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Marrow transplantation for non-Hodgkin's lymphoma: a multi-centre study from the European Co-operative Bone Marrow Transplant Group.

Twenty-five patients with intermediate- or high-grade non-Hodgkin's lymphoma (NHL) were treated by allogeneic bone marrow transplantation. For the nine patients transplanted in first complete remission the disease-free survival was 100%; of the nine patients transplanted in subsequent remissions four (44%) achieved long-term disease-free survival but two died of relapsed lymphoma. For the seven patients transplanted at a time when they had active disease, the initial complete remission rate was high but four died of progressive lymphoma and no patient achieved long-term disease-free survival. The incidence of complications associated with allogeneic bone marrow transplantation was similar to that observed in other series of patients transplanted for haematological malignancy and was related to the status of the disease at the time of transplant. Thus allogeneic bone marrow transplantation is a radical but effective treatment for patients with NHL who have 'minimal residual disease'. Efforts to define further the subset of patients who can most successfully be treated by transplantation may improve the overall results.

Adolescent↗

The evaluation of candidates for renal transplantation. The current practice of U.S. transplant centers.

The criteria for acceptance of candidates for renal transplantation varies throughout the United States. The Patient Care and Education Committee of the American Society of Transplant Physicians conducted a survey of all U.S. centers that participate in the United Network for Organ Sharing (UNOS) concerning their evaluation of adult candidates for kidney transplantation. The response to each question was examined according to the specialty of the individual who filled out the questionnaire, as well as the type of transplant center (university or private) and the size of the center. The response rate to the survey was 81% (147/182). We found the following: (1) university-based and larger centers accepted more medically complicated patients; (2) 83% noted that attendance to dialysis was an important indicator of compliance after transplantation; (3) 79% did not require preoperative blood transfusions for cadaver kidney recipients; (4) 66% set no specific upper age limit for transplantation; (5) 56% excluded patients with chronic active hepatitis in the setting of hepatitis B antigenemia; (6) 50% had no specific policy for evaluating hepatitis C antibody-positive patients, while 54% excluded the use of hepatitis C antibody-positive donors, and (7) 15% obtained coronary angiography on all diabetic patients. U.S. transplant centers have a heterogeneous approach to the evaluation of patients for renal transplantation, particularly in the areas of viral hepatitis, cardiovascular disease, and noncompliance. University-based centers and centers that perform a larger number of transplants accept more medically complicated patients.

Adult↗

[Results of liver transplantations in Geneva or 32 consecutive transplantations without mortality in 2 years].

Between 1 january 1992 and 31 december 1993, 32 liver transplantations were performed in 29 patients (5 transplants in 3 children and 27 transplants in 26 adults) at Geneva University Hospital. Despite 5 super-urgent transplantations (3 fulminant hepatitis, 1 end-stage Wilson disease and 1 primary nonfunction), all patients are still alive and all have lived more than 10 months. On 1 october 1994, all patients were at home and 93% were in good general condition. No patient of this series had been transplanted for cancer and all patients positive for hepatitis B surface antigen receive long-term administration of anti-HBs immune globulin: in this respect, the long-term mortality risk of the present series of patients seems to be very low. Although these results highlight that liver transplantation can be performed safely by a competent medico-surgical team, two significant difficulties have to be outlined. First, patients are likely to die on the waiting list due to unavailable grafts, especially in emergency cases. Second, the postoperative period of patients with decompensated end-stage liver disease at the time of liver transplantation is still one of high morbidity. These facts underline that chronic liver disease patient should be evaluated for liver transplantation prior to the terminal decompensated stage of the disease, when the candidate's invariably poor general condition precludes successful liver transplantation.

Adolescent↗

Are patients with acute leukaemia, alive and well 2 years post bone marrow transplantation cured? A European survey. Acute Leukaemia Working Party of the European Group for Bone Marrow Transplantation (EBMT).

We investigated the occurrence of late events (beyond 2 years) in patients with acute leukaemia who received an allogeneic (BMT) (n = 1059), or an autologous bone marrow transplantation (ABMT) (n = 656) in Europe during the period from January 1979 to December 1990. Patients with no recurrence of leukaemia at 2 years had overall 82% chance of being alive in complete remission at 9 years following transplantation regardless of the nature of the leukaemia, the status at transplant, and the type of transplant. The incidence of late relapses continuously decreased with time. The latest relapses in acute myelogenous leukaemia (AML) were observed following BMT at 6.6 years in a patient transplanted in first remission (CR1) and at 3.7 years in a patient transplanted in second remission (CR2), and following ABMT at 6 years and 5.1 years respectively. The latest relapses in acute lymphoblastic leukaemia (ALL) were observed following BMT at 4 years in a patient transplanted in first remission (CR1) and at 6.8 years in a patient transplanted in second remission (CR2), and following ABMT at 5.3 years and 4.5 years respectively. Several factors predictive for late relapse or death were identified. Patients allografted experienced a lower frequency of late relapse than patients autografted. Of the numerous other prognostic factors studied, female sex in AML, the use of total body irradiation (TBI) in ALL and status in CR1, rather than CR2-3, for both ALL and AML allografted were correlated with a lower relapse incidence. The use of TBI in ALL was also associated with a better LFS and survival. The absence of acute graft-versus-host disease (GVHD) in allografted AML correlated with better LFS and better survival, but had no influence on the relapse incidence. This study indicates that patients alive and well at 2 years post transplant have a very high probability of being cured, but the possibility of late relapse still remains.

Adolescent↗

Health status of heart transplant recipients versus patients awaiting heart transplantation: a preliminary evaluation of the SF-36 questionnaire.

Measures of the effects of health care on patients' lives are being requested to evaluate heart transplantation programs. A relatively short, 36-item, questionnaire (SF-36) designed to measure health status is being evaluated as an outcome measure for a variety of conditions. The SF-36 was sent to all adults awaiting heart transplantation (n = 48) and heart transplant recipients (n = 177) at the University of Minnesota as a pilot study of the SF-36 applied to heart transplantation. Response rates were 88% and 81%, respectively. Heart transplant recipients had significantly (p < 0.0001) better scores for general health perceptions (70 +/- 21 versus 33 +/- 21), vitality (62 +/- 19 versus 39 +/- 2), physical function (71 +/- 22 versus 36 +/- 24), ability to perform roles without physical limitations (62 +/- 41 versus 27 +/- 35), and social function (85 +/- 18 versus 63 +/- 31) compared with patients awaiting heart transplantation. Mental function and ability to perform roles without emotional problems were good in both groups and not significantly different. Mean SF-36 scores for the heart transplant recipients were uniformly not as high as scores for a historical group with only minor medical problems. These preliminary data suggest that the SF-36 is sensitive to the effects of heart transplantation. Additional studies of the SF-36 as an outcome measure for heart transplantation are warranted and should include methods to control for extraneous variability and to provide unbiased data collection.

Female↗

[Advances in transplantation biology and transplantation of vital organs in the era of immunosuppression with cyclosporin A].

Advances in transplantation biology and transplantation of vital organs during the 15 years are described. Immunosuppressive therapy has greatly benefited from the introduction of cyclosporin A into postoperative care of transplant patients. Other immunosuppressive agents recently used are monoclonal antibody OKT 3 and the preparation FK 506. Cadaver kidney transplantation has been improved by HLA-DR antigen typing. A new preservation solution developed at the University of Wisconsin has increased the quality of transplant organs over a prolonged period of preservation. The whole period is marked with successful transplantation of the lung, the heart-lung, the small intestine, parts of the liver, multiorgan transplantation and liver transplantation combined with other organs or cells. Xenotransplantation of the liver and the heart, however, have failed. Renal, cardiac and hepatic transplantations have now become a recognised therapeutic measure for end-stage disease which cannot be treated by drugs.

Cyclosporine↗

Outcome of cardiac transplantation in children. Survival in a contemporary multi-institutional experience. Pediatric Heart Transplant Study.

BACKGROUND: Meaningful analysis of survival and risk factors for death in children who undergo heart transplantation is problematic because of the small number of heart transplantations performed at individual institutions. METHODS AND RESULTS: To more accurately examine survival and risk factors for death in children undergoing heart transplantation, we analyzed 191 patients between 1 and 18 years old who received transplants at 22 centers in the Pediatric Heart Transplant Study between January 1, 1993, and December 31, 1994. Cardiac diagnosis was congenital heart disease in 74 patients (39%), dilated cardiomyopathy in 73 (38%), and other in 44 (23%). Actuarial survival was 93% at 1 month, 82% at 1 year, and 81% at 2 years after transplantation. The major causes of death (n = 31) were rejection (29% of deaths), early graft failure (19%), infection (16%), sudden death (13%), and other causes (23%). By multivariate analysis, risk factors for death were assist devices (P = .02), nonidentical ABO blood types (P = .05), and younger age (P = .10). CONCLUSIONS: Contemporary survival for pediatric heart transplant recipients > or = 1 year old is comparable to survival after adult heart transplantation. Risk factors for death are the need for assist devices, nonidentical ABO blood types, and younger age. Rejection is the most common cause of death after pediatric heart transplantation.

Adolescent↗

Does distance between home and transplantation center adversely affect patient outcomes after heart transplantation?

BACKGROUND: The emergence of heart transplantation referral centers, in an era of cost-conscious managed care programs, frequently leads to long-distance patient consultation and care. The purpose of this project was to review one center's experience regarding the effect of long distances from home to transplantation hospital on outcomes. METHODS: Three hundred twelve adult, noninternational, transplant recipients surviving at least 3 months were assessed for 10 events: rejection episodes, number of endomyocardial biopsies, emergency department visits, hospital admissions, return to full-time work or school, infections, coronary allograft vasculopathy, malignancies, retransplantation, and death. Presence of a locally involved physician was also determined. Distance from the transplantation center was analyzed in three discrete groups: 0 to 150 miles (n = 207), 151 to 300 miles (n = 69), and >300 miles (n = 36). RESULTS: There were no differences among the groups in mean length of follow-up (40.6, 36.9, 39.0 months, p = 0.27) or number of biopsies (20.5 +/- 0.16, 18.3 +/- 1.1, 18.0 +/- 1.1, p = 0.07). As the distance increased from the transplantation center, there was no greater incidence of adverse outcomes. Cellular rejection was the same among the groups (45%, 45%, 36%, p = 0.58). Likewise, emergency department visits and hospital admissions also did not vary: (9.7%, 5.8%, 8.3%, p = 0.61) and (22.2%, 13.0%, 16.7%, p = 0.23, respectively). There were no differences in the incidence of coronary vasculopathy (9.2%, 11.6%, 13.9%, p = 0.63). More importantly, the three groups did not differ in death/retransplantation rates (3-year survival, 84.5, 94.0 and 86.9, p = 0.14). Patients cared for by a local physician in addition to their transplant cardiologist had better survival rates than patients without a local physician (3-year survival rate, 90.7 vs 72.6, p = 0.0008). CONCLUSIONS: Long-distance management of heart transplant recipients is successful and is not associated with an increase in adverse outcomes. By itself, distance should not represent a contraindication to transplantation. Patients should be encouraged to maintain contact with a local physician, in addition to the regularly scheduled visits at the transplantation center.

Adolescent↗

Does lung transplantation prolong life? A comparison of survival with and without transplantation.

BACKGROUND: Because of the assumed beneficial effect of lung transplantation on survival, controlled trials to assess the therapeutic benefit of lung transplantation are considered to be unethical. Therefore other methods must be used to provide control data. In this study the effect of lung transplantation on survival for patients with end-stage pulmonary disease was analyzed, with waiting list survival rates used as control data. METHODS: The analysis was based on 157 consecutive patients who were put on the waiting list of the Dutch lung transplantation program during the period November 1990 to January 31, 1996, of whom 76 underwent transplantation. Following the principles of control group estimation as set out in the context of heart transplantation, a stepwise approach was used to arrive at a multivariate time-dependent Cox regression model. The following prognostic variables were included in the analyses: age, forced expiratory volume in 1 second, partial pressure of carbon dioxide, partial pressure of oxygen, and diagnosis. RESULTS: The 1- and 2-year waiting list survival rates were 78% and 58%, respectively. The 1- and 2-year transplantation survival rates (i.e., survival from placement on the waiting list, including posttransplantation survival) were 79% and 64%, respectively. The multivariate time-dependent Cox analysis showed that lung transplantation reduced the risk of dying by 55% (95% confidence interval, 3% to 79%). For patients with emphysema the risk of dying was estimated to be 77% lower than for patients with other diagnoses (96% confidence interval, 50% to 89%). CONCLUSIONS: With Cox regression, adjusting for age, forced expiratory volume in 1 second, partial pressure of carbon dioxide, partial pressure of oxygen, and diagnosis, lung transplantation showed a statistically significant effect on survival in selected patients with end-stage pulmonary disease.

Adult↗

Oxygen tension in isolated transplanted rat islets and in islets of rat whole-pancreas transplants.

Despite similar immunosuppressive protocols having been applied, the success rate of pancreatic islet transplantation has been much lower than that of whole-pancreas transplantation. We compared the oxygen tension in syngeneically transplanted isolated rat islets and islets of syngeneic rat whole-pancreatic grafts, with native islets, using Clark-type microelectrodes. An oxygen tension of approximately 40 mmHg was recorded in both native islets and in islets of the whole-pancreas graft. Isolated islets transplanted under the renal capsule had a markedly lower oxygen tension ( approximately 6 mmHg). The exocrine parenchyma of the native and of the transplanted pancreatic gland had an oxygen tension of approximately 30 mmHg. The lower oxygen tension in transplanted isolated islets may be one explanation for the more frequent failures of transplanted islets compared with the outcome when the whole pancreatic gland is transplanted.

Animals↗

Long-term results of cardiac transplantation from live donors: the domino heart transplant.

BACKGROUND: Hearts explanted from the recipients of heart-lung transplants provide a unique source of transplants from live donors. This article presents long-term results with this procedure at our center. METHODS: We performed a retrospective chart review of domino transplantations performed in our institution between 1989 and 1998. RESULTS: We analyzed 131 domino transplants (123 orthotopic, 8 heterotopic). Domino hearts were from patients with cystic fibrosis (69%), primary pulmonary hypertension (15%), and other diagnoses (16%). The mean recipient pulmonary vascular resistance (PVR) was 3.1 Wood units, 25% of patients having values >4 Wood units. Thirty-day mortality was 13%. The 1-, 5-, and 10-year graft survival was 75% (70% confidence interval [CI], 65-74), 70% (70% CI, 65-74), and 58% (70% CI, 52-64), respectively. Patients with PVR >4 Wood units had 1-year survival (76%; 70% CI, 69-84) similar to that of patients with PVR of < or =4 units (74%; 70% CI, 69-80). Recipients of hearts from patients with cystic fibrosis survived longer (5-year survival, 76%; 70% CI, 71-82) vs 65% for non-cystic fibrosis hearts (70% CI, 57-74) p = 0.09). One-year survival was decreased after transplantation of hearts from female donors (66%; 70% CI, 60-72)) compared with hearts from male donors (85%; 70% CI, 79-90); p = 0.06). Late deaths caused by coronary artery disease and malignancy were uncommon. CONCLUSION: Although the rate of early mortality after domino transplantation was slightly higher than after cadaveric transplantation, we noted a remarkably low long-term attrition rate in recipients of domino grafts, up to 10 years. In addition, successful transplantation of patients with high PVR supports the hypothesis that heart-lung recipients may provide superior donor hearts for this patient group, many of whom traditional listing criteria would exclude.

Adult↗

Allogeneic stem cell transplantation reduces disease progression compared to autologous transplantation in patients with multiple myeloma.

This study compares the probability of disease progression, progression-free survival, and overall survival between patients undergoing an allogeneic or autologous transplant for multiple myeloma using an identical preparative regimen. Patients received a preparative regimen of TBI, busulfan, and cyclophosphamide followed by an allogeneic or autologous transplant. In the allogeneic group (n = 21), six patients received bone marrow and 15 received G-CSF mobilized PBSC; all autologous patients (n = 35) received PBSC mobilized with cyclophosphamide and G-CSF. Allogeneic donors were HLA-identical (n = 20) or one-antigen mismatched (n = 1) siblings. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus (n = 10), tacrolimus/methotrexate (n = 6), cyclosporine/methotrexate (n = 4), or cyclosporine (n = 1). The groups were evenly matched for gender, pretransplant therapy, disease status at time of transplant, myeloma subtype, and time from diagnosis to transplant. The median age was significantly lower in the allogeneic group (48 vs 55 years, P < 0.01). In the allogeneic group the probabilities of developing acute GVHD grade II-IV and chronic GVHD were 55% and 82%, respectively. The Kaplan-Meier probability of disease progression was significantly lower in the allogeneic group (11% vs 64%, P < 0.001) compared to the autologous group. Although progression-free (60% vs 30%, P = 0.19) and overall survival at 2 years (60% vs 42%, P = 0.39) favored the allogeneic group, this did not reach statistical significance. Within the allogeneic transplant group, patients age 50 years or under had a 3-year overall survival significantly higher when compared to older patients (79% vs 29%, P = 0.03). Using identical preparative regimens, allogeneic transplantation reduced disease progression compared to autologous transplantation for myeloma. This suggests that allogeneic transplantation induces a graft-versus-myeloma (GVM) effect.

Actuarial Analysis↗

Second autologous transplantation after failure of a first autologous transplant in 18 patients with non-Hodgkin's lymphoma.

High-dose chemotherapy and autologous marrow or peripheral stem cell support offers the best chance of cure in some subgroups of patients with non-Hodgkin's lymphoma (NHL). Less is known about the role of a second course of myeloablative chemotherapy in patients who relapse after a first autologous transplant. The aim of this retrospective study was to evaluate the disease outcome, morbidity and mortality associated with second autologous transplantation in patients with NHL. Between 1985 and 2001, 225 patients who had received autologous transplantation for NHL in two institutions in Lyon relapsed. Of these 225 patients 18 underwent a second autologous transplantation. The median age at second transplant was 41 years. There were six indolent lymphomas and 12 aggressive lymphomas. The median follow-up from the second transplant was 42 months. The OS rate at 2 and 5 years were 58 and 27%, respectively. The PFS rate at 2 and 5 years was 36%. Five patients are alive without disease 20 to 100 months after the second transplant. Seven patients died of disease recurrence. Four (22%) toxic deaths occurred: one of pulmonary fibrosis, one of fungal infection and cardiac failure and two of acute leukaemia. A minority of patients with NHL recurrence after a first transplant can be cured by a second course of myeloablative chemotherapy at the cost however of high-risk toxic death.

Adult↗

Islet transplantation. The connection of experiment and clinic exemplified by the transplantation of islets of Langerhans.

Since approximately 25 years islet transplantation as a mean for the treatment of diabetes has been developed from early attempts in rodents to first clinical applications in man in recent years. The review describes the results obtained in diabetic rats including metabolic effects as well as prevention of late complications. In the syngeneic system (Lewis-rats) the intraportal transplantation of 1,000-2,000 isolated islets may cure streptozotocin-induced diabetes for the whole lifespan of the animal. In the allogeneic system (across a major histocompatibility barrier), however, isolated islets are highly immunogenic. According to present knowledge, mainly class-II antigen bearing cells are responsible while the role of the endocrine cells seems to be less important. By various in vitro methods (e.g. low temperature culture at 24 degrees C) it was possible to induce immunoalteration of allogeneic islets which was followed by long-term acceptance by the host in rodents. Whether the same technique is effective in larger animals and in man remains open. New technologies for the isolation of high numbers of pure islets from human pancreatic glands have been the key for the use of islet transplantation in man in several centers. The review describes the details regarding institutions as well as results in patients on the basis of the International Islet Transplant Registry which is located at Giessen University. Although longer lasting insulin independency (longest lasting effect 2 1/2 years) has been observed only in a few patients, islet transplantation has been proven to be a very safe procedure for the patient. It is hoped that with increasing experiences regarding the factors which at present limit the function as number and quality of islets, immunosuppressive protocols etc. islet transplantation will develop to a definite alternative to whole-organ transplantation. One of the most important challenges for modern medicine is the fact of a worldwide increase of diabetic long-term complications such as kidney failure, coronary and peripheral vascular disease, blindness and neuropathy. Although intensified insulin treatment in a small percentage of patients may moderate morbidity and mortality, from experimental work there is sufficient evidence suggesting that only the restoration of normoglycemia early in the course of the disease may prevent complications. This, however, can only be achieved by the replacement of the destroyed islets of Langerhans either by transplantation of an intact vascularised pancreas or by isolated islets.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Autologous bone marrow transplantation for recurrent malignant lymphoma after liver transplantation.

BACKGROUND: Cancer chemotherapy in chronic carriers of hepatitis B virus is known to promote viral replication, and, when immunosuppressive treatment is stopped, the return of immune competence can be followed by a fulminant hepatitis. Liver transplantation may be required and has been successfully performed for this condition. However, malignancy recurrence after transplantation has not been reported yet. METHODS AND RESULTS: We here report the case of an asymptomatic hepatitis B surface antigen carrier who developed a malignant lymphoma, which was treated by chemotherapy. After cessation of chemotherapy, he developed a fulminant hepatitis, requiring liver transplantation. Three years later, he developed a recurrent malignant lymphoma, which was treated successfully by autologous bone marrow transplantation. In order to prevent viral replication, lamivudine and intermittent administration of fresh-frozen plasma highly concentrated in anti-HBs immunoglobulin was initiated before the bone marrow transplantation. The patient remains well 12 and 56 months after autologous bone marrow and liver transplantation, respectively. CONCLUSIONS: This experience suggests that all hepatitis B surface antigen-positive patients for whom chemotherapy is indicated would benefit from prophylactic antiviral hepatitis B virus therapy. Furthermore, successful autologous bone marrow transplantation is possible after liver transplantation.

Bone Marrow Transplantation↗

Lung transplantation after allogeneic marrow transplantation in pediatric patients: the Memorial Sloan-Kettering experience.

BACKGROUND: Chronic lung disease and pulmonary failure are complications that can occur after bone marrow transplantation (BMT) and are associated with severe morbidity and mortality. METHODS: We report on four patients who developed chronic, progressive, and irreversible lung disease 1 to 3 years after allogeneic BMT in childhood. These patients had chronic graft-versus-host disease (n=3) or radiation-related pulmonary fibrosis (n=1). Three patients underwent double lung transplants and one patient underwent a single lung transplant 2 to 14 years after BMT. RESULTS: All four patients tolerated the lung transplantation procedure well and showed significant clinical improvement with normalization of pulmonary function tests by 1 year posttransplant. One patient died from infectious complications 3 years after lung transplantation, and one patient died after chronic rejection of the transplanted lungs 6 years posttransplant. Two patients remain alive without significant respiratory impairment 2 and 7 years after lung transplantation. CONCLUSION: We conclude that lung transplantation offers a viable therapeutic option for patients who develop respiratory failure secondary to BMT.

Adolescent↗

Autologous transplantation for diffuse aggressive non-Hodgkin's lymphoma in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry.

PURPOSE: To evaluate the results of high-dose chemotherapy and autologous hematopoietic stem-cell transplantation (autotransplants) in patients with diffuse aggressive non-Hodgkin's lymphoma (NHL) who never achieve a complete remission with conventional chemotherapy. PATIENTS AND METHODS: Detailed records from the Autologous Blood and Marrow Transplant Registry (ABMTR) on 184 patients with diffuse aggressive NHL who never achieved a complete remission with conventional chemotherapy and subsequently received an autotransplant were evaluated. Transplants were performed between 1989 and 1995 and were reported to the ABMTR by 48 centers in North and South America. RESULTS: Seventy-nine (44%) of 184 patients achieved a complete remission or a complete remission with residual imaging abnormalities of unknown significance after autotransplantation. Thirty-four (19%) of 184 had a partial remission and 55 (31%) of 184 had no response or progressive disease. Eleven patients (6%) were not assessable for response because of early death. The probabilities of progression-free and overall survival at 5 years after transplantation were 31% (95% confidence interval [CI], 24% to 38%) and 37% (95% CI, 30% to 45%), respectively. In multivariate analysis, chemotherapy resistance, Karnofsky performance status score less than 80 at transplantation, age > or = 55 years at transplantation, receiving three or more prior chemotherapy regimens, and not receiving pre- or posttransplant involved-field irradiation therapy were adverse prognostic factors for overall survival. CONCLUSION: High-dose chemotherapy and autologous hematopoietic stem-cell transplantation should be considered for patients with diffuse aggressive NHL who never achieve a complete remission but who are still chemotherapy-sensitive and are otherwise transplant candidates.

Adolescent↗

Reactivation of human herpesviruses after allogeneic peripheral blood stem cell transplantation and bone marrow transplantation.

Reactivation of latent herpesviruses results in outcomes ranging from asymptomatic shedding of viruses to severe diseases, depending on the immunological competence of the host. Severe and prolonged suppression of cellular and humoral immunity after hematopoietic stem cell transplantation is accompanied by a high incidence of symptomatic recurrent herpesvirus infections. Subclinical reactivation also occurs more frequently than previously expected in transplant recipients. An increasing viral load in the blood detected by an antigenemia assay or PCR and viral shedding in regional fluids have a predictive value for subsequent diseases. Monitoring of viral DNA in the peripheral blood after allogeneic bone marrow transplantation (allo-BMT) reveals unique temporal profiles of detection for each herpesvirus. Recent studies demonstrate that recovery of CD4+ T cells is enhanced within one month after allogeneic peripheral blood stem cell transplantation (allo-PBSCT) compared to allo-BMT. To clarify whether this immunological advantage could affect the reactivation of human herpesvirus (HHV), we monitored the emergence of viral DNA by a nested-double polymerase chain reaction in peripheral blood leukocytes. Detection rates of HHV-6 DNAs which peak at 3-4 weeks post-transplant, were significantly reduced after allo-PBSCT compared to allo-BMT, while those of other herpesviruses which tend to be reactivated later than this period (Epstein-Barr virus and cytomegalovirus) were similar between the two types of transplants. Detection of HHV-6 DNA within the first month after the transplant was associated with delayed platelet engraftment. These results underscore the important role of CD4+ T reconstitution in inhibiting virus reactivation post-transplant.

Bone Marrow Transplantation↗