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Biomedical subjects

J C Biggs

Publications and source records attributed to J C Biggs.

At least 73 records · Page 4Linked to original sources
PubMed1988

The clinical diagnosis of acute graft-versus-host disease: a diversity of views amongst marrow transplant centers.

The diagnosis and grading of acute graft-versus-host disease (AGVHD) is based on a spectrum of clinical and laboratory features. To evaluate the reliability of current diagnostic and scoring criteria, six clinical vignettes were evaluated by 49 transplant physicians from 42 bone marrow transplant center worldwide. Responses were analysed to determine: (1) the degree of concordance among transplanters in diagnosing, scoring and treating AGVHD, and (2) the degree of concordance in assigning primary and contributing causes of death in patients with multiple complications of bone marrow transplantation. Concordance for the diagnosis of AGVHD ranged from 24 to 76%; concordance for grading AGVHD was 55%. Concordance for the decision to treat for AGVHD ranged from 43 to 55%; concordance for assigning the primary cause of death ranged from 71 to 100%. The findings demonstrate the need for (1) improved uniformity of reporting complications of bone marrow transplantation; (2) periodic revision and validation of diagnostic and grading criteria, and (3) methods of analysis that allow for multiple causes of death.

Acute Disease↗
PubMed1987

The development of the acquired immunodeficiency syndrome after bone-marrow transplantation.

Since bone-marrow transplant recipients receive considerable quantities of packed-cell, platelet and sometimes leukocyte transfusions, as well as the donor marrow infusion, it would be predictable that acquired immunodeficiency syndrome (AIDS) by blood-product transfusion would occur in this patient population. We report here two patients who received HLA-identical sibling bone-marrow transplants for acute non-lymphoblastic leukaemia during their first remission. Both developed category-A AIDS at days 342 and 546 after transplantation, respectively. Neither patient belonged to any known high-risk group for AIDS, other than having received a blood-product transfusion. One of the two patients is now known to have received blood from a donor who was human immunodeficiency virus (HIV) seropositive. Both patients developed Pneumocystis carinii pneumonia and other opportunistic infections, and both have died of AIDS without evidence of recurrence of their leukaemia. One patient had no chronic graft-versus-host disease (GVHD) and the other had mild chronic GVHD of the mouth. Since severe opportunistic infections are rare after transplantation in the absence of GVHD, their late occurrence after transplantation should raise the suspicion of AIDS. This complication is likely to have an adverse impact on the long-term survival of patients who received bone-marrow transplants between 1981 and the introduction of effective screening tests for HIV infection in blood donors.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Donor marrow progenitors (CFU-Mix, BFU-E and CFU-GM) and haemopoietic engraftment following HLA matched sibling bone marrow transplantation.

Bone marrow multipotent (CFU-Mix) and unipotent (CFU-GM and BFU-E) progenitor cells in the donor marrow inoculums were measured in 24 histocompatible sibling bone marrow transplants. The number of donor marrow nucleated cells, CFU-Mix, CFU-GM and BFU-E given per kilogram (kg) of recipient's body weight were 2.4 +/- 0.6 X 10(8), 3.6 +/- 4.2 X 10(3), 4.9 +/- 3.3 X 10(-4) and 4.3 +/- 4.1 X 10(4) respectively (mean +/- S.D.). Fast engraftment patients, as assessed by rise in peripheral blood neutrophils (greater than or equal to 0.5 and greater than or equal to 1.0 X 10(9)/l) and platelets (greater than 20 and greater than 50 X 10(9)/l), received a significantly greater amount of CFU-Mix/kg (greater than 3 X 10(3)/kg, p less than 0.025) and CFU-GM/kg (greater than 3 X 10(4)/kg, p less than 0.05 except for plat greater than or equal to 20 X 10(9)/l) than the slow recovery patients. Significant correlations were found between the donor CFU-Mix/kg infused and neutrophil recovery to 1 X 10(9)/l and platelet to 50 X 10(9)/l (Spearman's rank correlation coefficient r = 0.38, p = 0.04 and r = 0.58, p = 0.003, respectively). The amount of donor CFU-GM/kg given also correlated significantly to neutrophil (1 X 10(9)/l) and platelet (50 X 10(9)/l) recovery, (r = 0.33 and r = 0.37, respectively, p less than or equal to 0.05). There was no association between BFU-E, and marrow nucleated cells infused per kg and haemopoietic recovery. A number of clinical parameters were also examined to determine other factors that may influence the rate of engraftment. Acute graft vs host disease (greater than or equal to grade II) and methotrexate therapy post-transplant delayed the platelet regeneration. The results of the present report indicate that in vitro measurement of donor CFU-Mix and CFU-GM progenitors infused, correlate with the speed of granulocyte and platelet recovery in clinical allogeneic bone marrow transplants.

Blood Grouping and Crossmatching↗
PubMed1987

Chromosomal analysis of bone marrow stromal fibroblasts in allogeneic HLA compatible sibling bone marrow transplantations.

Karyotyping was performed on bone marrow stromal fibroblasts and marrow haemopoietic cells on six patients who received bone marrow transplants from siblings of the opposite sex. Three patients with severe aplastic anaemia received unmanipulated donor bone marrow cells. Three other patients with leukaemia and conditioned with high dose chemotherapy (+ total body irradiation in two patients) received T-cell depleted marrow mononuclear cells. Marrow chromosomal analysis was performed on samples obtained between 6 weeks and 1 yr post-transplant. All marrow fibroblasts studied were of recipient origin, whereas all haemopoietic cells were of donor origin. These results demonstrate that in allogeneic sibling marrow transplantation, recipient bone marrow stromal cells regenerate and repopulate the bone marrow and this is not influenced by the conditioning regimen used, the type and dose of marrow cells given and the pre-existing disease.

Anemia, Aplastic↗
PubMed1987

Haemopoietic reconstitution after allogeneic bone marrow transplantation in man: recovery of haemopoietic progenitors (CFU-Mix, BFU-E and CFU-GM).

Haemopoietic reconstitution was evaluated in 44 patients given HLA compatible sibling bone marrow transplants. The mean peripheral blood haemoglobin, neutrophil and platelet counts were markedly reduced early post-graft but returned to normal by 26 weeks post transplant. Bone marrow multipotent (CFU-Mix), erythroid (BFU-E) and myeloid (CFU-GM) progenitor cell reconstitution were also assessed at regular intervals up to 2 years post-graft. The mean value of CFU-GM increased gradually and attained a normal value by 52 weeks. The BFU-E value did not reach a normal value until after 52 weeks post-graft. However, CFU-Mix growth appeared to be impaired even up to 2 years post-transplant. The occurrence of graft versus host disease at 3 months post-transplant was associated with significantly lower mean numbers of platelets, marrow CFU-GM, BFU-E and CFU-Mix. Post-transplant patients who were on methotrexate therapy were also shown to have lower marrow CFU-GM and neutrophil values compared to those patients who received cyclosporin post-transplant. This study demonstrated that although peripheral blood counts were normal after 26 weeks post-graft, marrow stem cell reserve in these patients was reduced. This might in part explain the documented increase in risk of severe infections or thrombocytopenia in some of these patients, particularly during viral infection, graft-versus-host disease or immunosuppressive treatment.

Adult↗
PubMed1987

Risk factors for acute graft-versus-host disease.

Acute graft-versus-host disease (GvHD) is an important complication of bone marrow transplantation in humans. Risk factors are imprecisely defined and controversial. We analysed data from 2036 recipients of HLA-identical sibling transplants for leukaemia or aplastic anaemia to identify risk factors for GvHD. Analyses indicate that grading of GvHD can be reproducibly divided into absent or mild versus moderate to severe; 2-year actuarial probability was 54% (95% confidence interval 52-56%) for absent or mild and 46% (44-48%) for moderate to severe. Factors predictive of development of moderate to severe GvHD include donor/recipient sex-match (female----male greater than others, relative risk 2.0, P less than 0.001). This risk was markedly increased if female donors for male recipients were previously pregnant or transfused (relative risk 2.9, P less than 0.0001). Older patients were at increased risk of GvHD (relative risk 1.6, P less than 0.001), but the age gradient was modest, even the youngest patients had a substantial risk of GvHD and, if parous or transfused female----male transplants were excluded, age was not a significant risk factor. Cyclosporine or methotrexate were equally effective at preventing GvHD and were superior to no prophylaxis (relative risk 2.3, P less than 0.01). These data should be useful in estimating the risk of acute GvHD in an individual patient and in designing clinical trials to investigate methods to modify or prevent GvHD.

Acute Disease↗
PubMed1987

T cell depletion of bone marrow for clinical marrow allografting: optimalization of conditions for depletion by anti-CD2 and anti-CD8 monoclonal antibodies with rabbit complement, and for detection of residual T cell content.

Normal bone marrow obtained at harvest for bone marrow transplantation was passed over a Ficoll density gradient to obtain the mononuclear cell fraction. These cells were incubated with anti-T cell monoclonal antibodies (MAb) anti-HuLym-1 and anti-HuLym-8 plus rabbit complement, washed, and the degree of T cell depletion was assessed by culture in phytohemagglutinin, by flow cytometry and by limiting dilution analysis. The optimal protocol for T cell depletion was found to be a 2-stage incubation with 2 cycles of complement treatment, using a bone marrow cell concentration as low as possible. The precise conditions of complement dilution and incubation temperature depended on the batch of complement used, and had to be assessed for each batch. Of the 3 methods used for assessing T cell contamination, culture in PHA was found to be inappropriate due to large variation in background proliferation of treated and untreated bone marrow cells. Flow cytometry was accurate for residual T cell content of greater than 1% (corresponding to a 90-95% depletion of T cells) but could not detect lower levels of T cell contamination. The limit dilution assay was found to be by far the most sensitive, being capable of detecting a T cell contamination of 1 in 10,000 cells. When combined with flow cytometry on untreated marrow for calculation of the cloning efficiency, it gave very accurate determinations of residual T cell content of marrow.

Animals↗
PubMed1987

Invasive Trichosporon cutaneum infection: an increasing problem in immunosuppressed patients.

Trichosporon cutaneum (syn. T. beigelii), a saprophytic fungal organism normally found in the soil, is increasingly being recognized as a cause of life-threatening systemic illness in immunosuppressed patients. Of 42 cases reported in the literature, 27 (64%) have died, including all four occurring after bone marrow transplantation. We report here a 44-year-old man who developed an invasive pulmonary infection and fungemia with T. cutaneum following bone marrow transplantation. The infection was manifest by severe respiratory distress and hypoxemia despite a clear chest X-ray, and was diagnosed by the identification of fungal hyphae on a percutaneous lung aspirate and by culture of the organism from the blood. Despite the previous reports indicating that there is a high mortality rate in this situation, the patient recovered following treatment with amphotericin B, miconazole and ketoconazole. T. cutaneum needs to be recognized as a potentially serious but treatable pathogen in severely immunosuppressed patients, including bone marrow transplant recipients.

Adult↗
PubMed1986

Ph1 negative haematological chimaerism after marrow transplantation in Ph1 positive chronic granulocytic leukaemia.

A 17-year-old girl with Philadelphia chromosome (Ph1) positive chronic granulocytic leukaemia (CGL) who has undergone two bone marrow transplants from her HLA identical brother is described. Following the second transplant, cytogenetic analysis of her bone marrow cells showed haematological chimaerism with equal numbers of normal male cells and Ph1 negative female cells indicating the probable eradication of the Ph1 positive clones with the retention of normal host stem cells.

Adolescent↗
PubMed1986

The impact of leukemia status at the time of HLA-identical sibling marrow transplantation on subsequent complication rate and survival of adults with acute leukemia.

Between March 1981 and March 1985, 76 patients with acute leukemia were treated with cyclophosphamide (120 mg/kg), 12 or 14 Gy total body irradiation, and an HLA-identical sibling marrow transplant. Forty-seven patients had acute non-lymphoblastic leukemia (ANLL) and 29 had acute lymphoblastic leukemia (ALL). Forty-one were transplanted during first remission and 28 during or after first relapse of their disease. An additional six patients were transplanted because their leukemia was refractory to conventional cytotoxic chemotherapy, and one was transplanted as initial therapy. Actuarial 42 month survival for those transplanted during first remission was 47% and for those transplanted in first relapse or later it was 22% (p = 0.02). There was no difference in either group between those with ANLL and those with ALL. Two of the six patients with refractory leukemia are alive more than 22 and more than 15 months after the transplant. The incidence of acute graft-versus-host disease and interstitial pneumonitis was 90% and 39%, respectively, for the first remission group, and 96% and 37% for those transplanted in first relapse or later. There was no significant difference in transplant-related mortality between the two groups (29% and 43%, respectively). The leukemia recurrence rate, however, was 13% for those transplanted in first remission and 67% for those transplanted in first relapse or later (p = 0.0003). Thus, the major factor determining the incidence of leukemia recurrence and survival after transplant was the status of the leukemia at the time of transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1986

Aplastic anemia: analysis of two methods of treatment.

Between 1981 and 1985, 27 patients with aplastic anemia have been treated by immunosuppression with antilymphocyte globulin and prednisolone or allogeneic bone marrow transplantation. Fifteen have undergone bone marrow transplantation and have an actuarial survival at 54 months of 65% +/- 12% (95% confidence limits). There have been four deaths from graft rejection, septicemia (two), and graft-versus-host disease. Twelve have received antilymphocyte globulin and have an actuarial survival at 56 months of 67% +/- 21%. Five of these now have a normal blood count and two have had good partial responses and are self supporting. Of the five non-responders, three survived, two with persistent aplasia and one after allogeneic bone marrow transplantation. Two are dead, one of hemorrhage and one after mismatched bone marrow transplantation. In this study antilymphocyte globulin produced survival equivalent to bone marrow transplantation although only 58% of patients had a response to the antilymphocyte globulin. The advantages and disadvantages of these two methods of treatment are discussed.

Adolescent↗
PubMed1986

Studies of hemopoietic stromal fibroblastic colonies in patients undergoing bone marrow transplantation.

We report here the results of serial bone marrow fibroblast cultures from recipients of histocompatible allogeneic bone marrow transplants (37 patients with acute leukemia, and seven with severe aplastic anemia). The mean value of marrow CFU-F growth for recipients at day 21 after transplant was significantly lower than that for normals and for patients before transplant. There were no obvious differences in the morphologic, ultrastructural, and cytochemical characteristics of the CFU-F between the normals and the patients who received transplants. The number of stromal CFU-F cells in S phase was increased during the early period after transplantation, as demonstrated by a significant reduction of CFU-F growth after short exposure to hydroxyurea. However, the return to normal was rapid, within six weeks. The presence of graft-vs-host disease (greater than or equal to grade II) and the choice of immunosuppressive drug, i.e., methotrexate or cyclosporine, did not affect the CFU-F recovery. The findings in the present study show that the marrow stromal compartment is compromised after marrow transplantation, but its regeneration is rapid. No in vitro CFU-F growth was obtained from peripheral blood of donors and patients, either before or after bone marrow transplant.

Bone Marrow Cells↗