Biomedical subjects
Publications and source records attributed to A Devergie.
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Four patients developed legionnaires' disease after bone marrow transplantation. Two cases occurred early after transplant and were considered as part of a hospital epidemic due to contamination of water supply. The other two cases were considered to be sporadic because they occurred 3-4 weeks after hospital discharge. The outcome was good in two patients. In the third patient, recurrent disease was probably due to acquired resistance to macrolides, and complete cure was achieved after treatment with pefloxacin and rifampicin. The fourth patient died of overwhelming infection despite early treatment with erythromycin and pefloxacin. During the same period we treated 14 patients with pefloxacin for prevention of bacterial infection, of whom none developed Legionella pneumophila infection, while three of the patients reported here were in a group of 11 patients who received only oral non-absorbable antibiotics for gut decontamination. The fourth patient in this report was receiving no antibiotics. Thus pefloxacin seems to be effective as prophylaxis against L. pneumophila infection. When the hospital water supply was heated to 60 degrees C and chlorinated, the nosocomial cases in the hospital completely disappeared.
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Systematic clinical and serological studies to evaluate the frequency of toxoplasmosis in bone marrow transplant recipients were performed in 80 consecutive patients. Antitoxoplasma antibody titres were measured in donors and recipients before transplant and subsequently post-transplant. Before bone marrow transplant, 54 recipients were seropositive and 26 were seronegative, whereas 35 donors were seropositive and 45 were seronegative. After bone marrow transplant, the frequency of clinical and serological manifestations of toxoplasmosis appeared closely related to the recipient's serological status before transplant. In the seronegative group of patients before transplant the incidence of toxoplasmosis was low: only two patients experienced seroconversion 3 months after bone marrow transplant and one developed clinical symptoms consistent with toxoplasmosis but without cerebral involvement. Clinical toxoplasmosis or secondary elevation of antibody titres was mostly observed in pre-bone marrow transplant seropositive patients; in this group, cerebral toxoplasmosis occurred in four patients and a significant secondary rise of antibody titres was observed in 16 patients. It thus appears that toxoplasmosis is most often related to a reactivation of latent cysts. Prophylactic treatment may be useful in patients presenting serological evidence of past or latent infection before bone marrow transplant.
Thirty-seven patients with chronic granulocytic leukemia have been treated with supralethal chemoradiotherapy followed by transplantation of bone marrow from HLA-identical donors. All patients showed engraftment, and the Philadelphia chromosome (PH1) disappeared in each case. Four patients had syngeneic grafts before blast crisis and are still alive; 2 are in remission not maintained by therapy, and 2 others are receiving chemotherapy after having relapsed in the chronic phase. Thirty-three patients had allogeneic grafts; only 2 received the grafts during blast crisis, and neither is a long-term survivor. Of the 13 patients who had grafts in the accelerated phase, 6 died of complications related to the transplantation, and 1 died after a myeloblastic relapse. Thus 6 patients are in unmaintained remission with a median follow-up of 13 months. Eighteen patients received grafts in the chronic phase. All 10 survivors are in unmaintained remission with a median follow-up of 14 months; in this group, no patient has relapsed. The granulocytic hyperplasia of the chronic phase can be more effectively ablated than established blastic leukemia. The mortality rate of transplant-related complications must be weighted against the typical rate of progression of chronic granulocytic leukemia. Although a longer follow-up period is needed for full evaluation, bone marrow transplantation may now be offered to patients in the chronic phase in an attempt to achieve long-term survival or cure of more than one-half of these patients.
Cytomegalovirus (CMV) viremia was systematically studied in 56 patients having undergone bone marrow transplantation for leukemia or aplastic anemia. Of the patients who survived at least three months, 57% had CMV viremia with a frequency peak between the 7th and the 9th weeks. We describe possible clinical signs associated with viremia, particularly late peripheral and/or central thrombocytopenia. The occurrence of viremia was studied according to the specific preexisting immune status of recipients and donors; granulocyte transfusions and graft-versus-host disease. The relationship between these parameters and viremia provides a basis for the analysis of prophylactic treatments of CMV infection.
Allogeneic bone marrow transplantation (BMT) successfully corrected type I thrombasthenia in a 4-year-old boy. The donor was his HLA-A, B and D identical 14-year-old brother who was heterozygous for thrombasthenia. A first transplant after conditioning with cyclophosphamide and thoracoabdominal irradiation was rejected, but a second transplant using CCNU, cyclophosphamide, procarbazine and horse antihuman thymocyte globulin in the preparative regimen was successful. Engraftment was proven by studies of platelet membrane antigens, PLA1 and glycoprotein IIb/IIIa complex and by platelet function studies. Haemorrhagic manifestations completely disappeared; platelet membrane markers and clot retraction returned promptly to normal values, and platelet aggregation tests more slowly. Twenty-four months after bone-marrow transplant, the patient was well with mild chronic hepatic graft versus host disease. BMT therefore appears to be a possible treatment for severe inherited platelet disorders.
Lung biopsy of 35 patients with interstitial pneumonitis following bone marrow transplantation (BMT) have been studied histologically, ultrastructurally and by immunofluorescence. Among infectious diseases, cytomegaloviruses (CMV) are the more frequently found, whereas Pneumocystis carinii infections are more frequently found in immunocompromised hosts without BMT. CMV infections are related to severe chronic graft-versus-host disease in allogenic or mismatched BMT. Hemorrhagic pulmonary oedema and vascular damage might be the consequence of high doses of cyclosporin A or of disseminated intravascular coagulation. Granulomatous and fibrosing lesions corresponded in 2 cases to an eosinophilic pneumonitis and in 11 cases to an "idiopathic" diffuse interstitial pneumonitis. 2 patients had concomitant diffuse lung fibrosis, sclerotic plaques of the skin and Sjögren-like syndrome. The pulmonary and cutaneous scleroses had common features in the types of collagen and in the composition of the infiltrate. Both fibroses might result from a common pathogenic mechanism related to an immunologic conflict between the lymphocytes of the graft and the cells from the host tissues.
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CMV infection is one of the major infection after bone marrow transplantation. CMV viremia was systematically studied in 66 patients with aplastic anemia or leukemia undergoing BMT. 57% patients had CMV viremia with a frequency peak between 7 and 9 weeks after transplant. Clinical symptoms found during viremia were pancytopenia, fever, cytolytic hepatitis. Interstitial pneumonitis was found only in 4 cases. In 3 cases, viremia was not associated with clinical symptoms. Survival was identical to the group of patients without viremia. Viremia was positively associated with the presence of high anti-CMV antibody titer in donor or recipient before transplant, or to a lymphocyte proliferative response against CMV antigens in donor or recipient before BMT. Granulocyte transfusions increased the frequency of CMV viremia. CMV infection was significantly associated with acute and chronic graft versus host disease. The relation showed between these parameters and viremia provides a basis for an accurate diagnosis of CMV infection and a better background for the study of prophylactic or curative treatment of CMV infection.
In a double-bind controlled study, oral Acyclovir has been compared to a placebo in a series of 39 consecutive patients undergoing bone marrow transplantation. A dose of 200 mg was given every 6 h from day 8 to day 35 after transplantation. Pharmacokinetic studies have shown the good absorption of the drug despite intestinal damage related to chemoradiotherapy or gut graft-versus-host disease (GVHD), there was no sign of toxicity. The protection against herpes simplex virus (HSV) infection was complete in the treated group when compared to the control group even in patients with high anti-HSV antibody titres. The same protection was observed against cytomegalovirus (CMV) infection. The incidence of HSV and CMV was the same in both groups after treatment ended. This study confirms the efficacy of Acyclovir against HSV infection and possibly against CMV infection when it is given prophylactically after bone marrow transplantation.
Thirteen skin biopsies were performed on 8 patients at different stages of skin sclerosis in chronic graft-versus-host disease (GVHD). On the same skin biopsies an immunostaining with antibodies directed against Types I and III procollagen, Types I, III, IV, V collagen, and laminin, and an ultrastructural study were performed. Alterations were observed at the dermal-epidermal junction and in the superficial dermis with a large deposit on Type III procollagen in the incipient scleroses and of Type I procollagen in the oldest ones. In this sclerotic superficial dermis, collagen fibers of irregular diameter were associated with mast cells and active fibroblasts, macrophages, and lymphocytes in close contact. The skin sclerosis in chronic GVHD might be considered a form of cutaneous fibrosis with features of excessive tissue repair related to an immunologic reaction between lymphocytes of the graft and tissue host cells.
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In vitro bone marrow GM-CFC (granulomonocyte colony forming cell) growth following E rosette (+) cell depletion was studied in 14 aplastic patients to determine whether an autoimmune factor could be involved in the pathophysiological process leading to the decrease in bone marrow colony formation. The increase in GM-CFC growth after E rosette (+) cell depletion was high in 8 cases, suggesting that in these cases an autoimmune mechanism may have been involved. All these patients responded within a month to treatment with antithymocyte globulin (ATG) or corticosteroids. Six patients did not respond to immunotherapy, none showed increased GM-CFC growth. The increase of in vitro GM-CFC growth after E rosette (+) cell depletion in aplastic anemia could therefore be a good indication for the trial of immunotherapy. However this study seems to be useful only in patients with at least a few months evolution after diagnosis.
In a double-blind controlled study, oral acyclovir was compared with placebo in 39 consecutive patients undergoing bone-marrow transplantation. Acyclovir was given at a dose of 200 mg every 6 h from 8 days before to 35 days after bone-marrow transplantation. Pharmacokinetic studies showed good absorption of the drug, despite intestinal damage related to chemoradiotherapy or gut graft-versus-host disease. There was no sign of toxicity. The protection against herpes simplex virus (HSV) infection was complete in the treated group compared with the placebo group even in patients with high anti-HSV antibody titres before transplantation. The same protection was observed against cytomegalovirus (CMV) infection. The frequencies of HSV and CMV infections were the same in both groups after the cessation of treatment.
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