Biomedical subjects
G Tertian
Publications and source records attributed to G Tertian.
[Recurrent thrombocytopenic thrombotic purpura associated to prostatic cancer. A case].
The association between thrombocytopenic thrombotic purpura (TTP) and infectious or multisystem disease, pregnancy, transplantation, drugs and toxins is well known. The onset of TTP in the course of neoplasm is rarely described. The authors report one case of TTP associated with prostatic tumor. TTP preceded the discovery of neoplasm by 12 months. Moreover, TTP showed an original course with four recurrences despite antiplatelet and hormonal therapies; the successive regressions were obtained with less and less effort, as TTP was discovered at an early stage.
A randomized trial of amsacrine and rubidazone in 39 patients with acute promyelocytic leukemia.
Thirty-nine patients with untreated acute promyelocytic leukemia (APL) were randomly allocated to receive rubidazone (zorubicin) 200 mg/m2/d, days 1 to 4 plus cytarabine (Ara C) 200 mg/m2/d, days 1 to 7 (arm A, 21 patients), or amsacrine (Amsa) 150 mg/m2/d, days 1 to 4 plus Ara C 200 mg/m2/d, days 1 to 7 (arm B, 18 patients). Prophylaxis of disseminated intravascular coagulation was made by platelet transfusions and heparin. In case of leukemic resistance, patients received a second course with 2 days of rubidazone (arm A) or Amsa (arm B) and 3 days of Ara C. Patients who achieved complete remission (CR) received three consolidation courses with the two drugs used for induction and maintenance therapy for 3 years. Two patients in arm A and one in arm B were allografted in first CR. Initial characteristics were similar in both arms. In arm A, 18 patients (86%) reached CR, two had hypoplastic death, and one had leukemic resistance after two courses. In arm B, 12 patients (66%) achieved CR, two had early death (CNS bleeding, one case; ventricular fibrillation, one case), and four had resistant leukemia after two courses. The difference in CR rate between the two arms was not significant. In arm A, disease-free survival (DFS) showed a plateau at 54.3% after 34 months (95% confidence interval [CI], 32.1% to 74.9%), with eight CRs longer than 34 months. In arm B, DFS was significantly shorter (P less than .03), showing a plateau at 16.7% after 38 months (95% confidence interval, 4.7% to 44.6%), and only two prolonged CRs were seen. The difference in DFS remained significant after censoring allografted patients and patients who died in CR (one in arm A, two in arm B). Our results suggest that Amsa-Ara C combinations may be inferior to anthracycline-Ara C combinations in the treatment of APL, because they seem to provide shorter DFS and, possibly, a higher incidence of initial leukemic resistance. However, studies with larger numbers of patients are required.
[Immune neonatal thrombocytopenia].
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Fetal platelet counts in thrombocytopenic pregnancy.
Fetal platelet counts were assessed by percutaneous umbilical blood sampling in 64 pregnancies (62 women) with maternal thrombocytopenia. In 33 pregnancies associated with chronic immune thrombocytopenia, 11 of the fetuses had platelet counts below 150 x 10(9)/l and 4 were severely thrombocytopenic (less than 50 x 10(9)/l). In 31 pregnancies with symptomless maternal thrombocytopenia as an incidental finding, 4 fetuses were thrombocytopenic, 1 of them severely. Maternal indices, including antiplatelet antibodies, did not correlate with risk of fetal thrombocytopenia; and in those with repeat measurements there was no evidence of benefit from treatment with either corticosteroids (4 cases) or intravenous immunoglobulin (3 cases). Percutaneous umbilical blood sampling, a safe procedure in experienced hands, provides accurate platelet counts in thrombocytopenic pregnancy, as an aid to decisions on mode of delivery and to assessment of treatments.
Low-dose cytarabine versus intensive chemotherapy in the treatment of acute nonlymphocytic leukemia in the elderly.
We conducted a randomized multicenter trial comparing low-dose cytarabine (LD ARA-C) (20 mg/m2 for 21 days) with an intensive chemotherapy (rubidazone [a daunorubicin-derived agent], 100 mg/m2 for 4 days, ARA-C 200 mg/m2 for 7 days) in 87 patients over 65 years of age with de novo acute nonlymphocytic leukemia (ANLL). Forty-one patients received LD ARA-C and 46 received intensive chemotherapy. The number of complete remissions (CRs) but also of early deaths was higher in the intensive chemotherapy group, while partial remissions (PRs) and failures were more frequent in the LD ARA-C group (P less than .001). Infectious complications during induction treatment were more numerous and more severe in the intensive chemotherapy group (P less than .01). Patients treated with LD ARA-C required fewer RBC transfusions (P less than .02), fewer platelet transfusions (P less than .01), and had a shorter hospital stay for induction treatment (P less than .01). Overall survival and CR duration were not significantly different in either group. In the LD ARA-C group, the survival of patients with PR and those of patients in CRs was identical. We conclude that in a selected group of elderly patients with de novo ANLL a higher number of CRs may be obtained with intensive chemotherapy, but that with LD ARA-C, the number of early deaths is lower, and long-lasting PRs are obtained, resulting in a similar overall survival.
Prognostic factors of acute non lymphoblastic leukemia in children and adults. Results from two multicentric trials (705 patients).
705 children and adults patients with de novo acute nonlymphoblastic leukemia were entered from 1981 to 1989 into 2 prospectives multicenter trials: 01AM81 and 01AM86. They received an intensive induction course with Rubidazone 200 mg/sqm/day x 4 days and cytosine arabinoside 200 mg/sqm/day x 7 days, then 3 consolidation courses at outpatients, and a maintenance treatment. Total duration of therapy was 3 years. The overall complete remission rate was 80%. The median overall survival time was 19 months and the 5-year survival rate is 26%. The median remission duration for the 568 remitters was 18 months and the 5-year first remission rate is 30%. Prognostic factors for the remission rate were age, initial leukocytosis, FAB subtype. Prognostic factors for remission duration were the delay until CR, initial leukocytosis and karyotype.
[Treatment of aggressive non-Hodgkin's lymphoma in aged patients with a combination of methyl-GAG, etoposide and prednimustine].
The authors report the results of a chemotherapy regimen of methyl-GAG, etoposide and prednimustine in 21 elderly patients (median age = 78 years) with aggressive non-Hodgkin's lymphoma. Sixteen patients responded (11 complete remissions, 5 partial remissions) with minor toxic side-effects. This regimen could be proposed for patients whose age and/or cardiovascular status prohibit treatment with usual anthracycline-containing chemotherapy programs.
Low-dose arabinosyl cytosine therapy of AML may be effective after failure of high or conventional doses.
In 3 patients with ANLL, chemotherapy including high or conventional doses of Ara-C had been ineffective. However subsequent treatment with low-dose (LD) Ara-C induced a PR or CR which were sustained with regular LD Ara-C reinduction courses. Survival of the 2 patients with PR was 24 and 8 months respectively. The patient with CR was alive 18 months after a bone marrow graft. In 2/3 cases, the cytogenetic abnormalities initially detected disappeared with treatment. These observations suggest that the cellular mechanism of action of LD Ara-C is different from that of HD Ara-C, but do not favour a differentiating action of LD Ara-C. LD Ara-C can be prescribed as a salvage therapy even after failure of high or conventional doses.
Pregnancy and paroxysmal nocturnal hemoglobinuria.
Our study concerns eight pregnancies, six of which were successful, in four patients with paroxysmal nocturnal hemoglobinuria (PNH). Several complications of PNH during pregnancy were prevented: chronic anemia, folate and iron deficiency, and deep-vein thrombosis. During puerperium, acute hemolytic crises, most probably triggered by delivery, were observed in two patients. Thrombotic complications could be prevented by early initiation of an anticoagulant therapy after delivery. The only neonatal complication, observed in two cases, was isoimmune hemolytic anemia related to the multiple blood transfusions received before and during pregnancy. These results show that successful pregnancies are possible in women with PNH provided that both the obstetricians and physicians in charge monitor the pregnancies closely.
[Deferoxamine (Desferal) dermatitis].
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Intravenous gammaglobulin treatment for thrombocytopenic purpura in patients with human immunodeficiency virus (HIV) infection.
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[Marchiafava-Micheli syndrome and pregnancy].
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder characterized by sensitive populations of erythrocytes, granulocytes and platelets. PNH is a disease of young adults with a slight female predominance. Several complications of PNH during pregnancy, could be prevented; chronic anemia, folate and iron deficiency, deep vein thrombosis. We report seven pregnancies, six of which were successful in four patients. One pregnancy was terminated after 25 weeks by a fetal death during an acute hemolytic crisis. Diagnosis of PNH was made in the four patients before the pregnancy by the acidified serum lysis assay and the sucrose lysis assay. During puerperium, acute hemolytic crisis, most probably triggered by delivery, were observed in two patients. Thrombotic complications could be prevented by early initiation of an anticoagulant therapy after delivery. The only neonatal complication, observed in two cases was iso immune hemolytic anemia related to the multiple blood transfusions received before and during pregnancy. These results show that successful pregnancies are possible in PNH women when monitoring is especially close. To allow optimal fetal development, patients were transfused with saline-washed or frozen-thawed packed red-cells to prevent the precipitation of hemolysis, so that the hemoglobin level remained higher than 10 g/dl. During the whole pregnancy, patients had to be given dietary supplementation with folic acid and iron therapy whenever deficiency was demonstrated, under close surveillance of hemolysis. To prevent thrombotic complications during pregnancy, anticoagulant therapy was used if the patients had to be bedridden, or within 8 hours following delivery.
Selective inhibition of the proliferation of various murine hemopoietic progenitor cells by cholera toxin.
We have studied in detail the effects of cholera toxin (CT), its pentameric B-chain subunit (toxoid) and the A-promoter chain on the differentiation of hemopoietic progenitor cells. Murine marrow cells were treated either with CT or its subunits. After stimulation with either the multilineage growth factor (multi-CSF; also called interleukin 3 or HCGF) or other hemopoietic regulators (colony-stimulating factors, or CSF), the clones grown in semisolid collagen cultures were scored in situ. Pluripotent stem cells (CFU-S) and multilineage (mixed CFU) or lineage-restricted progenitors (CFU-c) were estimated. We found that CT sensitivity is gradually gained by cells through the stepwise differentiation processes (i.e., CFU-S less than multilineage CFC less than committed CFC less than maturing cells). CT also has a selective, dose-dependent inhibitory effect (1 microM to 1 pM) on hemopoietic lineages (basophil-mast cells less than megakaryocytes less than neutrophils less than monomacrophages). These phenomena were obvious when the clonal growth was supported by multi-CSF but, interestingly, were not observed when lineage-restricted CSF were used. They furnished additional evidence that multi-CSF activates cells in a specific manner. This growth factor involved in progenitor cell self-renewal control may contribute to maintaining, on maturing cells, characteristics that are normally the attributes of progenitors.
[Transient remission after viral infection in 3 patients with chronic autoimmune thrombopenia].
We describe three patients with chronic autoimmune thrombocytopenia who exhibited transient remission during viral infection (varicella, hepatitis B, and influenza virus pneumopathy). In two patients, a male homosexual and an hemophiliac, thrombocytopenia was associated with AIDS-related complex. The third patient had classic idiopathic thrombocytopenic purpura. The mechanism of these rare remissions is discussed.
Intravenous gammaglobulin, thrombocytopenia, and the acquired immunodeficiency syndrome.
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[Non-Hodgkin lymphoma associated with a relapse of Hodgkin's disease].
We report the case of a patient treated for Hodgkin's disease (stage IIIEA) by combination of chemotherapy (MOPP regimen) and total nodal irradiation. Five months after the completion of radiotherapy the patient presented with a relapse of his Hodgkin's disease and simultaneous occurrence of diffuse non Hodgkin's lymphoma in a different lymph node territory. The relationship between these two malignancies is discussed and the literature is reviewed.