This study analyzed the characteristics of 257 HLA-identical sibling transplants of granulocyte colony-stimulating factormobilized peripheral blood progenitor cells depleted of T cells by CD34 ؉ positive selection (allo-PBT/CD34 ؉ ) for their effect on the incidence of graft failure. Twenty-four patients developed graft failure (actuarial probability, 11%; 95% confidence interval, 7.1-14.9). Prognostic factors considered were sex and age of donor and recipient, donor-recipient blood group compatibility, diagnosis, disease status at transplant, conditioning regimen, cytomegalovirus serology, number of CD34 ؉ and CD3 ؉ cells infused, and cryopreservation. The major factor associated with graft failure was the number of CD3 ؉ cells in the inoculum. Twentythree of 155 patients receiving a T-cell dose in the graft less than or equal to 0.2 ؋ 10 6 /kg experienced graft failure, compared with only one of 102 patients receiving more than 0.2 ؋ 10 6 /kg (actuarial probability 18% vs 1%, respectively; P ؍ .0001). The actuarial probability of graft failure progressively increased as the number of CD3 ؉ cells in the graft decreased, which was determined by grouping the number of CD3 ؉ cells in quartiles (log-rank P ؍ .03; log-rank for trend P ؍ .003). In the multivariate analysis by the proportional hazard method, 2 covariates entered into regression at a significant level: CD3 ؉ cells less than or equal to 0.2 ؋ 10 6 /kg (risk ratio ؍ 17; P < .0001), and patients with chronic myelogenous leukemia (CML) conditioned with busulphan-based regimens (risk ratio ؍ 4.8; P ؍ .001). From these results it appears that the number of CD3 ؉ cells in the inoculumwith a threshold of 0.2 ؋ 10 6 /kg or less-is the most critical factor in maintaining a sustained engraftment in allo-PBT/CD34 ؉ from HLA-identical siblings. In addition, for patients with CML receiving 0.2 ؋ 10 6 /kg or less CD3 ؉ cells, total body irradiation might be better than busulphan-based regimens.
A study on 315 patients undergoing transplantation with CD34 ؉ selected blood cells from HLA-identical siblings was performed to determine risk factors for acute GVHD (aGVHD). Recipients of a dose of CD34 ؉ cells (؋ 10 6 /kg) of 2 or less, more than 2 to 4, and more than 4 had a cumulative incidence of aGVHD grades I-IV of 21%, 35%, and 43%, respectively (log-rank P ؍ .01); similarly, recipients of a dose of CD3 ؉ cells (؋ 10 6 /kg) of 0.05 or less, more than 0.05 to 0.1, and more than 0.1 had a cumulative incidence of aGVHD grades I-IV of 18%, 35%, and 44%, respectively (log-rank P ؍ .007). Using a Cox regression model, 4 independent factors for aGVHD I-IV were identified: increased CD34 ؉ cell dose (P ؍ .02), increased CD3 ؉ cell dose (P ؍ .02), female patients (P ؍ .01), and higher patient age (> 42 years IntroductionAcute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after allogeneic stem cell transplantation. 1,2 Although widely accepted risk factors for aGVHD have been identified in patients receiving unmodified grafts, 3-6 these parameters may not have the same predictive value in patients receiving a graft in which donor T cells, the major determinant of GVHD, have been depleted. The isolation of risk factors for aGVHD in T-cell-depleted transplantations could be useful to identify individual patients at a high probability of developing this complication. The present study was directed at identifying factors predictive of aGVHD in 315 adult patients receiving an HLAidentical sibling transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells T-cell depleted by means of CD34 ϩ selection (allo-PBT/CD34 ϩ ). We observed a strong association between the incidence of aGVHD and 2 controllable variables: the number of CD34 ϩ and CD3 ϩ cells infused. Study designThis study included 315 consecutive adult patients with hematologic malignancies treated with an allo-PBT/CD34 ϩ from an HLA-identical sibling donor between March 1995 and December 2000. Granulocyte colony-stimulating factor administration and leukapheresis procedures have been previously described. 7 This study was approved by local ethic committees and by the Spanish Department of Health. Informed consent was provided according to the Declaration of Helsinki. Patient and donor characteristics are shown in Table 1. CD34 ϩ cells and CD3 ϩ cells were quantified as previously published. 7 There was no correlation between CD34 ϩ and CD3 ϩ cell dose (Pearson correlation coefficient Ϫ0.04; P ϭ .47). Phase of disease, time to engraftment, diagnosis of graft failure, and transplantation-related mortality (TRM) have been previously defined. 8 The diagnosis and grading of aGVHD was established according to the Seattle criteria. 9 Probabilities of aGVHD were calculated by the cumulative incidence method (marginal probability) and statistically compared by Gray method. 10,11 In this study, graft failure or relapse, without aGVHD, were considered competing risks. Characteristics consi...
Summary:megalovirus, as well as a low incidence of graft-versushost disease. 3,8,9 The major problem of long-term UCB banking is the One of the main problems for the establishment of umbilical cord blood (UCB) banks is the storage space storage space required for unprocessed units. Several attempts have been made to reduce the UCB volume withneeded for the frozen samples. The aim of this study was to find a method of reducing the volume of UCB out loss of progenitor cells. + + + cell quantification were done in whole blood and in the isorecovery of progenitor cells using rouleaux formation induced by 6% hydroxyethyl starch and centrifugation to lated fractions. The average volume of the 19 UCB samples processed was 103 ml. Separation by centrifugreduce both erythrocytes and plasma. Most of these techniques imply the addition of exogenous materials and are ation led to a mean volume reduction of 56% with red cell depletion of 59%. The white blood cell recovery was carried out in an open system with the risk of contamination. of 72% with a significant CD34 + + + cell recovery of 87%. This seems a promising method for cord blood volumeThe aim of this study was to find a method for volume reduction of UCB by centrifugation with partial removal of reduction and enrichment of CD34 + + + cells. Keywords: cord blood processing; CD34 + cells; cord red cells and plasma without significant losses of the HPC CD34 + cells, using a closed system for collection and problood bank cessing.Bone marrow transplantation plays an important role in the Materials and methods treatment of many congenital and acquired haematologic diseases, either malignant or benign.1 The early haematopoietic progenitor cells are essential for haematologic and UCB collection bags immunologic bone marrow reconstitution and express the A triple blood collection system (R1656B; Baxter, Lisbon, surface glycoprotein CD34.2 It is generally known that Portugal) with a 450 ml bag containing citrate-phosphatehuman umbilical cord blood (UCB) is a rich source of dextrose-adenin (CPD-A) anticoagulant was used to collect haematopoietic progenitor cells (HPC-CD34 + ) and has been the UCB. The volume of CPD-A was reduced to 20 ml successfully used as a source of progenitor cells for bone transferring the excess to the SAG manitol satellite bag, marrow reconstitution. [3][4][5][6][7] which was then sealed and removed, keeping the system Until 1996 more than 100 cord blood transplants had closed. been performed in children or adults with total or partially HLA-matched donors. 8 The UCB offers several advantages over bone marrow and peripheral blood as it is available UCB collection without risk to mother or infant, easy and cheap to collect, and has decreased transmission of infection, namely cyto-UCB were collected from full-term pregnancies with informed consent from the donors following delivery and clamping of umbilical cord. UCB was collected from the umbili- were stored at 4°C and processed within the following 24 h.
Summary:Tuberculosis is an uncommon infectious complication after stem cell transplantation. We report a patient who presented with a brain mass, 3 months after pulmonary tuberculosis had been diagnosed and while he was receiving triple antituberculous therapy. He had extensive chronic GVHD. The diagnosis was made after biopsy of the lesion. The cerebral mass was excised, antituberculous treatment was maintained and the patient made a complete neurologic recovery. Six months later, he died of gram-negative septic shock. Mycobacterial infections should be considered in allograft recipients with chronic GVHD and solid lesions in the brain. Bone Marrow Transplantation (2000) 25, 567-569. Keywords: stem cell transplantation; graft-versus-host disease; tuberculosis Tuberculosis remains a major problem in the world today. It is estimated that one third of the world population is infected with Mycobacterium tuberculosis, with more than eight million new cases and nearly three million deaths occurring each year.1 Tuberculosis is directly responsible for 7% of all deaths world-wide, and the global pandemic is likely to worsen as a result of the spread of drug-resistant organisms and the ongoing human immune-deficiency virus (HIV) epidemic.2 Stem cell transplant recipients have severely impaired cell-mediated immunity as a result of their underlying disease, pre-transplant chemotherapy and radiation, graft-versus-host disease (GVHD) and its treatment. Considering mycobacteria epidemiology characteristics and the severe immune-suppression after stem cell transplantation, a high incidence of mycobacterial infections would be expected. However, this infection is uncommon, even in endemic areas, and the literature is relatively sparse concerning this subject. 3,4
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