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Biomedical subjects

S R McCann

Publications and source records attributed to S R McCann.

At least 55 records · Page 3Linked to original sources
PubMed1994

Infection of donor lymphocytes with human T lymphotrophic virus type 1 (HTLV-I) following allogeneic bone marrow transplantation for HTLV-I positive adult T-cell leukaemia.

Human T lymphotrophic virus type 1 (HTLV-I) associated leukaemia has a poor prognosis even with chemotherapy. We describe a patient with adult T-cell leukaemia treated with allogeneic bone marrow transplantation from an HTLV-I negative identical sibling donor. During follow-up after bone marrow transplantation, HTLV-I could be repeatedly isolated inspite of anti-viral prophylaxis. The patient died of an acute encephalitis and HTLV-I could be detected in autopsy material from the brain. By a PCR-based technique using short tandem repeats (STRs) it was shown that the patient's haemopoiesis was of donor origin. This shows the infection of donor cells in vivo by an aetiological agent which has been implicated in the leukaemogenic process for adult T-cell leukaemia.

Bone Marrow↗
PubMed1994

Successful bone marrow transplant for Fanconi anaemia in transformation.

We present a patient who was diagnosed as suffering from Fanconi anaemia at the age of 36 years. At the time of diagnosis his bone marrow showed features of pre-leukaemic transformation. He received an allogeneic bone marrow transplant (BMT) from his HLA-identical sibling. The post-transplant course was unremarkable with evidence of trilineage engraftment at day +32 and no acute or chronic GVHD. He is well with sustained engraftment and no haematological evidence of Fanconi anaemia 18 months post-transplant.

Adult↗
PubMed1994

Retinal microvascular changes following bone marrow transplantation: the role of cyclosporine.

Three patients complained of deteriorating vision 16, 20 and 29 weeks following bone marrow transplantation (BMT) while receiving cyclosporine (CsA). Opthalmic examination revealed a marked microvascular retinopathy with multiple cotton-wool spots, macular stars and retinal oedema. These appearances could not be accounted for by the mild to moderate hypertension in two cases, the third patient being normotensive. Two of the patients had received total body irradiation (TBI) and cyclophosphamide (CY) as conditioning therapy for BMT as well as previous cranial irradiation for acute lymphoblastic leukaemia; one case with chronic myeloid leukaemia was conditioned with busulphan and CY. Withdrawal of CsA in two patients and reduction of dose in the third led to complete resolution of retinopathy and restoration of visual function. Previous reports have documented ischaemic fundus lesion in BMT recipients treated with CsA and TBI. Our findings suggest that CsA in association with busulphan can produce a similar retinopathy.

Adolescent↗
PubMed1994

Graft rejection and second bone marrow transplants for acquired aplastic anaemia: a report from the Aplastic Anaemia Working Party of the European Bone Marrow Transplant Group.

Six hundred and eighteen patients with acquired aplastic anaemia grafted from an HLA-identical sibling donor between 1976 and 1990 in eight European centres were reported to the Working Party for Severe Aplastic Anaemia (SAA) Registry and were evaluable for analysis of the incidence of graft failure/rejection and the outcome of second bone marrow transplants (BMT). The number of patients experiencing graft rejection declined significantly over the study period from 32% to 8% (p < 0.0001). This coincided with the introduction of cyclosporine to the conditioning regimen for BMT. The graft rejection rate in the post-hepatitis SAA group was significantly lower than in the group with idiopathic SAA (4% vs 20%) (p = 0.001). The use of irradiation in the conditioning regimen significantly reduced the number of patients experiencing graft rejection (7% vs 21%) (p = 0.004). Age, sex and severity of disease did not influence the rate of sustained engraftment. Of the 85 patients experiencing graft rejection, 41 received a second transplant: their survival is 33% vs 8% for patients not transplanted a second time (p = 0.003). The major factor predicting the outcome of second BMT for SAA was the interval from first BMT. Patients receiving a second BMT within 60 days from the first BMT had a significantly poorer outcome.

Adolescent↗
PubMed1993

Malignant tumors occurring after treatment of aplastic anemia. European Bone Marrow Transplantation-Severe Aplastic Anaemia Working Party.

BACKGROUND AND METHODS: Recent studies have shown that long-term survivors of acquired aplastic anemia may be at high risk for malignant diseases. We assessed the risk of cancer after aplastic anemia was treated with immunosuppression or bone marrow transplantation and sought to identify risk factors according to treatment. The study population consisted of 860 patients treated by immunosuppression and 748 patients who had received bone marrow transplants for the treatment of severe aplastic anemia. The risk of cancer was analyzed overall and according to treatment relative to the risk in the general population. In calculating relative risk, we excluded patients with myelodysplastic syndromes or acute leukemias arising less than 6 months after treatment, and solid cancers arising less than 12 months after treatment, because of a possible association with aplastic anemia itself rather than with the treatment received. RESULTS: Forty-two malignant conditions were reported in the 860 patients who received immunosuppressive therapy: 19 cases of myelodysplastic syndrome, 15 cases of acute leukemia, 1 case of non-Hodgkin's lymphoma, and 7 solid tumors. Nine were reported in the 748 patients who received bone marrow transplants: two cases of acute leukemia and seven solid tumors. After the exclusions listed above, the overall relative risk of cancer was 5.50 (P < 0.001) as compared with that in the general European population; the risk was 5.15 (P < 0.001) after immunosuppressive therapy and 6.67 (P < 0.001) after transplantation. The 10-year cumulative incidence rate of cancer was 18.8 percent after immunosuppressive therapy and 3.1 percent after transplantation. The risk factors for myelodysplastic syndrome or acute leukemia after immunosuppressive therapy included the addition of androgens to the immunosuppressive treatment (relative risk = 0.28), older age (relative risk = 1.03), treatment in 1982 or later, as compared with 1981 or earlier (relative risk = 3.01), splenectomy (relative risk = 3.65), and treatment with multiple courses of immunosuppression (relative risk = 2.26). Risk factors for solid tumors after bone marrow transplantation were age (relative risk = 1.11 per year) and the use of radiation as a conditioning regimen before transplantation (relative risk = 9.56); such tumors occurred only in male patients. CONCLUSIONS: Survivors of aplastic anemia are at high risk for subsequent malignant conditions. Myelodysplastic syndrome and acute leukemia tend to follow immunosuppressive therapy, whereas the incidence of solid tumors is similar after immunosuppression and after bone marrow transplantation.

Acute Disease↗
PubMed1993

A circadian distribution to febrile episodes in neutropenic patients.

Four-hourly temperature charts relating to 63 febrile neutropenic episodes in 32 patients were assessed for a circadian distribution to the onset of fever (> 37.5 degrees C) using the Edward's test. A highly significant distribution was found with the maximum incidence of febrile events between the hours of 5 p.m. and midnight (acrophase 9.30 p.m.). Patients were 5.53 times more likely to develop fever at 9.30 p.m. that 9.30 a.m.

Adolescent↗
PubMed1993

The combination of hydroxyurea and leucapheresis in the treatment of chronic myeloid leukaemia in pregnancy.

Treatment of malignancy during pregnancy is difficult because of the potential teratogenicity of chemotherapeutic agents. Leucapheresis was employed in the initial management of a pregnant patient with chronic myeloid leukaemia. It was subsequently replaced with oral hydroxyurea during the second trimester. Successful delivery of a live male infant was achieved and the child has normal growth and development to date.

Adult↗
PubMed1993

Recurrence of Philadelphia chromosome-positive leukemia in donor cells after bone marrow transplantation for chronic granulocytic leukemia.

Allogeneic bone marrow transplantation has been shown to be a very effective therapy for Chronic Granulocytic Leukemia with long term disease free survivals in excess of 60%. Relapse rates remain low at 15% following histocompatible sibling transplants and lower rates following matched unrelated donor grafts. Relapse rates however, are higher if BMT is carried out in transformation or blast crisis. Leukemic relapse in donor cells following transplantation for CGL is a rare event. The occurrence of donor leukemia however, may be under reported as accurate and sensitive investigation of the origin of relapsed leukemia following BMT requires DNA based technologies. A possible mechanism of donor leukemia in CGL is transfection of donor cells with the chimeric gene which is unique to this disease. It is possible that the malignant cells found in transformed or blast crisis of CGL may have a greater potential to transfect donor haematopoietic material. Careful evaluation of the incidence of donor leukemia using molecular biology methods may elucidate the frequency of this event following BMT for CGL.

Animals↗
PubMed1993

Mixed chimaerism; detection and significance following BMT.

Residual recipient haematopoietic cells may coexist with donor haemopoietic tissue following BMT. This is known as mixed chimaerism. The incidence of mixed chimaerism varies with the sensitivity of the detection system used; DNA based methodologies are the most sensitive. The influence of mixed chimaerism on leukaemia relapse and graft rejection is unclear. The lineages in which mixed chimaerism occurs may affect outcome.

Anemia, Aplastic↗
PubMed1992

Probability of finding a compatible sibling donor for bone marrow transplantation in Ireland.

This study was undertaken to ascertain the frequency of compatible sibling donors for individuals requiring bone marrow transplantation (BMT) in Ireland. During the study period 1984-89, a total of 392 patients were HLA typed. Of these, 218 (55.6%) had a compatible sibling donor. Among the latter there were 4 degrees of compatibility: 168 (42.9%) were HLA-A,B,DR identical MLC unreactive: three (0.8%) were HLA-A,B,DR identical MLC reactive: 12 (3.0%) were HLA-A,B,DR identical (no MLC performed) and 35 (8.9%) were HLA-A, B identical (no DR or MLC performed). The leukaemias and aplastic anaemia comprised 82.9% of all requests. The majority of patients with acute myeloid leukaemia (64.4%), acute lymphoblastic leukaemia (51.2%), chronic myeloid leukaemia (73.9%) and aplastic anaemia (77.3%) had a potential sibling donor. Subsequently 144 of these patients had an allogeneic BMT, 79.9% of which were for patients with leukaemia (acute and chronic). This study found that there was a higher probability of finding a donor within the family than reported in most series. A clear relationship was demonstrated between family size and the likelihood of obtaining a HLA-identical sibling donor.

Bone Marrow Transplantation↗
PubMed1991

Evaluation of mixed chimerism by in vitro amplification of dinucleotide repeat sequences using the polymerase chain reaction.

The influence of mixed hematopoietic chimerism (MC) after allogeneic bone marrow transplantation remains unknown. Increasingly sensitive detection methods have shown that MC occurs frequently. We report a highly sensitive novel method to assess MC based on the polymerase chain reaction (PCR). Simple dinucleotide repeat sequences called microsatellites have been found to vary in their repeat number between individuals. We use this variation to type donor-recipient pairs following allogeneic BMT. A panel of seven microsatellites was used to distinguish between donor and recipient cells of 32 transplants. Informative microsatellites were subsequently used to assess MC after BMT in this group of patients. Seventeen of the 32 transplants involved a donor of opposite sex; hence, cytogenetics and Y chromosome-specific PCR were also used as an index of chimerism in these patients. MC was detected in bone marrow aspirates and peripheral blood in 18 of 32 patients (56%) by PCR. In several cases, only stored slide material was available for analysis but PCR of microsatellites or Y chromosomal material could be used successfully to assess the origin of cells in this archival material. Cytogenetic analysis was possible in 17 patients and MC was detected in three patients. Twelve patients received T-cell-depleted marrow and showed a high incidence of MC as revealed by PCR (greater than 80%). Twenty patients received unmanipulated marrow, and while the incidence of MC was lower (44%), this was a high percentage when compared with other studies. Once MC was detected, the percentages of recipient cells tended to increase. However, in patients exhibiting MC who subsequently relapsed, this increase was relatively sudden. The overall level of recipient cells in the group of MC patients who subsequently relapsed was higher than in those who exhibited stable MC. Thus, while the occurrence of MC was not indicative of a poor prognosis per se, sudden increases in the proportions of recipient cells may be a prelude to graft rejection or relapse.

Anemia, Aplastic↗
PubMed1991

Mixed chimaerism.

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Anemia, Aplastic↗
PubMed1991

Stromal colonies can be grown from the non-adherent cells in human long-term bone marrow cultures.

The absence of a pluripotent stem cell assay for human cells means that we must rely on assays of committed progenitors as a means for examining the ability of long-term bone marrow culture (LTBMC) to support haemopoiesis. The CFU-GM assay has been employed by many authors to demonstrate that the proliferative capacity and differentiation potential has been retained in LTBMC. In this study the non-adherent cells from human LTBMC were set up using a liquid culture technique for the clonal proliferation of stromal colonies (CFU-F). Weekly plating of the non-adherent cells produced CFU-F for up to 7 wk. Morphological, cytochemical and antigenic characterisation of these colonies revealed that they were identical to those grown from bone marrow de novo. LTBMC can now be used to identify the interactions between the haemopoietic inductive microenvironment and stromal progenitors and allow us to investigate the precise role of cell-cell interactions or cytokine influences on the proliferative capacity of stromal cell progenitors.

Adolescent↗