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Biomedical subjects

F Isnard

Publications and source records attributed to F Isnard.

At least 55 records · Page 3Linked to original sources

Multiple chromosome abnormalities in patients with acute leukemia after autologous bone marrow transplantation using total body irradiation and marrow purged with mafosfamide.

Cytogenetic follow-up studies such as those reported after allogeneic bone marrow transplantation are not available in patients submitted to an autologous bone marrow transplantation (ABMT). Of 114 patients with acute leukemia (69 acute myelocytic AML, 43 acute lymphocytic ALL, 2 undifferentiated) who underwent an ABMT in our institution in the period from February 1983 to December 1989, 66 had evaluable cytogenetic data post-transplant. They all received a pretransplant regimen consisting of cyclophosphamide (CY) and total body irradiation (TBI) followed by reinfusion of marrow purged with mafosfamide. Twenty patients showed chromosomal damage at some time; of these, six relapsed early post-ABMT, one died while in persisting remission at 81 months post-ABMT from overwhelming pneumococcal sepsis related to a previous splenectomy, and 13 are still alive and well at 13 to 88 months post-transplant. The bone marrow cytogenetic abnormalities were complex: they included various numbers of clonal aberrations or variations or combination of those; they affected all but the Y chromosome, with a predominance however for chromosomes 1, 3, 6, and 7; they were often transitory and in some instances became modified with time. None of these chromosomal abnormalities was connected with the initial leukemia, even in the 6 patients who relapsed early. In the other 14 patients, these abnormalities have so far had no detectable unfavourable implication. The origin of these abnormalities is unknown: both the pretransplant regimen (CY and/or TBI) and/or marrow purging with mafosfamide can be incriminated. Additional studies in patients autografted with pretransplant regimen not containing TBI and/or with unpurged marrow are necessary to discriminate between these two possibilities.

Antineoplastic Agents↗

[Severe respiratory syncytial virus pneumonia following bone marrow autograft. 3 cases].

Three patients developed severe respiratory syncytial virus pneumonia after bone marrow autograft for acute leukaemia. Clinically, the disease presents as interstitial or bilateral alveolo-interstitial pneumonia with hypoxaemia. Signs of ENT infection (otitis media, sinusitis) are present in 30 percent of the cases. In all 3 patients, the syncytial virus was isolated by direct immunofluorescence in bronchoalveolar lavage fluid. In 2 patients the infection began soon after the autograft, in deeply aplastic subjects, and required intubation and assisted ventilation. These 2 patients died despite inhalation of aerosolized ribavirin combined, in one of them, with ribavirin injections. In the third patient the infection began some time after the autograft and responded well to ribavirin in aerosols. In these three cases the viral infection occurred in an epidemic and nosocomial context. The respiratory syncytial virus is usually transmitted by the hands. Owing to the severity of this infection with lung involvement in immunodepressed patients, specific prophylactic measures should be taken side by side with the conventional measures.

Administration, Inhalation↗

[Seraspenide (acetylSDKP): phase I-II trial study of inhibitor of hematopoiesis protects against toxicity of aracytine and ifosfamide monochemotherapies].

Seraspenide, a synthetic tetrapeptide, inhibits cell cycle entry of normal hematopoietic stem cells. In mice it protects hemopoiesis against the damage caused by cytarabine, cyclophosphamide and carboplatin. Seraspenide has been given to 53 cancer patients undergoing monochemotherapy with cytarabine and ifosfamide in a double-blind cross-over randomized study. A significant protection of peripheral blood cells has been observed. Seraspenide has been devoided of toxicity.

Cytarabine↗

Severe respiratory syncytial virus pneumonia after autologous bone marrow transplantation: a report of three cases and review.

Three patients with acute leukemia who underwent autologous bone marrow transplantation (BMT) in complete remission, developed a severe respiratory syncytial virus (RSV) pneumonia, which was fatal in two. Identification of RSV was made on the products of bronchoalveolar lavage by direct immunofluorescence. As already described by others, the initial course of RSV infection varies, depending on whether it occurs sooner or later after BMT with a better prognosis in the latter situation. Treatment consists of aerosolized ribavirin. Infection by RSV is caused by manual contact with infected persons and contaminated surfaces. The severity of lung RSV infection in the course of BMT suggests the need for prophylactic measures in addition to standard isolation precautions.

Acute Disease↗

GM-CSF instead of autologous bone-marrow transplantation after the BEAM regimen.

Five patients with resistant non-Hodgkin lymphoma (NHL) were given granulocyte-macrophage colony-stimulating factor (GM-CSF, 250 micrograms/m2 daily) after the BEAM pretransplant chemotherapy regimen (carmustine 300 mg/m2, etoposide 1.2 g/m2, cytarabine 800 mg/m2, melphalan 140 mg/m2) because persistent lymphoma cell infiltration of the bone marrow precluded autologous bone-marrow transplantation (BMT). In three patients full haemopoietic reconstitution occurred, with similar kinetics to that seen after autologous BMT. The other two patients died without sustained haemopoietic recovery. GM-CSF may replace autologous BMT in highly selected cases of NHL with progressive disease and bone-marrow involvement.

Adolescent↗

Feasibility of autologous bone marrow transplantation for early consolidation of follicular non-Hodgkin's lymphoma.

In contrast to intermediate- and high-grade non-Hodgkin's lymphomas (NHL), patients with follicular lymphomas retain a poor prognosis in the long run. Several reports suggested that they are incurable by conventional chemotherapy. 10 patients with follicular NHL were autografted for consolidation of early remission. One of these patients treated in 1979 received the TACC regimen with unpurged marrow. The other 9 (8 in first, 1 in second remission) treated since July 1987 received the BEAM regimen followed by autologous bone marrow transplantation (ABMT) with marrow purged in vitro by mafosfamide at levels individually adjusted. There were no toxic deaths. 8 patients remain in unmaintained CR 15 to 43 months post-ABMT-2 are beyond 2 years. The patient autografted in 1979 has relapsed 9 yr later. ABMT is feasible with no indue toxicity for consolidation of follicular NHL early in first remission, as an alternative aggressive strategy. Further studies and a longer follow-up will be needed to evaluate its antitumor efficacy.

Adult↗

Prophylactic heparin does not prevent liver veno-occlusive disease following autologous bone marrow transplantation.

Veno-occlusive disease (VOD) is a major cause of toxic death after autologous bone marrow transplantation (ABMT). We studied the potential role of continuous administration of low-dose heparin for VOD prevention in 234 consecutive patients who underwent ABMT in our institution. The population consisted of 98 patients autografted before October 1984 who did not receive heparin, and a series of 136 patients autografted from October 1984 to March 1989 containing 98 patients included in a randomized trial comparing heparin administration (n = 52) vs no heparin (n = 46), and an additional group of 38 patients who received non-randomized heparin in view of high-risk criteria to develop VOD (n = 31) or other reasons unrelated to VOD (n = 7). Overall, 90 patients (38%) received heparin and 144 (62%) did not. The global incidence of VOD was 13/234 (5-5%). Heparin did not reduce the risk of VOD in all subgroups studied. In particular, in the randomized trial, the incidence of VOD was 2.2% in the group without heparin vs 7-7% in the group receiving heparin. We analyzed in depth the 13 patients who developed VOD and we compared them to a control group of 13 patients pair-matched for age, sex, diagnosis and preparative regimen, who did not develop VOD. We found that abnormal LFT before ABMT predisposed patients to VOD; refractoriness to platelet transfusion was observed in 85% of the patients in the VOD group vs 15% in the control group (p less than 0.05). VOD patients had an increased requirement for red cells and platelet transfusions, a lower recovery (R less than 25%) after the second and third platelet transfusion, and shorter intervals separating the first four platelet transfusions. Further, the platelet reconstitution after ABMT in the VOD group was slower in comparison to the control group (p less than 0.01). Again, in this pair-matched analysis continuous infusion of low-dose heparin did not prevent VOD.

Adolescent↗

Expansion by folinic acid of the peripheral blood progenitor pool after chemotherapy: its use in autografting in acute leukaemia.

We have tested folinic acid (FA) for ability to increase peripheral blood stem cells (PBSC) after chemotherapeutic aplasia in acute leukaemia. Five adult patients (four AML, one ALL) entered the study, each patient underwent two series of three leukapheresis, the first following induction chemotherapy and the second following the first course of consolidation. The first leukapheresis of each series was done when the white blood cell count reached 10(9)/l with subsequent leukapheresis every other day. Folinic acid (Lederle Laboratories, France) was administered at a dose of 50 mg (i.v.) per day, 15 days from initiation of chemotherapy and continuing through the third leukapheresis of the series (days 25-30). PBSC were collected on a Haemonetics V50 cell separator. In these five cases we observed an increased yield of both colony-forming units, granulocyte macrophage (CFU-GM) and burst forming units-erythroid (BFU-E) expressed per ml of cytapheresis product: CFU-GM x 18, BFU-E x 3 and if expressed per 10(4)/kg of body weight: CFU-GM x 30, BFU-E x 3 (CFU-GM P less than 0.05, BFU-E less than 0.01). Long-term blood culture (LTSC) from FA stimulated leukapheresis, in an attempt to quantitate the most primitive stem cells, demonstrated that this expansion of the PBSC was sustained in time. We found by means of LTSC that FA did not stimulate CFU-L from patients with AML (two cases tested). Finally two AML patients were grafted with FA-PBSC after Cytotoxan and total body irradiation (TBI). Haematopoietic reconstitution was rapid complete and sustained in time in both patients. This indication for folinic acid should be further studied with or as an alternative to haematopoietic growth factors.

Adult↗

Type 2 diabetes in the elderly: an assessment of metformin (metformin in the elderly).

Metformin efficacy and safety in type 2 diabetes has not been studied in the elderly patient under conditions pertaining to clinical practice. We have therefore, studied prospectively over two months 24 patients aged between 70-88 years with 115% mean ideal body wt and glycemic control greater than 10 mol.l-1 fasting and/or greater than 14 mol.l-1 postprandial, and/or an HbA1 value greater than 10%. At entry into the study, patients were on metformin + sulfonylurea (n = 15), sulfonylurea (n = 3), metformin (n = 2), insulin (n = 1) or diet alone (n = 3). They received metformin as the sole therapy when possible (sulfonylureas were discontinued in 9 cases) at a dosage of either 850 mg or 1,700 mg/day dependent on creatinine clearance values of 30-60 ml.min-1 (n = 11) and greater than 60 ml.min-1 (n = 13), respectively. Compared to pretreatment values, glycemic control at 1 and 2 months were unchanged, with metformin blood levels remaining within expected values for both dosage groups. Blood lactate levels remained unchanged in the high dosage group but were reduced (p less than 0.05) on 850 mg/day probably because of the reduction of metformin dosage in patients already treated prior to the study. It is concluded that provided the dosage is adjusted to renal function, the metabolic tolerance of metformin therapy is satisfactory in the elderly type 2 diabetic patient. With regard to efficacy, longer observations are needed to know whether this therapy may offer on a long-term basis equivalent glycemic control compared to other treatment modalities.

Aged↗

[Bone marrow autograft treated with mafosfamide in the acceleration phase in chronic myeloid leukemia. Inversion of the clinical development].

A 21-year old male patient with Philadelphia chromosome-positive chronic myeloid leukaemia received an autologous bone marrow transplant in consolidation of the 2nd chronic phase. The bone marrow had been treated with mafosfamide in adequate doses. The post-transplantation course of the disease was marked by an inversion: the duration of the 2nd chronic phase was more than 4 times longer than that of the first one, suggesting some degree of effectiveness of autologous bone marrow transplantation performed in the 2nd chronic phase and/for of the in vitro treatment of the bone marrow with mafosfamide. Cytogenetic monitoring was pursued throughout the course of leukaemia: regression of the Philadelphia chromosome was only partial and transient, and 3 clones appeared, each of them involving chromosome 1, for which mafosfamide was most probably responsible.

Adult↗

Effect of yohimbine on blood pressure in patients with depression and orthostatic hypotension induced by clomipramine.

Orthostatic hypotension, one of tricyclic antidepressant treatment's side effects, is also a factor in limiting adequate antidepressant dosing. We tested in a double-blind, crossover, placebo-controlled study the effect of low doses (4 mg/t.i.d.) of yohimbine in 12 patients with depression with clomipramine-induced orthostatic hypotension. Yohimbine, a selective alpha 2-adrenoceptor antagonist, had a favorable effect in orthostatic hypotension and induced a significant increase in blood pressure. A pharmacodynamic and pharmacokinetic interaction between yohimbine and clomipramine or demethylclomipramine was discussed.

Adult↗