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Biomedical subjects

J L Byrne

Publications and source records attributed to J L Byrne.

At least 19 recordsLinked to original sources
PubMed2006

A study to determine the safety profile and maximum tolerated dose of micafungin (FK463) in patients undergoing haematopoietic stem cell transplantation.

This open-label, dose-escalation study assessed the maximum tolerated dose (MTD) of the new antifungal micafungin in patients undergoing haematopoietic stem cell transplantation (HSCT). Participants received 3, 4, 6 or 8 mg/kg/day micafungin intravenously from 7 days to a maximum of 28 days or until neutropaenia resolved. The MTD was defined as the highest dose not causing the same Grade 3 or 4 adverse event in three or more patients. All 36 participants received >/=8 days treatment for a median of 18 days (range: 8-28); 1 patient withdrew consent and a further 11 discontinued to receive another systemic antifungal agent for a suspected infection. No case of confirmed invasive fungal infection occurred. Adverse events were those expected for patients undergoing HSCT and showed no evidence of dose-related toxicity. Criteria for MTD were not met; no patient had a Grade 3 or 4 adverse event considered causally related to micafungin. Thus, the MTD of micafungin can be inferred to be 8 mg/kg/day or higher.

Adult↗
PubMed2005

Donor lymphocyte infusions can result in sustained remissions in patients with residual or relapsed lymphoid malignancy following allogeneic haemopoietic stem cell transplantation.

We treated 17 patients with refractory (n = 7) or relapsed lymphoid malignancy (n = 10) following allogeneic HSCT with donor lymphocyte infusions (DLI). Patients with low-grade disease received DLI alone (n = 7) or following radiotherapy (n = 1). Patients with aggressive disease (n = 9) received prior chemotherapy. Nine out of 15 patients receiving DLI from sibling donors responded after one (n = 6), two (n = 2) and three (n = 1) infusions. Both MUD recipients achieved CR after two and three DLI. In all, 10/17 patients achieved CR including 3/4 patients with chronic lymphatic leukaemia (CLL), 4/4 with mantle cell lymphoma (MCL), 3/4 with follicular NHL but 0/5 with aggressive NHL/Richters. The median CD3 cell dose to achieve CR for siblings was 2 x 10(7)/kg. One patient with CLL had a second transplant following DLI-induced aplasia and is in CR at 14 months giving a final CR rate of 64%. Grade II-IV acute GVHD developed in 45% and chronic GVHD in 8/9 evaluable patients. Of the 11 patients finally achieving CR, one patient with MCL relapsed at 18 months post-DLI but all others remain in remission with a median follow-up of 40 months (range 12-64 months). Low-grade NHL and MCL have a high response rate and sustained remissions following DLI. Aggressive disease responds poorly however, despite pre-DLI chemotherapy.

Adult↗
PubMed2005

Low dose erythropoietin is effective in reducing transfusion requirements following allogeneic HSCT.

Blood transfusions are frequently required for several weeks after allogeneic transplantation due to inadequate erythropoiesis and defective erythropoietin production. Because red cell transfusion is not without complications in this setting, we sought to avoid them using recombinant human erythropoietin (rhEpo) therapy. We treated 53 patients following allogeneic transplantation for haematological malignancy, using rhEpo at a dose of 10 000 units subcutaneously twice weekly. The median time of commencement of rhEpo was 61 days post-transplant (range 19-465 days), and the median haemoglobin (Hb) concentration was 9.4 g dL(-1) (range 7.0-10.7 g dL(-1)). Thirty patients responded to rhEpo and required no further transfusion with a median rise in Hb after 2 weeks of therapy of 1.5 g (0.7-4.1 g dL(-1)). Erythropoietin (Epo) was discontinued at a median of 5 weeks (range 2-36), when the median Hb concentration was 12.3 g dL(-1) (range 10.0-14.3 g dL(-1)). Those patients who failed to respond to rhEpo frequently had additional reasons for anaemia including cytomegalovirus (CMV) reactivation and treatment, major ABO incompatibility, disease relapse, graft rejection or other transplant-related complications. We conclude that a short course of rhEpo is an effective treatment for anaemia arising following allogeneic hematopoietic cell transplantation, and can avoid the need for transfusion in this setting.

Anemia↗
PubMed2004

Outbreaks of infectious diseases in stem cell transplant units: a silent cause of death for patients and transplant programmes.

Following the closure of the National Blood and Bone Marrow Transplant Unit in Dublin, because of an outbreak of vancomycin-resistant enterococcal infection, a survey was carried out by the EBMT to investigate the occurrence of outbreaks of infection in SCT units and the impact on patient morbidity, mortality and the administration of the transplant programme over a 10-year period from 1991 to 2001. A total of 13 centres reported 23 outbreaks of infection involving 231 patients: 10 bacterial, eight viral and five fungal outbreaks were reported and 56 deaths were attributed to infection. All fungal and bacterial deaths and the majority of viral deaths occurred in allograft recipients. In all outbreaks, the infection was reported to be hospital acquired and in all the viral, and half the bacterial infections, cross-infection was a major factor. All viral, four of 10 bacterial and three of five fungal outbreaks occurred in HEPA filtered rooms. A total of 12 SCT units reported a partial or total closure. The introduction of mandatory quality management systems such as JACIE should result in a change in attitude to 'incident reporting' and together with future surveys should reduce the incidence of infectious outbreaks in SCT units.

Aspergillosis↗
PubMed2003

Allogeneic transplantation for multiple myeloma: late relapse may occur as localised lytic lesion/plasmacytoma despite ongoing molecular remission.

Allogeneic SCT for myeloma may be curative for young patients, but its role remains controversial because of a reported high TRM in some series. Since 1991, we have performed 25 allografts for myeloma using fully matched sibling donors. Of the 18 evaluable patients, 13 achieved CR at a median time of 2.5 months post-transplant. The five patients who were not in CR when assessed at 3 months received a short course of alpha-interferon and four subsequently achieved CR with this approach at a median of 82 days. One patient who failed to respond to IFN went on to achieve CR after four doses of DLI therapy, thus giving an overall CR rate of 72%. Seven patients have relapsed at a median of 4.7 years post-transplant (range 1.38-7.7 years) including two patients who had received IFN therapy. In five of these cases, relapse has been as a localised area of bone disease or isolated plasmacytoma with no evidence of marrow involvement by trephine biopsy or molecular analysis. All patients with localised relapse were treated with local radiotherapy +/-DLI and four are currently disease free despite two patients having had further treatment for a second localised lesion. Six patients died of TRM (24%) and the OS at 8 years is currently 69% with an EFS of 26%. These results suggest that allogeneic SCT for myeloma can be carried out with an acceptable TRM and a high CR rate. However, late relapses as localised disease may be a frequent finding and may represent foci of myeloma not eradicated by the conditioning. The use of pretransplant MRI scanning and top-up radiotherapy to involved areas may be useful in preventing this type of relapse.

Adult↗
PubMed2003

High-dose melphalan followed by radical radiotherapy for the treatment of massive plasmacytoma of the chest wall.

We report three cases of massive chest wall plasmacytoma, each greater than 10 cm in diameter, without evidence of overt myeloma, whom we treated with a combination of VAD chemotherapy consolidated by high-dose melphalan and autologous peripheral blood stem cell transplantation and radical radiotherapy. All three patients completed all components of their therapy without experiencing any major side effects and one patient has had a durable remission. The other two patients have had disease progression but at sites other than the original tumour.

Antineoplastic Agents, Alkylating↗
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

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

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↗
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

Induction of remission after donor leucocyte infusion for the treatment of relapsed chronic idiopathic myelofibrosis following allogeneic transplantation: evidence for a 'graft vs. myelofibrosis' effect.

A 54-year-old man showed evidence of disease progression and a reduction in donor chimaerism by molecular microsatellite analysis 6 months after an allogeneic peripheral blood stem cell transplant for chronic idiopathic myelofibrosis. He was treated with a single infusion of donor leucocyte infusions (DLI), which led to the development of mild acute graft versus host disease (GVHD) and the rapid restoration of full donor haemopoiesis. This subsequently led to a progressive reduction in marrow fibrosis from grade IV to grade I over the following 6 months. We believe that this is the first report to provide clear evidence for the efficacy of DLI in this setting, which also provides evidence for the existence of a T-cell-mediated 'graft vs. myelofibrosis' effect similar to that seen against other haematological malignancies.

Chronic Disease↗
PubMed2000

Preliminary experience of allogeneic stem cell transplantation for lymphoproliferative disorders using BEAM-CAMPATH conditioning: an effective regimen with low procedure-related toxicity.

Autologous transplantation has an established role in the treatment of lymphoproliferative disorders, but allogeneic transplantation remains controversial. In an attempt to reduce the high procedure-related mortality reported with allografting in lymphoma, we have used BEAM (BCNU, etoposide, cytarabine and melphalan), a standard conditioning regimen for autologous transplantation. As BEAM may be insufficiently immunosuppressive to permit durable engraftment in the allogeneic setting, patients received additional pretransplant immunosuppression with the anti-CD52 antibody CAMPATH-1G from day -5 to day -1. Twelve patients (median age 46 years) underwent allogeneic transplantation for lymphoma (n = 11) or chronic lymphocytic leukaemia (n = 1) from HLA-identical (n = 9) or mismatched (n = 3) sibling donors. Cyclosporin A and methotrexate were used as graft-versus-host disease (GVHD) prophylaxis. One patient died of progressive lymphoma at day +12, the remaining 11 patients engrafted rapidly, with eight demonstrating full donor chimerism. One patient had an episode of rejection and received a further stem cell infusion with sustained recovery. Only one patient developed GVHD (grade I). The low incidence of acute GVHD may be in part related to persisting levels of in vivo CAMPATH-IG at the time of transplantation. Of 11 evaluable patients, nine achieved complete remission (CR), and a further patient achieved CR after donor lymphocyte infusion at 5 months. Our preliminary experience is that this regimen was well tolerated with a low risk of GVHD and appears no more toxic than a BEAM autograft. Further follow-up is required to see whether the low incidence of GVHD impacts upon relapse risk.

Adult↗