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P Ljungman

Publications and source records attributed to P Ljungman.

At least 19 recordsLinked to original sources
PubMed2001

Pregnancy outcomes after peripheral blood or bone marrow transplantation: a retrospective survey.

BACKGROUND: Some patients treated by transplantation of haemopoietic stem cells (peripheral blood or bone marrow) become permanently infertile, but others retain or recover fertility. We assessed the outcome of conception in women, and partners of men previously treated by autologous or allogeneic stem cell transplantation (SCT). METHODS: We sent questionnaires to 229 centres of the European Group for Blood and Marrow Transplantation. We sought details about the original disease, transplant procedure, and outcome of conception for both male and female patients. FINDINGS: 199 centres gave information relating to 19412 allogeneic and 17950 autologous transplant patients. 232 (0.6%) patients conceived after SCT. Crude annual birth rate for 4-month survivors of SCT was lower than the national average for England and Wales at 1.7 per 1000 patients. 312 conceptions were reported in 113 patients (74 allograft) and partners of 119 patients (93 allograft). Most pregnancies were uncomplicated and resulted in 271 livebirths. 28 (42%) of 67 allograft recipients had caesarean section compared with 16% in the normal population (difference =26% [95% CI 15-38]), 12 (20%) of 59 had preterm delivery compared with a normal rate of 6% (14% [4-24]), and 12 (23%) of 52 had low birthweight singleton offspring compared with a normal rate of 6% (17% [6-29]). INTERPRETATION: Pregnancy after SCT is likely to have a successful outcome. Pregnancies in allograft patients who have received total body irradiation should be treated as high risk for maternal and fetal complications.

Adolescent↗
PubMed2001

Prophylactic measures in the solid-organ recipient before transplantation.

Pretransplant screening affords an important opportunity to detect and treat preexisting active infection in the solid-organ transplant recipient. In this article, pretransplant strategies for preventing infections after solid-organ transplantation are reviewed. In addition to the search for active preexisting infection in the transplant candidate, immunization remains a cornerstone of preventive practice. Because there is a suboptimal response to vaccinations in patients who are receiving immunosuppressive therapy, as well as in patients with end-stage organ dysfunction, standard immunization of the transplant candidate should be updated as early as possible in the course of the illness, including pneumococcal, influenza, and hepatitis B vaccines. Liver transplant candidates should receive hepatitis A vaccine, and children should receive Haemophilus influenzae type B conjugate vaccine. All nonimmune pretransplant patients should be considered candidates for the varicella vaccine. The management of special risk groups is discussed in detail.

Adult↗
PubMed2001

Cidofovir for cytomegalovirus infection and disease in allogeneic stem cell transplant recipients. The Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation.

A retrospective study was performed to collect information regarding efficacy and toxicity of cidofovir (CDV) in allogeneic stem cell transplant patients. Data were available on 82 patients. The indications for therapy were cytomegalovirus (CMV) disease in 20 patients, primary preemptive therapy in 24 patients, and secondary preemptive therapy in 38 patients. Of the patients, 47 had received previous antiviral therapy with ganciclovir, foscarnet, or both drugs. The dosage of CDV was 1 to 5 mg/kg per week followed by maintenance every other week in some patients. The duration of therapy ranged from 1 to 134 days (median, 22 days). All patients received probenecid and prehydration. Ten of 20 (50%) patients who were treated for CMV disease (9 of 16 with pneumonia) responded to CDV therapy, as did 25 of 38 (66%) patients who had failed or relapsed after previous preemptive therapy and 15 of 24 (62%) patients in whom CDV was used as the primary preemptive therapy. Of the patients, 21 (25.6%) developed renal toxicity that remained after cessation of therapy in 12 patients. Fifteen patients developed other toxicities that were potentially due to CDV or the concomitantly given probenecid. No toxicity was seen in 45 (61.6%) patients. Cidofovir can be considered as second-line therapy in patients with CMV disease failing previous antiviral therapy. However, additional studies are needed before CDV can be recommended for preemptive therapy.

Adolescent↗
PubMed2001

An ethnic role for chronic, but not acute, graft-versus-host disease after HLA-identical sibling stem cell transplantation.

Among 424 HLA identical siblings undergoing stem cell transplantation, 364 were Scandinavians and 60 represented other ethnic groups. The cumulative probabilities of acute graft-versus-host disease grades II-IV were similar in both groups, 17% in Scandinavians and 12% in the others, p = 0.4. In a multivariate analysis, less effective immune suppression with cyclosporine or methotrexate alone (p = 0.001), recipient seropositive for three to four herpes viruses (p = 0.004), CMV-seropositive recipient (p = 0.05) and early engraftment (before day 15) (p = 0.05) were independent risk-factors for acute GVHD grades II-IV. The cumulative probabilities of chronic GVHD were 47% and 68% in the two ethnic populations, respectively (p = 0.004). In multivariate analysis, higher patient age (p < 0.001), non-Scandinavian population (p < 0.001) and immunised female donor to male recipient (p = 0.03) were independent risk factors for chronic GVHD. The higher incidence of chronic GVHD could not be explained by differences in HLA antigen frequencies. The cumulative probabilities of relapse were 37% in the both groups. This suggests that the Scandinavian population is more homogeneous with regard to minor histocompatibility antigens important for chronic, but not acute GVHD.

Acute Disease↗
PubMed2001

Pharmacokinetics of liposomal busulphan in man.

High doses of busulphan are used in conditioning regimens before stem cell transplantation. Great inter-patient variations in pharmacokinetics and a correlation between toxicity and high systemic exposure of busulphan have been shown in several studies. Some authors have suggested therapeutic drug monitoring and intravenous busulphan aiming to reduce the conditioning-related toxicity. Liposomal busulphan (LBu) might be an alternative to intravenous administration of high-dose busulphan in conditioning. In the present study, we investigated the pharmacokinetics of LBu in man. Seventeen consecutive patients were enrolled in the study. LBu as a single low dose (2 to 8 mg) was given to 12 patients (six adults and six children). Five patients received two high doses of LBu which replaced the first and the last doses of the conditioning regimen. The high dose of LBu was raised from 0.4 to 0.9 mg/kg. A significant linear correlation (r2 = 0.928) was found between the dose of LBu and the area under the plasma concentration-time curve (AUC) (P < 0.001). AUC corrected for 1 mg/kg was 5491 +/- 912 ng.h/ml and 5955 +/- 627 ng.h/ml (low dose of LBu in children and adults, respectively) and 6167 +/- 1385 ng.h/ml and 6933 +/- 656 ng.h/ml (ie the first and the last high doses of LBu, respectively). No significant correlation was found between clearance and age or apparent volume of distribution and age (r2 = 0.146 and r2 = 0.046, respectively). No toxicity related to the liposomal formulation of busulphan was observed. We conclude that LBu is suitable for conditioning before stem cell transplantation.

Adolescent↗
PubMed2001

Alpha-interferon maintenance treatment is associated with improved survival after high-dose treatment and autologous stem cell transplantation in patients with multiple myeloma: a retrospective registry study from the European Group for Blood and Marrow Transplantation (EBMT).

The purpose of this study was to evaluate the effect of alpha-IFN maintenance treatment after autologous stem cell transplantation (ASCT) for multiple myeloma in a retrospective registry analysis. 473 patients with multiple myeloma who received IFN maintenance treatment ASCT were compared with 419 patients who did not receive IFN-treatment. Patients who were evaluable for response and in complete or partial remission at 6 months after ASCT were eligible, after excluding patients with graft failure. Cox proportional hazards assumptions were checked and handled by stratification. The prognostic variables unevenly distributed between the two groups were statistically corrected for in the Cox analysis. 391 patients reached complete remission (CR) after ASCT (203 in the IFN group and 188 in the no-IFN group) and 501 were in partial remission (PR, IFN 270, no-IFN 231). Overall survival (OS) and progression-free survival (PFS) were significantly better in the IFN-group (OS, 78 vs 47 months, P = 0.007, and PFS, 29 vs 20 months, P = 0.006, respectively). The difference in OS and PFS was most strongly pronounced in the PR patients. 209 patients have died (IFN, 84; no-IFN, 125). Progressive myeloma was the cause of death in 94% of the IFN-treated patients and in 83% of the no-IFN group (P = NS). Thus, IFN maintenance treatment after ASCT was associated with better OS and PFS. Treatment seemed to be most beneficial in patients who did not achieve CR. The difference in median survival was as long as 2.5 years, and although part of this difference is attributable to differences in other prognostic factors, it might justify possible differences in quality-of-life due to adverse effects of interferon treatment.

Adolescent↗
PubMed2001

Respiratory virus infections after stem cell transplantation: a prospective study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation.

Community-acquired respiratory virus infections are a cause of mortality after stem cell transplantation (SCT). A prospective study was performed at 37 centers to determine their frequency and importance. Additional cases were also collected to allow the analysis of risk factors for severe infection. Forty episodes were collected in the prospective study and 53 additional episodes through subsequent case collection. The frequency of documented respiratory virus infections was 3.5% among 819 allogeneic and 0.4% among 1154 autologous SCT patients transplanted during the study period. The frequency of lower respiratory tract infections (LRTI) was 2.1% among allogeneic and 0.2% among autologous SCT patients. The mortality within 28 days from diagnosis of a respiratory viral infection was 1.1% among allogeneic SCT while no autologous SCT patient died. The deaths of five patients (0.6%) were directly attributed to a respiratory virus infection (three RSV; two influenza A). On multivariate analysis, lymphocytopenia increased the risk for LRTI (P = 0.008). Lymphocytopenia was also a significant risk factor for LRTI in patients with RSV infections. The overall mortality in RSV infection was 30.4% and the direct RSV-associated mortality was 17.4%. For influenza A virus infection, the corresponding percentages were 23.0% and 15.3%. This prospective study supports the fact that community-acquired respiratory virus infections cause transplant-related mortality after SCT.

Adolescent↗
PubMed2001

Progress in allogenic bone marrow and peripheral blood stem cell transplantation for multiple myeloma: a comparison between transplants performed 1983--93 and 1994--8 at European Group for Blood and Marrow Transplantation centres.

Out of 690 allogeneic matched sibling donor transplants for multiple myeloma reported to the European Group for Blood and Marrow Transplantation (EBMT) registry, 334 were performed during the period 1983-93 (all with bone marrow) and 356 during 1994-98 [223 with bone marrow and 133 with peripheral blood stem cells (PBSCs)]. The median overall survival was 10 months for patients transplanted during the earlier time period and 50 months for patients transplanted with hone marrow during the later period. The use of PBSCs was associated with earlier engraftment but no significant survival benefit compared to bone marrow transplants during the same time period. The improvement in survival since 1994 with the result of a significant reduction in transplant-related mortality, which was 38%, 21% and 25% at 6 months and 46%, 30% and 37% at 2 years during the earlier period, and the later period with bone marrow and PBSCs respectively. Reasons for the reduced transplant-related mortality appeared to be fewer deaths owing to bacterial and fungal infections and interstitial pneumonitis, in turn a result of earlier transplantation and less prior chemotherapy. Better supportive treatment and more frequent use of cytokines may also play a role. The improvement in survival was not directly related to the increased use of PBSCs.

Adult↗
PubMed2001

A randomized, double-blind trial of famciclovir versus acyclovir for the treatment of localized dermatomal herpes zoster in immunocompromised patients.

In this randomized, double-blind, multicenter, acyclovir-controlled study, the efficacy and safety of famciclovir were evaluated for the treatment of herpes zoster in patients who were immunocompromised following bone marrow or solid organ transplantation or oncology treatment. A total of 148 patients, 12 years or older with clinical evidence of localized herpes zoster, received either oral famciclovir, 500 mg three times daily, or acyclovir, 800 mg five times daily, for 10 days. Famciclovir was equivalent to acyclovir with respect to the numbers of patients reporting new lesion formation while on therapy (77% vs. 73%, respectively). There were no significant differences between the groups in the time to cessation of new lesion formation, full crusting, complete healing of lesions, or loss of acute phase pain. Treatment with famciclovir was well tolerated, with a safety profile comparable to that of acyclovir. Thus oral famciclovir is a convenient, effective, and well-tolerated regimen for immunocompromised patients with herpes zoster.

2-Aminopurine↗
PubMed2001

Comparable aciclovir exposures produced by oral valaciclovir and intravenous aciclovir in immunocompromised cancer patients.

The objective of this study was to evaluate the comparability of systemic aciclovir exposure at steady state in immunocompromised patients following oral valaciclovir 1000 mg tds and intravenous (iv) aciclovir 5 mg/kg tds. A two-centre, randomized, open label, two-way crossover study was undertaken. Patients aged 18-65 years who had undergone high-dose chemotherapy for cancer and were neutropenic (neutrophil count <0.5 x 109/mL) with normal renal function were recruited. The pharmacokinetic parameters of aciclovir after oral valaciclovir 1000 mg or iv aciclovir 5 mg/kg given as 1 h infusion, each administered every 8 h for seven doses, were compared. Fifteen patients were enrolled and 13 completed both treatments. The mean (s.d.) values for aciclovir after oral valaciclovir and iv aciclovir were: AUC0-8 76.3 (29.7) and 64.2 (20.0) microM x h; peak plasma concentration (Cmax) 26.6 (10.5) and 34.0 (11.9) microM; time to maximal plasma concentration (tmax) 2.01 (0.65) and 0.95 (0.19); and plasma elimination half-life (t1/2) 2.83 (0.91) and 2.44 (0.62) h, respectively. The mean absolute bioavailability of aciclovir from oral valaciclovir was 60 +/- 21%. Equivalent systemic exposure to aciclovir after oral valaciclovir 1000 mg and iv aciclovir 5 mg/kg was observed with AUC0-8 (oral/iv ratio = 1.16; 90% CI 0.98-1.39), whilst significantly reduced peak aciclovir concentrations were obtained with oral valaciclovir (ratio = 0.75; 90% CI 0.60-0.94). Oral valaciclovir offers a convenient, and possibly safer, alternative to iv aciclovir, delivering comparable systemic exposures with reduced peak levels. This may contribute to shorter hospitalization, reduced costs for healthcare providers and improved quality of life for patients.

Acyclovir↗
PubMed2001

Prophylaxis against herpesvirus infections in transplant recipients.

Herpesvirus infections are important after stem cell and organ transplant. During the last decades several antiviral agents have been introduced with efficacy against herpesviruses. These agents are the nucleoside analogues aciclovir, valaciclovir, famciclovir, and ganciclovir; the nucleotide analogue cidofovir; and the pyrophosphate analogue foscarnet. Several studies have been performed with antiviral agents with the aim to reduce morbidity and mortality associated with herpesvirus infections in transplant recipients. Aciclovir and valaciclovir have been examined in randomised, controlled trials in both solid organ and stem cell transplant patients, and were shown to be very effective for the prevention of herpes simplex virus (HSV) and varicella-zoster virus infections. In addition, these drugs were shown to reduce cytomegalovirus (CMV) infection and improve survival in allogenic stem cell transplant patients and to reduce CMV infection, CMV disease (aciclovir and valaciclovir), and acute rejection (valaciclovir) in renal transplant patients. Ganciclovir is very effective for the prevention of CMV infection and disease in both stem cell and solid organ transplant recipients. It can also be used in preemptive strategies in which the aim is to prevent CMV disease in patients who have ongoing CMV infection documented by antigenaemia or detection of CMV DNA. The latter strategy has the advantage of reducing the exposure to the drug and thereby the risk for toxicity. Foscarnet has also been shown to be effective as preemptive therapy for CMV in allogenic stem cell transplant patients and as therapy for aciclovir-resistant HSV infections. Finally cidofovir is an interesting agent with broad spectrum antiherpesvirus efficacy. However, because of the drug's toxicity profile, further studies are needed.

Antibiotic Prophylaxis↗
PubMed2000

Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer: a randomised trial. Scandinavian Breast Group 9401 study.

BACKGROUND: Chemotherapy drug distribution varies greatly among individual patients. Therefore, we developed an individualised fluorouracil, epirubicin, cyclophosphamide (FEC) regimen to improve outcomes in patients with high-risk early breast cancer. We then did a randomised trial to compare this individually tailored FEC regimen with conventional adjuvant chemotherapy followed by consolidation with high-dose chemotherapy with stem-cell support. METHODS: 525 women younger than 60 years of age with high-risk primary breast cancer were randomised after surgery to receive nine cycles of tailored FEC to haematological equitoxicity with granulocyte colony-stimulating factor (G-CSF) support (n=251), or three cycles of FEC at standard doses followed by high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin (CTCb), and peripheral-blood stem-cell or bone-marrow support (n=274). Both groups received locoregional radiation therapy and tamoxifen for 5 years. The primary outcome measure was relapse-free survival, and analysis was by intention to treat. FINDINGS: At a median follow-up of 34.3 months, there were 81 breast-cancer relapses in the tailored FEC group versus 113 in the CTCb group (double triangular method p=0.04). 60 deaths occurred in the tailored FEC group and 82 in the CTCb group (log-rank p=0.12). Patients in the CTCb group experienced more grade 3 or 4 acute toxicity compared with the tailored FEC group (p<0.0001). Two treatment-related deaths (0.7%) occurred in the CTCb group. Six patients in the tailored FEC group developed acute myeloid leukaemia and three developed myelodysplastic syndrome. INTERPRETATION: Tailored FEC with G-CSF support resulted in a significantly improved relapse-free survival and fewer grade 3 and 4 toxicities compared with marrow-supported high-dose chemotherapy with CTCb as adjuvant therapy of women with high-risk primary breast cancer.

Acute Disease↗
PubMed2000

Serum immunoglobulin levels in relation to levels of specific antibodies in allogeneic and autologous bone marrow transplant recipients.

BACKGROUND: The aim of this study was to investigate the correlation of total levels of immunoglobulins to levels of specific antibodies after allogeneic and autologous bone marrow transplantation. Autologous transplant patients had normal levels of IgA and IgG antibodies already at 6 months after transplantation. In allogeneic transplanted patients without chronic graft versus host disease the immunological recovery was slower. The IgA and IgG levels were at the limit for deficiency at 6 months after transplantation. In allogeneic transplant patients with chronic chronic graft versus host disease the immunological recovery was delayed further. The total IgG levels were low at 12 months after transplantation and the IgG subclass pattern did not normalize until 24 months after transplantation. IgA levels remained low at 24 months after transplantation in all allogeneic transplanted patients with chronic chronic graft versus host disease. Protective levels of specific antibodies against tetanus and pneumococci decreased during the first year after transplantation regardless of the total immunoglobulin levels, regardless of the donors immunity. Pneumococcal antibodies decreased only in allogeneic transplanted patients, although autologous transplant patients retained pretransplant immunity against pneumococci. There was no difference in levels of specific antibodies between patients with and without chronic chronic graft versus host disease at 12 months after transplantation. There was no correlation between total immunoglobulin levels to levels of specific antibodies against tetanus and pneumococci after transplantation in our study. Taken together, normalized immunoglobulin levels do not predict normalization of levels of specific antibodies against tetanus and pneumococci after transplantation.

Adolescent↗
PubMed2000

Real-time monitoring of cytomegalovirus infections after stem cell transplantation using the TaqMan polymerase chain reaction assays.

BACKGROUND: Real-time monitoring of cytomegalovirus (CMV) infections in transplant patients demands a rapid and high-throughput CMV DNA quantification method. METHODS: TaqMan polymerase chain reaction assays based on CMV immediate early protein exon 4 and glycoprotein B were developed and were compared with a COBAS AMPLICOR CMV MONITOR (CMM) test for quantifying CMV DNA in peripheral blood leukocytes from seven stem cell transplant patients having received antiviral treatment. RESULTS: There was a good correlation between the TaqMan assays and the CMM test for CMV DNA quantification. The throughput of the TaqMan assays was, however, about 3 times higher than that of the CMM test. The CMV DNA dynamics patterns determined by the TaqMan polymerase chain reaction were well in line with the outcome of the antiviral therapy. CONCLUSIONS: The TaqMan assays may potentially serve as a useful tool for rapid quantification of CMV infections in stem cell transplant patients.

Antiviral Agents↗
PubMed2000

Epstein-Barr virus (EBV) load in bone marrow transplant recipients at risk to develop posttransplant lymphoproliferative disease: prophylactic infusion of EBV-specific cytotoxic T cells.

A semiquantitative polymerase chain reaction assay was used to monitor the blood levels of Epstein-Barr virus (EBV)-DNA in 9 patients receiving allogeneic bone marrow transplants (BMT). Four of 5 recipients of HLA-mismatched T-cell-depleted grafts showed a 4- to 5-log increase of EBV-DNA within 1 to 3 months after BMT. Administration of 2 to 4 infusions of 10(7) EBV-specific cytotoxic T-lymphocytes (CTLs)/m(2) starting from the time of maximal virus load resulted in a 2- to 3-log decrease of virus titers in 3 patients. One patient, who received a T-cell culture lacking a major EBV-specific component, progressed to fatal EBV-positive lymphoma. Administration of EBV-CTLs before the onset of the EBV-DNA peak resulted in stabilization of the virus titers within 2 to 3 logs above the normal levels in the fifth patient. A moderate increase of virus titers was also detected in 3 of 4 patients receiving unmanipulated HLA-matched grafts, whereas 1 patient with Wiskott-Aldrich syndrome reached a 5-log increase of EBV-DNA load within 70 days after BMT. Our results suggest that a rapid increase of circulating EBV-DNA occurs in the absence of EBV-specific T-cell precursors or in the presence of congenital immune defects that prevent the reestablishment of virus-specific immunity. Prophylactic administration of EBV-CTLs early after BMT appears to provide the most effective protection against the development of EBV-associated lymphoproliferative disease.

Adolescent↗
PubMed2000

Outcome of 69 allogeneic stem cell transplantations for Fanconi anemia using HLA-matched unrelated donors: a study on behalf of the European Group for Blood and Marrow Transplantation.

Allogeneic stem cell transplantation is the only treatment that can restore a normal hematopoiesis in Fanconi anemia (FA). In this retrospective multicenter study, we analyzed the results of this approach using HLA-matched unrelated bone marrow donors, and tried to identify covariates predicting the outcome of the transplant. From January 1985 to June 1998, 69 FA patients were transplanted with unrelated HLA-matched donors. Patients' characteristics before and after transplant were provided by the European group blood and marrow transplant registry and were analyzed in collaboration with the European Fanconi Anemia Registry. The 3-year probability of survival was 33%. Extensive malformations, a positive recipient cytomegalovirus serology, the use of androgens before transplant, and female donors were associated with a worse outcome. Primary graft failures were observed more frequently when female donors were used, mainly because the grafts contained lower nucleated cell doses per kilogram of recipient body weight compared with grafts coming from male donors. The probability of grade III-IV acute graft-versus-host disease (GVHD) was 34%. Elevated serum alanine/aspartate transaminases before transplantation; limb, urogenital tract, or nephrologic malformations; and non-T-cell-depleted grafts were predictors of severe acute GVHD. This study shows the dramatic impact of preexisting congenital malformations on the outcome of FA patients transplanted with HLA-matched unrelated donors. If the use of T-cell depletion has led to a dramatic reduction of acute GVHD incidence, no significant outcome improvement was observed with this approach, mainly because of an increased risk of graft failure. (Blood. 2000;95:422-429)

Adolescent↗
PubMed2000

Treatment of acquired severe aplastic anemia: bone marrow transplantation compared with immunosuppressive therapy--The European Group for Blood and Marrow Transplantation experience.

Patients with severe aplastic anemia (SAA) can be successfully treated with bone marrow transplantation (BMT) or immunosuppressive therapy (IS). The current outcome using both forms of therapy among 3,669 patients treated in Europe between 1976 and 1998 is reviewed. Significant progress has been made and the overall risk of failure is now low, with survival rates greater than 80% for both treatments. Chronic graft-versus-host disease (GvHD) remains a problem for BMT patients, and carries a high risk of lethal complications. On the other hand, IS patients are exposed to late failure due to relapse or clonal/malignant diseases. First-line BMT from identical siblings is compared with IS therapy in an intent-to-treat analysis of 1,765 patients, regardless of subsequent transplant status. The outcome of SAA patients has improved considerably over time and is influenced by patient variables such as severity of the disease and age, but also by the choice of the initial treatment.

Anemia, Aplastic↗