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Biomedical subjects

D Guyotat

Publications and source records attributed to D Guyotat.

At least 91 records · Page 5Linked to original sources

Porphyria cutanea tarda after allogeneic bone marrow transplantation for chronic myelogenous leukemia.

A case of porphyria cutanea tarda (PCT) occurring after bone marrow transplantation (BMT) is reported. A 43-year-old male with chronic myelogenous leukemia received an human leukocyte antigen (HLA)-identical allogeneic transplantation with T-cell depleted marrow. Because of graft rejection, a second transplant was performed 4 months later. A grade II acute graft- vs.-host disease and a cytomegalovirus (CMV) infection were subsequently observed. Two years after the second transplant, cutaneous symptoms of PCT with typical biochemical abnormalities developed. Liver biopsy revealed signs of hepatitis with iron overload. CMV was isolated from liver tissue. The possible roles of underlying disease, BMT, and CMV liver disease are discussed in view of the recently reported cases of PCT in patients with AIDS or hematological disorders.

Bone Marrow Transplantation↗

Myeloid differentiation antigens identify leukemic cell subpopulations with different cell cycle characteristics.

In order to assess the proliferative capacity of leukemic subpopulations and to know whether it can be related to the stage of maturation, the expression of two surface antigens identifying distinct steps of leukocyte differentiation (CD15 and CD34) was studied by flow cytometry in correlation with DNA content in 16 cases of acute myeloid leukemia (AML). The surface markers were studied by indirect immunofluorescence, using the monoclonal antibodies VIMD5 (anti-CD15) and MY10 (anti-CD34). The percentage of cells stained by each antibody and the intensity of staining were heterogeneous. Double-staining showed that a small percentage of cells coexpressed both antigens. A correlation was found between the percentage of cells stained by MY10 and the percentage of cells in S + G2 + M in the whole population (p less than 0.05). The percentage of cells in S + G2 + M was significantly higher in MY10-positive than in MY10-negative cells (p less than 0.005), and also higher in VIMD5-positive than in VIMD5-negative cells (p less than 0.005). In the 14 cases expressing both antigens, the percentage of cells in S + G2 + M was higher in VIMD5-positive than in MY10-positive cells (p less than 0.05), whereas there was no difference between VIMD5-negative and MY10-negative cells. It is concluded that the phenotype heterogeneity observed in leukemic cell populations is associated with differences in proliferative capacities. The subset of leukemic cells with the more mature phenotype (CD15-positive) has the highest proliferative activity.

Antigens, CD↗

Myeloid surface antigen expression in adult acute lymphoblastic leukemia.

The expression of myeloid surface markers was investigated in 41 cases of untreated adult acute lymphoblastic leukemia (ALL). Nineteen cases (46%) reacted with at least one myeloid monoclonal antibody (CD15 in 16 cases, CD13 in 10 cases, CD14 in five cases, and CD33 in four cases). Double-staining confirmed the coexpression of myeloid and lymphoid markers. In addition, 35 samples were tested for CD34 expression. Fourteen of the 17 myeloid-positive cases tested were positive for CD34 vs. eight of 18 negative cases (p less than 0.05). A t(9;22) translocation was found in eight cases, and a t(4;11) translocation in two cases, all expressing CD34 and myeloid antigens. These findings confirm the high frequency of myeloid markers on the surface of adult ALL blasts, and suggest that these leukemias may originate in a poorly differentiated precursor cell with mixed differentiation capacities.

Adult↗

Pre-clinical evaluation of anti-lacto-N-fucopentaose III (CD15) monoclonal antibodies for ex vivo bone marrow purging in acute myeloid leukemia.

In order to eliminate residual leukemic cells from the marrow of patients with acute myeloid leukemia (AML) prior to autologous bone marrow transplantation, the optimal conditions of utilization of three CD15 murine monoclonal antibodies (MoAb) were investigated. The VIM-D5 MoAb was used with rabbit complement (C'), whereas the 8.27 and SMY15A MoAbs were used in the presence of human C'. These antibodies were also tested after fixation on magnetic beads. In a culture assay in semi-solid medium with a mixture of normal marrow and 1% HL60 cells, a lysis of clonogenic cells greater than 99% was achieved with the three antibodies and two rounds of complement, or with antibody-coated magnetic beads. Cultures of leukemic clonogenic cells (CFU-L) were performed in 47 cases. An inhibition equal to or greater than 90% was achieved in seven cases with VIM-D5, 16 cases with 8.27 and 11 cases with SMY15A and C'. The correlation with cytotoxicity of fresh cells was low. Twenty cases were purged with antibody-coated beads. An inhibition equal to or greater than 90% was observed in 10 cases with VIM-D5, 11 cases with 8.27 and 12 cases with SMY15A. The mean recovery of normal CFU-GM was higher than 70% and that of BFU-E higher than 95% with any method of treatment. It is concluded that efficient marrow purging of clonogenic AML cells can be achieved in some cases without toxicity for normal progenitors. The addition of other MoAbs seems necessary to obtain a significant purge in a majority of cases.

Antibodies, Monoclonal↗

Long-term follow-up after bone marrow transplantation for chronic myelogenous leukemia: factors associated with relapse.

Data on 281 patients with chronic myelogenous leukemia who received bone marrow transplants were analysed. The median follow-up time was 40 months; 170 patients were in first chronic phase, 14 were in second chronic phase, 73 were in accelerated phase and 24 were in blastic crisis. The overall actuarial survival was 50% at 5 years. In multivariate analyses, the probability of relapse correlated with the phase of the disease, the method of total body irradiation, the T cell depletion of the marrow and the occurrence of a chronic graft-versus-host disease (GVHD). The probability of survival was better for patients with grade 0-1 GVHD than for patients with grade 2-4 GVHD. In contrast, the probability of disease-free survival was significantly better for patients who received a non-T cell-depleted marrow than for recipients of T cell-depleted marrow. Interval between diagnosis and transplant, splenectomy before transplant, patient age and donor recipient sex match were not significantly associated with outcome. Bone marrow transplantation in first chronic phase with an HLA identical non-T cell depleted marrow offers the better chance of prolonged leukemia-free survival.

Adult↗

Response of hematopoietic precursor cells to hematopoietic growth factors in the myelodysplastic syndromes.

The in vitro effects of 4 recombinant hematopoietic growth factors on myelodysplastic syndrome cells from 22 patients were assessed by colony assays (CFU-GM, BFU-E). DNA synthesis, cytological and cell phenotypic studies. Growth factors seemed to be potent stimulators on cell proliferation, but showed only limited effects on cell differentiation. Combinations of factors were more efficient than factors used alone. Nevertheless, culture growth patterns remained abnormal. Cell proliferation was major in the cases with excess of blasts with, in 2 cases, stimulation of leukemic cells.

Cell Differentiation↗

Bone marrow transplantation for chronic myelogenous leukemia. Results of the French Cooperative Group (GEGMO).

Data on 281 patients with chronic myelogenous leukemia who received bone marrow transplants were analyzed. The median follow-up time was 48 months. One hundred and seventy patients were in 1st chronic phase, 111 were in more advanced disease. The overall actuarial survival was 50% at 5 years. In multivariate analyses, the probability of relapse was correlated with the phase of the disease, the method of total body irradiation, the T cell depletion of the marrow and the occurrence of a chronic GVHD. The probability of disease free survival was significantly better for the patients who received a non T cell depleted marrow than for recipients of T cell depleted marrow. Bone marrow transplantion in first chronic phase with an HLA identical non T cell depleted marrow offers the better chance of prolonged leukemia free survival.

Acute Disease↗

Phase II trial of plicamycin and hydroxyurea in acute myelogenous leukemia.

A total of 23 patients with high-risk acute myelogenous leukemia (AML) at diagnosis (2 patients), relapsing AML (14) or resistant AML (6) were treated with 25 micrograms/kg i.v. plicamycin every other day for 3 weeks and 500-4,000 mg hydroxyurea per day p. o. according to the WBC count. Aplasia was observed in only two patients. Severe extrahematologic toxicity included sepsis (four cases), vomiting (four patients), toxic hepatitis (three cases), and fibrinopenia (one patient). No partial or complete responses were observed. The 95% confidence interval limit of the overall response rate (CR + PR) was 0-14%.

Bone Marrow↗

Surface marker expression in adult acute myeloid leukaemia: correlations with initial characteristics, morphology and response to therapy.

The clinical significance of surface markers was investigated in 145 cases of acute myeloid (AML) or undifferentiated leukaemia (AUL), using a panel of six monoclonal antibodies directed to NHL-30.5 antigen (expressed on poorly differentiated myeloid cells), CD13, CD14, CD15, CD33 and CD34 antigens. Expression of CD14 was correlated with higher leucocyte count, higher serum lactate dehydrogenase level and presentation with extramedullary disease. There was no strict correlation with the French-American-British classification. However, the expression of CD14 was associated with monocytic subtypes. CD15 was mainly expressed in M2 and M3 subtypes, and NHL-30.5 and CD34 antigens in AUL and M1 leukaemias. All patients were treated with the same intensive induction treatment. Staining by three antibodies had a prognostic value. The complete remission (CR) rates were 38% (26/68) in NHL-30.5-positive versus 75% (62/77) in NHL-30.5-negative cases (P less than 10(-5), 50% (37/74) in CD34-positive versus 72% (51/71) in CD34-negative cases (P = 0.007) and 70% (77/110) in CD15-positive versus 31% (11/35) in CD15-negative cases (P less than 10(-4). Expression of NHL-30.5 and CD34 antigen was associated with shorter survival (P less than 10(-3) and P less than 10(-2) respectively), whereas survival was longer in CD15-positive cases (P less than 10(-3). In multivariate analysis, expression of NHL-30.5 antigen, absence of CD15, and high LDH level were associated with poor survival. CR duration was not influenced by any of the factors studied, including antigen expression. These results suggest that leukaemias with less differentiated phenotype have a lower response rate to induction treatment.

Acute Disease↗

Disseminated Geotrichum capitatum infection in a patient with acute myeloid leukemia.

A case of invasive Geotrichum capitatum infection is reported; a young patient had an acute leukemia for which he received a chemotherapy, and presented sepsis with blood cultures for Geotrichum capitatum, namely Dipodascus spicifer; this pathogen only described in cactus rot, is responsible for the first case of a human disseminated infection reported in literature. Then he developed a splenic and epididymic infection, with positive cultures for Geotrichum capitatum after splenectomy and castration. Treatment with amphotericin B and itraconazole was started with low minimal inhibitory concentration (0.1 microgram/ml). The patient died of massive hemoptisis. Autopsy findings demonstrated a lung, brain and kidneys seeding.

Adult↗

Treatment of acute myeloid leukemia in elderly patients. A retrospective study.

In an attempt to rationalize the use of therapy in acute myeloblastic leukemia (AML) in elderly patients, 69 cases of primary AML in patients older than 60 years of age were reviewed retrospectively. Therapy was empirical and 12 patients received supportive care (SC) only, 35 received aggressive chemotherapy (AC), and 22 received low-dose cytosine arabinoside (LD-araC). Patients receiving SC only often had a poor Karnofski index and their median survival was 17 days. Aggressive chemotherapy yielded complete remissions (CR) in 48% of the patients, whereas 23% of the patients had resistant disease (RD) and 29% had other failures (OF). Low-dose araC, which was administered to patients significantly older than those receiving AC, yielded 23% CR, 68% RD, and 9% OF, with important hematologic toxicity in most patients. Median survival was 211 days in patients receiving AC and 235 days in patients treated with LD-araC. Survival beyond 2 years from diagnosis was noted in the AC group only. A low Karnofski index was the strongest factor in poor prognosis, while age was not a prognostic factor. The initial characteristics of the patients did not allow us to define groups of patients who should be treated by either AC or LD-araC. We concluded that the decision to treat patients actively should rely more on the patient's general condition and socio-economical criteria than on age.

Aged↗

Hypereosinophilic syndrome with multiple organ dysfunction treated by allogeneic bone marrow transplantation.

A 26-year-old man with hypereosinophilic syndrome who had initial neurologic, cardiac, and pulmonary dysfunction, high eosinophil count, thrombocytopenia, and bone marrow fibrosis had only a transient response to conventional treatment with corticosteroids and hydroxyurea. He therefore received human lymphocyte antigen-identical allogeneic bone marrow transplantation (BMT) after conditioning with cytoxan and fractionated total body irradiation. Hematologic recovery was prompt, with normalization of blood counts and bone marrow. The patient died less than 3 months after transplantation from diffuse cytomegalovirus infection. Potential interest of BMT in patients with resistant hypereosinophilic syndrome and features of poor prognosis is discussed.

Adult↗

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↗

Expression of immunological markers on leukemic cells before and after cryopreservation and thawing.

We have studied the effects of cryopreservation on the viability and on the expression of surface antigens of acute leukemia cells. Marrow samples were obtained at initial diagnosis from 89 patients with acute myeloid leukemia (AML), acute undifferentiated leukemia (AUL), and acute lymphoid leukemia (ALL). In AML, the mean viability was greater than 90% in the types M1, M4, and M5 of the French-American-British classification, 79% in M2, and 3% in M3 types. The viability was 74% in AUL. In ALL, the viability was 95% for pre-B leukemias, but only 2% in T-cell leukemias. The expression of myeloid antigens was studied before and after freezing and thawing using three monoclonal antibodies (NHL30.5, against poorly differentiated granulocytic leukemias, VIMC6 against differentiated granulocytic leukemias and granulocytes; and UCHM1 or CRIS-6, against monocytic leukemias and monocytes). The percentage of cells stained by NHL30.5 and UCHM1 or CRIS-6 was very similar before and after cryopreservation. For VIMC6, the mean staining after cryopreservation was 60% of the initial one. In pre-B ALL, the stainings by anti common ALL antigen before and after cryopreservation were also very similar. We conclude that leukemic cryopreserved cells are suitable for immunologic studies. The recovery is, however, very low in promyelocytic AML and T-cell ALL.

Acute Disease↗