Umbilical cord blood (CB) from unrelated donors is increasingly used to restore hematopoiesis after myeloablative therapy. CB transplants are associated with higher rates of delayed and failed engraftment than are bone marrow transplants, particularly for adult patients. We studied the ex vivo expansion of CB in an attempt to improve time to engraftment and reduce the graft failure rate in the recipients. In this feasibility study, 37 patients (25 adults, 12 children) with hematologic malignancies (n = 34) or breast cancer (n = 3) received high-dose therapy followed by unrelated allogeneic CB transplantation. A fraction of each patient's CB allograft was CD34-selected and cultured ex vivo for 10 days prior to transplantation in defined media with stem cell factor, granulocyte colony-stimulating factor, and megakaryocyte growth and differentiation factor. The remainder of the CB graft was infused without further manipulation. Two sequential cohorts of patients were accrued to the study. The first cohort had 40% and the second cohort had 60% of their CB graft expanded. Patients received a median of 0.99 x 10(7) total nucleated cells (expanded plus unexpanded) per kilogram. The median time to engraftment of neutrophils was 28 days (range, 15-49 days) and of platelets was 106 days (range, 38-345 days). All evaluable patients who were followed for 28 days or longer achieved engraftment of neutrophils. Grade III/IV acute GVHD was documented in 40% and extensive chronic GVHD in 63% of patients. At a median follow-up of 30 months, 13 (35%) of 37 of patients survived. This study demonstrates that the CD34 selection and ex vivo expansion of CB prior to transplantation of CB is feasible. Additional accrual will be required to assess the clinical efficacy of expanded CB progenitors.
Post-hematopoietic stem cell transplantation (HSCT) adenovirus infections were identified in 31 of 204 consecutive pediatric HSCT patients, 18 of whom had severe manifestations of infection. Cidofovir treatment led to clinical improvement in 8 of 10 patients with severe infection and to virologic clearance in 9 patients. In vitro susceptibility to cidofovir was demonstrated in 12 clinical adenovirus isolates. Cidofovir is a promising treatment option for this population.Adenoviruses are serious pathogens among immunocompromised patients [1,2], with an incidence of infection of up to 20% among hematopoietic stem cell transplant (HSCT) recipients [3] and case-fatality rates that approach 60% [4]. Respiratory, gastrointestinal, and genitourinary infections with adenovirus are common in children undergoing HSCT [5,6], and disseminated illness is often fulminant and fatal. Cidofovir has in vitro activity against adenoviruses [7][8][9], and several case studies [3,[10][11][12][13][14] report successful use of cidofovir for treatment of adenovirus infection in HSCT and solid organ transplant recipients. We reviewed the findings regarding adenovirus infection in a pediatric HSCT population and describe our experience with cidofovir therapy.Methods. We reviewed data from a database on 204 con- secutive patients who underwent HSCT at our institution during the period of 1 January 1994 and 31 March 2003, and we analyzed records for patients with adenovirus infection for a minimum of 200 days after transplantation, because data for each patient were available for at least this duration at the start of the study. Testing for adenovirus infection was performed only for symptomatic patients; there was no routine surveillance. Diagnosis was confirmed by detection of adenovirus antigen in respiratory specimens by immunofluorescence, by observation of typical adenovirus particles in stool specimens concentrated by ultracentrifugation, and by conventional and shell-vial centrifugation culture of nasal secretions, bronchoalveolar lavage specimens, urine samples, or stool samples, with use of monoclonal antibodies and immunofluorescence for confirmation. Serotyping of adenovirus isolates was not done. Patients with adenovirus detected from 11 site during the same illness were classified as having disseminated infection.Patients with adenovirus infection were categorized as having severe infection either if they had disseminated infection or if infection at 1 site was accompanied by severe clinical manifestations attributable to the infection [12]; all other infections were categorized as mild. Resolution of infection was defined as clinical improvement and as virologic evidence of clearance; patients with intermittent positive test results after having symptomatic illness were considered to have continued infection until specimens yielded consistently negative test results with continued absence of symptoms over a 30-day period. Recurrence of infection was defined as evidence of adenovirus at any site 130 days after resolution of pr...
Summary:Pediatric acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) with monosomy 7 is associated with poor disease-free survival when treated by conventional chemotherapy, immunosuppression or supportive measures. Hematopoietic stem cell transplant (HSCT) may improve outcomes; however, data to support this are limited. To better understand the curative potential of HSCT in these patients, all cases of AML and MDS with monosomy 7 treated by two transplant programs (1992 to present) were reviewed. A total of 16 patients were treated, all by allogeneic HSCT. Primary diagnoses were MDS (N ¼ 5), therapy-related MDS (N ¼ 3), AML (N ¼ 5) and therapy-related AML (N ¼ 3). In all, 11 patients (69%) survive event-free at 2 years with median follow-up of 986 days (range 330-2011 days). Toxicity caused deaths of the five nonsurviving patients, four of whom were transplanted with active leukemia. Allogeneic HSCT is effective therapy for childhood AML and MDS associated with monosomy 7, particularly for patients with AML in complete remission and MDS.
We reviewed our experience in 79 children who had unrelated cord blood transplant (UCBT) between 1996 and 2007 with a major focus on GVHD, comparing both traditional and National Institute of Health (NIH) criteria. The cumulative incidence (CI) of acute GVHD (aGVHD, by day þ 100) was 0.42 for grade II-IV and 0.22 for grade III-IV. The CI of all aGVHD (NIH, that is, no time limit) at 1 year was 0.45 for grade II-IV and 0.32 for grade III-IV. Infused CD34 cell dose (41 Â 10 5 /kg), pretransplant bacterial infection and nonmalignant disorders were risk factors for grade II-IV aGVHD on univariate analysis. Infused CD34 cell dose remained significant on multivariate analysis. At 1 year, the CI of chronic GVHD (cGVHD) using the Seattle criteria was 0.27, whereas that for cGVHD (NIH) was 0.08. By NIH criteria, the classic form of cGVHD was uncommon (5%) after UCBT. Instead, the acute (71%) and overlap (24%) GVHD variants predominated. Grade II-IV aGVHD was a significant risk factor for cGVHD by both Seattle and NIH criteria. We conclude that GVHD after day þ 100 after UCBT typically carries features of aGVHD. Moreover, and in marked contrast to adult unrelated donor hematopoietic stem cell transplantation, the GVHD observed in this series did not adversely affect survival.
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