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PubMed1988

Survival and development of embryonic and postnatal cerebellum transplanted into adult rat hosts: effect of growth as explants in culture prior to transplantation.

The survival and organization of embryonic and postnatal cerebellum transplanted into intracephalic cavities in adult rat hosts was studied before and after growth as explants in tissue culture. It is well known that embryonic cerebellum survives transplantation and develops a typical cerebellar cytoarchitecture. This study demonstrates that early postnatal cerebellum survives transplantation poorly if at all using the intracephalic transplant paradigm. Postnatal cerebellum is capable of extensive growth and organization in explant culture; however, prior growth in explant culture did not enhance survival in the transplant situation. On the other hand, embryonic cerebellum grown in explant culture for as long as two weeks, to an age comparable to the postnatal cerebellar transplants, survives transplantation and develops similar cytoarchitectural features to directly transplanted embryonic cerebellum.

Aging↗
PubMed2002

The Transplant Effects Questionnaire (TxEQ): The development of a questionnaire for assessing the multidimensional outcome of organ transplantation - example of end stage renal disease (ESRD).

OBJECTIVES: To develop a questionnaire to assess the responses of transplant recipients to the receipt of an organ, including their self-care behaviour. DESIGN: Following a literature review, open-ended interviews and a focus group, a transplant questionnaire was developed. Two studies (Study 1: N = 231, Study 2: N = 105) were conducted to evaluate its psychometric properties. METHODS: A pool of 51 items was derived from themes identified in published studies and from interviews and a focus group discussion with renal transplant recipients. These were constructed into a questionnaire and were then administered to two renal transplant out-patients populations. Item responses of study sample 1 were subjected to principal components analysis (PCA) using varimax rotation to examine the structure of responses. In order to investigate the stability of the factor structure found in Study 1, item responses of the second sample were subjected to confirmatory factor analysis (CFA) using structural equation modelling. RESULTS: PCA indicated six factors that accounted for 64.2% of the variance. With extraneous items omitted, the final questionnaire derived from Study 1 has 24 items clustered around five conceptual coherent factors: worry about transplant (22.1%), guilt regarding donor (11.9%), disclosure (9.58%), medication adherence (8.73%), and responsibility (6.63%). CFA on the final 24-item version of the TxEQ revealed that the resulting model was a good fit for the Study 2 data (RMSEA = 0.08, pclose =.005). CONCLUSIONS: The TxEQ has potential application as a measure in the area of transplantation research. CFA demonstrated that the factor structure of the TxEQ is consistent across different renal transplant out-patients populations. Further research is currently in progress to assess other groups of transplant recipients and to examine its relationship to other measures.

Journal Article↗
PubMed1993

Comparative abilities of athymic nude mice and severe combined immune deficient (SCID) mice to accept transplants of induced rat mammary carcinomas: enhanced transplantation efficiency of those rat mammary carcinomas that have elevated expression of neu oncogene.

Grafts of primary carcinogen (DMBA)-induced mammary carcinomas from Sprague-Dawley rats have a poor transplantation efficiency in athymic nude mice. Further compromising these mice immunologically via whole-body irradiation and/or splenectomy, or the administration of hormonal growth factors (estrogen and progesterone) to these mice, did not significantly alter transplantation efficiency. Use of strains of mice that are more immune-impaired than the athymic nude mouse, i.e., the athymic nude-beige-XID mouse (T-cell and LAK-cell deficient) or mice with severe combined immune deficiency (SCID) (which lack functional T cells and B cells) also failed to improve transplantation efficiency. In contrast, transplantation efficiency was sharply increased when primary neu-induced rat mammary carcinomas from female Sprague-Dawley rats were used. These mammary carcinomas, unlike the DMBA-induced rat mammary carcinomas, have a very high level of expression of neu; transplantation of these tumors to either athymic nude mice or SCID mice was considerably more efficient. Thus, these data provide evidence that enhanced expression of neu confers heightened efficiency in the transplantation of primary rat mammary carcinomas to immune-deficient mice (athymic-nude or SCID). Increased neu expression was a greater determinant than more compromised immune states in the transplantation of these rat mammary carcinomas. This biological characteristic of neu expression in mammary carcinomas provides new, additional insight into the importance of this oncogene in mammary tumorigenic processes and may explain, at least in part, the reported inverse relationship between human breast carcinoma neu expression and patient prognosis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1998

Combined liver-kidney transplantation in patients with cirrhosis and renal failure: effect of a positive cross-match and benefits of combined transplantation.

Patients with renal failure after liver transplantation have a particularly poor prognosis. Therefore, in the setting of end-stage renal disease requiring dialysis or severe renal insufficiency that will not improve after liver replacement, combined liver-kidney transplantation (LKT) is the preferred approach. We have adopted a policy of LKT in patients with end-stage liver disease and renal insufficiency undergoing dialysis or with a creatinine clearance less than 35 mL/min and evidence of chronic renal dysfunction. Since 1991, we have performed 208 orthotopic liver transplantations. Fourteen patients (8%) have undergone combined LKT, including 6 patients undergoing hemodialysis. Cytotoxic cross-matches (modified Amos technique and antihuman globulin method) were performed on 13 of 14 patients and were positive in 3 patients. Two patients died less than 4 months after LKT and 12 patients are alive and well. Graft survival censored for patient death was 100% for liver allografts and 93% for renal allografts, with a mean follow-up of 39 +/- 24 months. The most recent serum creatinine level in the patients with the 11 functioning grafts was 1.1 +/- 0.6 mg/dL. Biopsy-proven acute rejection occurred in 50% of simultaneous liver allografts. By contrast, only a single episode (6%) of renal allograft dysfunction was attributable to acute rejection. All rejection episodes occurred in the first 90 days after transplantation and were steroid sensitive. Three of 14 combined procedures were performed in the setting of a positive cytotoxic cross-match. In 2 recent patients, the results were confirmed by positive cross-matches to the donor's T and B cells by flow cytometry. Flow cytometric cross-matches reverted to negative 1 hour after liver transplantation and several hours before the administration of antithymocyte globulin. The cross-matches remained negative on postoperative days 1 and 7. Presently, all 3 patients with a positive cross-match enjoy normal hepatic and renal function at 631, 706, and 2275 days follow-up. Renal scans were performed in 4 LKT recipients not previously undergoing hemodialysis and indicated varying and unpredictable degrees of function in the native and transplanted kidneys. In conclusion, combined LKT can be performed safely and is associated with a low rate of acute rejection, even in the setting of a positive cross-match. Predicting which patients with renal insufficiency will benefit from LKT remains challenging; however, these results suggest that LKT should be encouraged in patients with evidence of irreversible renal insufficiency who require liver transplantation.

Adult↗
PubMed1997

Co-transplantation of fetal lateral ganglionic eminence and ventral mesencephalon can augment function and development of intrastriatal transplants.

Methods to increase the development and sustained function of embryonic mesencephalic dopamine cells after transplantation into dopamine (DA)-depleted striatum are currently under investigation. Elements that are crucial for the maturation and connectivity of neurons during normal development of the brain may also play a role in the development and integration of grafted embryonic tissue. Based on in vitro and in vivo observations of the enhancing effects of striatal tissue on nigral dopaminergic cell development and survival, we demonstrate that inclusion of embryonic striatal cells, specifically from the lateral ganglionic eminence (LGE), produces dopaminergic transplants with augmented functional effects. Rats neonatally DA-depleted and co-transplanted with embryonic nigral and LGE cells developed improved functional outcome when compared with animals receiving only nigral cells, and they required the transplantation of fewer nigral cells to produce a strong behavioral effect. Anatomically, the inclusion of LGE cells produced increased DA cell survival, a higher density of reinnervation into the DA-depleted host striatum, and patches of DA fibers within the co-transplants. There were also an increased number of host striatal cells which induced the immediate-early gene c-fos in co-transplanted animals compared to animals receiving nigral cells alone, indicating a higher degree of host-cell activation. The ability to enhance function, cell survival, reinnervation, and host activation with nigral-striatal co-transplants in the presence of fewer nigral cells supports the hypothesis of a trophic influence of striatal cells on nigral DA cells.

Amphetamine↗
PubMed2003

Break of tolerance via donor-specific blood transfusion by high doses of steroids: a differential effect after intestinal transplantation and heart transplantation.

UNLABELLED: Tolerance requires active mechanisms. How immunosuppressors affects tolerance is poorly understood. METHODS: RA (RT1(p))/PVG (RT1(c)) rats were used as donor/recipient. Intestinal and heart transplant model were selected as highly and poorly immunogenic organs. Studied groups were 1, rejecting control; 2, received peritransplant steroids; 3, donor-specific blood transfusion (DSBT); 4, DSBT plus peritransplant steroids; and 5, DSBT+periDSBT Ste. RESULTS: Intestinal transplant recipients in group 1 died on posttransplant day (d) 18. In group 2, steroids did not change survival (17 days, P >.05 versus group 1). With DSBT (group 3), all rats survived >75 days, whereas with steroids those in group 4 survived 59 days (P >.05 vs group 3) and group 5 survived 51 days (P <.05 versus group 3). Survivors in group 2 were tolerant as evidenced by acceptance of secondary donor-specific (not third-party) graft. However, 100% and 33% of donor-specific secondary grafts were rejected in groups 4 and 5 (P <.05 and P >.05 versus group 3). In heart transplants, steroid treatment had no effect on graft survival (group 1 9 days; group 2 9 days; P >.05). DSBT (group 3) induced 100% tolerance (primary: >100 days, secondary: 100%). Unlike in intestinal transplantation, adjunction peritransplant steroids (group 4) allowed 100% of primary and 83% of secondary graft acceptance (P >.05 versus group 3). In group 5, (DSBT+periDSBT steroids) acceptance of primary and secondary grafts tended to be reduced (primary: 77 days; P >.05 versus group 3; secondary: 67%, P >.05 versus group 3). CONCLUSION: Steroid induction did not prolong graft survival after either intestinal or heart transplant. Adjunction of steroids to a DSBT tolerogenic regimen caused rejection of primary and secondary grafts, particularly after intestinal transplantation. Routine use of steroids in the clinics must be reconsidered, particularly when immunogenic organs are transplanted and when immunomodulation is applied.

Animals↗
PubMed2006

Risk of adverse post-transplant events after kidney allograft transplantation as predicted by CTLA-4 +49 and TNF-alpha -308 single nucleotide polymorphisms: a preliminary study.

Genetic differences between donor and recipient HLA haplotypes are of major importance for transplant rejection. Other genetic variations occurring in genes encoding cytokines and costimulatory molecules also appear to exert an influence on the manner the host immune system recognizes the allograft. The aims of this work were: 1) to study selected single nucleotide polymorphisms (SNPs) at the loci encoding the T-cell regulatory molecule CTLA-4 (CD152), and the cytokines interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, and transforming growth factor (TGF)-beta1 in a sample of healthy volunteers and a group of kidney-transplanted patients; and 2) to investigate whether an association exists between any of the SNPs studied and acute or chronic rejection, or non-responsiveness to steroid treatment during episodes of acute rejection (AR) after kidney allograft transplantation. When healthy volunteers were compared with transplanted patients, no significant differences were found in the distribution of genetic frequencies for any of the SNPs analyzed. However, in transplanted patients who received a kidney from a living related donor (KdTxL), a statistically significant association was found between carrying the CTLA-4 +49 A/A genotype and protection from experiencing acute rejection. No such association was found in the group of transplanted patients who received a kidney from a cadaveric non-related donor (KdTxCad). In both, KdTxL and KdTxCad patients, responsiveness to steroid treatment during acute rejection was also in association with the CTLA-4 (+49A/G) SNP. The CTLA-4 +49G allele was found at a very low frequency among steroid-resistant compared with steroid-sensitive patients. Finally, a statistically significant association was found between the presence of the TNF-alpha -308A allele and protection to suffer from chronic rejection. The genetic differences found may serve as risk predictors of adverse post-transplant events.

Adult↗
PubMed1999

[Combined renal and pancreas transplantation as treatment for chronic renal insufficiency of diabetic origin: a series of 50 consecutive transplantations].

STUDY AIM: The aim of this study was to report the results of 50 transplantations of kidney and pancreas performed in the same surgical centre for chronic renal insufficiency of patients with insulino-dependent diabetes. PATIENTS AND METHOD: From 1989 to 1999, 50 pancreatic transplantations were consecutively performed, 48 combined with a kidney transplantation and two in patients having a functioning kidney graft. The whole pancreas was transplanted in the right iliac fossa through an extraperitoneal approach with duodeno-vesical bypass of exocrine secretion. The kidney was transplanted in the left iliac fossa through a different extraperitoneal approach. Immunosuppression protocol included Azathioprine replaced by Mycophenolate Mofetil since 1996, associated with corticotherapy and Ciclosporine replaced by FK 506 since 1997. Recipients were 32 women and 18 men (mean age: 37 +/- 5 years) treated by insulinotherapy since 23 +/- 6 years and receiving 35 +/- 10 insulin units per day. Peptide C was 0.33 +/- 0.35 mg/mL and serum creatinin 726 +/- 260 mumol/L. RESULTS: One patient died on d10 from pulmonary artery thrombosis due to unknown drepanocytosis. The most frequent postoperative complications were leakage of duodeno-vesical anastomosis (n = 9) decreasing in frequency with experience, reoperated with preservation of the pancreatic graft in all cases and venous thrombosis of the pancreatic graft (n = 5) with a definitive loss of function. Secondary deaths occurred at 24, 36, 48, 50, 72 months with functioning grafts in two patients. With a mean 5-year follow-up, 44 patients were alive (88% of the whole series), 34 of them with two functional grafts (68% of the whole series) Sixteen pancreas grafts were lost: three by death of the patients, eight from surgical complications, four by rejection and one by transplantectomy of a functional graft. CONCLUSION: Combined kidney and pancreas transplantation is now very efficient in the treatment of diabetic renal insufficiency. Total pancreas transplantation through an extraperitoneal approach seems to be the safest method. A very strict selection of both donors and recipients is necessary.

Adult↗
PubMed2003

Nonmyeloablative bone marrow transplantation: Infectious complications in 65 recipients of HLA-identical and mismatched transplants.

Infections are a common complication of allogeneic bone marrow transplantation and the leading cause of transplantation-related mortality. It had been hypothesized that transplantation following nonmyeloablative preparative regimens would result in fewer infections by causing less mucosal injury, less graft-versus-host disease, and allowing earlier immune reconstitution. We have retrospectively reviewed the infectious complications of 65 consecutive patients with advanced hematologic malignancies who underwent bone marrow transplantation using a novel preparative regimen consisting of cyclophosphamide, thymic irradiation, and in vivo T-cell depletion. Cytomegalovirus (CMV) infection occurred in 52% of cases in which the donor or recipient had evidence of prior CMV exposure. Using a strategy of preemptive therapy and secondary prophylaxis with ganciclovir, no CMV disease occurred. Infections with gram-positive bacteria predominated over the first 100 days after bone marrow transplantation. Thereafter, the relative proportion of gram-negative infections increased without a significant increase in episodes of neutropenia. The rate of bacterial infections was not influenced by relapse of the underlying malignancy. Seven patients developed infections with Aspergillus species, which was the most common infectious cause of death in these patients. Infections with viruses other than CMV (n=10) and with protozoan organisms (n=2) also occurred. The use of HLA-mismatched donors, the occurrence of grade II-IV acute graft-versus-host disease, and treatment with corticosteroids did not influence the risk of CMV or bacterial or fungal infections in patients who underwent transplantation following this preparative regimen. Overall, the incidence and spectrum of infections in this series was similar to the reported incidence of infections following conventional myeloablative allogeneic stem cell transplantation. We conclude that a quantitative T-cell deficiency in these extensively T-cell depleted patients may be a risk factor for infection, even in the absence of graft-versus-host disease.

Adolescent↗
PubMed2001

Rejection profile of recent pediatric renal transplant recipients compared with historical controls: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

Historically, higher acute rejection rates, earlier first rejection, and an inability to reverse the rejection characterize pediatric renal transplantation. In recent years, short-term (1-year) graft survival of pediatric renal transplants has steadily improved. To test the hypothesis that these improvements were mediated by changes in acute rejection, we considered the rejection profile of patients who received a renal allograft between 1987 and 1989 (cohort A) and compared it with recipients transplanted between 1997 and 1999 (Cohort B). Cohort A comprised 1469 transplants and cohort B comprised 1189 transplants. Restricting the data to the first year of follow-up, rejection ratios were 1.6 and 0.7, respectively (p < 0.001). Sixty per cent of the later cohort (B) were rejection free at 1 year, compared with 29% for the earlier cohort (A) (p < 0.001). Controlling for donor source, the rejection reversal rate for the later cohort was significantly better than that of the early cohort (p < 0.001). Cumulative distribution of times to first rejection was significantly better for cohort B (p < 0.001). One-year graft survival for cohort B at 94% was significantly better than 80% for cohort A (p < 0.001). We conclude that the improved short-term graft survival is mediated by improvements in the rejection profile in more recently transplanted patients and that this may translate into a better half-life for pediatric renal transplant recipients who received an allograft in the years 1997-99.

Adolescent↗
PubMed1997

Increased incidence of cytomegalovirus (CMV) infection and CMV-associated disease after allogeneic bone marrow transplantation from unrelated donors. The Fukuoka Bone Marrow Transplantation Group.

Cytomegalovirus (CMV) infection and CMV-associated disease were monitored using the CMV antigenemia assay in 72 patients who received allogeneic bone marrow transplantation (BMT), and their incidences were compared between related and unrelated donor transplant patients. The incidence of CMV infection after BMT was significantly higher in patients who received transplants from HLA-matched unrelated donors than from HLA-matched sibling donors (87% vs 53%, P < 0.05). CMV-associated disease developed in 73% of unrelated and in 14% of sibling donor transplant patients (P < 0.01). The peak levels of CMV antigenemia were significantly higher in unrelated donors than in sibling donor transplant patients (16 vs 1 CMV antigen-positive cells per 50000 WBCs, P < 0.01). The median number of CMV antigen-positive cells on first detection was also significantly higher in unrelated donor transplant patients (15 vs 1, P < 0.01). The detection of CMV antigen-positive cells preceded the development of CMV-associated disease in 18% of unrelated donor transplant patients, suggesting a lower predictive value of CMV antigenemia for subsequent CMV-associated disease in unrelated donor BMT. Careful monitoring and further studies are needed for the early diagnosis and prevention of CMV-associated disease in unrelated donor BMT.

Adolescent↗
PubMed1997

European results of matched unrelated donor bone marrow transplantation for chronic myeloid leukemia. Impact of HLA class II matching. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

We have retrospectively analyzed the impact of prognostic factors on the outcome of serologically HLA-matched unrelated donor (UD) BMT for CML. For this purpose, we have studied a cohort of 366 patients transplanted in Europe between January 1985 and December 1994. The median age of the 211 males and 155 females was 34 years; 238 patients were transplanted in first chronic phase and 116 in advanced phases. The median interval from diagnosis to BMT was 827 days. GVHD prophylaxis consisted of CsA and MTX in 202 patients or of ex vivo or in vivo T cell depletion (TCD) in 129. Recently, DNA-based methods of HLA-class II typing have been used to improve donor selection. We obtained complete data on 300 donor/recipient (D/R) pairs. Among them, we have identified three groups of patients, according to specific HLA-DRB1 D/R compatibility. Two hundred and ten patients received marrow from donors identical for HLA-DRB1 (group 1). Thirty-one patients received BMT from a donor who was HLA-DRB1 mismatched (group 2) and 59 from a donor in whom specific HLA-DRB1 typing was not performed (group 3). The overall survival was 37 +/- 3% at 2 years and leukemia-free survival (LFS) was 31 +/- 3%. In univariate analysis, five variables had a favorable effect on LFS: transplant in first chronic phase (P = 0.0001), time interval from diagnosis to BMT shorter than the median (P = 0.01), prophylaxis of GVHD without TCD (P + 0.001), acute GVHD < grade III (P = 0.0009) and HLA-DRB1 D/R matching (P = 0.0001). Transplant-related mortality (TRM) was 49 +/- 4% in group 1, 79 +/- 8% in group 2 and 80 +/- 6% in group 3 (P = 0.0001). Multivariate analysis confirmed that HLA-DRB1 matching was the most significant factor influencing survival (P = 0.04), LFS (P = 0.013) and TRM (P = 0.0049). From these results, we have defined a 'good risk' group, ie patients transplanted in first chronic phase, from an HLA-DRB1 matched donor, without TCD as prophylaxis against GVHD. The 2 year LFS, TRM and relapse incidence for this group were 51 +/- 5%, 47 +/- 5% and 2 +/- 2%, respectively. This suggests that the long-term outcome of patients with favorable prognostic features can approach that of patients transplanted from geno-identical siblings. In contrast, the TRM for patients transplanted for advanced disease from non HLA-DRB1-identical donors was 94%. Such a high TRM clearly indicates that UD BMT is not justifiable for these individuals.

Adolescent↗
PubMed1998

Autologous stem cell transplantation (ASCT) for poor prognostic Hodgkin's disease (HD): comparative results with two CBV regimens and importance of disease status at transplant.

Clinical outcome of 47 consecutive patients with advanced HD who underwent ASCT in our Department was analyzed retrospectively. Median age was 28 years (28 males and 19 females). At transplant, 15 (32%) patients were in CR (five in first CR after two chemotherapy regimens and 10 in second CR), eight (17%) in PR (seven without a prior CR), 22 (51%) had relapsing disease (19 with sensitive relapse) and two had primary refractory disease. The CVB regimen with two different schedules was used: 22 (47%) patients received standard CBV (CY 6 g/m2, BCNU 300 mg/m2 and etoposide 600 mg/m2) and 25 (53%) received an increased CBV dose (CY 7.2 g/m2, BCNU 440 mg/m2 and etoposide 2 g/m2). Antitumor response for 28 evaluable patients was similar for both CBV regimens: 87 and 75% (P=0.39). At 7.2 years, actuarial overall survival (OS), progression-free survival (PFS) and event-free survival (EFS) for the whole series were 51.7+/-8%, 34+/-9% and 28+/-8%, with a median follow-up for the surviving patients of 3 years (0.7-7.6). No differences in these survival functions according to the CBV regimen used were observed (P=0.57). A history of a prior CR (P=0.003), duration of first CR >1 year (P=0.04), absence of bulky nodal disease at transplant (P=0.054), absence of extranodal disease at transplant (P=0.01), and a CR status at transplant (P=0.0006) were associated with a better PFS on univariant analysis. On multivariate analysis, only CR status at transplant remained significant (P=0.05). When patients in second CR at transplant and those in first sensitive relapse were analyzed separately, no differences in clinical characteristics or in treatment received pretransplant were observed; however, PFS was significantly different (P=0.01). In conclusion, CR status at transplant is useful in identifying 'good risk' patients and is necessary to obtain the greatest benefit from ASCT independent of the CBV regimen used.

Adolescent↗
PubMed1999

Using at least 5x10(6)/kg CD34+ cells for autologous stem cell transplantation significantly reduces febrile complications and use of antibiotics after transplantation.

For autologous stem cell transplantation, it is common practice to infuse at least 2 x 10(6)/kg CD34+ cells to ensure rapid engraftment. However it was recently claimed that increasing the threshold to 5 x 10(6)/kg leads to a faster platelet engraftment. To evaluate these threshold values in our patient population we undertook a retrospective analysis of 127 autologous transplants performed at our institution between 1992 and 1998. Diagnoses included Hodgkin's and non-Hodgkin's lymphoma, myeloma, acute leukaemias and solid tumours. The transplant was peripheral blood stem cells in 107 cases and CD34-selected peripheral blood stem cells in 20 cases. The median number of transplanted CD34+ cells was 3.2 x 10(6)/kg (range 0.64-25.9 x 10(6)/kg). Haematopoietic recovery to a neutrophil count >0.5 x 10(9)/l took a median of 10 (range 5-16) days from transplant. When comparing patients receiving at least 5 x 10(6)/kg and 2-5 x 10(6)/kg CD34+ cells we found a significant reduction in the median number of days with fever (1 vs 3.5 days, P = 0.0025), incidence of fever (78.8 vs 92.1%, P = 0.032) as well as duration of antibiotic treatment (7 vs 10 days, P = 0.038). This was paralleled by a faster neutrophil recovery to 0.5 x 10(9)/l (9 vs 10 days, P = 0.047). There was no significant difference in the number of platelet or red cell transfusions between the two groups. We conclude that transplantation with a stem cell dose of at least 5 x 10(6)/kg CD34+ cells reduces infectious complications and should thereby increase the safety of this type of therapy while reducing duration (and cost) of antibiotic therapy. The transplantation threshold should thus not remain at 2 x 10(6)/kg particularly in patients with a good stem cell mobilisation capacity.

Adolescent↗
PubMed2000

Autologous CD34+ enriched peripheral blood progenitor cell (PBPC) transplantation is associated with higher morbidity in patients with lymphoma when compared to unmanipulated PBPC transplantation.

High-dose chemotherapy followed by CD34+ enriched peripheral blood progenitor cell (PBPC) transplantation is used for the treatment of primary refractory or relapsed Hodgkin's and non-Hodgkin's lymphomas. The CD34+ enrichment procedure, while reducing tumor burden, may compromise immunological reconstitution in the transplanted patient and result in increased rates of post-transplant infection. We compared infectious complications in patients with lymphoma who were treated with high-dose chemotherapy and supported either with CD34+ enriched PBPC (n = 19) or unmanipulated PBPCs (n = 24). Analysis was limited to patients discharged from initial hospitalization for transplantation with a minimum of 1 year followup and free of lymphoma recurrence. We found a statistically significant increase in the number of patients with one or more infectious events in the CD34+ transplant group (14/19) compared with the unmanipulated PBPC group (9/24, P < 0.01). Greater numbers of patients with two or more infectious events were observed in the CD34+ group (7/19 vs 2/24, P < 0.03) and an increased incidence of bacterial infections was observed in the CD34+ group (10/19 vs 5/24, P < 0.05). Two deaths due to infectious complications were observed in the CD34+ group. There was no significant difference in blood lymphocyte or monocyte recovery between the groups. These data demonstrate a significant increase in the long-term incidence of infectious events in lymphoma patients transplanted with autologous CD34+ enriched PBPCs compared to unmanipulated PBPCs. Thus, patients who undergo CD34+ enriched PBPC transplantation should be followed closely for infectious complications and prolonged infectious prophylaxis should be considered.

Adult↗
PubMed2005

Use of intrathecal prophylaxis in allogeneic haematopoietic stem cell transplantation for malignant blood diseases: a survey of the European Group for Blood and Marrow Transplantation (EBMT).

SUMMARY: A survey was carried out among EBMT centres to describe the current practice concerning intrathecal (i.t.) prophylaxis in allogeneic stem cell transplantation for malignant diseases in patients with no central nervous system (CNS) manifestations of the disease at any time. A total of 90 centres reported their practice: 42 centres (47%) never used pre-transplant i.t. prophylaxis as part of the conditioning, whereas 48 centres (53%) gave i.t. prophylaxis to selected groups. The main indications were acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), and lymphoma (53, 33, and 23% of all centres, respectively). Prophylaxis was usually given to all patients with ALL, but often restricted to high-risk patients in AML and lymphoma. Of the 90 centres, 29 (32%) gave prophylactic i.t. treatment after the transplantation, mainly for the same indications as pre-transplant. This survey illustrates the heterogeneity in the current practice of i.t. prophylaxis in allogeneic transplantation for malignant blood disorders in Europe. The documentation in the literature to support the use of i.t. prophylaxis as part of transplantation for malignant diseases in patients without preceding CNS involvement is sparse. Based on the rarity of isolated CNS relapse after allogeneic stem cell transplantation, EBMT does not recommend routine i.t. prophylaxis to patients without prior CNS involvement.

Antineoplastic Agents↗
PubMed2005

Prognostic analysis of pre-transplant peripheral T-cell levels in patients receiving an autologous hematopoietic progenitor-cell transplant.

The purpose of this study was to evaluate pre-transplant T-cell status in autologous hematopoietic progenitor-cell transplantation (HPCT) recipients. Between 1999 and 2002 we prospectively enrolled 85 autologous HPCT recipients with solid tumors (N = 50) or hematological malignancies (n = 35). Patient diagnoses included breast cancer (N = 49), non-Hodgkin's lymphoma (N = 20), myeloma (N = 11), Hodgkin's disease (N = 3), germ-cell tumor (N = 1) and amyloidosis (N = 1). Levels of CD3, CD4, CD8, memory and naïve CD4, and CD8 T-cell subsets were analyzed before autologous HPCT. Autologous HPCT recipients presented with lower pre-transplant counts of CD3, CD4, but not CD8 T cells, as compared to healthy controls. Pre-transplant CD4 T-cell levels correlated with progression-free survival (PFS) (P = 0.002) and overall survival (OS) (P = 0.05), in patients with hematologic malignancies (P = 0.02) and breast cancer (P = 0.04). Specifically, pre-transplant memory CD4 + CD45RA - CD62L - T-cell levels correlated with PFS (P = 0.01). The prognostic effects of pre-transplant CD4 and CD4 + CD45RA - CD62L - T cells were independent of tumor diagnosis, tumor stage, tumor sensitivity, and, for breast cancer patients, Her2 / neu status. Our results suggest that pre-transplant CD4 T-cell status, specifically CD4 + CD45RA - CD62L - memory T cells, correlates with the outcome of autologous HPCT recipients. These observations suggest the feasibility of prospective identification of those patients at higher risk of relapse, based on their immune status.

Adult↗
PubMed2006

Biomarkers in transplantation: Prospective, blinded measurement of predictive value for the flow cytometry crossmatch after negative antiglobulin crossmatch in kidney transplantation.

This prospective, blinded observational study was conducted to measure the predictive value the of flow cytometric crossmatch for biopsy-proven acute rejection, graft loss, or death following kidney transplantation. Patients were selected for renal transplantation on the basis of a conventional antihuman globulin cytotoxic T-cell crossmatch. Flow crossmatch was performed simultaneously, but the results were not disclosed to the transplant team. A total of 257 kidney transplant recipients were enrolled in the study; 78 patients experienced biopsy-proven rejection in the first post-transplant year, and 41 patients lost their graft or died during the period of follow-up (mean: 2046 days). Kaplan-Meier estimates of rejection, graft loss, or patient death did not differ between subjects with a positive or negative flow crossmatch. Cox analyses showed no influence of the flow crossmatch on the risk of biopsy-proven acute rejection (P = 0.987). The sensitivity and specificity of the flow crossmatch for prediction of biopsy-proven rejection were 0.128 and 0.883, and the positive and negative post-test probabilities were 0.323 and 0.301, respectively. The magnitude of the channel shift did not influence the multivariate Cox regression model. The area under the receiver operating characteristic curve of the flow crossmatch was 0.483 (P = 0.71) and 0.572 (P = 0.38), respectively for the living and cadaver transplant recipients, indicating no discriminative value in this study population. Flow crossmatch appears to have no significant incremental value in predicting biopsy-proven acute rejection, graft loss, or death following kidney transplantation in patients who have a negative antihuman globulin cytotoxic T-cell crossmatch against their donor.

Adolescent↗