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Biomedical subjects

G Novakovitch

Publications and source records attributed to G Novakovitch.

At least 55 records · Page 3Linked to original sources
PubMed1988

Selective depletion of marrow-T cytotoxic lymphocytes (CD8) in the prevention of graft-versus-host disease after allogeneic bone-marrow transplantation.

In vitro depletion of mature pan-T lymphocytes has been widely and successfully used to prevent acute graft-versus-host disease (GVHD) after allogeneic bone-marrow transplantation (BMT). However, this procedure has been associated with a high incidence of graft failure and leukemic relapse. In this pilot study, we evaluated the efficiency of a selective depletion of human marrow T cytotoxic lymphocytes (CD8), a subset essential to induce GVHD in mice. Eleven patients with hematologic malignancies were included (7 HLA-matched BMT, 4 HLA-mismatched BMT). Marrow treatment with 7 anti-CD8 mAbs and rabbit complement resulted in a marked reduction of CD8+ lymphocytes from 15% (median value; range 7%-31%) to 1% (median value; range less than 1%-11%). Acute GVHD was not abolished by this procedure despite postgraft immunosuppression. One patient (HLA-mismatched BMT) rejected his graft and had a full autologous recovery. In conclusion, when compared to the data in the literature, CD8 depletion was shown to be less efficient than pan-T-cell depletion in the prevention of GVHD after allogeneic BMT and was still associated with a major complication associated with this procedure, i.e., graft failure.

Adolescent↗
PubMed1988

Repeated courses of high dose melphalan and unpurged autologous bone marrow transplantation in children with acute non-lymphoblastic leukemia in first complete remission.

Eleven children between the ages of 1 and 16 years with acute non-lymphoblastic leukemia (ANLL) in first remission were included in a study of double unpurged autologous bone marrow transplantation (ABMT). Prior to each ABMT patients received massive chemotherapy with melphalan at a dosage of 140 mg/m2. The first ABMT was done within a median of 4 months after the achievement of complete remission. As soon as the children had adequate hematologic recovery, a second marrow collection was done, followed by a second course of melphalan and a second ABMT. The duration of aplasia was significantly longer after the second ABMT than after the first, but the non-hematologic toxicity was relatively mild in each case and no patient died from the procedure. Four patients relapsed and seven are alive in unmaintained complete remission with a median duration of leukemia-free survival of 29 months (range 15-56 months) after the first ABMT. These data demonstrate the feasibility of repeating ABMT after melphalan in children with ANLL. The eventual impact of such therapy needs to be demonstrated in prospective randomized studies.

Adolescent↗
PubMed1988

[Bacteremias after bone marrow grafts in a protected environment: effects, various aspects and prognosis].

We evaluated retrospectively the incidence and prognosis of bacteremias after bone marrow transplantation treated in protected environment with intestinal decontamination. Bacteremias are more frequent during the extreme granulopenia (55% of the patients) than during recovery of granulocyte counts greater than 500/mm3 (35% of the patients). Gram + organisms are more frequently responsible of bacteremias (80%), mainly Staphylococcus epidermidis and Streptococci. Mortality is low (7%) and related to additional factors like GVH, resistant leukemia. These data invite to develop new approaches of prevention of bacterial infection, with measures possibly efficient on Gram + organisms.

Adolescent↗
PubMed1988

Partial chimerism after T-cell-depleted allogeneic bone marrow transplantation in leukemic HLA-matched patients: a cytogenetic documentation.

We evaluated serially by cytogenetics the blood and marrow chimerism of 38 leukemic recipients of HLA-matched bone marrow transplants (BMT) who were prepared by high doses of alkylating agents and fractionated total-body irradiation (2.2 Gy X 5). Donor or host mitoses were identified by examination of sex chromosomes in 32 patients or by evaluation of the polymorphism of other chromosomes after specific banding in six patients. Twenty-four patients were recipients of untreated BMT, and 14 were recipients of T-cell-depleted BMT. In the 24 patients who received untreated BMT, all showed successful engraftment, and only three had a transient mixed chimera. In the 14 recipients of T-cell-depleted BMTs, four rejected their grafts, and seven had mixed chimeras; these mixed chimeras were more frequent in blood lymphocytes than in marrow cells and could be detected up to 26 months after BMT. This high frequency of partial chimerism after T-cell-depleted BMT by comparison with a control group suggests that the donor's T cells play an important role in the eradication of host residual hematopoiesis after allogeneic BMT.

Adolescent↗
PubMed1987

[Use of allografts in oncology and traumatology].

Fresh allografts of bone are commonly used for repairing small defects, but preserved grafts are required for replacing large sections of long bones. We have collected these grafts in sterile conditions and then preserved the specimens in liquid nitrogen at minus 196 degrees Celsius. Biological, histological and biomechanical studies have confirmed the value of this technique. The method preserves the normal architecture of bone and viable cartilage cells. The medullary cells are gradually destroyed in situ leaving a protein matrix to which mineral components are fixed. Neither of these are antigenic in allografts and immunological problems are rarely encountered. When the recipient site is well vascularised the graft becomes fully integrated within two or three years. Doubt has been expressed as to the functional viability of the cartilage in large allograft joint replacements, and is has been suggested that metal prostheses might be better. Research is in progress in the use of ligament allografts and on the use of bank bone with large prostheses. The functional results are satisfactory in more than 90% of patients treated with these large allografts.

Adolescent↗
PubMed1986

Treatment of malignant lymphoma with high dose of chemo or chemoradiotherapy and bone marrow transplantation.

Twenty-eight patients with malignant lymphoma were treated with high dose chemo or chemoradiotherapy and allogeneic or autologous bone marrow transplantation. They can be divided in two groups: Group 1: (19 pts) consisted in patients in relapse or in n complete remission (n greater than 2) (high risk patients); Group 2 (9 pts) consisted in patients in first or second complete remission at time of bone marrow graft (standard risk patients). Complete remission was achieved in 11/17 patients evaluable for response (65%). Duration of response is very different for two groups: in group 1, all patients relapsed within a median of 2 months (range: 1-12) and died within a median of 7 months (range: 2.5-15). In group 2, 7/9 are alive and well in unmaintained CCR in a median of greater than 18 months (range: greater than 15- greater than 36) (P less than 0.01). This experience shows the feasibility of this approach, the obvious antitumoral activity of these conditioning regimens and invited us to use such therapy at an earlier stage of the disease.

Adolescent↗
PubMed1986

High-dose melphalan with or without marrow transplantation: a study of dose-effect in patients with refractory and/or relapsed acute leukemias.

Dose-effect relationships of high-dose melphalan were evaluated in 37 patients with measurable relapsed or refractory acute leukemias. Thirteen patients (Group 1) received 70-100 mg/m2 of melphalan without marrow rescue and 24 patients (Group 2) received 140-180 mg/m2 of melphalan followed by marrow transplantation. Patients in both groups were comparable with respect to age, sex, diagnosis, and status of the leukemia. The complete remission rate was 23% in Group 1 versus 75% in Group 2 (P less than 0.01). Hematological recovery of remission patients was not statistically different in either group. Nonhematological toxicity was comparable in the two dose ranges examined. These results demonstrate the existence of a dose-response effect of high-dose melphalan regimens in relapsed acute leukemias, without marked increases in nonhematological toxicity with these doses.

Acute Disease↗
PubMed1986

Modified chemotherapy with carmustine, cytarabine, cyclophosphamide, and 6-thioguanine (BACT) and autologous bone marrow transplantation in 24 poor-risk patients with acute lymphoblastic leukemia.

Twenty-four poor-risk patients with acute lymphoblastic leukemia received a modified regimen of carmustine, cytarabine, cyclophosphamide, and 6-thioguanine (BACT) followed by autologous bone marrow transplantation (ABMT). Nineteen patients were in second or subsequent complete remission (CR) when treated with this regimen; 3 died early, 2 died of pneumonia in CR, 11 relapsed within 3 months (median), and 3 remain in CR with no maintenance therapy 14-24 months after ABMT. Of the 5 patients with measurable disease who were treated, 3 had CR and 1 remains in CR without maintenance therapy more than 28 months after ABMT. The toxicity of this regimen was acceptable, but late pulmonary toxic effects remain a major concern. These results are poor in terms of efficacy, and new effective methods of eradicating acute lymphoblastic leukemia in patients with poor prognosis should be investigated.

Adolescent↗
PubMed1985

Phase-I-II study of high-dose melphalan and autologous marrow transplantation in adult patients with poor-risk non-Hodgkin's lymphomas.

Eleven adult patients with poor-risk non-Hodgkin's lymphoma were treated with high-dose melphalan (140 mg/m2) or high-dose combination chemotherapy (BCNU, Ara-C, vindesine and melphalan) followed by autologous bone marrow transplantation. Six of the eight patients evaluable for response achieved complete remission and one achieved partial remission. Response duration ranged from 1.5 to 12 months (median 2 months). Prompt hematological recovery occurred in all patients. The duration of aplasia and the extrahematological toxicity were similar in both groups. High-dose melphalan alone or associated with other drugs followed by marrow infusion appears to produce a high response rate and demonstrates the potential for salvaging patients with refractory lymphoma.

Adult↗
PubMed1983

High-dose melphalan and autologous bone marrow transplant for relapsed acute leukaemia.

Seven patients with relapsed acute leukaemia were treated with high-dose melphalan (HDM) followed by the infusion of autologous cryopreserved remission marrow. Toxicity was minimal and all seven patients had a complete response. Four patients are still in unmaintained remission at 14, 13, 10, and 3 months, the first two having received a second course of HDM to consolidate the result. The role of HDM as a form of intensification therapy for patients with acute myeloid leukaemia in first remission should be investigated.

Adult↗
PubMed1983

[Granulocytic progenitors in bone marrow autografts].

Granulocytic progenitor cells (CFC) are a better reflection of stem cell pools than precursors. Their total number can be estimated during hematologic steady-state (N = 70 +/- 29 x 10(5) CFC/kg); the amount of marrow necessary to perform a bone marrow transplantation is only 1% of the total pool. CFC are useful but have a mainly qualitative value in evaluating the viability of marrow stored for 24 h at room temperature (92%) or marrow thawed after DMSO cryopreservation (62%). Sequential study of CFC in patients receiving autologous marrow transplantation enables differentiation of engraftment from autologous recovery. In 11 recipients of autologous marrow transplantation, no statistical relation was observed between number of infused CFC and severity of granulocytopenia. Further studies will be necessary to evaluate a better marker of real hematopoietic stem cells.

Adolescent↗
PubMed1982

[Incidence, prognosis and prevention of septicaemias in patients under treatment for acute leukaemia (author's transl)].

Septicaemias are frequent and severe in patients with acute leukaemia under aplastic treatment. The present study concerns 69 such patients: 29 with acute lymphoblastic leukaemia (ALL), and 40 with acute non-lymphoblastic leukaemia (ANLL). All were treated in single rooms in the same hospital and in similar conditions. The overall incidence of septicaemia was 62%; it was 60% in patients with recently diagnosed ALL and 68% during relapses. More than 34% of ALL patients and 82.5% of ANLL patients had one or several episodes of septicaemia. Among the 74 pathogens isolated 50% were Gram-positive organisms, 45% Gram-negative organisms and 5% Candida spp.. The first episodes of septicaemias were predominantly caused by Gram-positive spp. (61%) and the subsequent ones by Gram-negative spp. (60%). The primary infection could only be diagnosed in 19% of the cases and was most frequently located in the digestive tract or perineal region. The most common focal complications were lung infections (18 cases), skin infections (12 cases) and septic shock (15 cases). Seventy-four p. cent of the patients survived with prompt and potent antibiotic therapy. Death occurred in 26% and was clearly related to the following factors: chemotherapy of relapsed leukaemia and/or blastic aplasia and/or successive episodes of septicaemia. The incidence and severity of septicaemias in leukaemic patients will only be reduced by improved prophylactic measures against infection and by less pronounced and shorter chemotherapy-induced granulocytopenia.

Acute Disease↗
PubMed1979

[P50 and stored blood (+4 degrees C and -80 degrees C). In vitro studies].

The authors studied the hemoglobin oxygen affinity (P50) and the 2,3 diphospho-glycerate (2,3-DPG) level in: 33 samples of total stored blood (ACD medium); 14 samples of the same blood after mixing with a solution including inosine, pyruvate, phosphate (I.P.P.); 9 samples of freezed erythrocytes. The increase of the hemoglobin oxygen affinity, associated with a decrease of the 2,3-DPG level appears to be very fast in the samples of ACD stored blood since two hours after sampling, the P50 decrease was of 4 torr. Exposure to the I.P.P. solution (1 H at 37 degrees C), caused the hemoglobin oxygen affinity and the 2,3-DPG concentration to return to their normal values (P50 = 25.4 torr +/- 0.4 torr); 2,3-DPG = 15.6 +/- 0.9 muM.gHb-1). When freezed red blood cells, were defreezed the P50 was found to be 4 torr lower than that of fresh blood and the 2,3-DPG level was also decreased (-4.1 muM.gHb-1). These decreases are probably related to the delay which occurred between blood sampling and freezing.

Blood Preservation↗
PubMedDate not supplied

Psychosocial aspects of haematopoietic stem cell donation for allogeneic transplantation: how family donors cope with this experience.

Peripheral blood stem cell (PBSC) allogeneic transplantation is an innovative medical procedure which has many advantages in comparison with bone marrow (BM) transplantation, but it involves administering haematopoietic growth factors (HGFs) to donors, the long-term physiological effects of which have not yet been established. The main aim of the present study was to analyse how family PBSC donors cope when confronted with this particular risk context. In addition to data collected on the personal and social aspects of the donors' experience, questionnaires were used to measure their quality of life (pain and anxiety) before, during and after donation, and they were subsequently interviewed in depth by a psychologist. Twenty-two donors participated in this study. They did not all react to the experience of blood cell donation in the same way, in terms of their own personal feelings, attitudes towards the donation, their relationships with the other members of the family, and their awareness of the risk involved.

Adaptation, Psychological↗
PubMedDate not supplied

[Tobacco consumption and carboxyhemoglobin levels in blood donors].

The authors studied the tobacco consumption of 283 blood donors and its consequences. 151 were nonsmokers and 132 were smokers (47.7% smoke more than 10 g/day). Their mean HbCO level was 4.3 +/- 0.2% (highest level 15%). HbCO levels are significantly correlated with daily tobacco consumption (p less than 0.001) and can be estimated with the following regression equation: HbCO% = 0.176 (tobacco in grams/day) + 1.976. For a similar consumption, inhalers exhibit significantly (p less than 0.001) higher HbCO levels than noninhalers and the increase is significantly higher (p less than 0.02) in inhalers who smoked 1 h or less prior to blood sampling. High HbCO levels have two consequences: in the donors they have caused a tobacco polycythemia syndrome and in the recipients they have caused acute problems in cases of massive blood transfusion and cardiovascular surgery with extracorporeal circulation.

Blood Donors↗