Immunoglobulin synthesis in myelodysplastic syndromes: normal B-cell and immunoregulatory T-cell functions

Peripheral blood cells from patients with myelodysplastic syndromes were assayed for B-cell and immunoregulatory T-cell functions. The B/T cell ratio in myelodysplastic patients (n = 11) was significantly higher than in controls (n = 12). These patients had a reduction in total T-cell (OKT3+) frequency and in T-cell subset (OKT4+/OKT8+) ratios. The response of patients' cells to both pokeweed mitogen (PWM) and phytohemagglutinin (PHA) was reduced, but patients' B cells responded normally to stimulation with Staphylococcus aureus Cowan (SAC). The levels of IgG and IgM detected in 7-day culture supernatants of PWM-stimulated patient and control cells were similar. Normal B-cell and immunoregulatory T-cell functions were subsequently demonstrated in allogeneic co-culture combinations of enriched T and B cells from patients and controls. The data presented indicate that the frequent infections of myelodysplastic patients are not causally related to impaired humoral mechanisms. The data also favor the possibility that the stem cell disorder in these syndromes is functionally expressed at a subsequent stage to the lymphoid differentiation pathway.     

Maintaining quality of life after palliative diversion for malignant ureteral obstruction

The records of 71 consecutive patients who underwent percutaneous nephrostomy for malignant ureteral obstruction were reviewed. The average post-nephrostomy survival time was seven months, of which 25% was spent in the hospital. When comparing these figures to older studies of open nephrostomy, the percutaneous procedure is associated with less morbidity and an increased percentage of time spent at home (75% compared to 36%). Long-term survival, however, is still poor, with only 25% of patients alive at one year. We suggest that the criteria previously adopted for open nephrostomy generally remain appropriate for patients being considered for percutaneous urinary diversion.     

Ibritumomab tiuxetan (Zevalin) combined with reduced-intensity conditioning and allogeneic stem-cell transplantation (SCT) in patients with chemorefractory non-Hodgkin's lymphoma

Allogeneic SCT is an effective therapy for lymphoma. Reduced-intensity conditioning (RIC) reduces non-relapse mortality (NRM) associated with myeloablative conditioning but relapse rates are high when performed in active disease. This study was designed to explore the safety and outcome of ibritumomab tiuxetan (Zevalin) combined with RIC in patients with advanced lymphoma. The study included 12 patients, median age 54 years (37-62), with a median of four prior treatments (2-6) and active disease documented on PET-CT. Zevalin 0.4 mCi/kg was given on day -14 and fludarabine combined with BU (n=6) or melphalan (n=6) was started on day -6. GVHD prevention was tapered 3 months after SCT to augment the graft-versus-lymphoma effect. All patients engrafted, a median of 14 days after SCT. Eighty-three percent achieved CR/PR. With a median follow-up of 21 months (12-37), 2-year PFS is 33%. Only three patients relapsed; cumulative incidence 25%. NRM was 42%, predominantly due to acute GVHD. Zevalin-RIC is feasible with consistent engraftment, acceptable organ toxicity, but high rates of acute GVHD. The low incidence of relapse suggests augmented anti-lymphoma effect. Zevalin-RIC merits further study. Better results may be achieved in patients earlier in disease course and with longer duration of immune-suppression.     

Comparison between two fludarabine-based reduced-intensity conditioning regimens before allogeneic hematopoietic stem-cell transplantation: fludarabine/melphalan is associated with higher incidence of acute graft-versus-host disease and non-relapse mortality and lower incidence of relapse than fludarabine/busulfan.

Reduced-intensity conditioning (RIC) regimens are increasingly used in allogeneic stem-cell transplantation (SCT). There are no data whether any of these regimens has advantage and in what setting. We retrospectively analyzed SCT outcomes in 151 patients given fludarabine-based RIC for various hematological malignancies; 72 conditioned with fludarabine and intravenous-busulfan (FB) and 79 with fludarabine and melphalan (FM). FM was more myelosuppressive. Grade III-IV organ toxicity occurred in 31 and 53% of FB and FM recipients (P=0.005) and acute graft-versus-host disease grade II-IV in 33 and 53%, respectively (P=0.01). Non-relapse mortality rate (NRM) was 16 and 40%, respectively (P=0.003). Active disease (HR 2.2, P=0.003) and prior autologous SCT (HR 1.7, P=0.04) predicted inferior overall survival (OS). Among patients transplanted in remission, OS was 72 and 36% after FB and FM, respectively (P=0.03) due to increased NRM with FM. Similarly, patients transplanted in active disease experienced higher NRM with FM, however lower relapse rates resulted in equivalent OS. In conclusion, there are marked differences in outcome between RIC regimens that are theoretically dose-equivalent. The FM regimen is more myelosuppressive and toxic but controls disease better. FB was associated with improved survival in patients transplanted in remission. These observations merit further study in prospective studies.     

A mimotope peptide-based vaccine against Schistosoma mansoni: synthesis and characterization

A panel of four mimotopes of the epitope recognized by the highly protective monoclonal antibody against Schistosoma mansoni (152-66-9B) was obtained by screening a solid-phase 8mer random peptide library. Three of the four mimotopes (p28, p29 and p30) were efficiently recognized in an in vitro radioimmunoassay by the monoclonal antibody and by sera from infected mice and one (p30) induced in vitro proliferation of primed lymphocytes. When the mimotopes were conjugated to bovine serum albumin (BSA) and the conjugates used to immunize C57BL/6J mice, only the p30-BSA-induced antibodies which were effective at complement-mediated killing of schistosomula. The level of complement-mediated killing obtained with the anti-p30 antibodies was comparable to that seen with serum from mice immunized with the protective 9B-antigen. Furthermore, following challenge infection of mimotope-BSA-immunized mice, a greater than 40% reduction in worm burden was observed in p30-BSA-immunized mice, a level comparable to that seen following immunization with the intact 9B-antigen. These results show that a simple synthetic peptide immunogen comprising an eight-amino acid mimotope of a conformational epitope on the 9B-antigen can induce protective immune responses against S. mansoni that are comparable to those obtained following immunization with the far more complex intact antigen. This mimotope may well represent a potential component of a synthetic peptide vaccine against S. mansoni. The inclusion of other B-cell- and T-cell-stimulating synthetic epitopes in such a vaccine, together with a more appropriate carrier, adjuvant and delivery systems may well result in a level of protection even greater than that seen with the single mimotope.     

Effect of ascorbate and alpha-tocopherol on resistance of beta-carotene to oxidation

The efficiency of ascorbate and α-tocopherol as stabilizers of β-carotene, which is widely used in complex therapy and prevention of some diseases accompanied by oxidative stress, was studied. The latency of induced β-carotene oxidation linearly depends on ascorbate concentration, while steady-state rate nonlinearly depends on the concentration of α-tocopherol, which attests to involvement of antioxidants in various stages of chain oxidation of β-carotene. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 7, pp. 59–62, July, 2000     

Color-coded Doppler sonography of the kidney blood vessels in childhood. II. Pathological findings

Pathologic flow profiles in renal arteries can be found in cardiovascular and renovascular disease. Obstructions of the left hart (aortic stenosis, hypoplastic left heart syndrome, coarctation of the aorta) cause diminished flow with low peak systolic velocities. In renal arteries of infants with leakage of the aortic "Windkessel" (persistent ductus arteriosus, truncus arteriosus communis etc.) a low diastolic amplitude can be found. Significant left-to-right shunts can lead to a diminished or even retrograde diastolic flow. In renal artery stenosis a high velocity jet with spectral broadening can be found in the region of the stenosis. Distal to the stenosis low blood flow velocities can be shown. In renal vein thrombosis the obstruction of the peripheral vessels cause a missing or even negative diastolic flow in the renal arteries, whereas venous blood flow is diminished or even missing. Kidney diseases with swelling of the organ (acute rejection of a transplanted kidney) can cause diminished, missing or even retrograde diastolic flow in the renal arteries dependent on the severity of the edema. These alterations can be used for the early diagnosis of acute rejection which offers the opportunity for early and efficient therapeutic management.     

Successful matched unrelated transplantation from a donor with idiopathic thrombocytopenic purpura (ITP)

The case of a 5 year old male is described who had acute myeloblastic leukaemia (AML M5) and was in third remission when he underwent an allogeneic T cell depleted bone marrow transplantation (BMT). The bone marrow was from an HLA matched unrelated donor (MUD) who suffered from chronic idiopathic thrombocytopenic purpura (ITP). In spite of this, the patient had rapid platelet engraftment post BMT (>50×10⁹ 1⁻¹ on day 20). He is now 12 months post-transplantation and has normal platelet counts, without any clinical or laboratory evidence of ITP. Autoimmune manifestations such as ITP occurring in bone marrow recipients following BMT have been previously reported. Furthermore, severe and protracted thrombocytopenia is a known complication following MUD transplantation and with its respective high risk of graftversus host disease (GVHD). In this case, no signs of ITP could be detected in the recipient despite the fact that the donor had ITP. Our data suggest that in the absence of an alternative choice, a person with ITP should be considered as an appropriate donor for transplantation.