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J M Cornish

Publications and source records attributed to J M Cornish.

33 records · Page 2Linked to original sources
PubMed1996

Unrelated donor bone marrow transplantation for children with relapsed acute lymphoblastic leukaemia in second complete remission.

Allogeneic sibling bone marrow transplantation (BMT) is the recommended treatment for relapsed childhood acute lymphoblastic leukaemia (ALL), but appropriate donors are only available in 30% of cases. Unfortunately, BMT from unrelated donors (UD) has been associated with high rates of severe graft-versus-host disease (GvHD) and transplant-related mortality (TRM). In an attempt to improve outcome in UD-BMT we have assessed the impact of T-cell depletion using CAMPATH-1 (anti-CD52) monoclonal antibodies in 50 consecutively referred patients with relapsed ALL in second remission. All were previously treated according to MRC protocols UKALL X and XI, and then given chemotherapy on MRC R1 from relapse until UD-BMT, 19 patients had relapsed on and 31 off therapy. Patients and donors were fully matched at HLA-A, -B, -DR and -DQ loci in 29 cases and mismatched in 21 (four mismatched for more than one antigen). Pre-transplant conditioning comprised CAMPATH-1G, cyclophosphamide and total body irradiation. Bone marrow was T-cell depleted in vitro using CAMPATH-1 antibodies. Additional GvHD prophylaxis consisted of cyclosporin A (42 cases), cyclosporin plus methotrexate (four) or none (four). 47 patients engrafted. The incidence of acute GvHD was very low: two patients with grade II disease in the matched group, four with grade II-IV in the mismatched group. Only four patients have chronic GvHD. The actuarial event-free survival (EFS) at 2 years is 53%, with no significant difference between the matched and mismatched group. Further leukaemic relapse was the most important cause of failure. These results are similar to the most favourable published reports for HLA-matched sibling BMT in relapsed ALL.

Acute Disease↗
PubMed1996

Bone marrow transplant indications for childhood leukemias: achieving a consensus. The EBMT Pediatric Diseases Working Party.

During the "2nd International Course on Bone Marrow Transplantation in Children" a multiple choice questionnaire on bone marrow transplant indications for children with acute leukemias was distributed with the aim of achieving a consensus. The answers obtained from the twenty representatives of fourteen European countries during the meeting were analyzed and assigned to one of the following groups: I. definitive indication: when more than 75% participants were in favour; II. acceptable indication: when 50% to 74% participants were in favour; III. requires further investigation: when 25% to 49% participants were in favour; IV. no indication: when less than 24% participants were in favour. In acute lymphoblastic leukemia the following circumstances were considered a definitive indication for allogeneic bone marrow transplant (BMT) from a matched sibling donor (MSD): infancy, "high risk" (HR) patients in 1st complete remission (CR1); CR2 patients after an early bone marrow relapse (defined as a relapse occurring up to six months after stopping therapy). Patients experiencing an early meningeal relapse and CR2 patients after a late relapse (defined as a relapse occurring later than six months after stopping therapy) were considered an acceptable indication. Further investigation was required in order to better define the role of BMT for patients experiencing an early isolated testicular relapse. If a MSD is not available, HR patients in CR1 and CR2 patients, after an early bone marrow relapse, were considered a definite indication for a matched unrelated donor (MUD). This latter group was considered an acceptable indication for a haploidentical BMT if a MUD was not available. Further investigation was required to better define the role of autologous bone marrow transplant (ABMT) for patients experiencing an early extramedullary relapse and for HR patients in CR1 all of whom lacked MSD's. In acute myeloblastic leukemia (AML), CR2 patients were considered a definitive indication and CR1 patients were considered an acceptable indication for BMT from a MSD. CR2 patients were considered a definitive indication for ABMT and CR1 patients an acceptable indication in cases lacking a MSD. AML was not considered an indication for MUD BMT.

Bone Marrow Transplantation↗
PubMed1995

Use of the Pastorex aspergillus antigen latex agglutination test for the diagnosis of invasive aspergillosis.

AIMS: To evaluate the Pastorex aspergillus antigen latex agglutination test for the diagnosis of invasive aspergillosis in patients undergoing liver or bone marrow transplantation. METHODS: Serum samples were taken at least twice weekly post-transplant and tested for Aspergillus antigen. Latex agglutination test results were compared with microbiological examination of respiratory, urine and bile specimens. Serum samples from liver transplant patients were also tested for antibodies to Aspergillus fumigatus by counter immunoelectrophoresis. RESULTS: Eight of the 91 patients studied developed invasive aspergillosis. Positive latex agglutination tests were obtained in eight of 187 (4.3%) serum samples from four of these eight patients. The other four patients with invasive aspergillosis gave consistently negative latex agglutination tests. A positive latex agglutination test was the first indication of invasive aspergillosis in two patients; these patients were already on amphotericin B. Positive latex agglutination tests were the only evidence of invasive aspergillosis in one patient who subsequently died of the infection. False positive latex agglutination tests were obtained in five of 83 (6%) patients with no evidence of invasive aspergillosis and misleading positive cultures seen in nine of 83 (10.8%). No antibodies were detected in three of four liver transplant patients with invasive aspergillosis. Conversely, antibodies were detected in 63 of 262 (24%) serum samples from 43 liver transplant patients with no evidence of invasive aspergillosis; one of these patients had an antibody titre of 1:2 on four separate occasions. CONCLUSIONS: The Pastorex aspergillus antigen latex agglutination test, when used alone, lacks sensitivity and specificity for the early diagnosis of invasive aspergillosis. A diagnosis was made in all patients with invasive aspergillosis when both culture and antigen tests were performed although using these criteria a false positive diagnosis would have been made in 13 of 83 (15.6%) patients. Microbiological and serial serological investigations for antigen should both be performed and the results considered in conjunction with radiological and clinical evidence.

Aspergillosis↗
PubMed1993

Immune reconstitution after BMT in children.

Serial assessment of peripheral blood T and B cell recovery and serum immunoglobulins was performed in 19 children for the first year following BMT and compared with normal values established from healthy children. Immunophenotypic analysis on bone marrow was performed in selected cases by Southern blotting of the immunoglobulin heavy chain (IgH) gene. We found no significant differences between T cell-replete or depleted allogeneic bone marrow transplants. Lymphocyte numbers were low until 9 months post-BMT. T cell numbers (CD2, CD3, CD5) were also low until 12 months but B cell numbers (CD19) became normal at 3 months. Both CD4+ and CD8+ T cell subsets were low post-BMT with depression of CD4+ greater and more prolonged than that of CD8+. No overshoot of CD8+ was seen. The principal effect of GVHD or its treatment was further depression of CD4+ cells but with no increase in CD8+; recovery of B cells was also delayed. Recovery of IgG was slow with only six of 11 children reaching an age-adjusted normal level by 1 year, whereas there was more rapid recovery of IgM and IgA. Several children had an increase in lymphocytes of immature appearance in their bone marrow at varying times post-BMT with increased cells of phenotype CD19+, CD10+, HLA-DR+ and TdT+. In each case Southern blotting showed a germline pattern of the IgH indicating a polyclonal early B cell regenerative population.

Adolescent↗
PubMed1993

Successful second unrelated donor BMT in a child with juvenile chronic myeloid leukaemia: documentation of chimaerism using the polymerase chain reaction.

A 3-year old child with juvenile chronic myeloid leukaemia received a T cell-depleted BMT from a male unrelated donor. There was early graft failure associated with increasing splenomegaly and hypersplenism. Splenectomy was performed 53 days post-transplant and was followed by autologous marrow recovery with return of leukaemia. A second unrelated donor BMT was performed 9 months later using T cell-replete marrow from a similarly matched female donor. Grade 2 GVHD involving the skin and gut responded to treatment with steroids. Chimaerism was assessed using Y-specific polymerase chain reaction (PCR) and microsatellites. Samples taken at the time of splenectomy showed no donor marrow engraftment but there was significant engraftment in the spleen. Following the second transplant, donor-type haematopoiesis was documented using a panel of microsatellite probes. The patient remains well 6 months after transplant. Splenectomy should be considered prior to transplant in patients with significant splenomegaly and hypersplenism. Partial chimaerism in the spleen, but not bone marrow, post-BMT, has not previously been documented. PCR technology is a useful and highly sensitive way to assess chimaerism post-BMT and is informative in sex-matched cases, whilst the small amount of material required is advantageous in paediatric patients.

Bone Marrow Transplantation↗
PubMed1991

Graft-versus-host disease in children receiving HLA-identical allogeneic bone marrow transplants with a low adjusted T lymphocyte dose.

Fourteen children with high risk leukaemia received allogeneic bone marrow transplants from HLA-identical MLC-compatible sibling donors. All bone marrows were T cell depleted and a T cell addback was prepared from the donor's peripheral blood so that the mean total number of CD3+ cells given was 2.6 (1.0-4.1) x 10(5)/kg recipient body weight. This was administered as a short infusion prior to the bone marrow. The children were conditioned with 1440 cGy fractionated total body irradiation and cyclophosphamide 120 mg/kg and were not given cyclosporin A or methotrexate. All patients engrafted and none showed late graft rejection. Acute graft-versus-host disease (GVHD) developed in nine of 14 children and required treatment with steroids. Two children with grade IV GVHD and one with grade I acute GVHD who subsequently developed severe chronic GVHD died. There have been two relapses (both fatal) and one death from cytomegalovirus pneumonitis. Survival is currently 57% (8/14) with a mean follow-up of 548 days (range 384-810). A high incidence of GVHD which was fatal in three patients can occur despite infusion of low T cell numbers in the absence of post-graft immunosuppression.

Adolescent↗
PubMed1990

Bone marrow processing on the Haemonetics V50 cell separator.

We have processed 27 bone marrow (BM) harvests using the Haemonetics V50 cell separator with a paediatric plasmapheresis set and programmed for lymphocyte collection. The mean starting volume of 843 mL was processed in 6-8 cycles to a buffy coat (BC) with a mean volume of 230 mL. The mean starting mononuclear cell (MNC) count was 1.22 x 10 8/kg recipient weight, and recovery was 92%. Clonogenic potential of the BC was assessed using CFU-GM assays and recovery was measured after cryopreservation or purging. On 4 occasions where major ABO incompatibility existed between donor and recipient, both BM and BC were consecutively diluted in compatible blood and processed twice. This achieved a calculated reduction in donor erythrocytes of 98%. The procedure was efficient and yielded a BC fraction suitable for cryopreservation and purging. Adequate stem-cells were retained as verified by CFU-GM assays and documentation of stable engraftment.

Adolescent↗
PubMed1990

Sputum induction as an aid to diagnosis of active cytomegalovirus infection following bone marrow transplantation.

An 8-year-old boy received an allogeneic bone marrow transplant (BMT) for relapsed T cell acute lymphoblastic leukaemia. Because he was seropositive for cytomegalovirus (CMV), serial virological specimens were taken throughout the transplant period, and included those obtained by sputum induction. Sixty-one days following BMT he became unwell, and was found to have mild tachypnoea and reduced oxygen saturations. All investigations were negative, apart from that obtained by sputum induction, which was positive for CMV. He received appropriate therapy with good response. We conclude that the technique of sputum induction can be applied to aid diagnosis of active CMV infection following BMT.

Bone Marrow Transplantation↗