Risk factors for capillary leakage syndrome after bone marrow transplantation

 Age, hematopoietic growth factors, cyclosporin A, mode of bone marrow transplantation (BMT) (autologous, allogeneic-related, unrelated), and underlying disease were assessed as potential risk factors for capillary leakage syndrome (CLS) in 96 patients after BMT. CLS was defined as unexplained weight gain of >3% within 24 h and nonresponsiveness to furosemide. CLS occurred in 9/21 patients after unrelated compared with 2/33 after allogeneic-related BMT (p=0.0017) for hematopoietic disorders (n=54) and in 6/7 patients after allogeneic-related compared with 3/35 after autologous BMT (p=0.0001) for solid tumors (n=42). Hematopoietic growth factors and cyclosporin A were no signficant risk factors on their own. We conclude that unrelated BMTs or high-intensity conditioning regimens used in combination with allogeneic-related BMT are the main risk factors for CLS. Received: 6 January 1997 / Accepted: 10 March 1997     

Primary metastatic (stage IV) Ewing tumor: Survival analysis of 171 patients from the EICESS studies

Background: In the multicenter European Intergroup Cooperative Ewing's Sarcoma Studies, localized Ewing tumors of bone were treated by combination chemotherapy with surgery and/or radiotherapy. Patients with primary metastases (pm-pts) were treated in high risk protocols.Patients and methods: One hundred seventy-seven pm-pts were registered from January 1990 to December 1995, 171 were evaluable for survival analyses. Thirty-six pm-pts received myeloablative megatherapy with stem cell rescue following conventional treatment. Bilateral whole lung irradiation (WLI) was administered in 57 pm-pts with pulmonary involvement. Event-free survival (EFS) rates were estimated by Kaplan–Meier analysis. Prognostic factors were identified by log-rank statistics, Cox procedures and logistic regression.Results: Eighty-nine deaths were recorded by 1 February 1997, EFS four years after diagnosis for all 171 pm-pts was 0.27. EFS for isolated lung metastases was 0.34, for bone/bone marrow (BM) metastases, 0.28, and for combined lung plus bone/BM metastases, 0.14 (P < 0.005). WLI improved outcome in case of isolated pulmonary involvement (0.40 vs. 0.19, P < 0.05). In pm-pts with combined pulmonary/skeletal metastases, intensification by megatherapy and/or WLI improved EFS from 0.00 to 0.27 (P = 0.0001).Conclusions: EFS four years after diagnosis in patients with disseminated Ewing tumors is 0.27. Whole lung irradiation and megatherapy improve outcome in subgroups of patients with disseminated Ewing disease.     

Effect of cloned inhibitor-resistant TEM beta-lactamases on the susceptibility of Haemophilus influenzae to amoxicillin/clavulanate

OBJECTIVES: To determine the effect of cloned inhibitor-resistant TEM beta-lactamases (IRTs) on the susceptibility of Haemophilus influenzae to amoxicillin/clavulanate. METHODS: IRT-2, -4 and -5 genes with various promoters were cloned into control strains of H. influenzae and the amoxicillin/clavulanate MICs were measured using Etests. RESULTS: IRT enzymes were able to raise the amoxicillin/clavulanate MICs to between 0.38/0.19 and 4.0/2.0 mg/L depending on the IRT and promoter genotype, compared with MICs of 0.19/0.09 to 0.5/0.25 mg/L for the corresponding strains with TEM-1. Strains with an IRT and altered penicillin-binding proteins had amoxicillin/clavulanate MICs as high as 8.0/4.0 mg/L. CONCLUSIONS: Cloned IRT enzymes in H. influenzae raise the amoxicillin/clavulanate MICs to an extent comparable to naturally occurring strains with decreased amoxicillin/clavulanate susceptibility.     

The T-cell CD2 determinant mediates inhibition of erythropoiesis by the lymphokine cascade

We examined the role of the T-cell antigen CD2 in the regulation of erythropoiesis by the lymphokine cascade. T-cell interleukin-2 (IL-2) receptors (p55) were induced via triggering of the antigen receptor- associated CD3 epitope. Before CD3 triggering T cells were preincubated with a CD2-blocking (Leu-5b) or isotype control antibody. T-cell pellets were employed during incubation to facilitate interaction between T-cell LFA-3 and CD2. CD2 blockade caused a 66% to 79% inhibition of p55 expression after three to six days of culture with IL- 2. Next we assessed the effect of CD2 blockade on IL-2. Next we assessed the effect of CD2 blockade on IL-2-induced inhibition of BFU-E in autologous cocultures containing CD3-triggered T cells. IL-2 caused a dose-dependent inhibition (52% to 92%) of BFU-E in the presence but not in the absence of CD3-triggered T cells. T-cell CD2 blockade prior to CD3 triggering caused a 65% to 87% abrogation of IL-2-induced inhibition of BFU-E at 10 to 10(2) U/mL IL-2. Preincubation of CD3- triggered T cells with isotype control antibody had no effect on IL-2- induced erythroid inhibition. Day 3 supernatants from CD3-triggered T cells or CD2-blocked, CD3-triggered T cells established in the presence of IL-2 were next assessed for modulation of BFU-E. CD3-triggered T- cell supernatants caused a 77% +/- 9% inhibition of BFU-E. Blockade of CD2 caused a 95% abrogation of T-cell-mediated BFU-E inhibition. In addition, CD2 blockade reduced interferon-gamma (IF gamma) release (84 to 128 U/mL) from CD3-triggered T cells by 81% at day 3 of culture. In control experiments, the addition of IF gamma-neutralizing monoclonal antibody to CD3-triggered T-cell supernatant established in the presence of IL-2 caused 75% abrogation of IL-2 inhibition of BFU-E. We conclude that blockade of the CD2 T-cell determinant induces down modulation of (a) T-cell p55 IL-2 receptor expression, (b) IL-2-induced inhibition of BFU-E, and (c) IL-2-induced marrow T-cell IF gamma release. These data suggest that the T-cell CD2 determinant can exert a regulatory effect on the control of erythropoiesis by the lymphokine cascade.     

Allogeneic and autologous stem-cell transplantation in advanced Ewing tumors

Background:An update of results from the High Risk Protocol ofthe Meta-EICESS Study, conducted at the Pediatric Stem-Cell Transplant Centersof Düsseldorf and Vienna. In order to evaluate a possible therapeuticbenefit after allogeneic SCT in patients with advanced Ewing tumors (AET), wecompared outcome after autologous and allogeneic stem-cell transplantation(SCT). Patients and methods:We analyzed 36 patients treated with themyeloablative Hyper-ME protocol (hyperfractionated total body irradiation,melphalan, etoposide ± carboplatin) between November 1986 and December1994. Minimal follow-up for all patients was five years. All patientsunderwent remission induction chemotherapy and local treatment beforemyeloablative therapy. Seventeen of thirty-six patients had multifocal primaryEwing's tumor, eighteen of thirty-six had early, multiple or multifocalrelapse, one of thirty-six patients had unifocal late relapse. Twenty-six ofthirty-six were treated with autologous and ten of thirty-six with allogeneichematopoetic stem cells. We analyzed the following risk factors, that couldpossibly influence the event-free survival (EFS): number of involved bones,degree of remission at time of SCT, type of graft, indication for SCT, bonemarrow infiltration, bone with concomitant lung disease, age at time ofdiagnosis, pelvic involvement, involved compartment radiation,histopathological diagnosis. Results:EFS for the 36 patients was 0.24 (0.21) ± 0.07.Eighteen of thirty-six patients suffered relapse or died of disease, nine ofthirty-six died of treatment related toxicity (DOC). Nine of thirty-sixpatients are alive in CR. Age 17 years at initial diagnosis (P< 0.005) significantly deteriorated outcome. According to the type ofgraft, EFS was 0.25 ± 0.08 after autologous and 0.20 ± 0.13after allogeneic SCT. Incidence of DOC was more than twice as high afterallogeneic (40%) compared to autologous (19%) SCT, even thoughthe difference did not reach significance (P = 0.08, Fisher's exacttest). Conclusions:Because of the rather short observation period,secondary malignant neoplasm (SMN) may complicate the future clinical courseof some of our patients who are currently viewed as event-free survivors. EFSin AET is not improved by allogeneic SCT due to a higher complication rate.The patient group was to small to analyze for a possiblegraft-versus-tumor effect.     

ICOS: a new costimulatory ligand/receptor pair and its role in T-cell activion

The inducible costimulator (ICOS) is a new member of the CD28/CD152 receptor family that regulates T-cell activation and function. ICOS binds to a specific ligand on antigen-presenting cells (APC) and cells of the peripheral tissue different from the CD28/CD152 ligands CD80 and CD86. ICOS-L can be induced by inflammatory stimuli in peripheral tissue and on some APC, including monocytes, but is downregulated in B-cell and myeloid leukemia. ICOS-L delivers distinct signals to T cells, presumably important for the maintenance of certain types of immune response, providing the rationale for the development of new therapeutic strategies for the treatment of diseases.     

Oncology patients in a pediatric intensive care unit--a 7-year experience

BACKGROUND: As a result of improved therapeutic and diagnostic modalities the survival rate of children with neoplastic disease has increased dramatically. The consequences of these scientific advances have led to increased malignancy-related critical complications requiring the expertise of intensive care practitioners. PATIENTS: From all children admitted to the pediatric intensive care unit (PICU) of the Martin-Luther University Halle those with hematologic-oncologic condition were evaluated. RESULTS: From 4068 PICU admissions 196 (4.8%) oncologic patients were identified. Most of them were admitted for postoperative care, monitoring or intervention. 24 patients were admitted because of severe disease or treatment related complications. 14 out of 24 (58%) patients died on PICU. Mortality was significant higher in a subgroup requiring mechanical ventilation or suffering from sepsis. All patients but two with multi-organ system failure (> or = 2 organs) died. CONCLUSIONS: Children with neoplastic disease can benefit from pediatric intensive care unit (PICU) support. Successful treatment of life-threatening complications requires a close cooperation of pediatric oncology and PICU. Further studies are necessary to improve therapeutic strategies in oncology patients requiring PICU admission.     

Unusual presentation of central nervous system relapse with oculomotor nerve palsy in a case of CD56-positive acute myeloid leukemia following allogeneic stem cell transplantation

Allogeneic stem cell transplantation (allo-SCT) plays an important role in the treatment of infants and children with acute myelogenous leukemia (AML). Leukemic relapse after allo-SCT is responsible for a high rate of treatment failure. Extra-medullary relapse (EMR), without involvement of bone marrow, is rare compared to medullary relapse. CD56, the neural cell adhesion molecule, may contribute to the higher frequency of CNS relapse in CD56-positive AML. We observed an isolated EMR on the oculomotor nerve of a 17-month-old girl 12 weeks after cord blood transplantation (CBT), who was transplanted because of CD56-positive AML. Diagnosis of relapse was suspected clinically and confirmed by magnetic resonance imaging (MRI), and fluorescence-activated cell sorter (FACS) and chimerism analysis of cerebrospinal fluid (CSF). Therapy consisted of intra-thecal chemotherapy, CNS irradiation, and systemic immunomodulation by cyclosporin A (CsA) and basiliximab withdrawal. Twenty-one months after relapse, the patient shows full remission of symptoms and previously described oculomotor nerve infiltration.