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Biomedical subjects

A Najman

Publications and source records attributed to A Najman.

At least 73 records · Page 4Linked to original sources
PubMed1991

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↗
PubMed1990

Combination of ABVD and radiotherapy in early stages of Hodgkin's disease: analysis of a series of 94 patients. Pierre and Marie Curie Group (GPMC).

In order to reduce, if not completely suppress, late complications of combined chemotherapy and radiotherapy in Hodgkin's disease (HD), MOPP regimen (mechlorethamine, vincristine, procarbazine and prednisone) was replaced by ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine). Ninety-four patients with HD clinical stages I to IIIA with no staging laparotomy were treated by three courses of ABVD followed by radiotherapy. Irradiation was performed on extended fields in 41 cases and on involved fields in 53 others. Consolidation chemotherapy was planned in 67 cases with at least one unfavorable prognostic factor, but achieved only in 33 cases. Seventeen patients relapsed within 1 to 46 months after the beginning of treatment. Ten patients died, 7 of HD and 3 of intercurrent diseases or accident. Disease-free survival rate with a median follow-up of 60 months is 80%. This study showed, on the one hand, many digestive and general side-effects after ABVD and, on the other, a satisfactory hematological tolerance. Furthermore, mediastinitis or cardiovascular complications were not more frequent than with MOPP. These results point out the development and use of better tolerated regimens for initial chemotherapy in HD, without jeopardizing the good results of the treatment.

Adult↗
PubMed1990

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↗
PubMed1990

The role of autologous bone marrow transplantation in 46 adult patients with non-Hodgkin's lymphomas.

Forty-six patients with non-Hodgkin's lymphoma (NHL) were treated with autologous bone marrow transplantation (ABMT) in two different institutions. All patients were pretreated with conventional chemotherapy. Three different conditioning regimens were used, and 20 patients underwent bone marrow purging. Twelve patients were treated in first complete remission (CR); eight are in unmaintained CR 8 to 104 months after ABMT. Five patients were grafted in first partial remission (PR) after conventional therapy; all achieved CR, and all remain in prolonged CR (first CR for four patients, second CR for one patient). Of 21 patients with chemosensitive relapses, 13 patients are in prolonged unmaintained CR 8 to 94 months after ABMT. Eight patients with resistant disease remained uncured by ABMT; all eight died, six from progressive illness and two from toxicity. The current 3-year disease-free probability is 60% for all patients, 0% for refractory disease; 82% for first PR or CR, and 60% for sensitive relapses (SRs). These results confirm the efficacy of ABMT in the treatment of chemosensitive NHL with bad prognosis.

Adolescent↗
PubMed1990

Successful autologous bone marrow transplantation in second remission of malignant histiocytosis.

This report describes an 18-year-old man with disseminated malignant histiocytosis (MH). The patient initially attained complete remission (CR1) with conventional chemotherapy and then relapsed 14 months later. In second complete remission (CR2) 2 years and 8 months after initial diagnosis, an autologous bone marrow transplantation (ABMT) was undertaken following conditioning with the BEAM regimen. Bone marrow collected in CR2 was incubated with mafosfamide at a dose adjusted to the individual sensitivity of normal CFU-GM according to our current protocol. At the time of writing, 4 years post-transplant, this patient remains disease free. This is the first report of ABMT with marrow treated in vitro by mafosfamide in MH.

Adolescent↗
PubMed1990

Secretion of tumor necrosis factor-alpha by fresh human acute nonlymphoblastic leukemic cells: role in the disappearance of normal CFU-GM progenitors.

The disappearance of normal hematopoiesis during acute nonlymphoblastic leukemia (ANLL) is poorly understood. Several reports indicate that conditioned medium obtained from leukemic cells might inhibit the formation of normal hematopoietic progenitors. However, these blast-conditioned medium (BCM) inhibitory activities are not well characterized. In order to evaluate whether BCM might contain an activity inhibiting the growth of normal marrow progenitors, BCM from 13 consecutive patients with ANLL were tested on normal bone marrow in methylcellulose assays. In all the cases, a significant inhibition of the growth of granulocyte-macrophage colony-forming unit (CFU-GM) progenitors was observed, whereas erythroid burst-forming unit (BFU-E) progenitors were not affected. Further characterization of the BCM inhibitory activity showed using both a biological assay and RIA, the presence of tumor necrosis factor-alpha (TNF-alpha) in 10 out of 13 BCM. Northern blot analysis performed in six patients showed a correlation between the expression of TNF-alpha mRNA by leukemic cells and the presence of TNF-alpha in BCM. Moreover, the BCM inhibitory activity could be neutralized with an anti-TNF-alpha antiserum. These data indicate that leukemic cells express and release frequently TNF-alpha, which may therefore play an important role in the inhibition of granulopoiesis during leukemia.

Adult↗
PubMed1990

Inhibition of human bone marrow progenitors by the synthetic tetrapeptide AcSDKP.

The purpose of this work was to study the effects of a tetrapeptide, acetyl-N-Ser-Asp-Lys-Pro (AcSDKP), an inhibitor of spleen colony-forming unit (CFU-S) entry into DNA synthesis, on human progenitor cells. Normal human mononuclear cells were incubated with concentrations of the synthetic tetrapeptide ranging from 10(-12) to 10(-7) M for 1.5 and 24 h and then plated in methylcellulose in the presence of human placenta-conditioned medium and recombinant human erythropoietin. The proportion of progenitors in DNA synthesis was determined by the thymidine suicide assay. Incubation with AcSDKP for 24 h leads to a significant inhibition of granulocyte-macrophage colony-forming unit (CFU-GM) and erythroid burst-forming unit (BFU-E) growth and in some cases of erythroid colony-forming unit (CFU-E) growth. The inhibition, which was never greater than 50%, was obtained with 10(-10)-10(-9) M AcSDKP, whereas no effect was seen at higher concentrations. The percentage of CFU-GM, BFU-E, and CFU-E in DNA synthesis was significantly reduced in five consecutive patients after incubation of cells for 24 h with inhibitory doses of the peptide, indicating that it is active on cycling cells. Therefore, these studies provide the first evidence that the tetrapeptide AcSDKP, originally obtained from bovine marrow and now chemically synthesized, is able to inhibit the in vitro growth of human progenitors and to decrease their proportion in cell cycle.

Amino Acid Sequence↗
PubMed1990

[Exudative enteropathy and interstitial cystitis due to systemic lupus erythematosus].

A 33-year-old woman presented with chronic diarrhea, vomiting and anasarca due to systemic lupus erythematosus with protein-losing enteropathy, interstitial cystitis and glomerulonephritis. Methylprednisolone could not prevent aggravation of diarrhea, obstructive uropathy, and nephrotic syndrome, and prolonged intestinal ileus developed. Because of this steroid-resistance, bolus injections of cyclophosphamide (1 g i.v. monthly) were decided. Protein-losing enteropathy and ileus both disappeared rapidly following the first injection. Protein-losing enteropathy, intestinal ileus and interstitial cystitis are exceptional manifestations of systemic lupus erythematosus; steroid-resistance of the digestive manifestations has only been reported in one case and our observation is the first reporting the efficacy of cyclophosphamide.

Adult↗
PubMed1990

The role of methylcellulose on colony growth of human myeloid leukemic progenitors (AML-CFU).

The use of a semisolid support like methylcellulose (MC) in a clonogenic assay prevents cell migration and nonspecific aggregation. However, the inhibitory effect of MC on myeloid cell lines has been reported. To assess the effect of MC on human leukemic progenitor cell growth (acute myeloblastic leukemia colony-forming units, AML-CFU), increasing concentrations of MC (0.36%, 0.72%, and 1.44%) were added in a double-feeder culture system. T-lymphocyte-depleted leukemic cells from 12 patients with AML were cultured in the presence of 2.5% phytohemagglutinin (PHA) in a liquid and a semisolid (MC) medium over a leukocyte feeder layer. The leukemic nature of the colonies was confirmed by cytogenetic studies. The median cloning efficiency in the optimal MC assay system was significantly higher (217 leukemic colony-forming units [CFU-L]/5 x 10(4) cells) than the one obtained in the liquid assay system (72.5 CFU-L/5 x 10(4) cells). However, three patterns of growth were observed: 1) colony formation was significantly better in MC than in the liquid assay system (seven of ten cases), 2) there was no difference in growth response (three of ten cases), and 3) colony formation was significantly better in the liquid assay system (one of ten cases). In the semisolid assay system, colony growth was dependent on MC concentration and varied among individual patients. A striking feature was the partial reduction of AML-CFU growth at 1.44% MC, with complete inhibition in 4/11 cases. This phenomenon was not observed for normal progenitors cultured under the same conditions. Cytological evaluation of AML-CFU showed an incomplete maturation to the myelocyte state, accompanied occasionally by macrophagic differentiation. In contrast, maturation of the granulocyte-macrophage colony-forming unit (CFU-GM) clones was harmonious, resulting in greater than 40% polynuclear cells, even from a 7-day culture. Despite a variable clonal response of leukemic progenitors from individual patients, we conclude that 0.72% MC is the optimal concentration of MC in our system, allowing clonal growth of AML-CFU.

Cell Division↗
PubMed1989

[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↗
PubMed1989

Human liquid bone marrow culture in serum-free medium.

Prolonged in vitro maintenance of human bone marrow progenitor cells was achieved using a serum-free (SF) liquid culture system. Culture medium was based on Iscove's medium supplemented with bovine serum albumin, human transferrin, bovine insulin, soybean lecithin, cholesterol, hydrocortisone and alpha-thioglycerol. Under these standardized culture conditions, CFU-GM were maintained for up to 4 weeks, as is the case when using conventional serum-dependent medium. Erythropoiesis exhibited a slower decline than that found using serum containing medium. Development of normal haematopoiesis was effective in spite of poor stromal cell development--a confluent adherent layer as classically described in serum conditions was never achieved. Our newly defined system provides a reliable technique for studying human haematopoietic stem cell proliferation and differentiation in vitro; it allows for rational utilization of currently available purified recombinant growth factors. It may be a promising tool in the clinical use of cultured haematopoietic stem cells.

Bone Marrow Cells↗