Establishment of minimally invasive ventral hernia repair with extraperitoneal mesh placement in a primary care hospital using the robotic platform.

Background: The progressive availability of robotic surgical systems opens new perspectives in abdominal wall surgery due to excellent visibility and dexterity of instruments. While complex hernias until today were treated primarily through an open access, we evaluated if this promising technology is suitable for treating the entire spectrum of a hernia center, including complex hernias. Material/methods: In 2017, minimally invasive hernia surgery with extraperitoneal mesh placement was started in Kempten hospital. Since 2019, a Da Vinci X system has been available for this purpose. In order to observe the process of transition we retrospectively analyzed all patients who underwent ventral hernia repair in the department of general and visceral surgery at our hospital between January 2016 and December 2020 and were indicated for mesh implantation. Results: In 2016, the percentage of minimally invasive procedures was 37.3%. In all of these cases an intraperitoneal mesh was implanted into the abdominal cavity. Open surgery was performed in 62.7%, of which an a retromuscular mesh was implanted in 75.7%, an intraperitoneal mesh in 21.6%, and an onlay mesh in 2.7%. In 2020, minimally invasive surgery accounted for 87.5%, of which 85.7% were performed robotically and 14.3 laparoscopically. In 94.3% of these minimally invasively treated patients the mesh was implanted in extraperitoneal position (75.8% in retromuscular and 24.2% in preperitoneal position). The percentage of complex hernias increased from 20.3% to 35.0% during the same period. Conclusion: The majority of ventral hernia procedures can be performed safely using the robot in a minimally invasive technique with extraperitoneal mesh placement without leading to an increase in complications. Robotically-assisted hernia repair is a promising new technique that is also practical for complex hernias.

[Ventral Hernia Repair in Endoscopically Total Extrapertoneal Technique (eTEP) - Evaluation of Postoperative Outcome and One Year Follow-up]. / Ventralhernienversorgung in endoskopischer total extraperitonealer Technik (eTEP) ­ Evaluation der postoperativen Ergebnisse und des 1-Jahres-Follow-ups.

BACKGROUND: Several recent meta-analyses have identified the retromuscular plane as the preferred mesh position in ventral hernia repair. Open surgery used to be the standard technique for these procedures. However, new minimally invasive techniques with totally extraperitoneal access and mesh positioning in the retromuscular plane have evolved. METHODS: Between September 2018 and March 2019, 18 consecutive patients with ventral hernia were treated endoscopically in the totally extraperitoneal technique. Depending on the localisation and size of the hernia, the appropriate access was chosen and an uncoated mesh was placed in the retromuscular space in all patients. Data of patients' characteristics as well as peri- and postoperative parameters were collected. One year after surgery, patients were asked about recurrence, pain and complications, using the questionnaire of the herniamed data base. RESULTS: No intraoperative complications were noted. Postoperatively, there was one retromuscular seroma that did not need treatment, one temporary paralysis of the radial nerve and one pulmonary embolism. None of these complications led to persistent problems. 17 of 18 patients were available for follow-up. One year follow-up showed no hernia recurrence. One patient had pain at rest requiring treatment. CONCLUSIONS: Totally extraperitoneal endoscopic hernia surgery is a safe and promising new technique that is also feasible in complex hernias and with satisfactory 1 year results. This technique can combine the advantages of minimally invasive surgery with those of extraperitoneal mesh placement.

Prospective trial of immuno(chemo)therapy before resection, definitive chemoradiotherapy or palliative therapy in patients with locally advanced or oligometastatic non-small cell lung cancer without a primary curative option.

BACKGROUND: Recent phase II-III trials of immuno(chemo)therapy before resection in locally advanced resectable non-small cell lung cancer (NSCLC) report high rates of pathological response and promising survival. However, primarily, patients who did not undergo resection were excluded from these studies. Moreover, there are no data on chemoradiotherapy (CRT) after immuno(chemo)therapy in patients who are primarily not amenable to CRT. We hypothesised that induction immuno(chemo)therapy may enable patients with NSCLC with a potentially curative stage (III-IVA), for whom primary curative treatment (either resection or CRT) is not possible for anatomical or functional reasons, to receive curative treatment. PATIENTS AND METHODS: We enrolled 35 patients with NSCLC with aforementioned characteristics into a prospective real-world trial of induction immuno(chemo)therapy followed by morphologic and metabolic reassessment and multidisciplinary board-guided curative treatment (resection [preferred] or CRT) or palliative therapy. The primary end-point was the proportion of patients receiving curative treatment. RESULTS: Thirty-two patients (91%) received curative treatment (11 resections and 21 CRT). 73% and 64% of patients who underwent resection had a major or complete pathological response, respectively. There were 14 recurrences: 2 (18%) in patients who underwent resection, 9 (43%) in patients who received CRT and 3 (100%) in patients who received palliative therapy (median follow-up 17 months). Eight tumour-related deaths occurred: 5 (24%) in patients who received CRT; and 3 (100%) in patients who received palliative therapy. There were no treatment-related deaths. CONCLUSIONS: In locally advanced or oligometastatic NSCLC without a primary curative option, induction immuno(chemo)therapy results in a high rate of curative treatment with promising early survival data. patients who underwent resection achieved a high rate of prognostically favourable pathological response.

Robotically assisted enhanced-view totally extraperitoneal repair (eTEP) of a recurrent umbilical hernia in a patient with peritoneal dialysis.

Background: Abdominal wall hernias are frequent in patients with peritoneal dialysis. Guidelines recommend an open hernia repair with extraperitoneal mesh placement to avoid access to the abdominal cavity. Method: We performed a lateral docking robotically assisted enhanced-view totally extraperitoneal repair (eTEP) of a recurrent umbilical hernia with diastasis recti in a patient with peritoneal dialysis due to polycystic kidney disease. After suturing of the midline a 20 x 28 cm mesh was placed in the retrorectus space, covering the whole area of preparation while also overlapping all trocar sites. A drainage was left in the retrorectus space until the first session of PD did not sample any form of leakage. Result: Robotically assisted totally extraperitoneal hernia repair was feasible. The patient was able to continue peritoneal dialysis without intermittent hemodialysis. There was no leakage of the dialysate to the retrorectus space. Postoperative recovery was uneventful. 6 months after surgery the patient was free from pain and showed no signs of recurrence. Conclusion: Robotically assisted totally extraperitoneal hernia repair in patients with umbilical hernia and peritoneal dialysis could be a promising surgical technique to combine the advantages of minimally-invasive surgery with totally extraperitoneal mesh placement without access to the abdominal cavity.

Evaluation of Prognostic Factors and Role of Participation in a Randomized Trial or a Prospective Registry in Pediatric and Adolescent Nonmetastatic Medulloblastoma - A Report From the HIT 2000 Trial.

PURPOSE: We aimed to compare treatment results in and outside of a randomized trial and to confirm factors influencing outcome in a large retrospective cohort of nonmetastatic medulloblastoma treated in Austria, Switzerland and Germany. METHODS AND MATERIALS: Patients with nonmetastatic medulloblastoma (n = 382) aged 4 to 21 years and primary neurosurgical resection between 2001 and 2011 were assessed. Between 2001 and 2006, 176 of these patients (46.1%) were included in the randomized HIT SIOP PNET 4 trial. From 2001 to 2011 an additional 206 patients were registered to the HIT 2000 study center and underwent the identical central review program. Three different radiation therapy protocols were applied. Genetically defined tumor entity (former molecular subgroup) was available for 157 patients. RESULTS: Median follow-up time was 7.3 (range, 0.09-13.86) years. There was no difference between HIT SIOP PNET 4 trial patients and observational patients outside the randomized trial, with 7 years progression-free survival rates (PFS) of 79.5% ± 3.1% versus 78.7% ± 3.1% (P = .62). On univariate analysis, the time interval between surgery and irradiation (≤ 48 days vs ≥ 49 days) showed a strong trend to affect PFS (80.4% ± 2.2% vs 64.6% ± 9.1%; P = .052). Furthermore, histologically and genetically defined tumor entities and the extent of postoperative residual tumor influenced PFS. On multivariate analyses, a genetically defined tumor entity wingless-related integration site-activated vs non-wingless-related integration site/non-SHH, group 3 hazard ratio, 5.49; P = .014) and time interval between surgery and irradiation (hazard ratio, 2.2; P = .018) were confirmed as independent risk factors. CONCLUSIONS: Using a centralized review program and risk-stratified therapy for all patients registered to the study center, outcome was identical for patients with nonmetastatic medulloblastoma treated on and off the randomized HIT SIOP PNET 4 trial. The prognostic values of prolonged time to RT and genetically defined tumor entity were confirmed.

Immunosuppressive Total Nodal Irradiation-Based Reconditioning Regimens After Graft Rejection or Graft Failure in Pediatric Patients Treated With Myeloablative Allogeneic Hematopoietic Cell Transplantation.

PURPOSE: This retrospective analysis aimed to address the efficacy of total nodal irradiation (TNI)-based reconditioning regimens in pediatric patients with graft failure/rejection after allogeneic hematopoietic cell transplantation. METHODS AND MATERIALS: Thirty-three pediatric patients with malignant (n = 25) and nonmalignant diseases (n = 8) were treated with a TNI-based reconditioning regimen. All patients received a 7-Gy single dose combined with anti-T lymphocyte antibody OKT3 (n = 16), anti-thymocyte globulin (n = 24), fludarabine (n = 31), and/or thiotepa (n = 28), followed by an infusion of peripheral blood stem cells (n = 31) or bone marrow transplant (n = 2). Twenty-eight of 33 patients had haploidentical family donors. RESULTS: After a median of 11 days, engraftment was seen in 32 of 33 children. Two children died 34 days after retransplantation because of either disease relapse or treatment-related multiple organ failure. Severe acute toxicity was reported in only 1 child (systemic inflammatory response syndrome-like reaction; recovery after cortisone treatment). The average follow-up was 60.2 months (range, 1.1-162.5 months). Event-free and overall survival rates at 2/5 years follow-up were 62.0%/58.6% and 65.1%/61.7%, respectively. Despite sustained engraftment, 12 patients died from disease relapse (n = 3), Moschkowitz syndrome (n = 1), or multiple organ failure (n = 8). Follow-up data were available for 18 of 21 survivors, with a median follow-up of 92.8 months (range, 3.6-162.5 months). Hypothyroidism was present in 78.6% of patients, and sex/growth hormonal insufficiencies were reported for 37.5%. Mean forced expiratory volume in 1 second after TNI was 84%; mean vital capacity was 79%. Severe growth failure (<3rd percentile) occurred in 28.6% (height) and 35.7% (weight) of patients. No secondary malignancies were reported. CONCLUSIONS: In the high-risk group of patients with graft failure/rejection after allogeneic hematopoietic cell transplantation, the TNI-based reconditioning regimen seems to allow sustained engraftment combined with a favorable toxicity profile, leading to long-term event-free and overall survival. Late toxicity after a median follow-up of over 7.5 years includes growth failure, manageable hormonal deficiencies, and a low risk of decrease of lung function.

Allogeneic haematopoietic cell transplantation offers the chance of cure for patients with transformed follicular lymphoma.

PURPOSE: In patients with follicular lymphoma, secondary transformation to aggressive lymphoma (tFL) implies a poor prognosis. In principle, allogeneic haematopoietic cell transplantation (allo-HCT) offers a chance of cure for tFL but is rarely practiced. Aim of this retrospective multicenter study was to define the actual significance of allo-HCT in treatment of tFL. METHODS: The database of the German Registry for Stem Cell Transplantation (DRST) was screened for patients who underwent allo-HCT for tFL 1998-2008. Confirmation of tFL-diagnosis by local and/or pathologists of the National NHL Board was mandatory for enrolment. Gaps in reported EBMT Minimum Essential Data datasets (MED-A) were filled by local DRST data managers. Relevant HCT outcome variables were evaluated by uni- and multivariate statistical analysis. RESULTS: Median age of enrolled 33 patients was 51 years with a post allo-HCT median follow-up of 7.1 years of surviving patients. At time of HCT 24/33 patients had chemosensitive disease. In 24/33 patients reduced intensity conditioning (RIC) was used. Estimated 1, 2, 5-year overall survival (OS) and event-free survival rates were 49/39/33, and 33/30/24%. Cumulative 100 days non-relapse mortality was 25%. Chemosensitive disease, RIC, and limited chronic GvHD were identified as independent prognostic factors for OS. CONCLUSIONS: Allo-HCT offers the chance of cure for tFL.

Resolution of atelectasis during radiochemotherapy of lung cancer with serious implications for further treatment. A case report.

Local failure is a major cause for low overall survival rates in advanced non small cell lung cancer (NSCLC). Among others, radioresistant tumor clones as well as geographical miss can explain these high local failure rates. One reason for geographical miss is a change of tumor related atelectasis in the course of radiotherapy. We present the case of a patient with UICC Stage IIIb NSCLC who presented with a large tumor related atelectasis. During definitive radiochemotherapy, the atelectasis resolved, which resulted in a massive tumor shift out of the planning target volume within 2 days. Without close monitoring by cone beam CTs and prompt replanning, this would have led to a geographical miss and relevant underdosage of the tumor. Furthermore, changes in anatomy and pulmonary function during treatment had implications for organs at risk and opened windows for dose escalation. We suggest at least biweekly CBCTs in patients with poststenotic atelectasis to ensure the rapid detection of geographical changes of the target and subsequent intervention if necessary.

Standardized Uptake Decrease on [18F]-Fluorodeoxyglucose Positron Emission Tomography After Neoadjuvant Chemotherapy Is a Prognostic Classifier for Long-Term Outcome After Multimodality Treatment: Secondary Analysis of a Randomized Trial for Resectable Stage IIIA/B Non-Small-Cell Lung Cancer.

PURPOSE: A confirmatory analysis was performed to determine the prognostic value of metabolic response during induction chemotherapy followed by bimodality/trimodality treatment of patients with operable locally advanced non-small-cell lung cancer. PATIENTS AND METHODS: Patients with potentially operable stage IIIA(N2) or selected stage IIIB non-small-cell lung cancer received three cycles of cisplatin/paclitaxel (induction chemotherapy) followed by neoadjuvant radiochemotherapy (RCT) to 45 Gy (1.5 Gy twice per day concurrent cisplatin/vinorelbine) within the ESPATUE (Phase III Study of Surgery Versus Definitive Concurrent Chemoradiotherapy Boost in Patients With Resectable Stage IIIA[N2] and Selected IIIB Non-Small-Cell Lung Cancer After Induction Chemotherapy and Concurrent Chemoradiotherapy) trial. Positron emission tomography scans were recommended before (t0) and after (t2) induction chemotherapy. Patients who were eligible for surgery after neoadjuvant RCT were randomly assigned to definitive RCT or surgery. The prognostic value of percentage of maximum standardized uptake value (%SUVmax) remaining in the primary tumor after induction chemotherapy-%SUVremaining = SUVmax(t2)/SUVmax(t0)-was assessed by proportional hazard analysis and receiver operating characteristic analysis. RESULTS: Overall, 161 patients were randomly assigned (155 from the Essen and Tübingen centers), and 124 of these received positron emission tomography scans at t0 and t2. %SUVremaining as a continuous variable was prognostic for the three end points of overall survival, progression-free survival, and freedom from extracerebral progression in univariable and multivariable analysis (P < .016). The respective hazard ratios per 50% increase in %SUVremaining from multivariable analysis were 2.3 (95% CI, 1.5 to 3.4; P < .001), 1.8 (95% CI, 1.3 to 2.5; P < .001), and 1.8 (95% CI, 1.2 to 2.7; P = .006) for the three end points. %SUVremaining dichotomized at a cut point of maximum sum of sensitivity and specificity from receiver operating characteristic analysis at 36 months was also prognostic. Exploratory analysis revealed that %SUVremaining was likewise prognostic for overall survival in both treatment arms and was more closely associated with extracerebral distant metastases (P = .016) than with isolated locoregional relapses (P = .97). CONCLUSION: %SUVremaining is a predictor for survival and other end points after multimodality treatment and can serve as a parameter for treatment stratification after induction chemotherapy or for evaluation of adjuvant new systemic treatment options for high-risk patients.

Treatment of graft failure with TNI-based reconditioning and haploidentical stem cells in paediatric patients.

Graft failure is a life-threatening complication after allogeneic haematopoietic stem cell transplantation (HSCT). We report a cohort of 19 consecutive patients (median age: 8·5 years) with acute leukaemias (n = 14) and non-malignant diseases (n = 5) who experienced graft failure after previous HSCT from matched (n = 3) or haploidentical donors (n = 16) between 2003 and 2012. After total nodal irradiation (TNI)-based reconditioning combined with fludarabine, thiotepa and anti-T cell serotherapy, all patients received T cell-depleted peripheral blood stem cell grafts from a second, haploidentical donor. Median time between graft failure and retransplantation was 14 d (range 7-40). Sustained engraftment (median: 10 d, range 9-32) and complete donor chimerism was observed in all evaluable patients. 5 patients additionally received donor lymphocyte infusions. Graft-versus-host disease (GvHD) grade II and III occurred in 1 patient each (22%); no GvHD grade IV was observed. 2 patients had transient chronic GvHD. The regimen was well tolerated with transient interstitial pneumonitis in one patient. Treatment-related mortality after one year was 11%. Event-free survival and overall survival 3 years after retransplantation were 63% and 68%. Thus, a TNI-based reconditioning regimen followed by transplantation of haploidentical stem cells is an option to rescue patients with graft failure within a short time span and with low toxicity.

Comparison of different adjuvant radiotherapy approaches in childhood bladder/prostate rhabdomyosarcoma treated with conservative surgery.

BACKGROUND AND PURPOSE: Multimodality treatment approaches provide high local control and satisfying overall survival (OS) for children with localized bladder and/or prostate rhabdomyosarcoma (BP-RMS). However, current strategies including surgery and conventional radiotherapy are compromised by high rates of long-term genitourinary adverse effects. Therefore, a planning study combining organ preserving surgery with three different innovative adjuvant radiotherapy approaches was performed. PATIENTS AND METHODS: A case of a 21-month-old boy with BP-RMS treated with polychemotherapy according to the CWS 2002-P protocol, prostatectomy, partial cystectomy, and adjuvant high dose rate brachytherapy (HDR-BT) was used to perform a planning study comparing HDR-BT with intensity-modulated radiotherapy (IMRT) and intensity-modulated proton therapy (IMPT) planning. RESULTS: All modalities provide good coverage of the target volume and spare critical normal tissues. Rectum doses could be reduced by 2/3 using IMPT and by 1/3 using BT compared to IMRT. In terms of sparing the pelvis growth plates, BT and IMPT are also superior to IMRT. CONCLUSION: All modalities provide good sparing of normal tissue. BT and IMPT are superior to IMRT with regard to doses on rectum and growth plates. BT is equivalent to IMPT in adequately selected tumors.

Advanced-stage III/IV follicular lymphoma: treatment strategies for individual patients.

BACKGROUND: In patients with advanced-stage III/IV follicular lymphoma (FL), there are many treatment options available. The current challenge is to choose the optimal strategy for the individual patient. METHODS: The literature was reviewed with respect to treatment strategies in patients with advanced FL by screening the PubMed databank. RESULTS: In advanced-stage III/IV FL, median survival may approach 8-10 years. Treatment strategies include a watch-and-wait strategy, chemoimmunotherapy, monotherapy with rituximab, and - as an experimental approach so far - radioimmunotherapy. The use of autologous hematopoietic stem cell transplantation (HSCT) for patients in first remission or chemosensitive relapse prolongs progression-free survival while the effect on overall survival remains unclear compared to standard chemotherapy. However, long-term results are flawed by high relapse rates and risk of secondary malignancies. In patients with relapsed/chemoresistant disease, allogeneic HSCT constitutes the only curative approach but is associated with high treatment-related mortality. In the palliative setting, low-dose involved-field irradiation constitutes an effective treatment option in order to control local symptoms with potential long-lasting response. CONCLUSION: In case of advanced-disease FL, asymptomatic patients can be managed expectantly. In symptomatic patients, chemoimmunotherapy is regarded as standard therapy. In symptomatic elderly patients with relevant comorbidities, rituximab +/- single-agent chemotherapy, or low-dose involved-field radiotherapy might be appropriate. For younger patients with chemoresistant/relapsed disease, allogeneic HSCT might be considered, since advances in supportive care and better patient selection have resulted in improved outcomes.

Nodal follicular lymphoma: the role of radiotherapy for stages I and II.

PURPOSE: To clarify the role of external-beam radiotherapy (RT) in patients with stage I and II nodal follicular lymphoma (FL). METHODS: The literature was reviewed with respect to different treatment strategies in patients with stage I and II nodal FL by screening the PubMed databank. RESULTS: In patients with stage I and II nodal FL, RT alone with different irradiation techniques (involved-field [IFI]/extended-field [EFI]/total nodal [TNI]/total lymphoid irradiation [TLI]) produces excellent local disease control (approximately 95%) resulting in disease-free survival and overall survival (OS) rates of 37-94% and 40-93% at 5-15 years, respectively. The main cause of failure is out-of-field recurrence. In nonrandomized trials, IFI led to higher relapse rates, but larger irradiation volumes failed to show an impact on OS and were associated with increased toxicity. Additional chemotherapy mostly failed to improve treatment results achieved with RT alone. CONCLUSION: Since there is no evidence so far that the prognosis of stage I and II nodal FL can be improved by the use of EFI/TNI/TLI, IFI is recommended internationally. Adequate irradiation doses range between 25-30 Gy to subclinical disease and 36-40 Gy to involved sites. To further improve the curative potential of RT in early-stage FL, novel combined approaches (e.g., RT + immunotherapy with rituximab) are under investigation.

Quality of training in radiation oncology in Germany. Results of a 2006 survey.

PURPOSE: To evaluate residents' satisfaction with their training in radiation oncology, the first nationwide survey was done in 2006. Results were presented at the 2006 annual meeting of the German Society of Radiation Oncology (DEGRO). MATERIAL AND METHODS: A questionnaire with 39 questions regarding training in radiation oncology in Germany was developed and sent by e-mail. Questionnaires were returned by mail and analyzed anonymously. RESULTS: 96 questionnaires were received. A total of 88% of respondents are pleased with their decision of training in radiation oncology. Residents are strongly motivated by their interest in oncology. Quality of training is heterogeneous and not optimal. Training in three-dimensional treatment planning, radiochemotherapy and intracavitary brachytherapy is judged adequate, whereas special techniques such as intensity-modulated radiotherapy (IMRT) and permanent prostate implants are not covered by the majority of institutions. Organization of training in the departments is often judged insufficient. CONCLUSION: Radiation oncology is attractive for young doctors. However, training quality for radiation oncologists in Germany was judged to be heterogeneous and needs to be optimized. For this, results of this survey may be helpful. The overall positive judgment may help to attract more students into the field of radiation oncology, an issue that becomes increasingly important given the shortage of doctors and the strong competition with other disciplines. Modern techniques, such as IMRT, need to be integrated into training programs in order to maintain the high standard of radiation oncology in Germany.

Immunosuppressive total lymphoid irradiation-based reconditioning regimens enable engraftment after graft rejection or graft failure in patients treated with allogeneic hematopoietic stem cell transplantation.

PURPOSE: To retrospectively evaluate the efficacy of total lymphoid irradiation (TLI)-based reconditioning regimens in patients with graft failure or graft rejection after allogeneic hematopoietic stem cell transplantation. METHODS AND MATERIALS: The results of 14 patients (7 adults and 7 children) with a variety of hematologic malignant diseases treated with a TLI-based reconditioning regimen with 7-Gy single-dose application plus anti-T-lymphocyte antibody OKT3 (n = 11) and/or antithymocyte globulin (n = 7)/fludarabine (n = 9), followed by an infusion of peripheral blood stem cells (n = 13) or bone marrow stem cells (n = 1) from related or unrelated donors, were retrospectively analyzed. RESULTS: Of the 14 recipients, the data from 11 were evaluable for engraftment after TLI-based reconditioning because 3 adults died early (at Day 2, 5, and 15) after the second transplantation of infectious complications. Engraftment in 4 adults was seen after a median of 12 days (range, 10-18) and occurred after a median of 10 days (range, 9-32) in the 7 children. TLI-based reconditioning was well-tolerated with no severe toxicity. The median overall survival and disease-free survival for the whole cohort was 140 days (range, 5-1,268). After a median follow-up of 681 days, the disease-free survival and overall survival rate was 85.7% and 85.7%, respectively, in the children. Despite engraftment in the 4 remaining adults, 1 died of fatal graft-vs.-host disease, 1 of infectious complications, 1 of disease relapse, and 1 of acute respiratory distress syndrome. CONCLUSIONS: In patients with graft failure or graft rejection after allogeneic hematopoietic stem cell transplantation, TLI-based reconditioning regimens allow sustained engraftment, paralleled by a favorable toxicity profile, potentially leading to long-term survival.

Retransplantation with stem cells from mismatched related donors after graft rejection in pediatric patients.

Graft failure is a life-threatening complication after transplantation of hematopoietic stem cells. We report a cohort of 11 pediatric patients with leukemias (n=8) and severe aplastic anemia (n=3) who experienced graft rejection after myeloablative transplantation from mismatched related donors (n=6) or after cord blood or matched unrelated donor transplantation (n=5). In the latter, the original donor was not available anymore. All patients were re-transplanted with CD34(+) selected or CD3/CD19 depleted stem cells from a second, haploidentical donor. Median time span from diagnosis of rejection to second transplant was 9 days. Reconditioning regimens comprised total lymphoid irradiation, thiotepa, fludarabine, ATG/OKT3 and were well tolerated. A median number of 23.5x10(6)/kg stem cells with 95,000/kg residual T-cells were infused. Sustained engraftment of neutrophiles/platelets and complete donor chimerism was achieved in all patients (ANC>500/microl: 9 (11-32) days). No GvHD>grade II was observed. 8/11 patients are disease free (median follow up 1.9 years; 1 year-EFS=72%). Causes of death were: pneumonitis, infection, relapse. Thus, haploidentical transplantation represents a realistic option to rescue patients with graft failure within a short time span, for whom a second donation from the original donor is not available. The use of different donors may contribute to avoid a second rejection.

Irradiation-induced pneumonitis mediated by the CD95/CD95-ligand system.

Pneumonitis is a dose-limiting side effect of radiotherapy. However, the underlying mechanisms of irradiation-induced pneumonitis are unclear. Several observations suggest that the CD95/CD95-ligand (CD95L) system is involved in this process. Therefore, we examined the development of pneumonitis in CD95- and CD95L-deficient and wild-type mice after single irradiation with 0 or 12.5 Gy by measuring breathing frequency, pulmonary resistance, and histopathologic changes. Although wild-type mice developed pathognomonic alterations characteristic of pneumonitis (judged by alveolar wall thickness, interstitial edema, and interstitial and peribronchial inflammation) that paralleled increased breathing frequency ratio on days 5-70 (P < .03) with a maximum at day 37 (12.5 Gy, mean ratio = 1.05, 95% confidence interval [CI] = 1.01 to 1.08; P = .004 versus 0 Gy, mean ratio = 0.997, 95% CI = 0.976 to 1.02; P = .05) and pulmonary resistance (day 42, 12.5 Gy, mean = 0.51, 95% CI = 0.44 to 0.58 versus 0 Gy, mean = 0.40, 95% CI = 0.32 to 0.47; P = .03) after irradiation, no such changes were detected in CD95- or CD95L-deficient mice. This report demonstrates for the first time, to our knowledge, that the CD95/CD95L system is important for the development of irradiation-induced pneumonitis.

Total-body irradiation--role and indications: results from the German Registry for Stem Cell Transplantation (DRST).

BACKGROUND AND PURPOSE: Total-body irradiation (TBI) is a key part of the conditioning regimen before hematopoietic stem cell transplantation (HSCT). The exact role of TBI as part of the conditioning regimen is largely unclear. In order to determine the relevance of TBI, the status of TBI utilization was analyzed on the basis of a nationwide registry. MATERIAL AND METHODS: 14,371 patients (1998-2002) documented in the German Stem Cell Transplantation Registry (DRST) were analyzed regarding TBI utilization prior to autologous or allogeneic transplantation, underlying disorder, type of donor, stem cell source, and size of the treatment center. RESULTS: For autologous HSCT approximately 10% of the patients (873/8,167) received TBI, with chronic lymphocytic leukemia (CLL, approximately 80%, 171/214) and low-grade non-Hodgkin's lymphoma (l-NHL, approximately 35%, 330/929) being the most important disorders. In the allogeneic setting 50% of the patients (2,399/4,904) received TBI, with acute lymphocytic leukemia (ALL, 85%, 794/930), acute myeloid leukemia (AML, 45%, 662/1,487) and chronic myeloid leukemia (CML, 49%, 561/1,156) being the key indications. The type of donor, stem cell source and center size did not strongly influence the use of TBI. CONCLUSION: TBI has only a limited role for the conditioning prior to autologous HCST. For allogeneic HSCT TBI is widely accepted with no major changes over the observation time. The use of TBI is generally accepted for ALL, whereas approximately half of the patients with CML or AML received TBI. Although a considerably large database was analyzed, no clear determinants for the use of TBI could be distinguished.