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A 20 years old man with peripheral primitive neuroectodermal tumor involving the bone marrow received 12 Gy fractionated total body irradiation, 140 mg/m2 melphalan, 1800 mg/m2 etoposide, and 1500 mg/m2 carboplatin for consolidation of first remission. Thereafter, 250 micrograms/m2/day recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF) (Behring Werke) were administered as continuous infusion 4 days after infusion of autologous bone marrow and peripheral stem cells to accelerate granulocyte reconstitution for control of a continued febrile state. The clinical picture of capillary leak syndrome developed with weight gain, pleural effusions and peripheral edema. The patient's condition stabilized after discontinuation of rh GM-CSF. Eight days later he died of invasive aspergillosis. The clinical course of our patient suggests a potentially fatal toxic effect of rh GM-CSF, even in low dose, in the setting of septicemia or fungemia.

As results of frontline and relapse protocols for children with acute lymphoblastic leukaemia (ALL) are improving over time, there is a strong need for prospective haematopietic stem cell transplantation (SCT) trials, ensuring well standardized procedures for all relevant components which are potentially responsible for heterogeneity in post-SCT outcome. Therefore, in 2003 the Berlin-Frankfurt-Münster (BFM)-Study Group initiated a prospective international multicenter trial (ALL-SCT-BFM 2003). Main goals are the standardization and harmonisation of the SCT procedure and the question, if nowadays SCT from a matched sibling donor (MSD) is equivalent to SCT from a very well matched donor (MD). Further, we want to determine the efficacy of a SCT from HLA-mismatched donors (MMD) compared to SCT from MD/MSD as well as the incidence of acute and chronic graft versus host disease (GvHD) after SCT. Between September 2003 and June 2007, 381 patients (185 in CR1, 196 in CR2 or after subsequent relapse) were recruited by 27 participating SCT centers in Austria, Germany and Switzerland. Indications for SCT were poor response to induction treatment, either detected by morphology on day 33 or by minimal residual disease load measured after 11 weeks of treatment, cytogenetic aberrations [t(9;22), t(4;11)], early bone marrow relapses of ALL, or any subsequent ALL relapse. 76 patients had an indication for a MSD, 131 patients for a MD, and 174 patients for a MMD. Compliance with HLA-typing procedures according to the trial guidelines (high resolution typing of HLA A, B, C, DRB1 and DQB1) improved over time: 54% in 2004, 83% in 2005, 90% in 2006, and so far 100% in 2007. Unmanipulated bone marrow was used in 73% of MSD- and MD-SCT as recommended by the protocol. The recommended conditioning regimens (TBI+VP16 for MSD, TBI+VP16+ATG for MD, and TBI+Flu+VP16+ATG for MMD; in children younger than 2 years, TBI was substituted by BU+Cy) were used in 80% of all patients. GvHD prophylaxis (cyclosporine A for MSD, and cyclosporine A plus “short methotrexate” for MD) was given in 83% of all patients according to the trial guidelines. In most cases, deviations were due to clinical reasons. As the trial ALL-SCT-BFM 2003 is ongoing till 2009, interim results regarding outcome will not be presented. Nevertheless, treatment-related mortality is still very low (7%) and has improved over time since the very early beginning. Final results will be a very stable basis for subsequent ALL-SCT trials, focussing on controlled modifications and interventions in those patients being at highest risk for relapse subsequent to SCT.

In trial ALL-BFM 2000, high-risk (HR) acute lymphoblastic leukemia (ALL) is defined by inadequate initial response to induction treatment [poor prednisone response on treatment day eight, non remission on treatment day 33, and/or a high load of minimal residual disease (MRD, ≥10E-3) after 12 weeks of treatment (TP2)] and/or by cytogenetics [t(4;11 or t(9;22)]. Between August 1999 and November 2006, 494 (15%) out of 3255 study patients were stratified into the HR branch of trial ALL-BFM 2000. 431 (87%) of these HR patients underwent successful MRD monitoring at TP2 with 274 (56%) patients having received additional extensive prospective MRD monitoring subsequent to TP2. Patients with an indication for stem cell transplantation (SCT) and a suitable donor were scheduled for SCT within six weeks after the third HR block of the intensive consolidation phase. The estimated 4-years event-free-survival (4y-pEFS) for the entire HR group was 68%+/−3%, estimated survival was 74%+/−3%. Patients with MRD load of ≤10E-4 at TP2 (n=231) had a 4y-pEFS of 82%+/−3%, patients with MRD levels of 10E-3 at TP2 (n=84) had a 4y-pEFS of 74%+/−6%, and patients with MRD of >10E-3 at TP2 (n=116) had a 4y-pEFS of 35%+/−5%. MRD-kinetics subsequent to TP2 revealed, that 85% of all patients with an MRD level of 10E-3 at TP2 continued to decrease their load below 10E-3 during the pulsatile intensive consolidation phase, whereas this was observed in only 35% of patients with an MRD level of >10E-3 at TP2. The 4y-pEFS of patients with an MRD load persisting at 10E-2 after application of three intensive HR blocks after TP2 was 0% if no SCT was performed, and 33%+/−11% after SCT in CR1. Our data reflect that extensive MRD measurements in HR-ALL patients allow a dynamic insight into the development of resistance, and serve as valuable tool for further clinical treatment adjustment. “MRD non-response” after three BFM HR blocks identifies a patient group in urgent need of alternative treatment elements, closely monitored by MRD, before going into SCT in CR1.

Background: Despite availability of potent anti-bacterial, anti-mycotic drugs and hematopoietic growth factors invasive bacterial or fungal infections remain a severe threat to neutropenic patients after chemotherapy or hematopoietic stem cell transplantation (HSCT). Granulocyte transfusions (GT) from granulocyte colony stimulating factor (G-CSF)-stimulated donors have been shown to increase the leukocyte count prior to expected hematopoietic regeneration, resulting in a shorter period of neutropenia and thus offer a therapeutic option for the control of severe infections. However, published studies rely on clinical observations of individual cases as no statistical comparison with control groups could have been established. The aim of this study was to define the clinical benefit and the leukocyte increment/duration of neutropenia after randomized administration of leukocyte transfusions in immunocompromized neutropenic patients. Patients and methods: Between 1999 and 2005 80 patients with underlying hematological diseases with or without allogeneic or autologous HSCT were randomized to receive either G-CSF, anti-infective treatment according to local standards with or without therapeutic or prophylactic application of GT from G-CSF-stimulated volunteer donors. The mean age was 47 years (range, 14 – 62 y). Indications were either fever in neutropenia and pulmonary infiltrates or soft tissue infiltration (therapeutic) or the history of invasive fungal infection during episodes of neutropenia following earlier chemotherapy courses and anticipated neutropenia of > 10 days (prophylactic). Results: 10 centers participated in the trial, however only five centers recruited patients (n=80) for randomization during the study period. This corresponds to ~50% of the expected sample size of 160 patients, hence results are statistically insignificant. Patient characteristics were comparable within the randomized cohorts (underlying disease, stage of disease, indication for GT, lenght of neutropenia). No significant difference in the clinical outcome was found between patients who received either therapeutic or prophylactic GT from G-CSF stimulated donors or no GT. The probability of survival on day 28 was 85% in both groups. Furthermore, no difference in the incidence and causes of death could be identified within the compared cohorts. Conclusion: The high percentage of infection clearance and survival in patients with severe infections in both groups contrasts with published results and own experiences. We speculate whether this is due a bias in including predominantly patients into the randomized study who presented with relatively favourable prognostic factors, as in the observation period numerous GT were performed in the participating centers without randomization. Most likely, existing clinical evidence for the benefit of this therapeutic measure was sufficient in many cases to exclude patients in serious conditions from randomization. Although well designed, a randomized trial may not always provide the expected results.

In the absence of an HLA identical donor, T-cell depleted haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) is an alternative option to treat children with very high risk acute lymphoblastic leukemia (ALL). However, little data is available in children. We have analyzed 118 children (≤16 years old) with ALL transplanted with a myeloablative Haplo-HSCT from 1995 to 2004 in Europe. Only transplants with 2 or more HLA disparities out of 6 (A, B and DRB1) were included. The median age was 8.5 years and median follow-up 56 months (8–116). At transplant, 21 (18%) were in CR1, 72 (61%) in CR2 or CR3 and 25 (21%) in more advanced phase. The 3-year leukemia free survival was 32±10%, 28±5% and 0%, respectively. Therefore we restricted the analysis to patients in remission (n=93) transplanted in 30 EBMT centers. Thirty-four (37%) patients were treated in centres performing more than 10 Haplo-HSCT in the study period (3 centres). The median age of recipient and donor was 8.7 and 37 years, respectively. Fifty four (65%) received a full Haplo-HSCT and 95% of the donors were parental. Twenty seven (29%) had t(9;21) or t(4;11). The majority of patients did not receive drugs for GVHD prophylaxis, ATG/ALG was used in conditioning in 74%, and 73% received TBI. The Clinimacs® device was used in 74% of selections. The median number of CD34+ cells infused was 12.8 106/Kg. Cumulative incidence with competing risk and KM estimates were used to calculate outcome probabilities. The median days of neutrophil recovery was 15 days (8–55) and 90% of patients had signs of engraftment. Acute GVHD II–IV was observed in 24% of the patients. In univariate analysis for LFS there was a trend towards better results for patients receiving higher CD34 cell dose (p=0.08) and a significant difference for patients transplanted in centres performing more Haplo-HSCT (49% versus 17%, p=0.002). Relapse incidence (RI) and non relapse mortality NRM) tended to be different between the experienced and less experienced centres. In less experienced centres NRM was 41% vs 27% (p=0.13) and RI 41% vs. 24% (p=0.10). There were patient, donor and transplant related differences between less and more experienced centres, specifically related to donor sex, Philadelphia positivity, year of transplantation, use of TBI, ATG and DLI and previous autograft. In conclusion, Haplo-HSCT is an alternative option to treat children with very high risk ALL in the absence of HLA identical donor. Centres with more experience have better LFS.

Allogeneic stem cell transplantation (SCT) has become an increasing treatment option for a variety of malignant and non-malignant disease. During immune reconstitution the host is at significant risk for viral infections. Human adenovirus (HAdV) infection is especially in children an important and serious complication. Virus-specific T-cells are essential for the clearance of HAdV, since antiviral chemotherapy has been insufficient to date. We present a new treatment option using virus-specific donor T-cells for adoptive transfer of immunity to patients with systemic HAdV-infection. We isolated in 6 patients with systemic HAdV-infection after SCT virus-specific T-cells of the donor, according to INF-γ secretion after short in vitro stimulation with viral antigen, resulting in a combination of CD4+ and CD8+ T-cells. Between 5-50x103/kg T-cells were infused for adoptive transfer. For follow-up, the infection and the in-vivo expansion of infused T-cells were evaluated. Isolated cells showed high specificity and markedly reduced but residual alloreactivity in-vitro. In three of four evaluable patients the infused T-cells underwent an in-vivo expansion and in these three patients the viral load decreased in peripheral blood after adoptive T-cell transfer. In-vivo expansion of specific T-cells was dose-independent. T-cell infusion was well tolerated. One patient experienced GvHD°II of the skin after T-cell transfer. In conclusion specific T-cell immunotherapy as a new treatment approach for children was performed in 6 cases of systemic HAdV-infection after allogeneic SCT. Induction of a specific T-cell response through adoptive transfer has been shown feasible and effective to protect from HAdV-related complications.

We examined the feasibility and efficacy of a salvage strategy of intensive re-induction chemotherapy followed by autologous or allogeneic hematopoetic stem cell transplantation (HSCT) for children and adolescents suffering from relapsed anaplastic large cell lymphoma after BFM front-line therapy. From 4/1990 to 2/2003, 75 evaluable patients, median age at relapse 9.8 (range 0.4–22.2) years, were enrolled. The median time from the start of first therapy to failure was 7.1 (range 1–76) months. 17 pts suffered from progressive disease during front-line chemotherapy. ALK staining was positive in 57 pts, negative in 5 pts and not available in 13 pts. CD3 reactivity was positive in 24, negative in 42 pts and not available in 7 pts. 2 pts had B-cell ALCL. Salvage therapy consisted of 2 or 3, 5-day chemotherapy courses based upon dexa, vindesine, cytarabine, etoposide, MTX 5g/m2, cyclophosphamide/ifosfamide, vincristine, doxorubicine, intrathecal therapy followed by HSCT. Conditioning regimen: total body irradiation (2x2 Gy day −7,−6,−5), etoposide 40 mg/kg day -4, cyclophosphamide 60 mg/kg/d days −3,−2. Data were updated as of April 1st, 2004. With a median follow-up of 6.9 [0.8–13.2] years, the probability of survival at 3 years after first relapse is 54+6%. 28 pts died of lymphoma, 6 pts of toxicity. 41 pts are alive in ≥CR2. 21 pts received no salvage or chemotherapy only (2 TRM, 18 death of disease, 1 CR). 39 pts received autologous HSCT (21 CR, 2 TRM, 16 re-relapses [6 >CR2]). 15 pts received allogeneic HSCT (10 CR, 3 TRM, 2 relapses). 3/17 pts with relapse during front-line survived compared to 37/57 pts who relapsed later (p We conclude that this strategy proved feasible and efficacious for pts who suffered a relapse after front-line therapy while outcome for pts with progressive disease during front-line treatment was poor. Autologous HSCT is an efficient consolidation for pts with relapses of CD3 negative ALCL but not efficacious for those with CD3 positive tumors. These patients may benefit from allogeneic HSCT.

The prognosis of Hodgkin’s lymphoma (HL) in pediatric patients (pts) with current combined chemoradiotherapy regimens in general is excellent. Even those pts suffering from recurrent disease have a realistic chance for cure with salvage therapy regimens. 74 patients (12 months after therapy). Prior to ASCT, pts had a median of 3 (range, 2–4) lines of therapy and a median of 2 (range, 1–4) relapses/PD. At transplant, 63 pts had chemosensitive disease, defined as complete (CR) or partial remission (PR) and 11 had chemoresistant disease, defined as no change (NC) or primary refractory disease (PRD). Conditioning regimens were BEAM or variants in 47, CVB in 19 and others in 6 pts. Peripheral blood stem cells were used for most patients (76%). All pts engrafted. Additional post transplant radiotherapy was given to 24 pts. At a median follow up of 2.7 years (range, 0.1–12.8) 45 pts (61%) are alive and 29 are dead, which was attributed to the original disease in 21 pts. 42 of 63 pts (68%) with chemosensitive are alive compared to 2 of 11 (18%) with resistant disease (p=.002). Time to first relapse significantly attributed to survival after ASCT (12 of 28 pts with PD, 24 of 34 pts with early and 9 of 12 with late relapses are alive; p=.02). 30 pts (42%) relapsed and only 9 of these (30%) are alive compared to 36 pts (86%) with no relapse after ASCT. One pt received a second ASCT without success and 7 were allografted (2 alive). Probability of overall survival (OS), failure-free survival (FFS), relapse rate (RR) and treatment related mortality (TRM) at 5 years were 59%, 50%, 44%, and 12%, respectively. The following factors were adversely related to OS: early recurrence (p=.046), chemoresistance (p=.003), relapse after SCT (p

MDS in children is a rare disorder characterized by dysplasia and defined genetic abnormalities. In most patients (pts) MDS arises without known predisposing conditions (primary MDS). Here, we report the results of 55 males and 30 females with advanced primary MDS enrolled in the prospective EWOG-MDS trial 97. Data were analysed according to the most advanced FAB-type prior to SCT: 32 pts were classified as RAEB, 40 as RAEB-t and 13 as myelodysplasia-related AML (MDR-AML). Median age at diagnosis was 9.5 yrs (0.1–17.6) and median time from diagnosis of advanced MDS to SCT 4 mo (0.5–31). Cytogenetics revealed monosomy 7 in 32 pts, trisomy 8 in 7, a complex karyotype in 9 and other abnormalities in 9; karyotype was normal in 26 pts and unknown in 2. 31 pts had received AML-like therapy prior to SCT. All pts were given an unmanipulated graft after condititioning with busulfan 16 mg/kg, cyclophosphamide 120 mg/kg and melphalan 140 mg/m. Source of stem cells was bone marrow in 56 pts, peripheral blood in 25, cord blood in 2 and unknown in 2. 36 pts were transplanted from an HLA-identical relative (MFD), 49 pts from an HLA-identical or 1-antigen disparate unrelated donor (UD). GVHD prophylaxis consisted of CSA alone for MFD, whereas recipients of a UD graft generally received CSA, methotrexate and anti-lymphocyte globulin. Two pts suffered graft failure. The cumulative incidence of grade II-IV acute GVHD and chronic GVHD was 40% (SE 5%) and 25% (SE 5%), respectively. 18 pts suffered transplant-related mortality (TRM), the cumulative incidence of TRM in pts grafted from a MFD or UD being 14 and 25%, respectively (p=n.s.). Presence of acute GVHD II-IV (p

Viral infections remain a major cause for transplant related mortality. The introduction of PCR-based assays permits rapid, specific and highly sensitive detection of various viral infections prior to clinical symptoms and thus facilitates preemtive treatment strategies. However a broad routine screening by PCR during the early post-transplant period is cost-intensive. Clinical benefit of broad vs restriced viral screening by PCR was evaluated in total of 98 consecutive pediatric SCT-patients(pts). The first 56 consecutive pts underwent broad viral screening including CMV, ADV, EBV, HSV, VZV, HHV6, HHV7, HHV8, PVB19, RSV, BKV, Enterovirus, Influenza A and B, and Parainfluenza 1–3. PCR-screening was performed twice weekly until day +28 and once weekly until day +100 in peripheral blood (PB), stool, urine and mouth wash. A total of 15675 samples were analyzed. HSV-IgG positive pts. received prophylactic acyclovir. All pts. received preemptive treatment for CMV viremia (gancyclovir) and ADV viremia (cidofovir). Pts with EBV-viremia exceeding 103 copies per ml PB received gancyclovir. In pts. undergoing the broad screening 50/56 pts were positive for at least one virus. The overall incidence of viremia was 61%. HHV6 was detectable in 66% (39% in PB), HHV7 in 16% (11% in PB), CMV in 36% (all in PB, in 23% additionally positive in other sites), EBV in 39% (35% in PB), ADV in 27% (5% in PB), BKV in 13% (all in urine) and PVB19 in one pts. Although the first detection of a viral infection occured before day +120 in all children, PCR positivity persisted throughout the first year post-transplant in many cases. There was no significant difference in the incidence of overall viral infection, viremia or multiple viremia between pts. with T-cell depleted grafts and those with unmanipulated grafts. However T-cell depletion was associated with significantly more lethal viral infections (32% vs 6%, p=0,0127). There was no significant difference in the incidence of viral infections, viremia and lethal viral disease between pts receiving myeloablative conditioning and those receiving reduced intensity conditioning. Isolated HHV6 or HHV7 viremia was not associated with any clinical symptoms and there was no difference concerning the incidence of CMV viremia, lethal viral disease or TRM between pts with and without HHV6 viremia. Of the 20 pts with CMV viremia, 6 pts had lethal CMV disease. 10% of the patients with EBV viremia were symptomatic, the disease being lethal in one case. The three pts who developed ADV viremia had previously been ADV positive in stool. All three pts died from disseminated ADV disease despite treatment with cidofovir. All pts with BKV positive urine had hemorrhagic cystitis. On the basis of these results, the viral screening for the subsequent 42 pts PCR screening was restricted to ADV, CMV and EBV in PB, ADV in stool and BKV in urine once weekly until day +28 and every two weeks thereafter, reducing the cost of the viral screening to 13%. For the patients undergoing restricted screening there was no difference concerning the incidence of CMV, EBV, ADV viremia and the incidence of lethal viral disease (18% vs 14%). We conclude that broad and cost intensive PCR screening for viral infections is of no clinical benefit.

Related donors for hematopoietic cell (HC) transplantation are a growing population in recent years because of expanding indications for allogeneic transplantation. The safety and welfare of the donor are major concerns for the transplantation community, especially for related sibling donors of young recipients who are children and, thus, not able to fully consent. Because donation of HC does not improve the donor's own physical health and carries a risk of side effects, careful assessment of medical risks specific to the individual donor, as well as consideration of ethical and legal aspects associated with donation from a child, must be considered. In addition, donor centers must balance the needs of both the donor and the recipient, understanding the inherent conflict parents may have as they can be overly focused on the very sick child receiving a transplant, rather than on the relatively less significant health or emotional problems that a sibling donor may have, which could impact risk with donation. Likewise, consideration must be made regarding the nature of the relationship of the sibling donor to the recipient and also aspects of performing research on pediatric HC donors. In this article, as members of the Donor Issues Committee of the Worldwide Network for Blood and Marrow Transplantation, we review key ethical concerns associated with pediatric donation and then give recommendations for screening potential child donors with underlying health conditions. These recommendations are aimed at protecting the physical and emotional well-being of childhood donors and arise out of the Third International Conference on Health and Safety of Donors sponsored by the Worldwide Network for Blood and Marrow Transplantation.

We analyzed the long-term outcomes of pediatric patients registered in the European Group for Blood and Marrow Transplantation database who underwent hematopoietic stem cell transplantation (HSCT) for severe treatment refractory autoimmune cytopenia. With a median follow-up of 100 months, event-free survival was 54% overall, with no significant difference between allogeneic HSCT (n = 15) and autologous HSCT (n = 7) recipients (58% versus 42%; P = .50). Despite a trend toward failure of response or relapse after autologous HSCT compared with allogeneic HSCT, the difference was not significant (43% versus 13%; P = .30). Treatment-related mortality was high in both HSCT groups (29% and 16%; P = .09). Based on the limited numbers of subjects in this retrospective analysis, both allogeneic and autologous HSCT may induce complete and persistent responses in approximately one-half of pediatric patients with severe refractory autoimmune cytopenia, although treatment-related toxicity is high.

Radionuclide method for evaluating the performance of hemodialysis in vivo.BackgroundSpecifications of dialyzer performance are generally based on in vitro measurements. There is, however, a shortage of data on dialyzer performance in vivo. The aim of this study was to use continuous measurement of technetium-99m-diethyltriaminepentaacetic acid (Tc-99m-DTPA) blood concentration as a means of continuously monitoring dialyzer function in vivo in patients undergoing routine hemodialysis.MethodsThe study population comprised 15 patients (45 to 80 years old; 13 males). Tc-99m-DTPA was administered intravenously 90 minutes before obtaining a blood sample and starting dialysis. Blood Tc-99m-DTPA activity was continuously monitored by passing the line carrying blood from the patient to the dialyzer close to a scintillation probe mounted in a shielded housing. At the end of hemodialysis, lasting 180 to 300 minutes, chromium-51-ethylenediaminetetraacetic acid (Cr-51-EDTA) was given intravenously and a blood sample taken 90 minutes later. Baseline dialyzer blood flow (Qb) and dialysate flow (Qd) were 250 to 350mL/min and 500mL/min, respectively. The rate constant, α, of the decrease in blood Tc-99m-DTPA activity was used as the measure of moment-to-moment dialyzer function. Pre- and postdialysis extracellular fluid volumes were calculated from the blood Tc-99m-DTPA and Cr-51-EDTA concentrations (VDTPA and VEDTA) before and after dialysis. Tc-99m-DTPA clearance was measured as the product of α and VDTPA. Dialyzer urea clearance was calculated from pre- and postdialysis urea nitrogen concentrations and the time of dialysis. The effects of brief changes in Qb and Qd on dialyzer function were assessed from the associated changes in α.ResultsThe Tc-99m-DTPA clearance profile was biexponential, becoming monoexponential about 1 hour after starting hemodialysis, with α remaining constant for as long as dialysis continued in five patients in whom Qb and Qd were left unaltered. Mean (SEM) plasma Tc-99m-DTPA clearance averaged over the entire period of dialysis in all 15 patients was 110 (3.1)mL/min. It correlated with urea clearance (r = 0.71) (P < 0.01) which was 225 (9.5)mL/min based on a total body water of 2.5 that of VDTPA and 212 (13)mL/min scaled to 40 L/1.73m2. Extracellular fluid volume decreased by 1.73 (0.74) l over dialysis, which was comparable to the change in weight [1.48 (0.57) kg]. The extraction fraction of Tc-99m-DTPA across the artificial kidney, directly measured from afferent and efferent blood samples under baseline Qb and Qd, was 0.5 (0.013). Average extraction fraction indirectly estimated from Tc-99m-DTPA blood clearance and Qb was 0.54 (0.019). These two measurements of extraction fraction correlated with each other under conditions of varying Qb and Qd (r = 0.74) (N = 27) (P < 0.001). Changes in α resulting from changes in Qb and Qd were similar to changes predicted from computerized modeling. The ratio of mass transfer coefficients of urea and Tc-99m-DTPA with respect to the dialyzer, calculated as if they were permeability-surface area products, was 3.3, similar to the ratio, obtained from the literature, in continuous capillary endothelium.ConclusionTc-99m-DTPA is a useful agent for continuously monitoring dialyzer function in vivo and provides a platform for the use of other radio-pharmaceuticals of different molecular sizes that could be used in an analogous fashion.

Sixty-one consecutive paediatric patients undergoing allogenic bone marrow transplantation (BMT) were screened prospectively for cytomegalovirus (CMV)-viraemia by PCR. Sixteen patients (26%) presented with single or recurrent CMV-viraemia between day -7 and + 100. Although only four of them had evidence of CMV-disease, there was a significant difference in the incidence of acute Graft versus Host Disease (GVHD) grade III-IV (75% vs 15.5%), liver-involvement (68% vs 13%) and the incidence of chronic GVHD (83% vs 13.8%) between CMV-PCR-positive and CMV-PCR-negative patients. Transplant-related mortality (TRM) was 43.7% in the CMV-PCR-positive group versus 13% in patients which had no evidence for CMV-viraemia. In all but one cases mortality in CMV-PCR positive patients was GVHD-associated. Pre-emptive therapy with gancyclovir in case of CMV-viraemia seemed to have no impact on incidence and severity of GVHD.