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1.
To determine whether receipt of an investigational anti-CD3 monoclonal antibody (BC3) increased the risk of human herpesvirus 6 (HHV-6) reactivation and development of encephalitis in bone marrow transplant (BMT) recipients, persons who had and had not received BC3 were compared. Odds of HHV-6 reactivation were higher among BC3 recipients than among control patients (odds ratio, 2.5; 95% confidence interval [CI], 1.3-4.7). In addition, BC3 recipients were more likely than control patients to develop encephalitis (risk ratio [RR], 3.5; 95% CI, 1.3-9.5), and this association followed a BC3 dose-dependent relationship (P=.03, by Mantel-Haenszel chi(2) test). In a multivariable model, HHV-6 reactivation and receipt of BC3 were associated with increased risk of encephalitis (RR, 5.4; 95% CI, 1.9-15.3, and RR, 3.3; 95% CI, 1.2-9.1, respectively). In conclusion, both HHV-6 reactivation and receipt of BC3 for prophylaxis of acute graft-versus-host disease independently increased the risk of encephalitis in allogeneic BMT recipients. Prospective studies to better define the relationship between HHV-6 reactivation and encephalitis in allogeneic BMT recipients are warranted.  相似文献   

2.
The efficacy and safety of ciprofloxacin as long-term antibacterial prophylaxis after allogeneic bone marrow transplantation were assessed prospectively. Eighty-nine recipients of lymphocyte-depleted marrow grafts were each given ciprofloxacin orally, 500 mg twice daily. Fever developed in 71 out of 78 evaluable patients (91%) and was accompanied by positive blood cultures in 42 cases (59%). 'Viridans' streptococci, all but one with reduced in vitro susceptibility to ciprofloxacin, accounted for 35 episodes of bacteraemia. Thirty-three episodes occurred in patients given anthracyclines compared with only two episodes in other patients (chi 2 = 5.58: p less than 0.05). All bacteraemic fevers occurred within 11 days post-transplant. Gram-negative sepsis did not occur in any patient. Sixteen patients died but none due to a bacterial cause. Allergy to ciprofloxacin was registered in three out of 76 assessable cases (4%).  相似文献   

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4.
We previously reported that the use of polymerase chain reaction (PCR) in detecting cytomegalovirus (CMV) DNA in serum (sPCR) enables the detection of CMV viremia, which has not been possible with other methods. In this study, the clinical usefulness of sPCR was investigated by comparison with the results of three other diagnostic methods, i.e., antigenemia assay (AG), shell vial culture test (shell vial), and complement-fixing (CF) antibody titer. The present study included 26 patients with hematological diseases who had undergone allogeneic bone marrow transplantation (BMT). A total of 347 samples were collected, and the results of the sPCR and AG methods were in agreement in 91.1% of the samples. When a subject was positive in both the sPCR and AG tests, and the other two tests (shell vial and CF) were also positive, CMV reactivation was surmised as definite. When only the result of the shell vial test or the CF test was positive, these results were taken as false-positives. The time at which the samples became positive in each of these four tests was 7.5 weeks post-BMT for sPCR, 7.0 weeks post-BMT for the AG test, 7.4 weeks post-BMT for the shell vial test, and 9.7 weeks post-BMT for the CF test. Thus, it was found that samples became positive at almost the same time for the sPCR, AG, and shell vial tests. Interstitial pneumonitis (IP) due to CMV developed in 3 subjects. These cases were positive in the sPCR, AG, and shell vial tests prior to the manifestation of symptoms of IP. The CF test did not become positive until after the onset of the disease. As the IP due to CMV was controlled with treatment, the sPCR and AG tests became negative. With the shell vial and CF tests, on the other hand, the test results continued to be positive even after the IP was cured. These findings demonstrate that the sPCR test method--like the AG test--yields few false-positive results. Therefore, the sPCR method is useful in early diagnosis of reactivation of CMV and for evaluation of the efficacy of therapy administered for IP. In addition, sPCR can be performed simultaneously on a large number of samples, and the evaluation of the test results is simple. We conclude that the sPCR test may be superior to the three other diagnostic methods for evaluation of serum samples from multiple institutions.  相似文献   

5.
Cytogenetic findings from the bone marrow (BM) and the peripheral blood (PB) of nine consecutive patients after allogeneic bone marrow transplantation (BMT) for acute or chronic myelogenous leukaemia are reported. After a conditioning regimen consisting of cyclophosphamide and fractionated total body irradiation (TBI) given in five or six fractions of 2 Gy, persistence of host cells was detected in four out of seven cases with permanent engraftment. While one of these patients relapsed 4 months after host cells had been found in BM and PB, the other patients stayed relapse-free 124, 257 and 347 d after grafting. Before transplantation, the leukaemic cells in all three cases carried unique cytogenetic abnormalities giving us the opportunity to distinguish the leukaemic population from chromosomally non-aberrant cells thought to represent residual normal host cells. As the persisting host cells after BMT lacked any cytogenetic abnormalities, it is suggested that they were members of residual normal clones not involved in the leukaemic process.  相似文献   

6.
Abstract: Human herpesvirus‐6 (HHV‐6) infects the majority of children under the age of 2 years causing roseola infantum. Following short self‐limited disease, the virus enters into a latency phase in peripheral blood lymphocytes (PBL). It has been previously reported that HHV‐6 reactivation from latency, in immunocompromised patients undergoing bone marrow transplantation (BMT), could result in febrile illness, pneumonitis, meningitis, and/or encephalitis. In our study, 14 BMT patients received two different antiviral prophylactic therapies: 8 patients received acyclovir, whereas 6 patients received ganciclovir. Clinical manifestations and virus recovery were monitored pre‐ and post‐BMT by polymerase chain reaction tests of cord blood cells cultured with the patients' PBL. No HHV‐6 recovery was shown in the 6 patients treated with ganciclovir, whereas 3 of the 8 acyclovir‐treated patients experienced virus reactivation 20–21 days post‐BMT. One of the 3 patients was asymptomatic but had late engraftment; the second patient had prolonged fever, skin rash, and hemorrhage; the third patient experienced prolonged fever, pneumonitis, marrow rejection, and fatal encephalitis. It is concluded that viral reactivation may be prevented by prophylactic treatment with ganciclovir. Our observation awaits further documentation in prospective randomized trials in high‐risk BMT recipients.  相似文献   

7.
The clinical course of cytomegalovirus (CMV) pneumonia in seven consecutive bone marrow transplant (BMT) recipients during a 24-month period was studied. Retrospective analysis of clinical data on the recipients with CMV pneumonia during the illness and prospective follow-up of those who recovered from the pneumonia was performed. Those who had CMV as the sole pathogen and with lymphocytosis in the BAL or the peripheral blood during the illness recovered from the pneumonia. On the contrary, those who had mixed bacterial or fungal infection with peripheral lymphopenia died. Persistent lymphocytosis in the BAL and the peripheral blood, in the absence of CMV infection, was observed in the survivors. Two subsequently developed restrictive lung disease and two had relapse of their primary malignancy. These data suggest that CMV pneumonia in BMT patients is associated with significant long-term sequelae. The phenomenon of persistent lymphocytosis in the BAL and the peripheral blood, in the absence of CMV infection, supports Grundy's hypothesis that CMV pneumonia in BMT recipients is an immunopathologic condition.  相似文献   

8.
Summary Thirteen patients in complete remission from acute nonlymphoblastic leukaemia or in chronic phase of chronic myelocytic leukaemia were treated with total body irradiation, cyclophosphamide and allogeneic bone marrow transplantation (BMT). Ciclosporin (CS) was administered for the prevention and the treatment of Graft versus Host Disease. Blood concentrations of CS were determined by Radioimmunoassay (RIA) and by High Performance Liquid Chromatography (HPLC). Trough levels of CS in peripheral blood as measured by RIA exceeded HPLC derived levels in nearly all (56/58) samples with a ratio of RIA: HPLC ranging from 2.43±1.42 at day 12 to 3.65±1.86 at day 26 after BMT ( ±SD). A comparable ratio was found as regards the peak concentrations of CS in peripheral blood. Neither the dose of CS (0.5–3.0 mg/kg/day intravenously; 3.0–5.0 mg/kg/day per os) nor the duration of treatment (12, 19, 26 or 33 days after start of CS) were a significant factor as regards the ratio between HPLC and RIA. Concentrations of CS were also determined in bone marrow nucleated cells at 1 hour after the drug infusion had started. Here the ratio of RIA versus HPLC varied upon the duration of CS treatment with a highest ratio of 8.75±8.74 at day 12 after BMT. Bone marrow levels corresponded well with blood trough concentrations (p<0.01). It is concluded that the concentrations of CS in blood and bone marrow as determined by RIA and HPLC differ significantly, though consistently. At present, no advantage can be attributed to either method of analysis for routine clinical monitoring, as long as detailed information on the immunosuppressive and the toxic characteristics of CS metabolites in humans is lacking.  相似文献   

9.
SUMMARY. We describe the clinical course of three cytomegalovirus-antibody-positive allogeneic marrow graft recipients who developed progressive pancytopenia during the third month post-transplant. Bone marrow biopsy cores were hypocellular without evidence of disease recurrence. Haemopoietic progenitor assays demonstrated a decrease of all assayable progenitors. Cytomegalovirus was identified from the blood and urine of all three patients. However, none of the patients developed other manifestations of cytomegalovirus infection such as pneumonitis, hepatitis and enteritis. The therapeutic use of ganciclovir and intravenous immunoglobulins resulted in prompt resolution of both viraemia and viruria in all three patients, and of pancytopenia in two patients.  相似文献   

10.
This is a dose-finding study using foscarnet for CMV prophylaxis after allogeneic bone marrow transplantation (BMT) in 20 high risk patients (unrelated donors, or T cell depleted, and/or advanced disease). Foscarnet was started on day +1 after BMT and continued until day +100. We explored four different dose levels, patients being entered at the lowest dose level until one patient experiences CMV-reactivation, identified as two consecutive positive CMV antigenemias (CMVAg-emia). The four dose levels expressed as mg/kg/day between days 1 and 30 (induction) and between days 31 and 100 (maintenance) were respectively: dose level I = 60/30 (n = 5); dose level II = 120/60 (n = 4); dose level III = 120/90 (n = 5) and dose level IV = 120/120 (n = 6). All patients showed engraftment: PMN > or =0.5 x 109/l at a median interval of 16, 21, 17, 15 days after BMT, and Plt > or =30x10(9)/l on days 19, 16, 17, 17 respectively. CMVAg-emia was seen in 10 patients at a median interval of 53 days post-BMT (range 33-89) with a median of 10 CMV antigen+ cells (range 1-16). There was a dose effect of foscarnet on CMVAg-emia: respectively 4/5 patients (80%), 2/4 (50%), 3/5 (60%) and 1/6 (18%) at dose levels I, II, III, IV (P = 0.1). CMV disease was seen in 3/9 (33%) at dose levels I, II and 0/11 at dose levels III, IV (P = 0. 07). The median number of CMV antigen-positive cells at diagnosis of CMV infection was different: 13 in dose levels I-II and two in dose levels III-IV (P = 0.01). Increased creatininine was seen in 15 patients with a mean of 1.8 mg% (range 1.5-5.7) and was the cause of discontinuation in nine patients (45%). Renal toxicity was reversible in all nine patients. Overall actuarial TRM at 2 years was 31%: 47% for patients at dose levels I-II and 19% for patients at dose levels III-IV. In conclusion, foscarnet exhibits a dose-dependent prophylactic effect on CMVAg-emia, CMV disease and transplant-related mortality with acceptable and reversible renal toxicity.  相似文献   

11.
In order to investigate the incidence of pulmonary function complications following bone marrow transplantation (BMT), 17 patients with leukaemia and 8 with aplastic anaemia were sequentially assessed over a one year period. Before BMT, all the patients were free of respiratory symptoms and had both normal chest X-ray and routine lung function tests. However, 5 patients disclosed airway hyperreactivity. Aplastic anaemia patients had significantly lower haemoglobin-adjusted diffusing capacity for carbon monoxide (DLCO) than those with leukaemia, a finding significantly related to the lower haemoglobin values shown in the former individuals. Following BMT there were transient mild to moderate reductions in DLCO and static lung volumes; moreover, patients with leukaemia had lower DLCO than those with aplastic anaemia. Fourteen of the 25 patients had ventilatory defects, including 10 individuals with bronchial hyperresponsiveness. Post-BMT lung function changes were transiently accompanied by mild to moderate symptoms of respiratory disease in most of the patients.  相似文献   

12.
Abstract
Background:  Prophylactic low dose i.v. ganciclovir in patients at risk after allogeneic bone marrow transplantation (BMT) is highly effective in the prevention of cytomegalovirus (CMV) disease and infection.
Aim:  In this study, we sought to assess the tolerability of oral ganciclovir in patients after allogeneic BMT.
Methods:  CMV seropositive patients or those with CMV seropositive donors were randomised to be treated with i.v. ganciclovir 5 mg/kg three times weekly or oral ganci­clovir 3 g daily from engraftment to day 84. The period of accrual was from May 1997 to October 1998. Patients were monitored for CMV infection by weekly serology. Thirty-one patients received oral ganciclovir and 27 patients received i.v. ganciclovir, the treatment groups being balanced for clinical characteristics and prognostic factors.
Results:  Renal dysfunction, transfusion requirements and significant nausea and vomiting were not different. There were no documented cases of CMV disease during the study period although three patients developed CMV polymerase chain reaction positivity at various times. One patient treated with i.v. ganciclovir developed non-fatal gastrointestinal CMV disease after the study period on day 108. Eight patients in the oral group failed to complete planned therapy, whereas two patients failed to complete the i.v. course.
Conclusion:  We conclude that oral ganciclovir is a reasonable, well-tolerated alternative to i.v. ganciclovir for the prophylaxis of CMV disease after allogeneic BMT. (Intern Med J 2004; 34: 98−101)  相似文献   

13.
Sirolimus-based immunosuppressive regimens in organ transplantation have been associated with a lower than expected incidence of cytomegalovirus (CMV) disease. Whether sirolimus has a similar effect on CMV reactivation after allogeneic hematopoietic stem cell transplantation (HSCT) is not known. We evaluated 606 patients who underwent HSCT between April 2000 and June 2004 to identify risk factors for CMV reactivation 100 days after transplantation. The cohort included 252 patients who received sirolimus-tacrolimus for graft-versus-host disease (GVHD) prophylaxis; the rest received non-sirolimus-based regimens. An initial positive CMV DNA hybrid capture assay was observed in 225 patients (37.1%) at a median 39 days after HSCT for an incidence rate of 0.50 cases/100 patient-days (95% confidence interval [CI], 0.44-0.57). Multivariable Cox modeling adjusting for CMV donor-recipient serostatus pairs, incident acute GVHD, as well as other important covariates, confirmed a significant reduction in CMV reactivation associated with sirolimus-tacrolimus-based GVHD prophylaxis, with an adjusted HR of 0.46 (95% CI, 0.27-0.78; P = .004). The adjusted HR was 0.22 (95% CI, 0.09-0.55; P = .001) when persistent CMV viremia was modeled. Tacrolimus use without sirolimus was not significantly protective in either model (adjusted HR, 0.66; P = .14 and P = .35, respectively). The protective effect of sirolimus-containing GVHD prophylaxis regimens on CMV reactivation should be confirmed in randomized trials.  相似文献   

14.
BACKGROUND AND OBJECTIVES: Cytomegalovirus (CMV) infection continues to be a major complication of bone marrow transplants (BMTs). Administration of leukoreduced unscreened cellular blood products at the bedside has been shown to be effective in preventing CMV transmission via transfusions in CMV-seronegative bone marrow transplant recipients who receive their transplants from CMV-seronegative donors. The aim of this study was to determine whether CMV infection occurred in CMV-seronegative BMT patients who received CMV-seronegative donor marrows and CMV untested blood products leukodepleted at the bedside. DESIGN AND METHODS: We collected data over a 2-year period from patients undergoing allogeneic transplantation who received leukoreduced cellular blood components that were not screened for CMV. All CMV-seropositive patients and donors were excluded from the study. The CMV status of both the donors and the patients was determined before the transplantations. CMV cultures of urine, blood buffy coat, bone marrow samples and bronchial washings were performed if necessary in patients. RESULTS: Thirty-six CMV-seronegative patient-donor pairs were included in the study. Five patients (13.89%) were serologically reactive, but their CMV cultures were negative and they did not show signs or symptoms of CMV infection. These patients received intravenous immunoglobulin and thus could have acquired anti-CMV passively. INTERPRETATION AND CONCLUSIONS: The confidence interval in this study is 0/36 incidence of CMV infection. Our present findings support those of prior studies showing the effectiveness of filtered unscreened blood components as an alternative transfusion support for CMV-seronegative marrow transplant recipients. Studies in larger number of patients are warranted.  相似文献   

15.
Summary:Infections are a major cause of morbidity and mortality in patients undergoing high-dose therapy and allogeneic bone marrow transplantation (BMT) despite prophylaxis, use of growth factors and newer antimicrobial drugs. We report the clinical profile of infections among 297 patients who underwent 304 allogeneic transplants between 1986 and December 2001. All patients developed febrile neutropenia. There were 415 documented infections among 304 transplants. This included bacterial (34.9%), viral (42.9%), fungal (15.9%) and other infections (6.3%) including tuberculosis. Bacterial pathogens were mainly Gram-negative bacteria (80%) as compared to Gram-positive (20%) bacteria. The common Gram-negative bacteria were nonfermenting Gram-negative bacteria (NFGNB) (24.9%), Pseudomonas (17.9%), Escherichia coli (17.9%) and Klebsiella (9.7%). The major source of positive cultures was blood (53.7%) followed by urine (25.5%) and sputum (8.9%). In all, 133/304 (43.7%) transplants had 178 documented viral infections. The common viral infections were due to cytomegalovirus, herpes group of viruses and transfusion-related hepatitis; and 60/304 (19.7%) transplants had 66 documented fungal infections. Common fungi included Aspergillus species (69.7%), Candida (22.2%) and Zygomycetes (8.1%). Tuberculosis was documented in 2.3% of the transplants. Catheter infections were suspected or documented in 7.8% of the transplants (24/304). The incidence of infections in this series from developing countries is not significantly different from reports from the West.Bone Marrow Transplantation (2004) 33, 311-315. doi:10.1038/sj.bmt.1704347 Published online 1 December 2003  相似文献   

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17.
Summary. HCMV DNA was retrospectively quantitated in the early post-transplant period in 36 paediatric bone marrow transplant (BMT) recipients prospectively monitored for human cytomegalovirus (HCMV) infection on the basis of antigenaemia and viraemia assays. Viral DNA was quantitated in peripheral blood leucocytes (PBL) by PCR using an internal control of amplification and a series of external standards. Densitometric analysis of hybridization results obtained on PCR products enabled construction of a standard curve from which DNA amounts of clinical samples, expressed in terms of genome equivalents (GE), were interpolated. Of the 36 BMT recipients, three had clinically symptomatic HCMV infection with mean peak levels of viral DNA > 5000 GE (antigenaemia and viraemia mean peak levels were 873 and 35, respectively), whereas 19 with HCMV reactivation were asymptomatic (five of them had abortive HCMV infection) showing mean peak DNA levels of 131 GE (and of 6-8 and 13 for antigenaemia and viraemia, respectively) (P≤0.01). Single or multiple courses of pre-emptive therapy with ganciclovir or foscarnet were given to 14/19 asymptomatic children in whom antigenaemia levels were > 2 or lower yet persisting. Overall, in the 14 asymptomatic treated patients the mean antigenaemia level was 9-3 (range 1-22), and the mean DNA level was 184-6 (range 20-710) GE. Antiviral drugs were also administered to the three symptomatic patients who, due to late diagnosis of HCMV infection, escaped preemptive therapy. Antiviral treatment caused marked decrease or disappearance of viral DNA, antigenaemia and viraemia in both symptomatic and asymptomatic patients. In conclusion, our study suggests that: (i) starting therapy in the presence of a mean antigenaemia level of 9′3 (range 1-22) corresponding to a mean DNA level of 184′6 (range 20-710) GE avoided occurrence of any major HCMV-related clinical complication; (ii) clinical symptoms were associated with antigenaemia levels > 100 and DNA levels > 1000 GE; (iii) the effect of antiviral treatment could be more carefully monitored by quantitation of viral DNA.  相似文献   

18.
To assess the impact of antiviral prophylaxis during the first 3 months after transplantation on the frequency, timing, and outcome of cytomegalovirus (CMV) pneumonia during the first year, 541 adult allogeneic blood and marrow transplant recipients were evaluated. Thirty-four patients (6.3%) developed 35 episodes of CMV pneumonia at a mean of 188 days after transplantation, with an associated mortality rate of 76%. Twenty-six episodes (74%) occurred late (after day 100). Of the patients with late CMV pneumonia almost all (92%) had chronic graft vs. host disease or had received T cell-depleted transplants. Fourteen late CMV pneumonias (54%) were associated with serious concurrent infections, and 100% of these episodes were fatal. In conclusion, although the frequency of CMV pneumonia in the early posttransplantation period may be substantially reduced by prophylaxis, CMV continues to be a major cause of morbidity and mortality in the late period. Some subsets of patients need more prolonged surveillance and prophylaxis and/or preemptive therapy.  相似文献   

19.
Despite an extensive literature, no consensus has emerged regarding the optimal preventive strategy for CMV in allogeneic bone marrow transplantation (BMT). No survey of CMV prevention in BMT centers in the United States has yet been published. A questionnaire was sent to all allogeneic BMT programs in the United States, as listed in the November 1998 National Marrow Donor Program (NMDP) address roster. Questions included whether universal prophylaxis, pre-emptive therapy, or some other strategy was used for CMV prevention, and which CMV diagnostic tests were utilized. Eighty-one of 96 programs (86%) responded to the survey. Of these, 46 (56%) utilize a pre-emptive ganciclovir strategy, whereas 17 (21%) utilize universal prophylaxis, and 15 (19%) utilize a hybrid strategy based on risk stratification. The most commonly utilized CMV diagnostic tests are CMV-DNA by PCR (55 centers), shell vial centrifugation culture (52), tissue culture (42), pp65 antigenemia assay (38), and CMV-DNA by Digene hybrid capture (14). Of these, the CMV-DNA by PCR, pp65 antigenemia assay, and shell vial culture are the most frequently utilized as triggers for pre-emptive therapy. Quantitative assays are common (PCR 42%, Digene 64%). We conclude that centers currently performing allogeneic BMT in the United States employ a variety of strategies for CMV prevention, and differ in their diagnostic tests of choice for CMV monitoring. These results emphasize the need for large-scale studies to identify optimal diagnostic and management protocols. Bone Marrow Transplantation (2000) 26, 763-767.  相似文献   

20.
Diarrhea is common in adults after solid organ transplantation (SOT) and bone marrow transplantation (BMT), but data in children are limited. Therefore, we aimed to determine the incidence and etiology of pediatric early-onset diarrhea in post SOT and BMT.We reviewed children aged 6 months to 18 years who underwent liver transplantation, kidney transplantation or BMT between January 2015 and December 2019 with duration of diarrhea > 72 hours within the first 6 months after transplantation. Clinical data and diarrheal course were collected. Regression analyses were performed to define factors associated with the interested outcomes.Among 252 transplanted patients, 168 patients (66.6%) had 289 documented episodes of diarrhea. A diagnosis of 68.2% of post-transplant diarrhea remained ‘indefinite’. Enteric infection in SOT and gastrointestinal acute graft-versus-host disease (GI-aGVHD) in BMT were the commonly identified etiologies. Among 182 episodes among BMT children, skin rash was more pronounced when compared the ones with diarrhea > 7 days vs ≤ 7 days (odds ratio [OR] 13.9; 95% CI 1.8, 107.6). Males were more likely to develop GI-aGVHD as compared to females (OR 8.9). We found that GI-aGVHD was more common in the ones with skin rash and the presence of white blood cells in stool examination (OR 8.4 and 3.1, respectively). Deaths occurred in 7.7%.Two-thirds of post-transplant children experienced at least one episode of early-onset diarrhea, of which the etiology mainly remains undefined. Various clinical factors of prolonged/chronic diarrhea and GI-aGVHD may help clinicians when managing these children.  相似文献   

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