Hematopoietic Stem Cell Transplantation Program Research Articles

The Map of BMT in Brazil

Brazil has a vast Hematopoietic Stem Cell Transplantation (HSCT) program with 126 teams and 86 Centers recognized by the Ministry of Health. Outcomes of these transplants are unknown. The objective of this work is to create a public database to help the public and health care professionals to find information on allogenic HSCT performed in Brazil. Methods: The team chose indicators, outcomes, and developed tools to accept secure data input using e-DBtC, Access, RedCap and excel spreadsheet. All data was inserted into the Virtual Analytics platform after careful validation and then presented as tables and graphics in separate portals for healthcare professionals and general public. Results: 29 HSCT centers participating in the project sent data on all consecutive allogeneic transplants performed between August 2019-2020. We gathered data from 943 transplants, with results arranged in graphs and tables, with the possibility of using various filters, so users can customize their search. In conclusion, more than 60% of all allogenic transplants performed in the country are now included in the Map of BMT, in an easy and accessible way to be searched. We hope to continue this initiative and extend it to other services, emphasizing great accomplishment of the Brazilian transplant community.

Some clinical lessons from one Blood and Marrow Transplantation Unit in Medellin, Colombia

After more than 60 years of the first successful bone marrow transplant (BMT) by D.E. Thomas for the treatment of hematological malignant diseases and more than 46 years since the first bone marrow transplant by Alberto Restrepo-Mesa in Medellin-Colombia for the treatment of a female triplet patient with paroxysmal nocturnal hemoglobinuria and aplastic anemia, in Colombia only around 750 bone marrow transplants are performed annually.
 With the experience accumulated during these years by each one of us, the León XIII Clinic of the Universidad de Antioquia began the hematopoietic stem cell transplantation (HSCT) program for adults in 2014. In this review, we report some clinical lessons drawn from the different phases of the HSCT in 109 adult patients with hematological malignancies. The progression-free survival (PFS) and the five-year overall survival (OS) were for autologous stem cell transplantation (ASCT) (87% and 70%), allogeneic stem cell transplantation (Allo SCT) (50% and 40%) and haploidentical stem cell transplantation (Haplo SCT) (25% and 18%) respectively.

Outpatient Haploidentical Stem Cell Transplantation Using Post-Transplant Cyclophosphamide Is Feasible. Experience in a Single Latin-American Center

Introduction: Only a minority of patients can find a fully matched donor for hematopoietic stem cell transplantation (HSCT). HLA-haploidentical HSCT is an attractive option since the likelihood of identifying a donor is high. Stimulated by economic constraints in developing countries and the significant expenses related to HSCT, in an effort to lower costs and resources, our center has performed an outpatient-based haplo-HSCT program since 2012. In the present study, we describe the characteristics of those patients and analyze the factors relating to the performance of a successful ambulatory procedure.Methods: Adult patients who underwent haplo-HSCT in an outpatient-intended basis were eligible. All were required to have a Karnofsky score ³70%, serum creatinine <2 mg/dL, residence near the hospital, an adequate caregiver, with appropriate educational level and treatment adherence. The conditioning regimen was delivered in all individuals as outpatients and consisted of fludarabine 25 mg/m2/day (day -5 to -3), cyclophosphamide (Cy) 350 mg/m2/day (day -5 to -3), and oral busulfan 4 mg/kg/day (day-2 to -1) or melphalan 50-100 mg/m2 (day -2 to -1). GVHD prophylaxis consisted of Cy (50 mg/kg/day, days 3 and 4), cyclosporine 6 mg/kg, and mycophenolate mofetil 1 g/day. After infusion, patients stayed at home and were seen in the outpatient clinic every day for the first 72 hours, every other day until hospitalization requirement or engraftment; afterwards weekly and bi-weekly through day +100, and thereafter according to physician criteria. Patients were instructed to report the presence of fever among other adverse effects at any hour of the day. Hospital beds were available for those needing admission.Results: Thirty-six consecutive patients from February 2013 to May 2017 were eligible for analysis. Median follow-up was 12 months (4-40). Median age was 23 years (range, 15-63); 13 were female. Acute leukemia (13 lymphoblastic and 5 myeloblastic) was the most common indication for HSCT, followed by Hodgkin's lymphoma (5), non-Hodgkin's lymphoma (4), chronic myeloid leukemia (3), aplastic anemia (3), chronic lymphocytic leukemia (2), and chronic myelomonocytic leukemia (1). Median PBSC CD34+ cells/kg was 7x106 (range, 2-16). Neutrophil engraftment was achieved at a median of 16 days (range, 11-23), with platelet recovery at a median of 16 days (range, 13-100). Seven patients (19%) were followed in a fully outpatient basis while the other 29 (81%) required hospitalization. The median length of stay (LOS) was 10 days (0-35). Seven patients (19%) stayed ≤7 days in hospital, while 22 patients >7 days. Febrile neutropenia was the most common reason for hospitalization (65.5%). Other reasons included mucositis (27.5%) and hemorrhagic cystitis (6.9%). The median day of admission was day +3 (1-14). The development of febrile neutropenia (P=0.004) and a slower neutrophil engraftment (P=0.023) were significantly associated with the need for hospital admission. Eight of the 18 patients admitted for febrile neutropenia had a rapid response and no source of infection evidenced, thus LOS was ≤10 days in 9 patients. Age, gender, mucositis, and acute graft versus host disease were not associated with hospitalization need. The 2-year overall survival (OS) was 50% for patients with a completely ambulatory transplant vs. 28% for those requiring hospitalization (log rank P=0.08).Conclusion: Currently conventional transplantation is unaffordable for the majority of patients living in the developing world. Almost 20% of our patients did not require hospital admission. Although 62% of the patients were admitted, most of them had a short LOS. Our outpatient haploidentical HSCT program is feasible, potentially resulting in cost savings and perhaps a higher quality of life. [Display omitted] DisclosuresGomez-Almaguer:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Establishment of a cell processing laboratory to support hematopoietic stem cell transplantation and chimeric antigen receptor (CAR)-T cell therapy

Cell processing laboratories are an important part of cancer treatment centers. Cell processing laboratories began by supporting hematopoietic stem cell (HSC) transplantation programs. These laboratories adapted closed bag systems, centrifuges, sterile connecting devices and other equipment used in transfusion services/blood banks to remove red blood cells and plasma from marrow and peripheral blood stem cells products. The success of cellular cancer immunotherapies such as Chimeric Antigen Receptor (CAR) T-cells has increased the importance of cell processing laboratories. Since many of the diseases successfully treated by CAR T-cell therapy are also treated by HSC transplantation and since HSC transplantation teams are well suited to manage patients treated with CAR T-cells, many cell processing laboratories have begun to produce CAR T-cells. The methods that have been used to process HSCs have been modified for T-cell enrichment, culture, stimulation, transduction and expansion for CAR T-cell production. While processing laboratories are well suited to manufacture CAR T-cells and other cellular therapies, producing these therapies is challenging. The manufacture of cellular therapies requires specialized facilities which are costly to build and maintain. The supplies and reagents, especially vectors, can also be expensive. Finally, highly skilled staff are required. The use of automated equipment for cell production may reduce labor requirements and the cost of facilities. The steps used to produce CAR T-cells are reviewed, as well as various strategies for establishing a laboratory to manufacture these cells.

The Incidence and Associated Risk Factors in Central Venous Catheter Associated Infectious Complications within the Autologous Stem Cell Transplant Population of Eastern Health

Background: Central venous catheters (CVCs) carry a risk of infectious complication with associated morbidity and mortality. Hematologic malignancies are a known independent risk factor for these complications. Patients undergoing hematopoietic stem cell transplant (HSCT) are at increased infectious risk with an incidence of 24.7-31.3%. Proposed contributors to this risk are the underlying malignancy, extended neutropenia, and increased requirement for blood products. Existing cohort studies of HSCT patients have been unable to identifying consistent, modifiable risk factors to target with infection prevention and control initiatives. This single-centre retrospective cohort study examines an autologous stem cell transplant population to identifying risk factors associated with CVCs. Objectives:To determine the incidence and incidence rate per 1000 catheter-days within the autologous HSCT program at Eastern HealthTo identify protective and risk factors associated with CVCs in HSCT patientsDescribe the causative agents in CVC infectious complication identified by blood and catheter-tip culture results Methods: Charts of all adult patients with hematologic malignancy who underwent HSCT with CVC placement at Eastern Health between January 1, 2014 and March 1, 2020 were examined to determine which patients experienced any of a catheter-related bloodstream, tunneled-line or exit site infectious complication as defined by the Public Health Agency of Canada's surveillance definitions. Risk factors assessed included patient factors (age, malignancy, history of bacteremia, fungemia or radiation therapy), immunosuppressive factors (lines of chemotherapy, total 90 day corticosteroid burden, erythropoietin use, days to polymorphonuclear cells &amp;gt;500/µL), and CVC factors (line type, insertion site, antibiotic prophylaxis, heparin impregnation, training level of radiologist, days indwelling, thrombotic complication. Additional data captured included 90-day mortality, whether the CVC was terminated and the causative organism identified by blood or catheter-tip culture. Preliminary Results: The incidence of total infectious complications was 56.2% with an incidence of catheter-related bloodstream infection (CR-BSI) of 22.9%. The incidence rate for total infectious complications was 6.51 per 1000-catheter days, with a CR-BSI infectious rate of 2.65. Both incidence and incidence rate were below results found in other centres. In univariate analysis found single-line of chemotherapy (HR 0.114, p=0.001), use of Permacath (HR 0.03, p=0.002), right internal jugular placement (HR 0.048, p=0.006) to be protective for infectious complication. Multivariate analysis identified a history of bacteremia (OR 763.1, p=0.039) and total days CVC indwelling (OR 0.94, p=0.011) to be associated with CVC infectious complication. Conclusion: Modifiable risk factors associated with CVC infectious complication are choice of device and placement site. Risk factors such as multiple lines of previous chemotherapy or history of bloodstream infection signal need to increased observation for infection. Disclosures No relevant conflicts of interest to declare.

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.

Hematopoietic Stem Cell Transplantation in Egypt: Challenges and Opportunities.

Hematopoietic stem cell transplantation (HSCT) is now an established treatment modality with definitive indications for many hematological disorders. However, HSCT requires tremendous resources, and it is increasingly challenging for transplantation experts to practice in the developing world and to reach a compromise between requirements and available resources. Based on 30 years of experience and 4256 transplants (60% allogeneic and 40% autologous), this article focuses on the challenges our HSCT program encountered since it started in 1989 and what opportunities we see to solve them. Since 1997, HSCT procedures increased dramatically with the opening of 15 HSCT units distributed all over Egypt.

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.

Let's Talk about Sex: Using Evidence to Promote Safe Sex Practices for Patients Following Hematopoietic Stem Cell Transplants

Topic Significance & Study Purpose/Background/Rationale Hematopoietic stem cell transplant (HSCT) patients at Boston Children's Hospital (BCH) are taught sexual activity guidelines that were published in 2011. Current guidelines state that while patients are immunocompromised (generally 3 months for autologous transplants and 9-12 months for allogeneic transplants), no kissing, vaginal, or anal intercourse is permitted. Patients are only allowed to receive oral sex but not offer it to their partners. Anecdotally, nurses find the current recommendations outdated, confusing, and exclusive of all sexual practices, leading to discomfort providing this education. As a result, patients either receive no teaching at all or non-standardized teaching. Providing patients with up-to-date, evidence-based guidelines regarding safe sexual activities is necessary to prevent infection while optimizing quality of life. Methods, Intervention, & Analysis A review of the evidence was conducted using peer-reviewed articles, benchmarking clinical practice guidelines from other pediatric and adult institutions, and obtaining expert opinions. Findings & Interpretation There is insufficient evidence in the literature regarding infection risk related to sexual behavior for patients following HSCT. Until future research provides greater evidence on this subject, institutions will continue to rely on expert opinion to provide recommendations for safe sexual activity in the post-stem cell transplant population. Discussion & Implications For BCH's HSCT program, sexual activity guidelines have been revised to permit kissing, masturbation, oral sex, and intercourse with protection (excluding anal penetration) for all non-neutropenic patients with platelets counts > 20,000 cells/uL and no active cold sores. This education will be provided via a revised written education sheet translated into Spanish and Arabic for patients and families. The creation of revised teaching tools standardizes education and enhances nurses’ comfort discussing sensitive topics related to sexual activity. This work will benefit patients psychosocially as sexual health impacts quality of life.

Two decades of experience in a combined adult/pediatric allogeneic hematopoietic stem cell transplantation center in Algiers, Algeria.

Hematopoietic stem cell transplantation (HSCT) has evolved from an experimental to a successful treatment modality reaching worldwide 80.000 HSCT/year. Distribution and trends of HSCT, however, remain heterogeneous. Activities range from none to more than 511/10 million population between countries and regions. Here, we report on a successful autologous and allogeneic HSCT program for adult and pediatric patients started two decades ago in Northern Africa. From 1998 to December 2017, a total of 2828 HSCT was performed of which 2059 were allo-HSCT (1474 adults and 585 children). The activities were analyzed according to indication, donor type, stem cell source, and trends over time. There was a significant difference in indications according to age. Adult patients were transplanted more often for hematological malignancies. In children, the indications were distributed equally between malignant and non-malignant diseases. Overall activities increased substantially in AML and to a lower extent in ALL and CLL despite sharp reduction of activity in CML after 2005. Finally, a higher transplantation rate (33/10 million population) was reached as compared to most regions of the world except Europe and USA/Canada. Overall survival in children with AML was 56.0% at 15years, in adults 61.3% at 5years, and in patients with CML 55.5% at 15years without difference between reduced intensity condition (RIC) and myeloablative conditioning (MAC). Patients with Ph+ ALL had the lowest survival reaching 26.7% at 5years. Highest survival was observed in patients with aplastic anemia, Fanconi anemia, and thalassemia reaching 77.3%, 73.5%, and 75.7% at 15years respectively. Long distances and late referral remain a challenge for this large country.

Longitudinal Changes in the Intestinal Microbiome Composition Following Gut Decontamination in Pediatric Allogeneic Hematopoietic Stem Cell Transplant Patients: A Pilot Study

Introduction: Early preclinical studies demonstrating that eradication of intestinal bacteria could prevent the development of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) led many adult and pediatric HSCT programs to practice "gut decontamination" (GD) with non-absorbable oral antibiotics for aGVHD prophylaxis. However, there is insufficient data supporting a clear benefit for GD in HSCT patients. Recent adult HSCT studies show that GVHD-related mortality is associated with decreased bacterial diversity in the gut microbiome, suggesting that certain bacterial species are protective against aGVHD. GD may decrease microbiome diversity and lead to worse post-HSCT outcomes. Methods: We conducted a randomized phase 2 study to examine the impact of GD on intestinal microbiome composition in pediatric allogeneic HSCT patients. 20 patients were enrolled and randomized to receive (GD) or not receive (no GD) oral vancomycin-polymyxin per our institutional standard from day -5 through engraftment. Stool samples were collected pre-transplant, weekly until neutrophil engraftment, monthly through day +100, then at 6 months and 1-year post-HSCT. Our primary endpoint is bacterial diversity, quantified by Shannon diversity index, at 2 weeks post-HSCT. Change in diversity is defined as the delta of diversity before transplantation compared to the minimum diversity seen in a single patient in a one-week window (around 14 days post-transplantation). This change in diversity was then averaged (mean) across each treatment arm. The stool microbiome was characterized using shotgun metagenomic sequencing (Nextera Tagmentation and Illumina HiSeq4000 Sequencing) for 10 patients to date, with median count of 1.4x107 reads per sample (range 1.3x106 to 3.3x107). Following quality control (FastQC, Trim Galore, Super Deduper), reads are assigned taxonomic designations using Kraken2 and GenBank (Oct. 2018) database. Secondary endpoints include the frequency of diarrhea (defined as &gt;3 bowel movements per day in the first 7 days post-HSCT), incidence of aGVHD and bacteremia during the first 100 days post-transplant, immune reconstitution, survival, and malignant disease relapse at 2 years after study entry. Comparisons by treatment group were performed with Fisher's exact test (binary) or Wilcoxon rank-sum test (continuous). Results: Baseline patient characteristics were similar between the two arms (Table 1). At present,5 patients (25%) have completed 2 years of follow up, 4 of 15 patients with malignant disease (27%) have had relapse (3 GD, 1 No GD), and 2 patients (10%) in the No GD arm have died (1 malignant relapse, 1 refractory chronic GVHD). Microbiome analysis in the first 10 patients (4 GD, 6 No GD) demonstrates that the average change in Shannon diversity score at 2 weeks is 1.7 (SD 0.86) in GD and 0.65 (SD 0.61) in No GD (Table 2). Diarrhea occurred in 4/10 patients in GD vs 4/10 patients in no GD (p≥0.99).1/10 patients in GD and 3/10 in No GD developed aGVHD grade II or above(p=0.58). Bacteremia within the first 100 days post-HSCT occurred in 1/10 patient in GD, whereas 5/10 patients in No GD had 8 different bacteremia events (p=0.14) (Table 3). Conclusions: This is the first randomized study of gut decontamination in pediatric patients undergoing HSCT with long-term prospective post-transplant stool sample collection and immune monitoring. Though the small sample size is currently not powered to detect differences in clinical outcomes between the 2 study arms, the descriptive microbiome and immune reconstitution data will inform larger studies. There is no statistical difference in the diarrhea, aGVHD, or bacteremia incidence between the two groups but it is interesting that there was 1 vs 8 bacteremia events in GD vs No GD. Microbiota diversity results from our pilot study with 10 patients indicate a trend toward lower diversity at 2 weeks post-transplant in the GD arm. Microbiome analysis of the remaining samples from the remaining 10 patients is underway as well as longitudinal analysis of samples from all patients. Describing the changes to the microbiota composition over time in two groups will provide insight to practice of GD, potential targets for aGVHD, and will provide preliminary data to understand which microbes and microbial gene-pathways may influence immune reconstitution. Disclosures London: United Therapeutics: Consultancy; ArQule, Inc: Consultancy. Ritz:Draper Labs: Consultancy; Kite Pharma: Research Funding; Avrobio: Consultancy; LifeVault Bio: Consultancy; Merck: Research Funding; TScan Therapeutics: Consultancy; Talaris Therapeutics: Consultancy; Celgene: Consultancy; Aleta Biotherapeutics: Consultancy; Equillium: Research Funding. Bhatt:ArcBio: Other: Scientific Advisory Board; January.ai: Other: Scientific Advisory Board; Caribou Bioscience: Other: Scientific Advisory Board; Kaleido Biosciences: Consultancy, Other: Paid Consultant; Janssen Human Microbiome Institute: Consultancy, Other: Paid Consultant; Illumina: Honoraria; 10x Genomics: Other: Research collaboration without funding support; Illumina: Other: Research collaboration without funding support; Agilent: Research Funding; Global Oncology, Inc: Other: Nonprofit Board.

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

Worldwide Network for Blood and Marrow Transplantation (WBMT) recommendations for establishing a hematopoietic stem cell transplantation program in countries with limited resources (Part II): Clinical, technical and socio-economic considerations

The development of hematopoietic stem cell transplantation (HSCT) programs can face significant challenges in most developing countries because such endeavors must compete with other government health care priorities, including the delivery of basic services. While this is may be a limiting factor, these countries should prioritize development of the needed expertise to offer state of the art treatments including transplantation, by providing financial, technological, legal, ethical and other needed support. This would prove beneficial in providing successful programs customized to the needs of their population, and potentially provide long-term cost-savings by circumventing the need for their citizens to seek care abroad. Costs of establishing HSCT program and the costs of the HSCT procedure itself can be substantial barriers in developing countries. Additionally, socioeconomic factors intrinsic to specific countries can influence access to HSCT, patient eligibility for HSCT and timely utilization of HSCT center capabilities. This report describes recommendations from the Worldwide Network for Blood and Marrow Transplantation (WBMT) for establishing HSCT programs with a specific focus on developing countries, and identifies challenges and opportunities for providing this specialized procedure in the resource constrained setting.

Current Practice in Vitamin D Management in Allogeneic Hematopoietic Stem Cell Transplantation: A Survey by the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation.

Beyond its impact on bone health, numerous studies have investigated the immune-regulatory properties of vitamin D and shown how its deficiency can affect outcomes in allogeneic hematopoietic stem cell transplantation (HSCT), particularly in acute or chronic graft-versus-host disease. This survey, carried out by the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation (EBMT), describes the current clinical practice discrepancies across the EBMT HSCT programs. We therefore recommend the development of evidence-based guidelines to standardize evaluation criteria and to harmonize the management of vitamin D deficiency in patients undergoing allogeneic HSCT.

Worldwide Network for Blood and Marrow Transplantation Recommendations for Establishing a Hematopoietic Stem Cell Transplantation Program in Countries with Limited Resources, Part II: Clinical, Technical, and Socioeconomic Considerations.

The development of hematopoietic stem cell transplantation (HSCT) programs can face significant challenges in most developing countries because such endeavors must compete with other government health care priorities, including the delivery of basic services. Although this is may be a limiting factor, these countries should prioritize development of the needed expertise to offer state-of-the-art treatments, including transplantation, by providing financial, technological, legal, ethical, and other needed support. This would prove beneficial in providing successful programs customized to the needs of their population and potentially provide long-term cost savings by circumventing the need for their citizens to seek care abroad. The costs of establishing an HSCT program and the costs of the HSCT procedure itself can be substantial barriers in developing countries. In addition, socioeconomic factors intrinsic to specific countries can influence access to HSCT, patient eligibility for HSCT, and timely utilization of HSCT center capabilities. This report describes recommendations from the Worldwide Network for Blood and Marrow Transplantation for establishing HSCT programs, with a specific focus on developing countries, and identifies challenges and opportunities for providing this specialized procedure in resource-constrained settings.

Nutrition Practices in Hematopoietic Stem Cell Transplantation (HSCT): A Comparison between Guidelines and Clinical Practice

Background Several professional societies have established nutrition guidelines for patients undergoing HSCT. We surveyed HSCT programs to understand how these compare with clinical practice. Methods Qualitative surveys were emailed to HSCT dietitians. Surveys addressed malnutrition screening; dietary recommendations including nutrition support, graft-versus-host disease (GVHD), immune enhancing nutrients, and prebiotics/probiotics; and nutrition-related preventive care screening. Results Twenty adult programs (19 United States (US), 1 Australia) and 3 pediatric programs (3 US) responded. Annual volume across the 22 US programs was 5405 patients, representing 25% of all transplants in the US. Nineteen programs (83%) follow guidelines for nutrition screening and fourteen for nutrition therapy in the inpatient setting (Table 1); six (26%) follow guidelines for screening and therapy in the outpatient setting. All programs adhere to food safety recommendations and 5 (22%) have additional institutional precautions. However, only 2 programs (9%) report frequent adherence to guidelines for use of enteral nutrition. While there are no guidelines for GVHD diet and uncertainty over alternative nutrition practices, 8 programs (35%) follow a stepwise GVHD diet; 4 (17%) allow immunonutrition supplements; 2 (9%) allow prebiotics, and 7 (30%) allow probiotics after the resolution of neutropenia. With regard to adherence to preventive screening recommendations, only 4 programs (17%) screen for diabetes, 6 (26%) screen for hyperlipidemia, and none screen for abdominal obesity. There are no guidelines for vitamin D deficiency screening, but 10 programs (43%) screen for this. Discussion Wide variations in nutrition practices exist across HSCT programs. Similarly, with the exception of food safety recommendations, there are also wide variations in adherence to established nutrition guidelines. The use of enteral nutrition and preventive screening is particularly varied. Efforts are needed to understand barriers to guideline implementation and their correlation to patient outcomes. Further research is needed regarding new interventions such as immunonutrition, prebiotics, and probiotics.

Depression and Infection Rates in Hematopoietic Stem Cell Transplant Patients

Introduction and Objectives Clinical and epidemiological data suggest that depression may increase the risk for infection. Infection is a major cause of morbidity and mortality in patients undergoing stem cell transplantation. We investigated the impact of depression on infection rates in patients undergoing autologous or allogeneic stem cell transplant at a single center. Methods We analyzed data from University of California San Diego's Hematopoietic Stem Cell Transplant program to compare outcomes after autologous (n= 472) and allogeneic (n= 259) transplants in patients with hematologic malignancies and with an existing diagnosis of depression versus no depression. Using chi-square testing, we compared the infection rates between patients with or without depression. Results The study included 162 (22.2%) patients with depression versus 568 (77.9%) without depression who underwent allogeneic and autologous stem cell transplant between 2012 and 2017. Using Pearson Chi-square testing, patients with depression had a higher rate of infections (55.6%) versus patients without depression (41%, p=0.001). Depression was associated with multiple infection sites (25% vs 17%, p=0.029), increased risk for bacterial infection (44% versus 28.5%, P Conclusion In our retrospective analysis depression was associated with higher rates of overall infection, bacterial, and fungal infection among hematopoietic transplant patients. Depression was also associated with increased risk for both acute and chronic graft versus host disease. If our observation is confirmed prospectively, then interventions aimed at depression, might improve infection rates in transplant patients.

Treatment Patterns and Outcomes of Unselected Elderly Acute Myeloid Leukemia (AML) Patients Referred to a Combined Acute Leukemia and Hematopoietic Stem Cell Transplant (HSCT) Program

The median age of acute myeloid leukemia (AML) diagnosis is 69 years with 60% of newly diagnosed patients > 60 years. Due to a perceived intolerance to therapy, many elderly AML patients do not receive therapy. Of those that do, few are eligible for curative intent therapy with hematopoietic stem cell transplantation (HSCT) due to perceived lack of fitness, excessive comorbidity or absence of a donor. To better understand the outcomes of elderly AML patients, we evaluated a cohort of 323 consecutive elderly AML patients (≥60 years) referred to the Leukemia Program at Northside Hospital from January 2009 to December 2017 for evaluation and management. Our treatment algorithm is to offer intensive chemotherapy (IC) to all potentially eligible patients and HSCT to all transplant-eligible non-favorable risk patients that achieve complete remission, with or without complete platelet recovery (CR1(p)). Median patient age was 70 years (range 60-88). AML occurred de novo in 218 (67%), therapy-related in 33 (10%) and secondary in 72 (22%) patients. NCCN risk category was favorable (fav) in 48 (15%), intermediate (int) in 112 (35%) and poor in 161 (50%). Leukemia induction therapy, either IC (n=204) or hypomethylating agents (HMA, n=58), was given to all but 61 (19%) patients (IC - 78%, HMA - 22%). Of patients receiving IC, the major regimens were FLAG+/-Ida (n=117), 7+3 (n=58) and CPX-351 (n=18). Of the IC/HMA-treated patients (n=262), 130 (50%) achieved CR1(p) with the first induction, while 158 (60%) ultimately achieved CR1(p). In patients with fav, int and poor risk AML, CR1(p) was achieved in 73%, 52% and 41% respectively. HSCT was performed on 63 patients (59 - int/poor risk, 4- fav risk): autologous [5], matched sibling donor [21], matched unrelated donor [24], haploidentical donor [13]. Of the non-fav risk AML CR1(p) patients, where the treatment goal is HSCT if feasible, 57 (46%) of 124 received HSCT. After a median f/u of 34 months, 2-year overall survival (OS) for the whole cohort was 31%; corresponding rates for fav, int and poor risk AML was 58%, 35% and 20% respectively. Survival was similar in patients aged 60-66 and 67-72 years (2-yr OS 35% and 38%), but superior to those in the 73-88 yr tertile (2-yr OS 19%, p<0.001). The 2-yr OS was similar for IC- or HMA-treated patients (40% and 33% respectively) vs. 0% for patients not receiving induction therapy. For patients achieving CR1(p), 2-yr OS was 50% vs. 16% for those never reaching CR1(p). Of the patients receiving HSCT, 2-yr OS was 64%. In the subset of non-fav risk AML CR1(p) patients, OS was improved with HSCT (p<0.001, 2-yr OS 66% vs. 27%). In multivariate analysis, we analyzed factors associated with mortality including age, gender, race, year of diagnosis, WBC, de novo vs. secondary, NCCN risk category, and induction chemo type (receipt of HSCT was not analyzed given inherent bias in such as analysis). Factors associated with superior OS included WBC <2.5 at diagnosis (2.5-25.7, HR 1.92, p<0.001; ≥25.8, HR 1.93, p<0.001), NCNN fav risk (int, HR 2.02, p=0.002; poor, HR 2.71, p<0.001) and receipt of either IC or HMA induction (no induction vs. IC, HR 7.65, p<0.001; HMA vs. IC, HR 1.20, p=0.315). With the caveat that any such analysis is subject to referral bias, these results suggest that survival may be improved in elderly AML patients through a coordinated approach of remission induction therapy followed by HSCT when feasible. [Display omitted] DisclosuresSolh:Celgene: Speakers Bureau; Amgen: Speakers Bureau; ADC Therapeutics: Research Funding.