Biomedical subjects

H Pape

Publications and source records attributed to H Pape.

At least 19 recordsLinked to original sources

PubMed2006

G-CSF during large field radiotherapy reduces bone marrow recovery capacity.

OBJECTIVE: Side effects of chemo- and radiotherapy are granulo- and thrombocytopenia. However, the long-term effects of in vivo granulocyte-colony-stimulating factor (G-CSF) stimulation of the hematopoietic system during radiotherapy are not yet completely understood. In the present study, we sought to determine the bone marrow effect of G-CSF during radiotherapy. MATERIAL AND METHODS: In a prospective, randomized clinical trial 10 patients (6 m, 4 f, 30-64 yrs, mean 50.6 yrs) were assigned to large field radiotherapy (RT). 7 patients (pat.) with non-Hodgkin lymphoma, one patient with Hodgkin's disease and 2 patients with small-cell carcinoma of the lung were included. The patients were randomized to either radiotherapy alone (group A) or radiotherapy with simultaneous G-CSF (group B) treatment and assessed for acute and late toxicity. Blood samples were drawn and analyzed before and after G-CSF stimulation. The mobilization effectivity of G-CSF on CD34 superset+ progenitor cells was measured using flow cytometry and colony forming units (CFU) testing on admission and during the complete follow-up period (1, 3 and 18 months post RTx). RESULTS: Overall, 50 pat. were intended to be included to the protocol. However, the preliminary analysis revealed a significant decrease of thrombocytes and CD34 superset+ progenitor cells in the G-CSF treatment group. According to the study protocol further treatment was stopped. Peripheral leukocyte counts ranged between 2800 - 4375 /mul in 9/10 pat. In group B mean thrombocyte levels dropped below 30.000 mg/l and CD34 superset+ progenitor cells to 50% (interruption criteria, p<0.02, Student's t-test). Hemoglobin values did not vary. Differential blood smears showed differences in granulocyte counts and a higher proportion of neutrophils in group B. Lymphocyte counts of patients randomized to group A were significantly decreased when compared to group B. In group A, 3/5 pat. developed an overshooting reaction (4,7 x increase) after G-CSF-stimulation. In arm B circulating CD34 superset+ progenitor cells dropped. In arm A, 3/5 pat. had an initial overshoot reaction when compared to none in group B. CFU (> 40 cells) and cluster (4 -39 cells) showed considerable variations. CONCLUSION: Our results demonstrate that simultaneous treatment with G-CSF during radiotherapy reduces the mobilization of CD34+ progenitor cells and exhaust the bone marrow capacity while peripheral leukocyte counts remain at baseline levels.

Adult↗

PubMed2006

Three cases of renal relapse after allogeneic hematopoietic stem cell transplantation for childhood acute lymphoblastic leukemia.

Isolated renal relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT) in children with acute lymphoblastic leukemia (ALL) is a rare condition. Generally, in ALL, the sites most frequently affected by extramedullary relapse are the central nervous system (CNS) and the testicles. Here we report on three young boys with relapsed B-precursor ALL, who underwent alloHSCT from HLA-identical siblings and suffered a histopathologically proven isolated unilateral renal relapse (two patients) or a combined renal and testicular relapse (one patient) 6, 10 and 12 months post alloHSCT. In all patients at the time of relapse bone marrow showed complete remission with complete donor hematopoiesis. They all received total body irradiation with partial shielding of the kidneys as part of their conditioning therapy, such that renal shielding could be an explanation for the observed accumulation of renal relapses. Moreover, during the past few years so called immune privilege has been postulated for frequent relapse sites such as the CNS, the testicles and the anterior chamber of the eye. Impaired accessability of these organs by cytotoxic T-cells (CTLs) with a reduced graft-versus-leukemia (GvL) effect after alloHSCT is based on a number of different molecular and cellular mechanisms. Similar mechanisms have been shown to be effective in the tubulointerstitial space of the kidney, rendering the kidney a potentially immune privileged site. Due to these observations we advocate sufficient treatment of the kidneys during conditioning therapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Transplantation of allogeneic CD34+-selected cells followed by early T-cell add-backs: favorable results in acute and chronic myeloid leukemia.

BACKGROUND: The aim of this study was to investigate preservation of anti-leukemic activity and protection from opportunistic infections after transplantation of allogeneic + cells in patients with hematologic malignancies and bad prognosis. Methods Thirty-three patients [median age 42 years, range 23-55 years, diagnosis AML/myelodysplastic syndrome (MDS) 14, ALL nine, CML seven and multiple myeloma (MM) three] received myeloablative conditioning followed by infusion of selected CD34+ cells from matched unrelated donors (31) or HLA-identical siblings (two). Early donor lymphocyte infusions (DLI; 0.5 and 1.0 x 10(6) CD3+ cells/kg) were given while patients were on immunosuppressive therapy. RESULTS: Ninety-seven per cent of patients engrafted and 24 of 29 patients surviving more than 30 days received at least one pre-emptive DLI. Three patients (10%) developed acute (a)GvHD (two grade I-II, one grade III-IV) spontaneously, and 16 patients (67%) developed aGvHD after DLI (12 grade I-II, four grade III-IV). Eight of 24 evaluable patients developed chronic (c)GvHD (33%, six limited, two extensive). After a median follow-up of 590 days (range 138-1610 days) 18 patients were alive (55%), 16 in complete remission (CR), one in hematologic and one in molecular relapse. Seven patients died after relapse (21%) and eight died from transplantation-related causes (24%). Patients with myeloid malignancies had a significantly better survival than patients with ALL or MM (74%+/-10 vs. 30%+/-13, P<0.05). DISCUSSION: Early pre-emptive low-dose DLI following transplantation of selected CD34+ cells from unrelated donors after myeloablative conditioning is feasible and effective without undue toxicity, especially in patients with myeloid malignancies.

Adult↗

PubMed2003

Isolation of phages infecting Actinoplanes SN223 and characterization of two of these viruses.

Phages infecting the industrially important Actinoplanes strain SN223 were isolated from soil samples collected at the shores of inland waters in Germany. The genome sizes range from 53 kb to 58 kb. Preliminary analyses revealed G+C contents comparable with the G/C bias of the host. Electron microscopy of three selected viruses displayed no obvious morphological differences, the phage heads being icosahedral and their tails non-contractible. Two of the phages (phiAsp2, phiAsp3.1) characterized in more detail are capable of provoking putative pseudolysogenic growth of the host bacterium. The carrier state for phiAsp2, in which cells are tightly packed with viruses, was demonstrated by electron microscopy. The latter phage is apparently widely distributed, as it was isolated from regions which are distantly located, i.e. more than 600 km apart from each other.

Bacteriolysis↗

PubMed2003

High-dose therapy for patients with primary multifocal and early relapsed Ewing's tumors: results of two consecutive regimens assessing the role of total-body irradiation.

PURPOSE: Risk stratification of metastatic and relapsed Ewing's tumors (ETs) has been a matter of debate during the last decade. Patients with bone or bone marrow metastases or early or multiple relapses constitute the worst risk group in ET and have a poorer prognosis than patients with primary lung metastases or late relapses. In this article, the results of the present Meta European Intergroup Cooperative Ewing Sarcoma Study (MetaEICESS) (tandem melphalan/etoposide [TandemME]) were compared with the result of the previous study (hyper melphalan/etoposide [HyperME]), both at 5 years, in a patient population within the same high-risk stratum to determine toxicity. PATIENTS AND METHODS: Among 54 eligible patients, 26 were treated according to the HyperME protocol, and 28 were treated according to TandemME protocol. Patients received six cycles of the Cooperative Ewing Sarcoma Study treatment in HyperME and six cycles of the EICESS treatment in TandemME as induction chemotherapy. Patients also received involved-compartment irradiation for local intensification and myeloablative systemic intensification consolidation with hyperfractionated total-body irradiation (TBI) combined with melphalan/etoposide in HyperME or two times the melphalan/etoposide in TandemME followed by autologous stem-cell transplantation. RESULTS: The event-free survival (EFS) rate +/- SD in HyperME and TandemME was 22% +/- 8% and 29% +/- 9%, respectively. The dead of complication rate was 23% in HyperME and 4% in TandemME. CONCLUSION: TandemME offers a decent, albeit still not satisfactory, rate of long-term remissions in most advanced ETs (AETs), with short-term treatment and acceptable toxicity. TBI was not required to maintain EFS level in this setting but was associated with a high rate of toxic death. Future prospective studies in unselected patients are warranted to evaluate high-dose therapy in an unselected group of patients with AET.

Adolescent↗

PubMed2003

Relapse after high-dose therapy in relapsed Ewing's tumor patients: effects of maintenance chemotherapy in two selected patients?

BACKGROUND: The prognosis for patients with high-risk Ewing's tumor, i.e. primarily multifocal or early relapsed disease, is extremely poor with conventional relapse therapy. High-dose radio/chemotherapy (HDC) with subsequent stem cell transplantation seems to improve outcome in this patient cohort. In spite of this intensified therapy however, relapse remains the most frequent cause of death. In the majority of patients the time to second relapse after HDC is shorter than the time to first relapse after conventional therapy (3.4 vs. 18 months). Event-free survival in Ewing's tumor patients who suffer a second relapse after first-line therapy (EICESS 92) is 2% after 18 months. CASE REPORT: The present report describes the clinical course of two girls who relapsed after HDC and subsequently received low-dose oral trofosfamide and etoposide. The patient with very late multifocal relapse after first-line treatment and a second localized relapse 30 months after HDC remains disease-free for 5 years after the last relapse. However, the other patient with 2 early relapses after first-line treatment and HDC, respectively, did not benefit from this regime. CONCLUSION: We propose that low-dose maintenance therapy may be beneficial in the subgroup of Ewing's tumor patients with late relapse after HDC.

Adolescent↗

PubMed2001

Treatment of recurrent malignant sacrococcygeal germ cell tumors: analysis of 22 patients registered in the German protocols MAKEI 83/86, 89, and 96.

PURPOSE: To evaluate therapeutic options for recurrent malignant sacrococcygeal germ cell tumors (GCT) following three-agent, cisplatinum-based, first-line chemotherapy and tumor resection. PATIENTS AND METHODS: Twenty-two patients were evaluated in 22 first-, 14 second-, five third-, and two fourth-relapse situations. One patient, who relapsed with pure teratoma, was excluded from the analysis of adjuvant treatment. RESULTS: Seventeen patients presented with an isolated local recurrence, two patients showed a distant relapse, and three patients suffered from a combined local and distant recurrence. Twelve patients achieved complete remission (CR) after surgery (n = 12) and adjuvant platinum chemotherapy (n = 10). Seven of these patients remain in continuous CR, and five patients relapsed. All patients who achieved only a partial remission developed a second relapse. Three of 14 patients could be cured after a second (or further) relapse. Altogether, 10 patients survived disease free, and 12 patients died as a result of tumor progression (n = 11) or therapy-related complications (n = 1). The completeness of salvage surgery and clinical remission status after first salvage treatment were the most important prognostic parameters. In addition, patients in first or second relapse with locally advanced or poorly responding tumors benefited from preoperative chemotherapy in combination with regional hyperthermia (RHT). In some patients after microscopically incomplete resection, irradiation at doses > 45 Gy contributed to a favorable outcome. CONCLUSION: The complete resection of the local recurrence represents the cornerstone of salvage treatment. Preoperative platinum-based chemotherapy, combined with RHT in some patients, facilitates complete tumor resection. Radiotherapy should be reserved for those patients with microscopically incomplete tumor resection. As the chance of cure decreases with further relapses, it is important to establish a stringent therapeutic strategy to avoid significant treatment delays and, most importantly, insufficient local therapy.

Actuarial Analysis↗

PubMed2001

Identification, cloning, expression, and characterization of the extracellular acarbose-modifying glycosyltransferase, AcbD, from Actinoplanes sp. strain SE50.

An extracellular enzyme activity in the culture supernatant of the acarbose producer Actinoplanes sp. strain SE50 catalyzes the transfer of the acarviosyl moiety of acarbose to malto-oligosaccharides. This acarviosyl transferase (ATase) is encoded by a gene, acbD, in the putative biosynthetic gene cluster for the alpha-glucosidase inhibitor acarbose. The acbD gene was cloned and heterologously produced in Streptomyces lividans TK23. The recombinant protein was analyzed by enzyme assays. The AcbD protein (724 amino acids) displays all of the features of extracellular alpha-glucosidases and/or transglycosylases of the alpha-amylase family and exhibits the highest similarities to several cyclodextrin glucanotransferases (CGTases). However, AcbD had neither alpha-amylase nor CGTase activity. The AcbD protein was purified to homogeneity, and it was identified by partial protein sequencing of tryptic peptides. AcbD had an apparent molecular mass of 76 kDa and an isoelectric point of 5.0 and required Ca(2+) ions for activity. The enzyme displayed maximal activity at 30 degrees C and between pH 6.2 and 6.9. The K(m) values of the ATase for acarbose (donor substrate) and maltose (acceptor substrate) are 0.65 and 0.96 mM, respectively. A wide range of additional donor and acceptor substrates were determined for the enzyme. Acceptors revealed a structural requirement for glucose-analogous structures conserving only the overall stereochemistry, except for the anomeric C atom, and the hydroxyl groups at positions 2, 3, and 4 of D-glucose. We discuss here the function of the enzyme in the extracellular formation of the series of acarbose-homologous compounds produced by Actinoplanes sp. strain SE50.

Acarbose↗

PubMed2000

[Conventional and virtual simulation in retrobulbar irradiation].

BACKGROUND: Radiotherapy is commonly used in Grave's ophthalmopathy. The target volume encompasses the ocular muscles and the orbital tissue. The result of conventional simulation can be examined by means of CT simulation. PATIENTS AND METHODS: Twenty-five planning CTs with Grave's ophthalmopathy were studied. The conventional simulation of 4 x 4 cm2 lateral portals confined anteriorly by the fleshy canthus was performed on a CT-simulator using the observer's eye view (OEV) and digitally reconstructed radiographs (DRR). The coverage of the target volume and sparing of the eye lenses were studied on axial CT slices and multiplanar reconstructions (MPR). The distances between the apex of the orbita and cornea, fleshy canthus, and bony canthus were measured as well as the distance between cornea and posterior face of the lens. RESULTS: The pituitary gland and the ocular lenses were spared in each case (25/25). The orbita was entirely covered in 24 cases (96%). However, anterior parts of the external eye muscles were not completely encompassed in 7 cases (28%). The distance from the apex of the orbita to the cornea was 54.6 mm (53.3 to 55.8 mm, 95% confidence interval), to the fleshy canthus 40.3 mm (39.4 to 41.2 mm), and to the bony canthus 31.4 mm (30.2 to 32.5 mm). The distance between cornea and posterior face of the lens was 8.3 mm (7.9 to 8.7 mm). The distance between cornea and canthus differed significantly from normal eyes while the distance between cornea and posterior face of the lens was very similar to normal eyes. CONCLUSIONS: Conventional simulation of orbital irradiation with lateral fields confined anteriorly by the fleshy canthus ensures protection of the ocular lenses and the pituitary gland. However, anterior parts of the eye muscles may occasionally not completely be covered. The fleshy canthus and the cornea are more reliable landmarks as compared to the bony canthus.

Computer Simulation↗

PubMed2000

Interdisciplinary treatment in pediatric patients with malignant CNS tumors.

Despite sophisticated surgical methods only a few pediatric CNS tumors can be controlled by operation alone. Therefore multimodality treatment regimens are needed to improve quality of life and survival, which is most important in malignant neoplasms. Since 1998 we have treated 16 children with malignant CNS tumors. All 16 patients have been treated on an interdisciplinary basis and are therefore accompanied by a pediatric neurooncology group consisting of a neurosurgeon, pediatric oncologist, and radiotherapist. Depending on tumor histology, child's age, and extent of surgery, further adjuvant therapy is planned by this group. Newly diagnosed tumors are typically treated by a specific chemotherapy protocol according to a multi-institutional study. In recurrent tumors more individual treatment regimens are considered. Data concerning surgery, adjunctive treatment, complications, and outcome of all patients and four case reports are presented.

Adolescent↗

PubMed2000

Allogeneic and autologous stem-cell transplantation in advanced Ewing tumors. An update after long-term follow-up from two centers of the European Intergroup study EICESS. Stem-Cell Transplant Programs at Düsseldorf University Medical Center, Germany and St. Anna Kinderspital, Vienna, Austria.

BACKGROUND: An update of results from the High Risk Protocol of the Meta-EICESS Study, conducted at the Pediatric Stem-Cell Transplant Centers of Düsseldorf and Vienna. In order to evaluate a possible therapeutic benefit after allogeneic SCT in patients with advanced Ewing tumors (AET), we compared outcome after autologous and allogeneic stem-cell transplantation (SCT). PATIENTS AND METHODS: We analyzed 36 patients treated with the myeloablative Hyper-ME protocol (hyperfractionated total body irradiation, melphalan, etoposide +/- carboplatin) between November 1986 and December 1994. Minimal follow-up for all patients was five years. All patients underwent remission induction chemotherapy and local treatment before myeloablative therapy. Seventeen of thirty-six patients had multifocal primary Ewing's tumor, eighteen of thirty-six had early, multiple or multifocal relapse, one of thirty-six patients had unifocal late relapse. Twenty-six of thirty-six were treated with autologous and ten of thirty-six with allogeneic hematopoietic stem cells. We analyzed the following risk factors, that could possibly influence the event-free survival (EFS): number of involved bones, degree of remission at time of SCT, type of graft, indication for SCT, bone marrow infiltration, bone with concomitant lung disease, age at time of diagnosis, pelvic involvement, involved compartment radiation, histopathological diagnosis. RESULTS: EFS for the 36 patients was 0.24 (0.21) +/- 0.07. Eighteen of thirty-six patients suffered relapse or died of disease, nine of thirty-six died of treatment related toxicity (DOC). Nine of thirty-six patients are alive in CR. Age > or = 17 years at initial diagnosis (P < 0.005) significantly deteriorated outcome. According to the type of graft, EFS was 0.25 +/- 0.08 after autologous and 0.20 +/- 0.13 after allogeneic SCT. Incidence of DOC was more than twice as high after allogeneic (40%) compared to autologous (19%) SCT, even though the difference did not reach significance (P = 0.08, Fisher's exact test). CONCLUSIONS: Because of the rather short observation period. secondary malignant neoplasms (SMN) may complicate the future clinical course of some of our patients who are currently viewed as event-free survivors. EFS in AET is not improved by allogeneic SCT due to a higher complication rate. The patient group was to small to analyze for a possible graft-versus-tumor effect.

Adolescent↗

PubMed1999

[Young victims in Oslo--a problem of immigration?].

There has been considerable concern over victimization from violence in Norway over the last couple of years. This study investigated risk groups for victimization with special emphasis on the importance of immigrant background. All students enrolled in the secondary school system in Oslo (ages 13-18, N = 10,812) filled in a questionnaire at school. 79% had a background from Norway, the rest had a background from other countries. 32% had experienced mild victimization, 12% had experienced moderately serious victimization, while 6% had experienced serious victimization--defined as being hurt so hard as to need medical treatment. Serious victimization was related to working-class background, having parents who were economically inactive, living in the eastern part of Oslo, and to immigrant background. However, immigrant adolescents also had low rates of mild and moderate victimization, and thus high rates of non-victimization. These associations to immigrant background persisted, also when we controlled for other variables. Overall, immigrant background is associated with reduced risk for victimization. However, a sub-segment of immigrants are at increased risk of serious violent victimization, also when we control for other risk factors.

Adolescent↗

PubMed1999

[Problematic puberty?].

This paper shows how involvement in problem behaviour among 13- and 14-year-olds varies according to level of pubertal development. Furthermore, it explores whether psychosocial factors such as characteristics of the peer network (deviance and gang membership), parental behaviour (supervision, care, and parents' frequency of alcohol intoxication) and masculine gender identity mediate this relationship. The data stem from a nation-wide representative survey of the general youth population in Norway (n = 3,139, response rate 97%). The prevalence of problem behaviour (i.e. shoplifting, truancy, vandalism etc.) increased with increasing levels of physical maturation for both sexes. The association was strongest among boys, however. Further analyses revealed that this gender difference could be attributed to the fact that early mature boys, to a greater extent than early mature girls, associate with deviant peers.

Adolescent↗

PubMed1999

[Changes in hemoglobin concentrations in combined radio- and chemotherapy in locally advanced ORL tumors].

BACKGROUND: Despite multimodality treatment strategies of locally advanced head and neck cancers long-term results leave much to be desired. There is evidence that oxygenation status of head and neck tumors is directly influenced by the hemoglobin concentration. The aim of this study was to verify changes in the hemoglobin level during combined radio-chemotherapy of locally advanced head and neck tumors. PATIENTS AND METHODS: Sixty-eight patients with locally advanced head and neck cancer had primary or adjuvant radiotherapy with doses of 60 to 74 Gy in combination with cisplatin- (+/- 5-FU) or carboplatin chemotherapy in the first and fifth week of treatment. Hemoglobin levels were analyzed before and at the end of radiotherapy. RESULTS: In 41% of all patients the initial hemoglobin concentration was below normal levels. The mean hemoglobin values in all patients dropped significantly from 12.9 +/- 1.7 g/dl before to 11.6 +/- 1.6 g/dl at the end of treatment. In 12 cases (18%) allogeneic erythrocytes had to be transfused during treatment. At the end of treatment 76% of all patients had anemic hemoglobin levels. In the groups of patients with cisplatin and carboplatin chemotherapy a significant decrease in hemoglobin levels was seen without meaningful statistical difference between these 2 groups. CONCLUSIONS: In patients with locally advanced head and neck cancer a high initial rate of anemia was registered (41%): This rate was nearly doubled during chemoradiation (76%). Since several studies have shown a correlation between hemoglobin levels and local tumor control, there is evidence, that this group might benefit from correcting anemia before combined radio-chemotherapy.

Adult↗

PubMed1999

Radiotherapy and high-dose chemotherapy in advanced Ewing's tumors.

BACKGROUND: Ewing's tumors are sensitive to radio- and chemotherapy. Patients with multifocal disease suffer a poor prognosis. Patients presenting primary bone marrow involvement or bone metastases at diagnosis herald a 3-year disease-free survival below 15%. The European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) has established the following indications for high-dose therapy in advanced Ewing's tumors: Patients with primary multifocal bone disease, patients with early (< 2 years after diagnosis) or multifocal relapse. PATIENTS AND METHOD: As of 1987, 83 patients have been treated in the EICESS group, 39 of them at the transplant center in Düsseldorf, who have been analyzed here. All individuals received 4 courses of induction chemotherapy with EVAJA and stem cell collection after course 3 and 4. Consolidation radiotherapy of the involved bone compartments was administered in a hyperfractionated regimen 2 times 1.6 Gy per day, up to 22.4 Gy simultaneously to course 5 and 22.4 Gy to course 6 of chemotherapy. The myeloablative chemotherapy consisted of melphalan and etoposide (ME) in combination with 12 Gy TBI (Hyper-ME) or Double-ME with whole lung irradiation up to 18 Gy (without TBI). RESULTS: The survival probability at 40 months was 31% (44% DOD; 15% DOC). Pelvic infiltration did not reach prognostic relevance in this cohort. Radiotherapy encompassed 75% of the bone marrow at maximum (average 20%). Engraftment was not affected by radiotherapy. CONCLUSION: High-dose chemotherapy can improve outcome in poor prognostic advanced Ewing's tumors. The disease itself remains the main problem. The expected engraftment problems after intensive radiotherapy in large volumes of bone marrow can be overcome by stem cell reinfusion.

Adolescent↗

PubMed1999

Multimodality diagnostics and megatherapy in poor prognosis Ewing's tumor patients. A single-center report.

BACKGROUND: The prognosis of Ewing's tumor patients has been improved gradually through cooperative therapy studies, so that meanwhile 55 to 65% of the patients survive relapse-free in the long term. Patients with multifocal primary, early or multiply-relapsed Ewing's tumors have a dismal prognosis. Megatherapy with subsequent stem cell transplantation seems to improve outcome in this patient cohort. Feasibility of this intense megatherapy regimen is crucially dependent on collaboration and multidisciplinary coordination of radiologists, radiotherapists, surgeons and oncologists. PATIENTS AND METHODS: Since 1988, 25 patients were treated with megatherapy consisting of melphalan, etoposide and total-body irradiation followed by stem cell transplantation. All patients received 6 courses of an induction therapy. Before the fourth therapy block, tumors that were bulky at initial diagnosis (> 200 ml) were excised, as well as lung metastases which could still be detected after the third chemotherapy block. During the fifth and sixth chemotherapy block, patients received local irradiation on all infiltrated sites. Persisting immunosuppression after high-dose treatment may facilitate the incidence of relapse. To improve proliferation and cytotoxic activity of early regenerating NK-cells, adoptive immunotherapy with systemic IL-2 therapy after megatherapy is part of the treatment protocol. RESULTS: Of 25 patients treated with megatherapy, 10 patients are still alive with a follow-up time of 6 months to 9 years after megatherapy. The time up to engraftment was decreased from 15 +/- 6 days down to 9 +/- 2 days through the use of G-CSF and CD34+ selected stem cells. At the same time, erythrocyte and platelet replacement was shortened. Frequently occurring complications were mucositis and infections. One patient died after developing septicemia and multi-organ failure, another patient developed a myelodysplastic syndrome 4.5 years after megatherapy. However, relapse is still the major cause of death. The influence of IL-2 on event-free survival cannot valued because 21 of 25 patients were treated with adoptive immunotherapy. CONCLUSION: The complex diagnostic and therapeutic strategy renders and EFS of 34% for a patient group with otherwise dismal prognosis. To clarify the efficiency of megatherapy in patients with advanced Ewing's tumors, a standardized treatment strategy is necessary to accumulate a sufficient number of patients for large cooperative studies in this subject.

Adolescent↗

PubMed1999

[Optimal timing for secondary surgery in polytrauma patients: an evaluation of 4,314 serious-injury cases].

INTRODUCTION: It has been argued that secondary operations in multiple trauma patients impose an additional systemic burden, representing an additional risk of organ dysfunction. We investigated whether the timing of a secondary operation of > 3 h duration is related with the development of organ dysfunction. METHODS: In a retrospective analysis, 4,314 polytrauma patients treated at our institution between January 1975 and January 1999 were investigated. Patients were divided according to the presence ( + MOF) or absence (-MOF) of organ failure (Goris' criteria). RESULTS: In both groups, the injury severity, rescue time, duration and incidence of primary operations were comparable. Secondary surgery in patients who later developed organ failure was significantly more often performed between day 2 and 4, whereas patients without organ failure were usually operated between day 6 and 8 (P < 0.0001). The initial laboratory data in these two groups were comparable. If patients with organ failure were operated on days 6-8, significantly worse initial laboratory data were determined, indicating that these patients were at high risk of developing MOF. CONCLUSION: In patients with severe trauma requiring secondary operations of > 3 h duration, performance of this operation should be avoided on post trauma days 2-4.

Adult↗

PubMed1999

[Optimal duration of primary surgery with regards to a "Borderline"-situation in polytrauma patients. Arbeitsgemeinschaft "Polytrauma" der Deutschen Gesellschaft für Unfallchirurgie].

Primary stabilization of major fractures in polytrauma patients is known to represent an important principle of treatment and has been shown to reduce the incidence of posttraumatic complications and of organ failure. However, in critically injured patients it has been discussed that extensive primary definitive treatment may also cause adverse effects due to its systemic burden by blood loss, loss of temperature etc. Patients who deteriorated unexpectedly following primary surgery have been named "borderline patients". In these patients it appears necessary to limit the amount of operative procedures, e. g. by performing temporary fixation of major fractures primarily. The threshold beyond which surgical procedures may cause more harm than good has not been well defined. This holds true especially for the duration of primary surgery. We investigated the clinical outcome in a large number of prospectively documented multiple trauma patients with respect of the duration of primary fracture stabilization. If a primary surgical procedure exceeded 6 hours in multiple trauma patients with an ISS of 25 points, patients demonstrated a significantly elevated ventilation time, an increased mortality, and a higher incidence of death from MOF in comparison with patients that were injured comparably, but were submitted to shorter primary operative procedures.

Adult↗