Results of hematopoietic stem cell transplantation after treatment with different high-dose total-body irradiation regimens in five Dutch centers.

Purpose: To evaluate results of high-dose total-body irradiation (TBI) regimens for hematopoietic stem cell transplantation.

Methods And Materials: A total of 1,032 patients underwent TBI in one or two fractions before autologous or allogeneic hematologic stem cell transplantation for acute leukemia and non-Hodgkin's lymphoma. The TBI regimens were normalized by using the biological effective dose (BED) concept.

Prevention of coagulase-negative staphylococcal central venous catheter-related infection using urokinase rinses: a randomized double-blind controlled trial in patients with hematologic malignancies.

Purpose: Fibrin deposition at the intraluminal surface of the indwelling part of the central venous catheter (CVC) surface increases the risk of CVC-related coagulase-negative staphylococci (CoNS) infection. Therefore, repetitive enzymatic dissolution of fibrin by urokinase might reduce the risk of CVC-related infection. We undertook this study to investigate whether three times weekly urokinase rinsing of CVC reduces the incidence or severity of CVC-related infections by CoNS in patients undergoing intensive cytotoxic treatment for hematologic malignancies.

Thalidomide in induction treatment increases the very good partial response rate before and after high-dose therapy in previously untreated multiple myeloma.

In the prospective phase 3 HOVON-50/GMMG-HD3 trial, patients randomized to TAD (thalidomide, doxorubicin, dexamethasone) had a significantly higher response rate (at least PR) after induction compared with patients randomized to VAD (vincristine, adriamycin, dexamethasone, 72% vs. 54%, p<0.001).

Differential activation of the death receptor pathway in human target cells induced by cytotoxic T lymphocytes showing different kinetics of killing.

Background And Objectives: Cytotoxic T lymphocytes (CTL) may use two effector mechanisms to kill their target cells: perforin (PFN) and granzyme B (GrB)-dependent granule-mediated cell death and death receptor-mediated cell death. Controversy exists whether, in addition to PFN/GrB-mediated apoptosis, death receptor-induced apoptosis contributes to the elimination of human tumor cells by CTL.

Design And Methods: Since the two CTL-mediated effector mechanisms differ in time required to eliminate target cells, lysis of target cells was analyzed using CTL clones with slow and rapid kinetics of killing derived from a patient with chronic myeloid leukemia.

Case-referent comparison of cognitive functions in patients receiving haematopoietic stem-cell transplantation for haematological malignancies: two-year follow-up results.

During bone marrow or haematopoietic stem-cell transplantation (HSCT), potentially neurotoxic treatments are used. Previous studies identified cognitive disturbances in patients treated with HSCT, but prospective studies with longitudinal assessment are sparse. We examined cognitive functions up to 20 months after a first baseline assessment in 101 patients undergoing HSCT and in 82 reference patients with a haematological malignancy treated with non-myeloablative cancer therapies.

Comparable incidence and severity of cytomegalovirus infections following T cell-depleted allogeneic stem cell transplantation preceded by reduced intensity or myeloablative conditioning.

Reports on infectious complications following reduced intensity conditioning (RIC) before allogeneic stem cell transplantation (allo-SCT) are equivocal. This prospective follow-up study compared the impact of cytomegalovirus (CMV) infections following RIC with fludarabine, ATG and busulphan or conventional myeloablative conditioning (MAC). Forty-eight RIC and 59 MAC patients were enrolled.

Assessment of disseminated adenovirus infections using quantitative plasma PCR in adult allogeneic stem cell transplant recipients receiving reduced intensity or myeloablative conditioning.

Objectives: Disseminated adenovirus (AdV) infections following allogeneic stem cell transplantation (allo-SCT) are increasingly recognised, particularly in children. This study evaluated the clinical relevance of disseminated AdV infections in adult allo-SCT recipients, after different conditioning regimens.

Methods: In a cohort of 107 adult allo-SCT recipients, receiving either reduced intensity conditioning (RIC, n = 48) or myeloablative conditioning (MAC, n = 59), AdV DNA levels in plasma were determined retrospectively at 1, 3 and 6 months following transplantation.

Liver chimerism after allogeneic blood stem cell transplantation.

Unlabelled: Blood stem cells can mature into elements of many different lineages. We investigated the presence and nature of donor-derived (chimeric) cells within the liver after allogeneic stem cell transplantation.

Methods: Liver biopsy autopsy specimens were examined from nine female patients who had undergone allogeneic bone marrow (n = 6) or peripheral stem cell (n = 3) transplantation from a male donor.

Involvement of caspase-8 in chemotherapy-induced apoptosis of patient derived leukemia cell lines independent of the death receptor pathway and downstream from mitochondria.

Resistance of leukemic cells to chemotherapy frequently occurs in patients with acute leukemia, which may be caused by alterations in common apoptotic pathways. Controversy exists whether cytostatic agents induce the mitochondrial or death receptor pathway of apoptosis. In the mitochondrial pathway cytochrome C release and caspase-9 activation play a central role in the induction of apoptosis, while formation of a Death Inducing Signaling Complex (DISC) and caspase-8 activation have been reported to be essential in death receptor-induced apoptosis.

Outcomes after myeloablative unrelated donor stem cell transplantation using both in vitro and in vivo T-cell depletion with alemtuzumab.

HLA-matched unrelated donor (MUD) stem cell transplantation (MUD) is complicated by a high incidence of graft-versus-host-disease (GVHD) resulting in significant morbidity and mortality. To circumvent this problem we included alemtuzumab for in vivo and in vitro T-cell depletion in a myeloablative MUD-SCT regimen. After SCT, no severe acute GVHD was observed in the 30 transplanted patients.

A multicenter randomized study of the efficacy of transfusions with platelets stored in platelet additive solution II versus plasma.

Randomized studies testing the clinical efficacy of platelet additive solutions (PASs) for storage of platelets are scarce and often biased by patient selection. We conducted a multicenter, randomized study to investigate clinical efficacy of platelets stored in PAS II versus plasma, also including patients with clinical complications associated with increased platelet consumption. A total of 168 evaluable patients received pooled buffy coat-derived platelet concentrates (PCs) suspended in either plasma (n = 354) or PAS II (n = 411) stored up to 5 days.

The mechanisms of Ara-C-induced apoptosis of resting B-chronic lymphocytic leukemia cells.

Background And Objectives: Cytarabine (Ara-C) is commonly used for the treatment of acute leukemia. Incorporation of Ara-C into DNA is a key event in the mechanism of killing of proliferating leukemic cells. Previously, we demonstrated that Ara-C was cytotoxic to proliferating but not to resting (G(O)) malignant cells from patients with acute leukemia.

Long-term follow-up of myeloablative allogeneic stem cell transplantation using Campath "in the bag" as T-cell depletion: the Leiden experience.

Graft-versus-host disease (GVHD) is a major cause of mortality and morbidity after allogeneic stem cell transplantation (alloSCT) but can be prevented by removing T-lymphocytes from the graft. Campath (anti-CD52) antibodies have been widely used in vivo for T-cell depletion following conventional and reduced intensity conditioning regimens. The use of Campath in vivo was associated with a significant reduction in GVHD but at the cost of impaired immune reconstitution.

Clinical relevance of quantitative varicella-zoster virus (VZV) DNA detection in plasma after stem cell transplantation.

Detection of Varicella-Zoster virus (VZV) DNA in plasma can facilitate the early recognition of complicated VZV-infection in immunocompromised hosts. The correlation of VZV-DNA in plasma with clinical presentations of VZV-infection and subsequent aciclovir treatment in allogeneic stem cell transplant (allo-SCT) recipients was studied. In 81 consecutive VZV-IgG positive allo-SCT recipients, VZV-DNA was measured at regular time points (1, 2 and 4 months) following allo-SCT and patient records were screened for VZV-related symptoms and aciclovir treatment.

Retrospective comparison of reduced-intensity conditioning and conventional high-dose conditioning for allogeneic hematopoietic stem cell transplantation using HLA-identical sibling donors in myelodysplastic syndromes.

In this multicenter retrospective study, the outcomes of 836 patients with myelodysplastic syndrome (MDS) who underwent transplantation with a human leukocyte antigen (HLA)-identical sibling donor were analyzed according to 2 types of conditioning: reduced-intensity conditioning (RIC) in 215 patients, and standard myeloablative (or high-dose) conditioning (SMC) in 621 patients. In multivariate analysis, the 3-year relapse rate was significantly increased after RIC (hazard ratio [HR], 1.64; 95% confidence interval [95% CI], 1.

Oral valganciclovir as pre-emptive therapy has similar efficacy on cytomegalovirus DNA load reduction as intravenous ganciclovir in allogeneic stem cell transplantation recipients.

The efficacy and safety of oral valganciclovir was compared to ganciclovir i.v. in pre-emptive treatment of cytomegalovirus (CMV) in T-cell-depleted allogeneic stem cell transplant (allo-SCT) recipients.

Efficacy and toxicity of gemtuzumab ozogamicin in patients with acute myeloid leukemia.

Gemtuzumab ozogamicin (GO) is a recently developed antibody-targeted chemotherapeutic agent and has been expected to be less toxic than conventional chemotherapy. We retrospectively evaluated the use of GO in 38 patients. Patients with acute myeloid leukemia (AML) at diagnosis and relapsed AML were treated with 6 and 9 mg/m(2) GO.

High dose chemotherapy and syngeneic stem cell transplantation in a patient with refractory rheumatoid arthritis: poor response associated with persistence of host autoantibodies and synovial abnormalities.

Background: Immunoablative therapy combined with haematopoietic stem cell transplantation (SCT) is a possible treatment for patients with severe rheumatoid arthritis (RA).

Case Report: A patient with rheumatoid factor positive, progressively erosive RA, refractive to treatment, was treated with high dose cyclophosphamide, followed by reinfusion of an unmanipulated peripheral blood graft derived from her identical twin sister. The clinical response was unsatisfactory, necessitating reinstitution of treatment with disease modifying antirheumatic drugs, which was associated with persistence of host serum autoantibodies and a cellular infiltrate in synovium, notably of plasma cells.

Allogeneic stem cell transplantation for patients with acute myeloid leukemia or myelodysplastic syndrome who have chromosome 5 and/or 7 abnormalities.

Background And Objectives: Chromosome 5 and/or 7 abnormalities are cytogenetic findings indicative of a poor prognosis in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The only potential cure for such patients is allogeneic stem cell transplantation (SCT). As data on allogeneic SCT in this context are limited we did a retrospective study of allogeneic SCT in patients with AML or MDS who had chromosome 5 and/or 7 abnormalities.

Cytokine-dependent proliferation of human CD34+ progenitor cells in the absence of serum is suppressed by their progeny's production of serine proteinases.

In this study, we demonstrate that the synthesis and release of serine proteinases by hematopoietic cells affects the in vitro proliferation of hematopoietic progenitor cells (HPCs) in response to proteins, including hematopoietic growth factors (HGFs), transferrin, insulin, and albumin in serum-free cultures. In serum-free cultures, bone marrow mononuclear cells or the CD34- progeny of the CD34+ cells were shown to release the serine proteinases human neutrophil elastase (HNE), cathepsin G (Cath G), and proteinase 3 (Pr3). In the absence of serum, we showed that HNE, Cath G, and Pr3 rapidly and dose-dependently degraded HGF and other proteins present in the medium, resulting in decreased proliferation of HPCs.

Primary allogeneic T-cell responses against mantle cell lymphoma antigen-presenting cells for adoptive immunotherapy after stem cell transplantation.

Purpose: In patients treated with allogeneic stem cell transplantation for advanced mantle cell lymphoma (MCL), complete sustained remissions have been observed illustrating susceptibility of MCL cells to a graft-versus-lymphoma effect. To potentiate this graft-versus-lymphoma effect, adoptive transfer of in vitro selected MCL-specific CTL can be an attractive approach. The lack of expression of costimulatory molecules on MCL cells hampers the generation of MCL-reactive T-cell responses.

Assessment of pre-treatment cognitive performance in adult bone marrow or haematopoietic stem cell transplantation patients: a comparative study.

The aim of this study was to examine cognitive performance in patients prior to bone marrow or haematopoietic stem cell transplantation (SCT) and in haematological patients who received non-myeloablative cancer therapies. A consecutive sample of 101 SCT patients and 82 haematological patients completed a neuropsychological test battery and five questionnaires assessing subjective cognitive complaints, psychological functioning, health-related quality of life and fatigue. Results were compared with normative data.