Search PubMed⌕ Search

Biomedical subjects

J Aschan

Publications and source records attributed to J Aschan.

At least 55 records · Page 3Linked to original sources
PubMed1997

Ribavirin therapy in bone marrow transplant recipients with viral respiratory tract infections.

Treatment with ribavirin was instituted in 12 allogeneic and one autologous bone marrow transplant (BMT) recipients with proven respiratory syncytial virus (RSV), influenza B virus or parainfluenza virus infections. RSV was diagnosed in six cases, influenza B virus in four and parainfluenza virus in three patients. Ribavirin was given orally or intravenously (15-20 mg/kg/day in three divided doses) and in nine cases with the addition of ribavirin inhalations (6 g/day). Three patients required ventilator support. Three out of seven patients with pneumonia, including one patient with RSV who developed pulmonary infiltrates 10 days after the start of therapy, died despite treatment with ribavirin (two RSV, one influenza B). Multiple etiological agents were found in the fatal cases. The clinical condition improved in 10 of 13 patients during therapy. No serious adverse effects of systemic ribavirin were noticed. Two patients had reversible signs of hemolysis but only one patients required more erythrocyte transfusions than expected after BMT. Obstructive respiratory distress was often observed (6/9 patients receiving ribavirin inhalation therapy), which resulted in discontinuation of aerosolized therapy in four cases. Time to engraftment (WBC < 0.2 x 10(9)/l) did not differ from other non-treated BMT patients. We conclude that ribavirin is well tolerated both orally and intravenously and it may, if instituted before development of hypoxia, reduce morbidity and mortality of RSV, influenza B and parainfluenza in this group of patients.

Administration, Oral↗
PubMed1996

Oral ribavirin for prevention of severe liver disease caused by hepatitis C virus during allogeneic bone marrow transplantation.

Four allogeneic bone marrow transplant patients who were infected with hepatitis C virus (HCV) before bone marrow transplantation (BMT) were treated with oral ribavirin during and after transplantation. None of the patients had severe liver complications. One patient died early. Polymerase chain reaction analysis revealed that two patients who were HCV RNA-positive before BMT became HCV RNA-negative during therapy and remained HCV RNA-negative during 6 and 12 months of follow-up, respectively. No severe side effects of ribavirin were documented. Ribavirin therapy can be given safely to patients undergoing BMT and can result in clearance of HCV RNA.

Administration, Oral↗
PubMed1996

Use of a semi-quantitative PCR for cytomegalovirus DNA as a basis for pre-emptive antiviral therapy in allogeneic bone marrow transplant patients.

The aim of this study was to evaluate the efficacy of pre-emptive antiviral therapy, based on a semi-quantitative nested PCR for cytomegalovirus (CMV) DNA in leukocytes, for the prevention of CMV disease after allogeneic BMT. Fifty-eight patients were prospectively followed with PCR for CMV DNA and antiviral therapy with ganciclovir was initiated after two consecutive positive tests. The levels of CMV DNA were determined by serial dilutions of the positive samples. The probability of detection of CMV DNA was 48.3% and the probability of CMV disease 6% at 100 days after BMT. Patients with CMV disease had higher CMV DNA levels compared with patients without CMV disease (P = 0.001). In comparison to 58 matched historical controls detection of CMV DNA was 5 days earlier (NS) and antiviral therapy could be initiated 10 days earlier in patients followed by PCR (P = 0.05). Pre-emptive antiviral therapy was given to 28 patients in a total of 36 courses. Patients became negative in PCR after 28 of 36 courses (77%). We conclude that PCR for CMV DNA can be used for early detection of CMV infection and as the basis of initiation of pre-emptive antiviral therapy in BMT patients.

Antiviral Agents↗
PubMed1996

Foscarnet for pre-emptive therapy of CMV infection detected by a leukocyte-based nested PCR in allogeneic bone marrow transplant patients.

Fifteen allogeneic BMT patients in a phase II study were given foscarnet 60 mg/kg twice daily for 14 days as pre-emptive therapy against CMV disease. CMV infection was diagnosed by a leukocyte-based nested PCR. All 15 patients were evaluable for toxicity. One patient did not fulfill the inclusion criteria of two consecutively positive CMV PCR tests and therefore was not evaluable for efficacy. Thus, 14 of 15 patients were evaluable for development of CMV disease. None of the patients developed CMV disease and all 14 assessable patients had a negative CMV isolation at the end of therapy. None of the 15 patients had to discontinue therapy due to toxicity. Six patients reported mild gastrointestinal disturbances, three patients headaches, and three patients mild urethritis or hemorrhagic cystitis. Serum-electrolyte disturbances were common including abnormal magnesium, potassium and calcium levels. Two patients developed mild serum-creatinine increases requiring adjustment of the foscarnet dosage according to protocol. We conclude that a dosage of foscarnet of 60 mg/kg given twice daily seems to be safe and effective in preventing CMV disease in allogeneic BMT recipients. A study comparing foscarnet and ganciclovir is indicated.

Adolescent↗
PubMed1995

Does high-dose intravenous immune globulin treatment after bone marrow transplantation increase mortality in veno-occlusive disease of the liver?

Forty-five recipients of bone marrow from HLA-identical siblings were given intravenous immune globulin (IVIG) 0.5 g/kg once a week during the first 3 months after transplantation. Fifty-three consecutive previously transplanted HLA-identical siblings were included as controls. Only patients who were cytomegalovirus (CMV) seropositive or had a CMV-seropositive donor were included. There were no major differences in patient characteristics between the two groups. However, more patients in the IVIG group received individualized graft-versus-host disease (GVHD) prophylaxis with less cyclosporine (P < 0.01), more controls received liposomal amphotericin B (P = 0.01), and more patients in the IVIG group received low-dose heparin as prophylaxis against veno-occlusive disease of the liver (P < 0.001). Median follow-up was 21 months in the IVIG group and 47 months in the control group. There were no differences between the groups with regard to time to engraftment, hospitalization time, or days with fever. No differences between the IVIG group and control group were detected in the incidence of acute GVHD grade II-IV (17% vs. 23%) or chronic GVHD (30% vs. 42%). The incidence of bacterial septicemias (53% vs. 63%) and invasive fungal infections (9% vs. 6%) was unaffected by IVIG treatment. The incidence of symptomatic CMV infection was the same in the two groups (14% vs. 16%). One control patient died of CMV interstitial pneumonitis, and 1 patient from each group died from viral interstitial pneumonitis of other origin. The incidence of veno-occlusive disease (VOD) was 16% in the IVIG group versus 6% in the controls (P = NS). Fatal VOD occurred in 11% of the IVIG group compared with none of the controls (P = 0.02). Other transplant-related complications did not differ between the two groups. Two-year survival was 62% in the IVIG group and 60% in the controls (P = NS). No significant beneficial effect was seen with IVIG, which may increase mortality in VOD. The use of high dose IVIG as prophylaxis in marrow transplant recipients is questioned.

Adult↗
PubMed1995

Long-term effects of hepatitis C virus infection in allogeneic bone marrow transplant recipients.

A total of 161 patients transplanted between 1978 and 1991 and who had survived at least 2 years after allogeneic bone marrow transplantation (BMT) were studied. Of 161 surviving patients, 28 (17.4%) were positive for hepatitis C virus (HCV) either by serology or polymerase chain reaction (PCR). Twenty-five patients were positive for HCV RNA by PCR, and 26 of the 28 patients had HCV antibodies detected by enzyme-linked immunosorbent assay (ELISA). The median follow-up time of HCV-positive patients was 6.1 years (range, 2.8 to 14.0 years). There was no difference in the frequency or degree of liver dysfunction between patients who were PCR-positive or -negative before BMT. Six patients developed severe liver dysfunction after BMT, and five of these patients did so after discontinuation or tapering of immunosuppression. No patient has developed liver failure. Serum transaminases were abnormal at the time of last follow up in 19 of 28 (68%) patients. Fifteen patients have had liver biopsies. No biopsy showed development of cirrhosis. We conclude that HCV is not a major contributing factor to morbidity and mortality during the first 5 to 10 years after allogeneic BMT.

Adolescent↗
PubMed1995

Similar incidence of graft-versus-host disease using HLA-A, -B and -DR identical unrelated bone marrow donors as with HLA-identical siblings.

Among 42 consecutive recipients of unrelated marrow were 39 HLA-A, -B, -DR identical, matched unrelated donors (MUD) and three with one HLA antigen mismatch. The majority were genomically typed for DRB, DQA, DQB and DPB. The recipients of MUD marrow were compared with 39 recipients of marrow from HLA-identical siblings with similar diagnoses, disease status and age. Each group included 24 patients with hematological malignancies, 6 with severe aplastic anemia and 9 inherited disorders. Immunosuppression consisted of anti-thymocyte globulin (ATG; pre-BMT mainly to recipients of unrelated marrow), CsA and four doses of MTX. Grade I acute GVHD was treated with prednisolone 2 mg/kg. In a comparison of MUD marrow recipients and HLA-identical siblings 34 of 39 and 36 of 39 of the patients engrafted, respectively. Recipients of MUD marrow and HLA-identical siblings achieved 0.2 x 10(9) WBC/l on day 16 (median) and 14, respectively (P = 0.03). Furthermore, the recipients of MUD marrow needed more platelet transfusions (P = 0.04). The incidence of acute GVHD grade II-III was 15% in the MUD marrow recipients compared with 11% among the HLA-identical siblings. The 2-4 year cumulative incidence of chronic GVHD was 29% and 22% in the two groups, respectively. The overall 2-year survival was 59 and 78%, respectively. Among patients with CML in chronic phase or accelerated phase (n = 26), 2-year relapse-free survival was 79% in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Long-term follow-up of a randomized trial comparing T cell depletion with a combination of methotrexate and cyclosporine in adult leukemic marrow transplant recipients.

Forty-eight adult leukemic recipients of HLA-identical sibling marrow were randomized to T cell depletion using anti-CD8 and anti-CD6 antibodies plus complement (n = 28) or prophylaxis with methotrexate (MTX) and cyclosporine (CsA) (n = 25). Patient characteristics were comparable in the two groups. The median observation time was 5 1/2 years. Transfusions, infections, and acute GVHD did not differ between the groups. Chronic GVHD occurred in 52% of patients receiving T cell-depleted marrow and 23% of those receiving MTX + CsA (P = 0.06). Overall probability of relapse was similar in both groups and actuarial leukemia-free survivals at 5 years were 39% and 35% in the two groups, respectively. Among patients with chronic myeloid leukemia (CML), leukemia-free survival at 5 years was 25% in patients receiving T cell-depleted marrow compared with 51% in those given MTX + CsA (P = 0.09). In patients with acute leukemia the probability of relapse was 24% in the group receiving T cell-depleted marrow compared with 73% in those treated with MTX + CsA (P = 0.06). Leukemia-free survival was 55% and 21% in the two groups, respectively (NS). CML patients tended to have a poorer prognosis and those with acute-leukemia better outcome with T cell depletion than with combined MTX + CsA. It is concluded that T cell depletion is unsuitable for patients with CML, but may be considered in patients with acute leukemia.

Adolescent↗
PubMed1994

Long-term immunity to measles, mumps, and rubella after allogeneic bone marrow transplantation.

A total of 124 patients who had survived at least 2 years after allogeneic bone marrow transplantation (BMT) were studied. Serum was collected at least once yearly. IgG antibodies were determined by enzyme-linked immunosorbent assay for measles and mumps. Rubella antibodies were analyzed by radial hemolysis. Antibody levels were interpreted as representing immunity, seronegativity, or seropositivity, but with uncertain immunity. The median follow-up of the patients was 6.5 years (range, 2 to 13.5 years). The calculated probabilities of being immune to measles at 3, 5, and 7 years from BMT were 47%, 27%, and 20%, respectively. The corresponding probabilities for mumps were 37%, 12%, and 6%, respectively; and for rubella, 47%, 33%, and 28%, respectively. The probabilities for being seronegative for measles, mumps, and rubella at 5 years after BMT were 60%, 73%, and 52%, respectively. When compared with those patients who had experienced previous natural measles disease (P < .05), the only factor that was important for immunity to measles after BMT was whether the patient had been immunized before BMT. There was no influence of donor seropositivity on the probability of becoming seronegative to mumps during follow-up. We conclude that most allogeneic patients will become seronegative to measles, mumps, and rubella during follow-up. Therefore, long-term B-cell memory function is not maintained, regardless of the immune status of the donor.

Adolescent↗
PubMed1994

Treatment of moderate to severe acute graft-versus-host disease: a retrospective analysis.

Seventy-one patients with moderate to severe acute GVHD after BMT were analysed retrospectively. At the start of therapy 96% of the patients had rashes, 45% liver abnormalities and 54% gut dysfunctions. Forty-four patients (62%) had been treated for grade I GVHD with systemic corticosteroids. First therapy for moderate to severe acute GVHD was with corticosteroids (n = 59), psoralen with ultraviolet light (PUVA) (n = 14), cyclosporin (CsA) (n = 10), antithymocyte globulin (ATG) (n = 7), methotrexate (MTX) (n = 2), monoclonal antibodies (n = 1) or thalidomide (n = 1). In 18 of these patients two or more agents were combined. Resolution of skin disease and evaluable liver and gut disease were seen in 48%, 44% and 47% of cases, respectively. Overall complete resolution was seen in 37%. Thirty-two patients received a second treatment, resulting in complete resolution in 31%. Patients with a complete response had an actuarial transplant-related mortality of 37% compared with 82% or worse for patients with other outcomes (p < or = 0.003). Combined treatment was superior to ATG, but not better than corticosteroids. In multivariate analysis a low total sum severity score was the only factor associated with complete response (p = 0.02). AML diagnosis (p = 0.01) and GVHD of the liver (p = 0.02) were independent risk factors for treatment failure.

Acute Disease↗
PubMed1994

Individualized prophylaxis against graft-versus-host disease in leukemic marrow transplant recipients.

Seventy-three leukemic HLA-identical siblings undergoing BMT received individualized prophylaxis against GVHD based on estimated risk of GVHD development. Patients with an estimated low risk of GVHD were given MTX. MTX + CsA were given to patients having a high risk of GVHD. CsA treatment was discontinued as early as possible after engraftment followed by weekly MTX until 3 months after BMT. Conditioning was busulfan + CY (BuCY, n = 35) or CY/TBI (n = 38). CY/TBI patients given MTX combined with CsA for 1 year served as retrospective controls (n = 39). The incidence of acute GVHD was similar in the three groups. The incidence of chronic GVHD was 59% in the BuCY group and 40% in the CY/TBI group compared with 25% in the controls (p = 0.002 vs BuCY). The incidence of relapse at 2 years was 6% in the BuCY group and 35% in the CY/TBI group (p = 0.01) vs 36% in the control group (p = 0.01 vs BuCY). Actuarial 2-year relapse-free survival was 76, 58 and 51% in the three groups, respectively (p = 0.06, BuCY vs controls). In multivariate analysis individualized prophylaxis was associated with chronic GVHD. Poor survival correlated with high risk leukemia and absence of chronic GVHD. Poor relapse-free survival was associated with high risk leukemia and TBI.

Adolescent↗