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Biomedical subjects

G Socie

Publications and source records attributed to G Socie.

At least 37 records · Page 2Linked to original sources
PubMed1995

Allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia in second remission: factors predictive of survival, relapse and graft-versus-host disease.

Between 1983 and 1993, 42 patients with acute lymphoblastic leukemia (ALL) in second complete remission (CR) underwent an allogeneic HLA-identical bone marrow transplant (BMT; there was one family mismatched graft). The conditioning regimens varied, consisting of cyclophosphamide (CY) and total body irradiation (TBI; n = 10); CY, TBI, Ara C, VP-16 (n = 11); TBI, Ara C, melphalan (n = 20) (TAM) or other (n = 1). Cyclosporine A (CsA) (n = 15) or CsA and methotrexate (MTX) (n = 24) were the main regimens for prophylaxis of graft-versus-host disease (GVHD). Nineteen of 42 patients are alive in CR ranging from 1 to 72 months after BMT with a median follow-up of 36 months. The 4-year actuarial survival rate was 53%. The actuarial relapse rate was 17%. Twenty three patients died: 4 patients of leukemic relapse, 9 of infection, 2 of acute GVHD, 2 of multiorgan failure after chronic GVHD, 2 of a secondary tumour and 4 patients died of other causes. Several pre- and post-transplant characteristics were analyzed to determine predictive factors for survival, relapse and GVHD. The relapse rate was significantly influenced by the type of conditioning regimen with no relapse in the TBI, Ara C, melphalan group. The analysis of long-term sequelae shows that there are no severe complications in this last group. Our results confirm that allogeneic BMT can lead to long-term survival for children with ALL in second CR and suggest an advantage of using the TAM conditioning regimen in the eradication of the leukemic disease.

Actuarial Analysis↗
PubMed1994

Consequences of two different doses to the lungs during a single dose of total body irradiation: results of a randomized study on 85 patients.

PURPOSE: To evaluate the incidence of lung complications and leukemia recurrences after two different doses to the lungs during total body irradiation. METHODS AND MATERIALS: Seventy-nine patients with acute leukemia (AML or ALL) in first complete remission or chronic myeloid leukemia in the chronic phase, five patients with high grade lymphoma, and one with chronic lymphocytic leukemia were entered in the study. They were given a single dose of total body irradiation (10 Gy over 4 h) with two different doses to the lungs (6 Gy or 8 Gy) prior to bone marrow transplantation. The median dose rate was 0.04 Gy/min. The median follow-up for both groups of patients was 24 months. RESULTS: The actuarial 5-year overall survival rate was similar in both groups, 59% and 43% for patients given 8 Gy and 6 Gy to the lungs, respectively. The lung complication rate was similar in the two groups (28% vs. 22% for the 8 Gy and 6 Gy group, respectively). The actuarial leukemia recurrence rate was significantly higher in the group of patients given 6 Gy to the lungs (25%) vs. 0% in the 8 Gy group. Interestingly, all recurrences occurred in the group of patients who were given 6 Gy to the lungs, who had acute leukemia, and no chronic graft vs. host disease (GVHD). CONCLUSIONS: Although the number of patients was not very large and the follow-up relatively short, these findings suggest that a lower dose to the lungs could lead to an increased incidence of leukemia recurrences due to a lower dose to the thoracic wall or to lower incidence of chronic GVHD.

Adolescent↗
PubMed1994

Single dose versus fractionated total body irradiation before bone marrow transplantation: radiobiological and clinical considerations.

PURPOSE: This present review is intended to evaluate the specific influence of fractionation of total body irradiation on the outcome of a subsequent bone marrow transplantation. METHODS AND MATERIALS: Available experimental and clinical data on the influence of fractionation on leukemia cell killing, immunosuppression, and sparing of normal tissues were analyzed. RESULTS: Review of available data shows: (a) The role of fractionation on leukemia cell killing may vary with the leukemia type. For acute nonlymphoblastic leukemia, a few experimental and several clinical studies show no or little fractionation effect; a 12-13 Gy fractionated scheme could, therefore, be more efficient than a conventional 10 Gy single dose total body irradiation. For chronic myelogenous leukemia, some sensitivity to fractionation is suggested, so that an increase in total or fractional dose may be necessary in fractionated schemes to equate the efficacy of a 10 Gy single dose. For acute lymphoblastic leukemia, a high fractionation sensitivity was observed for some leukemic cell lines in vitro, without undisputable clinical confirmation for the moment. (b) Numerous experimental studies have demonstrated that the immunosuppressive effect of total body irradiation, a major determinant of engraftment, is highly fractionation sensitive. In humans, high rates of graft failures have been reported when T-cell depletion of the graft was associated to fractionated total body irradiation schedules. (c) A large amount of radiobiological and clinical data have demonstrated that late radiation-induced injuries to normal tissues and organs are highly fractionation sensitive. However, in a context of total body irradiation for bone marrow transplantation, the number of other determinants of normal tissue damage makes it difficult to demonstrate a clear-cut advantage of fractionated over single dose scheme, with a possible exception for children. CONCLUSIONS: In 1994, available data suggest that very cautious attempts could be made to adapt total body irradiation schedules to the potential normal tissue toxicity, T-cell depletion, and to the type of leukemia.

Bone Marrow↗
PubMed1994

Haemopoietic growth factors in aplastic anaemia: a cautionary note. European Bone Marrow Transplant Working Party for Severe Aplastic Anaemia.

We are concerned about the inappropriate use of haemopoietic growth factors in patients with severe aplastic anaemia (SAA). The treatment of choice for this disorder is bone-marrow transplantation from an HLA-identical sibling donor if the patient is younger than 45 years, but it must be done soon after onset before the patient becomes sensitised by multiple red-cell and platelet transfusions. Other patients should receive immunosuppressive therapy with antithymocyte globulin alone or with cyclosporin or oxymetholone. Haemopoietic growth factors may have a role in stimulation of granulopoiesis after immunosuppressive therapy, but there is no evidence that they can correct the underlying stem-cell defect in SAA, and therefore no justification for their use alone in newly diagnosed SAA. Such treatment is harmful because it delays bone-marrow transplantation, or immunosuppressive therapy in older patients and those without suitable donors, thus reducing the chances of a successful outcome.

Age Factors↗
PubMed1994

Fasciitis in chronic graft-versus-host disease. A clinicopathologic study of 14 cases.

OBJECTIVE: To describe the clinicopathologic features of fasciitis in patients with chronic graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation from human leukocyte antigen (HLA)-identical donors. DESIGN: A retrospective cohort study. SETTING: Tertiary care center. PATIENTS: Patients who had allogeneic bone marrow transplantation and developed chronic GVHD with clinical and pathologic signs of fasciitis. MAIN OUTCOME MEASURE: Analysis of clinical presentations and of deep cutaneo-muscular biopsy specimens. RESULTS: Between January 1974 and January 1991, 14 of 475 patients who had allogeneic bone marrow transplantation developed chronic GVHD that began with the sicca syndrome and liver or digestive tract involvement, or both, 60 to 170 days after the graft was received. Sudden and painful skin swelling was reported 350 to 3745 days after the graft was received. Follow-up over 2 to 7 years showed failure of the fasciitis to respond to steroid therapy or to any conventional treatment of chronic GVHD. Although 7 patients showed moderate improvement, the others remained functionally disabled because of skin tightness, joint stiffness, contractures, and sores. Patients with fasciitis in chronic GVHD had no specific immunogenetic profile and no history of L-tryptophan intake or phytonadione injections. CONCLUSION: Among alloimmune syndromes, fasciitis is a distinct entity that leads to functional disability. This rare form of chronic GVHD may provide clues to understanding the mechanisms involved in fasciitis from other causes.

Adolescent↗
PubMed1994

Secondary solid malignant tumors occurring after bone marrow transplantation for severe aplastic anemia given thoraco-abdominal irradiation.

PURPOSE: We have evaluated irradiation doses received at location of secondary solid tumors occurring after bone marrow transplantation (BMT) in five of 147 patients grafted for severe aplastic anaemia. RESULTS: All 5 tumors occurred within the radiation field penumbra. The estimated received dose varied from 6 Gy for one inner field secondary tumor, to 2.5 Gy for the remaining secondary tumors. CONCLUSION: Tumors may arise in the zone where the delivered radiation dose drops dramatically. Irradiation, with associated cofactors, may promote the development of epidermoid carcinoma in irradiated patients for BMT.

Abdomen↗
PubMed1994

Detection of recipient cells after non T-cell depleted bone marrow transplantation for leukemia by PCR amplification of minisatellites or of a Y chromosome marker has a different prognostic value.

We used polymerase chain reaction amplification of minisatellite sequences (33.6.3, MS51, YNZ22) and of a Y chromosome-specific sequence (DYZ1) to document prospectively chimerism in 23 leukemia patients grafted with non T-cell depleted marrows from HLA-identical sibling donors. Twenty-two patients had a complete hematopoietic chimerism (within the sensitivity limit of the method used: 1%) early (about 1 month) after transplantation and one had detectable residual host cells (partial chimerism). These cells were still present after 8 months, and this patient relapsed 16 months after transplantation. Two patients with early complete chimerism relapsed 16 and 17 months after transplantation. Seven patients died from toxicity or infections and 13 are in clinical remission with a follow-up of 16 to 48 months. Nine male patients grafted with the marrow from a female donor were also studied by amplification of the DYZ1 marker (0.01% sensitivity). In all nine cases, residual male nucleated cells were detected early and up to 1 year after transplantation. These results suggest that the detection of persistent residual recipient cells above a 1% level might be predictive of relapse but that the detection of such cells in a 0.01-1% range is probably unrelated to relapse and does not seem to influence the outcome of the transplantation procedure.

Bone Marrow Transplantation↗
PubMed1993

Follow-up thallium-201 scintigraphy after mantle field radiotherapy for Hodgkin's disease.

PURPOSE: Assessment of the long-term cardiac effects of mediastinal radiotherapy for Hodgkin's disease, by Thallium scintigraphy. METHODS AND MATERIALS: 32 patients (14 males and 18 females) who underwent mantle field radiotherapy for Hodgkin's disease were included in this study. Twenty patients received 4 fractions of 2.5 Gy per week and 12, five fraction of 2 Gy per week, delivered on alternate days. All the patients, except three, performed exercise testing electrocardiogram and Thallium-201 tomoscintigraphy. The average time interval from completion of treatment to the study was 7 years (range 3-13 years). No patients had clinical symptoms of cardiac disease. Mean age at the time of the study was 35 years (range 23-48 years). RESULTS: Two electrocardiograms revealed left bundle branch block and the patients were excluded from the study. Only one out of 27 exercise electrocardiograms was abnormal in a patient with mitral valve prolapse, who was also excluded from the study. Twenty-six scintigraphies were evaluable. Twenty-two (85%) were clearly abnormal with partial or complete redistribution on delayed images. The anterior region was affected in 19 of these cases (86%). Four explorations were undoubtedly normal. Coronary angiography was not performed for ethical reasons in these asymptomatic patients. CONCLUSION: Despite possible false positive tests, the high rate of abnormality (85%) in this small series is striking. These preliminary data justify larger studies and a close long-term follow-up of these patients.

Adult↗
PubMed1993

Predictive value of in vitro radiosensitivity parameters in head and neck cancers and cervical carcinomas: preliminary correlations with local control and overall survival.

PURPOSE: To determine whether in vitro radiosensitivity parameters are predictive of treatment outcome. METHODS AND MATERIALS: Biopsies were obtained from patients with head and neck cancers (57) and cervical carcinomas (20) and in vitro radiosensitivity parameters were obtained using the CAM plate assay. RESULTS: In most cases (75%) patients were treated with radiation alone. The median follow up was 461 days. When the whole group of head and neck cancers and cervical carcinomas was considered, patients with a SF2 value below 0.36 had a higher 2-year local control rate (93% versus 68%) and a higher 2-year survival rate (71% vs. 62%) than those with SF2 values above that threshold, but differences were not significant. These trends persisted when head and neck cancers were considered alone with a higher local control rate (86% vs. 67%) and a higher survival rate (75% vs. 52.5%) obtained for patients with a SF2 value below 0.36. When the alpha value was evaluated for the whole group of patients a significantly higher local control rate (80.5% vs. 40.5%) and overall survival rate (71% versus 37.5%) at 2 years were obtained for patients with alpha values above 0.07 Gy-1. When only the group of head and neck cancers was considered, local control rate was significantly higher (79% vs. 33%) but overall survival rate (65.5% vs. 33%) was not significantly higher for alpha values above 0.07 Gy-1. CONCLUSION: These results are encouraging but need to be confirmed with a larger number of patients with a longer follow-up.

Carcinoma, Squamous Cell↗
PubMed1993

Prospective study of the clinical symptoms of therapeutic whole body irradiation.

Thirty-one selected patients with various haematological malignancies who received a 10 Gy-4 h total body irradiation (TBI) at the Institut Gustave Roussy 24 h before high dose cyclophosphamide for bone marrow transplantation, were prospectively evaluated for gastrointestinal symptoms, body temperature, consciousness, headache, xerostomia, parotiditis, ocular symptoms, blood pressure, and respiratory and cutaneous signs for 24 h. In spite of prophylactic administration of various anti-emetic agents, 90% of the patients experienced nausea and 80% experienced vomiting. An almost constant body temperature peak--up to 40.8 degrees C--was registered 6 h after the start of irradiation. No drowsiness was reported since the introduction of the new anti-emetic agent Ondansetron. Nearly half the patients (42%) complained of headache. The proportion of patients experiencing early (during TBI) xerostomia was 61%. 74% of patients complained of parotiditis in the first 24 h. Although this low dose rate whole body irradiation is not likely to be exactly replicated in many accidental human exposures, the incidence rate and the time-course of the observed prodromal phase symptoms may prove helpful for early triage in the case of accidental irradiation.

Adolescent↗
PubMed1993

Class I and II HLA typing after a 10 Gy-4 hour therapeutic total body irradiation.

Class I and II HLA typing was investigated before and at various intervals after a 10 Gy total body irradiation delivered over 4 h, prior to allogeneic bone marrow graft for various hematological malignancies, in 14 patients. A reliable class I HLA typing appeared to be possible in almost all cases 6-8 hours after the start of irradiation but was only possible in 5 patients after 24 h. Preliminary results with class II antigens might suggest a more marked "fragility" of this antigen class after irradiation. These results encourage the drawing of blood samples for HLA grouping as soon as possible after accidental whole-body irradiation.

Accidents↗
PubMed1992

Cancer after bone marrow transplantation. IBMTR and EBMT/EULEP Study Group on Late Effects.

Cancer may be serious late effect of marrow transplantation. Radiation, chemotherapy, immunosuppression and the original disease for which transplantation was performed may predispose to the development of cancer. 116 of 9732 patients reported to the IBMTR (International Bone Marrow Transplant Registry) have developed a new malignancy. Late effects were evaluated by the EBMT-EULEP (European Bone Marrow Transplant-European Late Effect Project) Late Effect Study Group in 147 patients surviving 6 years and 79 patients surviving more than 10 years. New malignancies developed in 11 of these patients. Lymphomas and leukemia comprised 73 cases reported to the IBMTR and one case reported to the EBMT-EULEP study. Tumors of the skin, oropharynx, vulva vagina and cervix prevailed in 41 patients with solid tumors. The distribution of malignancies is similar to that observed in organ transplant patients not given radiation or chemotherapy and suggests immunosuppression as a major contributory factor. In dogs the incidence of malignancies was studied after either chemotherapy or total body radiation in various regimens and marrow transplantation. Both chemotherapy and radiation shortened tumor-free survival in comparison to untreated dogs. Higher doses, larger fractions and shorter treatment schedules enhanced earlier tumor development. Soft tissue sarcomas and thyroid carcinoma were most frequent in treated, mammary carcinoma in untreated dogs. In treated dogs deaths from cancer were observed starting at the age of 5 years as compared to untreated dogs at the age of 9 years. The data from animal experiments indicate that the incidence of solid tumors in marrow transplant patients may still rise in the coming decades.

Animals↗
PubMed1991

Bone marrow transplantation in 107 patients with severe aplastic anemia using cyclophosphamide and thoraco-abdominal irradiation for conditioning: long-term follow-up.

Since 1980, 107 consecutive patients (pts) underwent bone marrow transplantation (BMT) for nonconstitutional severe aplastic anemia (SAA) at our institution. All received conditioning with Cytoxan (150 mg/kg) and thoraco-abdominal irradiation (6 Gy) from an HLA-identical sibling donor. Mean age was 19 years (5 to 46 years). Forty-nine pts had less than 0.2 x 10(9)/L PMN and 53 failed to respond to previous immunosuppressive therapy before BMT. Graft-versus-host disease (GVHD) prophylaxis consisted of methotrexate (22 pts), cyclosporine (52 pts), or both (33 pts). With a median follow-up of 45 months (12 to 120 months), overall actuarial survival was 68% (confidence interval 95%:9.7). Of 16 factors tested, five were shown to adversely influence survival by multivariate analysis: grade greater than or equal to 2 acute GVHD (relative risk [RR]: 5.5), prior immunosuppressive therapy (RR: 3.5), female as donor (RR: 2.4), nonidiopathic SAA (RR: 2), and more than 0.2 x 10(9)/L PMN AA (RR: 2). Because acute GVHD was the most potent factor for survival, we analysed risk factors for acute GVHD. By multivariate analysis, 2 of 14 factors tested were independent: male as recipient (RR: 3) and previous alloimmunization of the donor (RR: 4.3). On long-term follow-up, chronic GVHD was observed in 49 pts of 89 surviving more than 100 days (55%). Multivariate analysis showed that infection before transplant (RR: 1.3) and previous history of acute GVHD (RR: 1.8) were associated with an increased risk of chronic GVHD.

Abdomen↗
PubMed1991

Influence of the fractionation of total body irradiation on complications and relapse rate for chronic myelogenous leukemia. The Groupe d'Etude des greffes de moelle osseuse (GEGMO).

One hundred eighty patients with chronic myelogenous leukemia, who received an unmanipulated marrow graft from an Human Leucocyte Antigen identical sibling donor, were reported to our group (G.E.G.M.O.) by 21 transplant teams. All were grafted after a total body irradiation-cytoxan conditioning regimen. Of these 180 patients, 126 were non-randomly assigned to single dose total body irradiation (STBI group) and, 54 to fractionated total body irradiation (FTBI group). With a median follow-up of 40 months, there is no statistically significant difference in the 5-year survival rate between the two groups (51% for the whole population). In a first step we demonstrate by multivariate analysis that total body irradiation fractionation can dramatically decrease the incidence of interstitial pneumonitis. However, a multivariate analysis of potent risk factors for relapse post-transplant strongly suggests that TBI fractionation is also linked to an increased relapse rate. So, a sparing effect of fractionation for lung tissue could be offset by a less effective leukemic stem cell kill. Those results from a retrospective, non-randomized, multi-institutional study clearly need additional clinical data, ideally from a randomized study.

Bone Marrow Transplantation↗