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Biomedical subjects

A Devergie

Publications and source records attributed to A Devergie.

At least 109 records · Page 6Linked to original sources

Phenotype and function of T lymphocytes infiltrating the skin during graft-versus-host disease following allogeneic bone marrow transplantation.

Seven lymphocyte populations were expanded from skin samples of patients with acute or chronic GVHD following allogeneic genotypically identical BMT. After amplification without in vitro antigenic stimulation or addition of mitogens, 5 of the 7 cell lines showed a large majority of mature CD4+ T cells (in contrast to published immunopathological data). One cell line showed an equal number of CD4+ and CD8+ cells, and another a predominance of CD4+ cells along with a large number of cells with a phenotype suggestive of non-MHC-restricted CTLs. After in vitro antigenic stimulation, various cytotoxicity patterns were seen: specific antihost cytotoxicity was seen in half the cell lines, NK activity was seen in 5 of the 7 lines, and a strong LAK activity was seen in 1 of the 7 cell lines. These results point to a diversity of cytotoxic effectors involved locally in GVHD and emphasize the need for further study of these local events. The cell lines established now constitute basic functional material for the in vitro study of cellular and humoral interactions at the site of GVHD lesions.

Adolescent↗

Long-term follow-up of severe aplastic anaemia patients treated with antithymocyte globulin. Severe Aplastic Anaemia Working Party of the European Cooperative Group for Bone Marrow Transplantation (EBMT).

468 severe aplastic anaemia (SAA) patients registered in the EBMT-SAA registry who did not undergo bone marrow transplantation and were treated with immunosuppressive therapy (IS; 96% of patients received ATG) were evaluated. Their median age was 23 years (range 1-73) at initial IS therapy, 59% were males; in 69% the aetiology of SAA was idiopathic. Of these 468 patients, 245 had a follow-up of less than 2 years after IS 166/245 died, 71/245 are still alive, 8/245 are lost to follow-up. Of 223 patients who survived greater than or equal to 2 years (LTS long-term survivors), 191 are alive, 21 died greater than 2 years and 11 are lost. Median follow-up of 223 LTS was 4.1 years (range 2.0-10.9). Comparison of 166 patients who died less than 2 years and 223 LTS revealed no difference at time of initial IS therapy as regards sex, duration of AA, or its aetiology, but the age distribution and, in particular, severity of SAA differed significantly: more LTS were between 21 and 40 years old (44% v. 32%, P less than 0.02), less LTS had reticulocytes less than 20 x 10(9)/l (63% v. 80%, P less than 0.001), polymorphonuclear granulocytes (PMN) less than 0.2 x 10(9)/l (30% v. 57%, P less than 0.001), haemorrhages (58% v. 79%, P less than 0.002) and infection (30% v. 49%, P less than 0.005) at time of IS. A gradual improvement of blood counts was seen in patients alive greater than or equal to 2 years after IS. At 2 years after IS 80% had a normal haemoglobin and PMN greater than 0.5 x 10(9)/l, but only after 5 years 80% of cases had platelets greater than 50 x 10(9)/l. Development of clonal disease was reported of 31 LTS: 19 developed paroxysmal nocturnal haemoglobinuria (PNH), one acute leukaemia, 11 myelodysplastic syndromes and of these 11 five subsequently acute leukaemia. The majority of these patients (23/31) are still alive. Actuarial mortality of LTS is 22% at 8 years, but so far no plateau was achieved. It is concluded that SAA patients who become LTS following IS, show an improvement in haematological status but are probably not cured and are prone to develop clonal (malignant) disease.

Adolescent↗

Long-term study of chimaerism in bone marrow transplantation recipients for severe aplastic anaemia.

We used minisatellite probes to analyse by DNA fingerprints the long-term engraftment (median 4.3 years, range 1-2) of 21 bone marrow transplantation recipients for severe aplastic anaemia. Patients received their graft from histocompatible siblings. They were conditioned with cyclophosphamide (150 mg/kg) and a 6GY thoracoabdominal irradiation and did not have ex-vivo T cell depletion of marrow donor. DNA was extracted peripheral mononuclear cells and analysed by Southern blotting with 32P-labelled single-stranded RNA probes. Seven out of 21 donor-recipient pairs were sex-mismatched and additionally studied with a probe detecting a male specific repeated sequence on the Y chromosome. Red cell surface phenotype was also used as marker of engraftment in most cases. Long-term engraftment appeared complete for all patients studied with respect to the three methods.

Adolescent↗

Pediatric bone marrow transplantation for leukemia and aplastic anemia. Report of 222 cases transplanted in a single center.

We report a single center experience of 222 patients (pts) less than 18 years old transplanted from 1973 to 1987. The median age was 11 years (1-18). The donor was a monozygotic twin (9 pts), an HLA-id sibling (193 pts), an HLA-id, parent (9 pts), a mismatched related donor (9 pts) and a matched unrelated donor (1 pt). Ninety-six pts were transplanted for SAA. Conditioning varied with time but the majority (59 pts) received CY 150 mg/kg and 6 Gy TAI. The long term actuarial survival is 66% with a median follow-up of 3 years. The group who received CY 200 mg/kg and MTX had a 33% long term survival (LTS). GVH was the main complication with 40% acute and 37% chronic GVHD. Chronic GVHD tended to improve with time after 2 to 4 years of evolution. Ninety pts were transplanted for leukemia (35 AML, 45 ALL and 11 CGL), 20 pts were in relapse. Pts in CR had a LTS of 40%, in pts in relapse, it was 12%. The main causes of death were: interstitial pneumonitis (30%), relapse (27%), GVH (15%). Thirty-five pts were transplanted for constitutional disease: Fanconi anemia (FA) (26 pts), Dyskeratosis congenita (2 pts), Blackfan-Diamond erythroblastopenia (2 pts), Glanzmann thrombasthenia (1 pt), osteopetrosis (1 pt) and Gaucher's disease (1 pt). In FA, the LTS is 70% with a CY 20 mg/kg, 5 Gy TAI regimen. In all disease categories, we did not find any influence of donor's sex on GVH and survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

A randomized study comparing ciclosporin A and antithymocyte globulin for treatment of severe aplastic anemia.

UNLABELLED: This report summarizes results of the treatment of SAA with ciclosporin A (CSA) or antithymocyte globulin (ATG) in 82 patients (pts) randomized since January 1986 from 28 centers. STUDY DESIGN: at diagnosis, pts with established international criteria of SAA and without an HLA identical sib donor were randomized between 2 groups: CyA 4 to 6 mg/kg/d orally for 6 months, or H. ATG 15 mg/kg IV for 5 days associated with Methyl-Prednisolone 5 mg/kg for 5 days then gradually tapered off until day 60. At 3 months follow up, pts with a complete response (CR) or a partial response (PR) received no further therapy, pts with a failure (F) or minimal response (MR) were switched in the other group. All patients were followed regularly for at least 1 year. RESULTS: at 3 months, all pts with CyA were alive (36 pts) and only 26/35 in the ATG group because of 9 early deaths due to severe infection. In the CyA group, 5 were in CR or PR and 31 in MR or F. Subsequently, 5 received a mismatched BMT and died, 8 remained on CyA, 20 had ATG with, at 1 year, 3 F and 11 PR + CR, 5 pts are too early to evaluate. In the ATG group, 26 pts were alive at 3 months, 6 had a CR or PR, 20 failed. Two pts received a mismatched BMT and died. Fifteen received CyA with, at 1 year, 1 failure and 7 responses (7 pts are too early to evaluate at 1 year).(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Aplastic↗

Role of immunosuppressive drugs for prevention of graft-v-host disease after bone marrow transplantation.

In a series of 198 patients we compared various methods of prevention of GVHD. One hundred and thirty-three patients were treated with CSA alone, 44 with the combination of CSA and MTX, and 21 with CSA after marrow T cell depletion. The incidence of GVHD greater than or equal to II was 35% in the CSA group, 22% in the CSA+MTX group and 14% in the T depleted group. The actuarial survival was 55.4%, 52.3% and 55.1% respectively. These results show that the improvement of methods of prevention of GVHD did not affect significantly long term survival after BMT.

Adolescent↗

Transient cyclic neutropenia following GM-CSF in a patient with chronic granulocytic leukemia transplanted with HLA-identical T cell-depleted donor bone marrow.

Treatment with GM-CSF or G-CSF is becoming widely used in patients with chronic neutropenia, or who are aplastic following chemotherapy or autologous or allogeneic bone marrow transplantation. Recently, some authors have described a phenomenon analogous to cyclic agranulocytosis following treatment with G-CSF in a patient with chronic neutropenia. We wish to describe the same phenomenon in a patient with chronic granulocytic leukemia who received GM-CSF (Sandoz) after T cell depletion in order to accelerate hematological reconstitution.

Agranulocytosis↗

Unusual localization of cutaneous chronic graft-versus-host disease in the radiation fields in four cases.

Chronic graft-versus-host disease (GVHD) is a very heterogeneous entity with variable clinical expression. The pathophysiology involves autoimmune disorders and features of fibrosis. Four patients transplanted for severe aplastic anaemia conditioned with cyclophosphamide and thoraco-abdominal irradiation developed skin scleroderma specifically localized in the irradiation fields. This syndrome was remarkable for its late onset and the absence of factors known to trigger chronic GVHD. It is postulated that irradiation used in this protocol may induce keratinocyte damage and trigger chronic GVHD.

Abdomen↗

Fulminant hepatitis due to reactivation of chronic hepatitis B virus infection after allogeneic bone marrow transplantation.

A case of hepatitis B reactivation following bone-marrow transplantation for leukemia in a previously healthy HBsAg carrier is reported. A number of changes in HBV serum markers were contemporary to the acute episode. All of them (increase of HBsAg concentration, conversion from anti-HBe to HBeAg, appearance of anti-HBc IgM and of serum HBV-DNA) were suggestive of a "switching-on" of viral replication. Institution of corticosteroid treatment at the onset of the acute phase did not prevent the fatal outcome.

Adult↗

[Prevention of bacterial infections after bone marrow graft by broad-spectrum oral antibiotics, absorbable (pefloxacin, penicillin) and non absorbable (cephalosporin, gentamycin, bacitracin)].

In a consecutive series of 65 patients treated by allogeneic bone marrow transplantation, we have compared the efficacy on prevention of bacterial infection of total gut decontamination with oral non absorbable antibiotics or with oral absorbable broad spectrum antibiotics. On day-8, all patients were randomly allocated to one group: Group I received orally pefloxacin 400 mg/day and penicillin 3 M UI/day. Group II received capsules containing cephalothin 250 mg, gentamicin 20 mg and bacitracin 150 UI. Each patient received 9 to 12 capsules per day according to body weight. Patients less than 5 years old or with severe hepatic abnormalities were excluded from the study. All patients were treated in LAF room with usual precautions of asepsis. They received sterile food. In addition, they were on ketoconazole for prophylaxis of fungal infections and acyclovir for prevention of herpes infections. Antibiotics were started on day-8 before bone marrow transplantation and stopped 15 days after discharge from the hospital. 32 patients were allocated to Group I and 33 in Group II. There was no difference between both groups according to age, sex, diagnosis. After transplant, the one year survival and the complications were similar in both groups. The median time of decontamination was 65 days, the mean number of days of agranulocytosis was 20 days, the mean number of days of fever was 7 days in both groups. The compliance was better in Group I but the treatment had to be modified in 9 patients of Group I because of liver abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Host-graft interactions after allogenic bone marrow transplantation; choice of donor].

The complexity of host-graft interactions after bone marrow transplantation explains the criteria of choice of the donor. Graft rejection, graft-versus-host disease, graft-versus-leukemia, delayed immune reconstitution, often associated or mutually exclusive are observed even with an HLA identical sibling donor. Syngeneic transplants may be complicated by leukemic relapse related to the loss of the graft-versus-leukemia effect. The compilation of files of unrelated donors increases the possibility of finding a matched unrelated donor. Preliminary results suggest that clinical results may be equivalent to those achieved with HLA identical sibling donors. Overall results of HLA mismatched transplants are disappointing because of the increase of immunological complications. Attempts at preventing graft-versus-host disease with T cell depletion led to an increase of immunological complications: rejection and leukemic relapse. Modifications of the conditioning regimen and use of in vivo monoclonal antibodies are currently being investigated. Ethical, legal, and psychological considerations have also to be taken into account in the donor choice especially with the increase of the donor pool.

Bone Marrow Transplantation↗

Systemic evaluation of Sjögren-like syndrome after bone marrow transplantation in man.

A systematic evaluation of Sjögren-like syndrome (SLS) was performed in 68 bone marrow transplant (BMT) recipients (60 allogeneic and 8 syngeneic recipients). At day 100, the patients underwent clinical evaluation, functional salivary scintigraphy, and lip biopsy. If any findings were abnormal, the examinations were repeated annually for 3 years. Twenty-two patients with SLS and extensive chronic graft-versus-host disease (CGVHD) had abnormal scintiscan and lip biopsy at day 100. Marked keratoconjunctivitis sicca and xerostomia developed between 12 and 24 months after BMT and, thereafter, progressively decreased. Twenty-seven irradiated recipients (7 syngeneic and 20 allogeneic recipients without CGVHD) had isolated xerostomia and disturbed scintiscan but normal biopsy. Seven other patients with limited CGVHD had a lymphocytic infiltrate on lip biopsy but no SLS and a normal scintiscan. Schirmer's test, functional salivary scintigraphy, and lip biopsy allowed us to distinguish SLS from radiotherapy sequelae. As early as day 100, these 3 tests have a predictive value for SLS, one of the criteria for extensive CGVHD.

Biopsy↗

Clinical and immunological restoration in patients with AIDS after marrow transplantation, using lymphocyte transfusions from the marrow donor.

The diagnosis of transfusion-associated acquired immunodeficiency syndrome (AIDS) was made in 2 patients who developed delayed opportunistic infections and severe cytopenias--56 months for the former (patient 1) and 22 months for the latter, (patient 2) following bone marrow transplantation (BMT) for aplastic anemia. In the third case, grafting for acute leukemia (patient 3) (HIV) infection was probably responsible for the failure of hematological and immunological reconstitution 8 months after allogeneic BMT. Each patient received 6 lymphocyte transfusions from the marrow donor for 3 weeks, combined with a 3-month course of low-dose recombinant alpha interferon. This treatment was followed by recombinant gamma interferon for 3 months. We showed that these 3 patients could resume a normal life for 9 months, at least, and that hematological restoration was observed. Our treatment succeeded in correcting the defect of proliferative response to Candida and the impairment of gamma interferon generation for 4 months in one patient and for more than 12 months in the other two recipients. Nevertheless T4 lymphocyte levels increased only slightly and HIV can still be isolated from the patients' blood. At the time of writing, patients 1 and 3 remain in good health with a partial immunological restoration while patient 2 has died of neurological impairment 2 years after the AIDS diagnosis. Although we cannot generalize this successful therapeutic approach to all patients with AIDS, the results may provide an interesting model of the potential effect of lymphocyte transfusions and the role of interferon therapy.

Acquired Immunodeficiency Syndrome↗

[Allogenic bone marrow grafts in chronic myeloid leukemia].

Between August 1979 and April 1986, we treated 70 patients with chronic myeloid leukemia by supralethal chemoradiotherapy followed by bone marrow transplantation (BMT) from HLA identical sibling donors (65 patients) or from identical twins (5 patients). All patients were splenectomized before BMT. To prevent graft versus host disease Cyclosporin alone or associated with Methotrexate was given; in addition 13 patients received a T cell depleted marrow. All patients showed engraftment. Of the 5 patients treated by syngenic BMT, 2 patients relapsed but all are alive in remission, 2 of them after a successful second BMT. Of the 36 patients treated by allogeneic BMT in the chronic phase, 20 are alive in unmaintained remission after a median follow-up of 24 months (range 6 to 58). No patients have relapsed. The actuarial survival at 2 years was 60%. Of the 29 patients with more advanced disease, 19 have survived with the actuarial survival at 2 years 50%. We conclude that the probability of cure after BMT is very high, especially if BMT is performed while the patient remains in the chronic phase. Only 3 patients grafted in accelerated or blast phase died with relapse. The main cause of death was interstitial pneumonitis (15 patients) and 10 patients died from other transplant-related complications.

Adolescent↗