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H Dombret

Publications and source records attributed to H Dombret.

At least 73 records · Page 4Linked to original sources
PubMed1995

Unexpected high incidence of intracranial subdural haematoma during intensive chemotherapy for acute myeloid leukaemia with a monoblastic component.

We report a high incidence of subacute, chronic and sometimes occult intracranial subdural haematoma (SDH) occurring during intensive chemotherapy for acute myeloid leukaemia (AML) with a monoblastic component. Between March 1990 and January 1993, 86 AML patients from our institution were randomized in the multicentric French AML 90 trial. Eight patients (9%) presented a grade > 2 haemorrhagic event, which was intracranial SDH in five of them. All these five SDH patients had hyperleucocytic AML4 or AML5 and had experienced at least one lumbar puncture (LP) before SDH diagnosis (with intrathecal chemotherapy in four cases). SDH diagnosis was assessed on a brain computed tomography scan which was performed 1-9 d after initial SDH symptoms (mainly mild headaches considered a result of prior LP). All these five patients recovered from this severe event after a specified therapy. SDH does not appear to be an uncommon complication of AML4 and AML5 therapy. Its incidence might be under-reported because of poor symptomatology. Lumbar punctures, known to cause exceptional SDH in nonleukaemic patients, might trigger these haemorrhagic events, eventually in combination with other predisposing factors such a haemostasis disorders or leukaemic CNS infiltration.

Acute Disease↗
PubMed1995

In vivo thrombin and plasmin activities in patients with acute promyelocytic leukemia (APL): effect of all-trans retinoic acid (ATRA) therapy.

APL-associated hemostasis disorders result from at least two distinct mechanisms due to the release of procoagulant activities and plasminogen activators from the leukemic cells. These two mechanisms (thrombin activation and plasmin activation) may cleave the fibrinogen molecule, but their respective roles in low fibrinogen levels and bleeding diathesis genesis remain in dispute. In vivo ATRA therapy induces a rapid correction of both low fibrinogen level and bleeding tendency, but no clear explanation of this beneficial effect has been proposed. We prospectively investigated 27 APL patients at presentation for diffuse intravascular coagulation (DIC) markers (prothrombin activation fragment and thrombin/antithrombin complexes) and plasmin-dependent primary fibrinogenolysis markers (alpha 2 plasmin inhibitor consumption +/- plasmin/alpha 2 plasmin inhibitor complexes). Fourteen of these patients were then serially studied during the first 2 weeks of ATRA therapy. Four of them, however, developed an hyperleukocytosis requiring additional chemotherapy before the end of the 2nd week. At presentation, low level of fibrinogen was clearly associated with alpha 2 plasmin inhibitor deficiency (p < 0.01), while DIC was equally present in fibrinogenopenic and non-fibrinogenopenic patients. Moreover, was observed a rapid simultaneous correction of low fibrinogen levels and plasmin activation markers in APL patients undergoing ATRA therapy (before day 5), but a more prolonged persistence of DIC markers (until day 14). Initial bleeding syndrome seemed more frequent in patients with initial low fibrinogen level. These data indicate that plasmin-dependent primary fibrinogenolysis is the major etiologic factor of low fibrinogen level in APL patients. In vivo differentiation ATRA therapy induces a rapid decrease in the plasmin activation and a normalization of fibrinogen level, while DIC may in vivo persist for several weeks. Prospective studies evaluating antifibrinolytic agents as therapy of APL-associated hemostasis disorders should be considered. Additionally, prophylactic heparin therapy might be useful after day 5 in patients undergoing ATRA therapy, since they present a prolonged procoagulant tendency.

Adolescent↗
PubMed1995

De novo acute myeloid leukemia in patients with Crohn's disease.

Crohn's disease (CD) has been occasionally reported to be associated with myelodysplastic syndromes (MDS) or acute myeloid leukaemia (AML). From October 1991 to June 1993, four AML patients with a previous history of CD but no history of MDS were referred to our institution. Three presented AML with a monoblastic proliferation (one AML4 and two AML5). Cytogenetic analysis revealed a normal karyotype in two patients, an inv(16) in another and a del(11)(q24-25) in the fourth. Interestingly, the three patients with AML4/AML5 had not received high doses of immunosuppressive agents, prior CD therapy ranging from 1 to 4 months sulfasalazine with additional azathioprine in one case.

Adult↗
PubMed1995

Neutrophilic dermatoses during granulocytopenia.

BACKGROUND AND DESIGN: Noninfectious cutaneous neutrophilic lesions can occur during granulocytopenia, but their mechanism remains unknown. We undertook a retrospective study of the neutrophilic dermatoses that developed during granulocytopenia induced by chemotherapy for acute myelogenous leukemia. RESULTS: Seven men and one woman were included (2.6% of treated cases of acute myelogenous leukemia); half had acute myelogenous leukemia subtypes 4 and 5. The male-to-female ratio was 7:1. Neutrophilic eccrine hidradenitis was diagnosed in five cases, Sweet's syndrome in two cases, and difficult-to-classify neutrophilic dermatoses in one case. Cutaneous lesions appeared 12.5 days after the start of chemotherapy, and the mean leukocyte count was 0.426 x 10(9)/L. Three patients needed corticosteroids systemically. CONCLUSION: Neutrophilic dermatoses during chemotherapy-induced granulocytopenia seem to occur more frequently in men with acute myelogenous leukemia subtypes 4 and 5.

Adult↗
PubMed1995

Changes in microrheology of acute promyelocytic leukemia cells during all-trans retinoic acid (ATRA) differentiation therapy: a mechanism for ATRA-induced hyperleukocytosis?

According to French and European experience, hyperleukocytosis occurs during ATRA differentiation therapy in about 70% of de novo and 25% of relapsed APL cases. The most frequently suggested cause for this side-effect is an ATRA-induced proliferation of APL cells. However, no definite explanation for such a proliferative effect has been clearly established. Another mechanism directly related to the differentiation of marrow leukemic cells could be a change in their microrheology, allowing their release from the bone marrow and their transfer toward peripheral blood (PB) and tissues. Using a single cell aspiration assay into a glass restrictive channel, we measured APL cell viscosity values in five de novo APL patients. A deformability index (DI) was defined as the ratio of mean normal neutrophil viscosity x 100/mean APL cell viscosity. Results were the following: (1) at diagnosis, two patients had high marrow DI (96 and 250%) and three patients had low marrow DI (16, 17, and 40%); (2) when PB and marrow APL cells were simultaneously tested, PB APL cells display higher DI than marrow APL-cells; (3) the two patients with high initial marrow DI experienced an ATRA-induced hyperleukocytosis after only 1 day of treatment; (4) in the three patients with low initial marrow DI, the DI was increasing during ATRA therapy and hyperleukocytosis seemed to occur when a large amount of maturing APL cells reached a viscosity value similar to that of mature neutrophils. These results suggest that an asynchronism between rheological and morphological maturation in each APL cell might explain the occurrence of hyperleukocytosis in some patients during ATRA differentiation therapy.

Adult↗
PubMed1995

Methotrexate related B lymphoproliferative disease in a patient with rheumatoid arthritis. Role of Epstein-Barr virus infection.

A 57-year-old woman receiving low dose methotrexate (MTX) for rheumatoid arthritis (RA) developed a B lymphoproliferative disease (LPD) that was initially considered as large cell non-Hodgkin's lymphoma of B cell phenotype. Epstein-Barr virus (EBV) cytotoxic latent membrane protein-1 (LMP-1) expression was found in some large cells. The lymphoproliferative disease reversed with MTX discontinuation and without chemotherapy. These EBV-associated LPD in patients with RA receiving MTX or other immunosuppressive agents seem to be similar to those triggered by EBV in transplant patients receiving cyclosporine A. MTX withdrawal and short followup should be considered before chemotherapy since spontaneous regression is possible.

Arthritis, Rheumatoid↗
PubMed1994

Simultaneous occurrence of two rare cutaneous markers of poor prognosis in myelodysplastic syndrome: erythema elevatum diutinum and specific lesions.

We report the concomitant occurrence of erythema elevatum diutinum and specific skin lesions in a patient with a myelodysplastic syndrome (MDS). This patient's course, and review of other reported cases, support the opinion that neutrophilic dermatoses are associated with a poor prognosis of MDS. The simultaneous appearance of these manifestations could be the consequence of a particular chemotactism of myeloid cells, expressed after acute transformation.

Aged↗
PubMed1994

Induction treatment of acute promyelocytic leukemia using all-trans retinoic acid. Controversies about dosage, advantages and side-effect management.

All-trans retinoic acid (ATRA) in acute promyelocytic leukemia (APL) represents the leading example of targetted drugs for inducing an in vivo differentiation of malignancy (1,2). A fixed dose of 45 mg/m2/day was proposed for the treatment of patients (3), according to the results obtained by retinoic acid derivatives in skin diseases. We report that 25 mg (4), and even 15 mg/m2/day are still effective dosages. Absence of drug resistance, rapid correction of fibrinogenopenia and the absence of hypoplasia are the apparent major advantages and consequently high frequency of early mortality generally reported during chemotherapy is expected to be reduced. In fact the same risk of early death (10%) is recorded in all available data (5), due to coagulation disorders and to a leukocyte activation syndrome. Management of these side-effects is based on the prevention and treatment of the irreversible state as soon as first symptoms appear. Actually the major advantage of ATRA treatment in addition to chemotherapy is the decrease of relapse rate (6), the increase of event-free survival, and thus the increase of survival.

Adolescent↗
PubMed1994

[Microrheology of marrow promyelocytes from patients suffering from acute myeloblastic leukemia type 3].

Viscosity values of marrow cells from patients suffering from acute promyelocytic leukemia (acute myeloid leukemia of type 3) have been determined before and during a treatment with all-trans retinoïc acid (active metabolite of the vitamin A, inducing cell differentiation and maturation). Evaluated from aspiration tests into a glass micropipette, the marrow cell viscosity has been compared to that of normal neutrophils. Results seem to point out that the induced hyperleucocytosis is favoured by both a low standard deviation of pathological cell viscosity and a cell viscosity value close to that of normal neutrophils. The systematic study of cell viscosity could therefore help the clinicians to individualize the treatment.

Granulocytes↗
PubMed1993

Fusarium solani cutaneous infection in a neutropenic patient.

A 47-year-old woman with acute myeloblastic leukemia developed disseminated papules and pustules after chemotherapy. A skin biopsy specimen revealed fungal vasculitis and grew Fusarium solani. The patient died despite treatment with amphotericin B. The isolate was resistant to amphotericin B, imidazole and 5-fluocytosine. Fusarium should be recognized as a potential cause of deep fungal infection in immunocompromised patients.

Dermatomycoses↗
PubMed1993

Coagulation disorders associated with acute promyelocytic leukemia: corrective effect of all-trans retinoic acid treatment.

The bleeding diathesis in patients with acute promyelocytic leukemia (APL) is generally attributed to disseminated intravascular coagulation (DIC), initiated by the release of procoagulant activity from leukemic cells. Primary fibrinogenolysis, mediated by the release of leukocyte proteases, may also contribute to this disorder. We analyzed coagulation parameters in 15 non-septic APL patients. Before treatment, there was evidence of thrombin activation with DIC: increased levels of circulating thrombin-antithrombin III complexes, prothrombin fragments 1 + 2 and D-Dimer complexes. This DIC syndrome was probably limited, since no prothrombin time decrease, no significant factor V consumption, and normal levels of coagulation inhibitors (antithrombin III and protein C) were observed in APL patients when compared to normal controls. In this context, marked hypofibrinogenemia suggested primary fibrinogenolysis as the predominant etiology. Despite normal or high tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI-1) antigen levels, the plasma PAI-1 activity and the formation of tPA/PAI-1 complexes were lower in APL patients than in normal controls, suggesting a proteolytic degradation of PAI-1, not able to complex tPA. Two other fibrinolytic inhibitor molecules (alpha-2 plasmin inhibitor antigen and histidine-rich glycoprotein antigen) were also significantly reduced, as well as the two subunits of fibrin stability factor XIII, although only subunit A is known to be susceptible to thrombin action. Evidence of degraded forms of von Willebrand factor in the plasma suggested an extended proteolytic activity. Four patients treated with all-trans-retinoic acid (ATRA) as a single differentiating agent were studied serially. A dissociation between these two syndromes--DIC and fibrinogenolysis/proteolysis--was observed. The rapid correction of the lysis markers contrasted with a more prolonged persistence of the procoagulant activity. We observed persistently high elastase/alpha 1-proteinase inhibitor complex levels during ATRA therapy, despite progressive correction of all lysis markers. Thus, the release of elastase from promyelocytic leukemic cells is probably not the only determinant of the fibrinogenolytic/proteolytic syndrome. In summary, the present findings provide new arguments for the association of DIC and proteolysis syndromes in APL-associated coagulation disorders. Further prospective studies are needed in order to confirm the persistence of thrombin activation in course of ATRA therapy.

Adolescent↗
PubMed1993

Alterations in natural anticoagulant levels during allogeneic bone marrow transplantation: a prospective study in 27 patients.

The natural anticoagulants (antithrombin III, protein C, protein S), plasminogen and tissue plasminogen activator antigen (t-PA ag), were measured in 27 consecutive patients following allogeneic BMT. Thrombosis and veno-occlusive disease were not seen in this study. Changes in the levels of these proteins occurred mainly during acute GVHD. There were 14 patients who had no acute GVHD (group I) and 13 patients who had acute GVHD (group II). No changes in antithrombin III (ATIII), protein C, protein S and t-PA levels were found in group II before the appearance of acute GVHD when compared with group I. However, we noted a significant rise in protein S (p = 0.01), antithrombin III (p = 0.001) and t-PA ag (p = 0.0004) levels during acute GVHD. In contrast, protein C levels decreased early in GVHD (p = 0.005), and then increased progressively over the course of a month post-GVHD. No changes in plasminogen levels were observed. These results might reflect activation of and/or damage to endothelial cells during GVHD.

Acute Disease↗
PubMed1992

Unexpected consistent involvement of V beta gene segments in inappropriate T-cell receptor beta gene rearrangements occurring in B-lineage acute lymphoblastic leukemias.

T-cell receptor beta (TCR beta) gene rearrangements occur in a third of early B-cell acute lymphoblastic leukemias (ALLs). V, D, and J segments involved in these inappropriate rearrangements remain unknown and are of interest, both because partial D beta J beta and complete V beta D beta J beta recombinations occur at distinct stages of thymic maturation and because these rearrangements are regulated differently. We have therefore studied in detail seven cases of B-lineage ALL that show inappropriate clonal TCR beta gene rearrangements. Analysis of genomic DNA by Southern hybridization with C beta, J beta 1, V beta 8, and V beta 11 probes suggested the involvement of V beta segment in tumor cell rearrangements. A complete genomic library constructed from one case was screened with a C beta probe, and the TCR beta gene rearrangement was cloned and fully sequenced to show an out of frame V beta 2.2-J beta 2.6 recombination. TCR beta gene rearrangements occurring in other cases were further analyzed by polymerase chain reaction (PCR) using J beta and V beta primers and the resulting specific PCR products were sequenced. Evidence of clonal V beta rearrangements was obtained in all cases. These unexpected findings represent the first definitive demonstration that complete V beta(D beta)J beta rearrangements can occur in B-lineage cells and contrast with the previously reported lack of V beta(D beta)J beta rearrangement in B cells from V beta-J beta-C beta-E mu transgenic mice. In the context of increasing evidence that rearrangements are linked to transcription of unrearranged gene segments, these data prompt a search in B-lineage ALL cells for the presence of germline V beta transcripts whose deregulated expression may be linked to early transforming events.

Animals↗