%, 21%). INTERPRETATION AND CONCLUSIONS: In conclusion, TRM has been significantly reduced in first remission patients, suggesting an allograft should be considered in this phase, when appropriate, without delay. There has been no improvement in survival for patients beyond first remission, due to persisting high risk of infections and organ toxicity, a possible consequence of prolonged pre-transplant chemotherapy and neutropenia.

Actuarial Analysis↗