Allogeneic hematopoietic stem cell transplantation (HSCT) with reduced intensity conditioning (RIC) offers a curative option for patients with hematologic malignancies who are unable to undergo ...myeloablative conditioning, but its success is limited by high rates of relapse. Several studies have suggested a role for T-cell doses in peripheral blood stem-cell grafts in RIC HSCT. Since T-cell dose is typically not known until after the collection, and apheresis blood volume is easily modifiable, we hypothesized that higher donor apheresis blood volumes would improve transplant outcomes through an effect on graft composition. We therefore analyzed the relationships between apheresis volume, graft composition and transplant outcomes in 142 consecutive patients undergoing unrelated donor allogeneic RIC HSCT.
We found that apheresis volume 15L or greater was associated with a significantly decreased risk of relapse (adjusted hazard ratio (aHR) 0.48, 95% CI 0.28–0.84), p=0.01) and improved relapse-free survival (aHR 0.56, 95% CI 0.35–0.89, p=0.02) and overall survival (aHR 0.55, 95% CI 0.34–0.91, p=0.02). A high apheresis volume was not associated with increased rates of acute or chronic GVHD. These results demonstrate that an apheresis volume of at least 15L is independently predictive of improved transplant outcomes after RIC allogeneic HSCT.
On August 30, 2017 the US Food and Drug Administration approved tisagenlecleucel (Kymriah; Novartis, Basel, Switzerland), a synthetic bioimmune product of anti-CD19 chimeric antigen receptor T cells ...(CAR-T), for the treatment of children and young adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL). With this new era of personalized cancer immunotherapy, multiple challenges are present, ranging from implementation of a CAR-T program to safe delivery of the drug, long-term toxicity monitoring, and disease assessments. To address these issues experts representing the American Society for Blood and Marrow Transplant, the European Society for Blood and Marrow Transplantation, the International Society of Cell and Gene Therapy, and the Foundation for the Accreditation of Cellular Therapy formed a global CAR-T task force to identify and address key questions pertinent for hematologists and transplant physicians regarding the clinical use of anti CD19 CAR-T therapy in patients with B-ALL. This article presents an initial roadmap for navigating common clinical practice scenarios that will become more prevalent now that the first commercially available CAR-T product for B-ALL has been approved.
Abstract Allogeneic stem cell transplantation (ASCT) is a complex medical procedure for some patients with hematologic malignancies. Most ASCTs occur at academic centers where either medical ...residents (house staff HS) or advanced practice providers (APPs) provide daily care. As a result of increasing work-hour regulations, APPs have assumed greater responsibilities, including those traditionally held by HS. In this study we evaluate ASCT patient outcomes by inpatient provider service. A retrospective, single-center chart review of ASCT patients was performed. ASCT patients admitted to an HS service from May 2011 to May 2012 (N = 86) were compared with ASCT patients admitted to a newly formed APP service from October 2012 to October 2013 (N = 81). As part of a secondary sensitivity analysis, we compared ASCT patients on the APP service to a subset of ASCT patients admitted to the HS service also from October 2012 to October 2013 (n = 27). Our primary outcomes were 100-day survival and relapse-free survival rates. Additional outcomes included length of stay (LOS), inpatient complications, and ordering behavior. Our primary pre- and post-analyses found no differences in 100-day overall survival and 100-day relapse-free survival rate between the services. The rate of pneumonia was lower on the APP service (15% versus 28%, P = .04), with no significant differences in other infectious complications. HS ordered more blood cultures (6.7 versus 4.2, P = .03) per patient than the APP service. There was no difference in LOS, readmission rates, or inpatient mortality. With regards to our secondary sensitivity analysis, no differences were found in 100-day overall survival and 100-day relapse-free survival rates between the services. There was a decreased LOS on the APP service (29.4 versus 37.2 days, P = .01). HS ordered more blood cultures (9.3 versus 4.2, P < .01) and more radiological films (8.1 versus 5.2, P = .05) per patient than the APP service. This increased ordering and LOS was associated with an increase in mean hospital charges on the HS service ( P = .04). ASCT patients on an APP service had similar 100-day outcomes as those on the HS service. In the setting of limited resources, APPs are potential alternative providers for complex transplant inpatients.
Abstract We evaluated effects of graft transport time on outcomes after transplantation of 938 unrelated donor bone marrow (BM) or 507 peripheral blood progenitor cells (PBPC) in patients with acute ...or chronic leukemia and myelodysplastic syndrome (MDS). BM grafts were collected at 107 centers and PBPC, 89 centers. Median time from end of collection to infusion was 14 hours for BM and 15 hours for PBPC. Platelet recovery was less likely in BM recipients when the interval from end of collection to receipt at transplant center was ≥20 hours (odds ratio 0.47, P = .010) and when the interval from receipt to infusion was ≥6 hours (odds ratio 0.57, P = .001). Mortality rates were higher in recipients of HLA-matched BM when the interval from end of collection to receipt at transplant center was ≥20 hours (relative risk 2.67, P < .001) after adjustment for other significant prognostic factors. Mortality after HLA-mismatched BM transplants was not associated with transport time. Transport times had no demonstrable effect on outcomes after PBPC transplants. These data support a general review of current transport procedures, especially for BM grafts requiring longer transport time and every effort made to minimize time from collection to infusion.
Donor stem cells for allogeneic transplant are traditionally collected and transfused “fresh” into the recipient on the day of transplant. Alternatively, donor stem cells can be collected in advance ...and cryopreserved until needed. Due to historical momentum and concerns that the cryopreservation and thawing process may damage the graft and worsen clinical outcomes, most institutions favor the former approach. The use of cryopreserved grafts has, therefore, traditionally been reserved for extreme circumstances of questionable donor reliability or availability. This trend is, however, slowly changing as some individual centers are favoring the use of frozen grafts in their related donor transplants due to increased ease of transplant coordination. Similarly, The National Marrow Donor Program (NMDP), which authorizes the collection of all cryopreserved unrelated grafts, has noticed an increasing trend in the use of frozen stem cell products. The total of cryopreserved stem cell grafts, however, still represents less than 2% of all unrelated products (R King; NMDP, personal communication).
In this invited contribution, we discuss technology options for bandwidth-variable transceivers which are key components for the realization of flexible software-defined optical networking. ...Bandwidth-variable transceivers enable the software-controlled adaptation of physical layer parameters such as transmitted bit rate, spectral efficiency and transparent reach according to the traffic demands at hand. In particular, we focus on recent advances in four-dimensional modulation formats and in modulation format transparent data-aided digital signal processing. It is argued that four-dimensional modulation formats present an attractive complement to conventional polarization-multiplexed formats in the context of bandwidth-variable transceivers, where they enable a smooth transition with respect to spectral efficiency while requiring marginal additional hardware effort. Results of numerical simulations and experiments supporting this statement are presented. For the cost-efficient hardware implementation of bandwidth-variable transceivers supporting several polarization-multiplexed and four-dimensional modulation formats, digital signal processing algorithms are required which operate format transparent and consume little hardware resources. We discuss data-aided signal processing as one possible option, in particular with respect to carrier frequency recovery and channel estimation in combination with frequency domain equalization.
Background:
The injection of mesenchymal stem cells (MSCs) mitigates fat accumulation in released rotator cuff muscle after tendon repair in rodents.
Purpose:
To investigate whether the injection of ...autologous MSCs halts muscle-to-fat conversion after tendon repair in a large animal model for rotator cuff tendon release via regional effects on extracellular fat tissue and muscle fiber regeneration.
Study Design:
Controlled laboratory study.
Methods:
Infraspinatus (ISP) muscles of the right shoulder of Swiss Alpine sheep (n = 14) were released by osteotomy and reattached 16 weeks later without (group T; n = 6) or with (group T-MSC; n = 8) electropulse-assisted injection of 0.9 Mio fluorescently labeled MSCs as microtissues with media in demarcated regions; animals were allowed 6 weeks of recovery. ISP volume and composition were documented with computed tomography and magnetic resonance imaging. Area percentages of muscle fiber types, fat, extracellular ground substance, and fluorescence-positive tissue; mean cross-sectional area (MCSA) of muscle fibers; and expression of myogenic (myogenin), regeneration (tenascin-C), and adipogenic markers (peroxisome proliferator-activated receptor gamma PPARG2) were quantified in injected and noninjected regions after recovery.
Results:
At 16 weeks after tendon release, the ISP volume was reduced and the fat fraction of ISP muscle was increased in group T (137 vs 185 mL; 49% vs 7%) and group T-MSC (130 vs 166 mL; 53% vs 10%). In group T-MSC versus group T, changes during recovery after tendon reattachment were abrogated for fat-free mass (–5% vs –29%, respectively; P = .018) and fat fraction (+1% vs +24%, respectively; P = .009%). The area percentage of fat was lower (9% vs 20%; P = .018) and the percentage of the extracellular ground substance was higher (26% vs 20%; P = .007) in the noninjected ISP region for group T-MSC versus group T, respectively. Regionally, MCS injection increased tenascin-C levels (+59%) and the water fraction, maintaining the reduced PPARG2 levels but not the 29% increased fiber MCSA, with media injection.
Conclusion:
In a sheep model, injection of autologous MSCs in degenerated rotator cuff muscle halted muscle-to-fat conversion during recovery from tendon repair by preserving fat-free mass in association with extracellular reactions and stopping adjuvant-induced muscle fiber hypertrophy.
Clinical Relevance:
A relatively small dose of MSCs is therapeutically effective to halt fatty atrophy in a large animal model.
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