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R Childs

Publications and source records attributed to R Childs.

35 records · Page 2Linked to original sources
PubMed2000

CD34+ cell dose predicts relapse and survival after T-cell-depleted HLA-identical haematopoietic stem cell transplantation (HSCT) for haematological malignancies.

Seventy-eight patients with haematological malignancies, received T-cell-depleted stem cell transplants and cyclosporin followed by delayed add-back of donor lymphocytes to prevent leukaemia relapse. The source of stem cells was bone marrow in 50 patients and granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood in 28 patients. In univariate analysis, only the CD34+ cell dose (but not the stem cell source or the T lymphocyte dose) and disease status were predictive for transplant-related mortality, relapse and survival. Patients receiving >/= 3 x 106 CD34+ cells/kg had an overall actuarial survival of 68% compared with 52%, 35% and 10%, respectively, for cell doses of 2-2.99, 1-1.99 and < 1 x 106/kg. Multivariate analysis of risk factors for relapse identified disease risk and CD34+ cell dose as the only factors. Relapse was 62.5% in 38 patients at high risk of relapse vs. 25% for 40 patients at intermediate or low risk. CD34+ cell doses of >/= 3 x 106/kg were associated with a 13.5% relapse vs. 48% for recipients of lower doses. This favourable effect of CD34+ cell dose on relapse was apparent in both high- and intermediate- plus low-risk groups. Our results support the potential benefit of a high stem cell dose in lowering transplant-related mortality (TRM) and in reducing relapse after allogeneic marrow or blood stem cell transplants.

Adult↗
PubMed1999

Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: full donor T-cell chimerism precedes alloimmune responses.

Nonmyeloablative allogeneic stem cell transplantation has recently been explored as a safer alternative to conventional high-dose transplant regimens. Although a high incidence of mixed chimerism after nonmyeloablative procedures has been reported, the exact kinetics of engrafting donor cells in specific cellular lineages has yet to be defined. We investigated lineage-specific chimerism in 15 patients receiving an allogeneic peripheral blood stem cell (PBSC) transplant from an HLA-identical (n = 14) or a 5/6 antigen-matched sibling donor after a preparative regimen of cyclophosphamide and fludarabine. Donor chimerism was assessed weekly in T lymphocytes and myeloid cells by polymerase chain reaction (PCR) of minisatellite regions. Eight patients survived between 121 to 409 days after transplant. Ten of 14 patients surviving more than 30 days (71.4%) had delayed disease regression consistent with a graft-versus-malignancy (GVM) effect. One patient rejected the transplant with subsequent recovery of autologous hematopoiesis. Hematological recovery was rapid (median, 11 days to >/=500 neutrophils/microL) and was initially predominantly recipient in origin. Donor myeloid chimerism gradually supplanted recipient hematopoiesis and became fully donor in all survivors by 200 days after transplantation. In contrast, T-cell engraftment was more rapid, with full chimerism in 7 patients by day 30 and in 6 further patients by day 200 after cyclosporine withdrawal and donor lymphocyte infusion. Full donor T-cell engraftment preceded donor myeloid engraftment, acute graft-versus-host disease, and disease regression, consistent with a requirement for 100% donor T-cell chimerism for full expression of the alloresponse. These results emphasize the importance of lineage-specific chimerism analysis to successfully manipulate engraftment after nonmyeloablative allogeneic PBSC transplantation.

Adult↗
PubMed1999

The impact of knowledge and opinions on the implementation of public policies for mentally ill offenders.

New legislation may not always have its intended effect. Agencies targeted by the legislation must be aware of it, understand its demands, develop procedures to insure implementation, and monitor compliance. This paper reports a study of the extent to which several new state statutes impacted policy, procedures, and services for mentally ill offenders in a large urban Texas county. Key informant-interviews, document reviews and surveys of knowledge and opinions were used to assess implementation, understanding, and acceptance of these new statutes. Results were reported to local constituencies, and used to shape recommendations for local action. Following the study, the community formed a council that has made specific improvements in the system.

Commitment of Persons with Psychiatric Disorders↗
PubMed1999

High-dose corticosteroid therapy for diffuse alveolar hemorrhage in allogeneic bone marrow stem cell transplant recipients.

In a series of 74 patients with hematological malignancies undergoing allogeneic bone marrow or peri- pheral blood stem cell transplants from an HLA-identical sibling donor, four developed diffuse alveolar hemorrhage (DAH) between days 0 and 23 post transplant. Diagnosis was made by the radiographic finding of diffuse bilateral lung opacities, and bloody lavage fluid on bronchoscopy. Two patients required mechanical ventilatory support. They were treated with methylprednisolone 0.25-1.5 g/day for at least 4 days with slow tapering thereafter. All patients showed an immediate response and two became long-term survivors with normal respiratory function. Two had a relapse of DAH, developed acute respiratory distress syndrome (ARDS) and died with multi-organ failure. Risk factors for DAH were one or more courses of intensive chemotherapy pretransplant vs no treatment or low-dose chemotherapy (4/4 DAH vs 23/70 no DAH; P = 0.015), and second transplants (2/2 DAH vs 1/70 with no DAH; P = 0.006). These results indicate that DAH is life-threatening but is potentially reversible by prompt treatment with high doses of steroids.

Adult↗
PubMed1999

Human G-CSF-mobilized CD34-positive peripheral blood progenitor cells can stimulate allogeneic T-cell responses: implications for graft rejection in mismatched transplantation.

To investigate mechanisms of stem cell graft rejection we studied the allo-stimulatory potential of G-CSF mobilized peripheral blood progenitor cells (PBPC). CD34+ cells were purified (>95%) in a two-step procedure using immunoaffinity columns for CD34 selection and T-depletion. The capacity of CD34+ cells to stimulate allogeneic T-cell responses was compared with other cells from the same individual. CD34+ cells induced potent proliferative responses at stimulator:responder ratios of 1:20, but were approximately 50-fold less efficient compared to dendritic cells. Furthermore, CD34+ cells primed responses from partially matched allogeneic T cells in bulk cultures. Dual-colour flow cytometry showed that the co-stimulatory molecules B7.1, CD40 and ICAM-1 were absent on resting CD34-positive progenitor cells, but were induced during incubation with allogeneic lymphocytes due to a cytokine-mediated effect. Up-regulation of accessory molecules on CD34+ cells was reproduced by incubation with interferon-gamma or GM-CSF which enhanced the allo-stimulatory activity of CD34+ cells. Blocking studies with inhibitory antibodies suggested co-stimulatory functions for B7.2, ICAM-3, CD40 and LFA-3. CD34+ cells were more efficient in inducing allogeneic T-cell responses when compared to the unprocessed leukapheresis products. The reduced allo-stimulatory ability of G-CSF mobilized PBPC could be explained by the presence of CD3+ 4+ and CD3+ 8+ lymphocytes with suppressor activity. We conclude that current methods of stem cell selection for transplantation do not avoid allosensitization of the recipient and that further graft manipulation with add-back of lymphocytes or selection of subsets of CD34+ cells with reduced allo-stimulatory ability may reduce graft rejection.

Antibodies, Blocking↗
PubMed1999

Molecular remission of chronic myeloid leukaemia following a non-myeloablative allogeneic peripheral blood stem cell transplant: in vivo and in vitro evidence for a graft-versus-leukaemia effect.

Two patients with chronic myeloid leukaemia (CML) received a non-myeloablative preparative regimen of cyclophosphamide and fludarabine, followed by an unmanipulated, G-CSF-mobilized, peripheral blood stem cell transplant from an HLA-identical sibling. Chimaerism, evaluated in myeloid and T-lymphoid lineages by PCR of minisatellite variable regions, showed day 14 post-transplant haemopoietic recovery to be 90% autologous in both patients. On day 30 the bone marrow showed only 1/20 and 2/18 donor metaphases. By day 100 post transplant both had 100% donor myeloid and lymphoid lineages as assessed by karyotype and minisatellite chimaerism analysis. They subsequently became RT-PCR negative for BCR-ABL. Both survive 7 and 14 months post transplant in molecular remission of CML. In one, donor T cells, stimulated with pre-transplant CML cells, induced 30-50% inhibition of pre-transplant leukaemic CFU-GM, but did not inhibit CFU-GM in the day 60 marrow (46% Ph-negative recipient, 54% donor). These results show that a non-myeloablative allotransplant can induce molecular remissions of CML through a graft-versus-leukaemia effect.

Adult↗
PubMed1998

High incidence of adeno- and polyomavirus-induced hemorrhagic cystitis in bone marrow allotransplantation for hematological malignancy following T cell depletion and cyclosporine.

Nine of 56 (20% actuarial) patients receiving a T cell-depleted, HLA-identical sibling BMT for hematological malignancy developed hemorrhagic cystitis (HC) 15-368 days post BMT. Hematuria was severe and prolonged (median duration 18 days). In eight patients (89%), a viral etiology was confirmed (four adenovirus, four polyomavirus). HC was associated with significant morbidity, with all patients requiring continuous bladder irrigation and transfusion support for blood loss and thrombocytopenia. HC occurring before day 100 was significantly associated with a reduction in long-term survival: 1/7 (14.3%) patients developing HC before day 100 became long-term survivors vs 21/49 (42.8%) without HC by day 100 (P = 0.034). In univariate analysis, HC was associated with a diagnosis of multiple myeloma (P = 0.02). There was a trend towards a higher incidence of HC in patients reactivating cytomegalovirus (CMV) compared with those remaining CMV negative (18.4 vs 5.5% respectively, P = 0.17). HC was not associated with graft-versus-host disease, or with the transplant dose of CD34+ progenitors or CD3+ cells, patient age or sex. Life-threatening, viral-induced HC and the unusually high incidence of adenovirus-induced HC may have been caused by immune deficiency associated with T cell depletion in this series.

Adenoviridae Infections↗
PubMed1983

Monoclonal antibody against a cross-reactive idiotypic determinant found on human autoantibodies with anti-I and -i specificities.

A monoclonal antibody has been raised against a cross-reactive idiotypic determinant expressed on human autoantibodies with anti-I and -i specificities. The McAb is directed against a conformational epitope requiring interaction of H- and L-chains for maximal expression. This epitope was strongly expressed on the monoclonal protein of one out of 100 patients with paraproteinaemia and the peripheral blood lymphocytes of one out of 50 cases of B-cell leukaemia. A small amount of the epitope is detectable among immunoglobulins in normal serum.

Agglutinins↗
PubMed1977

An immunoglobulin heavy chain variable region (VH) marker associated with cross-reactive idiotypes in man.

The VH specificities of two rabbit antisera raised against the H chains of two human IgM cold agglutinins were studied with the aid of proteins on which the VH sequence data are available. They were found to recognize a new VH antigen (VHMar), which may represent a subgroup of VHI. This antigen is found on anti-Ii antibodies which have cross-reactive idiotypes. It is moderately well-expressed in normal gamma globulin and strongly expressed on 8% of unselected myeloma and macroglobulinaemia proteins. There is evidence to suggest that a proportion of the cross-reactive idiotypes among the anti-Ii antibodies involve this VH antigen.

Agglutinins↗
PubMed1976

Kappa chain (V kappa III) subgroup-related activity in an idiotypic anti-cold agglutinin serum.

In a search for H- or L-chain-related cross-idiotypic specificity among human anti-I and anti-i cold agglutinins, two idiotypic antisera raised against the IgMkappa cold agglutinin Da were tested for their binding activity to isolated cold agglutinin H and L chains. Negligible H-chain binding activity was found, but there was high-titre L-chain binding activity in one of the antisera. This was an unsuspected VkappaIII subgroup activity which enabled the classification of VkappaIII proteins into three subgroups. The kappa chains of five out of six anti-I and anti-i cold agglutinins belonged to the antigenically most active VkappaIII subgroup. Absorption of the idiotypic antiserum with a Bence Jones protein of this latter subgroup did not appreciably alter the precipitating cross-idiotypic activity of the antiserum when tested with intect cold agglutinins. However, these studies do not rule out the possible existence of a VkappaIII subgroup-associated conformational antigen in an intact Fab region, which is seen as a 'cross idiotypic' antigen by heterologous (rabbit anti-human) antisera.

Agglutinins↗
PubMed1975

The blood group I and i antigens of amniotic fluid. I. Association of I and i antigens with blood group A, B and H antigens.

Human amniotic fluid has been shown to contain blood group i as well as I antigens. Crude extracts of amniotic fluids at 16-23 weeks of gestation were in general more active than those obtained at term. A pool of amniotic fluids which had A, B, H as well as I and i activity was fractionated with an insolubilized anti-I (Group 3 type) immunoadsorbent column. There was evidence for the occurrence of I and i determinants on macromolecules carrying A, B and H determinants, for the fraction specifically retained by the column was enriched by 50-60-fold in I and i activity and by at least 10-fold in A, B and H activity. In the fraction not retained by the column there remained the bulk of the A, B, H activity in addition to I activity of Group I type which is known to be distinct from the Group 3 determinant. With the aid of specific immunochemical fractionation procedures, human amniotic fluid should prove useful in structural studies of the several I and i determinants and of their relationship to other blood group determinants.

ABO Blood-Group System↗