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Autologous hematopoietic cell transplants (auto-HCTs) remain the standard of care for transplant-eligible MM patients. The general practice has been to undergo upfront apheresis following induction to collect sufficient number of CD34+ cells to facilitate two auto-HCTs. However, 5-30% of MM patients do not initially mobilise a sufficient number of hematopoietic stem cells and are classified as poor mobilizers (PM). We compared the baseline characteristics and outcomes of 61 PMs and 816 non-PM patients who underwent a second auto-HCT and who were enrolled in the non-interventional CALM study (NCT01362972). Only patients who collected CD34+ prior to auto-HCT1 were included. Auto-HCT2 comprised both tandem and salvage transplants. PMs were re-mobilized with plerixafor (n = 24, 39.3%) or non-plerixafor-based regimens (n = 37, 60.7%). There were no significant differences in engraftment, progression-free survival (PFS) or overall survival (OS) after the second auto-HCT between PM and non-PM patients. There was a trend to shorter PFS in PM patients undergoing salvage auto-HCT (median 9.6 vs. 12.9 months; p = 0.08) but no significant difference in OS. The median OS was 41.1 months for PM and 41.2 months for non-PM patients (p = 0.86). These data suggest that salvage mobilization is effective and does not affect overall outcomes after a second auto-HCT., Competing Interests: Competing interests: JDS – honoraria AbbVie, Roche, Janssen, Astra Zeneca, SOBI, Takeda, BMS, Novartis, Swixx; Advisory board meetings organized by Janssen-Cilag, Sanofi, AstraZeneca, Roche, BeiGene; AP - honoraria from Behring and Abbvie, participation in scientific Advisory board meetings organized by Abbvie, Janssen-Cilag, Novartis, Pfizer, Sanofi and Takeda; none of COI directly related to the study. Ethics approval: This retrospective study was approved by the Chronic Malignancies Working Party (CMWP) of the EBMT and was performed in accordance with the Declaration of Helsinki., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Limited magnetic resonance imaging (MRI) data on autograft dilatation following the Ross procedure in congenital cohorts presents challenges in understanding its evolution and impact on clinical outcomes. This study, spanning from February 2003 to December 2022, included patients under 40 years at the time of the Ross procedure, with MRI follow-ups assessing dimensions at key aortic sites. Among 307 patients, 132 MRIs were analyzed from 76 individuals, revealing that autograft z-scores increase primarily with time post-procedure (Coef. 0.13; 95% CI:0.051-0.216; P = 0.002). Additionally, older patients at the time of surgery showed larger ascending aortic dimensions (Coef. 0.13; 95% CI:0.099-0.165; P = 0.001). Notably, autograft dilation at the sinus of Valsalva significantly predicted higher reintervention risks (HR 1.57; 95% CI:1.21-2.04; P = 0.001). Surgical reinforcement techniques of the autograft, via subcoronary implantation or external support, prevented such dilation (P < 0.001) and mitigated aortic regurgitation. In conclusion, our model predicted autograft dilation over time in patients after Ross procedure, aiding clinicians in making data-driven decisions regarding the optimal timing of the procedure and the selection of the most effective surgical strategy., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Autologous peripheral blood stem cell (PBSC) transplantation is a standard treatment of multiple myeloma (MM), Hodgkin lymphoma and various subtypes of non-Hodgkin lymphoma. Cryopreservation of hematopoietic stem cells is standard practice that allows time for delivery of conditioning regimen prior to cell infusion. The aim of this Worldwide Network for Blood & Marrow Transplantation (WBMT) work was to assess existing evidence on non-cryopreserved autologous transplants through a systematic review/meta-analysis, to study feasibility and safety of this approach. We searched PubMed, Web of Science and SCOPUS for studies that utilized non-cryopreserved autologous PBSC transplantation. Identified literature was reviewed for information on mobilization, apheresis, preservation and viability, conditioning regimen, engraftment, response, and survival. Results highlight collective experience from 19 transplant centers (1686 patients), that performed autologous transplants using non-cryopreserved PBSCs. The mean of infused CD34+ was 5.6 × 10 6 /kg. Stem cell viability at transplantation was >90% in MM and >75% in lymphomas, after a storage time of 24-144 h at +4 °C. Mean time-to-neutrophil engraftment was 12 days and 15.3 days for platelets. Pooled proportion estimates of day 100 transplant-related mortality and graft failure were 1% and 0%, respectively. Non-cryopreservation of apheresed autologous PBSCs appears feasible and safe., Competing Interests: Competing interests: MAB, DN, REF, DJW, SG, AR, AB, AH, YK, AK, TE, MM, WR declare no conflicts of interest MAK-D: declares research/grant from Bristol Myers Squibb, Novartis, and Pharmacyclics, and lecture/honoraria from Kite Pharma; LG: declares relationship with Bristol Myers Squibb, Sanofi, Janssen, Pfizer; IY-A: declares honoraria from Kite Pharma, Novartis and Bristol Myers Squibb; HG: declares speaker bureau and consultancy for Therakos, Gilead, Novartis, Stemline, Neovii, Sanofi, and Takeda; SOA: declares advisory board with Kite Pharma and Novartis, and speaker honoraria from Kite Pharma, Novartis, and Johnson & Johnson; CC: declares honoraria (personal and institutional) for lectures and advisory boards from Bristol Myers Squibb, Kite Pharma/Gilead, Janssen, Jazz, Novartis, and Miltenyi Biotec; SKH: declares educational/travel grants from Novartis, Pfizer, Janssen, Therakos, Vertex, MSD, Roche; UG: declares consultancy/Honoraria :Kite Pharma, Incyte, Astellas, Jazz,and Vor; NH: honoria from Janssen, Novartis, Takeda, Abbvie, Roche, Astellas, Bigene; AA: declares lecture-Advisor /honoraria from Kite Pharma, Novartis, Takeda and Janssen; MP: declares research with Bristol Myers Squibb, Janssen, Kite Pharma, Novartis, and consultancy for Bristol Myers Squibb, Novartis, and honoraria from Gilead; JS: declares consultancy for Sanofi and ADRx, honoraria from Sanofi, Alexion, AstraZeneca Rare Disease, Prevail Therapeutics (Eli–Lilly), Pfizer, Sobi Pharmaceuticals, and Novartis, advisory committees for Sanofi, AstraZeneca Rare Disease, Prevail Therapeutics (Eli–Lilly), Pfizer, Sobi Pharmaceuticals, Novartis, speaker bureau for Sanofi, AstraZeneca Rare Disease, Prevail Therapeutics (Eli–Lilly), Pfizer, Sobi Pharmaceuticals, Novartis; DMc: declares lecture/honoraria from GSK, Novartis, Abbvie. Research funding from Imago Biosciences; NW: declares speakers fees from BMS Celgene, Kite Gilead, Novartis, Pierre Fabre, Sanofi Genzyme, Therakos Mallinckrodt, Travel reimbursement from Jannsen, Pierre Fabre; RG: declares speaking honoraria from Biotest, Pfizer, Medac, Neovii and Magenta; YA: declares lecture/honoraria from Otsuka Pharmaceutical Co., Ltd, Chugai Pharmaceutical Co., Ltd., Novartis Pharma KK, Meiji Seika Pharma Co., Ltd, Janssen Pharmaceutical K.K., and consultancy fee from JCR Pharmaceuticals Co., Ltd and Kyowa Kirin Co., Ltd; MK: declares non-specified relationship with Kite Pharma, Takeda and Gilead; AS: declares honoraria from Takeda, Bristol Myers Squibb /Celgene, MSD, Janssen, Amgen, Novartis, Gilead Kite, Sanofi, Roche, Genmab, AbbVie, Jazz Pharmaceuticals, consultancy from Takeda, Bristol Myers Squibb/Celgene, Novartis, Janssen, Gilead, Sanofi, Genmab, AbbVie, speaker bureau for Takeda and Research support from Takeda; MA: declares lecture/honoraria from Kite Pharma and Vertex Pharma., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: The selection of appropriate materials and techniques for reconstructing skull base defects is crucial for restoring function, minimizing complications, and enhancing aesthetics. Dermal fat grafts (DFGs) have been established in many surgeries for contour correction. However, there is little literature describing the application of free dermal fat grafts for reconstruction of lateral skull base surgery defects. Therefore, the aim of this study was to evaluate the clinical effect of using free dermal fat grafts in the reconstruction of lateral skull base defects., Methods: In this study, 32 patients who underwent primary autologous free dermal fat graft reconstruction for lateral skull base defects were enrolled. Postoperative complications both in the donor and recipient area were evaluated. Three-dimensional (3D) reconstruction techniques were applied to visualize the fat graft shape and volume variations for the assessment of postoperative restoring function. A telephone questionnaire was used for the assessment of postoperative facial aesthetics and patient satisfaction., Results: A total of 32 patients who met the inclusion criteria were included in the study, showing satisfying results in safety and aesthetics. Participants' ages averaged at 42.03 years, with the youngest being 18 and the oldest at 75 years old. No patient had postoperative complications of abdominal wounds in the donor area, only two patients had postoperative infections and one patient had a postoperative effusion in the recipient area. The volume of the grafts ranged from a minimum of 24.4 cm³ to a maximum of 131 cm³, with the highest recorded resorption volume being 33.63 cm³. The average resorption rate of the dermal fat graft was 24.36%, ranging from a minimum of 11% to a maximum of 43%. 3D reconstruction based on MRI imaging data indicated that DFGs have a lower resorption rate than traditional free fat grafts. The telephone questionnaire revealed high patient satisfaction with facial aesthetics, with the majority rating their outcomes positively., Conclusions: Dermal fat grafts have fewer complication and can provide better resistance to infection and radiation aspect. Based on 3D reconstruction techniques via MRI imaging data, we found that dermal fat grafts have lower resorption rate than traditional free fat grafts, which can be a suitable material for reconstruction of lateral skull base defects., (© 2024. The Author(s).)

Donor stem cell health may be critically important to the success of hematopoietic stem cell transplantation (HSCT). Herein, we performed this systematic review and meta-analysis including meta-regression to assess the impact of donor-engrafted clonal hematopoiesis (CH) in allogeneic HSCT (allo-HSCT) and impact of pre-transplant CH in autologous HSCT (auto-HSCT). We applied random-effects models to analyze 5 allo-HSCT studies with 3192 donor-recipient pairs and 9 auto-HSCT studies with 2854 patients. We found that donor-engrafted CH after allo-HSCT decreased the risk of disease relapse [Hazard Ratio (HR) = 0.79, 95% Confidence Interval (CI): (0.67, 0.93)], but did not affect overall survival (OS) [HR = 0.91, 95% CI: (0.75, 1.11)], progression-free survival (PFS) [HR = 0.94, 95% CI: (0.63, 1.41)], or non-relapse mortality [HR = 1.06, 95% CI: (0.81, 1.39)]. In contrast, pre-transplant CH in auto-HSCT recipients resulted in inferior OS [HR = 1.30, 95% CI: (1.16, 1.46)], inferior PFS [HR = 1.35, 95% CI: (1.18, 1.54)], and higher risk for therapy-related myeloid neoplasm [HR = 4.85, 95% CI: (2.39, 9.82)] when compared to auto-HSCT recipients without CH. This study sheds light onto the debate about prospective "CHIP screening" for stem cell donors and addresses the impact of CH as a transmissible phenomenon., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The most widely used conditioning regimens in autologous haematopoietic stem cell transplantation (ASCT) for multiple sclerosis (MS) are BEAM with anti-thymocyte globulin (ATG) and high-dose cyclophosphamide with ATG (Cy/ATG). In this retrospective study, we compare efficacy and safety of these regimens when used for relapsing-remitting MS. We assessed 231 patients treated in Sweden before January 1, 2020. The final cohort comprised 33 patients treated with BEAM/ATG and 141 with Cy/ATG. Prospectively collected data from the Swedish MS registry were used for efficacy, and electronic health records for procedure-related safety. The Kaplan-Meier estimate of 'no evidence of disease activity' (NEDA) at 5 years was 81% (CI 68-96%) with BEAM/ATG and 71% (CI 63-80%) with Cy/ATG, p = 0.29. Severe adverse events were more common with BEAM/ATG, mean 3.1 vs 1.4 per patient, p = <0.001. Febrile neutropaenia occurred in 88% of BEAM/ATG patients and 68% of Cy/ATG patients, p = 0.023. Average hospitalisation was 3.0 days longer in BEAM/ATG patients from day of stem-cell infusion, p < 0.001. While both regimens showed similar efficacy, BEAM/ATG was associated with more severe adverse events and prolonged hospitalisation. In the absence of randomised controlled trials, Cy/ATG may be preferable for ASCT in patients with relapsing-remitting MS due to its favourable safety profile., (© 2024. The Author(s).)

Our hypothesis is that the peroneus longus (PL) is a great option for ligament reconstruction in the knee, and therefore the objective of the study is to determine if the use of this graft is safe and does not cause secondary damage to the harvested area. A prospective study was conducted between April 2019 and September 2022. Patients who underwent any type of knee ligament reconstruction using the PL or just the anterior half (AHPL) as grafts were followed up. These patients were evaluated according to the Tegner-Lysholm score and the International Knee Documentation Committee (IKDC) guidelines for functional evaluation of the knee and the American Orthopedic Foot and Ankle Score (AOFAS) and the Foot and Ankle Disability Index (FADI) for the functional evaluation of the ankle. Most patients had an increase in the IKDC score, Tegner-Lysholm score, AOFAS and FADI regardless of the graft used in the surgical procedure, with mean values at the 24-month follow-up of, respectively, 99.02± 0.02, 98.69± 0.08, 99.92± 0.07, and 99.92± 0.07 for those with PL grafts and 99.31± 0.54, 98.88± 0.95, 100± 0.00, and 100± 0.00 for those with AHPL grafts. The differences in the scores between the two graft groups during each of the follow-up periods were significant (P = 0.001). The use of the peroneus longus tendon as a graft in knee surgeries was shown to be adequate for achieving good knee functional results., (© 2024. The Author(s).)

Achilles tendon reconstruction is an effective method of repairing Achilles tendon rupture defects. We introduce a new approach for Achilles tendon reconstruction using transversal calcaneal anchored autogenous semitendinosus tendon graft. The study aimed to evaluate the clinical role of this new Achilles tendon reconstruction. We retrospectively enrolled patients who underwent Achilles tendon reconstruction using transversal calcaneal anchored autogenous semitendinosus tendon graft for acute Achilles tendon rupture defects from 2016 to 2021. The clinical and radiological results were assessed at the preoperative and the final postoperative follow-up with Visual Analog Score (VAS) scores, American Orthopaedic Foot & Ankle Society (AOFAS) scores and Achilles tendon Total Rupture Scores (ATRS). Besides, at the last postoperative follow-up, the difference in ankle range of motion between the two side of the patients and the incidence of postoperative complications were recorded. Results revealed patients had significantly lower VAS and higher AOFAS and ATRS (P < 0.01). Compared to the healthy ankle, the operative ankle showed significant deficits in ankle range of motion (P < 0.01). Additionally, radiological results showed no noticeable signs of tunnel enlargement in the calcaneus and no patient had re-rupture. Transversal calcaneal anchored Achilles tendon reconstruction with free semitendinosus tendon autograft is an effective treatment option for patients with acute Achilles tendon rupture with large defects and have high postoperative exercise demands., (© 2024. The Author(s).)

Design: An umbrella review of systematic reviews and meta-analyses on dental autotransplantation (DAT)., Aim: To provide a comprehensive overview of the current state of knowledge on prognostic factors, outcomes, and complications of DAT by synthesizing the evidence., Methods: A comprehensive search of six databases was conducted for systematic reviews and meta-analyses published up to June 30, 2022. Two authors independently performed study selection, data extraction, and quality assessment using the AMSTAR 2 tool. Raw data from primary studies were analyzed using a random effects meta-analysis, and meta-regression was performed to investigate the effect of open and closed apices on the outcomes., Results: Ten systematic reviews, of which nine included meta-analyses, were examined. The overall success rate of the studies was 89.4%, and the survival rate was 96.1%. The main complications were ankylosis (4.6%) and root resorption (7.4%). The analysis showed that a closed apex increased the proportion of ankylosis, resorption, and reduced survival but had no effect on success. The quality of the systematic reviews included varied, with 20% scoring moderate, 60% scoring low, and 20% scoring critically low on the AMSTAR 2 scale., Conclusions: Dental implant therapy is a reliable solution for replacing lost or damaged teeth, with high success and survival rates. However, it is a procedure that requires precision and attention to detail, along with careful selection of suitable candidates, comprehensive planning, and consideration of factors that may impact outcomes. To improve results and reduce potential complications, it is essential to establish standard clinical guidelines and conduct further extensive research., (© 2024. The Author(s), under exclusive licence to British Dental Association.)

There is currently no consensus on the role of upfront autologous transplantation (ASCT) for patients with peripheral T-cell lymphomas (PTCL), especially in patients achieving first complete remission (CR1) following chemotherapy, and data in the literature is conflicting. A systematic review and meta-analysis was performed to address this question. We searched key databases from January 2000 to February 2022. Six prospective and eleven retrospective studies were included among 2959 unique records. Median follow up in these studies ranged from 22 to 94 months. There was a trend towards benefit in PFS (HR = 0.80, 95% CI 0.62-1.05, p = 0.11) and OS (HR = 0.79, 95% CI 0.57-1.09, p = 0.15) in the ASCT compared to chemotherapy only group. Importantly, in transplant eligible patients in CR1, a significant benefit was demonstrated in both OS (HR = 0.59, 95% CI 0.36-0.95, p = 0.03) and PFS (HR = 0.61, 95% CI 0.47-0.81, p = 0.0004) in the ASCT group. Amongst the nodal PTCL subgroups, ASCT showed a significant PFS benefit for the AITL subgroup (HR = 0.43, 95% CI 0.20-0.94, p < 0.03) but not PTCL-NOS or ALK-ve ALCL subgroups. Our findings support upfront ASCT for transplant eligible PTCL patients achieving CR1 post chemotherapy. In particular, patients with AITL exhibited a significantly better PFS after upfront ASCT., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

This study investigates the efficacy of a collagen membrane as a substitute for autologous periosteum in atelocollagen-assisted autologous chondrocyte implantation (ACI) using J-TEC autologous cultured cartilage (JACC®). Sixty-nine patients with knee joint chondral defects underwent ACI using JACC®-34 with periosteum-covered ACI (P-ACIs) and 35 with collagen-covered ACI (C-ACIs). Clinical outcomes were compared through patient-reported measures, International Cartilage Repair Society (ICRS) Cartilage Repair Assessment (CRA) scores at second-look arthroscopy one year postoperatively, and adverse event incidence. Postoperative subjective scores significantly improved up to two years, with no significant differences between P-ACI and C-ACI groups. However, C-ACI exhibited a lower adverse event rate (p = 0.034) and significantly higher ICRS CRA scores (p = 0.0001). Notably, C-ACI outperformed P-ACI in both femoral condyle and trochlea assessments (p = 0.0157 and 0.0005, respectively). While clinical outcomes were comparable, the use of a collagen membrane demonstrated superiority in ICRS CRA during second-look arthroscopy and adverse event occurrence., (© 2024. The Author(s).)

Autologous matrix induced chondrogenesis (AMIC) is a bone marrow stimulating technique used for the surgical management of chondral defects of the talus. The present study evaluated the clinical outcomes and imaging of AMIC as revision procedure for failed AMIC surgery for osteochondral defects of the talus. Forty-eight patients with symptomatic osteochondral defects who received a revision AMIC were evaluated after a minimum of two years follow-up. Patients with previous procedures rather than AMIC, those who required additional surgical procedures (e.g. ligament repair or deformity correction), or those who had evidence of kissing, bilateral, or multiple lesions were excluded. Outcome parameters included the Visual Analogic Scale (VAS), Tegner Activity Scale, the American Orthopedic Foot and Ankle Score (AOFAS), and the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. All patients were followed by an assessor who was not involved in the clinical management. 27 patients were enrolled in the present study. The mean age of the patient was 34.9 ± 3.1 years, and the mean BMI 27.2 ± 5.1 kg/m 2 . The mean defect surface area was 2.8 ± 1.9 cm 2 . The mean follow-up was 44.3 ± 21.4 months. The mean hospital length of stay was 4.4 ± 1.4 days. At final follow-up, the mean VAS score was 4.1 ± 3.1, the mean Tegner 3.5 ± 1.6, the mean AOFAS 58.8 ± 20.6. The preoperative MOCART score was 22.1 ± 13.7 points, the postoperative MOCART score was 42.3 ± 27.9 points (+ 20.2%; P = 0.04), respectively. 30% (8 of 27 patients) experienced persistent pain and underwent a further chondral procedure. Concluding, AMIC could be a viable option as revision procedure for failed AMIC in recurrent symptomatic osteochondral defects of the talus. The PROMs indicated that patients were moderately satisfied with the procedure, and the MOCART score demonstrated a significant improvement from baseline to the last follow-up. A deeper understanding in prognostic factors and patient selection is critical to prevent failures., (© 2022. The Author(s).)

Chronic Kidney Disease (CKD) is a frequent complication in patients with multiple myeloma (MM) and is associated with adverse outcomes. The use of autologous stem cell transplantation (ASCT) has improved disease outcomes, however, the safety and efficacy of ASCT in patients with CKD has been the subject of debate. To investigate this, we conducted a retrospective analysis of 370 MM patients who underwent their first ASCT, including those with mild, moderate and severe CKD as well as normal renal function at the time of transplant. No significant difference in ASCT-related mortality, Progression-Free or Overall Survival was noted between the different renal function groups. A decline in estimated glomerular filtration rate (eGFR) at 1-year of >8.79% was associated with poorer overall survival (p < 0.001). The results of this study show that ASCT is a safe and effective option for myeloma patients with CKD, including those on dialysis. Patients who demonstrate renal deterioration at 1-year post-transplant should be closely monitored as this is a predictor for poor survival., (© 2022. The Author(s).)

Cytarabine-based immuno-chemotherapy followed by autologous stem cell transplantation (ASCT) consolidation is standard of care for fit patients with Mantle Cell Lymphoma (MCL). BEAM (Carmustine, Etoposide, Aracytine, Melphalan) is among the most frequently used conditioning regimen. Studies comparing BEAM with Bendamustine-EAM (BeEAM) have suggested that patients treated with BeEAM have a better progression-free survival (PFS). We performed a cross-study analysis to better evaluate BeEAM. Thirty-five patients from a retrospective study who received R-DHAP/BeEAM were compared to 245 patients from the LyMa trial (NCT00921414) who all received R-DHAP followed by R-BEAM. PFS and Overall Survival (OS) were estimated using Kaplan-Meier methods. At 2 years there was no difference between R-BEAM and BeEAM in either PFS (84.9% versus 87.9%; p = 0.95) or OS (91.8% versus 94.2%; p = 0.30). Analyses were repeated on a propensity score to reduce biases. Each patient from the BeEAM cohort (n = 30) was matched to three patients from the R-BEAM cohort (n = 90) for age, sex, MIPI score, pre-transplant status disease and rituximab maintenance (RM). PFS and OS at 2 years remained similar between R-BEAM and BeEAM with more renal toxicity in BeEAM group. MCL patients who received R-DHAP induction before ASCT have similar outcome after R-BEAM or BeEAM conditioning regimen., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Autologous liver transplantation (ALT) to cure end-stage hepatic alveolar echinococcosis (HAE) requires that hepatobiliary surgeons understand the invasion of intrahepatic structure and adjacent tissues or organs. Triphase contrast-enhanced CT of the liver has been widely used for diagnosis and preoperative evaluation of HAE. Three-dimensional (3D) reconstruction allows for accurate measurement of remnant liver volume (RLV). The objective of the study was to evaluate value of triphase contrast-enhanced CT together with 3D reconstruction in preoperative evaluation of indications for ALT in patients with end-stage HAE. This cohort include twenty-one consecutive patients with end-stage HAE, who preoperatively underwent triphase enhanced CT together with 3D reconstruction for ALT. To depict the indications, the 2D image data were reviewed statistically focusing on porta hepatis invasion, retrohepatic vena cava (RHVC) involvement and degrees of intrahepatic vessel invasion, and the 3D reconstruction was performed to obtain ratio of RLV to standard liver volume (SLV). The results showed that 95.24% patients (20/21) had porta hepatis invasion. When lesions located in right liver lobe, porta hepatis invasion occurred most commonly in the second and third porta hepatis (7/10), whereas the first, second and third porta hepatis were most commonly invaded by lesions in the right and caudate / left medial liver lobes (7/11) (P < 0.05). The mean value of longitudinal invasion of RHVC was 8.0 cm, and 95.2% (20/21) of patients had RHVC invasion with ≥ 180° circumferential invasion. As for the important vascular events, moderate and severe invasion occurred most commonly in the right hepatic vein, right branch of portal vein and RHVC each in 95.2% (20/21) patients (P < 0.05). We also found that preoperative CT had a good agreement with intraoperative findings in assessing intrahepatic vascular involvement by HAE (kappa index = 0.77). The estimated average ratio of RLV to SLV was 0.95 (range, 0.43-1.62). In conclusion, the 2D contrast-enhanced CT could well depict anatomic location and size of HAE, and invasion of porta hepatis and vascular by this disease, and involvement of other adjacent organs and tissues. Above all, 3D reconstruction could accurately measure RLV in patients with end-stage HAE for ALT., (© 2021. The Author(s).)

Kidney transplantation with grafts procured after donation-after-cardiac death (DCD) has led to an increase in incidence of delayed graft function (DGF). It is thought that the warm ischemic (WI) insult encountered during DCD procurement is the cause of this finding, although few studies have been designed to definitely demonstrate this causation in a transplantation setting. Here, we use a large animal renal transplantation model to study the effects of prolonged WI during procurement on post-transplantation renal function. Kidneys from 30 kg-Yorkshire pigs were procured following increasing WI times of 0 min (Heart-Beating Donor), 30 min, 60 min, 90 min, and 120 min (n = 3-6 per group) to mimic DCD. Following 8 h of static cold storage and autotransplantation, animals were followed for 7-days. Significant renal dysfunction (SRD), resembling clinical DGF, was defined as the development of oliguria < 500 mL in 24 h from POD3-4 along with POD4 serum potassium > 6.0 mmol/L. Increasing WI times resulted in incremental elevation of post-operative serum creatinine that peaked later. DCD120min grafts had the highest and latest elevation of serum creatinine compared to all groups (POD5: 19.0 ± 1.1 mg/dL, p < 0.05). All surviving animals in this group had POD4 24 h urine output < 500 cc (mean 235 ± 172 mL) and elevated serum potassium (7.2 ± 1.1 mmol/L). Only animals in the DCD120min group fulfilled our criteria of SRD (p = 0.003), and their renal function improved by POD7 with 24 h urine output > 500 mL and POD7 serum potassium < 6.0 mmol/L distinguishing this state from primary non-function. In a transplantation survival model, this work demonstrates that prolonging WI time similar to that which occurs in DCD conditions contributes to the development of SRD that resembles clinical DGF., (© 2021. The Author(s).)

Age affects the clinical outcomes of cancer treatment, including those for bone sarcoma. Successful reconstruction using frozen autograft after excision of bone sarcoma has been reported; however, little is known about the clinical outcomes of frozen autograft reconstruction according to age. The purpose was to evaluate the clinical outcomes of the frozen autograft reconstruction focusing on skeletally mature adolescents and young adults (AYAs) that was 15 to 39 years of age. A total of 37 AYA patients with primary bone sarcoma on the appendicular skeleton were enrolled in this study. The mean follow-up period was 89 months. The graft survival (GS), overall survival (OS), recurrence-free survival (RFS), complications and the function were retrospectively evaluated using medical records. The 10-year GS, OS, and RFS rates were 76%, 84%, and 79%, respectively. Bone union was achieved with a rate of 94% within 1 year after surgery, and nonunion (n = 1) and fracture (n = 2) were infrequently observed. Graft removal was performed in 7 cases, and the most common reason for the removal was infection (n = 5). The Musculoskeletal Tumor Society score was excellent in 23 cases of the available 29 cases. Frozen autograft reconstruction for AYAs showed excellent clinical outcomes, although the long-term follow-up is required., (© 2021. The Author(s).)

Cells/colony motion determined by non-invasive, quantitative measurements using the optical flow (OF) algorithm can indicate the oral keratinocyte proliferative capacity in early-phase primary cultures. This study aimed to determine a threshold for the cells/colony motion index to detect substandard cell populations in a subsequent subculture before manufacturing a tissue-engineered oral mucosa graft and to investigate the correlation with the epithelial regenerative capacity. The distinctive proliferating pattern of first-passage [passage 1 (p1)] cells reveals the motion of p1 cells/colonies, which can be measured in a non-invasive, quantitative manner using OF with fewer full-screen imaging analyses and cell segmentations. Our results demonstrate that the motion index lower than 40 μm/h reflects cellular damages by experimental metabolic challenges although this value shall only apply in case of our culture system. Nonetheless, the motion index can be used as the threshold to determine the quality of cultured cells while it may be affected by any different culture conditions. Because the p1 cells/colony motion index is correlated with epithelial regenerative capacity, it is a reliable index for quality control of oral keratinocytes.

Adipose-derived regenerative cell (ADRC) is a promising alternative source of autologous somatic stem cells for the repair of damaged tissue. This study aimed to assess the safety and feasibility of autologous ADRC implantation for therapeutic angiogenesis in patients with critical limb ischaemia (CLI). A clinical pilot study-Therapeutic Angiogenesis by Cell Transplantation using ADRCs (TACT-ADRC) study-was initiated in Japan. Adipose tissue was obtained by ordinary liposuction method. Isolated ADRCs were injected into the ischaemic limb. We performed TACT-ADRC procedure in five patients with CLI. At 6 months, no adverse events related to the TACT-ADRC were observed. No patients required major limb amputation, and ischaemic ulcers were partly or completely healed during the 6-month follow-up. In all cases, significant clinical improvements were seen in terms of rest pain and 6-min walking distance. Numbers of circulating CD34 + and CD133 + cells markers of progenitor cell persistently increased after ADRC implantation. The ratio of VEGF-A 165 b (an anti-angiogenic isoform of VEGF) to total VEGF-A in plasma significantly decreased after ADRC implantation. In vitro experiments, cultured with ADRC-conditioned media (CM) resulted in increased total VEGF-A and decreased VEGF-A 165 b in C2C12 cells, but not in macrophages. ADRC-CM also increased CD206 + cells expression and decreased TNF-α in macrophages. Autologous ADRC implantation was safe and effective in patients with CLI and could repair damaged tissue via its ability to promote angiogenesis and suppress tissue inflammation.

A retrospective cohort study was conducted in Singapore General Hospital to study the safety and efficacy of biosimilar granulocyte-colony stimulating factor (G-CSF) Nivestim for chemo-mobilization of stem cells for autologous stem cell transplant (autoSCT). All patients who underwent an autoSCT between January 2011 and December 2016 were screened for eligibility. A total of 194 patients were screened, and 131 were included. Nivestim was used in 65 patients and the originator G-CSF (Neupogen) in 66. Patient characteristics were similar between both arms except for chemo-mobilization regimen used (p < 0.0001). Mobilization success rates were found to be comparable, at 96.9% (Nivestim) and 97% (Neupogen). Adverse events rates were also similar. Median duration of G-CSF use and hospitalization were both found to be shorter in the Nivestim arm. Median drug acquisition cost per mobilization cycle was significantly lower in the Nivestim arm at $533.40 (range $213.40-$1280.20) as compared to $1261.90 (range $574-$2755.20) in the Neupogen arm (p < 0.0001). No difference was observed for neutrophil and platelet engraftment after autoSCT. Nivestim was found to be safe and non-inferior to Neupogen for chemo-mobilization of stem cells for autoSCT, and associated with lower cost and shorter length of hospitalization.

Melphalan is given at a dose of 200 mg/m 2 (Mel200) prior to ASCT for multiple myeloma (MM). Pharmacokinetic (PK) studies show a high degree of interpatient variability. We aimed to test the impact of clinical factors previously shown to affect melphalan PK such as hemoglobin (Hgb), fat-free mass (FFM), and creatinine clearance (CrCl) on outcomes. Median Hgb (from day -2 to -1) and FFM were grouped as low or high relative to their sample medians, and CrCl was divided into ≥60 or <60 ml/min. In 133 MM patients, median TFS (defined as time from ASCT to initiation of next subsequent line of therapy or death) was longer in patients with lower Hgb (35 vs. 16 months, p = 0.02). Patients with both lower Hgb and CrCl experienced longer TFS compared to those with higher Hgb and CrCl (35 vs. 13 months, p = 0.03). In multivariate analysis, lower hemoglobin, lower CrCl, and a combined low hemoglobin and CrCl were strongly associated with improved TFS. Patients with a lower hemoglobin or creatinine clearance experienced significantly more toxicity. We show for the first time that Hgb and CrCl are important predictors of outcomes after Mel200. PK-directed melphalan dosing may be beneficial in achieving optimal outcomes.

Autologous hematopoietic cell transplantation (auto-HCT) using melphalan is the standard of care in the management of myeloma. Auto-HCT is a safe procedure with tolerable toxicity except in Asian-Indians. We hypothesized either one or a combination of factors: (1) frailty (assessed by IMWG frailty score), (2) generic melphalan pharmacokinetic area under the curve (AUC) assessed by high-performance liquid chromatography, and (3) pharmacogenetics of glutathione S-transferase (GSTP1) assessed by Sanger sequencing, to be associated with toxicity and survival outcomes post auto-HCT. Disease response was evaluated by IMWG response criteria at day +100 post auto-HCT. Gastrointestinal (GI) toxicity, infections, hospital stay, progression-free survival (PFS) were also recorded. A total of 35 patients were evaluated over 2 years (2016-2018). Frailty, not HCT-comorbidity index correlated with GI toxicity and infections. Overall there was an 11-fold variation in melphalan AUC with a median of 27.88 mg h/L (10.06-110.26). Patients with AUC more than the median had more GI toxicity and infections. Patients with wild-type GSTP1 polymorphism had more GI toxicity and infections. Frailty, AUC, or GSTP1 polymorphism did not impact hospitalization duration or PFS. A combination of the factors frailty, melphalan pharmacokinetics, and pharmacogenetics impacts GI toxicity and infections after auto-HCT in myeloma.

High-dose melphalan (MEL200) followed by autologous stem cell transplantation (ASCT) remains a standard of care for multiple myeloma (MM). Bendamustine induces responses in MM resistant to other alkylators. Our prior Phase I trial adding bendamustine to MEL200 transplant conditioning resulted in no additional toxicity. We now report a single-arm, phase II study that evaluated the efficacy of bendamustine 225 mg/m 2 with MEL200 conditioning for ASCT in 18 patients with newly diagnosed MM (NDMM) and 17 with relapsed or refractory MM (RRMM). The primary end point was the complete response (CR/sCR) rate at day+ 100. Sample size was determined according to Simon's two-stage design. At stage 1, sixteen patients entered the study. As there were eight patients with CR/sCR, enrollment increased to 28 patients. Sixteen out of the first 28 evaluable patients achieved CR/sCR, meeting the design criteria. Enrollment was then expanded to a total of 35 patients. 51% achieved a CR/sCR. After a median follow-up of 65 months, 21 patients progressed, including 7 deaths. The median PFS for NDMM and RRMM was 48 and 45 months, respectively. Bendamustine/MEL200 conditioning resulted in excellent overall and depth of response as well as PFS, particularly in the RRMM patients, and is worthy of further investigation (NCT00916058).

Autologous stem cell transplantation (ASCT) is an integral component of the therapeutic arsenal in multiple myeloma. Given that overall survival (OS) is comparable between patients receiving up-front or delayed ASCT, some opt to collect stem cells and postpone transplant until the time of disease progression (i.e., salvage ASCT). It is unknown if induction should be repeated prior to salvage ASCT, or if patients should proceed directly. We identified 234 patients who underwent salvage ASCT at our institution: 188 (80%) were re-induced, whereas 46 (20%) proceeded directly without re-induction. There was no significant difference in time to next therapy (TNT) or OS from Day 0 between the two groups. Patients who were re-induced had a nonsignificant trend towards a higher rate of complete response post-ASCT (45 vs. 33%, p = .12). In multivariate models, re-induction did not affect TNT/OS. In the subgroup of 188 patients who were re-induced, patients with relapsed/refractory disease at the time of ASCT had significantly shorter TNT/OS compared to patients with deeper pre-ASCT responses. In summary, there was no survival difference for patients who were re-induced before salvage ASCT. However, many factors affect the decision to re-induce, and prospective studies would be required to discern its role definitively.

Clinical trials evaluating the role of autologous hematopoietic stem cell transplantation (auto-HCT) in multiple myeloma have mostly included patients aged <65 years. Therefore, this study was aimed to evaluate the efficacy and safety of auto-HCT in elderly patients with multiple myeloma in the era of novel agents. We retrospectively analyzed 2056 patients with multiple myeloma, who underwent auto-HCT in 2007-2014 (287 were aged ≥65 years). We evaluated the 100-day treatment-related mortality (TRM) and overall survival (OS) in two groups; elderly patients ( ≥65 years) who underwent auto-HCT compared with younger patients ( <65 years). In the propensity score-matched-pair analysis used to adjust for possible selection bias, the incidence of 100-day TRM between patients aged <65 (0.4%; 95% confidence interval [CI]: 0.0-2.0%) and ≥65 years (1.2%; 95% CI: 0.3-3.1%) showed no statistically significant difference (p = 0.31). The probability of the 5-year OS after transplantation in those aged <65 (62.5%; 95% CI: 58.6-66.1%) and ≥65 (63.5%; 95% CI: 52.2-72.7%) years was also not significantly different (p = 0.56). This study showed that the safety and efficacy of auto-HCT in elderly patients with multiple myeloma in the era of novel agents compared with younger patients were similar.

High-dose chemotherapy with autologous hematopoietic stem cell transplantation (autoHSCT) is a well-established treatment for pediatric central nervous system (CNS) tumors. Given the risks of toxicity and infection, pediatric autoHSCT has been historically performed on hospitalized children. As our practice evolved, some patients were transplanted as outpatients. We performed a retrospective cohort analysis of 37 patients who received 90 transplant procedures (49 outpatient and 41 inpatient) at Children's Hospital Colorado. The most common primary diagnosis was medulloblastoma (51.4%). Of the patients transplanted as outpatients, 69.4% were admitted for fever and neutropenia and had a median time to hospitalization of day +6, with fever and neutropenia being the most common reasons for admission. The median time to neutrophil engraftment was the same in both cohorts, 11 days. Median time to platelet engraftment was 13 days (8-82 days) vs 16 days (8-106 days) (p = 0.0008). At day +100, the transplant-related mortality (TRM) was 0% for both the cohorts. At a median follow-up of 1.7 years, overall survival (OS) for all patients was 66.1% and TRM was 0% for both the cohorts. Outpatient autoHSCT for properly selected children with CNS tumors is safe and effective.

High-dose chemotherapy followed by autologous hematopoietic cell transplantation (AHCT) is an effective salvage therapy for patients with relapsed chemosensitive non-Hodgkin's lymphoma (NHL). However, the optimal conditioning regimen is unclear. Different conditioning regimens prior to AHCT have been used with the two most common being BEAM (carmustine, etoposide, cytarabine, and melphalan) and BUCYVP16 (busulfan, cyclophosphamide, and etoposide). We sought to compare the two regimens for patients with relapsed NHL undergoing AHCT. We retrospectively compared the outcomes of patients treated with BEAM (N = 269) at The Ohio State University and BUCYVP16 (N = 409) at the Cleveland Clinic followed by AHCT between 2006 and 2014. The primary endpoints were progression-free survival (PFS), overall survival (OS), and cumulative incidence of relapse (CIR). Patient characteristics between the two groups were similar. After a median follow-up of 3.9 years for BEAM and 4.3 years for BUCYVP16 from AHCT, the rate of relapse (p = 0.69), PFS (p = 0.52), and OS (p = 0.11) were similar between the two conditioning regimens. No differences in survival outcomes were seen in disease subtypes. Multivariable analysis showed significant association toward improved OS with BEAM (HR: 1.56, 95% CI 1.16-2.10) (p < 0.01). Even though the study is limited by its retrospective nature and some differences in cohort, the findings indicate that BEAM could serve as an alternative conditioning regimen prior to AHCT for NHL.

The present study aimed at describing the outcome of patients with HIV-associated lymphomas following autologous hematopoietic stem cell transplantation (autoHCT) in the rituximab and combined antiretroviral therapy (cART) era. Eligible for this retrospective study were HIV-positive patients with lymphoma who received autoHCT between 2007 and 2013. A total of 118 patients were included with a median age of 45 years (range 24-66). Underlying diagnoses were diffuse large B cell lymphoma in 47%, Hodgkin lymphoma in 24%, Burkitt lymphoma in 18%, and plasmablastic lymphoma in 7% of patients. Disease status at autoHCT was complete remission in 44%, partial remission (PR) in 38%, and less than PR in 18% of the patients. With a median follow-up of 4 years, 3-year non-relapse mortality, incidence of relapse, progression-free survival (PFS) and overall survival (OS) were 10%, 27%, 63% and 66%, respectively. By multivariate analysis, disease status less than PR but not CD4+ cell count at the time of autoHCT was a significant predictor of unfavorable PFS and OS. In conclusion, in the era of cART and chemoimmunotherapy, the outcome of autoHCT for HIV-related lymphoma is driven by lymphoma-dependent risk factors rather than by characteristics of the HIV infection.

Autologous stem cell transplant (ASCT) has demonstrated to be an effective treatment for patients with light-chain (AL) amyloidosis. However, a high transplant-related mortality (TRM) rate was reported in previous series of patients and questioned the role of transplant in this disease. Recently, experienced groups have shown a significant TRM decrease that has been attributed to an accurate selection of patients. Moreover, application of several supportive measures has decreased toxicity over amyloid-involved organs. We analyzed a series of 66 patients with AL amyloidosis, who underwent ASCT at a single institution and evaluated the impact of these measures beyond patient selection. Four temporary groups were established: group-A (non-selection plus post-transplant G-CSF use) with 29 patients, group-B (selection) with 13, group-C (selection and G-CSF avoidance) with 14, and group-D (selection, G-CSF avoidance and corticosteroid's prophylaxis) with 10. A decreasing TRM was observed over time from group-A (38%), to group-D (0%); p = 0.02. We also observed a progressive increase of three-year OS from 62% in group-A to 100% in group-D; p = 0.049. On the multivariate analysis, cardiac involvement was the only independent predictor of survival. Therefore, tailored selection policy together with transplant supportive measures have allowed ASCT to be a safe procedure in AL amyloidosis.

High-dose melphalan is the standard conditioning regimen for patients with AL amyloidosis receiving autologous stem cell transplantation. Conventional formulations require propylene glycol (PG) as a co-solvent and melphalan has limited solubility and chemical stability after reconstitution, with potential risks for propylene glycol-related complications. Captisol-stabilized propylene glycol-free (PG-free) melphalan has been developed with improved solubility and chemical stability. We compared a cohort of patients with AL amyloidosis receiving PG melphalan (n = 96) to those receiving PG-free melphalan (n = 48) as conditioning for autologous stem cell transplantation. Median time to neutrophil and platelet engraftment was the same; 14 days PG melphalan vs 14 days PG-free melphalan, p = 0.73 and 16 days PG melphalan vs 16 days PG-free melphalan, p = 0.52, respectively. Hospitalization rate was similar in both cohorts, 68% PG melphalan vs 58% PG-free melphalan, p = 0.27. All-cause mortality at 100 days was not statistically significant, 3% PG melphalan vs 2% PG-free melphalan, p > 0.99. Overall response rate (ORR) and rates of complete response (CR) were similar (ORR 93% PG melphalan vs 94% PG-free melphalan, p > 0.99 and CR 39% PG melphalan vs 32% PG-free melphalan, p = 0.46). PG-free melphalan showed a comparable safety and efficacy profile to PG melphalan in patients with AL amyloidosis receiving stem cell transplantation.

High-dose chemotherapy and autologous hematopoietic cell transplantation (HDT-AHCT) remains an effective therapy in lymphoma. Over the past several decades, HDT with BEAM (carmustine, etoposide, cytarabine, and melphalan) and CBV (cyclophosphamide, carmustine, and etoposide) have been the most frequently used preparatory regimens for AHCT in Hodgkin (HL) and non-Hodgkin lymphoma (NHL). This article reviews alternative combination conditioning regimens, as well as novel transplant strategies that have been developed, to reduce transplant-related toxicity while maintaining or improving efficacy. These data demonstrate that incorporation of maintenance therapy posttransplant might be the best way to improve outcomes.

Cranial nerve injury is disabling for patients, and facial nerve injury is particularly debilitating due to combined functional impairment and disfigurement. The most widely accepted approaches for reconstructing nerve gap injuries involve using sensory nerve grafts to bridge the nerve defect. Prior work on preferential motor reinnervation suggests, however, that motor pathways may preferentially support motoneuron regeneration after nerve injury. The effect of motor versus sensory nerve grafting after facial nerve injury has not been previously investigated. Insights into outcomes of motor versus sensory grafting may improve understanding and clinical treatment of facial nerve paralysis, mitigating facial asymmetry, aberrant reinnervation, and synkinesis. This study examined motor versus sensory grafting of the facial nerve to investigate effect of pathway on regeneration across a 5-mm rodent facial nerve defect. We enrolled 18 rats in 3 cohorts (motor, sensory, and defect) and recorded outcome measures including fiber count/nerve density, muscle endplate reinnervation, compound muscle action potential, and functional whisker twitch analysis. Outcomes were similar for motor versus sensory groups, suggesting similar ability of sensory and motor grafts to support regeneration in a clinically relevant model of facial nerve injury.

Currently, uterus transplantation (UTx) is a clinical option for infertile women. Over the past three decades, treating benign or malignant gynecological diseases with minimally invasive gynecological surgery has improved, providing significant advantages over conventional open surgery. This study addresses the method used for laparoscopic live-donor ovariohysterectomy and graft harvest from a sheep model. Using a microsurgical practice, ten grafts were autotransplanted after uterine perfusion. End-to-end anastomosis techniques were used to approximate veins and arteries. Follow-ups were carried out 2-months after surgery and postoperative studies included ultrasound scan, diagnostic hysteroscopy, vascular angiography, and exploratory laparoscopy. All transplants were completed without complications. After vascular anastomosis, total reperfusion of the tissue was accomplished in all animals without confirmation of arterial or venous thrombosis. Angiographic explorations did not show any statistically significant dissimilarity in the arterial diameters between the different examination times. 3-months after uterine transplantation all animals underwent assisted reproduction techniques. Patent uterine arteries were observed 4, 8 and 12 months after the transplant. 6-months after transplantation, six sheep (60%) became pregnant with assisted reproduction practices. We noticed an increase in the degree of fibrosis of the cervix samples in non-pregnant animals of the transplant group. Laparoscopic surgery can be an advantageous approach for the uterus retrieval procedure during uterine transplantation. However, larger sample sized reports are needed in order to accomplish validation, standardization and wider use of this route.

Autologous stem cell transplantation (ASCT) remains a mainstay in the treatment of multiple myeloma (MM). While the procedure is generally safe, toxicities associated with high-dose melphalan conditioning are common and significantly affect patient quality of life. Recently, a propylene glycol-free melphalan formulation (PG-free MEL; Evomela®) was approved by the United States Food and Drug Administration as an ASCT-conditioning regimen for MM. PG-free MEL is more soluble and stable than propylene glycol-solubilized melphalan (PG-solubilized MEL; Alkeran®). As such, there is speculation that it could decrease toxicities and increase the efficacy of ASCT. We compared the outcomes of patients conditioned with PG-free MEL (n = 216) to PG-solubilized MEL (n = 200) at our institution. The baseline characteristics were similar between the two groups. After Day +0, there were no differences in terms of hospitalizations, neutropenic fevers, intravenous granisetron requirement, World Health Organization grade ≥ 2 oral/esophageal mucositis, intravenous fluid requirement, or narcotic requirement. However, PG-free MEL patients had a higher incidence of diarrhea, which was mostly C. difficile-negative (82% vs. 71%, P = 0.015*). Day + 100 hematologic responses and progression-free survival after ASCT were comparable. In summary, we demonstrate that switching to PG-free MEL did not significantly reduce short-term complications of ASCT or improve outcomes in MM.

Autologous stem cell transplantation (PBSCT) is standard for young patients in MM and its TRM has decreased after the 2000s. Bortezomib and immunomodulatory agents (IMiDs) in MM have improved the outcome. However, they seem to boost pro-inflammatory stage increasing the incidence of engraftment syndrome (ES). Favorable factors in PBSCT such as G-CSF could increase inflammatory stage during transplant. Corticosteroids have shown an excellent response of ES and some authors propose them as prophylaxis for ES. The aim was to analyze the impact of G-CSF avoidance and corticosteroids' prophylaxis in 170 patients diagnosed of MM treated with bortezomib/IMiDs that underwent PBSCT. We established three groups: Group-I [(G-CSF&#95;administration), 60 patients (35%)], group-II [(nonG-CSF), 60 patients (35%)] and group-III [(nonG-CSF plus corticosteroid's prophylaxis), 50 patients (30%)]. A decreased ES incidence among groups was observed: 62, 42, and 22% (P < 0.0001). The incidence of symptoms mimicking a capillary leak syndrome associated with ES dropped: 43, 32, and 0% (P = 0.03). The G-CSF avoidance and corticosteroids had impact over admission 24, 21, and 20 days (P = 0.001). The most important variables related to ES were HCT-CI >2 (p < 0.0001; HR 8.5) and risk groups (p < 0.0001; HR 7.2). Hence, G-CSF avoidance and corticosteroid's prophylaxis decrease morbidity in patients undergoing PBSCT with MM treated with bortezomib/IMiDs.

A recent shortage of melphalan has prompted the use of alternatives to BEAM (BCNU, Etoposide, Cytarabine, Melphalan) conditioning for autologous stem cell transplantion (ASCT). The BEAC (BCNU, Etoposide, Cytarabine, Cyclophosphamide) regimen has been employed as a conditioning regimen in lymphoma patients. However, there have been recent concerns about the toxicity of BEAC. We conducted a retrospective analysis of the EBMT database comparing the outcome of patients conditioned using BEAC with a matched cohort of patients conditioned with BEAM. In the BEAC cohort (n = 383), 25 patients died from non-relapse mortality (NRM) events (32% owing to MOF or cardiac toxicity). In the BEAM cohort (n = 766) there were 34 NRM events (23% owing to MOF or cardiac toxicity). The 1-year cumulative incidence of NRM was 4% in the BEAC cohort and 3% in the BEAM group (p = ns). The 2-year relapse/progression rate was 32% with BEAC and 33% with BEAM (p = ns). At 2 years the progression-free survival (PFS) and overall survival (OS) were 63% and 78% for BEAC and 63% and 77% for BEAM-conditioned patients (p = ns for PFS and OS). The toxicity observed with BEAC conditioning as measured by NRM was similar to that seen with BEAM. The outcomes following BEAC were similar to those seen with BEAM, suggesting that BEAC is a safe conditioning regimen.

Tandem autologous transplants are generally the preferred therapy for newly diagnosed intermediate- and high-risk myeloma patients. More Jehovah's Witnesses (JW) are receiving single autologous peripheral blood stem cell transplants (PBSCTs). However, tandem autologous transplants have not been reported in JW patients. We performed a retrospective study of 54 patients, including four JW patients who received tandem autologous transplants between August 2000 and January 2017 and the last 50 consecutive tandem autologous transplants performed between August 2014 and August 2016. The bleeding complications, number, and cost of transfusions of blood products were compared. The median number of CD34 cells infused in non-JW patients was 8.16 million cells/kg versus 9.44 million cells/kg in JW patients. During the first 30 days, one JW experienced Grade III pulmonary hemorrhage, while none of the non-JW patients had a Grade III or higher bleeding problem. After tandem autologous transplants, complete remission was achieved in 88% of non-JW, compared with 75% in JW patients. In the first 30 days post-transplant, median platelet and packed red blood cell (PRBC) transfusions in non-JW patients was 2 (range: 0-40) and 1 (range: 0-11), respectively. Total cost of PRBC and platelet transfusions for the 50 non-JW was $214,664 (average $2147/transplant). Tandem autologous transplants can thus be performed safely without a single blood transfusion.

Autologous stem cell transplantation (auto-HSCT) is an effective treatment strategy for hematological malignancies. The standard mode of handling hematopoietic progenitors for the autologous procedure (CRYO) consists on its collection and freezing with dimethyl sulfoxide (DMSO) and its subsequent thawing and re-infusion. This process is toxic and expensive. Non-cryopreserved (non-CRYO) is a less expensive mode of auto-HSCT. We designed a comparative study between both strategies performed in two different centers to analyze the short-term complications. In total 111 auto-HSCT were performed from January/2015 to October/2016 (42 non-CRYO and 74 CRYO). There were 74 males and 69 (62%) patients had the underlying diagnosis of multiple myeloma. No differences were seen on the characteristics of the apheresis products and their viability. Engraftment was significantly faster in the non-CRYO group (p = 0.001). Febrile neutropenia and severe mucositis were lower in the non-CRYO group (40% vs 92% p = 0.0001 and 11% vs 64%, p = 0.001, respectively). In addition, length of hospitalization was 5 days shorter in the non-CRYO group (p = 0.0001). Overall responses and transplantation outcomes were similar. Our data demonstrate a clear advantage of the non-CRYO over CRYO auto-HSCT with faster engraftment, lower incidence of febrile neutropenia and shorter hospital stay after the transplantation procedure. These data are especially relevant for centers with high transplant activity or with limited resources.

The purpose of this retrospective registry study was to investigate the outcome of autoSCT for primary mediastinal B-cell lymphoma (PMBCL) in the rituximab era, including the effects of eventual post-transplant radiotherapy (RT) consolidation. Patients with PMBCL aged between 18 and 70 years who were treated with a first autoSCT between 2000 and 2012 and registered with the EBMT were eligible. Eighty-six patients with confirmed PMBCL and the full data set required for this analysis were evaluable. Sixteen patients underwent autoSCT in remission after first-line therapy (CR/PR1), 44 patients were transplanted with chemosensitive relapsed or primary refractory disease (CR/PR >1), and 24 patients were chemorefractory at the time of autoSCT. With a median follow-up of 5 years, 3-year estimates of relapse incidence, progression-free survival, and overall survival were 6%, 94%, and 100% for CR/PR1; 31%, 64%, and 85% for CR/PR >1; and 52%, 39%, and 41% for REF, respectively. Whilst there was no significant benefit of post-transplant RT in the CR/PR >1 group, RT could completely prevent disease recurrence post d100 in the refractory group. In conclusion, autoSCT with or without consolidating RT is associated with excellent outcome in chemoimmunotherapy-sensitive PMBCL, whereas its benefits seem to be limited in chemoimmunotherapy-refractory disease.