[Laser Doppler vibrometric measurements on human temporal bones]. / Laser-Doppler-vibrometrische Messungen an humanen Felsenbeinen.

Laser Doppler vibrometric (LDV) measurements on human temporal bones represent the standard method for predicting the performance of active middle ear implants (AMEI) and are used as preclinical tests in the development, approval process, and indication expansion of AMEI. The quality of the coupling of the floating mass transducer to the mobile structures of the middle ear is decisive for the performance of the implant and patients' hearing perception. The cochlea can be stimulated via the oval window (forward stimulation) or the round window (reverse stimulation). For forward stimulation, the ASTM standard F2504-05 defines a method to ensure physiologically normal properties of the temporal bones used in the experiments. For reverse stimulation, which depends even more critically on the quality of the temporal bone, a comparable standard method is lacking. Appropriate preparation and storage of the human petrous bone as well as suitable LDV test setups with respect to calibration and reproducibility of measuring positions and angles provide results that allow a comparison of different types of coupling and also correlate well with clinical data.

[Functional results succeeding primary combined external radiotherapy and brachytherapy for head and neck tumors]. / Funktionelle Ergebnisse nach primärer kombinierter perkutaner/interstitieller Strahlentherapie bei Kopf-Hals-Tumoren.

BACKGROUND: Histologically proven radical resections often lead to severe functional problems especially in upper aero-digestive-tract tumors. Oncologically the combination of external radiotherapy and brachytherapy offers an alternative treatment option. The functional results and the complication rate in stage III and IV tumors of the oral tongue, floor of mouth and oropharynx are described in a patients series. METHOD: The follow-up includes 17 consecutive patients who were primarily treated by a combination of external radiotherapy and brachytherapy between 1997 and 2000. The oncological benefit (complete remission, disease-free survival), the functional results (mastication, swallowing, speech and pain) and the complications were reviewed. RESULTS: After the follow-up period 16/17 patients were alive. There were 3 major complications, one of them lethal. The functional results resembled those after surgical resections. CONCLUSIONS: A combined radiotherapy is a feasible method of treating patients who refrain from surgery. Moreover the application ranges from inoperability to postoperative radiotherapy in cases with close or positive margins. In connection with neck-dissections and therapy of recurrent cancer major complications may occur. In contrast to the general opinion radiation therapy was not superior to surgical resection concerning functional sequelae.

Rhenium 188-labeled anti-CD66 (a, b, c, e) monoclonal antibody to intensify the conditioning regimen prior to stem cell transplantation for patients with high-risk acute myeloid leukemia or myelodysplastic syndrome: results of a phase I-II study.

The conditioning regimen prior to stem cell transplantation in 36 patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) was intensified by treating patients with a rhenium 188-labeled anti-CD66 monoclonal antibody. Dosimetry was performed prior to therapy, and a favorable dosimetry was observed in all cases. Radioimmunotherapy with the labeled antibody provided a mean of 15.3 Gy of additional radiation to the marrow; the kidney was the normal organ receiving the highest dose of supplemental radiation (mean 7.4 Gy). Radioimmunotherapy was followed by standard full-dose conditioning with total body irradiation (12 Gy) or busulfan and high-dose cyclophosphamide with or without thiotepa. Patients subsequently received a T-cell-depleted allogeneic graft from a HLA-identical family donor (n = 15) or an alternative donor (n = 17). In 4 patients without an allogeneic donor, an unmanipulated autologous graft was used. Infusion-related toxicity due to the labeled antibody was minimal, and no increase in treatment-related mortality due to the radioimmunoconjugate was observed. Day +30 and day +100 mortalities were 3% and 6%, respectively, and after a median follow-up of 18 months treatment-related mortality was 22%. Late renal toxicity was observed in 17% of patients. The relapse rate of 15 patients undergoing transplantation in first CR (complete remission) or second CR was 20%; 21 patients not in remission at the time of transplantation had a 30% relapse rate. (Blood. 2001;98:565-572)

CD34+ selected cells in mismatched stem cell transplantation: a single centre experience of haploidentical peripheral blood stem cell transplantation.

Over the past 3 years we have performed 10 haploidentical peripheral blood stem cell transplants in patients with incurable haematological malignancies and no prospect of a matched unrelated donor within an adequate time period. Conditioning consisted of ATG, TBI, thiotepa, cyclophosphamide and additional radioimmunotherapy in five patients. All patients received G-CSF mobilized peripheral blood stem cell grafts. GVHD prophylaxis consisted of T cell depletion by CD34+ selection; no post-transplant immunosuppression was given in nine patients. Stable engraftment was achieved in nine patients; one case of acute graft rejection was observed. Seven patients developed grade I acute GVHD, and six patients have developed chronic GVHD. Infections were the most significant clinical problem post transplant. Two patients have suffered a relapse of their disease and two further patients have died of transplant-related complications. After a median follow-up of 13 months (range 5-37 months) six patients are surviving in remission. We conclude that haploidentical PBSCT is a reasonable alternative to a MUD transplant.

Non-infectious lung complications are closely associated with chronic graft-versus-host disease: a single center study of incidence, risk factors and outcome.

Non-infectious lung complications (NILC) are frequent, influencing morbidity and mortality of patients after allogeneic BMT. Although the term NILC encompasses a number of different entities, an association with GVHD has been noted for almost all of them. Our study was directed towards assessing the incidence and risk factors for developing NILC, as well as the response to treatment and long-term outcome. Forty (14.7%) out of 272 patients surviving for more than 3 months after allogeneic BMT, developed lung complications fulfilling the criteria for NILC. The evaluation was based on clinical investigation, radiologic imaging, lung function tests, broncho-alveolar lavage and biopsies. Risk factors were assessed by univariate and multiple statistical regression models, where chronic GVHD proved to be the only significant risk factor for the development of NILC (P = 0.011). In three patients NILC developed in direct association with donor lymphocyte infusions. The majority of patients responded well to treatment with corticosteroids and immunosuppressive drugs. NILC had no adverse effect on survival. The frequency of NILC was low in autologous (5%) as compared with allogeneic transplants (14.7%) but this difference was not statistically significant. Bone Marrow Transplantation (2000) 25, 1263-1268.

Radioimmunotherapy for the intensification of conditioning before stem cell transplantation: differences in dosimetry and biokinetics of 188Re- and 99mTc-labeled anti-NCA-95 MAbs.

UNLABELLED: A new concept is the intensification of preparative regimens for patients with advanced leukemia using monoclonal antibodies (MAbs) with an affinity for beta emitter-labeled bone marrow. 188Re is a high-energy beta emitter that has therapeutic promise. Our first aim was to clarify whether the therapeutic application of 188Re-MAb against nonspecific cross-reacting antigen 95 (NCA-95) can be predicted from biokinetic data derived from 99mTc-labeled NCA-95. Our second aim was to show that a radiation absorbed dose of > or =12 Gy in the bone marrow can be achieved using 188Re-MAb. METHODS: Dosimetric data were obtained for both radiotracers from multiple planar whole-body scans (double-head gamma camera), blood samples, and urine measurements from 12 patients with advanced leukemia. Radiation absorbed doses were calculated using MIRDOSE 3 software. RESULTS: Radiation absorbed doses to bone marrow, liver, spleen, lung, and kidney were 2.24, 0.50, 1.93, 0.05, and 0.90 mGy/MBq, respectively, using 99mTc-MAb and 1.45, 0.43, 1.32, 0.07, and 0.71 mGy/MBq, respectively, using 188Re-MAb. These differences were statistically significant for bone marrow, spleen, and kidney. The main differences were less accumulation of 188Re-MAb in bone marrow (31%+/-13% compared with 52%+/-13%) and faster elimination through urine (25%+/-3% compared with 15%+/-5% after 24 h). On the basis of these data, a mean marrow dose of 14+/-7 Gy was achieved in 12 patients suffering from leukemia after application of approximately 10+/-2 GBq 188Re-MAb. CONCLUSION: Myeloablative radiation absorbed doses can easily be achieved using 188Re-MAb. 99mTc- and 188Re-MAb showed similar whole-body distributions. However, direct prediction of radiation absorbed doses from the 99mTc-MAb, assuming identical biokinetic behavior, is not valid for the 188Re-MAb in a single patient. Therefore, individual dosimetry using 188Re-MAb is needed to calculate therapeutic activity.

[Radiotherapy for tumor pain. Long-term freedom from pain with minimal side-effects]. / Strahlen gegen Tumorschmerzen. Langanhaltende Schmerzfreiheit bei geringen Nebenwirkungen.

Radiotherapy may be the treatment of choice in patients suffering pain from early-stage cancer and is used in curative intent. In addition, it is often used for palliative treatment in advanced tumor disease, when, thanks to local regression of the tumor, pain relief may be long-term and achieved with only mild or moderate side effects.