膦甲酸钠预防及抢先治疗造血干细胞移植中巨细胞病毒感染的临床研究

目的 观察膦甲酸钠用于异基因造血干细胞移植(allo-HSCT)预防及抢先治疗巨细胞病毒(CMV)感染的疗效及安全性.方法 回顾性分析2014年10月至2016年12月96例接受allo-HSCT患者临床资料.采用实时荧光定量聚合酶链反应(RQ-PCR)监测患者血浆巨细胞病毒(CMV)-DNA情况至移植后6个月,预防及抢先治疗分别采用膦甲酸钠每天60 mg/kg和每天120 mg/kg.观察CMV血症、CMV病发生情况,分析CMV感染的影响因素,分析膦甲酸钠治疗效果和安全性,评估患者生存情况.结果96例患者中42例(43.8%)移植后发生CMV感染,中位感染时间42 d.膦甲酸钠治疗的42例CMV感染患者中,疗效显著36例(85.7%),进展为CMV病6例(14.3%),其中CMV转阴5例,因CMV间质性肺炎死亡1例.半相合移植及Ⅱ~Ⅳ度移植物抗宿主病(GVHD)患者CMV血症发病率升高(χ2=3.834,P<0.05;χ2=16.807,P<0.001).膦甲酸钠不良反应轻微,无明显中性粒细胞减少.发生CMV血症42例中,死亡12例(28.6%),未发生CMV血症54例中,死亡6例(11.1%),两组总生存率差异无统计学意义(χ2=3.546,P=0.06).结论 应用膦甲酸钠对allo-HSCT患者预防及抢先治疗CMV感染的疗效确切,耐受性良好,尤其适用于造血未完全恢复的患者.     

The Impact of Direct-Acting Antiviral Agents on Cytomegalovirus Reactivation in Chronic Hepatitis C Infection

Objective: The co-infection of HCV/CMV may accelerate the progression of liver diseases and worsen responsiveness to IFN treatment. The Direct-acting antiviral agents (DAAs), currently approved therapy for HCV, may cause a transient change in immune status, favoring the reactivation of other viruses. The current study aims to evaluate the impact of DAAs treatment on the reactivation of latent CMV in HCV patients. Methods: The serological IgG, IgM Abs against CMV were detected by ELISA on192 HCV patients. The seronegative CMV IgM patients received (sofosbuvir/daclatasvir) regimen, then the CMV reactivation was examined by measuring the CMV IgM by ELISA and CMV DNA by real-time PCR. Results: The serological data revealed that all patients were positive for CMV IgG (100%) while (64%) patients were positive for CMV IgM. The seronegative CMV IgM (36%) received the DAAs protocol. The sustained virological response was monitored by measuring the HCV RNA viremia in the patient sera. The serological data revealed that 28.6% of patients had a reactivation of CMV, while 18.5% of patients had detectable CMV DNA viremia. Moreover, there was a significant improvement in liver function as well as a decrease in FIB-4 and APRI scores at EOT. SVR was reached 97.4% among the total studied patients (N= 192). Conclusion: CMV co-infection has no impact on the response rate to DAAs. However, the CMV reactivation might have occurred after the complete eradication of HCV by DAAs.     

Cytomegalovirus pneumonia in a patient with breast cancer on chemotherapy: Case report and review of the literature

Cytomegalovirus (CMV) pneumonia in the setting of non-transplantation patients is a rarity. We present a case of CMV pneumonitis in a woman with stage IV breast cancer, with brain metastases, receiving both chemotherapy and systemic corticosteroids. A review of the literature reveals this as a unique case. Potential viral etiologies should therefore be considered in cancer patients with pneumonia receiving non-transplantation chemotherapy-regimens, particularly if steroids are a component of their therapy.     

Cytomegalovirus colitis--a severe complication after standard chemotherapy

We report on a case of cytomegalovirus (CMV) enterocolitis occurring in a 65-year-old patient after a first course of standard chemotherapy for a small cell lung carcinoma (SCLC). Colonic biopsies showed typical inclusion bodies, CMV IgM and IgG antibodies were found in the serum, and polymerase chain reaction for CMV-DNA was positive. Lymphopenia and diminished CD4 T-cell counts were observed. Diarrhoea ceased under ganciclovir treatment, the patient recovered, but died several months later of metastatic lung cancer. Significant immunosuppression leading to severe colitis by CMV infection or reactivation can occur after standard chemotherapy.     

Filgrastim and alemtuzumab (Campath-1H) for refractory chronic lymphocytic leukemia.

Alemtuzumab (anti-CD52; Campath-1H) is effective in fludarabine-refractory chronic lymphocytic leukemia (CLL), but is associated with infection and early onset neutropenia. To reduce toxicity, filgrastim (G-CSF) was administered concurrently with alemtuzumab. In total, 14 CLL patients (median age 59) with a median of 3.5 prior regimens (range 1--12) received i.v. alemtuzumab, stepped up from 3 to 30 mg the first week, then 30 mg thrice weekly for 12 weeks. Filgrastim 5 microg/kg was administered daily 5 days before and throughout alemtuzumab therapy. Six patients developed cytomegalovirus (CMV) reactivation 3--6 weeks into treatment; six patients developed fever, three neutropenia, and one pneumonia. The patient with CMV pneumonia died; ganciclovir cleared CMV in the other patients. Five patients developed early neutropenia (weeks 2--5). Four patients developed delayed neutropenia (weeks 10--13) unassociated with CMV reactivation. Nine patients ceased therapy because of infectious and hematologic toxicity. Five partial responses were noted, all in patients with lymph nodes>cm, lasting a median of 6.5 months (range 5--13). Filgrastim and alemtuzumab were given concurrently with manageable infusion toxicity and clinical activity, but the efficacy of this regimen was limited by delayed neutropenia of unclear etiology and CMV reactivation. Filgrastrim should not be administered prophylactically during alemtuzumab therapy outside clinical trials.     

Cytomegalovirus Colitis--A Severe Complication after Standard Chemotherapy

We report on a case of cytomegalovirus (CMV) enterocolitis occurring in a 65-year-old patient after a first course of standard chemotherapy for a small cell lung carcinoma (SCLC). Colonic biopsies showed typical inclusion bodies, CMV IgM and IgG antibodies were found in the serum, and polymerase chain reaction for CMV-DNA was positive. Lymphopenia and diminished CD4 T-cell counts were observed. Diarrhoea ceased under ganciclovir treatment, the patient recovered, but died several months later of metastatic lung cancer. Significant immunosuppression leading to severe colitis by CMV infection or reactivation can occur after standard chemotherapy.     

Detection of Epstein-Barr Virus and Cytomegalovirus in Gastric Cancers in Kerman,Iran

Gastric cancer (GC) is a multifactorial disease with different factors having roles in its genesis. Helicobacter pylori and Epstein-Barr virus (EBV) are known infectious agents that could contribute. In addition, there is evidence of a relationship with cytomegalovirus (CMV). Since data on CMV prevalence in gastric cancer are limited, we here evaluated the frequency of EBV and CMV in Iranian patients. Ninety paraffin blocks of GC tissues from patients in Kerman were evaluated for the presence of EBV and CMV genomes by real-time polymerase chain reaction. EBV was detected in 10 cases (11.1%) and CMV in seven. One out of 17 female patients (5.88%) and nine out of 73 male patients (12.3%) were positive for EBV, while one out of 17 female patients (5.88%) and six out of 73 male patients (8.22%) were positive for CMV. The mean age for EBV-positive patients was 60.514.9 years and the mean age for CMV-positive patients was 67.912.3years. This study shows that the frequency of EBV-associated GC is high in Kerman. It also indicates that further studies of associations between GC and CMV are warranted, covering larger samples and populations from different areas of the world.     

Role of cytomegalovirus and Epstein-Barr virus in patients with de novo colon cancer after renal transplantation

AIMS: The development of new effective immunosuppressive agents has provided long-term survival for transplant recipients, thereby increasing the risk of de novo malignancy in chronic immunocompromised hosts. Although de novo post-transplant lymphoproliferative diseases and skin cancer have been shown to have an increased incidence in long-term surviving solid organ transplant recipients, the association with colon cancer is controversial. PATIENTS AND METHODS: Over a 12-year period, 20 patients (5%) out of 400 renal transplant recipients (treated at the University Hospitals of Udine and Ancona) developed 24 de novo tumors; 11 skin cancers and 13 non-skin cancers. Three patients developed de novo colon cancer. Immunosuppressive therapy was reduced immediately after diagnosis, and all patients were shifted from cyclosporine to rapamycin within 30 days. The tumor was surgically resected with curative intent in 2 cases, and 1 patient had only palliative surgery due to metastatic disease. The postoperative course was uneventful, and all patients maintained normal graft function. RESULTS: Two of 3 patients died of progression of the neoplasm, within a median time from the diagnosis of 12 months. We analyzed the possible correlations between de novo colon cancer and "serology (hepatitis C virus-hepatitis B virus, HCV-HBV) status" infections, cytomegalovirus and Epstein-Barr virus reactivation, episodes of rejection, and blood transfusions. CONCLUSIONS: Differently from other de novo skin and non-skin tumors, our cases developed cytomegalovirus and Epstein-Barr virus reactivation within 3 months of transplantation. Therefore, we suggest a closer follow-up for de novo colon cancer in renal transplants with early cytomegalovirus and Epstein-Barr virus reactivation in order to avoid a delay in diagnosis.     

Fatal herpetic encephalitis during brain radiotherapy in a cerebral metastasized breast cancer patient

Herpes simplex encephalitis (HSE) is a life-threatening condition with high mortality. The pathogenesis underlying the reactivation of latent herpes simplex virus (HSV) remains undefined. We present the case of a 55-year-old female who developed HSE type 1 during brain irradiation and antioedematous dexamethasone treatment for leptomeningeal metastasized breast tumor with epileptic seizures. During the radiotherapy (RT), after a total of 32 Gray administrated in 16 fractions, our patient developed cognitive impairment and partial epileptic status without fever. Two days later the patient’s clinical conditions had deteriorated and high fever manifested. A diagnosis of HSE type 1 was made by a positive cerebrospinal fluid polymerase chain reaction. Antiviral therapy with high doses of acyclovir was practiced for four weeks but the comatose state persisted. The patient died 59 days after the last RT fraction. The temporal relationship of RT to the occurrence of HSE suggests that cranial irradiation may play a role in the reactivation of latent HSV. Although antiviral therapy resistance is infrequent in immunocompetent patients, it is one of the main problems in immunocompromized patients.     

Efficacy and tolerability of alemtuzumab (CAMPATH-1H) in the salvage treatment of B-cell chronic lymphocytic leukemia--change of regimen needed?

We report on the response rate and tolerability of Alemtuzumab (Campath-1H) in a series of heavily pretreated patients with B-CLL with a special focus on treatment-related problems. All patients tested positive for CD52 on B-lymphocytes before entering the trial. Thirteen patients with B-chronic lymphocytic leukemia (B-CLL), 1 prolymphocytic leukemia (PLL), 1 mantle cell lymphoma (MCL) and 1 leukemic immunocytoma (IC) transformed into a high-grade NHL were included. Median age was 62 years (range 40-73), and pretreatment consisted of median 3 prior regimens (range 1-11). All patients received 3, 10 and 30 mg of Campath-1H on sequential days, and then were subsequently scheduled for 30 mg 3 times weekly. Nine out of 16 patients responded. One patient attained complete remission (CR), 8 patients achieved partial remission (PR), while 4 patients had stable disease (SD). Three patients had progressive disease (PD). Beginning with initiation of treatment recurrent profound leukopenia became evident in 13 out of 16 patients leading to treatment discontinuation. Severe nonhematological toxicity (WHO grade IV bronchospasm) occurred in the first patient of this series, who initially had no concomitant steroids. Therefore, we developed a steroid co-medication regimen for the first 4 Campath-1H applications with quick tapering thereafter. Following this regimen, no infusion associated side effects WHO grade > II were observed. Infectious complications leading to treatment discontinuation consisted of pulmonary aspergillosis in one and bacterial pneumonia in another case. One patient with refractory B-CLL and Pneumocystis carinii pneumonia plus CMV reactivation died. In summary, Campath-1H appears to be effective against leukemic low-grade B-NHL, also in advanced stage. In our series, application 3 times weekly was not possible due to hematotoxicity. We recommend, therefore, flexible time intervals depending on the leukocyte counts. Whether a cumulative dosage according to 3 x 30 mg Campath-1H for 12 weeks is needed still remains to be clarified.     

The role of oxidative stress in EBV lytic reactivation,radioresistance and the potential preventive and therapeutic implications

Epstein‐Barr virus (EBV) is an important cancer causing virus. Cancer associated with EBV account for approximately 1.5% of all cancers, and represent 1.8% of all cancer deaths worldwide. EBV reactivation plays an important role in the development of EBV‐related diseases and is closely related with patients' survival and clinical stages of EBV‐related cancers. The therapy regarding to EBV‐related cancers is very urgent, especially in endemic areas. Generating oxidative stress is a critical mechanism by which host cells defend against infection by virus. In addition, ROS‐mediated oxidative stress plays a significant but paradoxical role acting as a “double‐edged sword” to regulate cellular response to radiation, which is the main therapy strategy for EBV‐related cancers, especially nasopharyngeal carcinoma. Therefore, in this review we primarily discuss the possible interplay among the oxidative stress, EBV lytic reactivation and radioresistance. Understanding the role of oxidative stress in EBV lytic reactivation and radioresistance will assist in the development of effective strategies for prevention and treatment of EBV‐related cancers.     

Cytomegalovirus isolations from cell cultures derived from Epstein-Barr virus-associated nasopharyngeal carcinoma

Cytomegalovirus (CMV) was isolated in cell cultures derived from 2 of 11 nasopharyngeal carcinoma (NPC) biopsy specimens from North African patients. All these cases were Epstein-Barr virus (EBV)-associated NPC. Morphologic cytopathic changes and viral replication not associated with EBV were observed after 2 months in culture. Virus identification was achieved by immunofluorescence studies, and cell culture antigens were tested by the use of complement fixation and indirect hemagglutination. All these NPC patients had been infected by herpes simplex virus, varicella-zoster virus, and CMV, but the antibody titers determined by complement fixation and immunofluorescence were normal. CMV, which is not associated with this cancer, could nevertheless favor carcinogenesis in facilitating fusion between epithelial cells and EBV-positive lymphocytes.     

Cytomegalovirus Retinitis and Retinal Detachment following Chimeric Antigen Receptor T Cell Therapy for Relapsed/Refractory Multiple Myeloma

Cytomegalovirus (CMV) retinitis is a rare end-organ disease of CMV infection and is a marker of severe immunosuppression, especially in human immunodeficiency virus (HIV)-positive patients. In multiple myeloma (MM) patients, CMV retinitis has been reported in the post-transplant setting, with an incidence lower than 0.2%, and in patients receiving lenalidomide. Here, we describe the first case of CMV retinitis in myeloma patients following B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor T (BCMA CAR-T) cell therapy. In addition to CMV, the patient developed multiple infections including a mouth ulcer, pneumonia, and fungal enteritis. While the complete remission (CR) status of MM was maintained, he regained a visual acuity of 20/1000 after appropriate ophthalmologic treatment. This single case illustrates the potential of BCMA CAR-T therapy to induce profound humoral immunosuppression, and demonstrates an imperative need for an established standard of monitoring and prophylaxis of post-CAR-T infections.     

Epstein-Barr virus involvement is a predictive factor for the resistance to chemoradiotherapy of gastric diffuse large B-cell lymphoma

Primary gastric diffuse large B-cell lymphomas are generally well controlled by non-surgical treatment with combination chemotherapy followed by radiotherapy. We have previously reported that over 90% of patients achieved complete response (CR) with this therapeutic strategy: three cycles of cyclophosphamide, adriamycin, vincristine and prednisone followed by radiotherapy (40.5 Gy). Although the CR rate was very high, some patients still showed resistance to this combination therapy. In order to clarify the factors related to therapy resistance, we examined the relationship between Epstein-Barr virus (EBV), which was examined using an in situ hybridization technique, and the patients' clinical courses. Out of the 50 patients, four were EBV positive; over half of lymphoma cells were positive for EBV by in situ hybridization. Of the three EBV-positive patients, two showed progressive disease and one achieved partial response (PR). Two of the patients died of disease progression. The other patient achieved CR, but the lymphoma recurred with distant metastasis in the cerebellum 3 months after remission. In the present study, eight patients did not achieve CR or they relapsed, four patients showed progressive disease, one patient achieved PR, and three patients achieved CR with recurrence. Therefore, half of these unfavorable patients were EBV positive. This finding strongly indicated that EBV-associated gastric diffuse large B-cell lymphomas frequently show resistance to standard chemoradiotherapy, although some other adverse factors remain unclear.     

Fulminant anaplastic large cell lymphoma (ALCL) concomitant with primary cytomegalovirus (CMV) infection,and human herpes virus 8 (HHV-8) infection together with Epstein-Barr-virus (EBV) reactivation in a patient with asymptomatic HIV-infection

Background

Most malignant lymphomas in HIV-patients are caused by reactivation of EBV-infection. Some lymphomas have a very rapid fulminant course. HHV-8 has also been reported to be a cause of lymphoma. The role of CMV in the development of lymphoma is not clear, though both CMV and HHV-8 have been reported in tissues adjacent to the tumour in Burkitt lymphoma patients. Here we present a patient with asymptomatic HIV infection, that contracted a primary cytomegalovirus (CMV) infection and human herpes virus 8 (HHV-8) infection. Three weeks before onset of symptoms the patient had unprotected sex which could be possible source of his CMV and also HHV-8 infection He deteriorated rapidly and died with a generalized anaplastic large cell lymphoma (ALCL).

Methods

A Caucasian homosexual male with asymptomatic human immunodeficiency virus (HIV) infection contracted a primary cytomegalovirus (CMV) infection and human herpes virus 8 (HHV-8) infection. He deteriorated rapidly and died with a generalized anaplastic large cell lymphoma (ALCL). Clinical and laboratory records were compiled. Immunohistochemistry was performed on lymphoid tissues, a liver biopsy, a bone marrow aspirate and the spleen during the illness and at autopsy. Serology and PCR for HIV, CMV, EBV, HHV-1–3 and 6–8 was performed on blood drawn during the course of disease.

Results

The patient presented with an acute primary CMV infection. Biopsies taken 2 weeks before death showed a small focus of ALCL in one lymph node of the neck. Autopsy demonstrated a massive infiltration of ALCL in lymph nodes, liver, spleen and bone marrow. Blood samples confirmed primary CMV- infection, a HHV-8 infection together with reactivation of Epstein- Barr-virus (EBV).

Conclusion

Primary CMV-infection and concomitant HHV-8 infection correlated with reactivation of EBV. We propose that these two viruses influenced the development and progression of the lymphoma. Quantitative PCR blood analysis for EBV, CMV and HHV-8 could be valuable in diagnosis and treatment of this type of very rapidly developing lymphoma. It is also a reminder of the importance of prevention and prophylaxis of several infections by having protected sex.

     

A multicenter study of pandemic influenza A (H1N1) infection in patients with solid tumors in 3 countries: Early therapy improves outcomes

BACKGROUND:

Pandemic influenza A (hereafter 2009/H1N1) caused significant morbidity and mortality during the 2009 pandemia. Patients with chronic medical conditions and immunosuppressive diseases had a greater risk of complications. However, data regarding the characteristics and outcome of 2009/H1N1 infection in patients with solid tumors are nonexistent. Herein, the authors describe a series of influenza 2009/H1N1 in patients with solid malignancies at 3 major cancer hospitals worldwide.

METHODS:

The authors retrospectively reviewed the records of patients with solid organ malignancies and 2009/H1N1 from The University of Texas M. D. Anderson Cancer Center in Houston, Texas; the Mexican National Cancer Institute, Federal District of Mexico; and King Hussein Cancer Center in Amman, Jordan from the period of the 2009 H1N1 pandemia. Data on demographics, disease characteristics, and outcome were extracted.

RESULTS:

In total, 115 cases were identified during the pandemic influenza among the 3 institutions. High rates of hospitalization (50%), pneumonia (23%), and death (9.5%) were reported. Patients who developed pneumonia and those who died were moderately to severely immunocompromised (P = .001 and P = .006, respectively). A multivariate competing risk analysis demonstrated that a delay >48 hours in starting antiviral therapy was associated significantly with an increased risk of developing pneumonia (P = .013).

CONCLUSIONS:

The 2009/H1N1 pandemic caused severe illness in immunocompromised patients with cancer who had solid tumors, and heavily immunosuppressed patients were at greater risk of developing pneumonia and death. Early initiation of antiviral therapy is crucial in this patient population to decrease morbidity and probably mortality. Cancer 2012. © 2012 American Cancer Society.     

Cytomegalovirus infection in hematologic malignancy settings other than the allogeneic transplant

Cytomegalovirus (CMV) infection in clinical settings other than the allogeneic transplant represents a poorly explored issue. Thus, we performed a comprehensive review of the medical literature about CMV infection in patients undergoing autologous hematopoietic stem cell transplant and in other nontransplant‐related hematologic patients. In autologous hematopoietic stem cell transplant, a CMV reactivation is reported to occur in up to 41% of CMV seropositive patients, when a prospective monitoring of antigenemia and/or viremia by polymerase chain reaction was adopted. However, more contained frequencies, up to 12%, have been reported when the monitoring criteria were based on a clinically driven diagnostic strategy. The most relevant risk factors appear to be CD34 + selected autografts, total body irradiation, and prior treatment with Alemtuzumab, Fludarabine, or Bortezomib, respectively. Other possible risk factors (ie, prior treatment with Rituximab, T‐cell lymphomas, and pretransplant HBcIgG seropositivity) are still debated. In nontransplant settings, the data are very heterogeneous; thus, CMV infection incidence and risk factors are more difficult to establish. Overall, the rate of CMV infection/reactivation ranges between 2 and 67%. High‐dose steroids, advanced disease, poor performance status, and treatment with Alemtuzumab, Fludarabine, Bortezomib, and Rituximab appear as the most relevant, though putative, risk factors. Intravenous Ganciclovir represents the gold standard for first‐line treatment of CMV infection in these patients. Oral Valganciclovir and Foscarnet are other possible options. Extensive prophylaxis and preemptive therapy are not generally recommended, with the exception of high‐risk patients.     

Cytomegalovirus viremia during Campath-1H therapy for relapsed and refractory chronic lymphocytic leukemia and prolymphocytic leukemia

Campath-1H is effective therapy for patients with relapsed and refractory chronic lymphocytic leukemia (CLL) and prolymphocytic leukemia (PLL), but it is associated with profound lymphopenia and deficiencies in cell-mediated immunity. We report the incidence of cytomegalovirus (CMV) viremia in 34 patients treated with Campath-1H for relapsed or refractory CLL and PLL. All patients received infection prophylaxis during therapy and continuing for at least 2 months following Campath-1H. Five patients (15%) developed CMV viremia at a median of 28 days (range, 20-30 days) after the first dose of Campath-1H. The median CMV viral load was 860/mL (range, 420-2100/mL), as determined by quantitative plasma polymerase chain reaction (PCR). All 5 patients had a temperature > 38.5 degrees C, normal chest radiographs, normal liver function tests, and negative bacterial blood cultures with no clinical evidence of CMV disease at the time of presentation with CMV viremia. The median absolute neutrophil count (ANC) was 740/ microL (range, 340-1600/ microL), and the median absolute lymphocyte count (ALC) was 16/microL (range, 11-169/ microL) for the 5 patients at the time of CMV viremia. All 5 patients received ganciclovir therapy followed by prompt fever resolution and clearance of CMV viremia by plasma PCR. By univariate regression analysis, the following were not risk factors for CMV viremia: age, number of prior regimens, prior rituximab therapy, prior splenectomy, modified Rai stage at Campath-1H therapy (low/intermediate vs. high), ANC, and ALC; although, there was a trend towards significance for prior rituximab therapy (P = 0.07). Cytomegalovirus viremia may be a significant infectious complication during Campath-1H therapy and should be investigated further in future studies.     

Monitoring of Cytomegalovirus Reactivation in Bone Marrow Transplant Recipients by Real-time PCR

Cytomegalovirus (CMV) has been recognized as the most important viral pathogen in persons undergoing bone marrow transplantation (BMT). The aim was to develop a quantitative PCR assay to quantify CMV DNA in peripheral blood leukocytes (PBLs) of bone marrow transplantation (BMT) patients. An in-house real-time PCR assay based on TaqMan technology was developed to monitor the quantity of CMV DNA in PBLs of the BMT recipients. Sequential blood samples (415 specimens) were collected from 43 patients as weekly intervals until day 100 after transplantation. The CMV DNA was quantified in parallel with the pp65 antigenemia assay in PBL samples. Viral reactivation occurred in 51% and 41.8% of the recipients as detected by RQ-PCR and antigenemia assays respectively. There was a significant correlation between both assays (P < 0.0001); however, the RQ-PCR was more sensitive than the antigenemia. CMV DNA was detected by the RQ-PCR by a median of 14 days earlier than the antigenemia. Preemptive therapy was implemented in the antigenemia positive cases. The administration of ganciclovir led to a rapid decrease in the viral load. After preemptive therapy, the antigenemia achieved a negative result earlier than the RQ-PCR assay (a median of 17.5 days). An increase of viral load in both quantitative assays and of cyclosporine serum level were identified as the most significant risk factors for CMV reactivation. The quantitative CMV PCR might be a useful tool for monitoring the CMV reactivation and guiding the efficacy of the CMV preemptive therapy in BMT recipients.     

Effective treatment of a peripheral T-cell lymphoma/lymphoepitheloid cell variant (Lennert's lymphoma) refractory to chemotherapy with the CD-52 antibody alemtuzumab

Lymphoepitheloid cell lymphoma (Lennert's lymphoma) is a rare malignant disease usually affecting patients at advanced age. Although classified as a “low-grade” lymphoma in the past, the clinical course is highly unfavorable and currently available chemotherapeutic regimens have given disappointing results. We present the case of a 74-year-old male suffering from disseminated Lennert's lymphoma. The patient underwent standard treatment approaches including chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP); fludarabin and cyclophosphamide; and ifosfamide, carboplatin and etoposide (ICE). Due to progressive disease with all these regimens, chemotherapy was discontinued. As cells stained highly positive for CD52, immunotherapy with alemtuzumab (Campath-1H) was started using a standard dosing regime of 30 mg every third day. Although the patient received prophylactic anti-infective medication, leucocytopenia with reactivation of cytomegalovirus (CMV) infection was observed and the administration of alemtuzumab had to be stopped temporarily. Re-assessment of disease 5 weeks after the start of alemtuzumab disclosed a significant reduction of all thoracic and abdominal lesions, and therapy with alemtuzumab was continued after normalization of the number of CMV copies and is currently ongoing. Our observations indicate clinical activity of alemtuzumab in the treatment of Lennert's lymphoma, including even bulky nodal disease, particularly for patients who have failed conventional therapies.