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Biomedical subjects

M R Vowels

Publications and source records attributed to M R Vowels.

At least 37 records · Page 2Linked to original sources
PubMed1994

Common presentations and management of leukaemia in childhood.

The curability of childhood leukaemia (acute lymphoblastic, acute non lymphoblastic and chronic myeloid) has improved dramatically over the past 25 years. The author reviews the clinical presentations and current therapeutic approaches in broad principle. The importance of supportive care (both at the time of diagnosis and during therapy) and the potential for long-term side effects relevant to adult life are discussed.

Acute Disease↗
PubMed1994

Haemorrhagic cystitis in paediatric bone marrow transplant patients: an association with infective agents, GVHD and prior cyclophosphamide.

The frequency of haemorrhagic cystitis (HC) is evaluated in a paediatric population undergoing bone marrow transplantation (BMT) and its relationship to therapy with cyclophosphamide (CY) prior to conditioning for BMT (prior CY), infectious agents and graft-versus-host disease (GVHD) assessed. HC was defined as macroscopic haematuria with early onset HC occurring within 2 days of and delayed onset beyond 2 days from CY infusion. Sixty-three children received a total of 65 BMTs between July 1988 and January 1991, with 60 children receiving CY and 3 l/m2/24 h of post-hydration fluid post-CY as part of their conditioning. There were no cases of early onset HC. Eleven (17%) children had a total of 19 episodes of delayed onset HC. Overall, an infective agent was identified in the urine at the time of 17 of 19 (89%) episodes of HC. While papovavirus was the most common organism (12 episodes), adenovirus (2), cytomegalovirus (1) and bacteria (3) were also identified. The frequency of HC in transplants complicated by acute GVHD grade II-IV was 40% (p = 0.016), in children who had received prior CY was 43% (p < 0.001) and in mismatched transplants was 32% (p = 0.06). Four children who developed GVHD had exacerbations of symptoms associated with the use of high-dose steroid therapy. Our results suggest that most cases of delayed onset HC are temporally associated with an infective organism, predominantly papovavirus, and identify GVHD and prior CY as risk factors. Increased symptomatology was associated with acute GVHD and its treatment and this may be explained by the added immune suppression, resulting in greater viral reactivation and further mucosal damage.

Adolescent↗
PubMed1993

The experience of a single Australian paediatric oncology unit. 1000 patients 1964-1987.

OBJECTIVE: To determine the survival for children with malignant disease diagnosed in the period 1964-1987 and treated in a single paediatric oncology unit. DESIGN: Records of patients treated by the Department of Haematology and Oncology at the Prince of Wales Children's Hospital were reviewed to determine the survival of children with cancer according to decade of diagnosis and diagnostic group. PATIENTS: Patients were eligible for the study if referred for treatment at or soon after diagnosis of malignancy. One thousand patients were treated during the study period. There were 363 with acute lymphoblastic leukaemia (ALL), 126 with tumours of the central nervous system (CNS), 86 with acute non-lymphoblastic leukaemia (ANLL), 81 with lymphoma, 79 with neural crest tumours, 69 with renal tumours, 66 with bone sarcomas, 53 with soft tissue sarcomas, and 77 with various other diagnoses. Age range was one day to 20.75 years. INTERVENTIONS: Treatment included surgery, radiotherapy and chemotherapy in a variety of protocols. RESULTS: Ten-year survival for the 1960s, 1970s and 1980s was 15%, 51% and 64% respectively (P < 0.001), excluding tumours of the CNS. From 1985 onwards, actual survival at five years has been 79%. Survival from Wilms' tumour and Hodgkin's disease remained high throughout the study period, and significant improvement in survival occurred with ALL, non-Hodgkin's lymphoma (NHL) and osteogenic sarcoma. Survival remained poor with neuroblastoma and ANLL. CONCLUSIONS: Significant improvement in outcomes for childhood malignancy has been achieved over the last three decades, with five-year survival currently at 79% (excluding tumours of the CNS). Some diagnostic groups have had only small improvements in outcome and require new strategies.

Adolescent↗
PubMed1993

Long-term complications following bone marrow transplantation in children.

Seventeen children who underwent bone marrow transplantation (BMT) between 1975 and 1985 and survived for more than 2 years were evaluated for growth and development. The patients had a follow up of 2.1-13.1 years. Prior to transplant, children with malignancy had received multi-agent chemotherapy and nine had also received central nervous system irradiation. Transplant preparation for malignancy (group 1; n = 13) included high-dose cyclophosphamide (CPA) 120-200 mg/kg and total body irradiation (TBI) 10-13.2 Gy, whereas conditioning for non-malignant disorders (group 2; n = 4) included high-dose CPA 200 mg/kg with or without busulphan. Patients in group 1 showed a steady decline in height velocity following initial chemotherapy and cranial irradiation and the decline was even greater following BMT. Growth hormone (GH) deficiency developed in eight of nine children tested, hypergonadotrophic hypogonadism developed in 11 who reached puberty, thyroid hormone abnormalities were encountered in four out of 10 tested and 11 of 13 developed cataracts. Patients in group 2 did not show decline in linear growth rate, thyroid hormone abnormalities or cataracts after BMT. The only child tested had normal GH levels and the two patients who reached puberty showed delayed but complete gonadal recovery. Our data demonstrate that TBI leads to significant late effects on growth and gonadal function. Contrary to previous reports, a high incidence of cataract formation is observed after fractionated TBI. Conditioning regimens TBI should be considered in children undergoing BMT.

Adolescent↗
PubMed1993

Rate of marrow engraftment does not appear to be adversely affected by early marrow infusion after total body irradiation.

Bone marrow transplantation (BMT) provides a means of increasing chemo-radiotherapy doses beyond the limits imposed by marrow toxicity. The time interval between myeloablative therapy and marrow infusion needs to be optimized to ensure prompt engraftment. It has been suggested that early marrow infusion after completion of total body irradiation (TBI) may be detrimental to rapid marrow reconstitution. Hence a retrospective analysis of 75 BMT patients was performed to document the rate of marrow engraftment following marrow infusion given immediately after TBI. Engraftment rates (time to absolute neutrophil count to greater than 0.5 x 10(9)/L) of patients receiving different conditioning regimens were compared. Results show similar engraftment rates in patients receiving bone marrow infusion 27.7 and 32.1 hours after completion of chemotherapy in autologous (20.5 days) and allogeneic (18.5 days) transplants respectively, or 2.9 and 2.0 hours after completion of TBI in autologous (20.1 days) and allogeneic (19.4 days) transplants respectively. These results are similar to those reported for delayed marrow infusion after TBI and would support that early marrow infusion after TBI does not adversely influence rate of engraftment. Thus it appears appropriate to give marrow immediately after completion of TBI.

Bone Marrow↗
PubMed1992

Failure of allogeneic bone marrow transplantation to benefit HIV infection.

A 16 year old boy underwent allogeneic bone marrow transplantation (BMT) from an human leukocyte antigen (HLA)-identical sibling for severe aplastic anaemia. He was symptomatic for 7 years before transplantation and had received multiple red blood cell and platelet transfusions. Conditioning for BMT consisted of cyclophosphamide, antilymphocyte globulin and total lymphoid irradiation. Engraftment was rapid, there was no evidence of rejection despite the history of multiple blood product transfusions and he did not develop acute or chronic graft versus host disease. He was well for the first 8 months after transplantation but then developed fevers, interstitial pneumonia, herpes simplex infections and cytomegalovirus enteritis. Serological studies revealed antibodies to human immunodeficiency virus (HIV) and he was considered to have acquired immune deficiency syndrome (AIDS). Retrospective analysis of the serum samples showed that he was seronegative for HIV until approximately 10 months before transplantation when his serum became HIV positive. Lymphocyte function studies done after transplantation suggested immunologic recovery at 3 months post-transplant with a brisk though subnormal response to phytohaemagglutinin stimulation. T cell subset analysis performed subsequently showed complete absence of CD4 positive cells indicating immune incompetence which was associated with clinical features of AIDS. Bone marrow transplantation had failed to produce sustained immunologic reconstitution and prevent the progression of HIV to which he ultimately succumbed.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Searches for matched and closely matched related and unrelated bone marrow donors undertaken in a single paediatric unit.

Information regarding the likelihood of finding suitable marrow donors is limited. In order to determine this potential, all patients who received their primary care at a single paediatric institution over a 9 year period and in whom tissue typing studies were initiated are reviewed. Forty-five (31.3%) of 144 patients had a sibling who was human leucocyte antigen (HLA) identical. A further 16 (11.2%) patients had immediate or more distant relatives who were either HLA identical (2.7%) or matched for five of six HLA antigens (8.3%). The possibility that a parent was closely matched with the patient was suggestive from the typing of siblings alone in only half the cases. Unrelated HLA matched donors were identified in four (27%) of 17 bone marrow bank searches. Overall, a potential related donor was identified within the family for 42% of patients and this figure rose to 45% when successful marrow bank searches were included. It can be concluded that initial typing should include both the parents and siblings. If a suitable donor is not found then an extended family and/or bone marrow bank search will identify additional suitable donors in a significant number of families.

Bone Marrow Transplantation↗
PubMed1992

Successful pregnancy after total body irradiation and bone marrow transplantation for acute leukaemia.

We report successful pregnancies in two young women (aged 24 and 20 years) following allogeneic bone marrow transplantation (BMT) for acute non-lymphoblastic leukaemia. Conditioning therapy consisted of cyclophosphamide (120 mg/kg) and total body irradiation (TBI, 12 Gy) in 2 Gy fractions once daily for 6 days or twice daily for 3 days. Graft-versus-host disease prophylaxis was with methotrexate alone. Both women were amenorrhoeic after BMT and gonadal testing indicated hypergonadotrophic hypogonadism. Both women had normal pregnancies (2 years and 5 years after BMT) resulting in normal healthy infants. Previously successful pregnancy has been reported after TBI in three women in whom the TBI dose was less than 8 Gy. Our cases illustrate that normal outcome of pregnancy is possible at even higher doses of TBI.

Adult↗
PubMed1991

Second intracranial neoplasms following treatment of childhood acute lymphoblastic leukaemia.

We report a boy with acute lymphoblastic leukaemia (ALL) treated with chemotherapy and prophylactic cranial irradiation to a dose of 24 Gy. Six years after diagnosis he developed a glioma and died. Prior to 1979, four cases of second malignant neoplasm (SMN) of the brain had been reported in children treated for ALL. These SMNs occurred within 2 years of the original diagnosis (median 1.3 years) and at least two of four patients had not received prior radiotherapy. Since 1979, 28 cases of SMN of the brain have been reported including nine of 468 (1.9%) long-term survivors in one study. All occurred more than 3.7 years from diagnosis (median 6.5 years; range 4-13 years) and all received cranial irradiation (median 24 Gy; range 20-48 Gy). These data indicate a change in the pattern of SMNs which is most likely due to the introduction of cranial irradiation. As well, the frequency of SMNs in children treated for ALL appears to have increased, although it is still no greater than the risk of SMNs developing following the treatment of any other primary childhood neoplasm.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Bone marrow transplantation in children using closely matched related and unrelated donors.

Seventeen bone marrow transplants were undertaken on 15 patients with leukemia or aplastic anemia using marrow from closely matched (phenotypic or five out of six HLA-A, B and DR antigen matched related and unrelated) donors. Donors were siblings (four), parents (seven), aunt (one), great aunt (one) or matched unrelated (two). When compared with transplants using matched sibling donors, survival was not different (51.4 +/- 13.4% vs. 48.1 +/- 9.6%; p = 0.87) but transplant-related complications and morbidity were higher as follows: graft-versus-host disease (GVHD) (87% vs. 15%; p less than 0.001), interstitial pneumonitis (59% vs. 14%; p less than 0.003), days in hospital (51 vs. 26; p less than 0.001), and chronic transplant related morbidity 50% vs. 11%; p + 0.033). The age of donors who were closely matched was significantly greater than that of their recipients (29.7 +/- 13.9 years vs. 8.1 +/- 3.1 years; p less than 0.001) and was associated with poorer transplant outcome. Median transplant-related complication-free survival for patients receiving transplants from age non-disparate donors was 53 months (range 18-86 months) compared with 12 months (range 2-42 months) for age disparate donors (p = 0.028). Transplants from closely matched donors were undertaken in the ratio of one to every three matched donors, indicating the importance of this source of marrow in a transplant program.

Adult↗
PubMed1991

Immunomagnetic bone marrow purging of common acute lymphoblastic leukemia cells: suitability of BioMag particles.

Immunomagnetic bone marrow purging is becoming a widely used technique in many bone marrow transplant centres. Most centres use Dynabead magnetic particles to facilitate the procedure. The suitability of a novel magnetic particle (BioMag) for immunomagnetic purging was addressed in this study. Common acute lymphoblastic leukemia (ALL) cells were targeted using CD9 and CD10 mouse monoclonal antibodies prior to attachment of magnetic particles coated with anti-mouse immunoglobulin and depleted with samarium cobalt magnets. Immunofluorescent and clonogenic assays capable of measuring more than four log depletions of the Nalm 6 cell line showed that a single cycle of purging reduced target cells by 3.1 +/- 0.9 BioMag particles and 1.8 +/- 1.0 logs with Dynabeads. A second cycle of purging was advantageous, increasing target cell depletions to more than 4.5 logs with either particle type. Bone marrow granulocyte-macrophage colony-forming units were not significantly reduced. The results indicate that BioMag particles can be used for the efficient depletion of common ALL cells from bone marrow for transplantation.

Antibodies, Monoclonal↗
PubMed1990

Bone marrow transplantation: a review of a programme and its first 100 patients.

We review the first 100 patients receiving a bone marrow transplant as definitive therapy for their underlying disease. These patients were treated between May 1975 and June 1988. Median age was 8 years (range, 1 month to 43 years). Initially, patients were given transplants late in their disease but, as the programme progressed, patients were given transplants earlier and while in remission from their disease. The types of disease considered for treatment by bone marrow transplantation (BMT) expanded from leukaemia, and aplastic anaemia to include neuroblastoma, thalassaemia and immune deficiency. Initially matched donors were used but the source of marrow broadened to include mismatched family members, matched unrelated donors and autologous marrow. Problems after BMT were rejection (11%), acute graft-versus-host disease (GVHD) (45%), interstitial pneumonitis (22%) and relapse (36%). Recurrence of disease was the cause of half the deaths. GVHD was less frequent with the use of methotrexate and cyclosporin, T-cell depleted marrow or matched donors. Interstitial pneumonitis was more commonly associated with the use of mismatched donors and the development of GHVD. Relapse was less likely when BMT was undertaken in the first remission. At least one long-term side effect was seen in all patients treated with total body irradiation whereas no patient treated without irradiation had long-term side effects. The rate of disease free survival of patients at 24 months was 56% for matched, 48% for closely matched, 46% for autologous and 29% for mismatched transplants. For matched transplants mortality within the first 6 months after transplantation decreased from 28% before 1984 to 5% since 1984. Fifty-one patients have survived to June 1989, 49 of them disease free, for periods ranging from 12 to 123 months (median 29 months).

Adolescent↗
PubMed1990

Bone marrow transplantation for childhood acute lymphoblastic leukaemia after marrow relapse.

Children with acute lymphoblastic leukaemia in whom relapse in bone marrow occurs have a poor outlook when treated with chemotherapy alone. Twenty-seven patients with childhood acute lymphoblastic leukaemia were treated for marrow relapse with high-dose chemotherapy with or without total body irradiation followed by bone marrow transplantation (BMT). Twenty patients received allogeneic marrow from partially or completely matched histocompatible donors. In this group, nine patients (45%) were free of disease with a median follow-up of 57 months (range, 22 to 126 months) after transplantation, four (20%) died from interstitial pneumonitis and seven (35%) died after a further relapse. Seven patients received autologous marrow collected while they were in remission. In this group, one patient died from infection and six died after a further relapse. We conclude that allogeneic BMT is more effective than autologous transplantation and results in long-term disease-free survival in a significant number of patients. New methods are needed to eradicate residual disease in the patient and to purge marrow ex vivo.

Actuarial Analysis↗