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Biomedical subjects

G Flandrin

Publications and source records attributed to G Flandrin.

At least 145 records · Page 8Linked to original sources

[Monoblastic (M5a) form of relapse in acute myeloblastic (M2) leukemia with t(8;21)].

An exceptional case of acute myeloblastic leukemia (M2) with t(8;21) relapsed as an acute monoblastic leukemia (M5). At that time only a minority of metaphases exhibited a t(8;21) and/or abnormality of chromosome No 11 long arm whereas various other chromosomal changes were present. The existence of a relapse of M2 with t(8;21) as M5 is discussed in relation to the commitment of the cells which became leukemic, and to the possibility of a second leukemia.

Child↗

c-myc and c-fos expression during interferon-alpha therapy for hairy cell leukemia.

Low-dose interferon-alpha (IFN-alpha) therapy is consistently effective in the treatment of hairy cell leukemia (HCL). In two cases of resistance to IFN-alpha administration, we diagnosed variant HCL, a form of HCL with intermediate features between typical HCL and B cell prolymphocytic leukemia. We tried to distinguish variant and typical hairy cells (HCs) by Northern blot analysis of the oncogenes expressed in vivo. We report that variant HCs contain c-myc transcripts in contrast to typical HCs, whereas c-fos transcripts are detected in both cell types. We also report that the mRNA levels of c-myc are not modified in variant HCs by IFN-alpha treatment, whereas the level of c-fos mRNA is modulated in both types of HCs. Our findings suggest that the failure to modulate c-myc expression in vivo might indicate the limits of low-dose IFN-alpha therapy.

Cell Cycle↗

Treatment of hairy cell leukemia with recombinant alpha interferon: I. Quantitative study of bone marrow changes during the first months of treatment.

Seventeen patients with hairy cell leukemia (HCL) were treated with low doses of recombinant alpha interferon (IFN) for over 4 months. Marked improvement was observed in peripheral blood and bone marrow in 15 of 17 patients. Comparison of pretreatment values and hemograms obtained after 4 months of treatment showed a marked decrease in circulating hairy cells (P less than .01), a decrease in the number of lymphocytes (P less than .01), a rise in the number of platelets (P less than .05), granulocytes (P less than .05), and monocytes (P less than .01), and a rise in the hemoglobin level (P less than .01). Transient reduction in the number of granulocytes was noted during the first month. Correction of thrombocytopenia often appeared within 2 months and usually preceded improvement of anemia, monocytopenia, and neutropenia. Bone marrow biopsy specimens were taken before treatment and 2, 4, and 7 months after its initiation. The volumes occupied by hairy cells, cells of the myeloid lines, and adipocytes were studied by stereological analysis of semithin sections. Decrease in the volume occupied by hairy cells was seen after 4 months of treatment (P less than .01), and the volume continued to decrease at the seventh month (P less than .05). Hairy cells were no longer detected on bone marrow biopsies of 4 of 17 patients by the fourth month and in 3 of 8 additional patients by the seventh month. A rise in the volume occupied by normal myeloid cells was visible by the second month of treatment (P less than .01). Nevertheless, the volume occupied by granulocytes remained lower than in the normal controls (P less than .01). After an initial increase during the first 2 months of treatment (P less than .01), the overall cellularity remained unchanged at 4 months and decreased significantly (P less than .05) at 7 months. Except for biopsies at 2 months, mean cellularity was below that of control biopsies (P less than .01).

Biopsy↗

Two Burkitt's lymphomas with chromosome 6 long arm deletions.

Two new European Burkitt's lymphoma (BL) cases are reported. Their karyotypic abnormalities were unusual, without involvement of chromosomes #8, #14, #2, or #22. However, in both tumors, a 6q- chromosome was, present. These findings raise questions about the definition of BL and the involvement of various different DNA sequences in the mechanisms of BL genesis.

Adult↗

Cytogenetic studies on acute myelomonocytic leukaemia (M4) with eosinophilia.

Cytological and cytogenetic studies on 17 acute myelomonocytic leukemia with bone marrow eosinophilia (M4EO) are reported. Cytological criteria include an unusual high proportion of eosinophilic cells containing abnormal granules. Abnormal karyotypes have been found in 12 patients but chromosome 16 abnormalities were present in only 9. In two of them only one such mitosis was detected whereas in 7 others inv(16)(p13q22) and/or del (16)(q22) clones were present. However in 16 cases normal karyotypes were also present. Other abnormal clones coexisted in three patients, suggesting that chromosome 16 abnormalities are not linked to a primary leukemogenic event. M4EO was found to be associated with a favourable prognosis.

Adolescent↗

Criteria for the diagnosis of acute leukemia of megakaryocyte lineage (M7). A report of the French-American-British Cooperative Group.

For the diagnosis of M7, the bone marrow aspirate shows a leukemic cell infiltrate that comprises 30% or more of all cells. These cells are identified as being of megakaryocyte lineage by the platelet peroxidase reaction on electron microscopy or by tests with monoclonal or polyclonal platelet-specific antibodies. Myelofibrosis or increased bone marrow reticulin are a prominent aspect in most patients with M7. In patients with increased reticulin, the bone marrow sample may be difficult to obtain and the counts done on the marrow films may be misleading. In these patients, the diagnosis of M7 should be based on excellent bone marrow biopsy sections that show an excess of blasts and, at times, increased numbers of maturing megakaryocytes; and on the presence of unequivocal megakaryoblasts in the peripheral blood or bone marrow (or both) as shown by immunologic techniques.

Acute Disease↗

[Rearrangement of the proto-oncogene c-myc in fresh cells from Burkitt's leukemia (L3)].

The presence of a rearrangement of the proto-oncogene c-myc was investigated in the DNA of fresh cells isolated from the blood of two patients with Burkitt's leukemia (L3), and from the node biopsy of a patient with Burkitt's lymphoma. Both samples from the L3 leukemia patients had the characteristic t(8;14) translocation, while the lymphoma specimen presented no abnormality of chromosome 8. Only one of the leukemic DNA's presented a rearranged c-myc pattern, with the breakpoint region located between the first and the second exon. The c-myc pattern of the two other patients appeared normal. The finding of a rearranged c-myc oncogene in fresh cells from a Burkitt's leukemia is direct evidence for the implication of c-myc in the disease whereas most of the rearrangements previously described have been found in cell lines established in culture.

Base Sequence↗

[Acute myeloblastic leukemia with involvement of the basophilic cell line and anomalies of the short arm of chromosome 12 (12p)].

Among 16 leukemia patients with abnormalities of the short arm of chromosome 12 (12p) were found 5 patients with an increased number of marrow basophils and a special M2 cytological feature. This new correlation between 12p abnormalities and M2-baso phenotype is presented. The localisation of c-k ras 2 genes at the same 12p site suggests a possible mutation of this c-oncogene.

Basophils↗

Intensive chemotherapy of hairy cell leukemia in patients with aggressive disease.

Seven patients with hairy cell leukemia were treated by intensive chemotherapy because they were considered to have a progressive disease and a poor short-term prognosis. The mean age was 47 years (range, 36 to 58). Six of seven patients had prior splenectomies with minor or transient hematologic responses. One patient had no spleen enlargement. The seven patients had never received any cytotoxic drugs and had prolonged granulocytopenia (less than 300/microL) with recurrent, severe infectious episodes. Chemotherapy included Rubidazone (zorubicine hydrochloride) 450 mg/m2 on day 1, arabinosyl cytosine 200 mg/m2/d from day 1 to day 5, and cyclophosphamide, 2,000 mg/m2 on day 5. Responses were assessed through examination of repeat bone marrow biopsy specimens and blood counts. A complete response was defined as normal blood counts associated with the disappearance of hairy cell infiltration and fibrosis on the bone marrow biopsy specimens. A partial response was defined as normal blood counts with persistence of leukemic cells in the bone marrow. Three patients achieved a complete response, and one patient had a partial response. Three patients died of infectious complications during induction chemotherapy. For the responding patients, the mean duration of aplasia was 37 +/- 5 days. Follow-up for the responding patients has been 44+, 24, 32+, and 23+ months. One patient with a complete response died while on maintenance therapy. We conclude that complete and prolonged histologic remission of hairy cell leukemia can be obtained with intensive chemotherapy. The toxicity of chemotherapy is such, however, that progressive disease after splenectomy needs to be more clearly defined.

Adult↗

Automated classification of lymphoid cells.

A morphometric study using a commercially manufactured automated analyzer was carried out on 18,742 circulating blood lymphoid cells obtained from patients suffering from a lymphoid blood disorder and from healthy controls. A sequence of statistical procedures was applied to the multiparameter morphometric data, enabling us to divide up the cell population into classes and to represent a given cell sample by a vector whose coordinates correspond to the distribution of the cells among the different classes (the lymphoid differential count). Automatic classification of the samples was carried out using this model. The groups obtained roughly matched the cytologic diagnosis, even though no diagnostic indications were added to the morphometric data. The lymphoid differential also permits good discrimination between chronic lymphoid leukemia and acute lymphoblastic leukemia. The method, suitable for large data sets, performs a reduction of the data that, because of its flexibility, achieves a compromise between loss of information and ease of application. It appears well suited for multiparameter studies of cell subpopulations whose morphologic features form a continuum and for which prior delimitation of classes is difficult, poorly reproducible or artificial.

Blood Cells↗

[Value and limitations of puncture guided by x-ray computed tomography in hematology].

Interpretable cytologic data were obtained in 63% of a series of 68 punctures, for biopsy of hematologic affections, guided by CT scanning. The frequency of puncture of post-therapy residual masses (44 cases) explains the high incidence of non-significant examination results after lymph node puncture. The technique was most effective (78% of punctures exploitable) when used for thoracic masses and visceral localizations. The method is very safe: lack of serious incidents and minor reactions, mainly during thoracic puncture, in only 4.4%. The method is simple in use and should be employed, within certain limits that should be recognized, very widely in hematologic diseases.

Abdomen↗

[Hairy cell leukemia: study of the development of 211 cases].

Large series of patients with hairy cell leukaemia have only recently been published. The 211 cases reported here provide useful information on the clinical presentation, prognostic factors, evolution and management of this uncommon disease. At presentation, 28% of the patients had no spleen enlargement, and only 20% had severe pancytopenia. However, severe neutropenia (less than 0.5 X 10(9)/l) was present in 32% of the cases. Prognosis was primarily related to the degree of peripheral cytopenia, usually corrected by splenectomy, but it was poor in both non-splenomegalic and splenectomized patients with persistent anaemia and neutropenia, and it is in these patients that other treatments should be tested.

Adult↗