单倍体骨髓移植后巨细胞病毒感染的防治

目的:研究单倍型骨髓移植后,巨细胞病毒(CMV)感染的预防策略及发病情况。方法:98例单倍型骨髓移植患者,62例及1例CMVpp65阳性供者,接受更昔若韦预防治疗,受者5 mg／kg,2次／d,移植前-9 d～-2 d,31例移植后出现CMV抗原血症阳性患者,其中18／60例预防组,13／35例非预防组阳性病例,接受更昔若韦5 mg／kg,2次／d×2周,后改为5 mg／kg,1次／d,到CMVpp65转阴。移植后CMVpp65每周检测1次。结果:预防组18／60例移植后出现CMV抗原血症阳性,出现中位时间56(25～84)d。非预防组13／35例CMVpp65阳性,中位时间52(19～75)d,前者1例患者(1．6％)发展为CMV结肠炎,后者4例(11．4％),2例CMV肺炎,1例CMV结肠炎,1例CMV脑炎。结论:单倍型骨髓移植后,用CMVpp65检测CMV抗原血症是一种简便,可靠的方法。低剂量短疗程,静脉注射更昔若韦提前预防CMV病可能是一种有效的方法。     

Cytomegalovirus infection following unrelated cord blood transplantation for adult patients: a single institute experience in Japan

Cytomegalovirus (CMV) infection in 28 adult patients after cord blood transplantation (CBT) from unrelated donors was compared with that after bone marrow transplantation from HLA (human leucocyte antigen)-matched related (R-BMT) and unrelated (U-BMT) donors. Positive CMV antigenaemia was seen in 19 (79%) of 24 CMV-seropositive patients at a median of 42 d (range 29-85 d) after CBT, but in zero of four CMV-seronegative patients. This did not differ significantly from values observed after R-BMT and U-BMT (66%, P = 0.22, and 60%, P = 0.15 respectively). Based on the antigenaemia results, 16 patients (67%) received pre-emptive ganciclovir therapy from a median of 47 d (range 36-67 d) after CBT. This proportion was higher than that observed after R-BMT (28%, P = 0.0048), but did not differ from that after U-BMT (50%, P = 0.21). In addition, the probability of requiring more than two courses of ganciclovir therapy after CBT (21%) was higher than after R-BMT and U-BMT (0%, P = 0.015 and 0.039 respectively). One patient (5%) developed CMV disease after U-BMT, whereas no patients developed CMV disease after CBT or R-BMT. The CMV serostatus, use of a steroid and HLA disparity affected the probability of requiring ganciclovir therapy after CBT (P = 0.024, 0.032 and 0.017 respectively). These results suggest that recovery of CMV-specific immunity after CBT is delayed when compared with BMT.     

Cytomegalovirus infection in recipients of related and unrelated donor bone marrow transplants: no evidence of increased incidence in patients receiving unrelated donor grafts

Recent reports suggest an increased incidence of cytomegalovirus (CMV) infection in recipients of unrelated donor (UD) bone marrow transplantation (BMT).
In this study we have collated the incidence of CMV infection and disease in sequential UD ( n  = 119) and related donor (RD; n  = 79) BMT performed in a single institution over a 7-year period. Low-risk patients (CMV seronegative recipient and donor) accounted for 51% of UD BMT ( n  = 61) and 62% of RD BMT ( n  = 49), with CMV excretion documented in one RD BMT only. The remaining high-risk patients received identical prophylaxis regimens with aciclovir and intravenous immunoglobulin (IVIG). Two groups consisting of 58 UD BMT (median age 9.0 years, range 0.7–45.3 years) and 30 RD BMT (median age 13.6 years, range 1.6–47.6 years) were analysed. CMV reactivation/re-infection was documented in 15 UD BMT (26%) and 10 RD BMT (33%) ( P  = 0.72), and CMV disease in four UD BMT (8%) and four RD BMT (13%) ( P  = 0.533). In this series the risk of CMV excretion and disease following UD BMT was similar to that following RD BMT.     

A comparison of prophylactic vs pre-emptive ganciclovir to prevent cytomegalovirus disease after T-depleted volunteer unrelated donor bone marrow transplantation

The prophylactic and pre-emptive use of ganciclovir (GCV) both reduce significantly the incidence of CMV disease after sibling BMT but it is unclear which of these strategies is best for volunteer unrelated donor (VUD) BMT patients. We reviewed 49 consecutive patients, who received a T-depleted VUD BMT (from March 1990 to March 1996) for the treatment of CML in chronic phase, and were CMV seropositive before transplant or had a CMV seropositive donor. Patients were conditioned with cyclophosphamide (120 mg/kg for 2 days) and total body irradiation (13.2-14.4 Gy). Prophylaxis for GVHD was cyclosporin A and methotrexate with ex vivo or in vivo T cell depletion. Twenty-seven patients received pre-emptive GCV if CMV infection was detected by short-term culture before day +120 post BMT. Twenty-two patients received prophylactic GCV from engraftment until day +120 post BMT. The probabilities of CMV infection and disease occurring by 1 year post-BMT were greater in the pre-emptive GCV group than in the prophylactic GCV group (73.8% and 64.0% vs 53.1% and 30.0%, respectively; P=0.04 and 0.07). The incidence of death from CMV disease was similar in both groups (3/12 (25%) vs 3/10 (30%), respectively) and there was no difference in 1 year survival (55.6% vs 54.2%, respectively). New strategies are urgently required for the prevention of CMV disease after T-depleted VUD BMT.     

Prevention of Cytomegalovirus Infection by Valaciclovir after Allogeneic Bone Marrow Transplantation from an Unrelated Donor

In this prospective single-center study, we evaluated the efficacy and safety of valaciclovir (VACV) in the prevention of cytomegalovirus (CMV) infection after allogeneic bone marrow transplantation (BMT). The study population consisted of 12 patients who underwent allogeneic BMT from an unrelated donor. Patients received acyclovir (ACV) intravenously until they became able to take VACV orally. VACV was administered at a daily dose of 3000 mg and continued until day 100. CMV infection was monitored by CMV antigenemia assay and real-time polymerase chain reaction analysis of plasma. Thirty-five patients who did not receive any form of CMV chemoprophylaxis served as control subjects. CMV infection was detected in 4 (33.3%) of the 12 patients and in 24 (68.6%) of the 35 control subjects (P < .05). The onset of CMV infection was significantly delayed in the VACV group (median, day 43) compared with the control group (median, day 28.5; P < .01). Gastrointestinal symptoms as an adverse event due to VACV administration were observed in 2 patients. The plasma levels of ACV after VACV administration were measured in 8 patients and were similar to those in the healthy subjects. In conclusion, VACV shows normal absorption, even in the early posttransplantation period, and may prevent or delay CMV infection effectively and safely in allogeneic BMT recipients.     

Oral valganciclovir as preemptive therapy for cytomegalovirus infection post allogeneic stem cell transplantation

Antiviral compounds including ganciclovir, foscarnet, and cidofovir are routinely used in the treatment of cytomegalovirus (CMV) infection and disease; however, these agents have a poor oral bioavailability and have the inconvenience and expense of intravenous administration. AIM OF THE STUDY: To evaluate the safety and efficacy of oral valganciclovir (VGCV) for preemptive treatment of CMV reactivation in the setting of allogeneic hematopoietic stem cell transplantation (HSCT). PATIENTS AND METHODS: We treated 15 patients receiving allogeneic HSCT from related (n=9) or unrelated (n=6) donors. In all patients, either the donor, host, or both were CMV Ig G positive pretransplant. Indication for therapy was preemptive treatment of CMV infection defined as one or two consecutive positive tests of pp65 antigenemia assay or CMV-polymerase chain reaction (PCR). VGCV was administered orally in a dosage of 900 mg b.i.d. for 2 weeks, followed by 450 mg b.i.d. for 2 additional weeks. RESULTS: Patients developed a positive CMV-PCR after a median of 52 days (range 37-427) post HSCT and a positive pp65 antigenemia after a median time of 74 days (range 37-427) post HSCT. Preemptive treatment with VGCV was started a median time of 56 days (range 37-429) after transplant. In all, 11 patients (73%) completed the 28 days of therapy with VGCV. All patients showed a complete clearance of the virus. The median time to achieve a negative CMV-PCR was 6 days (range 4-18). A relapse of CMV infection after VGCV preemptive therapy occurred in 6 patients (40%). No patient developed early or late CMV disease. Six patients (40%) presented hematological toxicity including neutropenia and/or thrombocytopenia that required drug discontinuation in 4 cases. CONCLUSION: VGCV administered as preemptive therapy for CMV infection in patients receiving an allogeneic HSCT showed promise for treating this frequent complication. Prospective randomized studies in this setting are mandatory to yield more definitive results.     

Cytotoxic T-lymphocyte response to cytomegalovirus after human allogeneic bone marrow transplantation: pattern of recovery and correlation with cytomegalovirus infection and disease.

The high rate of severe cytomegalovirus (CMV) disease after bone marrow transplantation (BMT) is related to the profound immunodeficiency posttransplant. Because cytotoxic T lymphocytes (CTL) have been implicated in resistance to viral infections, we examined the restoration of the CMV-specific CTL response in 20 patients who received bone marrow from HLA-matched, CMV-seropositive donors. Blood specimens were obtained from patients at 1, 2, and 3 months after BMT and from the donors on a single occasion. Peripheral blood mononuclear cells were cocultured with CMV-infected donor-derived fibroblasts for 2 weeks and then tested for cytotoxicity against CMV-infected and uninfected autologous or HLA-mismatched fibroblasts. Cytolytic activity was detected in all 20 donors, with specificity for autologous CMV-infected targets demonstrable in 17 (median CMV-specific lysis at an effector:target ratio of 15:1 was 32%, range 18% to 83%). Specific lysis was mediated by CD8+, class I-restricted T cells, as shown by inhibition with anti-class I monoclonal antibody and by selective depletion of effector cells. By contrast, CMV-specific CTL were detected in only 10 of 20 patients after BMT (median lysis 29% at 3 months post-BMT). None of these 10 patients developed CMV pneumonia, whereas 6 of the 10 patients with an undetectable CMV-specific CTL response after BMT died with CMV pneumonia. These results demonstrate that restoration of CMV-specific CTL responses may require an extended time period after BMT in some patients, and that such patients are at increased risk of developing severe CMV disease. Approaches to reconstitute CMV immunity in BMT patients by adoptive transfer of CMV-specific CD8+ CTL clones derived from the bone marrow donor are now being pursued.     

Primary familial polycythaemia associated with a novel point mutation in the erythropoietin receptor

To identify and treat patients at high risk of cytomegalovirus (CMV) pneumonia after bone marrow transplantation (BMT), we tested for CMV viraemia weekly, and performed broncho-alveolar lavage (BAL) on day 35 post-transplant in 63 recipients. 36 allogeneic BMT recipients were at a high risk of CMV pneumonia (25 CMV-seropositive recipients and 11 patients receiving marrow from a CMV-seropositive donor). Patients with a positive BAL or viraemia received a 14 d course of ganciclovir or foscarnet. CMV was detected in 29 (46%) of the 63 BMT recipients and excretion of CMV in blood and BAL was significantly linked. However, among the 29 patients who excreted the virus, only 10 (35%) shed CMV in blood and BAL at the same time; 19 patients (65%) had detectable CMV in blood (11 patients) or BAL (eight patients) only. Therefore, on the basis of viraemia or BAL alone, 21/29 patients (70%) and 18/29 patients (60%), respectively, would have received antiviral treatment. BAL increased the CMV detection rate by 13% (8/63 patients) relative to viraemia. With this strategy, the incidence of CMV pneumonia was reduced to 3% in allografted patients. Only two of the 19 autografted patients developed fatal CMV pneumonia. We avoided anti-CMV treatment in 54% of all the BMT recipients. In conclusion, CMV should be tested for in both blood and BAL fluid of BMT recipients at high risk of CMV pneumonia.     

Risk factors for cytomegalovirus infection after human marrow transplantation

The records of 545 patients were reviewed for risk factors associated with cytomegalovirus (CMV) infection after marrow transplant. CMV infection occurred among 36% of seronegative patients and 69% of seropositive patients. Among seronegative patients, significant risk factors for CMV infection included positive serology of the marrow donor (relative rate, 2.3) and the use of granulocyte transfusions from seropositive donors (relative rate, 2.5). Among both seronegative and seropositive patients, the occurrence of acute graft-versus-host disease (GVHD) significantly increased the risk of CMV infection (average relative rate, 1.8) and of subsequent CMV pneumonia (average relative rate, 2.6). CMV excretion and viremia were each associated with subsequent pneumonia, but the positive predictive values were low. One-third of long-term survivors excreted CMV at greater than 250 days after transplantation. The only risk factor for late excretion was CMV infection that occurred in the first 150 days after transplantation. In contrast to the effect of acute GVHD on CMV infection, CMV infection did not increase the risk of either acute or chronic GVHD.     

Reduced risk of persisting cytomegalovirus pp65 antigenemia and cytomegalovirus interstitial pneumonia following allogeneic PBSCT

In order to evaluate the risk of cytomegalovirus (CMV) associated disease after allogeneic stem cell transplantation (SCT), 158 consecutive patients at risk for infection were analyzed. BMT was performed in 101 patients and peripheral blood stem cell transplantation (PBSCT) in 57 patients. CMV antigenemia was found in 57 cases (56%) after BMT and 27 cases (47%) after PBSCT, respectively. CMV antigenemia resistant to a 14-day course of GCV was found in 26 patients (26%) after BMT but in only four patients (7%) after PBSCT (P < 0.01). Eighteen patients (11%) developed CMV disease, 14 post BMT and four post PBSCT. Lethal CMV-related interstitial pneumonia (CMV-IP) occurred in 13 cases of whom 12 patients were bone marrow recipients (P = 0.04). The subgroup of seronegative patients with a CMV seropositive donor had a significantly lower risk of developing CMV antigenemia, GCV-resistant CMV antigenemia (P < 0.01) and CMV-related disease (P = 0.01). In conclusion, the incidence of persistent CMV antigenemia and CMV-IP was significantly reduced when allogeneic transplantation was performed with peripheral blood stem cells instead of bone marrow. These findings suggest that our previous in vitro data on improved immune reconstitution after allogeneic PBSCT as compared to allogeneic BMT have clinical relevance.     

Foscarnet prophylaxis of cytomegalovirus infections in patients undergoing allogeneic bone marrow transplantation (BMT): a dose-finding study

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.     

Prevention and treatment of respiratory infections in leukemia patients

Among infections in leukemia patients during their first induction treatment pneumonia was the third most frequent infection (11.4%) following fever of unknown origin and sepsis. Granulocytopenia was suggested to be very closely related to the onset of pneumonia. Laminar air flow rooms seemed very effective for preventing exogenous infections including pneumonia. They reduced pneumonia from 30 to 0 in 106 patients with acute leukemia during their first induction treatment. Bone marrow transplantation (BMT) is one of the most intensive immunosuppressive treatments. Major causes of failure were interstitial pneumonitis (IP) due to cytomegalovirus (CMV), relapse of leukemia and bacterial and fungal infections. The incidence of IP was reduced by fractionation of total body irradiation and selection of CMV antibody negative donor for platelet transfusion. Administration of anti CMV immunoglobulin has also reduced the incidence of IP significantly from 37.5% to 11.5%. Colony stimulating factor appeared to stimulate the recovery of leukocytes after BMT. By several modifications of BMT techniques, mainly for the prevention of infection and IP, the survival of patients after BMT has improved significantly from 20% to 85%. In conclusion, prevention and treatment of respiratory infections are important in the treatment of leukemia, both for chemotherapy and BMT.     

Cytomegalovirus DNA in the sera of patients with cytomegalovirus pneumonia

We attempted to detect cytomegalovirus DNA (CMV-DNA) in the sera of four leukaemia patients who underwent an allogeneic bone marrow transplant (BMT), in six leukaemia patients who suffered from pneumonia and in 16 healthy subjects, using the polymerase chain reaction (PCR). Three of the four BMT patients subsequently developed CMV pneumonia. In two cases, CMV-DNA was detected in the sera at about the time the pneumonia occurred, and the amount of DNA increased with disease progression. The serum of the third patient became positive for CMV-DNA before he developed pneumonia. The fourth patient did not develop CMV pneumonia, but his urine became persistently positive for CMV-DNA soon after the BMT, whereas the serum was negative. A relationship was found between the occurrence of pneumonia and the serum level of CMV-DNA. CMV-DNA was also detected in three of six pneumonia patients whose anti-CMV IgM antibodies were elevated in the circulation. Sera from the 16 normal subjects were negative for CMV-DNA, regardless of their being seropositive or seronegative for CMV. While it had been previously thought that CMV did not exist in serum, we detected CMV-DNA in serum by PCR in the active disease stage. Our results suggest that PCR would be useful for the early diagnosis of CMV pneumonia and in monitoring its course.     

CMV pneumonia in allogeneic BMT recipients undergoing early treatment of pre-emptive ganciclovir therapy

The incidence, treatment and outcome of CMV interstitial pneumonia (CMV-IP) were reviewed in 139 consecutive allogeneic BMT patients undergoing extended CMV antigenemia surveillance and two different ganciclovir (GCV) strategies to control CMV infection. Nineteen cases of CMV-IP were reviewed, 16 of 63 patients (25.4%) who received early GCV treatment (ET) and three of 76 patients (3.9%) who received preemptive (PE) GCV therapy. In the ET group, the median time for occurrence of CMV-IP was 55 (range 36 to 311) days. Two patients had three episodes of CMV-IP recurrences after day +100. CMV-IP-related death occurred in two patients (15.4%). In the PE group, 41 patients received pre-emptive GCV therapy prompted by the appearance of positive antigenemia > or =2 cells. The median time for the occurrence of CMV-IP was 92 (range 48 to 197) days. Response to therapy was observed when GCV was introduced within 6 days of antigenemia positivity. The use of IVIg in association with GCV did not play a major role in response to therapy. The median time for occurrence of CMV-IP was delayed during PE strategy and the cost-effectiveness of CMV surveillance after day +100 should be investigated in this population.     

Immunoglobulins A, G, and M to cytomegalovirus during recurrent infection in recipients of allogeneic bone marrow transplantation.

Occurrence and significance of specific IgA and IgM to cytomegalovirus (CMV) in recurrent CMV infection was evaluated in 21 allogeneic T lymphocyte-depleted bone marrow transplantation (BMT) recipients who had been previously CMV seropositive. Of 17 patients with CMV infection, viruria was detected in 94%, CMV-specific IgA in 88% and IgM in 76%, and a fourfold rise in IgG in 65%. The median time between BMT and detection of viruria was 69 days, of IgA 70, of IgM 62, and of IgG 88 days. The IgM and IgA responses lasted for 14 and 30 days (median time), whereas high IgG titers persisted. Twelve patients developed CMV disease; in these the appearance of viruria, IgA, and IgM preceded the rise of IgG (P less than .02). CMV-specific IgA and IgM are valuable diagnostic tools in BMT recipients with recurrent CMV infection.     

Cytomegalovirus infection after autologous bone marrow transplantation with comparison to infection after allogeneic bone marrow transplantation

Cytomegalovirus (CMV) infection was detected in 65 of 143 (45%) autologous bone marrow transplant (BMT) patients. CMV pneumonitis occurred in only 2% of the patients and CMV retinitis occurred in none. Infection occurred in half of the 40 initially seronegative patients and 47% of the 94 initially seropositive patients. Among initially seropositive patients, platelet recovery was slower in infected patients than in those not infected (97 v 35 days median, P = .003), and neutrophil recovery was slightly delayed in infected patients (31 days v 24 days, P = .02). Although the incidence of CMV infection was comparable in autologous and allogeneic BMT patients, CMV pneumonitis was less frequent in autologous BMT patients (2% v 12%, P less than .001). The risk for CMV pneumonitis in autologous BMT patients was comparable with that in allogeneic BMT patients without graft-v-host disease (GVHD) (2% v 6%), but significantly lower than the risk in allogeneic BMT patients with GVHD (2% v 23%, P less than .001).     

Interstitial pneumonia (IP) in bone marrow transplantation in leukemia--120 cases analysis in Nagoya Bone Marrow Transplantation Group

Results of the bone marrow transplantation (BMT) for 120 cases of leukemia, which were done in nine institutes in Nagoya (Nagoya Bone Marrow Transplantation Group) last ten years, were analyzed to determine the factors associated with an increased risk of developing interstitial pneumonia (IP). IP developed 49 out of 120 patients (49.8%) and case fatality rate was 63.3%. The median time from transplantation to onset of IP was 81 days (range 13-575 days), in 30 out of 49 cases (61.2%), this complication developed within 100 days after transplantation. Of the 49 patients who developed IP, cytomegalovirus (CMV) infection was associated in 18 cases (36.7%), no cases of P. carinii infection was detected. Five factors were associated with an increased risk for developing IP, (1) older age (greater than or equal to 47.0%: less than 10 y. 10.0%) (p less than 0.01) (2) disease stage at BMT (non-remission 76.2%: remission 32.5%) (p less than 0.01) (3) presence of acute GVHD ((+) 52.5% (-) 28.8%) (p less than 0.05) (4) onset day after BMT (less than or equal to 100 days 61.2%: greater than 100 d. 38.8%) (p less than 0.01) (5) sex matching between donor and patient (sex match 28.8%: sex mismatch 57.1%) (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cytomegalovirus infection in heart-lung transplant recipients: risk factors, clinical associations, and response to treatment.

The risk factors, clinical associations, and response to treatment of cytomegalovirus (CMV) pneumonia and infection were studied in 65 recipients of heart-lung transplantation. There were 29 episodes of CMV pneumonia in 22 patients. In 80% (20/25) of episodes of CMV pneumonia treated with intravenous ganciclovir, the histologic changes resolved and the patient survived. Among seronegative recipients, a seropositive donor was a significant risk factor for CMV pneumonia and infection in the first 90 days after heart-lung transplantation (P = .004 and .002, respectively). Among seropositive recipients, there was no additional risk associated with a sero-positive donor. Rates of CMV pneumonia and infection were significantly increased when treatment with augmented immunosuppression had been given in the preceding 30 days (P less than .001). A significant association was found between CMV pneumonia or infection and pulmonary bacterial infections occurring 30 days before or after such an episode (P less than .001).     

Cytomegalovirus pneumonia in adult autologous blood and marrow transplant recipients

CMV pneumonia is a major cause of morbidity and mortality among allogeneic BMT recipients. To assess the frequency, timing, risk factors and response to therapy of CMV pneumonia among autologous BMT recipients, we reviewed our experience with 795 patients. Sixteen (2%) patients were diagnosed with CMV pneumonia. The frequency was higher among patients who were seropositive than those who were seronegative (3.3% vs 0%, P = 0.008). Among seropositive patients, the frequency was higher among patients with hematological malignancies than patients with solid tumors (5.0 % vs 1.0%, P = 0.019). Eleven cases occurred <30 days, and five cases occurred >100 days post transplant. The overall CMV pneumonia-related mortality rate was 31%. Seven (78%) of nine patients treated with ganciclovir and IVIG prior to respiratory failure survived; neither of two patients treated after respiratory failure survived. Four of five (80%) untreated patients survived. In conclusion, CMV is a not infrequent cause of pneumonia among autologous BMT recipients. Risk factors include CMV seropositivity and an underlying hematological malignancy. A favorable response hinges on the prompt initiation of therapy. The survival of 25% of the patients without antiviral therapy suggests that the isolation of CMV from a BAL specimen occasionally reflects oropharyngeal contamination or that CMV pneumonia may sometimes be self-limited in more immunocompetent autologous BMT recipients.     

Randomized study of valacyclovir as prophylaxis against cytomegalovirus reactivation in recipients of allogeneic bone marrow transplants

Oral valacyclovir for cytomegalovirus (CMV) prophylaxis in bone marrow transplantation (BMT) was investigated in a randomized, double-blind, acyclovir-controlled, multicenter clinical trial in recipients of allogeneic BMT who were CMV seropositive (or donor positive) before transplantation and were aged 13 years or older. Patients were randomized before BMT. All initially received intravenous acyclovir (500 mg/m(2)) 3 times daily until day 28 after transplantation or after discharge, then oral valacyclovir (2 g) or acyclovir (800 mg) 4 times daily until week 18 after transplantation. Evidence of CMV infection, CMV disease, and death were documented for 22 weeks. Primary end points were time to CMV infection (detection of CMV in blood, broncho-alveolar lavage) or CMV disease and survival. Preemptive CMV therapy was permitted. Seven hundred twenty-seven patients were evaluable for efficacy. After the administration of intravenous acyclovir, valacyclovir was significantly more effective than oral acyclovir in reducing the incidence of CMV infection. CMV infection or disease developed in 102 (28%) valacyclovir patients, compared with 143 (40%) acyclovir patients (HR, 0.59; 95% CI, 0.46-0.76; P <.0001). Survival did not differ between treatments (76% and 75% in the valacyclovir and acyclovir groups, respectively). The safety of oral valacyclovir was similar to that of high-dose oral acyclovir. Valacyclovir was more effective than acyclovir in preventing CMV reactivation in BMT recipients and showed a similar safety profile. CMV disease incidence was low, and no differences were observed between oral valacyclovir and acyclovir. Survival was similar in each group. Valacyclovir prophylaxis provides a clinically valuable intervention but must be part of an overall strategy for CMV prevention in BMT.