Antilymphocyte Globulin Research Articles

Intracellular Fas ligand is elevated in T lymphocytes in severe aplastic anaemia.

Increased expression of Fas receptor by haemopoietic progenitors in aplastic anaemia (AA) suggests that excessive apoptosis contributes to multilineage bone marrow (BM) failure. To investigate the role of Fas ligand (FasL) in triggering progenitor cell death, we examined FasL levels in T lymphocytes of patients with severe untreated AA (n = 8). Expression of FasL on the surface of CD3+ cells was not detectable. However, flow cytometric analysis of saponin-permeabilized cells demonstrated higher levels of intracellular FasL in AA than in normal T cells (P < 0.005), both prior to and following activation with phytohaemagglutinin. Confocal microscopy revealed that FasL-specific signals overlapped with cathepsin D staining, indicating that intracellular FasL is stored in lysosomal granules. Levels of intracellular FasL in patients examined 1 month after immunosuppression with antilymphocyte globulin and cyclosporin A were lower than prior to treatment. The caspase inhibitors, DEVD and zVAD, enhanced colony formation and prolonged survival of AA BM cells in liquid cultures by about 10-fold (P < 0.05). Taken together, these data provide further evidence that apoptosis by the Fas/FasL system plays a role in the depletion of stem cells in AA.

Single-center experience with mycophenolate mofetil in pediatric renal transplant recipients.

Mycophenolate mofetil (MMF), a potent and specific inhibitor of guanosine nucleotide synthesis, is a new immunosuppressive drug used to prevent rejection in transplant patients. Extensive data on its utility and efficacy exists in adult patients but there is limited experience in pediatrics. Twenty-four children (14 male, 10 female; 2-19 yr of age), eight of whom had received living-related donor (LRD) transplants and 16 of whom had received cadaveric donor (CD) transplants, have been treated with MMF in our institution since September 1996. MMF was administered for a duration ranging from 13 weeks to 38 months, at an average dose of 600 mg/m2 (range: 200-1,000 mg/dose) every 12 h, for a total experience of 304 patient months. MMF capsules were used in 16 patients and/or pediatric suspension in eight. Five patients were switched to MMF from azathioprine as a result of rejection episodes or inability to taper prednisone, between 5 weeks and 3.5 yr post-transplant. All patients received prednisone, cyclosporin A (CsA), and induction therapy with anti-lymphocyte globulin (19 patients), anti-thymocyte globulin (one patient) or daclizumab (four patients). In 12 patients started on MMF at the time of CD transplant, five (42%) had an acute rejection episode. In seven who received a LRD transplant, one (14%) had an acute rejection episode. No patients who were converted to MMF were treated for acute rejection following conversion to MMF. One LRD graft was lost at 19 days following injury to the donor artery at the time of retrieval. At the last follow-up, the average creatinine level was 93 micromol/L and average urea level was 8.6 mmol/L. One patient developed epigastric distress. Three patients developed diarrhea/abdominal pain requiring dose adjustment. Five episodes of leukopenia and one episode of thrombocytopenia required dose adjustment. Two patients developed symptomatic cytomegalovirus (CMV) infection, one while on acyclovir prophylaxis. No malignancy has been encountered to date. Hence, MMF can be administered safely to children with good effect and with an acceptable side-effect profile.

Successful therapy of acute vascular rejection with combined plasma-exchange and monoclonal antibody

ESPITE advances in the immunological monitoring of transplant recipients, better immunosuppressive drugs and understanding of humoral and cellular host responses, rejection remains a major cause of graft loss in kidney transplant recipients. The majority of grafts with acute vascular rejection (AVR) undergo irreversible loss of function as they fail to respond to increased levels of immunosuppression. 1 AVR is a clearly defined histological entity characterized by endothelial swelling and intimal mononuclear cell infiltration with or without fibrin deposits. Immunoflourescence examination shows deposits of IgM and C3 in the vessel wall in most cases. 2 While acute cellular rejection (ACR) usually responds to high dose steroids and/or antilymphocyte globulin, appropriate treatment of AVR is still not clear. There have been attempts at treating AVR with monoclonal CD3 antibody (OKT3), plasma exchange (PE) and steroids with variable results. 1‐ 6 Combined use of OKT3 and PE in the treatment of AVR has not been reported until today to the best of our knowledge. Hence, we report our limited experience in the treatment of AVR with combined use of OKT3 and PE.

Treatment with immunotoxin.

T-cell depletion prior to or beginning at the time of transplantation has been shown to be a valuable adjunct to the induction of immunological unresponsiveness. Both total lymphoid irradiation and anti-lymphocyte globulin have been used for this purpose in experimental models of transplantation as well as in human organ transplant recipients. However, these methods of T-cell depletion are limited in their ability to deplete T cells selectively due to non-specific targeting and limited efficacy. A new anti-CD3 immunotoxin has been developed with a far more potent ability to deplete T cells selectively as measured by flow cytometry analysis of peripheral blood T lymphocytes as well as lymph node lymphocytes. This immunotoxin is well tolerated by rhesus monkeys when administered in vivo. When administered as a single immunosuppressive agent pretransplant, it substantially promotes allograft survival, inducing tolerance in at least one-third of recipients as measured by subsequent acceptance of donor skin grafts and rejection of third-party skin grafts. When administered on the day of transplant in combination with steroid pretreatment and a brief course of deoxyspergualin or mycophenolate mofetil (4 to 14 days), long-term unresponsiveness is also produced and in a more reliable manner than using immunotoxin alone. A new immunotoxin directed at the human CD3epsilon has been developed with excellent potency in T-cell killing and lacking the Fc portion of the CD3 antibody. This construct may be useful for T-cell depletion in humans and has a potential application in tolerance induction in human organ transplantation. Lessons learned from anti-CD3 immunotoxin in the non-human primate model to date include (i) profound (2-3 log) depletion of T-cells can be accomplished safely without inducing lymphoma or infection, (ii) such depletion is a useful adjunct for tolerance induction to allogeneic organ transplants, and (iii) tolerance to both allogeneic renal transplants and xenogeneic islet transplants has been accomplished using such strategies to date in non-human primates and in pigs. Immunotoxin may be useful for the induction of chimerism using strategies that include donor bone marrow infusion. Successful strategies for tolerance induction have also been developed using immunotoxin without the adjunct of donor bone marrow or stem cell infusion. Clinical application of immunotoxin will use a newly engineered construct with the potential for causing cytokine release, less susceptibility to neutralization by anti-diphtheria antibody and not dependent on chemical conjugation of an antibody and toxin. The usefulness of immunotoxin is directly related to its tremendous potency for depleting T cells. Based on results in nonhuman primates, it is anticipated that it will become a useful agent in tolerance induction in humans.

Tacrolimus as a rescue immunosuppressant after heart transplantation.

The purpose of this retrospective study is to review our experience with tacrolimus as a rescue immunosuppressant for heart transplant recipients with refractory rejection or cyclosporine intolerance. From June 1995 to November 1998, 15 cardiac transplant recipients were converted from our standard cyclosporine-based immunosuppressive regimen to a tacrolimus-based treatment. Each patient had been treated with cyclosporine, azathioprine and steroids. Six were switched to tacrolimus for persistent rejection, four for recurrent acute rejection and five for severe debilitating side-effects attributed to cyclosporine. All ten patients converted to tacrolimus because of rejection had been treated with high-dose methylprednisolone intravenously and four had also received anti-lymphocyte globulin (ALG; one patient) or anti-thymocyte globulin (ATG; three patients) preparations. The time between transplantation and conversion to tacrolimus ranged from 44 to 1866 (median, 380) days. The range of follow-up after conversion was 84-1379 (median, 806) days. Eleven patients are alive with a follow-up period of 764+/-435 (median, 820) days. Four patients died between 90 and 930 (median, 464) days after conversion. The average number of episodes of acute rejection/recipient decreased from 2.1+/-1.6 on the cyclosporine regimen to 0.2+/-0.4 on the tacrolimus regimen (P<0.001). When the incidence of acute rejection was normalized for follow-up times (episodes/100 patient-days), the results were 1.1+/-1.4 and 0.07+/-0.2, respectively (P<0.01). The persistent/recurrent rejection resolved in all ten patients who were converted to tacrolimus. None of the five cyclosporine intolerant patients converted to tacrolimus experienced rejection after the changeover. In our experience, conversion from a cyclosporine-based to a tacrolimus-based maintenance immunosuppression has been shown to be an effective and safe approach to the management of patients with persistent or recurrent cardiac allograft rejection or those with cyclosporine intolerance.

Telomere length changes in patients with aplastic anaemia.

To investigate telomere changes in patients with aplastic anaemia (AA) and clinical factors influencing the telomere dynamics, telomere length (TL) was measured in peripheral blood mononuclear cells using Southern blot analysis of 42 patients with AA and 39 healthy normal controls. Nineteen patients received supportive treatment only, while the remaining 23 patients received immunosuppressive therapy with anti-thymocyte globulin or anti-lymphocyte globulin +/- cyclosporin A. In AA patients, TL was on average 1.41 kb shorter than that of age-matched normal controls (P < 0.001). In patients treated with immunosuppression, the mean TL of non-responders was significantly shorter than that of age-matched normal controls (P < 0.001), while no difference in TL was detected in responders compared with controls. Positive correlation was observed between the extent of telomere shortening, the severity of neutropenia (P = 0.05) and the degree of mean corpuscular volume elevation (P = 0.005) at the time of the study. However, there was no correlation with time elapsed since diagnosis (P = 0.214). These findings suggest that haematopoietic stem cells in patients with AA rapidly lose TL at the onset of the disease. The TL shortening may reflect the severity of impairment of haematopoiesis.

Combination of antilymphocyte globulin and leflunomide leads to superior grafts

Combination of antilymphocyte globulin and leflunomide leads to superior grafts

Umbilical cord blood transplantation from unrelated HLA-matched donor in an adult with severe aplastic anemia

A 23-year-old male suffering from severe aplastic anemia (SAA) weighing 60 kg was successfully treated by unrelated allo-CBSCT (cord blood stem cell transplantation). A six-loci HLA-identical umbilical cord blood (UCB) was infused after conditioning with low-dose cyclophosphamide (CTX) and antilymphocyte globulin (ALG). The prophylaxis of GVHD consisted of CsA and MTX. The infused cord blood provided 1.89 x 10(7) nucleated cells per kg, CD34-positive cells: 0.89%. Neutrophils >0.5 x 10(9)/l were reached 10 days after transplant, and platelets greater than 50.0 x 10(9)/l at day 26. RBC and platelet transfusion independence were reached on days 15 and 18. The patient developed grade 1 skin GVHD 10 months after engraftment of the donor cells. Microsatellite DNA fingerprinting indicated a stable and persistent donor-recipient mixed chimerism, whilst the circulating red cells remain of host origin.

Bone marrow failure in children with acute liver failure.

Aplastic anemia is a rare but well-recognized complication of acute hepatitis and acute liver failure. The cause is unknown, and the condition is fatal without bone marrow recovery. Treatment includes immunosuppression regimens or bone marrow transplantation. The purpose of this study was to investigate the incidence, cause, treatment, and outcomes of this disorder in children. Retrospective chart review of 75 patients with acute liver failure in a major pediatric liver center. Eight patients had evidence of bone marrow failure. Of those, six had aplastic anemia, and two had transient bone marrow suppression. There were five boys, median age 57 months (range, 36-132 months). Two had parvovirus B19, six had non-A, non-B, non-C hepatitis. Five underwent liver transplantation: auxiliary in one, orthotopic in four. The interval between initial symptoms and development of aplastic anemia and/or bone marrow suppression was 21 to 99 days (median, 39 days). Four patients with aplastic anemia received intravenous antithymocyte globulin (ATG) or antilymphocyte globulin (ALG). Median recovery period of granulopoiesis was 62 days (range, 27-115 days). Two made a full recovery, one had myelodysplasia, and one with unresponsive disease died of septic complications. Four did not receive ATG/ALG, two had aplastic anemia, and two had bone marrow suppression. Three underwent liver transplantation, and all four resumed granulopoiesis. One child who underwent liver transplantation died of sepsis with chronic rejection. Median recovery of granulopoiesis was 99 days (range, 20-153 days). Bone marrow failure occurs in 10.7% of children with acute liver failure. It sometimes occurs in association with non-A, non-B, non-C hepatitis and parvovirus B19 infection. Treatment with ATG/ALG is successful and is well tolerated in most cases.

Bone Marrow Failure in Children With Acute Liver Failure

ABSTRACTBackgroundAplastic anemia is a rare but well‐recognized complication of acute hepatitis and acute liver failure. The cause is unknown, and the condition is fatal without bone marrow recovery. Treatment includes immunosuppression regimens or bone marrow transplantation. The purpose of this study was to investigate the incidence, cause, treatment, and outcomes of this disorder in children.MethodsRetrospective chart review of 75 patients with acute liver failure in a major pediatric liver center.ResultsEight patients had evidence of bone marrow failure. Of those, six had aplastic anemia, and two had transient bone marrow suppression. There were five boys, median age 57 months (range, 36–132 months). Two had parvovirus B19, six had non‐A, non‐B, non‐C hepatitis. Five underwent liver transplantation: auxiliary in one, orthotopic in four. The interval between initial symptoms and development of aplastic anemia and/or bone marrow suppression was 21 to 99 days (median, 39 days). Four patients with aplastic anemia received intravenous antithymocyte globulin (ATG) or antilymphocyte globulin (ALG). Median recovery period of granulopoiesis was 62 days (range, 27–115 days). Two made a full recovery, one had myelodysplasia, and one with unresponsive disease died of septic complications. Four did not receive ATG/ALG, two had aplastic anemia, and two had bone marrow suppression. Three underwent liver transplantation, and all four resumed granulopoiesis. One child who underwent liver transplantation died of sepsis with chronic rejection. Median recovery of granulopoiesis was 99 days (range, 20–153 days).ConclusionsBone marrow failure occurs in 10.7% of children with acute liver failure. It sometimes occurs in association with non‐A, non‐B, non‐C hepatitis and parvovirus B19 infection. Treatment with ATG/ALG is successful and is well tolerated in most cases.

A quantitative flow cytometry assay for the preclinical testing and pharmacological monitoring of rabbit antilymphocyte globulins (rATG)

Rabbit antilymphocyte or antithymocyte globulins (rATG) are currently used as immunosuppressive agents in clinical organ and bone marrow transplantation, but because of differences in antigen source and purification processes between manufacturers, determination of the dose to be administered remains empirical. Dosage may be adjusted to peripheral blood T cell counts or limited by side effects such as neutropenia or thrombocytopenia. We report here a measurement by indirect immunofluorescence of the amount of antibodies from rATG that bind to different blood cell types. A concentration-related immunofluorescence signal was obtained with reasonable replicability, allowing comparison of different rATGs by reference to the same rATG batch as internal standard. Ratios of antilymphocyte to undesirable antibodies (directed against antigens expressed on neutrophils, platelets or red cells) could be calculated for each rATG preparation. Finally, the method is applicable to the measurement of free antibodies in sera from patients treated with rATG and to the analysis of the effects of in vivo absorption of rATG during its administration. Marked differences in antibody content per mg of rIgG account for the differences in rATG dosage that were empirically established for clinical applications.

International Pediatric Nephrology Association resolutions

We have performed ten pediatric kidney transplantations from living-related ABO-incompatible donors. All patients underwent preoperative plasmapheresis with or without immunoadsorption to reduce isoagglutinin. Primary immunosuppression consisted of methyl-prednisolone, cyclosporin or tacrolimus, azathioprine, anti-lymphocyte globulin, and/or deoxyspergualin. At transplantation splenectomy was simultaneously performed in all patients. Median follow-up is 65 months (range 4-95 months). The patient and graft survival rates are 100% to date. Post-transplantation isoagglutinin titers did not increase more than 1:32, except for 1 patient, without uncontrollable vascular rejection episodes. Despite the heavy immunosuppressive regimen, cytomegalovirus infection occurred in only three patients, who were successfully treated with ganciclovir and cytomegalovirus high-titer gamma globulin. Our small series clearly shows that the preoperative reduction of isoagglutinin, splenectomy, and strict immunosuppressive therapy lead to successful long-term results in children.

Management of Acquired Aplastic Anemia

Acquired aplastic anemia is an uncommon disorder of unknown pathogenesis characterized by peripheral blood pancytopenia and a hypocellular marrow, where normal hematopoietic tissue is replaced by fat cells. About 15% of cases follow exposure to drugs or a hepatitic‐like illness. The differential diagnosis includes congenital aplastic anemia, myelodysplastic syndrome (MDS) or leukemias presenting with hypocellular phase and, rarely, antibody‐mediated pancytopenias. Support with blood products and the avoidance and treatment of infection provide the essential platform for more definitive therapy. Allogeneic stem cell transplantation from a human leukocyte antigen (HLA)‐matched sibling donor is the most appropriate first‐line treatment for children and young adults (&lt; 45 years of age) with severe or very severe aplastic anemia. Immunosuppression with antilymphocyte globulin or antithymocyte globulin followed by cyclosporine is the most appropriate treatment for the remaining patients. The response to therapy is determined mainly by the severity of the disease and is independent of the etiology. Immunosuppressive therapy is equally effective in older patients as in younger. Sibling transplantation is successful in 70–90% of cases — the results seem to improve year by year. About two out of three patients respond to a first course of immunosuppressive therapy, but relapse or late complications occur in 25–40% of patients so treated over 10 years. In patients who do not respond to the first course of immunosuppression, subsequent courses can be given with the expectation of success, although the response is slow. Late complications include the emergence of abnormal clones, e.g. paroxysmal nocturnal hemoglobinuria, MDS and acute leukemia. The place of stem cell transplantation from unrelated volunteer donors has yet to be properly defined.

Acute humoral rejection of kidney allografts in patients with a positive flow cytometry crossmatch (FCXM).

The patients with a positive flow cytometry crossmatch (FCXM) are categorized as a high-risk group causing hyperacute or accelerated acute rejection after kidney transplantation. According to the successful results of ABO-incompatible renal transplantation, we have performed the living related transplant operations in the recipients with positive FCXM for donor T cells, but having a negative complement-dependent lymphocytotoxic reaction test. We have followed the clinical course of 4 FCXM-positive patients, and 2 of them have developed acute humoral rejection. We report the strategies for FCXM-positive living kidney transplantations and the characteristics of pathological findings of acute humoral rejection in FCXM-positive renal transplants. We have had few episodes of acute humoral rejection in ABO-incompatible kidney transplantations under immunosuppressive regimens, including cyclophosphamide, but 2 patients of 4 with FCXM-positive kidney transplantations developed acute humoral rejections. The differences in immunosuppressive regimen between ABO-incompatible and FCXM-positive kidney transplantations concern anti-lymphocyte globulin (ALG) and splenectomy. We have not performed splenectomy and ALG administration in FCXM-positive kidney transplantations. Severe acute rejection episodes have been experienced on post-operative days 7 and 9 in 2 of 4 FCXM-positive recipients. The early acute rejection episodes were clinically and pathologically diagnosed as typical humoral rejections. We have examined an immunofluorescent study to prove the diagnosis of humoral rejection in FCXM-positive kidney transplantations; both immunoglobulin M and C3 were positive for the whole course of humoral rejection. The 2 patients with acute humoral rejection recovered after treatment with double filtration plasmapheresis or plasma exchange to remove their anti-donor antibodies. The gold standard of success in FCXM-positive kidney transplantations is to suppress the production and reduce the level of anti-donor antibodies after transplant operations.

An Extended Lymphocytotoxicity Test for Patients Treated with Lymphocytotoxic Antibodies

Background and Objectives: After organ transplantation, HLA antibodies (HLA–Ab) stimulated by transplant or transfusion are usually indistinguishable from passive therapeutic lymphocytotoxic antibodies (LyAb), e.g. antilymphocyte globulin (ALG), antithymocyte globulin (ATG) and OKT3, by standard lymphocytotoxicity tests (LCTs). Herein, an extended technique capable of distinguishing between these two types of antibodies is described. Materials and Methods: Serum samples from 11 patients who received therapeutic antibodies were screened for HLA–Ab by LCTs. The administered LyAb were murine OKT3 (n = 2), equine ALG (n = 3), rabbit ATG (n = 2), and combinations of ALG and OKT3 (n = 1), ATG and ALG (n = 1), and ATG and OKT3 (n = 2). To discriminate between therapeutically applied antibodies and active HLA alloimmunization, the sera were preincubated with species–specific anti–Fc IgG, thus blocking the therapeutic antibodies. Results: The sera of all patients treated showed strong positive lymphocytotoxic reactions [panel reactive antibodies (PRA) 50–100%]. After incubation with the corresponding Fc antibodies, in 9 of the 11 samples the amount of PRA decreased to the level present before transplantation (0–18%). In the remaining cases, new–onset alloimmunization was detected. Conclusion: This extended LCT allows the screening of serum samples for active HLA–Ab even in the presence of therapeutic LyAb.

An Extended Lymphocytotoxicity Test for Patients Treated with Lymphocytotoxic Antibodies

Abstract Background and Objectives: After organ transplantation, HLA antibodies (HLA‐Ab) stimulated by transplant or transfusion are usually indistinguishable from passive therapeutic lymphocytotoxic antibodies (LyAb), e.g. antilymphocyte globulin (ALG), antithymocyte globulin (ATG) and OKT3, by standard lymphocytotoxicity tests (LCTs). Herein, an extended technique capable of distinguishing between these two types of antibodies is described. Materials and Methods: Serum samples from 11 patients who received therapeutic antibodies were screened for HLA‐Ab by LCTs. The administered LyAb were murine OKT3 (n = 2), equine ALG (n = 3), rabbit ATG (n = 2), and combinations of ALG and OKT3 (n = 1), ATG and ALG (n = 1), and ATG and OKT3 (n = 2). To discriminate between therapeutically applied antibodies and active HLA alloimmunization, the sera were preincubated with species‐specific anti‐Fc lgG, thus blocking the therapeutic antibodies. Results: The sera of all patients treated showed strong positive lymphocytotoxic reactions [panel reactive antibodies (PRA) 50–100%]. After incubation with the corresponding Fc antibodies, in 9 of the 11 samples the amount of PRA decreased to the level present before transplantation (0–18%). In the remaining cases, new‐onset alloimmunization was detected. Conclusion: This extended LCT allows the screening of serum samples for active HLA‐Ab even in the presence of therapeutic LyAb.

Posttransplant lymphoproliferative disorders in renal allograft recipients: report of 53 cases of a French multicenter study

Abstract New immunosuppressive therapies are currently being developed in renal transplantation and their relative risk in terms of post-transplant lymphoproliferative disorders (PTLD) must be carefully evaluated. For this purpose, a French registry of PTLD occurring after renal transplantation was set up. Among 10000 patients presently followed up in 30 French renal transplantation centers, we prospectively identified 53 new PTLD (0.5 %) since January 1998. Patients (34 male, 19 female) ranged from 3 to 72 years (mean age: 46 years), and the median time between grafting and diagnosis of PTLD was 63 months (2 months to 14 years). Ninety percent of recipients were Epstein-Barr virus (EBV) positive before transplantation. Most patients received a quadruple sequential therapy with polyclonal anti-lymphocyte globulin. Sites involved in PTLD were isolated lymph nodes in 13 cases, stomach or bowel in 10 cases, allograft in 14 cases, central nervous system in 6 cases, oropharynx in 4 cases, and skin or mucosa in 4 cases. Only three PTLD expressed markers of T lineage. Out of 40 studied tumors, 31 (78%) were EBV positive. Tumors were classified as polymorph in 26 cases and monomorph in 23 cases. Genotype studies in 18 PTLD showed a monoclonal pattern in 13 cases. In most patients, treatment consisted of reduction of immune suppression, 21 patients were given additional anti-viral therapy, 13 patients had anti-CD20, 23 patients underwent chemotherapy, and 4 patients were given cerebral radiotherapy. Five patients underwent transplantectomy. Sixteen patients (30 %) died within the 1st year and 7 patients returned to dialysis (13 %). The outcome of patients with PTLD remains poor, and the optimal approach to therapy is largely unknown. This ongoing registry is not only a national observatory but also a task force designed to improve the treatment strategy of PTLD.

Living unrelated donors in kidney transplants: better long-term results than with non-HLA-identical living related donors?

Given the severe organ shortage and the documented superior results obtained with living (vs. cadaver) donor kidney transplants, we have adopted a very aggressive policy for the use of living donors. Currently, we make thorough attempts to locate a living related donor (LRD) or a living unrelated donor (LURD) before proceeding with a cadaver transplant. We compared the results of our LURD versus LRD transplants to determine any significant difference in outcome. Between 1/1/84 and 6/30/98, we performed 711 adult kidney transplants with non-HLA-identical living donors. Of these, 595 procedures used LRDs and 116 used LURDs. Immunosuppression for both groups was cyclosporine-based, although LURD recipients received 5-7 days of induction therapy (antilymphocyte globulin or antithymocyte globulin), whereas LRD recipients did not. LURD recipients tended to be older, to have inferior HLA matching, and to have older donors than did the LRD recipients (all factors potentially associated with decreased graft survival). Short-term results, including initial graft function and incidence of acute rejection, were similar in the two groups. LURD recipients had a slightly higher incidence of cytomegalovirus disease (P=NS). We found no difference in patient and graft survival rates. However, the incidence of biopsy-proven chronic rejection was significantly lower among LURD recipients (16.7% for LRD recipients and 10.0% for LURD recipients at 5 years posttransplant; P=0.05). LRD recipients also had a greater incidence of late (>6 months posttransplant) acute rejection episodes than did the LURD recipients (8.6% vs. 2.6%, P=0.04). The exact reason for these findings is unknown. Although LURD recipients have poorer HLA matching and older donors, their patient and graft survival rates are equivalent to those of non-HLA-identical LRD recipients. The incidence of biopsy-proven chronic rejection is lower in LURD transplants. Given this finding and the superior results of living donor (vs. cadaver) transplants, a thorough search should be made for a living donor-LRD or LURD-before proceeding with a cadaver transplant.

Opportunistic pulmonary infection after renal transplantation

INFECTIOUS complications in kidney transplant recipients are associated with significant morbidity and mortality. The risk of infection is based on two main factors: recent or past exposure to infectious agents, and the patient’s level of immunosuppression. Bacterial infections usually occur in the first month following transplantation, and technical issues related to the procedure can play an important etiologic role. Most febrile illness that occurs in kidney recipients between 1 and 6 months posttransplantation is caused by cytomegalovirus (CMV) and other opportunistic agents. The regimen and level of immunosuppression are important in the pathogenesis of these infectious complications. Kidney recipients whose grafts have come from cadavers tend to develop more frequent and severe infectious complications than living-donor kidney recipients due to the increased level of immunosuppression that is usually needed in the former group. Also, recipients of cadaveric kidneys who receive induction antilymphocyte globulin (ATG) preparations have higher infection rates than those who do not receive this treatment. Further, research has shown that patients who receive azathioprine as their primary immunosuppressive agent have a higher rate of infection than patients on cyclosporine-based regimens. Beyond 6 months, in patients with well-functioning allografts who are on stable maintenance immunosuppression the pattern of infection is similar to that in the general population. Another significant finding is that transplant recipients often develope infection that simultaneously involves several causal agents. This underlines the importance of considering concomitant infection in patients who do not respond to the initial line of treatment. While the incidence of tuberculosis (TB) after kidney transplantation in highly industrialized countries is low, the figure for developing regions is significantly higher. Mycobacterial disease should be considered in any patient with fever of unknown etiology. Most cases of Mycobacterium tuberculosis infection in kidney transplant recipients are due to reactivation of latent TB lesions. Important risk factors for reactivation include nonwhite race, history of active TB, presence of a marked abnormality on a chest radiograph, exposure to a person with a confirmed case of TB, and skin test positivity. In transplant patients, the clinical presentation of tuberculosis may be atypical, and extrapulmonary and miliary tuberculosis is seen more frequently than in the normal population. With regard to fungal infection, in kidney transplant recipients these most commonly present as prolonged fever that does not respond to antibiotic therapy. These infections are associated with very high mortality. The most common fungal infections reported in first series from developing countries were candidiasis, aspergillosis, and cryptococcosis. Several factors influence the development of symptomatic CMV infection after kidney transplantation, but most important are the CMV serologic statuses of the donor and recipient. Symptomatic CMV infection can be primary, can occur due to reactivation of latent infection, or can arise secondary to superinfection. The most severe form is usually observed when a CMV-seronegative recipient receives a graft from a CMV-seropositive donor. Host cell–mediated immunity and the type and level of immunosuppressive therapy influence the development of symptomatic CMV infections. Polyclonal and monoclonal antilymphocyte antibody treatments have the highest CMVpromoting effect, and represent the most important factor in the development of CMV infections after kidney transplantation. Nocardia is a filamentous gram-negative soil organism that can cause pneumonia. This infection also frequently disseminates to the brain and results in abscess formation. The overall mortality associated with nocardiosis in kidney transplant recipients is 25%, but this figure jumps to 44% in patients who have central nervous system involvement.

Very severe aplastic anemia following resection of lymphocytic thymoma: Effectiveness of antilymphocyte globulin, cyclosporin A, and granulocyte‐colony stimulating factor

Very severe aplastic anemia following resection of lymphocytic thymoma: Effectiveness of antilymphocyte globulin, cyclosporin A, and granulocyte‐colony stimulating factor