Activity and safety of crizotinib in patients with alveolar soft part sarcoma with rearrangement of TFE3: European Organization for Research and Treatment of Cancer (EORTC) phase II trial 90101 'CREATE'.

Background: Alveolar soft part sarcoma (ASPS) is an orphan malignancy associated with a rearrangement of transcription factor E3 (TFE3), leading to abnormal MET gene expression. We prospectively assessed the efficacy and safety of the MET tyrosine kinase inhibitor crizotinib in patients with advanced or metastatic ASPS. Patients and methods: Eligible patients with reference pathology-confirmed ASPS received oral crizotinib 250 mg bd. By assessing the presence or absence of a TFE3 rearrangement, patients were attributed to MET+ and MET- sub-cohorts. The primary end point was the objective response rate (ORR) according to local investigator. Secondary end points included duration of response, disease control rate (DCR), progression-free survival (PFS), progression-free rate, overall survival (OS) and safety. Results: Among 53 consenting patients, all had a centrally confirmed ASPS and 48 were treated. A total of 45 were eligible, treated and assessable. Among 40 MET+ patients, 1 achieved a confirmed partial response (PR) that lasted 215 days and 35 had stable disease (SD) as best response (ORR: 2.5%, 95% CI 0.6% to 80.6%). Further efficacy end points in MET+ cases were DCR: 90.0% (95% CI 76.3% to 97.2%), 1-year PFS rate: 37.5% (95% CI 22.9% to 52.1%) and 1-year OS rate: 97.4% (95% CI 82.8% to 99.6%). Among 4 MET- patients, 1 achieved a PR that lasted 801 days and 3 had SD (ORR: 25.0%, 95% CI 0.6% to 80.6%) for a DCR of 100% (95% CI 39.8% to 100.0%). The 1-year PFS rate in MET- cases was 50% (95% CI 5.8% to 84.5%) and the 1-year OS rate was 75% (95% CI 12.8% to 96.1%). One patient with unknown MET status due to technical failure achieved SD but stopped treatment due to progression after 17 cycles. The most common crizotinib-related adverse events were nausea [34/48 (70.8%)], vomiting [22/48 (45.8%)], blurred vision [22/48 (45.8%)], diarrhoea (20/48 (41.7%)] and fatigue [19/48 (39.6%)]. Conclusion: According to European Organization for Research and Treatment of Cancer (EORTC) efficacy criteria for soft tissue sarcoma, our study demonstrated that crizotinib has activity in TFE3 rearranged ASPS MET+ patients. Clinical trial number: EORTC 90101, NCT01524926.

Association of aromatase inhibitors with coronary heart disease in women with early breast cancer.

As compared to tamoxifen aromatase inhibitors (AIs) may increase the risk of heart disease. Here we explored the association between the use of AIs and coronary artery disease (CAD) in a population-based observational study. In a small and heterogeneous population of 74 women with early breast cancer who received adjuvant hormonal therapy and subsequently underwent cardiac angiography, AIs significantly increased the hazard for CAD (HR 3.23, 95% confidence intervals [CI] 1.26-8.25, p = .01) compared to tamoxifen. Our results suggest that therapy with AIs may increase the risk for CAD.

Risk factors for late relapse and death in patients with early breast cancer.

Adjuvant treatments reduce the risk for recurrence and death from breast cancer; but even 10-15 years after diagnosis, these risks persist. The aim of our study was to identify prognostic factors for relapse and death in the second decade after primary surgery. Patients with early breast cancer treated from 1983-1987 (n=1035) were included. Patients' characteristics, tumor prognostic factors, treatments, data on recurrence and death were obtained from patients' charts and our cancer registry. Median follow-up was 17 (1-23) years. At 10 years after surgery, 515 (49.8%) patients were alive and of them 432 (41.7%) were relapse-free. Of the 432 patients being alive and relapse-free at 10 years 153 (35.4%) had an event thereafter, of them 38 (25%, 9% of all) had a relapse of breast cancer. For this period only the presence of lymphovascular invasion (LVI) and positive estrogen receptors (ER) were found as independent unfavorable prognostic factors for relapse-free (HR 2.09, p=0.007; HR 1.50, p=0.021, respectively) and overall survival (HR 2.15, p=0.006; HR 1.41, p=0.05, respectively) while tumor size, grade and nodal status had no prognostic significance. Positive ER and LVI are independent prognostic factors for relapse and death in the second decade after surgery in patients with early breast cancer.

Inoperable oropharyngeal carcinoma treated with concomitant irradiation, mitomycin C and bleomycin - long term results.

Patients with inoperable head and neck tumors were treated concomitantly with radiochemotherapy with mitomycin C and bleomycin in our prospective randomized clinical trial (1991- 1993). For the subgroup of patients with oropharyngeal carcinoma the results with radiochemotherapy were significantly superior to irradiation alone. Such scheme of treatment was then adopted as standard method. Here we present the long-term results and dose- response relationships in patients with inoperable oropharyngeal carcinoma treated by the same radiochemotherapy scheme till 1997. Ninety-five patients with stage III and IV inoperable oropharyngeal squamous cell carcinoma were treated with curative intent, concomitantly with supra-voltage irradiation 2 Gy/day 5 times weekly to 60-73 Gy, bleomycin 5 mg 2 times weekly and. one application of mitomycin C 15 mg/m(2) after 10 Gy. Logistic dose- response curve was calculated. Median follow-up was 85 months. The loco-regional control, disease- free survival and overall survival at 5 years were 55%, 51% and 32% (95% CI: 44-67%, 41-62%, 22-42%), respectively. The probability of new primary malignancy at 5 years was 23%. In multivariate analysis performance status, biological equivalent dose, dose of bleomycin, and stage were identified as independent prognostic factors for loco-regional control, disease-free, and overall survival. Th gamma-value of dose response curve was 2.86. The outcome of the disease was directly proportional to intensity of irradiation and chemotherapy. It appears that in our concomitant radiochemotherapy MiC increased radioresponsiveness of the tumor by its effect on hypoxic fraction.

Survival and fertility of patients with malignant ovarian germ cell tumours.

Disease-free survival (DFS), overall survival (OS) and fertility of patients treated for malignant ovarian germ cell tumours at the Institute of Oncology Ljubljana from 1990-2000 were assessed. Twenty-three patients with a median age of 25 (15-67) years were treated. Five had pure dysgerminoma, three endodermal sinus tumour, ten immature teratoma and five had mixed germ cell tumours. Eleven patients had FIGO Stage I and the others advanced stage disease. All patients underwent initial surgery; in 13 of 15 patients under 35 years unilateral salpingo-oophorectomy was performed. Twenty-one patients received adjuvant cisplatin-based chemotherapy. At the median follow-up of 68 (11-140) months DFS was 74% and OS 87%. Six patients (two did not receive adjuvant chemotherapy) relapsed at a median of 16 (3-63) months after surgery. At relapse four were treated with surgery and chemotherapy, one with chemotherapy only and one with palliative radiotherapy only: two are still in complete remission, one has residual disease and three died of disease. Ten of 13 patients with fertility-preserving surgery regained menstrual cycles and one gave birth to a normal child. DFS and OS in our group of patients (over 15 years of age) are comparable to other institution's experience. Fertility in young patients can be preserved without compromising outcome.

Hemoglobin as a factor influencing the outcome in inoperable oropharyngeal carcinoma treated by concomitant radiochemotherapy.

The aim of the study was to analyze the prognostic significance of hemoglobin (Hb) concentration for loco-regional control and survival of patients with inoperable carcinoma of the oropharynx. Seventy patients with inoperable squamous cell carcinoma of the oropharynx were prospectively treated by concomitant regimen of conventional radiotherapy and chemotherapy with Mitomycin C and Bleomycin. The prognostic value of Hb concentration before the therapy (Hb-S) and at the end of the therapy (Hb-E), the difference between both (DHb), and the average Hb concentration (Hb-Av) were analyzed. Hb concentration was falling significantly (median values, from 139 g/L to p<0.0001) during the first three weeks of the therapy; after that, it reached a plateau. In the last week of therapy, a slight increase (p=0.08) in Hb concentration was recorded. Significant correlation (p<0.0001) was found between Hb-S and other Hb-related parameters. The median follow-up of the patients alive on close-out date was 5.7 years (range 4-10.5 years). Longer disease-free survival (DFS) and disease-specific survival (DSS) correlated with higher values of Hb-S (p=0.0005, p=0.008) and Hb-E (p=0.02, p=0.02), while the Hb-Av was predictive for DFS only (p=0.004). The most significant difference between low- and high-Hb groups was calculated at cut-off concentrations of 122 (Hb-S), 116 (Hb-E), and 120 (Hb-Av) g/L. Only Hb-S was tested in multi- variate model where its independent value for predicting both, DFS (p=0.002; RR 3.6) and DSS (p=0.01; RR 2.9), was confirmed. In our patients, Hb-Swas proved to bean independent prognostic factor in predicting DFS and DSS. We believe that the concentration of Hb > or =120 g/L should be maintained during radiotherapy course.

Selection of candidates for oral etoposide salvage chemotherapy in heavily pretreated breast cancer patients.

Metastatic breast cancer (MBC) is still in most cases an uncurable disease and the main goal of treatment is a good quality of life for these patients. Therefore it is very important to select patients who are appropriate candidates for the particular salvage chemotherapy (CT) schedule. The aim of our study was to assess treatment response to oral etoposide, and to analyze its relationship with patients' and disease characteristics. Seventy-five patients with bidimensionally measurable MBC were included into our study. For most of the patients treatment with etoposide was third-line CT regimen and most of them (90%) had been exposed to previous anthracycline-based CT. Etoposide was administered orally at a dose of 100 mg/day for 10 days every 3 weeks. The overall response rate was 37% (95% CI: 27-50%) with a median time to progression (TTP) and survival of 4.5 and 12 months, respectively. Patients with a long disease-free interval, predominant soft tissue and bone metastases, and less than three metastatic sites responded better to oral etoposide; however, a significantly better response was achieved only in those who had responded to previous CT (46 versus 19%, p=0.04), especially to anthracyclines (50 versus 17%, p=0.016). Response to previous anthracycline-based regimen was the only characteristic that significantly influenced TTP (median TTP: 7 versus 2.5 months, p=0.0066) and survival (median survival: 13.8 versus 5 months, p=0.0072). Toxic side effects were generally mild. Salvage CT with oral etoposide is an appropriate treatment for patients who respond to previous CT, particularly to anthracyclines. It combines a favorable toxicity profile with the major advantage of an oral drug administered at home.

Detection of hepatitis C virus RNA from gingival crevicular fluid and its relation to virus presence in saliva.

BACKGROUND: To search for a possible source of hepatitis C virus (HCV) in saliva, the presence and shedding patterns of HCV in gingival crevicular fluid (GCF) and saliva of HCV viremic patients were assessed based on clinical, biochemical, histological, virological, and oral health parameters. METHODS: Saliva and GCF samples of 50 HCV viremic patients were collected to detect HCV RNA by a modified commercial polymerase chain reaction (PCR) assay. Clinical oral examination was performed and periodontal status at the collection sites was monitored. The results were correlated to specified parameters. RESULTS: HCV RNA was detected in 59% (29/49) of the GCF specimens and in 35% (17/48) of the saliva specimens. In saliva specimens, HCV RNA was detected only in cases which also had detectable HCV RNA in the GCF samples (P=0.00002) and was significantly related to the presence of blood in saliva (P=0.03). Higher, but not significant, values of oral clinical parameters at the sites of fluid collection were found in GCF specimens harboring HCV RNA. In GCF specimens with no blood detected, HCV RNA was more often present in cases with higher plasma viral load (P=0.05). CONCLUSIONS: The results suggest that besides blood, the other most probable source of HCV in saliva is GCF. Unknown endogenous HCV inhibitory mechanisms in the oral cavity may explain the discrepancies in HCV appearance between saliva and GCF. The results provide a biologic basis for further investigation of the role of HCV in the pathogenesis of periodontal disease.

Neurological symptoms in patients whose cerebrospinal fluid is culture- and/or polymerase chain reaction-positive for Mycoplasma pneumoniae.

We describe 13 patients with neurological signs and symptoms associated with Mycoplasma pneumoniae infection. M. pneumoniae was isolated from the cerebrospinal fluid (CSF) of 9 patients: 5 with meningoencephalitis, 2 with meningitis, and 1 with cerebrovascular infarction. One patient had headache and difficulties with concentration and thinking for 1 month after the acute infection. M. pneumoniae was detected, by means of PCR, in the CSF of 4 patients with negative culture results. Two had epileptic seizures, 1 had blurred vision as a consequence of edema of the optic disk, and 1 had peripheral nerve neuropathy.

Proviral HIV-1 DNA in gingival crevicular fluid of HIV-1-infected patients in various stages of HIV disease.

The oral cavity is rarely reported to be a site of human immunodeficiency virus (HIV) transmission, despite detectable virus in saliva and relatively frequent prevalence of periodontal disease in HIV-infected persons yielding increased excretion of mononuclear-cell-enriched gingival fluid. To search for possible sources of HIV in saliva, and using the polymerase chain-reaction technique, we sought the presence and shedding patterns of proviral HIV-1 DNA in gingival crevicular fluid in a group of patients previously determined as HIV-1-seropositive. Periodontal status at the collection sites was monitored by several clinical parameters, including Plaque Index, Gingival Index, probing depth, and clinical attachment loss. Gingival crevicular fluid samples were collected by means of paper points. Proviral HIV-1 DNA was detected in the gingival fluid of 17 out of 35 HIV-1-infected patients. Its detection correlated significantly with higher plasma HIV-1 RNA viral load (p = 0.03) and not with peripheral blood CD4+ cell count, the presence of blood in gingival fluid, or oral lesions. There was a significant correlation between clinical attachment loss at the sites of fluid collection and plasma HIV-1 RNA viral load (p = 0.002), and borderline correlation between the latter and probing depth (p = 0.54) in the group of patients harboring proviral HIV-1 DNA in gingival crevicular fluid. The results of our study suggest that mononuclear cells present in gingival crevicular fluid and harboring proviral HIV-1 DNA could represent a potential source of HIV-1 in the presence or absence of local bleeding, especially in persons with advanced HIV infection and increased loss of clinical attachment.

Severe forms of tick-borne encephalitis in children.

Records of patients aged 0 to 15 years, hospitalised between 1993 and 1998 at the intensive care unit (ICU) of the Department of Infectious Diseases, Ljubljana, Slovenia, suffering from a severe attack of tick-borne encephalitis (TBE), were reviewed. Of 133 children hospitalised due to TBE virus infection during the observation period, 7 (5.2%) were treated in the ICU. All patients were male, aged 6 to 14 (mean, 11.1) years. In six cases, focal encephalitis was diagnosed, and in one case it was suspected. All patients survived. After a mean follow-up period of 7.9 (range, 1.5 to 17) months, one patient was found to have severe neurologic sequelae and two patients had moderate sequelae. In conclusion, the results of our retrospective study of severe forms of TBE in children demonstrate that this disease can run a severe course and may lead to permanent sequelae, most often in boys of school-going age who present with focal encephalitis. Therefore, immunisation of school children against TBE in endemic areas is strongly recommended.

Hyperbaric oxygenation, plasma exchange, and hemodialysis for treatment of acute liver failure in a 3-year-old child.

A girl aged 3 years and 4 months weighing 16 kg was treated with plasma exchange (PE), hemodialysis (HD), and hyperbaric oxygenation (HBO) for acute hepatic failure and coma. She was given a total of 13 PEs, 13 HD sessions, and 9 HBO treatments over a period of 1 month. The initial 4 PEs were followed by HD sessions while the other 8 PE treatments were given simultaneously with HD. There was no renal failure; HD was instituted to improve ammonia elimination. In 1 HD session, 20% human albumin (370 ml) was used as the dialysate to enhance bilirubin elimination. Three volumes of plasma (2,000 ml) per PE were exchanged and replaced with fresh frozen plasma (FFP). The Bellco BL 791 plasmapheresis monitor and Gambro PF1000 and PF2000 plasma filters were used. Heparin was added to prevent clotting. A dual lumen pediatric HD catheter (7 Fr) placed percutaneously into the femoral vein was used as a blood access. The Fresenius 2008 C HD monitor and the Filtral 10 dialyzer were used for HD. PE and HD were instituted simultaneously to prevent the tetanic (hypocalcemic) cramps observed with 2 previous PEs due to citrate in the FFP. The extracorporeal circuit was primed with a mixture of concentrated red cells, human albumin, and saline solution and was discarded at the end of the procedure. The average blood flow rate in PE and/or HD circuits was 80 ml/min. During HBO, the girl breathed 100% oxygen at 2.5 atm for 90 min. Throughout the treatment, the patient was in good clinical, physical, and mental condition, but she was dependent on blood purification procedures. She was referred to a liver transplant center and successfully transplanted. The etiology of liver failure has not been clarified.

Concomitant radiotherapy with mitomycin C and bleomycin compared with radiotherapy alone in inoperable head and neck cancer: final report.

PURPOSE: To compare the efficacy of concomitant irradiation with mitomycin C and bleomycin in patients with inoperable head and neck carcinoma with radiotherapy alone. METHODS AND MATERIALS: Between March 1991 and December 1993, 64 patients with inoperable head and neck carcinoma (41 with oropharyngeal site) were randomized to radiotherapy alone (group A) or radiotherapy combined with simultaneous application of mitomycin C and bleomycin (group B). In both groups patients were irradiated five times weekly with 2 Gy to a total dose of 66-70 Gy. The planned concomitant treatment in group B was: bleomycin 5 units twice a week i.m., total dose 70 units, mitomycin C 15 mg/m2 i.v. after delivery of 10 Gy, and 10 mg/m2 i.v. on the last day of radiotherapy. To enhance the effect of these two drugs, patients received also nicotinamide, chlorpromazine, and dicoumarol. Because significantly better results were achieved in arm B for patients with inoperable oropharyngeal carcinoma, the study was closed and such patients were after December 1993 routinely treated with the combined therapy (as in arm B). Until October 1996, we treated and followed up 48 such consecutive patients. RESULTS: Median follow-up of our study patients is 42 months. Complete remission (CR) rate in group A was 31% and in group B 59% (p = 0.04); disease-free survival (DFS) in group A was 8% and in group B 37% (P = 0.01); and overall survival (OS) was 7% in group A and 26% in group B (p = 0.08). CR rate for patients with oropharyngeal carcinoma was 29% in group A (N = 21) and 75% in group B (N = 20) (p = 0.007); DFS in group A was 10% and in group B 48% (p = 0.001); and the OS was 10% in group A and 38% in group B (p = 0.019). In patients with inoperable oropharyngeal carcinoma treated after December 1993, complete remission was achieved in 32/48 (67%, 95% CI: 52%-80%). DFS at the median follow-up of 14 months was 60% (95% CI 43-77%) and OS 58% (95% CI 42-74%). CONCLUSION: From the results of our study it seems that the concomitant treatment significantly improves CR rate, DFS, and OS in patients with inoperable oropharyngeal carcinoma in comparison with radiotherapy alone.

Invasive bladder cancer: our experience with bladder sparing approach.

PURPOSE: Muscle-invasive bladder cancer (MIBC) is a disease associated with several unresolved therapeutic questions. Radical cystectomy still represents the most frequent treatment approach. The aim of our study was to evaluate the effect and feasibility of bladder-sparing treatment by transurethral resection (TUR) and sequential chemoradiotherapy in patients with biopsy-proven invasive bladder cancer. METHODS AND MATERIALS: After maximal TUR, 105 patients were treated with two to four cycles of methotrexate, cisplatinum, and vinblastine polychemotherapy. In complete responders, the treatment was continued by radiotherapy (50 Gy to the bladder and 40 Gy to the regional lymph nodes), whereas in nonresponders, cystectomy was performed when feasible. RESULTS: Complete response after TUR and chemotherapy was achieved in 52% of patients. After a median follow-up of 42 months, 52 of 75 patients (69%) selected for bladder preservation were without evidence of disease in the bladder. Freedom from local failure in complete responders to chemotherapy was 80% [95% confidence interval (CI), 69-91%) at 4 years. The actuarial survival of the entire group was 58% (95% CI, 47-69%), whereas the survival rate with the bladder intact was 45% (95% CI, 34-56%) at 4 years. Survival was significantly better in patients who responded to chemotherapy (79%) than in nonresponders (35%, p < 0.0001). There was no significant difference in survival between nonresponders who underwent cystectomy and nonresponders who completed treatment with radiotherapy (approximately 30% at 3 years). CONCLUSION: The present study confirms that MIBC is a heterogeneous disease, and that in more than half of patients who are affected, a bladder-sparing approach is safe. Our study has also demonstrated that in nonresponders, radical cystectomy as the treatment of choice is questionable.

Immunological differentiation between tickborne encephalitis with and without concomitant neuroborreliosis.

Cerebrospinal fluid lymphocyte subsets in patients with tickborne encephalitis (TBE) and in patients with TBE with concomitant neuroborreliosis (double infection) were analysed by flow cytometry. In the TBE group, higher percentages of CD4+DR+ T cells (p = 0.02) and CD25+ T cells (p = 0.0002) were observed, while in the group with double infection, higher percentages of CD19+ cells (p = 0.007), CD8+DR- T cells (p = 0.04), and CD3+CD71 + T cells (p = 0.0002) were found. It was concluded that several differences in immune cell parameters are present between the two groups of patients. Three variables (CD19+ cells, CD3+CD25+ T cells, CD3+CD71+ T cells) were included in the logistic regression model for calculation of probability for double infection. Flow cytometric characterisation of lymphocyte subsets in CSF can further substantiate the diagnosis of concomitant neuroborreliosis in patients with TBE.

Early glottic cancer: the influence of primary treatment on voice preservation.

PURPOSE: Retrospective analysis was performed to assess the influence of primary surgical or irradiation treatment on local control, survival, and final preservation of larynx in comparable groups of patients with T1N0 and T2N0 glottic cancer. METHODS AND MATERIALS: Two hundred sixty-three previously untreated patients with invasive squamous cell carcinoma of the glottis (187T1 and 76T2) were treated with primary radiotherapy (159T1 and 60T2) or primary surgery (28T1 and 16T2) between January 1976 and December 1990, at the University of Ljubljana, Slovenia. Conventional one daily fraction of 2 Gy to doses of 60-74 Gy (median: 65 Gy) were used in 98% of primarily irradiated patients through out the observed period. To enable better comparison between the two treatment groups, primarily irradiated patients were retrospectively stratified by the criteria of suitability for primary voice-sparing operation. Several host, tumor, and treatment parameters were analyzed. RESULTS: Only the stage of the disease significantly influenced both 10-year recurrence-free and disease-specific survival regardless primary treatment modality (p = 0.0002). In all primary irradiated patients local control was significantly better for those with overall treatment time of less than 48 days (p = 0.007). In patients suitable for voice-sparing operation, local control of primarily operated patients was similar to that of patients primarily irradiated with shorter overall treatment time, which was 93 and 88% for T1 and 67 and 64% for T2 tumors, respectively. Ultimate local control in primary surgery and radiotherapy group was 96 and 96% for T1 and 89 and 88% for T2 tumors, respectively. Equal larynx preservation of 100% in T1 and 90% in T2 patients was achieved in finally cured primarily operated patients and those patients primarily irradiated with a shorter overall treatment time. If treatment time was longer than 48 days, significantly worse final larynx preservation of 84% in T1 and 75% in T2 patients was observed (p = 0.003). In patients unsuitable for voice sparing operation, 87% of T1 and 50% of T2 patients in primary radiotherapy group finally had their larynx preserved. CONCLUSION: Stratification based on criteria of possibility for initial voice-sparing operation is important when comparing primary surgery with primary radiotherapy treatment in early glottic cancer. The detrimental effect of prolonged treatment time of irradiation resulted not only in inferior local control rate but also in worse final larynx preservation.

First-line chemotherapy with cisplatin, methotrexate and vinblastine in metastatic bladder cancer.

To determine the effectiveness of combination chemotherapy with cisplatin, methotrexate and vinblastine (CMV), we treated 21 chemotherapy naive patients with metastatic transitional cell carcinoma of the bladder. Chemotherapy consisted of methotrexate (30 mg/m2 i.v. days 1 and 8), vinblastine (3 mg/m2 i.v. days 1 and 8) and cisplatin (100 mg/m2 i.v. day 2) every three weeks. Dominant metastatic sites were: soft tissues (7 patients), bone (6 patients), lung and liver (8 patients). A complete remission was achieved in 5/21 patients (24%, 95% CI 8-47%) and partial remission in 9/21 patients (43%, 95% CI 22-66%). The median duration was 6 months (2-11) and 9 months (2-26) for complete and partial remissions, respectively. The median survival for all 21 patients was 10 months. Although overall toxicity was mild, we observed myelosuppression grade IV in 2 patients, stomatitis grade III in 2 patients, cystitis grade III in 1 patient and infection grade III in 6 patients. There were no treatment-related deaths. Our data indicate that treatment with the CMV regimen is effective and that side effects are tolerable.