Clinical Practice Recommendations for Hematopoietic Cell Transplantation and Cellular Therapies in Follicular Lymphoma: A Collaborative Effort on behalf of The American Society of Transplantation and Cellular Therapy and the European Society of Blood and Marrow Transplantation.

Follicular lymphoma (FL) is the most common indolent B-cell non-Hodgkin lymphoma (NHL), accounting for nearly one-third of all NHL. The therapeutic landscape for patients with FL has significantly expanded over the past decade, but the disease continues to be considered incurable. Hematopoietic cell transplantation (HCT) is potentially curative in some cases. Recently, the emergence of chimeric antigen receptor T-cell therapy (CAR-T) for patients with relapsed/refractory (R/R) FL has yielded impressive response rates and long-term remissions, but definitive statement on the curative potential of CAR-T is currently not possible due to limited patient numbers and relatively short follow up. A consensus on the contemporary role, optimal timing, and sequencing of HCT (autologous or allogeneic) and cellular therapies in FL is needed. As a result, the American Society of Transplantation and Cellular Therapy (ASTCT) Committee on Practice Guidelines endorsed this effort to formulate consensus recommendations to address this unmet need. The RAND-modified Delphi method was used to generate 15 consensus statements/recommendations. Of note, the use of bispecific antibodies in R/R FL was not in the scope of this project. Key statements/recommendations are as follows: 1) Autologous HCT is recommended as an option for consolidation therapy in patients with progression of untransformed disease within 24 months of front line chemoimmunotherapy and upon achieving a complete (CR) or partial response (PR) to salvage second line therapies; 2) CAR-T is considered as a treatment option for patients who did not achieve CR or PR after second or subsequent lines of therapies; 3) Allogeneic HCT is considered as consolidative treatment in relapsed FL patients with chemosensitive disease who have received 3 or more lines of systemic therapy and are the following clinical scenarios: post CAR-T failure; lack of access to CAR-T or have therapy related myeloid neoplasm. These clinical practice recommendations will help guide clinicians managing patients with FL.

Autotransplantation with Adjunctive Application of Enamel Matrix Derivatives Using a Digital Workflow: A Prospective Case Series.

OBJECTIVES: Digital protocols and bioactive materials may reduce complications and improve tooth autotransplantation (ATT) success and survival rates. This prospective study assesses the performance of a fully digital autotransplantation protocol of close-apex molars with the adjunctive application of Enamel Matrix Derivatives (EMD). METHODS: Twelve adult patients with 13 hopeless molar teeth were replaced with autotransplantation of closed apex third molars. Outcomes, including success and survival rates, clinical, endodontic, radiographic, patient-reported outcome measures (PROMs), and digital image assessments, were conducted over a two-year follow-up period. RESULTS: Survival and success rates were 100% and 91.2%, respectively, with no progressive inflammatory or replacement root resorption (ankylosis) except for one tooth presenting radiographic furcation involvement. A significant probing depth reduction of 2.4 ± 2.58 mm and CAL gains of 2.8 ± 3.03 mm were observed in transplanted teeth compared to the hopeless receptor teeth. Radiographic bone levels remained stable throughout the study period (-0.37 ± 0.66 mm), and digital image assessments showed minimal alveolar ridge width changes (-0.32 to -0.7 mm) and gingival margin changes (-0.95 to -1.27 mm) from baseline to last visit. PROMs indicated very high patient satisfaction. CONCLUSION: The use of a digital ATT protocol with adjunctive use of EMD in closed-apex third molars demonstrated promising short-term high success and survival rates. Additionally, this type of therapy adequately preserves the dimensions of the alveolar ridge in the receptor site.

Long-term engraftment and maturation of autologous iPSC-derived cardiomyocytes in two rhesus macaques.

Cellular therapies with cardiomyocytes produced from induced pluripotent stem cells (iPSC-CMs) offer a potential route to cardiac regeneration as a treatment for chronic ischemic heart disease. Here, we report successful long-term engraftment and in vivo maturation of autologous iPSC-CMs in two rhesus macaques with small, subclinical chronic myocardial infarctions, all without immunosuppression. Longitudinal positron emission tomography imaging using the sodium/iodide symporter (NIS) reporter gene revealed stable grafts for over 6 and 12 months, with no teratoma formation. Histological analyses suggested capability of the transplanted iPSC-CMs to mature and integrate with endogenous myocardium, with no sign of immune cell infiltration or rejection. By contrast, allogeneic iPSC-CMs were rejected within 8 weeks of transplantation. This study provides the longest-term safety and maturation data to date in any large animal model, addresses concerns regarding neoantigen immunoreactivity of autologous iPSC therapies, and suggests that autologous iPSC-CMs would similarly engraft and mature in human hearts.

Predictive factors for peripheral blood stem cell mobilization in multiple myeloma in the era of novel therapies: A single-center experience.

OBJECTIVE: Multiple myeloma (MM) is the leading indication of autologous hematopoietic stem cell transplantation. The aim of this study was to determine the incidence of mobilization failure and characterize the risk factors associated with poor mobilization (PM) of MM patients in novel therapies era. METHODS: We conducted a retrospective study of 211 MM patients who received their first peripheral blood stem cells (PBSC) mobilization at our single center. The following data were collected: age, gender, clinical stage, disease status, complete blood cell count, induction regimen, CD34+ cell count in peripheral blood (PB), and PBSC collections. RESULTS: In addition to conventional drugs, 22 (10.4%) patients received daratumumab containing induction, and 33 (15.6%) patients used plerixafor for poor mobilization (pre-apheresis PB CD34+ cells <20/µL). Failure of collection occurred in 24 (11.4%) patients and was correlated with low white blood cell (WBC), ≥3 cycles of lenalidomide treatment before mobilization, steady-state mobilization and nouse of plerixafor are associated with mobilization failure. Daratumumab-based induction treatment ≥2 courses, albumin >41 g/L before mobilization, and steady-state mobilization were risk factors for PM in subgroups of patients treated with lenalidomide for <3 courses. In addition, Hepatitis B virus infection at baseline, thalassemia and measurable residual disease positivity were recognized as predictive factors for PM in subset of chemo-mobilization patients. CONCLUSION: In addition to some well-recognized risk factors, baseline WBC count and daratumumab exposure ≥2 courses before mobilization were revealed as the predictive factors of mobilization failure, providing consultation for preemptive use of plerixafor.

The Efficacy and Safety of Tandem Transplant Versus Single Stem Cell Transplant for Multiple Myeloma Patients: A Systematic Review and Meta-Analysis.

While high-dose therapy and autologous stem cell transplant (ASCT) remain integral to the primary treatment of newly diagnosed transplant-elble multiple myeloma (MM) patients, the challenge of disease progression persists. The primary objective of this meta-analysis is to evaluate the efficacy and safety of tandem ASCT compared to single ASCT. We conducted a systematic review and meta-analysis of randomized controlled trials and observational studies comparing tandem ASCT with single ASCT in patients with newly diagnosed MM. We searched PubMed, EMBASE, Cochrane Library, and Clinical Trials databases for studies published up to January 2024. The primary outcomes were progression-free survival (PFS), overall survival (OS), overall response rate (ORR), complete response rate (CRR), and treatment-related mortality (TRM). We used a random-effects model to calculate pooled hazard ratios (HRs) and relative risks (RRs) with 95% confidence intervals (CIs). Study quality was assessed using the Cochrane risk of bias tool and Newcastle-Ottawa Scale. Twelve studies involving 5057 patients met the inclusion criteria. Tandem ASCT was associated with a significantly higher CRR compared to single ASCT (HR 1.33, 95% CI 1.03-1.71, I2 = 15%), but no significant differences were observed in PFS (HR 0.75, 95% CI 0.42-1.34, I2 = 14%), OS (HR 0.60, 95% CI 0.33-1.10, I2 = 27%), or the ORR (RR 0.80, 95% CI 0.59-1.08, I2 = 33%). However, tandem ASCT was associated with a significantly higher risk of TRM (RR 1.78, 95% CI 1.00-3.18, I2 = 0%). Tandem ASCT improves the CRR but does not provide significant benefits in terms of PFS, OS, or ORR compared to single ASCT in patients with newly diagnosed MM. Moreover, tandem ASCT is associated with a higher risk of TRM. The decision to pursue tandem ASCT should be made on an individual basis, carefully weighing the potential benefits and risks in light of each patient's unique clinical situation. Future research should focus on identifying patient subgroups most likely to benefit from tandem ASCT and exploring strategies to optimize the efficacy and safety of this approach in the context of novel agent-based therapies.

Deciduous pulp tissue implantation into the root canal of mandibular incisor resulted in pulp revascularization: a case report with a 5-year follow-up.

To explore a new method to implant deciduous tooth pulp into the canal of young permanent teeth with necrotic pulps and apical periodontitis for the regenerative endodontic treatment of tooth no: 41 in a 7-year-old male. Briefly, 1.5% Sodium Hypochlorite (NaOCl) irrigation and calcium hydroxide-iodoform paste were used as root canal disinfectant at the first visit. After 2 weeks, the intracanal medication was removed, and the root canal was slowly rinsed with 17% Ethylene Diamine Tetraacetic Acid (EDTA), followed by flushing with 20 mL saline and then drying with paper points. Tooth no: 72 was extracted, and its pulp was extracted and subsequently implanted into the disinfected root canal along with induced apical bleeding. Calcium hydroxide iodoform paste was gently placed over the bleeding clot, and after forming a mineral trioxide aggregate (MTA) coronal barrier, the accessed cavities were restored using Z350 resin composite. The root developments were evaluated via radiographic imaging at 6 months, 1 year and 5 years after treatment. Imaging and clinical analysis showed closure of the apical foramen, thickening of the root canal wall, and satisfactory root length growth. Autologous transplantation might be useful to regenerate dental pulp in necrotic young permanent teeth.

Silicon-induced biofilm improves peripheral nerve defect in rats mediated by VEGF/VEGFR2/ERK.

Background: Injury of peripheral nerve capable of regeneration with much poorer prognosis affects people's life quality. The recovery of nerve function after transplantation for peripheral nerve injury remain a worldwide problem. Silicon-induced biofilms as vascularized biological conduits can promote nerve regeneration by encapsulating autologous or allogeneic nerve graft.Objective: We proposed to explore the effect of silicon-induced biofilms on nerves regeneration and whether the VEGF/VEGFR2/ERK pathway was involved in the present study.Methods: Biofilms around the transplanted nerves in peripheral nerve injury rats were induced by silicon. Vascularization and proteins related to VEGF/VEGFR2/ERK were measured. Pathology and morphology of nerves were investigated after encapsulating the transplanted nerves by silicon-induced biofilms.Results: Our results indicated that the biofilms induced by silicon for 6 weeks showed the most intensive vascularization and the optimal effect on nerve regeneration. Moreover, silicon-induced biofilms for 4, 6 and 8 weeks could significantly secrete VEGF with the highest content at week 6 after induction. VEGFR2, VEGF, p-VEGFR2, ERK1, ERK2, p-ERK1 and p-ERK2 were expressed in the biofilms. p-VEGFR2, p-ERK1 and p-ERK2 expression were different at each time point and significantly increased at week 6 compared with that at week 4 or week 8 which was consistent with that 6 week of was the optimum time for biofilms induction to improve the nerve repair after peripheral nerve injury.Conclusion: Our results suggested that combination of silicon-induced autologous vascularized biofilm and autologous transplantation may promote the repair of rat sciatic nerve defect quickly through VEGF/VEGFR2/ERK pathway.

Current status of total pancreatectomy with islet autotransplantation for chronic and recurrent acute pancreatitis.

Total pancreatectomy with islet autotransplantation (TPIAT) is an established and effective treatment modality for patients diagnosed with intractable chronic pancreatitis (CP) and recurrent acute pancreatitis (RAP). TPIAT primarily aims to manage debilitating pain leading to impaired quality of life among patients with CP or RAP, which can be successfully managed with medical, endoscopic, or surgical interventions. TPIAT is significantly successful in relieving pain associated with CP and improving health-related quality of life outcomes. Furthermore, the complete loss of pancreatic endocrine function attributed to total pancreatectomy (TP) can be compensated by autologous islet transplantation (IAT). Patients receiving IAT can achieve insulin independence or can be less dependent on exogenous insulin compared with those receiving TP alone. Historically, TPIAT has been mainly used in the United States, and its outcomes have been improving due to technological advancements. Despite some challenges, TPIAT can be a promising treatment for patients with CP-related intractable pain. Thus far, TPIAT is not commonly performed in Japan. Nevertheless, it may improve health-related quality of life in Japanese patients with CP, similar to Western patients. This review article aimed to provide an overview of the indications, related procedures, and outcomes of TPIAT and to discuss future prospects in Japan.

Tandem autologous hematopoietic stem cell transplantation for patients with multiple myeloma: a systematic review and meta-analysis.

To evaluate whether patients with multiple myeloma (MM) could benefit from tandem autologous hematopoietic stem cell transplantation (auto-HSCT), PubMed, Embase, Web of Science and Cochrane Library databases were systematically searched, and 10 eligible studies were included after data extraction and quality evaluation. Meta-analysis showed that compared to single autologous hematopoietic stem cell transplantation, tandem auto-HSCT does not improve OS, EFS or efficacy in MM patients, and may even lead to higher treatment-related mortality (TRM). MM patients who received autologous tandem allogeneic HSCT did not achieve better response compared to tandem autologous HSCT. In summary, compared to single autologous hematopoietic stem cell transplantation, tandem autologous hematopoietic stem cell transplantation cannot provide survival advantages for MM patients, and MM patients cannot benefit from autologous tandem allogeneic hematopoietic stem cell transplantation.

A novel method for the establishment of autologous skin cell suspensions: characterisation of cellular sub-populations, epidermal stem cell content and wound response-enhancing biological properties.

Introduction: Autologous cell suspension (ACS)-based therapy represents a highly promising approach for burns and chronic wounds. However, existing technologies have not achieved the desired clinical success due to several limitations. To overcome practical and cost-associated obstacles of existing ACS methods, we have established a novel methodology for rapid, enzymatic disaggregation of human skin cells and their isolation using a procedure that requires no specialist laboratory instrumentation and is performed at room temperature. Methods: Cells were isolated using enzymatic disaggregation of split-thickness human skin followed by several filtration steps for isolation of cell populations, and cell viability was determined. Individual population recovery was confirmed in appropriate culture medium types, and the presence of epidermal stem cells (EpSCs) within keratinocyte sub-populations was defined by flow cytometry via detection of CD49 and CD71. Positive mediators of wound healing secreted by ACS-derived cultures established on a collagen-based wound-bed mimic were detected by proteome arrays and quantified by ELISA, and the role of such mediators was determined by cell proliferation assays. The effect of ACS-derived conditioned-medium on myofibroblasts was investigated using an in-vitro model of myofibroblast differentiation via detection of α-SMA using immunoblotting and immunofluorescence microscopy. Results: Our methodology permitted efficient recovery of keratinocytes, fibroblasts and melanocytes, which remained viable upon long-term culture. ACS-derivatives comprised sub-populations with the CD49-high/CD71-low expression profile known to demarcate EpSCs. Via secretion of mitogenic factors and wound healing-enhancing mediators, the ACS secretome accelerated keratinocyte proliferation and markedly curtailed cytodifferentiation of myofibroblasts, the latter being key mediators of fibrosis and scarring. Discussion: The systematic characterisation of the cell types within our ACS isolates provided evidence for their superior cell viability and the presence of EpSCs that are critical drivers of wound healing. We defined the biological properties of ACS-derived keratinocytes, which include ability to secrete positive mediators of wound healing as well as suppression of myofibroblast cytodifferentiation. Thus, our study provides several lines of evidence that the established ACS isolates comprise highly-viable cell populations which can physically support wound healing and possess biological properties that have the potential to enhance not only the speed but also the quality of wound healing.

Monitoring Humoral Response Following BNT162b2 mRNA Vaccination against SARS-CoV-2 in Hematopoietic Stem-Cell Transplantation Patients: A Single-Center Prospective Study along with a Brief Review of Current Literature.

Data on antibody response (AR) after vaccination against SARS-CoV2 in hematopoietic stem-cell transplantation setting (HSCT) were initially scarce, mainly due to the exclusion of such patients from approval studies. Shortly after the worldwide application of vaccination against SARS-CoV-2 in vulnerable populations such as patients with hematologic malignancies, limited single-center trials, including HSCT patients, were published. However, there was a great heterogeneity between them regarding the type of underlying malignancy, co-current treatment, type of vaccine, method of AR measurement, and time point of AR measurement. Herein, we present the results of a prospective study on AR after vaccination for SARS-CoV-2 using the BNT162b2 vaccine in a cohort of 54 HSCT recipients-mostly autologous from a single Unit-along with a broad review of the current literature. In our cohort, the AR positivity rate at 1 month was 80.8% and remained positive in 85.7% of patients at 3 months after vaccination. There were only nine non-responders, who were more heavily pretreated and more frequently hypogammaglobulinemic compared to responders. High antibody titers (AT), [AT ≥ 1000 U/mL], were detected in 38.5% and 30.6% of the patients at m1 and m3, respectively. A significant decline in AT between m1 and m3 was demonstrated-p < 0.0001; median AT1 and AT3 were 480.5 and 293 U/mL, respectively. A novel finding of our study was the negative impact of IgA hypogammaglobulinemia on response to vaccination. Other negative significant factors were treatment with anti-CD20 antibody at vaccination and vaccination within 18 months from HSCT. Our data indicate that HSCT recipients elicit a positive response to the BNT162b2 vaccine against SARS-CoV-2 when vaccinated at 6 months post-transplant, and vaccination should be offered to this patient population even within the post-pandemic COVID-19 era.

Graft-versus-host disease after autologous stem cell transplantation in a recipient who underwent allogeneic stem cell transplantation 20 years earlier.

A literature review does not provide information about the safety of autologous hematopoietic stem cell transplantation (HSCT) in a recipient who has previously received allogeneic HSCT. We treated a 69-year-old woman with diffuse large B cell lymphoma. The patient received autologous stem cell transplantation (ASCT) in the second complete remission of malignant lymphoma. The patient had undergone allogeneic hematopoietic SCT (allo-HSCT) for chronic myeloid leukemia 20 years ago. Chronic myeloid leukemia had been in complete remission for the previous 20 years. Thus, the patient received autologous and allogenic HSCT 20 years apart. ASCT involves the patient receiving "self" hematopoietic cells from an allogeneic donor. In other words, this is immunologically the second allo-HSCT. The allo-HSCT 20 years ago was undergone by a related healthy brother, a human leukocyte antigen (HLA) 8/8 full matched donor. The conditioning regimen was reduced-intensity consisting of fludarabine and busulfan. The patient did not experience acute or chronic graft-versus-host disease (GVHD) after allo-HSCT. The second transplantation, ASCT was performed to the MEAM conditioning regimen. Engraftment was uneventful, and complete donor chimerism had been achieved even after ASCT. She suffered from an acute gastric mucosal lesion 52 days after ASCT. Pathological finding of gastric mucosa was nonspecific acute gastritis with significant neutrophil infiltration. Sex chromosome analysis of gastric mucosa demonstrated that mucosal cells had XX signals, whereas infiltrating neutrophils had XY signals. We speculated the patient onset of an acute gastric GVHD in this recipient after the second transplantation. This case remarked infiltration of neutrophils triggered GVHD reaction by resetting allogeneic immune reaction after the second transplantation. We describe a rare occurrence of GVHD reaction in a recipient of ASCT following allo-HSCT.

Número de células CD34+ circulantes como predictor de recolección exitosa de progenitores hematopoyéticos por aféresis en trasplante autólogo / Number of circulating CD34+ cells as a predictor of successful collection of hematopoietic progenitors by apheresis in autologous transplantation

RESUMEN Introducción. El trasplante autólogo de células progenitoras hematopoyéticas es una terapia eficaz en neoplasias malignas hematológicas. El número de células que CD34+ en sangre periférica es el mejor predictor del rendimiento de recolección de células progenitoras hematopoyéticas. Objetivo. Determinar el número de células CD34+ en sangre periférica asociado al éxito de recolección de progenitores hematopoyéticos por aféresis en trasplante autólogo. Métodos. Se evaluó retrospectivamente los datos de 236 procedimientos de aféresis de células progenitoras hematopoyéticas para el trasplante autólogo en el Hospital Edgardo Rebagliati Martins (Lima, Perú) de julio del 2020 a julio del 2023. Se utilizó la curva ROC (características operativas del receptor) para determinar el número de células CD34+ en sangre periférica necesario para lograr una recolección por aféresis ≥ 2 x 106 células CD34+/kg. Resultados. El 61% fueron hombres, con mediana de edad de 58 años, el valor de corte fue de 18,38 células CD34+/μL (sensibilidad de 94,1% y especificidad de 96,9%). Conclusión. El número de células CD34+ sangre periférica para una recolección exitosa de células progenitoras hematopoyéticas para el trasplante autólogo fue de 18,38 células CD34+/μL.

ABSTRACT Introduction. Autologous hematopoietic progenitor cell transplantation is an effective therapy in hematological malignancies, the number of CD34+ cells in peripheral blood is the best predictor of hematopoietic progenitor cell harvesting performance. Objective. To determine the number of CD34+ cells in peripheral blood associated with the successful collection of hematopoietic progenitors by apheresis in autologous transplantation. Methods. The data of 236 hematopoietic progenitor cell apheresis procedures for autologous transplantation at the Edgardo Rebagliati Martins Hospital (Lima, Peru) were retrospectively evaluated from July 2020 to July 2023. The ROC (receiver operating characteristics) curve was used to determine the number of CD34+ cells in peripheral blood necessary to achieve an collection by apheresis ≥ 2 x 106 CD34+ cells/kg. Results. 61% were men, with a median age of 58 years, the cut-off value was 18.38 CD34+ cells/μL (sensitivity of 94.1% and specificity of 96.9%). Conclusion. The number of peripheral blood CD34+cells for successful collection of hematopoietic progenitor cells for autologous transplantation was 18.38 CD34+ cells/μL.

Inhibition of Toll-like Receptor 4 Using Small Molecule, TAK-242, Protects Islets from Innate Immune Responses.

Islet transplantation is a therapeutic option to replace ß-cell mass lost during type 1 or type 3c diabetes. Innate immune responses, particularly the instant blood-mediated inflammatory reaction and activation of monocytes, play a major role in the loss of transplanted islet tissue. In this study, we aimed to investigate the inhibition of toll-like receptor 4 (TLR4) on innate inflammatory responses. We first demonstrate a significant loss of graft function shortly after transplant through the assessment of miR-375 and miR-200c in plasma as biomarkers. Using in vitro models, we investigate how targeting TLR4 mitigates islet damage and immune cell activation during the peritransplant period. The results of this study support the application of TAK-242 as a therapeutic agent to reduce inflammatory and innate immune responses to islets immediately following transplantation into the hepatic portal vein. Therefore, TLR4 may serve as a target to improve islet transplant outcomes in the future.

Evaluation of Bone Growth around Autotransplanted Teeth Using Cone-Beam Computed Tomographic Images.

INTRODUCTION: The aim of this observational study was to evaluate bone growth at the recipient site of autotransplanted teeth using cone-beam computed tomography (CBCT) images and to compare it to the control tooth. METHODS: Bone growth was measured on CBCT images obtained from the anterior region of the maxilla, which received a single transplant of immature premolars due to early loss of the central incisor. The results were compared to the bone growth of contralateral central incisor that served as control. The sample consisted of 13 autotransplanted teeth and 13 control teeth. It was determined the thickness of the buccal bone of the marginal ridge, the thickness of the palatal bone of the marginal ridge, the height of the maxillary bone, and the thickness of the maxillary bone at its mid-height. The measurements were analyzed statistically, adopting a significance level of 5%. RESULTS: The mean interval between the dental autotransplantation surgery and the CBCT scan was 16.2 years. The mean thickness of the buccal bone of the marginal ridge, thickness of the palatal bone of the marginal ridge, height of the maxillary bone, and thickness of the maxillary bone at its mid-height were, respectively, 0.85, 0.94, 19.6, and 8.85 mm for autotransplanted teeth and 0.79, 1.09, 18.88, and 8.5 mm for control teeth. There were no significant differences in the bone measurements between autotransplanted and control teeth (P > .05). CONCLUSIONS: The growth of maxillary bone in the region that received the autotransplanted tooth was proportional to that of maxillary bone that supports the contralateral tooth. Thus, autogenous transplantation is efficient in maintaining the bone architecture at the recipient site.

[Local flap reconstruction techniques after frontal sinus drainage type II and III according to Draf]. / Lokale Lappenplastiken bei der Stirnhöhlendrainage Typ II und III nach Draf.

BACKGROUND: Extended endonasal endoscopic frontal sinus surgery is characterized by bone resection beyond the lamellae of the frontal sinus and is currently classified according to Draf as type IIa, type IIb, modified type III (also referred to as type IIc), and type III. This approach is indicated when the surgical goal cannot be achieved through complete removal of the anterior ethmoidal cells. Numerous studies indicate restenosis rates ranging from 7 to 36%, despite creation of maximal openings. Exposed bone, which tends to epithelize slowly with significant crusting and the risk of uncontrolled wound healing depending on the local environment and other factors, is considered a contributing factor. Covering the exposed bone with mucosa can significantly reduce the risk of restenosis. METHODS AND RESULTS: A variety of flap techniques for frontal sinus drainage in Draf III procedures are presented, including some variants that were part of presentations at the 2023 Congress of the European Rhinologic Society in Sofia, Bulgaria. These include combinations of free mucosal grafts, pedicled mucosal flaps, and hybrids combining both techniques. Additionally, the results of current studies are presented. CONCLUSION: The results and achieved opening areas in contemporary Draf III surgeries are significantly improved and larger compared to the early stages of these procedures. A multitude of published studies consistently demonstrate that outcomes are markedly improved with mucosal coverage. Depending on the prevailing anatomy, mucosal conditions, and the extent of the surgical intervention, the most suitable technique should be selected. Therefore, proficiency in various methods is crucial. The use of a flap technique (free, pedicled, or combinations thereof) should be defined as the standard when performing extended frontal sinus surgery (Draf IIb, IIc, III, or endonasal frontal sinus surgery [EFSS] 4-6).

The Treatment of Burkitt Lymphoma With the Berlin-Frankfurt-Münster Protocol With Rituximab and Consolidative Autologous Transplantation.

INTRODUCTION: Intensive treatment approaches are required for adult patients with Burkitt lymphoma (BL), although an univocal standard of care still does not exist. The use of frontline autologous stem cells transplantation (ASCT) is debated. PATIENTS AND METHODS: Between 2004 and 2020, 50 patients with BL were treated with the Berlin-Frankfurt-Münster (BFM). Treatment plan consisted of 3 blocks, A (ifosfamide, vincristine, methotrexate, etoposide, and cytarabine), B (vincristine, cyclophosphamide, methotrexate, and doxorubicin), and C (vindesine, methotrexate, etoposide, and cytarabine), each repeated twice, every 28 days. Rituximab was given at day 1 each block. Intrathecal prophylaxis was given once per each block. ASCT was scheduled at the end of the 6 blocks after conditioning. RESULTS: Median age at onset was 38 years (range 16-72); stages III-IV disease was observed in 82% of cases; bulky disease occurred in 44% of the patients, with B-symptoms in 38%. Stem cell harvest was performed in 72% of patients, who all received a subsequent ASCT. The full 6 blocks treatment was completed in 70% of the patients. The overall response rate was 74%, with a complete response rate of 60%. Ten-year overall survival and progression-free survival were 83.7% and 76.0%, respectively, without reaching the median. Ten-year disease-free survival was 80.3%. Grades 3-4 neutropenia, thrombocytopenia, anemia, and mucositis were seen in 96%, 60%, 32%, and 24% of patients. Infections occurred in 60% of patients. CONCLUSION: Intensive treatment according to BFM protocol, with rituximab and ASCT, appears feasible, safe, and highly effective in adult patients with BL, as confirmed by long-term survival rates reflecting response maintenance.

An evidence-based and risk-adapted GSF versus GSF plus plerixafor mobilization strategy to obtain a sufficient CD34+ cell yield in the harvest for autologous stem cell transplants.

BACKGROUND: Plerixafor is a bicyclam molecule with the ability to reversibly bind to receptor CXCR-4 thus leading to an increased release of stem cells (SC) into the circulation. This study aims to evaluate the efficacy of G-CSF plus plerixafor versus G-CSF alone mobilizing regimens on the basis of CD34+ cell yield and engraftment kinetics following hematopoietic SC transplants. METHODS: The study incorporated 173 patients with plasma cell neoplasms (PCN), Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL), undergoing mobilization and following autologous SC-transplant. For patients with mobilization failure and those predicted to be at risk of harvesting inadequate CD34+ yields (poor-responders), plerixafor was administered. Data was collected and compared in relation to the harvesting protocols used, cell quantification, cell-engraftment potential and overall clinical outcome. RESULTS: A total of 101 patients received plerixafor (58.4 %) and the median CD34+increase was 312 %. Chemotherapy-mobilized PCN-patients required less plerixafor administration (p = 0.01), no difference was observed in lymphoma groups (p = 0.46). The median CD34+cell yield was 7.8 × 106/kg bm. Patients requiring plerixafor achieved lower, but still comparable cell yields. Total cell dose infused was in correlation with engraftment kinetics. Patients requiring plerixafor had delayed platelet engraftment (p = 0.029). CONCLUSIONS: Adequately selected plerixafor administration reduces "mobilization-related-failure" rate and assure a high-level cell dose for SC transplants, with superior "therapeutic-potential" and safety profile. The mobilization strategy that incorporates "just-in-time" plerixafor administration, also leads to a reduction of hospitalization days and healthcare resource utilization. For definitive conclusions, further controlled/larger clinical trials concerning correlation of CD34+ cell count/yield, with hematopoietic reconstitution are required.

[Treatment of osteochondritis dissecans]. / Therapie der Osteochondrosis dissecans.

Osteochondritis dissecans (OD) is a rare condition with an incidence of 30/100,000. It especially affects male patients aged 10-20 years old. During the staged progression the osteochondral fragments can detach from their base. These can damage the adjacent articular cartilage, which can lead to premature osteoarthritis. Most commonly affected are the knee, ankle and elbow joints. The exact pathogenesis of OD has so far not been clearly confirmed. Several risk factors that can lead to the development of OD are discussed. These include repeated microtrauma and vascularization disorders that can lead to ischemia of the subchondral bone and to a separation of the fragments close to the joint and therefore to the development of free joint bodies. For an adequate clarification patients should undergo a thorough radiological evaluation including X­ray imaging followed by magnetic resonance imaging (MRI) to assess the integrity of the cartilage-bone formation with determination of the OD stage. The assessment is based on criteria of the International Cartilage Repair Society (ICRS). The instability of the cartilage-bone fragment increases with higher stages. Stages I and II with stable cartilage-bone interconnection can be treated conservatively. For stages III and IV, i.e., instability of the OD fragment or the presence of free fragments, surgical treatment should be performed. Primarily, refixation of a free joint body should be carried out depending on the size and vitality of the fragment. In cases of unsuccessful conservative treatment or fixation, a debridement, if necessary in combination with a bone marrow stimulating procedure, can be employed corresponding to the size of the defect. For larger cartilage defects, an osteochondral graft transplantation should be considered. Overall, OD lesions in stages I and II show a good healing tendency under conservative treatment. In cases of incipient unstable OD, refixation can also lead to good clinical and radiological results.

Surface morphology of osteochondral grafts harvested from femoral condyles with free-hand technique: a cadaveric study.

PURPOSE: The purpose of this cadaver study was to examine the surface morphology of the osteochondral grafts harvested from the femoral condyles using the free-hand graft harvesting technique. MATERIALS AND METHODS: One hundred osteochondral grafts were harvested with 6.5 mm chisels at ten different donor sites using the free-hand technique in five paired knee specimens (Mean age: 56.4 years). The cartilage and subchondral bone surface angles were measured through multiplanar reconstruction computerized tomography examination. The cartilage thickness was measured with a MicroScribe G2X digitizer with an accuracy of 0.02 mm. An acceptable congruity could be obtained when these plugs were transferred to a perpendicular socket (articular step-off of less than 1 mm and 0.5 mm) was evaluated. RESULTS: Four plugs were damaged or broken during harvesting due to technical difficulties; thus remaining 96 plugs were analyzed. The cartilage thickness varied between 1.36 mm and 3.26 mm across the donor sites. The cartilage was the thinnest in the medial intercondylar notch and thickest in the lateral supracondylar notch. Twenty of ninety-six plugs (20.8%) had unacceptable cartilage surface inclination according to the > 0.5 mm protrusion criteria. Of these plugs, 14 were harvested from the lateral intercondylar notch, whereas five of 96 plugs (5.2%) had unacceptable cartilage surface inclination according to the > 1 mm protrusion criteria. Of these plugs, all were harvested from the lateral intercondylar notch. CONCLUSIONS: High rates of unacceptable plugs (up to 100%) might be harvested from the lateral intercondylar notch. In large chondral lesions that require multiple plugs, lateral and medial supracondylar ridges were the best donor sites for perpendicular plug harvesting, whereas lateral intercondylar notch should be avoided.