PubMed Health⌕ Search

Biomedical subjects

J C Biggs

Publications and source records attributed to J C Biggs.

At least 19 recordsLinked to original sources
PubMed1992

Treatment of chronic myeloid leukemia with allogeneic bone marrow transplantation after preparation with BuCy2.

One hundred fifteen patients with chronic myelocytic leukemia (CML) were administered busulphan 4 mg/kg for 4 days and cyclophosphamide 60 mg/kg on each of 2 days (BuCy2) followed by allogeneic bone marrow transplantation from histocompatible sibling donors. For 62 patients in chronic phase, 26 in accelerated phase, and 27 in blast transformation, the actuarial survival at 3 years was 58%, 41%, and 25%, respectively. Actuarial probability of relapse was 3%, 12%, and 27%, respectively. Only two patients in chronic phase showed a transient cytogenetic relapse and one of these died from subsequent transplant-related complications, whereas the other remains cytogenetically normal 697 days posttransplant. Patients who were transplanted within 1 year of diagnosis in chronic phase had a survival of 70% compared with 40% when transplanted beyond 1 year from diagnosis. This significant difference in survival was due to transplant-related complications and was correlated with previous exposure to high doses of busulphan. This study indicates that BuCy2 is a useful conditioning regimen for marrow transplantation in patients with CML and results in similar survival statistics and transplant-related mortality as would be expected with conditioning regimens containing total body irradiation. It is possible that relapse after BuCy2 may be lower than expected with regimens containing total body irradiation, but larger analyses are required.

Adolescent↗
PubMed1992

Bone marrow transplants may cure patients with acute leukemia never achieving remission with chemotherapy.

About 30% of adults with acute lymphoblastic leukemia (ALL) and 20% to 40% of children and adults with acute myelogenous leukemia (AML) never achieve remission, even with intensive chemotherapy. Most die of resistant leukemia, often within 6 months or less. In this study of 126 patients with resistant ALL or AML, allogeneic bone marrow transplants from HLA-identical siblings produced remissions in 113 of 115 (98%) evaluable patients. The 3-year probability of leukemia-free survival was 21% (95% confidence interval, 15% to 29%). Leukemia-free survival was similar in ALL (23%, 12% to 40%) and AML (21%, 14% to 31%). Only 3 of 27 patients at risk relapsed more than 2 years posttransplant.

Adolescent↗
PubMed1992

Bone marrow transplantation for severe aplastic anemia: influence of conditioning and graft-versus-host disease prophylaxis regimens on outcome.

Data for 595 patients with severe aplastic anemia receiving HLA-identical sibling bone marrow transplants were analyzed to determine the effect of pretransplant conditioning and graft-versus-host disease (GVHD) prophylaxis on outcome. Transplants were performed between 1980 and 1987 and reported to the International Bone Marrow Transplant Registry. Three conditioning regimens (cyclophosphamide alone, cyclophosphamide plus limited field radiation, and cyclophosphamide plus total body radiation) were studied; none was associated with superior long-term survival. Three GVHD prophylaxis regimens (methotrexate, cyclosporine, and methotrexate plus cyclosporine) were studied. Recipients of cyclosporine with or without methotrexate had a significantly higher probability of 5-year survival (69%, 95% confidence interval 63% to 74%) than patients receiving methotrexate only (56%, 49% to 62%, P less than .003). Higher survival with cyclosporine resulted from decreased risks of interstitial pneumonia (P less than .0002) and chronic GVHD (P less than .005). Additional risk factors adversely associated with survival included infection pretransplant (P less than .004), use of parous or transfused female donors (P less than .005), older patient age (P less than .005), and 20 or more pretransplant transfusions (P less than .006). These data may prove useful in planning randomized clinical trials and in identifying patients at high-risk of treatment failure.

Adolescent↗
PubMed1992

Radiation-free preparation for allogeneic bone marrow transplantation in adults with acute lymphoblastic leukemia.

PURPOSE: The study was undertaken to investigate the effectiveness of allogeneic bone marrow transplantation from HLA-identical siblings after preparation with busulfan and cyclophosphamide in adults with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Thirty-nine patients aged 15 to 42 years underwent transplantation at three different centers from November 1984 through November 1990. All patients received 16 mg/kg busulfan and 120 mg/kg cyclophosphamide as preparative therapy. Cyclosporine plus methotrexate or cyclosporine plus corticosteroids with or without methotrexate were given for prevention of graft-versus-host disease (GVHD). RESULTS: Twelve patients died of treatment-related complications, 12 patients relapsed, and 15 patients are leukemia-free survivors. For 27 patients in group 1 (first remission, second remission, first relapse), the estimated leukemia-free survival (LFS) rate is 42.3% (95% confidence interval [CI], 22.9% to 71.7%) at 3 years. For 12 patients with more advanced disease (group 2), the 1-year LFS rate is 13.5% (95% CI, 0% to 37.1%). Chronic GVHD occurred at an estimated incidence of 63.3% and developed significantly more frequently among patients who received corticosteroids for prevention of acute GVHD. Chronic GVHD was associated with a significantly lower incidence of relapse and with improved LFS rates. CONCLUSION: LFS rate in this study is comparable to that obtained with radiation-containing regimens; however, the effectiveness of this preparative regimen in ALL requires further study.

Actuarial Analysis↗
PubMed1992

Second HLA-identical sibling transplants for leukemia recurrence.

We analysed data from 114 recipients of HLA-identical sibling transplants who relapsed and received a second transplant between 1978 and 1989. Twenty-nine patients had acute lymphoblastic leukemia, 46 acute myeloid leukemia and 39 chronic myelogenous leukemia. Median (range) interval between first and second transplants was 15 (1-80) months. Following the second transplant, graft failure occurred in 2%, acute graft-versus-host disease (GVHD) in 27% and chronic GVHD in 21% of patients at risk. Risks of interstitial pneumonia and hepatic veno-occlusive disease were higher after the second than the first transplant. Two-year probabilities (95% confidence interval) of treatment-related mortality, relapse and leukemia-free survival were 41% (30-53%), 65% (53-75%) and 21% (14-30%), respectively. Leukemia-free survival was 7% (2-19%) among patients relapsing less than 6 months after their first transplant, with high rates of both relapse, 77% (49-92%), and treatment-related mortality 69% (46-85%). In contrast, leukemia-free survival was 28% (19-41%) in those relapsing more than 6 months after the first transplant; in this group the probability of relapse was 59% (45-72%) and treatment-related mortality 30% (20-43%). Factors correlated with better outcome included a diagnosis of chronic myelogenous leukemia, relapse more than 6 months after the first transplant, acute leukemia in remission prior to the second transplant and good performance status.

Adolescent↗
PubMed1991

Treatment for acute myelocytic leukemia with allogeneic bone marrow transplantation following preparation with BuCy2.

One hundred twenty-seven patients with acute myelocytic leukemia (AML) were given busulfan 4 mg/kg on each of 4 days and cyclophosphamide 60 mg/kg on each of 2 days (BuCy2) followed by allogeneic bone marrow transplantation from an HLA-identical or one antigen disparate sibling. For 71 patients in first complete remission, 23 in second complete remission or initial relapse, and 33 patients with primary refractory disease, second or subsequent relapse, or a preceding hematologic disorder, the 3-year leukemia-free survival (LFS) is 63.1%, 32.6%, and 24.2% respectively. The actuarial probability of relapse for each group is 14.1%, 40.6%, and 61.0%. In multivariate analyses, relapse and decreased LFS were associated with advanced disease phase and with M4/M5 French-American-British classification. The LFS of first remission patients was adversely associated with a short time interval from diagnosis to transplantation. This study indicates that BuCy2 is an attractive preparative regimen for marrow transplantation in patients with AML and that prognostic factors for relapse and LFS are similar those described for regimens containing total body irradiation.

Adult↗
PubMed1991

GM-CSF after allogeneic bone marrow transplantation: accelerated recovery of neutrophils, monocytes and lymphocytes.

Ten patients given HLA-identical sibling marrow transplants for lymphoid malignancy received recombinant human granulocyte macrophage-colony stimulating factor (GM-CSF) from day 7 to day 13 inclusive post transplant. Patients were prepared for transplantation with busulphan 16 mg/kg and cyclophosphamide 120 mg/kg. Immunosuppression to minimise the risk of graft-versus-host disease (GVHD) was cyclosporin/short methotrexate. Results were compared with a historical control group of patients (n = 16) given matched sibling transplants for acute leukaemia and receiving the same immune suppressive regime but not given GM-CSF. Recovery of total white cells, neutrophils, monocytes and lymphocytes was more rapid in the GM-CSF recipients (p less than 0.02). There was a suggestion of a decrease in non-viral infections in the first 30 days in the GM-CSF recipients (p = 0.09). There was, however, no significant difference in the severity of oropharyngeal mucositis nor in the duration of the transplant hospitalisation. Surprisingly, the severity of acute GVHD was higher in the GM-CSF recipients with six of eight evaluable patients having grade II-IV acute GVHD (p = 0.003). Two GM-CSF recipients developed a fluid retention/capillary leak syndrome. These findings indicate a need for caution in the use of GM-CSF after allogeneic marrow transplantation.

Adolescent↗
PubMed1991

Erythropoietin concentrations in obstructive sleep apnoea.

Eight patients with obstructive sleep apnoea and a normal haemoglobin concentration underwent nocturnal studies during which oxyhaemoglobin saturation was recorded continuously with an ear oximeter and serum erythropoietin concentration was measured hourly by means of a radioimmunoassay. Serum erythropoietin concentrations remained within the normal range throughout the study despite falls in oxyhaemaglobin saturation in individuals to 33-78%. There was no relation between the degree of nocturnal hypoxaemia and serum erythropoietin concentrations. The brief cyclical episodes of hypoxaemia typical of obstructive sleep apnoea may not be a sufficient stimulus for erythropoietin secretion.

Adult↗
PubMed1991

An acute pulmonary syndrome possibly representing acute graft-versus-host disease involving the lung interstitium.

An acute pulmonary syndrome possibly representing acute graft-versus-host disease (GVHD) involving lung interstitium occurred in a patient given an allogeneic bone marrow transplant for haematological malignancy. He presented at day 34 with acute GVHD of skin and bowel, and this was associated with cough, dyspnoea and an asymmetrical change on chest X-ray. Lung biopsy demonstrated an interstitial and peribronchial lymphocytic infiltrate and acute bronchial epithelial degeneration. He responded symptomatically to high dose intravenous methylprednisolone. The radiological change resolved completely. This case, thought to represent GVHD involving lung interstitium, emphasizes the need for tissue procurement in the management of non-bacterial lung disease after marrow transplantation.

Acute Disease↗
PubMed1991

Bladder irrigation does not prevent haemorrhagic cystitis in bone marrow transplant recipients.

Thirty-four patients receiving allogeneic bone marrow transplants as treatment for haematological malignancy were prospectively randomized to receive or not to receive bladder irrigation by indwelling urinary catheter during preparation for transplant. Twenty-two patients received busulphan and cyclophosphamide, four received busulphan, cyclophosphamide and irradiation, and eight received cyclophosphamide and total body irradiation. The actuarial incidence of haemorrhagic cystitis in those randomized to receive bladder irrigation was 48% for the whole group and 52% in those receiving busulphan and cyclophosphamide only. In those randomized not to receive bladder irrigation the incidence of haemorrhagic cystitis was 29% for the overall group and 38% in those receiving busulphan and cyclophosphamide. There was no statistically significant difference between the two groups. We conclude that bladder irrigation does not minimize the risk of haemorrhagic cystitis in this patient population.

Adolescent↗
PubMed1990

Serum erythropoietin changes in autologous and allogeneic bone marrow transplant patients.

Sequential changes in serum erythropoietin (sEPO) levels were measured by radioimmunoassay in six patients receiving autologous rescue (AR) and 11 patients receiving an allogeneic bone marrow transplant (BMT) for malignant disease. Longitudinal studies showed an inverse relationship between sEPO and haemoglobin levels in the autologous rescue and allogeneic transplant patients throughout the 130 d post-transplant study period. Early post-conditioning EPO responses were normal for the haemoglobin level in both groups, but after day 14 post-transplant, erythropoietin production in response to anaemia became impaired in one autologous rescue patient and eight of the 11 allogeneic transplant patients. There was no clear association between late impairment of sEPO production and conditioning therapy, infection, graft-versus-host disease, immunosuppressive therapy or serum creatinine. Blood transfusion requirements were similar for both groups in the first month after transplantation, but from days 31 to 90 post-transplant, BMT patients required an average of 5.5 units per patient compared with 1 unit per patient for the autologous group. Marrow transplant procedures do not affect early EPO responses but may diminish late responses. The potential value of exogenous rHuEPO in hastening engraftment and decreasing transfusion requirements, particularly for those patients who appear to have impaired EPO responses, remains to be shown by clinical trials.

Adolescent↗
PubMed1990

Peripheral blood and bone marrow findings in patients with acquired immune deficiency syndrome.

In 4 years (1984-1987), 183 bone marrow examinations were performed on 155 human immunodeficiency virus (HIV) antibody positive patients. One hundred and fifty three had category IV AIDS. One-third of the marrows yielded specific information. This included opportunistic infection, in particular Mycobacterium Avium Intracellulare Complex (MAI) (24%), malignancy (4%), consistent with ITP (9%) and iron deficiency (1%). In the remaining two thirds of the bone marrows the most frequent non-specific abnormalities were dyserythropoiesis, erythroid hypoplasia, reticuloendothelial iron block, granulomas, lymphoid aggregates, plasmacytosis and histiocytosis. Common peripheral blood findings were anemia, lymphopenia, anisocytosis, rouleaux and atypical lymphocytes. Peripheral blood and bone marrow examinations on 16 patients on AZT are included. These patients have more pronounced blood and bone marrow abnormalities. The causes of these abnormalities are multifactorial and include low T4 levels, severe viral and other infections and therapy with marrow toxic drugs.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Marrow transplantation for acute lymphoblastic leukemia: factors affecting relapse and survival.

Transplant outcome was analyzed in 690 recipients of bone marrow transplants (BMTs) for acute lymphoblastic leukemia (ALL) in first (n = 299) or second remission (n = 391). Actuarial 5-year leukemia-free survival was 42% +/- 9% (95% confidence interval) and 26% +/- 6%, respectively; relapse rates were 29% +/- 9% and 52% +/- 8%, respectively. Five-year leukemia-free survival was 56% +/- 18% in children and 39% +/- 10% in adults (P less than .02) transplanted in first remission. In first-remission adults, non-T-cell phenotype, male to female donor-recipient sex-match and graft-v-host disease (GVHD) were associated with decreased leukemia-free survival; inclusion of corticosteroids in the regimen to prevent GVHD was associated with increased leukemia-free survival. Variables associated with decreased leukemia-free survival after second-remission transplants were age greater than or equal to 16 years and relapse occurring while on therapy. Variables associated with increased probability of relapse were similar for first- and second-remission transplants and included GVHD prophylaxis without methotrexate and absence of GVHD. In first-remission transplants, leukocyte count greater than or equal to 50 x 10(9)/L at diagnosis was also associated with increased relapse; in second remission, relapse while receiving chemotherapy was also associated with increased posttransplant relapse. These data emphasize the importance of both disease- and transplant-related variables in predicting outcome after BMT. They may be used to explain differences between studies, design future trials, and identify persons most likely to benefit from BMT.

Adolescent↗