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Biomedical subjects

N H Russell

Publications and source records attributed to N H Russell.

At least 37 records · Page 2Linked to original sources
PubMed2002

Nosocomial transmission of Saccharomyces cerevisiae in bone marrow transplant patients.

Saccharomyces cerevisiae is an unusual cause of clinical infection. We describe three bone marrow transplant patients on a haematology unit who developed possible invasive disease with the organism. Two patients died and both these patients appeared to have a related strain of S. cerevisiae. Screening for S. cerevisiae from throat and stool samples revealed four further patients who were carriers. Genotyping of the invasive and carriage strains demonstrated an indistinguishable strain from patients who had been on the unit at the same time, suggesting cross-infection.

Adult↗
PubMed2001

Quantitation of minimal disease levels in chronic lymphocytic leukemia using a sensitive flow cytometric assay improves the prediction of outcome and can be used to optimize therapy.

Previous studies have suggested that the level of residual disease at the end of therapy predicts outcome in chronic lymphocytic leukemia (CLL). However, available methods for detecting CLL cells are either insensitive or not routinely applicable. A flow cytometric assay was developed that can differentiate CLL cells from normal B cells on the basis of their CD19/CD5/CD20/CD79b expression. The assay is rapid and can detect one CLL cell in 10(4) to 10(5) leukocytes in all patients. We have compared this assay to conventional assessment in 104 patients treated with CAMPATH-1H and/or autologous transplant. During CAMPATH-1H therapy, circulating CLL cells were rapidly depleted in responding patients, but remained detectable in nonresponders. Patients with more than 0.01 x 10(9)/L circulating CLL cells always had significant (> 5%) marrow disease, and blood monitoring could be used to time marrow assessments. In 25 out of 104 patients achieving complete remission by National Cancer Institute (NCI) criteria, the detection of residual bone marrow disease at more than 0.05% of leukocytes in 6 out of 25 patients predicted significantly poorer event-free (P =.0001) and overall survival (P =.007). CLL cells are detectable at a median of 15.8 months (range, 5.5-41.8) posttreatment in 9 out of 18 evaluable patients with less than 0.05% CLL cells at end of treatment. All patients with detectable disease have progressively increasing disease levels on follow-up. The use of sensitive techniques, such as the flow assay described here, allow accurate quantitation of disease levels and provide an accurate method for guiding therapy and predicting outcome. These results suggest that the eradication of detectable disease may lead to improved survival and should be tested in future studies.

Adult↗
PubMed2001

Successful engraftment of a second transplant using non-myeloablative conditioning as treatment for graft failure following unrelated donor BMT.

A 32-year-old man with CML in second chronic phase developed primary graft failure following matched unrelated donor transplantation using cryopreserved marrow cells. He was successfully regrafted within 60 days from a second fully matched donor using a non-myeloablative conditioning regimen, with minimal toxicity. He remains in complete haematological, cytogenetic and molecular remission 2 years after second transplant. We believe that reduced intensity or 'mini-transplants' may be preferable for patients requiring second allografts which are usually associated with a high transplant-related mortality.

Adult↗
PubMed2001

Accelerated telomere shortening following allogeneic transplantation is independent of the cell source and occurs within the first year post transplant.

Telomere shortening has been documented in the blood cells of recipients of allogeneic bone marrow transplants compared with their donors. Allogeneic peripheral blood progenitor cells (PBPCs) have been increasingly used as an alternative to bone marrow. Their advantages include earlier engraftment and immune reconstitution following transplantation. We have measured telomere length of neutrophils and T cells in fully engrafted recipients of allogeneic bone marrow (n = 19) and allogeneic PBPC (n = 17) and also measured sequential telomere length in four patients after transplantation. Overall, significant telomere shortening occurred in recipients in neutrophils (0.3 kb, P < 0.001) and T cells (0.2 kb, P = 0.045). The data demonstrate that first, the degree of shortening was the same for BM and PBPC transplants and was not related to the time taken to engraft neutrophils and platelets and second, telomere shortening occurs in the first year post transplant without further shortening during the period of observation. These data suggest that the superiority of engraftment seen in PBPC transplants is independent of telomere shortening and other mechanisms such as homing or seeding may be more important.

Adolescent↗
PubMed2001

Naso-jejunal feeding in allogeneic bone marrow transplant recipients: results of a pilot study.

Patients undergoing allogeneic bone marrow transplants (BMT) are often malnourished prior to commencing the procedure. They face intensive treatment with often marked nutritional consequences. There is no consensus on the optimal nutritional management of these patients. Elective parenteral nutrition (PN), beginning pre-transplant irrespective of the patients nutritional status, or the use of "salvage" PN, beginning during the post-transplant period if the patient fails to maintain nutritional status with oral diet, have been used. Enteral nutrition may benefit the patient by maintaining nutritional support throughout the transplant period, avoiding the complications and expense of PN and possibly, by using specific diets, protecting the gastrointestinal tract from the effects of chemoradiation. However, naso-gastric feeding during a transplant is not without risks, including the safe insertion of a tube in patients with mucositis and pan-cytopenias, tube displacement by vomiting and aspiration from gastro-oesophageal reflux. An alternative approach is to use naso-jejunal (NJ) feeding tubes which are associated with less risk of loss due to vomiting and less risk of aspiration. We report a pilot study of 15 allogeneic BMT patients who had elective NJ feeding initiated before conditioning therapy irrespective of perceived nutritional compromise. This was well tolerated and feasible with a motivated nutritional team.

Bone Marrow Transplantation↗
PubMed2001

Progress in allogenic bone marrow and peripheral blood stem cell transplantation for multiple myeloma: a comparison between transplants performed 1983--93 and 1994--8 at European Group for Blood and Marrow Transplantation centres.

Out of 690 allogeneic matched sibling donor transplants for multiple myeloma reported to the European Group for Blood and Marrow Transplantation (EBMT) registry, 334 were performed during the period 1983-93 (all with bone marrow) and 356 during 1994-98 [223 with bone marrow and 133 with peripheral blood stem cells (PBSCs)]. The median overall survival was 10 months for patients transplanted during the earlier time period and 50 months for patients transplanted with hone marrow during the later period. The use of PBSCs was associated with earlier engraftment but no significant survival benefit compared to bone marrow transplants during the same time period. The improvement in survival since 1994 with the result of a significant reduction in transplant-related mortality, which was 38%, 21% and 25% at 6 months and 46%, 30% and 37% at 2 years during the earlier period, and the later period with bone marrow and PBSCs respectively. Reasons for the reduced transplant-related mortality appeared to be fewer deaths owing to bacterial and fungal infections and interstitial pneumonitis, in turn a result of earlier transplantation and less prior chemotherapy. Better supportive treatment and more frequent use of cytokines may also play a role. The improvement in survival was not directly related to the increased use of PBSCs.

Adult↗
PubMed2001

Microsatellite instability occurs in defined subsets of patients with acute myeloblastic leukaemia.

Using a sensitive fluorescent-polymerase chain reaction technique we looked for microsatellite instability (MSI) as functional evidence of mismatch repair defects in 71 cases of acute myeloblastic leukaemia (AML). MSI was assessed at 11 loci in matched leukaemic and constitutional DNA. Nine out of 71 patients (13%) were found to have MSI. Four of these patients had therapy-related leukaemia and the remaining five were all over the age of 60 years. There was a high incidence of adverse-risk cytogenetics in the patients with MSI, including abnormalities of chromosomes 5 and/or 7. Of the nine cases of t-AML included in this study, four (44%) had MSI. MSI was also seen in five of 51 cases (10%) over the age of 60 years but not in any cases under the age of 60 years with de novo AML. Using a sensitive assay, our results suggest that MSI occurs in two subgroups of patients with AML: those with t-AML and the elderly (> 60 years), but is rare in younger patients.

Adolescent↗
PubMed2001

Allogeneic transplantation using peripheral blood stem cells.

Over the past 9 years there has been a remarkable increase in the use of peripheral blood stem cells (PBSC) for allogeneic transplantation, primarily for matched sibling transplants but also increasingly for unrelated donor transplantation. In 1999 over 50% of all sibling transplants and over 25% of unrelated donor transplants reported to the European Group for Blood and Marrow Transplantation (EBMT) used PBSC. The major reason for this increasing use of PBSC relates to the rapid haemopoietic recovery seen which mirrors the advantages of using PBSC in autologous transplantation. This improvement in engraftment is a consequence of the larger number of stem cells that can be collected from G-CSF-mobilized peripheral blood compared to bone marrow. Evidence from randomized trials now shows a survival advantage for the use of PBSC in patients with advanced leukaemia. The reason for this improved survival appears primarily to relate to a reduced risk of transplant-related mortality and, possibly, a reduced risk of relapse, However, these randomized studies have also confirmed that there is an increased risk of chronic graft-versus-host disease associated with PBSC transplantation and further follow-up is required to determine the long-term impact on outcome.

Blood Cells↗
PubMed2001

Allogeneic stem-cell transplantation for lymphoproliferative disorders using BEAM-CAMPATH (+/- fludarabine) conditioning combined with post-transplant donor-lymphocyte infusion.

BACKGROUND: We report our updated experience of allogeneic transplantation in lympho-proliferative disorders using a reduced-intensity conditioning regimen combining BEAM (plus fludarabine in three cases) with pre-transplant CAMPATH. Post-transplant donor lymphocytes have been infused for persisting disease or relapse, and both chimerism and minimal residual disease have been monitored utilizing molecular techniques. METHODS: Thirty patients with median age 47.6 years underwent allogeneic transplantation for relapsed or high-risk lymphoproliferative disease using HLA-identical (sibling n = 25, unrelated n = 2) or one antigen mismatched sibling donors (n = 3). Twenty-one had NHL, three had HD and six had CLL/PLL. Stem-cell source was PBSC (n = 24), BM (n = 5) or both (n = 1) with a median CD34 dose of 4.5 x 10(6)/kg. GvHD prophylaxis was with CYA and MTX. RESULTS: Engraftment was prompt in the majority of patients, with a median of 15 days to both ANC > 0.5 and platelets > 20. There have been three transplant-related deaths secondary to viral pneumonitis or bacterial pneumonia. Seven patients developed Grade I-II acute GvHD post-transplant. Of 28 evaluable patients, 18 achieved a CR at assessment 2-3 months post-transplant and a further patient converted from PR to CR following DLI, to give an overall CR rate of 68%. Three patients had early progressive disease and six have relapsed from CR or progressed from PR (two of whom have achieved CR following DLI therapy). Overall survival is 67% and event-free survival 48% at 3 years. With a median follow-up of 1.3 years 57% of patients are currently alive and lymphoma-free. A molecular remission has been achieved in nine of 12 informative patients. DISCUSSION: These encouraging results show that this reduced-intensity conditioning regimen is effective, with a low-toxicity profile compared with conventional TBI-based conditioning, and certainly merits further evaluation in this setting.

Adolescent↗
PubMed2000

DNA repair mechanisms and acute myeloblastic leukemia.

DNA repair mechanisms play a vital role in maintaining genomic integrity. With the wealth of knowledge gained recently on these processes it is becoming clear that defects in repair proteins and proteins associated with the regulation of repair are connected to many different human diseases including cancer. This paper has aimed to review the four major DNA repair processes and in particular concentrate on their association with acute myeloblastic leukemia (AML).

Animals↗
PubMed2000

Fas receptor-Fas ligand system is independent of both CD34 status and chemosensitivity in acute myeloid leukemia.

OBJECTIVE: To determine whether the Fas receptor-Fas ligand (FasR-FasL) system, which triggers apoptosis in sensitive cells, is an important mechanism of cytotoxicity in acute myeloblastic leukemia (AML). MATERIALS AND METHODS: We investigated FasR expression in primary AML cells and its upregulation by tumor necrosis factor (TNF), as well as the apoptosis induced by anti-Fas antibody and the potential interaction between the FasR-FasL system and the cytotoxic drug daunorubicin (DNR). RESULTS: FasR was expressed on all 25 AML samples and three normal bone marrow harvests. The intensity of expression was variable (range 1. 6-2.1 in normal bone marrow CD34(+) cells and 1.5-5.1 in AML cells, median 2.4) and was related to the morphologic FAB classification, with the highest expression in FAB types M4 and M5 (range 1.6-5.1, median 3.2). No relationship was found between FasR expression and expression of the CD34 antigen. FasR was heterogeneously upregulated in all AML cells on treatment with TNF-alpha. The degree of FasR upregulation induced was found to be related to the FAB subtype, with the greatest response observed in immature FAB types M1, M2, and M6 (range 11.0-207.1%, median 48.7%). Apoptosis could be induced in all AML samples, but not in normal bone marrow CD34(+)ve cells, by the CH11 anti-FasR antibody, although the response was variable (range 4.1-37.6%, median 16.5%). The monocytic differentiated M4 and M5 AML cells exhibited the greatest sensitivity to Fas-mediated apoptosis (range 4.4-37.6, median 20.65%); however, no relationship was found between sensitivity to Fas-mediated apoptosis and FasR expression or CD34 positivity. Apoptosis in response to DNR was observed in all AML cases; however, sensitivity was heterogeneous and found to be unrelated to FasR expression or sensitivity to Fas-mediated apoptosis. The blocking anti-FasR antibody ZB4 blocked anti-FasR-mediated apoptosis but had no inhibitory effect on DNR-induced apoptosis in AML blasts. No cytotoxic synergistic effect was demonstrated when anti-FasR antibody was used in combination with DNR. CONCLUSION: In AML, DNR induces apoptosis through an Fas-independent pathway. However, the induction of apoptosis through the Fas pathway might be a novel and effective approach for leukemia immunotherapy, particularly because Fas-mediated apoptosis was noted in CD34(+) and CD34(-) cases.

Antigens, CD34↗
PubMed2000

The effect of the serotherapy regimen used and the marrow cell dose received on rejection, graft-versus-host disease and outcome following unrelated donor bone marrow transplantation for leukaemia.

Unrelated donor (UD) transplantation is the only potentially curative therapy for many leukaemia patients but is associated with a high mortality and morbidity. We sought to identify factors that could be optimised to improve outcome following UD transplantation in adults. Data was retrospectively analysed on 55 patients sequentially receiving UD transplants for CML or acute leukaemia (AL), all of whom received serotherapy for the prevention of GVHD and rejection. All patients received standard conditioning regimens. The first 28 patients transplanted also received combined pre- and post-transplant serotherapy with Campath 1G (days -5 to +5) and standard dose CsA plus MTX as GVHD prophylaxis (protocol 1). The subsequent 27 patients received a 5-day course of pre-transplant serotherapy alone either with ATG (CML patients) or Campath 1G (AL patients) on days -5 to -1 inclusive, with high-dose CSA plus MTX (protocol 2). The incidence of acute GVHD was low with no patient receiving either protocol developing > grade 2 disease. The use of protocol 2 and the administration of a bone marrow cell dose above the median (2.17 x 10(8)/kg) were the most important factors predicting engraftment (P = 0.03 and P = 0.001, respectively) but this only remained significant for cell dose in multivariate analysis (P = 0.03). Overall survival for the group was 45% at 3 years and was influenced by both age (P = 0.02) and disease status at transplantation (P = 0.001). Receiving a cell dose above the median was also associated with a trend towards better survival (P = 0.08), due primarily to a reduction in the TRM to 8.2% compared with 54.5% in those receiving a lower cell dose (P = 0.002). We conclude that pre-transplant serotherapy alone is highly effective at preventing acute GVHD following UD BMT and that additional post-transplant serotherapy does not confer any benefit. Furthermore, a high marrow cell dose infused has a major effect in reducing transplant related mortality following UD BMT.

Adolescent↗
PubMed2000

Rapid onset retinopathy in a diabetic patient following bone marrow transplantation.

We report a 38-year-old man who presented in 1998 with advanced multiple myeloma and newly diagnosed diabetes mellitus (DM). Subsequent BMT has been successful after conditioning with melphalan and total body irradiation, but significant ischaemic retinopathy has developed. Chemotherapeutic agents, total body irradiation, and DM are likely to have been co-factors in precipitating the rapid onset of retinopathy. Routine ophthalmic surveillance is recommended for all patients after BMT, particularly for those with additional risk factors for the development of retinopathy such as DM.

Adult↗