Long-term prognosis for 1-year relapse-free survivors of CD34+ cell-selected allogeneic hematopoietic stem cell transplantation: a landmark analysis.

CD34+ cell selection significantly improves GvHD-free survival in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, specific information regarding long-term prognosis and risk factors for late mortality after CD34+ cell-selected allo-HSCT is lacking. We conducted a single-center landmark analysis in 276 patients alive without relapse 1 year after CD34+ cell-selected allo-HSCT for AML (n=164), ALL (n=33) or myelodysplastic syndrome (n=79). At 5 years' follow-up after the 1-year landmark (range 0.03-13 years), estimated relapse-free survival (RFS) was 73% and overall survival (OS) 76%. The 5-year cumulative incidence of relapse and non-relapse mortality (NRM) were 11% and 16%, respectively. In multivariate analysis, Hematopoietic Cell Transplantation Comorbidity Index score⩾3 correlated with marginally worse RFS (hazard ratio (HR) 1.78, 95% confidence interval (CI) 0.97-3.28, P=0.06) and significantly worse OS (HR 2.53, 95% CI 1.26-5.08, P=0.004). Despite only 24% of patients with acute GvHD within 1 year, this also significantly correlated with worse RFS and OS, with increasing grades of acute GvHD associating with increasingly poorer survival on multivariate analysis (P<0.0001). Of 63 deaths after the landmark, GvHD accounted for 27% of deaths and was the most common cause of late mortality, followed by relapse and infection. Although prognosis is excellent for patients alive without relapse 1 year after CD34+ cell-selected allo-HSCT, risks of late relapse and NRM persist, particularly due to GvHD.

Long term renal survival in patients undergoing T-Cell depleted versus conventional hematopoietic stem cell transplants.

Calcineurin inhibitor (CNI)-sparing T-cell depleted (TCD) hematopoietic stem cell transplants (HSCTs) are presumed to be less nephrotoxic than conventional HSCTs. We evaluated incidence and risk factors for kidney failure and chronic kidney disease (CKD) in 231 TCD and 212 conventional HSCT recipients. Kidney failure required a median glomerular filtration rate (GFR) <60 ml/min/1.73 m2 for ⩾100 days anytime after 180-days post-HSCT. Two-year cumulative incidence (CI) of kidney failure was 42% in the conventional versus 31% in the TCD group (P=0.005). TCD, age, acute kidney injury and number of toxic CNI levels all impacted on kidney failure, which was associated with increased all-cause mortality (hazard ratio 2.86 (95% CI: 1.88-4.36), P<0.001). Renal recovery occurred in 28% of kidney failure patients whereas the remaining patients were defined to have CKD. In those with baseline GFR>60 ml/min/1.73 m2, only exposure to nephrotoxic medications was associated with CKD (P=0.033). In the myeloablative-conditioning subgroup only total body irradiation was associated with CKD (P=0.013). Of all patients, five (1.13%) required dialysis. These results confirm an impact of TCD on kidney failure but not CKD for which other risk factors such as radiation or nephrotoxic drug exposure may have a role.

Prospective assessment of white matter integrity in adult stem cell transplant recipients.

Hematopoietic stem cell transplantation (HSCT) is often used in the treatment of hematologic disorders. Although it can be curative, the pre-transplant conditioning regimen can be associated with neurotoxicity. In this prospective study, we examined white matter (WM) integrity with diffusion tensor imaging (DTI) and neuropsychological functioning before and one year after HSCT in twenty-two patients with hematologic disorders and ten healthy controls evaluated at similar intervals. Eighteen patients received conditioning treatment with high-dose (HD) chemotherapy, and four had full dose total body irradiation (fTBI) and HD chemotherapy prior to undergoing an allogeneic or autologous HSCT. The results showed a significant decrease in mean diffusivity (MD) and axial diffusivity (AD) in diffuse WM regions one year after HSCT (p-corrected <0.05) in the patient group compared to healthy controls. At baseline, patients treated with allogeneic HSCT had higher MD and AD in the left hemisphere WM than autologous HSCT patients (p-corrected <0.05). One year post-transplant, patients treated with allogeneic HSCT had lower fractional anisotropy (FA) and higher radial diffusivity (RD) in the right hemisphere and left frontal WM compared to patients treated with autologous HSCT (p-corrected <0.05).There were modest but significant correlations between MD values and cognitive test scores, and these were greatest for timed tests and in projection tracts. Patients showed a trend toward a decline in working memory, and had lower cognitive test scores than healthy controls at the one-year assessment. The findings suggest a relatively diffuse pattern of alterations in WM integrity in adult survivors of HSCT.

Arrhythmias in the setting of hematopoietic cell transplants.

Prior studies report that 9-27% of persons receiving a hematopoietic cell transplant develop arrhythmias, but the effect on outcomes is largely unknown. We reviewed data from 1177 consecutive patients ⩾40 years old receiving a hematopoietic cell transplant at one center during 1999-2009. Transplant indication was predominately leukemia, lymphoma and multiple myeloma. Overall, 104 patients were found to have clinically significant arrhythmia: 43 before and 61 after transplant. Post-transplant arrhythmias were most frequently atrial fibrillation (N=30), atrial flutter (N=7) and supraventricular tachycardia (N=11). Subjects with an arrhythmia post transplant were more likely to have longer median hospital stays (32 days vs 23, P=<0.001), a greater probability of an intensive care unit admission (52% vs 7%; P<0.001), greater probability of in-hospital deaths (28% vs 3%, P<0.001), and greater probability of death within 1 year of transplant (41% vs 15%; P<0.001) compared with patients without arrhythmia at any time. In a multivariate model including age at transplant, diagnosis, history of pretransplant arrhythmia, and transplant-related variables, post-transplant arrhythmia was associated with a greater risk for death within a year of transplant (odds ratio 3.5, 95% confidence interval: 2.1, 5.9; P<0.001). Our data suggest that arrhythmias after transplants are associated with significant morbidity and mortality. A prospective study of arrhythmia in the transplant setting is warranted.

Comparison of outcomes at two institutions of patients with ALL receiving ex vivo T-cell-depleted or unmodified allografts.

We compared outcomes of adult patients receiving T-cell-depleted (TCD) hematopoietic SCT (HCT) without additional GVHD prophylaxis at Memorial Sloan Kettering Cancer Center (MSKCC, N=52), with those of patients receiving conventional grafts at MD Anderson Cancer Center (MDACC, N=115) for ALL in CR1 or CR2. Patients received myeloablative conditioning. Thirty-nine patients received anti-thymocyte globulin at MSKCC and 29 at MDACC. Cumulative incidence of grades 2-4 acute (P=0.001, 17.3% vs 42.6% at 100 days) and chronic GVHD (P=0.006, 13.5% vs 33.4% at 3 years) were significantly lower in the TCD group. The non-relapse mortality at day 100, 1 and 3 years was 15.4, 25.0 and 35.9% in the TCD group and 9.6, 23.6 and 28.6% in the unmodified group (P=0.368). There was no difference in relapse (P=0.107, 21.3% vs 35.5% at 3 years), OS (P=0.854, 42.6% vs 43.0% at 3 years) or RFS (P=0.653, 42.8% vs 35.9% at 3 years). In an adjusted model, age >50, cytogenetics and CR status were associated with inferior RFS (hazard ratio (HR)=2.16, P=0.003, HR=1.77, P=0.022, HR=2.47, P<0.001), whereas graft type was NS (HR=0.90, P=0.635). OS and RFS rates are similar in patients undergoing TCD or conventional HCT, but TCD effectively reduces the rate of GVHD.

Clinical guide to fertility preservation in hematopoietic cell transplant recipients.

With broadening indications, more options for hematopoietic cell transplantation (HCT) and improvement in survival, the number of long-term HCT survivors is expected to increase steadily. Infertility is a frequent problem that long-term HCT survivors and their partners face and it can negatively impact on the quality of life. The most optimal time to address fertility issues is before the onset of therapy for the underlying disease; however, fertility preservation should also be addressed before HCT in all children and patients of reproductive age, with referral to a reproductive specialist for patients interested in fertility preservation. In vitro fertilization (IVF) and embryo cryopreservation, oocyte cryopreservation and ovarian tissue banking are acceptable methods for fertility preservation in adult women/pubertal females. Sperm banking is the preferred method for adult men/pubertal males. Frequent barriers to fertility preservation in HCT recipients may include the perception of lack of time to preserve fertility given an urgency to move ahead with transplant, lack of patient-physician discussion because of several factors (for example, time constraints, lack of knowledge), inadequate access to reproductive specialists, and costs and lack of insurance coverage for fertility preservation. There is a need to raise awareness in the medical community about fertility preservation in HCT recipients.

Graft-versus-host disease after double-unit cord blood transplantation has unique features and an association with engrafting unit-to-recipient HLA match.

Manifestations of and risk factors for graft-versus-host disease (GVHD) after double-unit cord blood transplantation (DCBT) are not firmly established. We evaluated 115 DCBT recipients (median age, 37 years) who underwent transplantation for hematologic malignancies with myeloablative or nonmyeloablative conditioning and calcineurin inhibitor/mycophenolate mofetil immunosuppression. Incidence of day 180 grades II to IV and III to IV acute GVHD (aGVHD) were 53% (95% confidence interval, 44 to 62) and 23% (95% confidence interval, 15 to 31), respectively, with a median onset of 40 days (range, 14 to 169). Eighty percent of patients with grades II to IV aGVHD had gut involvement, and 79% and 85% had day 28 treatment responses to systemic corticosteroids or budesonide, respectively. Of 89 engrafted patients cancer-free at day 100, 54% subsequently had active GVHD, with 79% of those affected having persistent or recurrent aGVHD or overlap syndrome. Late GVHD in the form of classic chronic GVHD was uncommon. Notably, grades III to IV aGVHD incidence was lower if the engrafting unit human leukocyte antigen (HLA)-A, -B, -DRB1 allele match was >4/6 to the recipient (hazard ratio, 0.385; P = .031), whereas engrafting unit infused nucleated cell dose and unit-to-unit HLA match were not significant. GVHD after DCBT was common in our study, predominantly affected the gut, and had a high therapy response, and late GVHD frequently had acute features. Our findings support the consideration of HLA- A,-B,-DRB1 allele donor-recipient (but not unit-unit) HLA match in unit selection, a practice change in the field. Moreover, new prophylaxis strategies that target the gastrointestinal tract are needed.

A prospective evaluation of changes in brain structure and cognitive functions in adult stem cell transplant recipients.

Hematopoietic stem cell transplantation (HSCT) is an efficacious treatment for many hematologic malignancies. However, the conditioning regimen of high-dose (HD) chemotherapy with or without total body irradiation (TBI) can be associated with neurotoxicity. In this prospective study, we used quantitative neuroimaging techniques to examine regional gray matter and ventricular volumes, and standardized neuropsychological tests to assess cognitive function before and 1 year after HSCT in 28 patients with hematologic malignancies and in ten healthy controls evaluated at similar intervals. Nineteen patients received conditioning treatment with HD chemotherapy alone and nine had both TBI and HD chemotherapy. There was a significant reduction in gray matter volume in the middle frontal gyrus bilaterally and in the left caudate nucleus in the patient group (all patients combined) but not among healthy controls over the 1-year follow-up period. There was a significant increase in left lateral ventricle volume and in total ventricle volume in the patient group, relative to healthy controls. Similar brain structural changes were seen for patients treated with HD chemotherapy alone. The neuropsychological results showed that 21% of patients could be classified as impaired at baseline. The Reliable Change Index suggested no significantly different rates of cognitive decline between patients and healthy controls. The findings suggest that HSCT patients may be at an increased risk for developing regional brain volume loss, and that subgroups may experience cognitive dysfunction prior to and 1 year following the transplant.

Palifermin is efficacious in recipients of TBI-based but not chemotherapy-based allogeneic hematopoietic stem cell transplants.

Palifermin, a recombinant human keratinocyte growth factor, is commonly given to prevent mucositis following autologous transplantation. In the allogeneic hematopoietic stem cell transplant (allo-HSCT) setting, safety and efficacy data are limited. We conducted a retrospective study in 251 patients undergoing allo-HSCT, 154 of whom received peritransplant palifermin. In all patients, palifermin significantly decreased the mean number of days of total parenteral nutrition (TPN, 13 vs 16 days, P=0.006) and patient-controlled analgesia (PCA, 6 vs 10 days, P=0.023), as well as the length of initial hospital stay (LOS, 32 vs 37 days, P=0.014). However, the effect of palifermin was only significant in patients who received a TBI- but not BU-based chemotherapy conditioning regimen. In TBI recipients, palifermin decreased the mean number of days of TPN (13 vs 17 days, P<0.001) and PCA (7 vs 12 days, P=0.033), and the length of stay (32 vs 38 days, P=0.001). Palifermin did not affect GVHD, graft failure or relapse. Therefore, in the largest analysis with this patient population to date, we demonstrate that palifermin is safe in allo-HSCT patients, decreases TPN and PCA use and decreases LOS following TBI-based but not chemotherapy-based allo-HSCT.

Prospects for advanced electron cyclotron resonance and electron beam ion source charge breeding methods for EURISOL.

As the most ambitious concept of isotope separation on line (ISOL) facility, EURISOL aims at producing unprecedented intensities of post-accelerated radioactive isotopes. Charge breeding, which transforms the charge state of radioactive beams from 1+ to an n+ charge state prior to post-acceleration, is a key technology which has to overcome the following challenges: high charge states for high energies, efficiency, rapidity and purity. On the roadmap to EURISOL, a dedicated R&D is being undertaken to push forward the frontiers of the present state-of-the-art techniques which use either electron cyclotron resonance or electron beam ion sources. We describe here the guidelines of this R&D.

Disseminated Mycobacterium marinum infection in a hematopoietic stem cell transplant recipient.

Mycobacterium marinum is a photochromogenic mycobacterium that is ubiquitous in the aquatic environment. In the general population, exposure to aquaria is the most common cause of M. marinum infection. Known as "swimmer's granuloma" or "fish tank granuloma," M. marinum is an occupational hazard for aquarium cleaners and fishermen. There are several reports in the literature of M. marinum infection in immunocompromised hosts, including those with solid organ transplants, but none in patients who have received stem cell transplants (SCTs). To our knowledge, this is a first report of disseminated M. marinum infection in an SCT recipient who continued to develop new skin lesions even after months of targeted therapy. The implications are that elderly patients who receive T-cell-depleted SCTs may be at prolonged risk for pathogens dependent on cellular immunity, and the presentation of illness with such pathogens may be more severe and widely disseminated than might otherwise be expected.

Hepatic safety of voriconazole after allogeneic hematopoietic stem cell transplantation.

Voriconazole is increasingly used in allogeneic hematopoietic stem cell transplantation (HSCT) for prophylaxis and treatment of fungal infections. Hepatic dysfunction is common in patients undergoing HSCT and may have an impact on the clinical decision to institute voriconazole. We conducted a retrospective review of all adult and pediatric HSCT recipients who received >2 consecutive doses of voriconazole between January 2005 and February 2008. Clinical hepatotoxicity was defined as the subjective attribution of liver enzyme elevation (even a mild one) to hepatotoxicity because of voriconazole by the treating physician and leading to discontinuation of voriconazole. Biochemical hepatotoxicity was defined as an elevation in one or more liver enzymes to >3 times the upper limit of normal or >3 times the baseline value if abnormal at baseline. Liver enzymes assessed included aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total bilirubin. Simple and multiple logistic regressions were used to define the risks for hepatic dysfunction. The Wilcoxon signed-rank test was used to assess the differences in liver function test values before, during, and after the use of voriconazole. Sixty-eight of 200 patients (34%) developed hepatotoxicity while on voriconazole. The median duration of voriconazole therapy was 72 days (range, 1-804 days). Biochemical hepatotoxicity occurred in 51 patients (75%); clinical hepatotoxicity, in 17 patients (25%). Thirty-five (51%) of the patients with hepatotoxicity required discontinuation of therapy. In simple logistic regression, acute graft-versus-host disease (GVHD) was a risk factor for hepatotoxicity, and receipt of a T-cell depleted allograft was protective. In multiple logistic regression, acute GVHD (P = .002) remained significant. There were no cases of liver failure or death attributed to voriconazole. In this cohort of patients undergoing allogeneic HSCT, the rate of hepatotoxicity while on voriconazole was 34%. In general, the hepatic dysfunction was mild and reversible. Voriconazole therapy with monitoring appears to be reasonably safe for use in HSCT recipients at high risk for invasive fungal infections.

Second-line age-adjusted International Prognostic Index in patients with advanced non-Hodgkin lymphoma after T-cell depleted allogeneic hematopoietic SCT.

T-cell depleted allogeneic hematopoietic SCT (TCD-HSCT) have shown durable disease-free survival with a low risk of GVHD in patients with AML. We investigated this approach in 61 patients with primary refractory or relapsed non-Hodgkin lymphoma (NHL), who underwent TCD-HSCT from January 1992 through September 2004. Patients received myeloablative cytoreduction consisting of hyperfractionated total body irradiation, followed by either thiotepa and cyclophosphamide (45 patients) or thiotepa and fludarabine (16 patients). We determined the second-line age-adjusted International Prognostic Index score (sAAIPI) before transplant transplant. Median follow-up of surviving patients is 6 years. The 10-year OS and EFS were 50% and 43%, respectively. The relapse rate at 10 years was 21% in patients with chemosensitive disease and 52% in those with resistant disease at time of HSCT. Nine of the 18 patients who relapsed entered a subsequent CR. OS (P=0.01) correlated with the sAAIPI. The incidence of grades II-IV acute GVHD was 18%. We conclude that allogeneic TCD-HSCT can induce high rates of OS and EFS in advanced NHL with a low incidence of GVHD. Furthermore, the sAAIPI can predict outcomes and may be used to select the most appropriate patients for this type of transplant.

S-nitroso human serum albumin given after LPS challenge reduces acute lung injury and prolongs survival in a rat model of endotoxemia.

Endotoxemia leads to the induction of inducible nitric oxide synthase (NOS-2) and increased expression of numerous inflammatory mediators contributing to endotoxin-induced acute lung injury. We tested the hypothesis that supplementation of nitric oxide (NO) by the novel NO donor S-nitroso human serum albumin (S-NO-HSA) given after lipopolysaccharide (LPS) challenge may reduce NOS-2 expression, lung inflammation and acute lung injury. Rats were divided into four groups: sham-operated (no treatment), LPS, LPS+HSA (human serum albumin), and LPS+S-NO-HSA. LPS was administered intravenously (20 mg kg(-1)) resulting in acute lung injury and a high mortality rate within 6 h (>90%). LPS-induced lung injury was characterized by an increased lung edema (lung wet/dry weight ratio), pulmonary neutrophil infiltration (myeloperoxidase activity, MPO) as well as a robust inflammatory response [increased expression of intercellular adhesion molecule-1 (ICAM-1), NOS-2, and cyclooxygenase-2 (COX-2)]. Infusion of S-NO-HSA or HSA was started 2 h after LPS and continued for 4 h (total dose of 72 mg kg(-1)) at a rate of 300 microg kg(-1) min(-1). S-NO-HSA but not HSA prolonged survival of endotoxemic rats, reduced the hypotensive response to LPS, minimized LPS-induced lung edema and injury, normalized MPO activity as well as diminished lung expression of pro-inflammatory molecules such as ICAM-1, NOS-2, and COX-2. Continuous supplementation of NO by S-NO-HSA after LPS challenge prevents induction of NOS-2, provides significant protection of endotoxin-induced acute lung injury, and prevents early mortality in endotoxic shock in rats. Our results suggest a potential therapeutic role for S-NO-HSA in endotoxemia.

Risk factors and attributable mortality of late aspergillosis after T-cell depleted hematopoietic stem cell transplantation.

AIM: Invasive aspergillosis occurs in 5-15% of allogeneic hematopoietic stem cell transplant (HSCT) recipients. Through the 1990s there has been an increase in the incidence of late aspergillosis (LA). We report on the incidence, risk factors, and attributable mortality of LA in a cohort of 398 adult and pediatric patients at Memorial Sloan-Kettering Cancer Center from January 1999 through December 2003. METHODS: LA was defined as occurring > 40 days post HSCT. LA cases were identified by prospective surveillance and examination of a computerized database. Probable or definite aspergillosis was defined by standard EORTC/MSG criteria. Mortality was attributed to LA if it caused or significantly contributed to death. RESULTS: The overall incidence of LA in our cohort was 4.1%. Median time from stem cell infusion to diagnosis of LA was 164 days (range 68-677) after HSCT. The incidence of LA among unmodified, T-cell depleted, or reduced intensity HSCT was 2.2%, 4%, and 6.8%, respectively (P not significant). Risk factors for LA were grade II-IV acute graft-versus-host disease (GVHD) (P=0.002), chronic GVHD (P=0.01), secondary neutropenia (P=0.02), and reduced intensity conditioning containing alemtuzumab (P=0.01). LA was the immediate cause of death in 1 of 10 (10%) T-cell depleted, 2 of 2 (100%) unmodified, and 1 of 4 (25%) of reduced-intensity HSCT. CONCLUSIONS: LA developed a median 164 days post HSCT. All-cause 30-day mortality of LA was 56.3%. The majority of LA cases died of concurrent infections and not from invasive aspergillosis.

Long-term follow-up of patients treated with daclizumab for steroid-refractory acute graft-vs-host disease.

Daclizumab has been shown to have activity in acute GVHD, but appears to be associated with an increased risk of infection. To investigate further the long-term effects of daclizumab, we performed a retrospective review of 57 patients who underwent an allogeneic hematopoietic stem cell transplant from January 1993 through June 2000 and were treated with daclizumab for steroid-refractory acute GVHD. The median number of daclizumab doses given was 5 (range 1-22). GVHD was assessed at baseline, days 15, 29 and 43. By day 43, 54% patients had an improvement in their overall GVHD score, including 76% patients aged < or =18. Opportunistic infections developed in 95% patients. Forty-three patients (75%) died following treatment with daclizumab. The causes of death included active GVHD and infection (79%), active GVHD (5%), chronic GVHD (2%) and relapse (14%). Patients with grade 3-4 GVHD had a significantly shorter median survival than patients with grade 1-2 GVHD (2.0 vs 5.1 months, P=0.001). Daclizumab has no infusion-related toxicity, is active in steroid-refractory GVHD, especially among pediatric patients, but is associated with significant morbidity and mortality due to infectious complications. Careful patient selection and aggressive prophylaxis against viral and fungal infections are recommended.

Predictors for persistent cytomegalovirus reactivation after T-cell-depleted allogeneic hematopoietic stem cell transplantation.

UNLABELLED: Cytomegalovirus (CMV) reactivation occurs in up to 60% of CMV-seropositive recipients after allogeneic hematopoietic stem cell transplantation (HSCT). The incidence of CMV disease among T-cell-depleted HSCT patients has been reported from 5-15%. The incidence of reactivation refractory to antivirals in this population is not well studied. METHODS: In this retrospective study we characterized the outcome of CMV reactivation in a cohort of 255 adult and pediatric patients who underwent T-cell-depleted HSCT at Memorial Sloan-Kettering Cancer Center from September 1999 through August 2004. CMV infection was monitored by the pp65 antigenemia assay (CMV Ag). Persistent reactivation was defined as antigenemia positivity >21 days on antiviral therapy. RESULTS: Of 118 CMV-seropositive recipients, 69 (58.4%) had reactivated CMV. Twenty of 69 (29%) developed persistent reactivation at first episode of reactivation, and 7 (10%) in subsequent episode. All patients with persistent reactivation received >/=2 antivirals and CMV hyperimmune globulin; 45% received combination antiviral therapy. The median duration of persistent reactivation was 98 days, range 31-256 days. In multivariate analysis, maximum CMV Ag >25 cells/slide was associated with persistent reactivation (odds ratio 16.2%, 95% confidence interval 4-64, P<0.0001). CMV disease occurred in 6/27 (22%) patients with persistent reactivation. Patients with persistent reactivation had lower CD4(+) and CD8(+) lymphocyte counts compared with those with non-persistent reactivation at day +90 post HSCT (P=0.01 and 0.02, respectively). CONCLUSIONS: Persistent reactivation occurred in 39% of T-cell-depleted HSCT despite treatment with currently available antivirals. Maximum CMV Ag >25 cells/slide was associated with persistent CMV reactivation. More effective treatment modalities are needed for this high-risk population to reduce CMV-associated morbidity and mortality.

Invasive adenoviral infections in T-cell-depleted allogeneic hematopoietic stem cell transplantation: high mortality in the era of cidofovir.

BACKGROUND: Adenovirus (ADV) infection occurs in 5-21% of allogeneic hematopoietic stem cell transplants (HSCT). Symptomatic enteritis and hemorrhagic cystitis may be encountered but are seldom fatal. In contrast, mortality rates of up to 75% are reported for adenoviral pneumonia or hepatitis. Cidofovir is currently being increasingly used for treatment of adenoviral infections after HSCT. The efficacy of cidofovir in patients with invasive adenoviral infection is not established. FINDINGS: We reviewed 687 adult and pediatric patients who received allogeneic HSCT at our institution from 1998 through June 2005. ADV was isolated from 64 (9.3%) patients. Eleven patients received cidofovir for invasive disease occurring at median 39 days (range 3-145) post HSCT. The median age was 40 (range 6-61) years. Seventy-three percent received a T-cell-depleted graft and 18% had grade 3-4 graft-versus-host disease (GVHD) of the gut. Three out of 3 (100%) patients with adenoviral pneumonia died. One patient with hepatitis, cholecysitis, and viremia cleared the infection after 3 months. Two out of 7 (28.6%) patients with hemorrhagic colitis or cystitis died of ADV (1 with extensive GVHD). CONCLUSION: Mortality rates of ADV pneumonitis after allogeneic HSCT remain high in the era of cidofovir. Clinical trials are needed to evaluate management strategies for this life-threatening infection.