Werner Rabitsch

Prospective Oral Mucositis Audit: Oral Mucositis in Patients Receiving High-Dose Melphalan or BEAM Conditioning Chemotherapy—European Blood and Marrow Transplantation Mucositis Advisory Group

PURPOSE The Prospective Oral Mucositis Audit assessed the incidence, duration, and determinants of severe oral mucositis (OM; WHO oral toxicity scale grades 3 to 4) in patients with multiple myeloma (MM) or non-Hodgkins lymphoma (NHL) receiving high-dose conditioning chemotherapy before autologous stem-cell transplantation. PATIENTS AND METHODS Patients with MM (n = 109; mean age, 57 +/- 8 years) or NHL (n = 88; mean age, 50 +/- 13 years) were treated with high-dose melphalan (200 mg/m(2)) or carmustine 300 mg/m(2), etoposide 800 mg/m(2), cytarabine 800 to 1,600 mg/m(2), and melphalan 140 mg/m(2) chemotherapy, respectively, in 25 European centers. OM assessments were made daily until 30 days after transplantation or hospital discharge. High quality of OM assessment was ensured by an intensive training program. RESULTS Severe OM occurred in 46% (95% CI, 36% to 56%) of patients with MM and 42% (95% CI, 32% to 53%) of patients with NHL, with a mean duration of 5.3 days (95% CI, 4.4 to 6.1 days) and 5.5 days (95% CI, 4.5 to 6.7 days), respectively. Time from start of conditioning to peak OM score was 12.1 +/- 2.6 and 14.6 +/- 2.4 days. Severe OM risk and/or duration was significantly associated with higher chemotherapy dose per kilogram of body weight and poor performance status, but in contrast with some previous reports, this was not related to age. CONCLUSION Severe OM is more common in the transplantation setting than previously reported, justifying effective preventative and therapeutic measures.

Comparison of a conventional tracheal airway with the Combitube in an urban emergency medical services system run by physicians

This prospective randomised study was performed to compare the use of the Esophageal-Tracheal Combitube(R) (ETC; Tyco Healthcare, Mansfield, MA; http://www.combitube.org) with a conventional tracheal airway (ETA) for airway management by experienced physicians of the Emergency Medical Services System of the City of Vienna in the prehospital setting. Access to the patients head, time of arrival of the ambulance, ease of insertion, time of insertion, potential substitution by the alternate airway, efficacy of adrenaline (epinephrine) administered via the airway, survival to the intensive care unit (ICU) ward and survival to discharge from the hospital were evaluated. One hundred and seventy-two non-traumatic cardiac arrest patients (131 males, 41 females) were enrolled in this study during a 12 months period. In 83 patients (48.3%), the conventional ETA (group 1) was used for the initial intubation attempt which was successful in 78 patients (94%). The remaining five patients of group 1 could not be intubated with an ETA, but were successfully managed with the ETC. Eighty-nine patients (51.7%) were intubated with the ETC (group 2) as first choice (79 in oesophageal position (89%); eight in tracheal position: (9%)), which was successful in 87 (98%) patients. The remaining two patients in group 2 (2%) were successfully managed with the ETA. Success of intubation and ventilation with ETC was comparable to the ETA. Recorded time of insertion was shorter with the ETC versus ETA (P<0.05). The Combitube worked well in cases of difficult access to the patients head and in bleeding and vomiting patients. Both devices served as successful substitutes for each other. Adrenaline (epinephrine) applied via ETC with a 10-fold dosage was as effective as via the conventional ETA. To our knowledge this is the first study using physicians comparing ETC and ETA in the prehospital setting.

Regeneration of erythropoiesis after related- and unrelated-donor BMT or peripheral blood HPC transplantation: a major ABO mismatch means problems.

BACKGROUND: Blood group incompatibility in allogeneic BMT is common but does not appear to affect the outcome in terms of incidence of graft rejection or delayed engraftment. However, major ABO incompatibility may be associated with prolonged erythroid aplasia.

Hematopoietic Stem-Cell Transplantation for Advanced Systemic Mastocytosis

PURPOSE Advanced systemic mastocytosis (SM), a fatal hematopoietic malignancy characterized by drug resistance, has no standard therapy. The effectiveness of allogeneic hematopoietic stem-cell transplantation (alloHCT) in SM remains unknown. PATIENTS AND METHODS In a global effort to define the value of HCT in SM, 57 patients with the following subtypes of SM were evaluated: SM associated with clonal hematologic non-mast cell disorders (SM-AHNMD; n = 38), mast cell leukemia (MCL; n = 12), and aggressive SM (ASM; n = 7). Median age of patients was 46 years (range, 11 to 67 years). Donors were HLA-identical (n = 34), unrelated (n = 17), umbilical cord blood (n = 2), HLA-haploidentical (n = 1), or unknown (n = 3). Thirty-six patients received myeloablative conditioning (MAC), and 21 patients received reduced-intensity conditioning (RIC). RESULTS Responses in SM were observed in 40 patients (70%), with complete remission in 16 patients (28%). Twelve patients (21%) had stable disease, and five patients (9%) had primary refractory disease. Overall survival (OS) at 3 years was 57% for all patients, 74% for patients with SM-AHNMD, 43% for those with ASM, and 17% for those with MCL. The strongest risk factor for poor OS was MCL. Survival was also lower in patients receiving RIC compared with MAC and in patients having progression compared with patients having stable disease or response. CONCLUSION AlloHCT was associated with long-term survival in patients with advanced SM. Although alloHCT may be considered as a viable and potentially curative therapeutic option for advanced SM in the meantime, given that this is a retrospective analysis with no control group, the definitive role of alloHCT will need to be determined by a prospective trial.

Diverse T-cell responses characterize the different manifestations of cutaneous graft-versus-host disease.

Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (HCT) and can present in an acute (aGVHD), a chronic lichenoid (clGVHD), and a chronic sclerotic form (csGVHD). It is unclear whether similar or different pathomechanisms lead to these distinct clinical presentations. To address this issue, we collected lesional skin biopsies from aGVHD (n = 25), clGVHD (n = 17), and csGVHD (n = 7) patients as well as serial nonlesional biopsies from HCT recipients (prior to or post-HCT) (n = 14) and subjected them to phenotypic and functional analyses. Our results revealed striking differences between aGVHD and clGVHD. In aGVHD, we found a clear predominance of T helper (Th)2 cytokines/chemokines and, surprisingly, of interleukin (IL)-22 messenger RNA as well as an increase of IL-22-producing CD4(+) T cells. Thymic stromal lymphopoietin, a cytokine skewing the immune response toward a Th2 direction, was elevated at day 20 to 30 post-HCT in the skin of patients who later developed aGVHD. In sharp contrast to aGVHD, the immune response occurring in clGVHD showed a mixed Th1/Th17 signature with upregulated Th1/Th17 cytokine/chemokine transcripts and elevated numbers of interferon-γ- and IL-17-producing CD8(+) T cells. Our findings shed new light on the T-cell responses involved in the different manifestations of cutaneous GVHD and identify molecular signatures indicating the development of the disease.

Successful lung transplantation for bronchiolitis obliterans after allogeneic marrow transplantation.

Background. Bone marrow transplantation (BMT) is an established therapy for a variety of hematological diseases with curative potential. However, despite improvements in supportive care, pulmonary complications remain a significant cause of morbidity and mortality. Methods. We report on a patient who received a double lung transplantation (LTX) for therapy-refractory bronchiolitis obliterans (BO) associated with extensive chronic graft-versus-host disease (GVHD) after allogeneic BMT. Results. At present, 38 months after BMT and 23 months after LTX, the patient is in complete hematological and cytogenetic remission and without signs of respiratory distress. Conclusions. This case illustrates that lung transplantation could be a therapeutic option in selected patients with BO after allogeneic BMT that is associated with extensive chronic GVHD and who are refractory to conventional immunosuppressive therapy.

Comorbidity predicts survival in myelodysplastic syndromes or secondary acute myeloid leukaemia after allogeneic stem cell transplantation.

Background  Recent data suggest that, among other factors, comorbidity may be an important prognostic variable in patients with myelodysplastic syndromes (MDS) who are eligible for haematopoietic stem cell transplantation (SCT).

Comparison of Mucosal Pressures Induced by Cuffs of Different Airway Devices

Background:High pressures exerted by balloons and cuffs of conventional endotracheal tubes, the Combitube® (Tyco Healthcare Nellcor Mallinckrodt, Pleasanton, CA), the EasyTube® (Teleflex Ruesch, Kernen, Germany), the Laryngeal Mask Airway ™ (LMA North America, San Diego, CA), the Intubating Laryngeal Mask Airway ™ (Fastrach®; LMA North America), the ProSeal ™ (LMA North America), and the Laryngeal Tube (LT; VBM Medizintechnik, Sulz, Germany) may traumatize the pharyngeal mucosa. The aim of this study was to compare pressures exerted on the pharyngeal, tracheal, and esophageal mucosa by different devices designed for securing the patient’s airways. Methods:Nineteen fresh cadavers were included. To measure mucosal pressures, microchip sensors were fixed on the anterior, lateral, and posterior surfaces of the proximal balloon and the distal cuff of the investigated devices. Depending on the respective airway device, the cuff volume was increased in 10-ml increments at the proximal balloon starting from 0 to a maximum of 100 ml, and in 2-ml increments at the distal cuff starting from 0 up to 12 ml. Results:Tracheal mucosal pressures were significantly higher using the Combitube® compared with the endotracheal tube and the EasyTube®. Maximal esophageal pressures were significantly higher using the EasyTube® compared with the Combitube®. Using cuff volumes according to the manufacturers’ guidelines, we found the highest pharyngeal pressures with the Intubating Laryngeal Mask Airway ™ versus all other devices. At maximal volumes, the Laryngeal Mask Airway ™, the Intubating Laryngeal Mask Airway ™, and the ProSeal ™ induced significantly higher pharyngeal pressures compared with all other devices. Using a pharyngeal cuff volume of 40 ml, the Intubating Laryngeal Mask Airway ™ followed by the Laryngeal Mask Airway ™ exerted significantly higher pressures compared with the other devices. Conclusions:Although some devices exhibit a somewhat higher mucosal pressure when compared with others, the authors believe that the observed differences of the cuff pressures do not suggest a clinically relevant danger, because the investigated devices, except the endotracheal tubes, are not intended for prolonged use.

Closed Suctioning System Reduces Cross-Contamination Between Bronchial System and Gastric Juices

In this prospective, randomized study, we evaluated whether a closed suctioning (CS) system (TrachCare) influences crossover contamination between bronchial system and gastric juices when compared with an open suctioning system (OS). The secondary aims were an analysis of the frequency of ventilator-associated pneumonia (VAP) and an analysis of alteration in gas exchange. Antibiograms were performed from tracheal secretions and gastric juice aspirates on Days 1 and 3 of intubation in 24 patients in a medical intensive care unit. Five cross-contaminations were observed in the OS group on Day 3 versus Day 1; the 5 strains shared common genotypes as determined by random amplification of polymorphic DNA. No cross-contaminations were seen in the CS group (P = 0.037). VAP occurred in 5 patients of the OS group but in none of the CS group patients (P = 0.037). Spao(2) decreased significantly in the OS group compared with presuctioning values--the opposite of the CS group. Whereas presuctioning values were comparable between groups, postsuctioning Spao(2) was significantly higher in the CS group. CS significantly reduced cross-contamination between bronchial system and gastric juices and reduced the incidence of VAP when compared with OS. Hypoxic phases can be reduced by the help of CS.

Insulin-like growth factor-1 receptor (IGF-1R) expression does not predict for resistance to trastuzumab-based treatment in patients with Her-2/ neu overexpressing metastatic breast cancer

Purpose: Her-2/neu and the insulin-like growth factor-1 receptor (IGF-1R) share common postreceptor-signaling pathways, and pre-clinical models have implicated IGF-1R-signaling in resistance to treatment with the anti-Her-2/neu antibody trastuzumab. The present analysis was performed to evaluate the clinical relevance of IGF-1R expression within the context of trastuzumab-based therapy. Patients and methods: We performed immunohistochemical (IHC) analysis for IGF-1R expression in tumor specimens from 72 patients receiving trastuzumab-based treatment for Her-2/neu-overexpressing metastatic breast cancer at a single institution. IGF-1R status was evaluated using different cut-offs for positivity regarding staining intensity and staining pattern. IGF-1R positivity was then correlated with clinical patient and biological tumor characteristics and the clinical course of disease of patients under trastuzumab-based therapy. Results: No pattern or intensity of staining for IGF-1R correlated with any of the clinical or biological characteristics. Likewise, response, clinical benefit, progression-free and overall survival were independent of IGF-1R expression in both, univariate and multivariate analyses (all P>0.05). Conclusions: We conclude that IGF-1R expression is not a major predictor of the clinical efficacy of trastuzumab-based treatment in patients with Her-2/neu- overexpressing metastatic breast cancer.