Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission: a prospective sibling donor versus no-donor comparison.

While commonly accepted in poor-risk acute lymphoblastic leukemia (ALL), the role of allogeneic hematopoietic stem cell transplantation (allo-SCT) is still disputed in adult patients with standard-risk ALL. We evaluated outcome of patients with ALL in first complete remission (CR1), according to a sibling donor versus no-donor comparison. Eligible patients (433) were entered in 2 consecutive, prospective studies, of whom 288 (67%) were younger than 55 years, in CR1, and eligible to receive consolidation by either an autologous SCT or an allo-SCT. Allo-SCT was performed in 91 of 96 patients with a compatible sibling donor. Cumulative incidences of relapse at 5 years were, respectively, 24 and 55% for patients with a donor versus those without a donor (hazard ratio [HR], 0.37; 0.23-0.60; P < .001). Nonrelapse mortality estimated 16% (+/- 4) at 5 years after allo-SCT. As a result, disease-free survival (DFS) at 5 years was significantly better in the donor group: 60 versus 42% in the no-donor group (HR: 0.60; 0.41-0.89; P = .01). After risk-group analysis, improved outcome was more pronounced in standard-risk patients with a donor, who experienced an overall survival of 69% at 5 years (P = .05). In conclusion, standard-risk ALL patients with a sibling donor may show favorable survival following SCT, due to both a strong reduction of relapse and a modest nonrelapse mortality. This trial is registered with http://www.trialregister.nl under trial ID NTR228.

High acquisition and environmental contamination rates of CC17 ampicillin-resistant Enterococcus faecium in a Dutch hospital.

BACKGROUND: Enterococcus faecium has rapidly emerged as a nosocomial pathogen worldwide, and the majority of these isolates belong to clonal complex-17 (CC17). In Europe, CC17 isolates are usually ampicillin-resistant, but most are still vancomycin-sensitive. We aimed to study ampicillin-resistant E. faecium (ARE) epidemiology in our hospital. METHODS: In a 3 month study, 210 of 358 admissions (59%) to haematology and gastroenterology/nephrology were screened for rectal ARE colonization on admission (<48 h) and 148 of 210 (70%) also at discharge (<72 h). In a second (3 month) study, environmental swabs from eight predetermined sites were obtained from ARE-colonized haematology patients once weekly. All ARE isolates were genotyped by multiple-locus variable-number tandem repeat analysis (MLVA). RESULTS: ARE admission prevalence was 10% and 16% and acquisition rates were 39% and 15% in haematology and gastroenterology/nephrology, respectively. Carriage on admission was associated with previous admission <1 year (OR 5.0, 95% CI 1.8-14.0) and acquisition with beta-lactam (OR 2.7, 95% CI 1.1-6.7) and quinolone use (OR 3.1, 95% CI 1.1-8.2). Five of the 57 (9%) colonized patients developed invasive ARE infections. Genotyping revealed 12 genotypes (all CC17) with two MLVA types responsible for 94% of acquisitions. In 18 of the 19 colonized patients, the environment was contaminated with ARE. Sites most often contaminated were the toilet seat (43%), over-bed table (34%) and television remote control (28%). CONCLUSIONS: CC17 ARE epidemiology is characterized by high admission (10% to 16%), acquisition (15% to 39%) and environmental contamination (22%) rates, resulting from cross-transmission, readmission and antibiotic pressure. A multifaceted infection control approach will be needed to curtail further spread.

Frequent detection of respiratory viruses in adult recipients of stem cell transplants with the use of real-time polymerase chain reaction, compared with viral culture.

BACKGROUND: Respiratory virus infections have been recognized as important causes of severe pneumonia in patients who have undergone stem cell transplantation (SCT). Reported incidences of respiratory virus infection in adult SCT recipients vary in the literature from 3.5% to 36% when determined by viral culture. However, a more sensitive method to assess the presence of respiratory viruses in the lower airways may be important for delineation of the true incidence of respiratory virus-associated pneumonia and may be essential for guidance on implementation of antiviral therapy and prevention or limitation of nosocomial spread of infection with respiratory viruses. METHODS: To determine the incidence and severity of respiratory tract illness (RTI) and to assess the diagnostic value of real-time reverse-transcriptase polymerase chain reaction (RT-PCR) versus viral culture, 72 SCT recipients were monitored during a 6-month period. RESULTS: A respiratory virus was detected in 21% of episodes of RTI by viral culture and in 63% of RTI episodes by real-time RT-PCR (P<.0001). In lower respiratory tract illness, real-time RT-PCR was much more sensitive than viral culture for detection of respiratory virus (73% vs. 9%; P=.008). The mortality rate for patients with respiratory virus-associated lower respiratory tract illness (25%) was similar to rates reported elsewhere. Respiratory viruses (predominantly rhinovirus) were detected by real-time RT-PCR in 9% of samples obtained from symptom-free SCT recipients at predetermined times by real-time RT-PCR and by viral culture in 1% (P<.0001), indicating that asymptomatic shedding of respiratory viruses also occurs. CONCLUSION: We conclude that, although asymptomatic shedding of respiratory virus occurs, respiratory viruses are frequent causes of RTI in SCT recipients.

Autologous bone marrow transplantation as consolidation therapy in the treatment of adult patients under 60 years with acute myeloid leukaemia in first complete remission: a prospective randomized Dutch-Belgian Haemato-Oncology Co-operative Group (HOVON) and Swiss Group for Clinical Cancer Research (SAKK) trial.

The question as to whether autologous stem cell transplantation (SCT) after consolidation chemotherapy improves the probability of survival of patients with acute myeloid leukaemia (AML) in first remission has not been settled. Here, we present the results of a phase III study conducted in newly diagnosed adult AML patients aged <60 years. Patients who had reached a complete remission (CR) after two courses of induction chemotherapy and who were not eligible for a human leucocyte antigen-matched sibling SCT (n = 130), were randomized after a third consolidation cycle of chemotherapy between high-dose cytotoxic treatment and autologous bone marrow transplantation or no further treatment. No significant differences in disease-free survival and overall survival were observed between the two treatment arms. A slightly better overall survival in the no further treatment arm was because of fewer deaths in the first CR and a significantly better overall survival after the first relapse. The results are discussed in relation to the generic problems of applying autologous transplantation and in the perspective of the limited statistical power of this and other previously published studies.

Effect of antithymocyte globulin on quantitative immune recovery and graft-versus-host disease after partially T-cell-depleted bone marrow transplantation: a comparison between recipients of matched related and matched unrelated donor grafts.

The effect of antithymocyte globulin (ATG) on quantitative immune recovery and graft-versus-host disease (GVHD) after partially T-cell-depleted bone marrow transplantation was analyzed in 59 and 32 recipients of grafts from matched related donors and matched unrelated donors (MUDs), respectively. The conditioning regimen was similar in all patients, except for ATG which was given only to MUD recipients. Thirteen MUD patients were treated with high-dose (20 mg/kg) ATG and 19 with low-dose (8 mg/kg) ATG. During the posttransplant period, CD3+, CD4+, and CD8+ T-cell numbers and the incidence of acute and chronic GVHD were significantly lower in MUD recipients compared with matched related donor recipients. MUD recipients treated with high-dose ATG showed the worst T-cell and subsets recovery. These data indicate that ATG, often used as part of conditioning regimens in recipients of T-cell-depleted grafts from MUDs, contributes to the severe and prolonged T-cell deficiency that is typical of these patients. On the other hand, it effectively reduces the incidence and severity of GVHD.

Influence of antithymocyte globulin dose on outcome in cytomegalovirus-seropositive recipients of partially T cell-depleted stem cell grafts from matched-unrelated donors.

The adverse impact of positive-recipient Cytomegalovirus (CMV) serostatus on the outcome of matched-unrelated donor (MUD) grafts has been stressed. We evaluated whether CMV-seropositive MUD recipients transplanted after 1999 still showed inferior outcome compared with CMV-seronegative recipients. Two important changes in transplantation procedure were introduced in 1999: (1) reduction of antithymocyte globulin dose, (2) introduction of sequence-based typing of HLA-DRB1. Thirty-six patients received partial T cell-depleted grafts before 1999, and 44 after 1999. CMV-seropositive patients transplanted before 1999 showed a highly significant inferior outcome compared with seronegative recipients. In contrast, no difference in outcome was observed between the two groups of patients transplanted after 1999.

Influence of cytomegalovirus seropositivity on outcome after T cell-depleted bone marrow transplantation: contrasting results between recipients of grafts from related and unrelated donors.

We analyzed the effect of cytomegalovirus (CMV) serostatus on overall survival (OS) and transplant-related mortality (TRM) in 253 consecutively treated patients receiving partially T cell-depleted (TCD) bone marrow from either matched related donors (MRDs; n=205) or matched unrelated donors (MUDs; n=48). Short-course, low-dose preemptive therapy with ganciclovir was provided as soon as a positive antigenemia assay result was obtained. Ganciclovir prophylaxis, which was identical to preemptive therapy, was given to patients with acute graft-versus-host disease (GVHD) grades II-IV who had to be treated with high-dose steroids. In recipients of transplants from MRDs, inferior OS and increased TRM were predicted by extensive chronic GVHD (P<.001). High-risk disease status and older age adversely influenced OS (P=.001) and TRM (P=.002), respectively; older age resulted in a trend toward decreased OS (P=.066). In recipients of transplants from MUDs, OS and TRM were strongly influenced by patient CMV seropositivity (P=.013 and.007, respectively). In conclusion, CMV seropositivity is not an adverse risk factor for OS and TRM in recipients of transplants from MRDs. However, in recipients of transplants from MUDs, patient CMV seropositivity strongly affects OS and TRM.

Factor V Leiden in central venous catheter-associated thrombosis.

Subclavian vein thrombosis is a well-recognized complication following central venous catheter insertion and is associated with significant morbidity. The factor V Leiden mutation is an important risk factor for deep venous thrombosis and pulmonary embolism. Whether this mutation also predisposes patients fitted with a central venous catheter to subclavian vein thrombosis is not known. The occurrence of central venous catheter-associated thrombosis was investigated in 277 consecutive patients receiving an allogeneic bone marrow transplantation. All patients received a tunnelled double or triple catheter positioned in the subclavian vein. Catheter-associated thrombosis was diagnosed on the basis of clinical signs of thrombosis, i.e. swelling and/or redness of the limb or venous engorgement and was confirmed with a colour-flow Doppler ultrasound. Thirteen patients were heterozygous for the factor V Leiden mutation. Seven of these patients had a subclavian vein thrombosis (54%), while this occurred in only 9% of the factor V Leiden-negative patients, corresponding with a relative risk of 7.7 (95% CI 3.3-17.9). Factor V Leiden is attributable for 17.3% of all thrombosis in patients with central venous catheters. The majority of patients with the factor V Leiden mutation with a central venous catheter will develop thrombosis. Patients with a factor V Leiden mutation should receive adequate thrombosis prophylaxis upon catheter introduction and the catheter should be removed immediately after the treatment. Based on this very high risk, we advise testing for factor V Leiden in all bone marrow transplantation patients receiving a central venous catheter.

Early and late invasive pneumococcal infection following stem cell transplantation: a European Bone Marrow Transplantation survey.

Streptococcus pneumoniae (S. pneumoniae) may cause severe and lethal infections months and years following stem cell transplantation (SCT). In a prospective survey over a 3.5-year period, we assessed the incidence, risk factors and outcome for invasive pneumococcal infection (IPI) following SCT. Fifty-one episodes of IPI were reported: 43 episodes after bone marrow transplantation (BMT) and 8 after peripheral blood stem cell transplantation (PBSCT); 35 after allogeneic SCT and 16 after autologous SCT. Seven IPI episodes, all bacteraemias, were defined as early, occurring 1-35 d (median 3 d) post transplantation. Forty-four episodes were defined as late (> or = 100 d post SCT), occurring 4 months to 10 years (median 17 months) post transplantation. The incidences of early and late IPI were 2.03/1000 and 8.63/1000 transplantations respectively (P = 0.001). A higher incidence of late IPI was observed after BMT than after PBSCT (10.99 versus 3.23/1000; P < 0.01) and after allogeneic versus autologous SCT (12.20 versus 4.60/1000; P < 0.01). There was a higher estimated incidence of IPI in allogeneic patients with than in those without graft-versus-host disease (GVHD) (18.85 versus 8.25/1000; P = 0.015). The mortality rate was 20%, including 2/7 of early and 8/44 of late IPI. S. pneumoniae is a rare but important complication during the aplastic phase after SCT. In conclusion, S. pneumoniae is a significant cause of morbidity late post-transplantation, especially in allogeneic patients, and particularly those with GVHD. The high IPI mortality rate, both early and late post-transplantation, requires preventive approaches, mainly effective immunization.