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Biomedical subjects

J Aschan

Publications and source records attributed to J Aschan.

At least 73 records · Page 4Linked to original sources
PubMed1994

Prognostic factors for long-term survival in leukemic marrow recipients with special emphasis on age and prophylaxis for graft-versus-host disease.

Long-term survival of 182 leukemic patients after allogeneic bone marrow transplantation (BMT) was analyzed retrospectively regarding the type of graft-versus-host disease (GvHD) prophylaxis and patient age. Monotherapy with either methotrexate (MTX) (n = 59) or cyclosporin (CSA) (n = 40) was given to 79 patients less than 30 years of age and to 20 older patients. These patients were compared to those receiving a combination of MTX+CSA (n = 55) or T-cell depletion (TCD) (n = 28) (38 patients < or = 30 and 45 > 30 years of age). Patient characteristics were similar in the two pairs of groups. The median follow-up time was between 4.7 and 9.6 years in the different groups. In younger patients, the incidence of grade II-IV acute GvHD was 38% amongst those treated with MTX or CSA and 14% in the MTX+CSA/TCD group (p = 0.008). Forty percent of older patients on monotherapy developed grade II-IV acute GvHD compared to 26% of those over 30 treated with MTX+CSA/TCD (ns). As a consequence, mortality from GvHD among younger patients was 19% in the monotherapy group and 3% in the MTX+CSA/TCD group (p = 0.03) with 37% and 10% (p = 0.04) in the older patient groups. The cumulative incidence of chronic GvHD was similar amongst treatments in the younger patients (39% in monotherapy and 39% in MTX+CSA/TCD), but was significantly lower in the MTX+CSA/TCD group among patients > 30 (55% vs 25%, p = 0.05). The actuarial overall survival at 5 years was unchanged in patients < or = 30, 49% and 43% in the monotherapy and MTX+CSA/TCD groups, respectively. However, in older patients survival increased from 25% to 46% (p = 0.04). An increase in leukemic relapse associated with MTX+CSA/TCD among both younger (26% vs 48%, p = 0.05) and older patients (0% vs 46%, p = 0.05) influenced the relapse-free survival, 48% vs 39% (ns) in younger and 25% vs 37% (ns) in older patients. Risk-factors for survival were dependent on the type of GvHD prophylaxis used. Using monotherapy, in contrast to combination therapy or TCD, multivariate analysis showed that recipient age > 30 years and HLA disparity between donor and recipient were correlated with poor outcome. In patients receiving MTX + CSA or TCD, a female donor to a male recipient correlated significantly with poor survival, which was not the case with monotherapy. Disease status beyond 1st complete remission (1 CR) or 1st chronic phase (1 CP), grade II-IV acute GvHD and recipient CMV seropositivity were significant risk-factors among all patients regardless of the type of GvHD prophylaxis.

Adolescent↗
PubMed1993

Influenza A in immunocompromised patients.

Immunocompromised patients with influenza A were identified in Stockholm during two influenza seasons. The predominant subtypes were H3N2 during 1988-1989 and H1N1 during 1990-1991. The median age of the 25 patients was 43 years (range, 3-80 years). Twelve patients had received renal transplants and had ongoing immunosuppression. Seven patients had received bone marrow transplants between 2 days and 3 years before becoming infected with influenza virus A. Two patients were in an aplastic phase, and four had chronic graft-versus-host disease with ongoing immunosuppression. Six patients had hematologic malignancies. Two of the 25 patients had severe infections. One of these infections occurred in a bone marrow transplant recipient during an aplastic phase and was fatal; the other affected a patient who had received a renal transplant. One bone marrow transplant patient had mild but protracted infection. The remaining 22 patients had mild influenza A. We conclude that influenza A in immunocompromised patients occasionally causes severe complications but in most patients is mild and self-limiting.

Adolescent↗
PubMed1993

Cytomegalovirus viraemia and specific T-helper cell responses as predictors of disease after allogeneic marrow transplantation.

Risk factors for cytomegalovirus viraemia and disease, the relation between viraemia and disease, effect of antiviral treatment, and T-helper cell response to cytomegalovirus antigen were analysed retrospectively among 279 patients who underwent bone marrow transplantation at Huddinge Hospital. Ninety-one of 279 (32.6%) patients developed viraemia. Donor and recipient pre-transplant serologic status and degree of acute graft-versus-host disease were independent risk factors for viraemia. Forty-nine patients (17.6%) developed cytomegalovirus disease and 44 of these patients had viraemia. Seventeen patients (6%) developed cytomegalovirus pneumonia and 14 of these patients had preceding viraemia. Among patients with viraemia, acute graft-versus-host disease and total body irradiation were risk factors for pneumonia. Antiviral treatment initiated within 7 d of development of viraemia was associated with lower risk for development of pneumonia (P < 0.05). Sixty-seven patients with viraemia were repeatedly tested by lymphocyte stimulation with cytomegalovirus antigen. No patient who developed cytomegalovirus pneumonia had measurable specific helper T-cell response at the time of viraemia detection compared to 42% of patients with other concurrent or subsequent cytomegalovirus disease, and 75% of patients without subsequent disease. We conclude that viraemia is a major risk factor for development of cytomegalovirus disease. Furthermore, early antiviral treatment based on detection of viraemia can be effective in preventing cytomegalovirus disease. The length of antiviral treatment might be decided through measurements of the helper T-cell response to cytomegalovirus antigen.

Adolescent↗
PubMed1993

Increased risk of relapse in patients with chronic myelogenous leukemia given T-cell depleted marrow compared to methotrexate combined with cyclosporin or monotherapy for the prevention of graft-versus-host disease.

Fifty-two patients with chronic myelogenous leukemia (CML) who underwent bone marrow transplantation (BMT) at Huddinge Hospital were analyzed retrospectively regarding type of graft-versus-host disease (GvHD) prophylaxis. With T-cell depletion (TCD) (n = 13) the incidence of grade II-IV acute GvHD was 8% compared to 27% among patients given short course methotrexate (MTX) + cyclosporin (CSA) (n = 23) (ns) and 60% in patients who received MTX or CSA alone (n = 16) (p = 0.006 vs TCD and 0.03 vs MTX + CSA). The incidence of chronic GvHD was 56%, 31% and 75%, in the three groups, respectively (p = 0.02 combination vs monotherapy). Probability of relapse differed significantly, with most relapses in the TCD group, 62% compared to 20% in the MTX + CSA group (p = 0.02) and no relapse in the monotherapy group (p = 0.01 TCD vs monotherapy). Patient survival at 6 years was 54%, 59% and 38%, in the three groups, respectively (ns). Relapse-free survival was 23% in the TCD group, 55% in the combination group (p = 0.06) and 38% in the monotherapy group (ns). We conclude that TCD in patients with CML is correlated with an increased risk of relapse and a tendency towards a decreased long-term relapse-free survival compared to patients receiving other kind of GvHD prophylaxis.

Adolescent↗
PubMed1992

A randomized trial comparing the use of fresh and stored platelets in the treatment of bone marrow transplant recipients.

Patients undergoing allogeneic bone marrow transplantation (BMT) were randomized into two groups. One group (n = 21) received single donor platelet concentrates (PC) that were as fresh as possible, the other group (n = 18) received single donor PC stored for 2 to 5 days. Actual mean storage times for PC were 1.12 +/- 1.25 (mean +/- SD) and 2.67 +/- 1.30 d, respectively (p < 0.001). The total need for platelets during 60 d after BMT in patients receiving fresh PC was 22.1 +/- 17.8 x 10(9) platelet/liter blood volume/d, and for stored PC 29.2 +/- 19.2 x 10(9) platelets/liter blood volume/d (n.s.). A multiple regression analysis of the data showed no correlation between PC storage time and the PC requirement (p = 0.85). Posttransfusion corrected count increment (CCI) at 1 hour was 10.4 +/- 5.1 for PC stored 0-1 d, 10.3 +/- 7.0 for PC stored 2-3 d, and 11.4 +/- 9.2 for PC stored 4-5 d. The corresponding CCI, at 18 h were 6.5 +/- 4.4, 5.4 +/- 3.3 and 6.8 +/- 4.6. We conclude that there is no major difference between fresh and stored single donor PC.

Adolescent↗
PubMed1992

Foscarnet for treatment of cytomegalovirus infections in bone marrow transplant recipients.

42 episodes of verified or clinically suspected cytomegalovirus (CMV) infection in 40 bone marrow transplant (BMT) recipients were treated with foscarnet (trisodium phosphonophormate hexahydrate). CMV infection was verified in 31/42 treatment episodes. Symptoms treated were pneumonia (n = 17), pancytopenia with or without fever (n = 12), enteritis (n = 5), fever (n = 4), encephalitis (n = 2), retinitis (n = 1) and hepatitis (n = 1). Foscarnet was given as a continuous intravenous infusion. Side-effects observed were increase in serum creatinine (38%), decrease in serum calcium (19%), increase in serum bilirubin (12%), decrease in hemoglobin concentration (7%), increase in serum calcium (5%), increase in serum transaminase (5%), hypophosphatemia (2%) and tremor (2%). CMV was eradicated from blood and/or urine in 11/25 (44%) of assessable treatment episodes with infection verified by isolation. Overall clinical improvements including eradication of CMV, afebrility and/or improvements in laboratory abnormalities were seen in 14/31 (45%) episodes of verified infection. All 15 patients with CMV interstitial pneumonia (CMV IP) died. We conclude that foscarnet is nephrotoxic but otherwise well tolerated with moderate clinical and virostatic effects on CMV infection. The effect on CMV IP is discouraging.

Adolescent↗
PubMed1991

Pharmacokinetics of high-dose busulphan in relation to age and chronopharmacology.

Busulphan levels in plasma were measured in 27 patients during conditioning therapy (1 mg/kg x 4 for 4 days) before bone marrow transplantation. The mean minimal concentration found in children aged less than 5 years (237 ng ml-1) was lower than that observed in adults or older children (607 and 573 ng ml-1, respectively). The AUC for the last dose was significantly lower in young children (2.315 h ng ml-1) than in adults or older children (6,134 and 5,937 h ng ml-1, respectively). The elimination half-life for the last dose in young children was shorter (2.05 h) than that in either adults (2.59 h) or older children (2.79 h). When the AUC was normalized for body surface area, the difference between young children and the other groups was smaller but remained statistically significant. The total body clearance was significantly higher in young children (7.3 ml min-1 kg-1) as compared with both older children and adults (3.02 and 2.7 ml min-1 kg-1, respectively). The plasma levels of busulphan showed circadian rhythmicity, especially in young children. The concentration measured during the night in some patients was up to 3-fold that observed during daytime. We conclude that the busulphan dosage for children must be reconsidered and that further studies are urgently needed to develop an optimal therapy.

Adolescent↗
PubMed1991

Methotrexate combined with cyclosporin A decreases graft-versus-host disease, but increases leukemic relapse compared to monotherapy.

Forty patients with leukemia receiving HLA-identical sibling marrow and treated with four doses of methotrexate (MTX) in combination with cyclosporin A (CSA) for prevention of graft-versus-host disease (GVHD) were compared with retrospective controls consisting of 57 patients treated with MTX alone and 30 patients treated with CSA alone. Follow-up time ranged from 2.6 to 6.7 years after bone marrow transplantation. Patients in the MTX + CSA group were older and received a smaller marrow cell dose, but were otherwise comparable regarding disease status, donor/recipient sex match and seropositivity for cytomegalovirus (CMV) and other herpes viruses. Engraftment was slowest in the MTX + CSA group and fastest in the CSA group (p = 0.005 vs MTX and p less than 0.001 vs CSA). The incidence of moderate to severe acute GVHD (grade II-IV) was 8% among patients on MTX + CSA and 26% and 47% in the MTX (p = 0.028) and CSA (p = 0.0001) groups respectively. The corresponding figures for chronic GVHD were 25, 42 and 40% (n.s.). The incidence of CMV interstitial pneumonia was 0% in patients treated with MTX + CSA compared to 23% in the MTX treated patients (p = 0.01) and 11% in the CSA treated patients (p = 0.05). The actuarial 3-year survival in the three groups was similar, 56% for the MTX + CSA patients and 53% for both the MTX and CSA patients (n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Prevention of graft-versus-host disease with T cell depletion or cyclosporin and methotrexate. A randomized trial in adult leukemic marrow recipients.

In adult leukemic marrow recipients of HLA identical sibling marrow, 23 patients were randomized to T cell depletion and 25 received cyclosporin (CSA) and four doses of methotrexate (MTX) to prevent graft-versus-host disease (GVHD). Anti-CD8 and anti-CD6 antibodies plus complement depleted 95.3 +/- 5.8% (mean +/- SE) CD3 cells. All patients engrafted except one who died early. Patients receiving T cell-depleted marrow had a faster time to 0.2 x 10(9) WBC/l (p less than 0.001), but required more erythrocyte units (p = 0.03). Platelet transfusions, infections and time in hospital did not differ. The incidence of grade II-III acute GVHD was 23% following T cell depletion and 12% for those receiving CSA + MTX. Chronic GVHD occurred in 51% and 23% in the two groups, respectively (p = 0.06). Recipients of T cell-depleted marrow who developed grade I-III acute GVHD received more T cells compared to those without acute GVHD (p = 0.02). The major cause of death in both groups was relapse, the cumulative incidence of which, at 4 years, was 39% in the recipients of T cell-depleted marrow and 54% in the CSA + MTX group. The 3-year actuarial leukemia-free survival was 42% and 44% in the two respective groups.

Adult↗
PubMed1990

Allogeneic bone marrow transplantations at Huddinge Hospital and strategies to improve survival.

At Huddinge Hospital 275 patients underwent allogeneic bone marrow transplantation. Among children in first remission of acute leukemia or chronic phase CML (early leukemia), with HLA-identical marrow the 8-year leukemia-free survival was 77%. This was better than 38% in children undergoing transplantation in second to fourth remission (p less than 0.0009). In adults with early leukemia, the 8-year leukemia-free survival was 47% compared to 21% for intermediate-risk adults (p = 0.007). Among 25 patients with severe aplastic anemia receiving marrow from HLA-identical siblings, the actuarial 10-year survival was 78%. In 14 patients with various metabolic disorders, of whom half received marrow from HLA-mismatched donors, the actuarial 7-year survival was 71%. Forty-three patients were given marrow from HLA-mismatched donors and had an increased incidence of acute graft-versus-host disease (GvHD) and death due to GvHD compared to recipients of HLA-identical bone marrow. The major causes of death among our patients were relapse of leukemia, death due to GvHD, cytomegalovirus (CMV) pneumonitis, bacterial infection and invasive fungal infections. By preventing GvHD with T-cell depletion or methotrexate (MTX) combined with cyclosporine (CsA) acute GvHD decreased, but the incidence of relapse increased compared to patients treated with MTX or CsA alone. This resulted in improved survival in patients older than 30 years, but a nonsignificant decrease in leukemia-free survival in younger patients. There was an association between herpes virus immunity in the recipient and GvHD. CMV pneumonitis increased following GvHD and decreased in patients treated with MTX combined with CsA. Invasive fungal infections may be treated or prevented using amphotericin B encapsulated in liposomes with few side effects.

Adult↗
PubMed1989

Influenza B in transplant patients.

Six cases of influenza B occurred in transplanted patients in a period of 3 weeks. Three renal allograft recipients recovered within 5 days without antiviral therapy. Two allogeneic bone marrow recipients were treated with ribavirin inhalations during the leukopenic phase. Treatment was given until influenza B was no longer detected and fever disappeared after 5 and 6 days, respectively. Engraftment was not delayed and no side-effects were noted. One recipient of autologous marrow was treated for 2 days, but ribavirin was discontinued due to pleuritic pain. We conclude that influenza B can be spread by asymptomatic carriers in the nursing staff and in spite of reversed isolation with the use of gown, hand wash and gloves.

Adult↗