Cell Transplantation Program Research Articles

Donor-intrinsic variables determine mobilization efficiency: analyses from a cohort of sixty twice-mobilized stem cell donors

BackgroundHealthy volunteer registry donors have become the backbone of stem cell transplantation programs. While most registrants will never become actual donors, a small minority are called upon twice, most commonly for the same patient because of poor graft function. Anecdotal evidence provides no hard reasons to disallow second-time mobilized apheresis, but few centers have treated enough two-time donors for definitive conclusions. Moreover, for reasons unknown, the efficiency of G-CSF varies greatly between donations.MethodsComparison of outcomes of first vs. second donations can formally confirm G-CSF responsiveness as intrinsically, likely genetically, determined. In our database, we identified 60 donors (1.3%) who received two cycles of G-CSF 24 days to 4 years apart and systematically compared mobilization outcomes.ResultsFirst and second mobilization and collection proceeded without severe or unusual adverse effects. First-time mobilization efficiency was highly predictive of second-time mobilization. Neither mobilization efficiency nor time lag between donations affected the similarity of first- and second-time mobilization outcomes.ConclusionsWith the caveat that only donors with an unremarkable first donation were cleared for a second, our data indicate that a second donation is feasible, equally tolerable as a first donation, and efficient. Moreover, the data strongly support the notion of donor-intrinsic variables dictating mobilization response and argue against relevant damage to the stem cell compartment during mobilization with rhG-CSF.

Real World Evaluation of Deviation Outcomes in an Immune Effector Cell Quality Program

Introduction City of Hope (COH) was one of the first institutions to be granted Immune Effector Cell (IEC) Therapy accreditation by the Foundation for the Accreditation of Cellular Therapy, which supports our mission to provide safe, high quality patient care through expanded standardization. As part of the accreditation requirements, COH expanded established processes developed to monitor standard of care (SOC) deviations for the Hematopoietic Cell Transplantation Program to our IEC Clinical Program. As part of process improvement, we monitored our IEC Quality program to determine if there were any outcome changes as a result of deviations. Therefore, we performed a retrospective analysis of electronically submitted SOC deviations for patients treated with commercially available chimeric antigen receptor (CAR) T cell products (tisagenlecleucel or axicabtagene ciloleucel [Axi-cel]) between December 2017- March 2020 at COH. Methods During the reporting timeframe, 122 patients were planned to be treated with an IEC product. We retrieved 28 requests for SOC deviations from our electronic database for 24 of 122 patients. We analyzed for volume, trends and patient outcomes of submitted deviation requests, including trends in type of deviation, transfer to the intensive care unit (ICU), length of inpatient hospital stay and safety outcomes at 30 days post infusion. Patients who did not receive their SOC product for any reason during the reporting timeframe, or were lost to follow-up were excluded from the outcomes analysis. Results Sixteen of 24 patients were planned to be treated with SOC Axi-cel and 8 of 24 patients were planned to be treated with tisagenlecleucel; only 19 of 24 patients (10 women and 9 men) underwent infusion with their respective SOC product, 15 with Axi-cel and 4 with tisagenlecleucel. Five of 24 patients, including 1 Axi-cel and 4 tisagenlecleucel patients were excluded due to change in medical condition or infusion after the reporting timeframe. We identified elevated creatinine levels as the most common reason for SOC deviation requests for patients to be treated with tisagenlecleucel (4 of 8 patients), while deviations relating to rest days between lymphodepletion and CAR T cell infusion were the most common submitted deviations for patients planned to be treated with Axi-cel (9 of 16 patients). We also descriptively compared patients who required SOC deviations to a cohort of patients (n=98) who did not require deviations and were treated with either axicabtagene ciloleucel (n=86) or tisagenlecleucel (n=12) during the same timeframe. Eight of 98 (8%) of patients who did not have requests for SOC deviation were transferred to the ICU compared to 4 of 19 (21%) patients who required SOC deviations. Seventeen of 19 and 94 of 98 patients were discharged. The median length of inpatient hospital stay post infusion for SOC deviations cohorts who were discharged was 16 days (11-40) and 15 days (8-100) for non-SOC deviations patients. When we descriptively compared survival outcomes at 30 days post infusion, we found that all (4 of 4) patients who required SOC deviations and received tisagenlecleucel survived compared to 11 of 12 patients without SOC deviations. For patients who received Axi-cel, 14 of 15 patients with SOC deviations survived at day 30 post infusion compared to 85 of 86 patients without SOC deviations. The response to treatment and toxicities will be reported at the meeting. Conclusion These data suggest that careful selection of patients who may benefit from SOC deviations and still receive their infusion may not negatively affect survival outcomes at 30 days. The SOC deviation review process offers physicians a forum to evaluate non-SOC eligible cases and advise on SOC policy changes. While preliminary, our quality review identifies a role for comprehensive analysis of all IEC SOC deviations as part of standard practice, especially as the field of cellular immunotherapy expands to include more SOC cellular products. Overall, further monitoring of SOC deviations in real world patient populations treated with commercially available IEC products will allow us to continue to support patient safety, assess patient care management practices, expand patient access, meet accreditation standards and monitor SOC practice changes while advancing the field of cellular immunotherapy. Disclosures Shouse: Kite Pharma: Honoraria, Speakers Bureau. Mott:Janssen/Johnson & Johnson: Consultancy; Juno/BMS: Consultancy. Budde:Gilead Sciences: Consultancy; AstraZeneca: Research Funding; Merck: Research Funding; Mustang Therapeutics: Research Funding; Kite, a Gilead Company: Consultancy; Roche: Consultancy; Amgen: Research Funding.

Characteristics of Hepatic Veno-Occlusive Disease from the Cell Therapy Transplant Canada Registry: A Retrospective Observational Study

Introduction:Hepatic venous occlusive disease (VOD) is a well-described early complication of allogeneic hematopoietic stem cell transplant (HSCT). The disease presents with elevated bilirubin, hepatomegaly, right upper quadrant pain, ascites and weight gain. Multi organ failure (MOF) can also occur, mainly renal and pulmonary failure, in severe cases. The incidence, pathogenesis, risk factors, and treatment of VOD remain poorly defined. Purpose:We aimed to determine the incidence of, risk factors, treatment patterns and resource utilization associated with VOD in Canada. Methods:Using the Cell Therapy and Transplant Canada (CTTC) database, which collects data from 15 stem cell transplant programs across Canada, a retrospective observational study was performed. Using patient demographics, disease and transplant characteristics, and the Center for International Blood & Marrow Transplant Research (CIBMTR) Form 2553 which collects information on patients diagnosed with VOD, data was collected. All allogeneic transplants performed on both children and adults between 2013 and 2019 were included in the analysis. Children and adults were analyzed as two separate cohorts. Results:The total incidence of VOD was 64/2507 (2.55%). The incidence of VOD was 27/464 (5.82%) in children and 24/2030 (1.18%) in adults. Risk factors for VOD for children and adults are shown in Tables 1 and 2, respectively. The most common treatments for VOD in children and adults were defibrotide (74.1% and 29.2%, respectively), diuretics (70.4% and 62.5%, respectively) and ursodiol (48.0% and 63.6%, respectively). The mean intensive care unit (ICU) visit duration and hospitalization in children with VOD was 7.0 days and 37.1 days, respectively. The mean ICU visit duration and hospitalization in adults with VOD was 8.2 days and 37.1 days, respectively. There were no differences in overall survival, relapse rates or non-relapse mortality between VOD patients and non-VOD patients in both children and adults. Discussion:Between 2013 and 2019, the incidence of VOD in allogeneic HSCT in Canada was 2.55%. This is consistent with recent reports from other countries including from the CIBMTR and a report from the United States at 3.3% and 5.4%, respectively. An unexpected finding was the difference in incidence between children and adults. Possible explanations for this include younger age being an actual risk factor for VOD, increased clinical vigilance amongst pediatric clinicians, reporting bias, alternative diagnoses because of more hepatic comorbidities in adults or a more obvious clinical presentation of VOD in children. This requires further investigation. Further to this, a higher proportion of children diagnosed with VOD received defibrotide than did adults diagnosed with VOD. It is unclear why this occurred. The significant risk factors identified in our study are similar to previously published risk factors for VOD. Although, comparative data with non-VOD patients was not available in this data set, VOD patients in both the pediatric and adult populations have longer hospitalizations than historical controls which have an average hospitalization of 23.6 days. No survival or relapse differences were found in our data however VOD cases were not divided into VOD and VOD-MOF. VOD-MOF has been associated with significant mortality of >80%. Weaknesses of our study include its retrospective nature, potential for reporting bias, variable reporting quality from multiple centres and lack of uniform diagnostic criteria for VOD. Conclusion:The incidence and risk factors for VOD in 15 Canadian HSCT centres are similar to previous reports from other countries. Children made up a higher proportion of VOD patients and a high proportion of children received defibrotide. Further study of the resource utilization associated with VOD is required. Acknowledgements:Veronique Baribeau and Jean Lachaine of PeriPharm Inc. for data analysis and Jazz Pharmaceuticals for funding, study design, data analysis and editorial contributions. Disclosures Paulson: Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Exploring the caregiver's experience in an innovative homebound hematopoietic stem cell transplantation program.

Home care for hematopoietic stem cell transplants (HSCTs), an alternative to traditional inpatient or outpatient recovery programs, is safe and feasible but may place greater demand on full-time caregivers. The goal of this study was to characterize the experiences of caregivers in a newly piloted homebound HSCT program as a means of identifying unmet needs and ensuring adequate support. A qualitative approach was utilized. Participants created self-recorded video diaries guided by open-ended prompts at designated time points throughout recovery and participated in a single follow-up interview within four weeks post-discharge. Diaries and interviews were transcribed, analyzed, and coded to identify recurrent ideas and themes. Data were collected from 12 caregivers of homebound HSCT patients. Thematic content analysis yielded four themes: facilitators (external support, sense of normalcy, and patient wellness), challenges (difficulties with transplant care instructions, managing the patient's physical and emotional health, and caregiver psychological distress), roles in recovery (caregiving responsibilities), and analysis of homebound experience (positive outcomes and suggestions for improvement). Caregivers perceived the homebound program as offering high-quality medical care in a setting that provided a sense of normalcy, privacy, and greater level of oversight. Unmet needs included lacking preparedness in completing nursing responsibilities and handling caregiver and patient distress. While the homebound program was preferred to routine hospital care, psychotherapeutic support and programming to improve caregiver preparedness in a homebound HSCT recovery program is indicated.

Nutritional support in stem cell transplantation programs: Results from a multicenter survey of nurses on behalf of the Nurses Group and Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation and the Gruppo Italiano Trapianto di Midollo Osseo.

Malnutrition in patients undergoing hematopoietic stem cell transplant (HSCT) can develop rapidly without appropriate nutritional support and affect morbidity and mortality. Guidance to monitor and manage nutrition status is described within the literature; however, whether this is applied in clinical practice is unclear. This paper describes a cross-sectional survey to explore current practice approaches in nutrition support management and adherence to international guidelines. A total of 108 nurses from 108 centers across 16 countries replied to the questionnaire. A significant variation was observed regarding the availability of documents supporting the monitoring and management of nutrition status, application of recommendations, and nutritional practices. The findings revealed that country was the most important factor influencing the differences in practice; however, significant differences were also observed based on patient age group (pediatrics vs. adults), department composition (hematology+HSCT unit vs. HSCT unit alone), and availability of nutrition health care professionals. Behavioral differences regarding nutritional practice approaches could be indicative of differences in knowledge or subject awareness, as well as a reflection of diversity across health care system policies. Guideline dissemination and raising awareness through educational campaigns are suggested approaches to improve health care professionals' knowledge and sensitivity to this important topic.

Overcoming barriers for the establishment of a consolidated hematopoietic cell transplantation program in a developing country.

The first hematopoietic cell transplantation (HCT) in Mexico was performed at our institution; however, outcomes were suboptimal the following years, until 1998, when a consolidated HCT was established. The aim of this study was to describe the barriers and the implemented strategies to establish a successful HCT program at a referral center in Mexico and to analyze the outcomes. Barriers were detected based on the results from 1980 to 1997. For the analysis of outcomes, a retrospective study was performed including consecutive patients undergoing autologous, allogeneic, and haploidentical HCT. From November 1998 to December 2018, 363 HCTs were performed (autologous, 59%) in 323 patients. Overall non-relapse mortality (NRM) in autologous and allogeneic HCT was 2% and 14%, respectively. The 5-year overall survival was 71% and 57% for autologous and allogeneic HCT, respectively. The cost of the medications was one of the main limitations for the patients and was successfully overcome by the creation of the non-governmental organization "Unidos". NRM was diminished after reducing the BuCy2 regimen along with the use of bone marrow. Our results highlight that the implementation of unique strategies at our center, led HCT to represent a financially viable and feasible procedure with optimal results.

Developing and Monitoring a Standard-of-Care Chimeric Antigen Receptor (CAR) T Cell Clinical Quality and Regulatory Program.

As the world of cellular therapy expands to include immune effector cell (IEC) products such as commercial chimeric antigen receptor (CAR) T cells, quality management (QM) professionals are faced with creating either new IEC stand-alone programs or expand existing hematopoietic cell transplantation (HCT) programs to promote patient safety and be aligned with quality, regulatory, and accreditation requirements. The team professionals at City of Hope (COH) recently expanded the quality HCT program to include IEC products and, in doing so, implemented new regulatory infrastructure while maintaining high quality patient care. At COH, we developed the quality structure of our cellular therapy program through collaborations between quality, regulatory, and CAR T patient care committees, which included physicians and nurse coordinators. To ensure the quality of our program, we monitor data collection and reporting, perform quarterly proactive audits of, for example, outcome analysis, and measure selected end-points for benchmarking purposes. QM professionals play a critical role in the monitoring and evaluation processes and provide guidance on how to implement accreditation requirements and what impact the requirements may have on care management. Here we describe the process by which COH expanded our HCT QM program to include IEC therapy. We share examples of how we developed our overall program structure and other key items such as how we addressed patient care management and accreditation to apprise other programs that wish to create and/or expand existing programs.

Impact of intensifying primary antibiotic prophylaxis in at-home autologous stem cell transplantation program for lymphoma patients

Despite the use of fluoroquinolone (FQ) prophylaxis, neutropenic fever (NF) is the most frequent cause of hospital readmission in ambulatory care programs for patients treated with autologous stem cell transplantation (ASCT). We analyzed the impact of intensifying primary prophylaxis with the addition of piperacillin/tazobactam (PT) to FQ. Between January 2002 and August 2018, 154 lymphoma patients conditioned with BEAM were included (40% received ceftriaxone (Ct) plus FQ and 60% PT plus FQ). NF and hospital readmission were required in 84 vs. 41% (p < .0001) and 12 vs. 1% (p = .007) of patients within the Ct and PT groups, respectively. The multivariate analysis showed that PT plus FQ retained its independent protective factor for NF (odds ratio (OR): 0.13; p < .001) and for hospital readmission (OR: 0.07; p = .01). The use of PT and FQ prophylaxis may effectively prevent episodes of NF and hospitalizations in lymphoma patients managed in our at-home ASCT care model.

Carta al editor

As Director of the hematopoietic stem cell transplant program at the Oregon Health and Science University, I am very pleased to congratulate my friend and colleague, Dr Guillermo Ruiz Arguelles for achieving the important milestone in having performed their 1000thhematopoietic stem cell transplant procedure at Clinica Ruiz, in Puebla, Mexico. To be honest, it is not Dr. Ruiz who is to be congratulated, but rather, the entire team and staff of the transplant program and as well, to the patients who have the benefit to be treated at this site. These numbers are milestones, and milestones are important. The milestone may be the first patient ever treated within the transplant program. Another milestone may be performing the first allogeneic transplant procedure in an established autologous transplant center and soon thereafter, the first cord blood or graft engineered allogeneic procedure. What does the milestone of having reached 1000 transplants for patients in need, mean? It indicates that a program is fully established and recognized for the services they provide. No transplant program will reach these milestones, if they are not providing high level service to their patient recipients. More importantly, what I feel that the milestone of 1000 transplant means, is that any patient who crosses the threshold can trust that there lives are in the hands of a very experienced and professional team. It is not just the doctors. It is the laboratory team members who handle the cellular products and the hematopathologists, who review complicated pathology specimens to provide accurate diagnoses. It is the nursing staff who on a daily basis, dedicate their lives to the care of the patient and provide personal support that the patient needs when undergoing aggressive therapies. When you reach 1000 transplants, there is nothing more confidence building to a patient than when a nurse can tell them that what they are going through is expected and that there is light at the end of the tunnel. Of course, there are the physical therapists and the occupational therapists who assist in guiding patients back to their normal life. And of course, there are social workers to address the non-medical issues and often the complex family interplay takes place when the patient needs a transplant procedure. These are the accomplishments and achievements of a program that reached and has performed 1000 transplants. This milestone allows all to pause and reflect on the initiation of a program, the establishment a program, the continual expansion of a program, and to confirm that the program has matured. It also allows one to reflect on its next milestones, t perhaps that of 2000 transplants performed and importantly, to be able to count the number of patients who have benefited and for whom a worse outcome would have been encountered, if you were not there.I applaud my professional colleagues and all of the care providers who assisted in gaining this important milestone. Congratulations to all, and l among others, look forward to following the success of your program at Clinica Ruiz, into the future.

Transformative Leadership: A Model for Building a Comprehensive Cellular Therapy Program Partnership

Transformative Leadership: A Model for Building a Comprehensive Cellular Therapy Program Partnership Introduction The third largest public safety net healthcare system in the United States established an outpatient Hematopoietic Cell Transplantation (HCT) program in 2007. In 2011, the Certificate of Need was obtained from the State of Florida to begin an inpatient (HCT) program. After ten years of low volumes leading to an inability to obtain allogeneic accreditation from the Foundation of Accreditation of Cellular Therapy (FACT), a transformative partnership for HCT was launched, in 2017, with a NCI designated comprehensive cancer center. The overall purpose of the partnership is to emulate the structure and quality of the NCI designated center's program and to increase patient access to HCT and other advanced cellular therapies in South Florida. Methods The HCT physicians and advanced practice providers are employed by the NCI center, but practice at the satellite campus. Essential program team members including the department administrator, HCT coordinators, quality program professionals, pharmacy, nursing and laboratory teams are employed by the public healthcare system. The partnership agreement is focused on quality indicators as the measure of success. A joint governance and a joint clinical operating committee, comprised of senior leadership from both institutions, were established to review metrics and quarterly outcomes, to ensure the partnership is meeting the clinical and operational program goals. Intellectual property including protocols, Standard Operating Procedures (SOP) for transplant, clinical pathways and quality initiatives are provided by the NCI center and adapted to fit the need of the program. The partnership also allows for a collaborative exchange of process improvements and best practices between operational areas including, information technology, managed care, revenue cycle, nursing, pharmacy, and laboratory. Joint educational activities include weekly grand rounds and monthly collaborative teleconferences for nursing, pharmacy, quality and coordination. Shared patient data allows for research activity between the two centers. Outcomes In the two years of partnership, the program has achieved FACT accreditation for autologous and allogeneic transplant. Prior to the partnership, the institution had referred out 149 patients for allogeneic transplant over the course of 10 years. Post-partnership, only three patients required referral for services the institution does not currently provide. Within one year of partnership launch, the program achieved certification as a National Marrow Donor Program Transplant Center and was approved as a center of excellence (COE) with three major managed care networks. Conclusion: Well-designed partnerships can allow for the establishment of accredited transplant and cellular therapy programs.

A reproducible and safe at-home allogeneic haematopoietic cell transplant program: first experience in Central and Southern Europe.

In 2015, we implemented an at-home allogeneic haematopoietic cell transplant (allo-HCT) program. Between 2015 and 2018, 252 patients underwent allo-HCT; 41 patients underwent allo-HCT in the at-home program (46% myeloablative; 63% unrelated donor; 32% posttransplant cyclophosphamide), and these patients were compared with 39 in-patients; safety, capacity to release beds for other programs, and economic efficiency cost were evaluated. We observed a lower incidence of febrile neutropenia in the at-home group compared with that in the in-patient group (32% versus 90%; p < 0.0001), whereas the incidence of aspergillosis was similar among groups (at-home 1% versus in-patient 3%; p = 0.5). The at-home patients showed a lower incidence of 1-year severe graft-versus-host disease (GVHD; 10% versus 29%; p = 0.03). There were no differences in 1-year transplant-related mortality, relapse, or overall survival among groups. The re-admission rate in the at-home group was 7%. The at-home setting was less expensive (9087 €/transplant), and its implementation increased capacity by 10.5 allo-HCTs/year. Moreover, a chimeric antigen receptor T-cell program could be established without increasing beds. Thus, our at-home allo-HCT program may be a safe modality to reduce febrile neutropenia and acute GVHD, resulting in lower re-admission rates.

Swiss Fetal Transplantation Program and Non-enzymatically Isolated Primary Progenitor Cell Types for Regenerative Medicine.

Primary progenitor cell types adequately isolated from fetal tissue samples present considerable therapeutic potential for a wide range of applications within allogeneic musculoskeletal regenerative medicine. Progenitor cells are inherently differentiated and extremely stable in standard bioprocessing conditions and can be culture-expanded to establish extensive and robust cryopreserved cell banks. Stringent processing conditions and exhaustive traceability are prerequisites for establishing a cell source admissible for further cGMP biobanking and clinical-grade production lot manufacture. Transplantation programs are ideal platforms for the establishment of primary progenitor cell sources to be used for manufacture of cell therapies or cell-based products. Well-defined and regulated procurement and processing of fetal biopsies after voluntary pregnancy interruptions ensure traceability and safety of progeny materials and therapeutic products derived therefrom. We describe herein the workflows and specifications devised under the Swiss Fetal Progenitor Cell Transplantation Program in order to traceably isolate primary progenitor cell types in vitro and to constitute Parental Cell Banks fit for subsequent industrial-scale cGMP processing. When properly devised, derived, and maintained, such cell sources established after a single organ donation can furnish sufficient progeny materials for years of development in translational musculoskeletal regenerative medicine.

Autologous stem cell transplant program in 2016-country report from Bangladesh.

We are describing eleven autologous hematopoietic stem cell transplants (ASCT) that were performed in 2016 at three different transplant centers in Bangladesh. Indications for those patients were multiple myeloma (MM) (n=4), diffuse large B cell lymphoma (DLBCL) (n=2), Hodgkin's lymphoma (HD) (n=2), peripheral T cell lymphoma (PTCL) (n=1), acute myeloid leukemia (AML) (n=1), and acute promyelocytic leukemia (APL) (n=1). All autologous stem cell products were cryo-preserved and transfused back to patients freshly thawed at 37℃. All were in second remission (CR2) except for the PTCL patient, who was in first remission (CR1). The bone marrow transplant (BMT) program was first initiated in Bangladesh in March 2014 at the Dhaka Medical College Hospital (DMCH), the country's largest and the leading government-run public hospital, in collaboration with the Massachusetts General Hospital in Boston, USA. Subsequently, two more centers, Apollo Hospitals Dhaka and the Combined Military Hospital (CMH), started transplant programs in 2016. Seven out of eleven ASCT were performed at the DMCH center, with two at Apollo Hospitals and two at CMH Dhaka. The median age for all patients was 39 (range 18-67) and the Male: Female ratio was 9: 2. The average time to neutrophil and platelet engraftment was day 9 (range 8-12) and day 12 (range 9-15), respectively. Major early complications were neutropenic fever, mucositis, and infection. There was no transplant related mortality (TRM) within the first 100 days. Over a median follow up of 2 years, overall survival is 82.0% and progression free survival is 63.6%.

Progenitor Biological Bandages: An Authentic Swiss Tool for Safe Therapeutic Management of Burns, Ulcers, and Donor Site Grafts.

Clinical experience gathered over two decades around therapeutic use of primary human dermal progenitor fibroblasts in burn patient populations has been at the forefront of regenerative medicine in Switzerland. Relative technical simplicity, ease of extensive serial multitiered banking, and high stability are major advantages of such cell types, assorted to ease of safety and traceability demonstration. Stringent optimization of cell source selection and standardization of biobanking protocols enables the safe and efficient harnessing of the considerable allogenic therapeutic potential yielded by primary progenitor cells. Swiss legal and regulatory requirements have led to the procurement of fetal tissues within a devised Fetal Progenitor Cell Transplantation Program in the Lausanne University Hospital. Proprietary nonenzymatic isolation of primary musculoskeletal cell types and subsequent establishment of progeny tiered cell banks under cGMP standards have enabled safe and effective management of acute and chronic cutaneous affections in various patient populations. Direct off-the-freezer seeding of viable dermal progenitor fibroblasts on a CE marked equine collagen scaffold is the current standard for delivery of the therapeutic biological materials to patients suffering from extensive and deep burns. Diversification in the clinical indications and delivery methods for these progenitor cells has produced excellent results for treatment of persistent ulcers, autograft donor site wounds, or chronic cutaneous affections such as eczema. Herein we describe the standard operating procedures for preparation and therapeutic deployment of the progenitor biological bandages within our translational musculoskeletal regenerative medicine program, as they are routinely used as adjuvants in our Burn Center to treat critically ailing patients.

Development of a clinical hematology and stem cell transplantation program to provide state-of-the-art and cost-effective treatment to patients: a successful collaboration between a medical college in India and a leading medical university in the United States

Development of a clinical hematology and stem cell transplantation program to provide state-of-the-art and cost-effective treatment to patients: a successful collaboration between a medical college in India and a leading medical university in the United States

Changing epidemiology of bloodstream infection in a 25-years hematopoietic stem cell transplant program: current challenges and pitfalls on empiric antibiotic treatment impacting outcomes.

We aimed to describe epidemiology changes in bloodstream infections (BSI) episodes in hematopoietic stem cell transplant (HSCT) recipients throughout a 25-year period (1993-2017), comparing five-year time spans, and we evaluate their impact on inappropriate empirical antibiotic treatment (IEAT) and mortality. During the study period, 1164 BSI episodes were documented in patients undergoing HSCT (71.6% allogenic and 29% autologous). A significant decrease in gram-positive cocci (GPC) and increase in gram-negative bacilli (GNB) were observed (p < 0.001). Among GP, coagulase-negative staphylococci (CoNS) significantly decreased whereas rising E. faecium BSI was documented. Among GNB, E. coli, Pseudomonas aeruginosa and K. pneumoniae rates increased. Multidrug-resistant (MDR) GNB, especially ESBL-E. coli and MDR-P. aeruginosa, emerged in 2008 and has gradually increased. IEAT against MDR-P. aeruginosa, but not in other MDR-GNB, augmented throughout the study period. Overall, 30-day and related mortality rates were 12.7% and 7.7% respectively, both increasing over time (p < 0.001 and p = 0.025). In GNB, 30-day and related mortality were 18.5% and 12.8%, respectively, increasing over time (p < 0.001 and p = 0.004). To conclude, important BSI epidemiological changes were described in a 25-year period. Concerning increase in IEAT for P. aeruginosa infections and rising 30-day mortality rate were documented.

The deduced probable HLA-C*03:187-associated human leukocyte antigen haplotype (A*24:02-B*35:01-C*03:187-DRB1*11:01) revealed in Taiwanese unrelated hematopoietic bone marrow stem cell donors.

Objective:HLA-C*03:187 is a rare frequency allele in the human leukocyte antigen (HLA)-C locus. The purpose of this investigation is to indicate the ethnicity of C*03:187 and its deduced plausible HLA haplotype in association in Taiwanese unrelated bone marrow stem cell donors.Materials and Methods:A DNA sequence-based typing procedure was used to verify the rare frequency allele C*03:187. Employing group-specific primer sets’ polymerase chain reaction was carried out to amplify exons 2 and 3 of HLA-A locus, HLA-B locus, exon 1 to exon 7 of the HLA-C locus, and exon 2 of the HLA-DRB1 locus. The amplified gene products were sequenced employing the BigDye® Terminator Cycle Sequencing Ready Reaction kits in both directions according to the manufacturer's instructions.Results:The DNA sequence of C*03:187 is identical to C*03:03:01:01 from exon 1 to exon 7, except for codon 152 of exon 3 where GAG of C*03:03:01:01 is replaced by GTG in C*03:187. The nucleotide replacement causes one amino acid change to the protein sequence of C*03:03:01:01 at position 152 where glutamic acid (E) is changed to a valine (V) in C*03:187. The deduced plausible HLA haplotype in association with C*03:187 in Taiwanese is as A*24:02-B*35:01-C*03:187-DRB1*11:01.Conclusion:The data on the deduced plausible HLA haplotype in association with the low-frequency C*03:187 allele that we described in this report are valuable for immunogenetics laboratories for reference purposes. In addition, they can be utilized by search coordinators in hematopoietic stem cell transplant programs to determine a strategy for locating compatible donors in unrelated bone marrow donor registries for a patient with this unusual HLA allele.

Basis of CD7 molecule and its research progress on immunotherapy in hematologic malignant diseases

CD7 molecule is a 40 kDa single-chain glycoprotein molecule, belonging to the immunoglobulin superfamily. It is an important surface marker on the human immune cell membrane and plays a role in synergistic stimulation of molecular receptors during lymphocyte development and maturation. As an abnormal marker on the surface of hematological malignant cells, it is highly expressed in acute T-lymphocytic leukemia(T-ALL)and T-cell lymphoma. About 30% of patients with acute myeloid leukemia(AML) have been detected the expression of CD7 antigen in tumor cells. CD7 molecule is thought to be involved with disease invasiveness, drug resistance, and poor prognosis. Potent chemotherapy, immunotherapy, hematopoietic stem cell transplantation(HSCT) and other programs have achieved very significant results in the treatment of hematologic malignant diseases. Despite this, there are still some cases of acquired treatment tolerance during the treatment. Molecular targeted therapy provides a safe, effective, and specific therapy regimen that has received increasing attention in recent years. Using of CD7 molecular as a new target for molecular targeted anti-tumor therapy may provide a new therapeutic direction for CD7-positive relapse or refractory hematological malignant diseases. The article intends to review the current progress in the basic and clinical research of CD7 molecules. Key words: Antigens, CD7; Hematologic neoplasms; Immunotherapy; Molecular targeted therapy; Chimeric antigen receptor

Real-world outcomes of unselected elderly acute myeloid leukemia patients referred to a leukemia/hematopoietic cell transplant program.

Due to perceived intolerance, many elderly AML patients do not receive therapy, and few are considered for hematopoietic cell transplantation (HCT). To better understand "real-world" outcomes, 323 consecutive AML patients ≥ 60 years referred from 2009 to 2017 were evaluated (median age 70 [60-88] years); favorable (fav) in 48 (15%), intermediate (int) in 112 (35%) and poor risk in 161 (50%). Remission induction therapy, either intensive chemotherapy (IC, n = 205) or hypomethylating agents (HMA, n = 57), was given to all but 61 (19%) patients. With median f/u of 34 months, 2-year overall survival (OS) for the whole cohort was 31%; 40 and 33% for IC- and HMA-treated vs. 0% for untreated patients. Early mortality was 14%. Remission (CR/CRi) was achieved in 60% of patients, with approximately half of these surviving 2 years. In transplant-eligible patients (60-75-year-old, int/poor risk, achieving remission), 54 (46%) of 118 received HCT. Transplanted patients had improved 2- and 3-year post-remission survival of 59% and 40% compared to 26% and 18% in similar patients not receiving HCT (HR = 0.59, 95% CI 0.37-0.93, p = 0.023). These results suggest that survival of elderly AML patients may be improved through a coordinated approach of remission induction therapy for most patients followed by HCT when feasible.

Editorial introductions

Current Opinion in Gastroenterology was launched in 1985. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of gastroenterology is divided into 12 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce one of the Section Editors for this issue. SECTION EDITORS Anthony N. KallooAnthony N. KallooDr Anthony N. Kalloo is a Professor of Medicine at Johns Hopkins University, Baltimore, USA. He is the Director of The Division of Gastroenterology and Hepatology at Johns Hopkins Hospital. He has special interests in Natural Orifice Surgery, therapeutic endoscopy, biliary and pancreatic diseases and sphincter of Oddi dysfunction. After receiving his medical degree from the University of West Indies Medical School, West Indies, Dr Kalloo interned and completed his residency in Internal medicine at Howard University Hospital in Washington, DC, USA. He completed his fellowship training program at the combined Georgetown University, USA, VA Medical Center, USA and NIH program. He was an Instructor in Medicine at Georgetown University prior to joining the faculty at Johns Hopkins in 1988. He was an Associate Editor of Gastrointestinal Endoscopy. He is the founder and immediate past medical director of The Hopkins Gastroenterology and Hepatology Resource Center, a 3000 page multilingual web resource for patients and physicians. He has authored over 200 scientific papers, articles, reviews and book chapters. He has also pioneered and has multiple patents including the use of Botulinum Toxin in the gastrointestinal tract, endoscopic cryotherapy and the winged biliary/pancreatic stent. He is the pioneer of Natural Orifice Translumenal Endoscopic Surgery (NOTES), a technique that will enable abdominal surgery without the use of incisions. NOTES was cited in 2014 as one of CNN's top ten medical innovations. Dr Kalloo is a Past Panel Chair for Gastroenterology and Urology Devices with the United States Food and Drug Administration. He is the recipient of the 2009 Distinguished Educator of the Year of the Award from the American Society for Gastrointestinal Endoscopy. In 2014, he received the Endoscopy Award of the German Society of Endoscopy for outstanding research and contribution in the field of endoscopy. He also received the BJ Vakil Oration from The Society of GI Endoscopy of India bestowed on an international expert for his contribution to the field of GI Endoscopy, in the year 2015. In the same year, he also became a member of the inaugural chapter of the National Academy of Inventors at Johns Hopkins University. This group represents the top 3% of all Faculty inventors since 1969, and the top 1.5% of active Johns Hopkins Faculty. Timothy B. GardnerTimothy B. GardnerDr Timothy B. Gardner grew up in Newtown, Connecticut and graduated in 1995 with a BA in History from Dartmouth College, New Hampshire, USA. He received his MD degree from the University of Connecticut, USA. He completed his internal medicine residency, chief residency and Gastroenterology fellowship at Dartmouth-Hitchcock Medical Center, USA. He received advanced training in Clinical Pancreatology and advanced endoscopy at Mayo Clinic in Rochester. In 2013, he received a Master's degree in Clinical and Translational Research from the Dartmouth Institute. He is currently an associate professor of medicine at the Geisel School of Medicine at Dartmouth. He is also the director of pancreatic disorders, director of the Gastroenterology and Hepatology fellowship program, co-director of the advanced therapeutic endoscopy fellowship and medical director of the islet cell transplant program at Dartmouth-Hitchcock Medical Center. His primary focus of research is the treatment of acute and chronic pancreatitis. He is an associate editor of the American Journal of Gastroenterology and serves on the editorial boards of Gastroenterology, Gastrointestinal Endoscopy, and the Journal of Clinical Gastroenterology.