Bone Marrow Transplant Program Research Articles

Eltrombopag Improved Cytopenias Due to Posttransplant Poor Graft Function: Experience from a Comprehensive Bone Marrow Transplantation Program in Jordan

Eltrombopag Improved Cytopenias Due to Posttransplant Poor Graft Function: Experience from a Comprehensive Bone Marrow Transplantation Program in Jordan

Barriers to Establishing a Chimeric Antigen Receptor T-Cell (CAR-T) Therapy Program without a Pre-Established Bone Marrow Transplant Program

Barriers to Establishing a Chimeric Antigen Receptor T-Cell (CAR-T) Therapy Program without a Pre-Established Bone Marrow Transplant Program

P.035 Autologous hematopoietic stem cell transplant for the treatment of refractory myasthenia gravis with anti-muscle specific kinase antibodies

Background: Several case series describe patients with refractory acetylcholine receptor antibody-positive (AChR) myasthenia gravis (MG) treated with hematopoietic stem cell transplant (HSCT). In this report, we describe four patients with anti-muscle-specific kinase (MuSK)MG treated with HSCT. Methods: We reviewed the records of all patients undergoing HSCT for MG in the Alberta Blood and Bone Marrow Transplant Program and identified 4 patients with anti-MuSK MG. Results: All 4 patients had severe disease (Myasthenia Gravis Foundation of America score IVb-V) and were refractory to multiple treatments, including rituximab. 3 patients improved with no clinical manifestations or mild symptoms and remained as such for 2, 3.5, and 5.5 years. In these 3 patients, adverse events ranged from treatable infections and transient dyspnea to persistent fatigue and premature menopause. The average worst Myasthenia Gravis Activities of Daily Living (MG-ADL) scores improved from 14.7 before to 0.3 after HSCT while their mean worst Myasthenia Gravis Quality of Life Questionnaire (MG-QoL15) scores improved from 26.7 to 0. The fourth patient developed pneumonia and passed away from respiratory failure 8 weeks post-transplant. Conclusions: In patients with severe refractory anti-MuSK MG, it may be reasonable to consider HSCT but with an appreciation of the associated risks.

Establishing and Sustaining a Peadiatric Bone Marrow Transplant Program in Developing Countries

Establishing and Sustaining a Peadiatric Bone Marrow Transplant Program in Developing Countries

Thalassemia care in Nepal: In dire need of improvement.

Thalassemia care in Nepal: In dire need of improvement.

Comparison of Patient and Provider Practices between Bone Marrow and Solid Organ Transplantation Programs for Patient Education on Increased Risk of Skin Cancer

Patients receiving immunosuppressive therapy following transplantation are at risk for skin cancer owing to dampened tumor surveillance. As long-term immunotherapy is necessary to prevent graft rejection, transplantation providers and recipients are expected to perform regular surveillance for the development of suspicious lesions, and recipients are encouraged to practice preventative sun safe behaviors. No consensus exists regarding the timing of full body skin exams, and despite the well-established risk, patient education is not always prioritized. We investigated whether differences exist between bone marrow transplant (BMT) and organ transplant (OT) recipients and their providers regarding prevention and screening. We distributed surveys to adult and pediatric BMT and OT recipients, as well as their providers, at a single academic institution. Results were evaluated using the chi-square test. The survey results show that most BMT recipients (69%) and OT recipients (77%) were aware of their increased risk for skin cancer, but despite this knowledge, only 13% of patients overall reported using sunscreen, 29% reported reapplying sunscreen, and 48% reported wearing sun protective clothing. Most OT recipients (63%) reported never having a total body skin exam, whereas only 34% BMT recipients reported having a total body skin exam every 6 months (P=.006). BMT providers recommended a total body skin exam every 6 or 12 months (44.4% each), and OT providers recommended a total body skin exam every 12 months (58.3%). Only 11.1% of BMT providers and 8.3% of OT providers reported performing a total body skin exam at each visit. Despite results indicating widespread patient knowledge of skin cancer risk, most patients do not practice adequate prevention. Inclusion of a transplantation dermatologist in the care team or use of risk stratification tools by providers may help streamline timely referrals to Dermatology.

Comparing the Quality of Life of Caregivers for Patients with Hematologic and Solid Malignancies in Kuwait: A Cross-Sectional Study

Cancer incidence is escalating globally, and the Middle East, including Kuwait, is no exception. This study delves into a comparative analysis of the Quality of Life (QOL) experienced by caregivers for patients with hematologic and solid malignancies in Kuwait. The prevalence of cancer in Kuwait is rising, becoming the second leading cause of death after cardiovascular diseases. Colorectal and breast cancer are predominant forms, with an increased occurrence in females. Notably, haematological malignancies, rooted partly in consanguineous marriages, exhibit a distinct prevalence pattern, accounting for a significant proportion of deaths. Kuwait has made substantial investments in bone marrow transplantation programs to address this issue. To understand the impact of caregiving on the QOL of individuals supporting cancer patients, a cross-sectional study was conducted. Caregivers were recruited from the Kuwait Cancer Control Centre outpatient clinics between February 25 and March 25, 2020. Caregivers’ QOL was assessed using the Caregiver Quality of Life Cancer Index (CQoLC) through face-to-face interviews. The study aimed to determine if caregivers were adequately informed before their patients’ discharge and analyse reasons for non-participation. Previous research on caregiver QOL has predominantly focused on Western societies, while this study addresses the Kuwaiti context. The expectation is that findings will contrast with Western studies due to unique cultural and societal dynamics, where women play a pivotal role in caregiving. While males may experience reduced QOL due to work-home time constraints, female caregivers in Arab countries tend to be efficient, albeit with potential skill deficiencies. The study enrolled 117 caregivers, with 65 supporting patients with solid malignancies and 52 caring for hematologic malignancy patients. The demographic characteristics of caregivers were analysed, revealing trends related to age, gender, marital status, employment, education, and living arrangements. Caregivers of solid malignancy patients displayed higher levels of burden compared to hematologic malignancy caregivers, with emotional strain, worry, and sadness being significant factors. While there was a notable refusal rate among potential participants, the study’s insights are valuable. To enhance the QOL of caregivers, especially those supporting outpatient cases, targeted interventions such as palliative care and training programs are crucial. The economic burden on caregivers necessitates policies addressing financial support. The findings of this study contribute to the ongoing efforts to improve the QOL of caregivers in Kuwait, thereby alleviating the multifaceted challenges posed by cancer and its care. This research underscores the importance of tailoring interventions to the specific cultural, social, and economic context of Kuwait to optimize caregiver well-being and patient outcomes.

265. Cryptococcal disease in Covid-19 infection: Case series from South Texas

Abstract Background Covid-19 infection is associated with a lack of immune resilience that may be magnified using immunomodulators to suppress the cytokine storm, facilitating the emergence of opportunistic infections. We describe five cases of cryptococcal infection complications among Covid-19 hospitalized patients. Methods This was a retrospective cohort study based on chart review performed at the Audie Murphy Veteran Affairs Hospital from 8/2020 to 8/2021; a level 1A facility with 232 beds and an active bone marrow transplantation program. We included patients aged ≥ 18 with a diagnosis of Covid-19 and subsequent Cryptococcal infection based on cultures or antigen testing. Results Our patients were all male with ages ranging between 64 to 80 years. Three had underlying type II diabetes, hypertension, and two had end-stage renal disease. Only one had underlying immunosuppression with hydroxychloroquine for rheumatoid arthritis and one had underlying cirrhosis. Four patients had disseminated disease/fungemia while one had localized pulmonary disease. All the cases had low CD4 counts (158-300) and low CD8 counts (92-290). Two of the fungemia cases were diagnosed by blood culture and the other two by serum cryptococcus antigen test. All the patients had received corticosteroids with or without remdesivir, while one received additional tocilizumab, one baricitinib and one convalescent plasma infusion. Four cases of fungemia received liposomal amphotericin B and three of them received additional flucytosine. The patient with cryptococcal pulmonary disease received only fluconazole. Four patients expired at 28 days after diagnosis, only one recovered and is still alive at 1-year follow up. Table 1.Case details. ESRD: end stage renal disease; DM-2: diabetes mellitus type ; HTN: hypertension; A-fib: Atrial Fibrillation; HFpEF: heart failure with preserved ejection fraction; PVD: peripheral vascular disease; RA: rheumatoid arthritis; PTSD: post traumatic stress disorder; BPH: benign prostatic hyperplasia; CAD: coronary artery disease; HLD: hyperlipidemia; CVA: cerebrovascular accident. Conclusion Cryptococcus infection has been described among patients with Covid-19 during the pandemic. This may be due to immunosuppression caused by the Covid-19 infection and its related-treatments. Most of our patients presented with disseminated cryptococcus infection complicating covid-19 with resulting high mortality rates. Low CD4/CD8 counts and corticosteroid use were documented in all cases. Further studies are needed to better characterize at-risk patients for cryptococcal infection that may benefit from cryptococcal prophylaxis. Disclosures All Authors: No reported disclosures.

2045. IVAC Plus in the Time of COVID-19: An Imperfect Metric?

Abstract Background Prior to the COVID-19 pandemic, the incidence of infection related ventilator associated complications plus possible ventilator associated pneumonias (IVAC+) was decreasing; however, as the number of COVID-19 hospitalizations increased, so did the number of IVAC+. Our goal was to investigate if there was a relationship between these two occurrences. Methods This was a retrospective study at the Audie Murphy VA Hospital (ALMVA) from October 2017 to December 2021. ALMVA is a level 1A facility with 232 beds and an active bone marrow transplant program in San Antonio, Texas. This study included acute care COVID-19 hospitalizations per 10,000 bed days of care and IVAC+ per 1000 ventilator days. Monthly acute and intensive care COVID-19 hospitalization rates were correlated with IVAC+ rates using Pearson correlation for the overall study period and in the subgroup of COVID pandemic months (Mar 2020-December 2021). Results During the overall study period, COVID-19 hospitalization rates were significantly associated with IVAC+ rates: acute care correlation 0.86 (p< 0.01) and intensive care correlation 0.33 (p=0.04). During the COVID-19 pandemic months, acute care COVID-19 hospitalizations but not intensive care COVID-19 hospitalizations, were correlated with IVAC+ (correlation 0.90, p< 0.01 and correlation 0.21, p=0.53, respectively). There were 0 IVAC+ before the pandemic months and this rose to 14 during (0 per 1000 ventilator days and 3.05 per 1000 ventilator days, respectively). All but 2 cases of IVAC+ had COVID-19. COVID-19 Hospitalizations and IVAC Plus, October 2017 to December 2021 A sharp increase in COVID-19 hospitalizations correlated with a rise in patients meeting criteria for IVAC Plus. Conclusion The natural history of COVID-19 disease has presented challenges for IVAC+ monitoring. COVID-19 can cause persistent fevers and worsening oxygenation, and antibiotic use is common during periods of clinical deterioration. These factors can fulfill criteria for IVAC+. In this study, each IVAC+ case was traced for safety bundle compliance. These bundles were followed, along with conservative fluid management, low tidal volume ventilation, and sedation breaks. Patients met NHSN criteria for IVAC+ despite these measures and most had COVID-19. Given the common occurrence of IVAC+ in COVID-19 patients, futures studies are needed to define if IVAC+ are preventable in this population and whether IVAC+ surveillance has any value among COVID-19 patients. Disclosures All Authors: No reported disclosures.

Hematopoietic Stem Cell Transplantation in Bangladesh : Activity and Outcome Update

Background : Hematopoietic stem cell transplantation(HSCT) is a potentially life saving curative modality of treatment procedure for many hematological malignancies, bone marrow failure syndromes and thalassemia. Bangladesh started first bone marrow transplant program with autologous transplant for myeloma in 2014 with the international collaboration between Massachusetts general hospital ( MGH) and Dhaka Medical College Hospital (DMCH). Since then it is growing in both public and private sector hospitals. Method : This is a multicenter retrospective study describing the demographics, activities and outcome of HSCT in Bangladesh. HSCT related Data were collected from three eminent HSCT centres of Bangladesh ( DMCH, Evercare hospitals and Combined Military Hospital Dhaka) and were analyzed. Result : As of June 2022, total 163 HSCT have been done in Bangladesh in major three centres as DMCH(52), Evercare hospital (62)and CMH Dhaka(49). Mean age of all patients is 39.4 years( range 15-69 Y) and sex distribution is M:F 3:1. Total autologous transplants were 125(77%) for myeloma(52), Hodgkins lymphoma(27) ,non-Hodgkins lymphoma(39) and others(7). Total allogeneic transplants were 38(23%) for AML(23), ALL(6), other hematological malignancy(03), Severe aplastic anemia (04) and thalassemia (02). Donor type wise majority were from matched sibling transplant (30/78%) from mostly male donor. Eight (08) haplo transplant were also successfully done. Each center follows specific infection control protocols, conditioning chemo protocols and growth factor protocols for the best patient care. Conditioning chemo protocols that usually used are high dose melphalan for MM, BEAM( Carmustine, Etoposide, Ara-C and Melphalan) for lymphoma and Bu-Cy( Busulphan-Cyclophosphamide) based for acute leukemia. Some leukemia patients received total body irradiation( TBI), thiotepa and Fludarabine based conditioning chemotherapy. All centres use irradiated blood components as transfusion products to avoid transfusion associated GVHD. As all centre used almost similar conditioning for particular disease, mean engraftment time in all centres were almost similar. Average time for neutrophil and platelet engraftment was 10-12 and 12-16 days post transplant respectively. Major early complications following transplant were neutropenic fever (>80%) and bacteraemia (25-30%) commonly with coagulase negative Staphylococcus, Pseudomonas sp, E. Coli and Klebsiella sp. Severe sepsis, pneumonia, typhlitis, hemorrhagic cystitis and CMV reactivation were observed in few cases. Acute GVHD ( G I to GII) was observed in almost all allogeneic transplanted patients. Mucositis, vomiting and diarrhoea were mild to moderate in most patients. Almost all patients required at least 1-3 red cell and platelet transfusion during the time waiting for engraftment. Progression free survival for all patients was variable in different centres (62% to 83%) since 2014 . Relapse of primary disease is more observed in autologous than allogeneic. Transplant related mortality( TRM) was 2% for autologous transplants and 5% for allogeneic transplant. Three early deaths were due to sepsis with COVID-19 infection in autologous transplant in pandemic period. Overall cost of transplantation is much lower in Bangladesh than that of developed countries. Approximate cost of autologous stem cell transplant is about $7000 and that for allogeneic transplant is $12000 to $15,000. Conclusion : Considering total population and burden of hematological malignancy in Bangladesh, the number of transplant is very low and it needs to be grown more rapidly to provide maximum benefit to save the lives as HSCT offers a curative approach to many hematological malignancies. Financial constrain, lack of health insurance and shortage of trained human resource are the main challenges for doing transplant in Bangladesh. National transplant registry and national donor registry both are yet to be developed. Comparing the cost difference with developed countries the overall outcome of stem cell transplantation is not inferior in Bangladesh.

Letermovir as Cytomegalovirus Prophylaxis in a Pediatric Cohort: A Retrospective Analysis

Letermovir is an attractive cytomegalovirus (CMV) prophylactic agent, but published data in children are scarce. This retrospective chart review aimed to describe our experience using letermovir as CMV prophylaxis in pediatric hematopoietic cell transplantation (HCT) recipients. Pediatric patients (age <20 years) undergoing allogeneic HCT and receiving letermovir prophylaxis in the Mayo Clinic Pediatric Bone Marrow Transplant Program were eligible for inclusion in this retrospective chart review. Medical records were reviewed to evaluate letermovir dosing, CMV levels, laboratory values, and reports of adverse effects. Between October 2020 and April 2022, 9 patients age 4 to 19 years undergoing allogeneic HCT in the Pediatric Bone Marrow Transplant Program received letermovir prophylaxis, either 240 mg or 480 mg daily at a mean and median dose of 10 mg/kg/day. Letermovir was crushed and administered via nasogastric tube in 4 of 9 patients. Two patients received letermovir for secondary CMV prophylaxis after initial treatment with ganciclovir/valganciclovir, and the remaining 7 received letermovir for primary prophylaxis. One patient, a 20-kg 6-year-old female receiving 240 mg (12 mg/kg), experienced low-level CMV viremia while on letermovir. No other patients experienced CMV reactivation while on letermovir prophylaxis. In 2 patients, transient mild transaminitis was noted within the first weeks of letermovir therapy, which resolved without intervention, and its relationship to letermovir could not be clearly established. Letermovir administration was feasible and well tolerated as CMV prophylaxis in our small cohort of pediatric patients undergoing HCT. Larger, prospective studies are warranted to confirm the safety and efficacy of letermovir in children. © 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

CT-098 Impact of T-Cell Dose on Outcome of T Cell–Replete HLA-Mismatched Allogeneic Peripheral Blood Stem Cell Transplantation

The outcome of allogeneic hematopoietic cell transplantation (HCST) relies on both disease-related factors and transplant-related factors including the conditioning regimen and immunotherapy exploiting the graft-versus-tumor (GVT) effect. CD3+ T cells are the main player in the GVT process, but an increased dose of these cells results in an increased risk of acute graft-versus-host disease (GVHD). We aimed to study whether the T-cell dose of allogeneic peripheral blood stem cell (PBSC) products influences transplantation outcomes in our patient population. This is a retrospective chart review study including patients over 18 years of age, diagnosed with AML, ALL, or MDS, who underwent PBSC mismatched allogeneic transplant, including haploidentical, one-antigen mismatched related, or 2-alleles mismatched related transplants at the King Hussein Cancer Center's bone marrow transplant program between January 2010 and December 2020. We calculated the median CD3 cell dose and divided all patients into 2 groups (Low and High dose groups) and then measured the cumulative incidence of acute GVHD, chronic GVHD, and 1- and 2-year overall survival (OS). Thirty-five patients were stratified according to the median CD3+ cell dose into the Low CD3 group, which included 18 (51%) patients with a mean dose of 13.7×107/kg (range: 2.8-19.7), and the High CD3 group, which included 17 (49%) patients with a mean dose of 29.7×107/kg (range: 19.8-93.1) (P-value: 0.000). The cumulative incidence of acute GVHD was 60% (n=12) in the Low CD3 group and 40% (n=8) in the High CD3 group (P-value: 0.24). The cumulative incidence of chronic GVHD was 64% (n=9) in the Low CD3 group and 35% (n=5) in the High CD3 group (P-value: 0.26). The overall survival for the cohort (n=35) at 12 months was 60.9% and reached 49.6% at 24 months. The 12-month OS for the Low and High CD3 groups was 66.7% and 52.9%, respectively. The 24-month OS for the Low and High CD3 groups was 66.7% and 33.1%, respectively (P-value: 0.084). Although the study showed a trend toward better OS in the Low CD3+ dose group, the difference was not statistically significant.

P10.01: How Did the War Affect Organ Transplantation in Syria?

Since 2011, the Syrian conflict has destroyed much of the country’s infrastructure. The deteriorating humanitarian situation has involved health workers and facilities. In 2010, before the war, 385 kidney transplants were performed in Syria. This number declined to 154 in 2013 (60% less) before increasing to 251 transplants in 2018, which is still 35% less than the number of transplants performed before the war. In addition, the number of operational kidney transplant centers has decreased from 8 in 2010, distributed over 3 cities, to only 4 in 2013, all located in Damascus, which increased to 6 centers in 2019. Interestingly, with regard to type of living donor, the percentage of unrelated kidney donors has decreased by 20% for unclear reasons. Another alarming statistic is that more than 50% of kidney transplant physicians and surgeons are no longer practicing transplant medicine in their centers, either because they have left the country or because their centers had become nonoperational. Since the war, free and timely provision of immunosuppressive drugs for all patients in all provinces has been a leading challenge for health authorities and transplant patients. This difficulty has led to adverse medical consequences for patients. A project to initiate liver transplant came to a halt because of complex reasons but mainly because foreign trainers could not visit Syria. Although the autologous bone marrow transplant program had slowed until recently, it has become more active, involving both autologous and allogeneic transplants. The deceased-donor program is still not available in Syria; the war has just reinforced the many reasons that prevented the start of this program before the conflict. The commitment of transplant teams despite these large challenges continues to be extraordinary. The Syrian conflict has affected all aspects of organ transplant, paralyzing new projects and negatively affecting existing programs.

Limiting Factors Analysis in Validation of a CryoShipper &amp; a CryoExtra Freezer for Cryo-samples Related to the Abu Dhabi Bone Marrow Transplantation Program

<i>Introduction: </i>CryoShipper and CryoFreezer tanks were designed to safely transport and store biological material at cryogenic temperatures. An adverse warming event may occur if the CryoShipper is tilted during transit if temperature and proper levels of liquid nitrogen (LN2) vapors are not maintained. Storing cryogenic hematopoietic stem cell samples for a short or long time requires validating all pieces of equipment employed in a bone marrow transplant program. <i>Objective:</i> To determine the limitations of the <i>MVE CryoShipper CX</i> and the <i>Thermo Fisher</i> <i>CryoExtra™ Cryogenic tank</i> for the Abu Dhabi Bone Marrow Transplantation Program. <i>Methods:</i> The MVE <i>CryoShipper CX</i> was weighted and primed with LN2, and the excess was removed. After stabilizing the temperature, the shipper was tilted onto its side for 24, 72, and 96 hours. The temperature was monitored and recorded at 15 minutes intervals using a <i>Datalogger</i>. After returning to the correct upright position, the dry shipper temperature was also observed for five days after refilling with LN2 to evaluate the secure timing of a shipment. For an LN2 filled <i>CryoExtra</i> tank, dual control of the LN2 level and the temperature was done using manual measurement and automatic display. Later, vials and a bag from three healthy donors’ frozen white blood cell buffy coat samples were kept inside and defrosted daily to measure total mononuclear cell counts CD45+/7AAD cells viability by flow cytometry for five days. <i>Results:</i> The <i>CryoShipper</i> maintained cryogenic temperatures below -150°C for the entire duration of each analysis. A maximum temperature of -182.7°C was reached during the 24-hour tilt experiment from the temperature probe. The <i>CryoExtra 0140</i> freezer temperature was always between -184°C / -194.2°C, and LN2 levels coincided in both measuring methods during the time slot. Stored and defrosted cells keep their % of viability and absolute number over the expected reference range and compare mean+/-standard deviation (SD) between them without assessing the statistical difference with p≥0.05. The defrosted cells’ mean viability of 83.12%, SD±9.04, and a mean of 1,781 cell/µL, SD±1,215. <i>Conclusion: </i>Our modern dry shipper controls much of the vapor within the shipper. The <i>CryoShipper</i> can withstand being tilted during transit for 96 hours without risks of an adverse warming event. The <i>CryoExtra 0140</i> tank its performance was under the established parameters. Both types of cryogenic devices can be used for the safe cryopreservation of cell samples keeping all the security measures and controls as advised.

Probability of Finding a Matched Unrelated Donor for An Asian Indian Patient Who Needs a Stem Cell Transplant.

Abstract 4343In March 2008 we initiated a matched unrelated donor (MUD) bone marrow transplant program. Forty three searches have been performed through the National Marrow Donor Program USA (NMDP) and through the German Registry (DKMS) and completed data is available on 17 patients. High resolution HLA typing for A, B, DRB1, C and DQB1 alleles was done by Histogenetics (USA), NMDP or DKMS. Of the 17 patients for whom the search process was completed we identified a 10/10 matched donor for 7 patients, a 9/10 for 7 patients and an 8/10 for one patient. The 8/10 mismatch was at the C and DQB1 loci. Thus 15 of 17 (88%) had a suitable donor identified. After the preliminary search 2 patients were unlikely to have a donor. Of the15 matched donors, 4 were Caucasian and 11 were Asian. HLA is determined by the racial background of the individual and therefore the probability of finding a high resolution allele matched donor for an Asian Indian would have been low in registries that are predominantly Caucasian. Identification of matches from among the primarily Caucasian donor pool is interesting and may reflect a Caucasoid background in some of the population in the sub continent. In 11 out of the 17 completed searches an Asian donor was identified (61%). The NMDP has 7.5 million donors of which 553,000 are Asian and Pacific Islanders, 141,462 are South Asian, and 36,790 are Southeast Asian. These data exclude Asian donors reported as being from multiple races. Thus there was a 61% probability of finding a matched donor from among the 141,462 South Asian donors registered with the NMDP.Eleven patients have had a MUD transplant (Acute Myeloid Leukemia: 8, Acute Lymphatic Leukemia: 2 and Myelofibrosis: 1): 3 patients died before engraftment, 8 engrafted, 5 remain in remission, 2 have relapsed and one died of sepsis 100 days post transplant. The remaining four patients with matched donors are awaiting transplant.Since identification of a well-matched donor (allele matched at HLA-A, B, C, DRB1) is important for good outcome after MUD transplantation, these early search data for Indian patients suggest the need for a greater number of donors in India to be available and HLA typed in order to increase the probability of finding a suitable match for patients needing a MUD transplant.Number of SearchesDonor 10/10Donor 9/10Donor 8/10No DonorDonor M/FDonor C/ADonor CMV +/-/?Matched donor able to proceed to collection Yes/NoTransplanted187 [39%]7 [39%]1 [6%]3 [17%]12/34/119/5/411/411C- Caucasian A- Asian Disclosures:No relevant conflicts of interest to declare.

Infused Autograft Absolute Lymphocyte Count Predicts Superior Survival in Diffuse Large B Cell Lymphoma Patients Post-Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation: A Matched Case-Control Study

Our group published a double phase III trial showing that patients infused with an autograft absolute lymphocyte count (A-ALC) ≥0.5×109 cells/kg experienced superior survival post-autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT). Based on the results from our phase III study, as well as published retrospective studies, on April 1, 2017, our Bone Marrow Transplant Program changed our standard practice to collect an A-ALC ≥0.5×109 cells/kg in addition to stem cells for lymphoma patients undergoing APBHSCT. The primary objective of the present study was to continue to assess the prognostic ability of A-ALC by evaluating overall survival (OS) and progression-free survival (PFS) of diffuse large B cell lymphoma (DLBCL) patients who underwent APBHSCT after April 1, 2017, compared with matched control groups at a 1:1:1 ratio with DLBCL patients infused with an A-ALC <0.5×109 cells/kg and A-ALC ≥0.5×109 cells/kg before April 1, 2017. Using the GREEDY algorithm, 85 DLBCL patients (cases) infused with an A-ALC ≥0.5×109 cells/kg after April 1, 2017, were matched at a 1:1:1 ratio with control groups of DLBCL patients who underwent transplantation before April 1, 2017: patients infused with an A-ALC <0.5×109 cells/kg (control 1) and patients infused with an A-ALC ≥0.5×109 cells/kg (control 2) before April 1, 2017. Groups were matched in terms of sex, age, stage, lactate dehydrogenase (LDH) level, performance status, extranodal disease, International Prognostic Index (IPI), and disease status before APBHSCT (complete or partial response). Survival follow-up was truncated at 3 years from the date of transplantation. Cases, control 1, and control 2 were balanced as to age (P=.8), sex (P=.9), LDH (P=.6), performance status (P=.5), extranodal disease (P=.2), IPI (P=.6), and disease status before APBHSCT (P=.2). Cases and control 2 showed superior OS and PFS compared with control 1. Multivariate analysis including all patients continued to show A-ALC ≥0.5×109 cells/kg as an independent predictor for OS (hazard ratio [HR], 0.382; 95% confidence interval [CI], 0.241 to 0.605; P < .0001) and PFS (HR, 0.437; 95% CI, 0.279 to 0.629; P < .0001). Our matched case-control study supports the results of previously published retrospective studies and our phase III study showing that the infusion of A-ALC is a prognostic factor for survival in DLBCL patients undergoing APBHSCT. Our findings support the practice of collecting not only enough stem cells for hematologic engraftment, but also enough immune effector cells (ie, A-ALC) to improve clinical outcomes in DLBCL patients post-APBHSCT.

Bioprocess and analytics priorities for the tissue engineered product and cell therapy fields

Julie Allickson, PhD is Chief Manufacturing Development Center Officer at Wake Forest Institute for Regenerative Medicine. She heads the clinical translation team streamlining development to create a robust pipeline of products in development and early phase clinical trials including cellular therapy, genetically engineered cellular therapy, tissue engineered organs and tissues, biomaterials and devices. Prior to the Institute, she was the Vice President of Research and Development and Laboratory Operations for Cryo-Cell International Inc. Dr. Allickson has 30 years of experience in clinical translation of cellular therapies and regenerative medicine products including regulatory affairs, business management and board directorship experience. Other experience as an executive officer of a publicly traded company building services for cellular banking including licensure of technology. Dr. Allickson was part of the team to perform the first Bone Marrow Transplant at the University of Miami in 1990’s and at Miami Children’s Hospital Bone Marrow Transplant Program. She has a Doctorate in Health Sciences- Clinical Immunology along with a Master’s Degree in Medical Laboratory Sciences. She is one of the founding members of the International Society of Cellular Therapy. She is on the Board of Directors for AABB Board, Regenerative Medicine Outcomes Foundation as a scientific advisor and Scientific Advisory Board for Alliance for Cell Therapy Now. She is an Associate Editor for Journal of Translational Medicine, on the Editorial board of CELLR4, Vice Chair for Cord Blood Association Quality Committee, Technical Advisory Board for Tissue Engineered Products under ICCBBA, grant reviewer for state funded initiatives such as CIRM and serves on the ISCT Commercialization Committee.

Decreased Mortality in 1-Year Survivors of Umbilical Cord Blood Transplant vs. Matched Related or Matched Unrelated Donor Transplant in Patients with Hematologic Malignancies

Allogeneic hematopoietic stem cell transplantation (HCT) has the potential to cure hematologic malignancies but is associated with significant morbidity and mortality. Although deaths during the first year after transplantation are often attributable to treatment toxicities and complications, death after the first year may be due to sequelae of accelerated aging caused by cellular senescence. Cytotoxic therapies and radiation used in cancer treatments and conditioning regimens for HCT can induce aging at the molecular level; HCT patients experience time-dependent effects, such as frailty and aging-associated diseases, more rapidly than people who have not been exposed to these treatments. Consistent with this, recipients of younger cells tend to have decreased markers of aging and improved survival, decreased graft-versus-host disease, and lower relapse rates. Given that umbilical cord blood (UCB) is the youngest donor source available, we studied the outcomes after the first year of UCB transplantation versus matched related donor (MRD) and matched unrelated donor (MUD) transplantation in patients with hematologic malignancies over a 20-year period. In this single-center, retrospective study, we examined the outcomes of all adult patients who underwent their first allogeneic HCT through the Duke Adult Bone Marrow Transplant program from January 1, 1996, to December 31, 2015, to allow for at least 3 years of follow-up. Patients were excluded if they died or were lost to follow-up before day 365 after HCT, received an allogeneic HCT for a disease other than a hematologic malignancy, or received cells from a haploidentical or mismatched adult donor. UCB recipients experienced a better unadjusted overall survival than MRD/MUD recipients (log rank P = .03, median overall survival: UCB not reached, MRD/MUD 7.4 years). After adjusting for selected covariates, UCB recipients who survived at least 1 year after HCT had a hazard of death that was 31% lower than that of MRD/MUD recipients (hazard ratio, 0.69; 95% confidence interval, 0.47-0.99; P = .049). This trend held true in a subset analysis of subjects with acute leukemia. UCB recipients also experienced lower rates of moderate or severe chronic graft-versus-host disease (GVHD) and nonrelapse mortality, and slower time to relapse. UCB and MRD/MUD recipients experienced similar rates of grade 2-4 acute GVHD, chronic GHVD, secondary malignancy, and subsequent allogeneic HCT. UCB is already widely used as a donor source in pediatric HCT; however, adult outcomes and adoption have historically lagged behind in comparison. Recent advancements in UCB transplantation such as the implementation of lower-intensity conditioning regimens, double unit transplants, and ex vivo expansion have improved early mortality, making UCB an increasingly attractive donor source for adults; furthermore, our findings suggest that UCB may actually be a preferred donor source for mitigating late effects of HCT.

Outcomes of Allogeneic Stem Cell Transplantation with Individualized Dosing of Antithymocyte Globulin

Background: Allogeneic hematopoietic stem cell transplantation (HCT) is a potentially curative procedure for a variety of hematologic malignancies. However, relapse disease and graft-versus-host disease (GVHD) remain to be the main obstacle for a successful HCT. Thus, adequate immune suppression to minimize the risk of high-grade GVHD while not over suppression of donor immunity to allow graft versus tumor effect is crucial. Matched unrelated donor transplant has a higher rate of GVHD as compared to matched sibling donor transplant due to minor histocompatibility mismatch. Rabbit antithymocyte globulin (ATG), a polyclonal antibody produced by immunizing rabbits with human thymocytes, has been utilized as prophylaxis against GVHD. ATG dosing by weight has been the standard. Recent pharmacokinetic (PK) studies revealed that ATG levels and clearance vary significantly among patients receiving weight-based dosing of ATG. Recipient lymphocyte count before receiving ATG has been described as a modulator of both ATG PK and clinical outcomes after ATG-conditioned HCT. The Parachute-Study utilizing an individualized ATG dosing approach has shown more rapid immune reconstitution without affecting the incidence of acute GVHD and graft failure. In this study, we are comparing the outcomes of individualized dosing of ATG versus weight-based dosing. Method: This is a single institutional study carried out at the Bone Marrow Transplant Program at the University of Oklahoma Health Science Center. It was started as a case-control cohort study in July 2018 when individualized dosing of ATG was initiated, and continues as a historically controlled non-randomized prospective clinical study investigating individualized versus weight-based dosing of ATG. Subjects over 18 years of age who are undergoing matched unrelated donor (MUD) stem cell transplant, with myeloablative or reduced-intensity conditioning, peripheral blood or bone marrow stem cell source, for myeloid or lymphoid malignancies were included in the study. We excluded subjects with HLA mismatch or sibling donors. Individualized dosing was based on the previously validated PK model with cumulative doses varying between 2 to 10 mg/kg, based on weight, recipient lymphocyte counts before the first dose of ATG, and stem cell source, starting day -9; while the standard weight-based dosing of ATG is 4 mg/kg divided into 3 days pre-transplant. The study endpoints are to evaluate the difference between treatment groups on (1) GVHD and its severity; (2) relapse-free survival (RFS) and (3) overall survival (OS). Univariate logistic regression analysis was used to evaluate the probabilities of GVHD in both treatment arms. Multivariable analysis was done to adjust for all covariates between study arms using adjusted logistic. OS and RFS were computed using the Kaplan-Meier curves. Results: The study included 38 subjects undergoing MUD HCT for myeloid or lymphoid malignancies. Subjects included are in 2 cohorts, 19 subjects in the intervention arm using individualized targeted ATG (tATG group), and 19 subjects in the matched control arm using weight-based dosing ATG (ATG group). In a univariate unadjusted logistic regression analysis, the risk of developing GVHD is numerically higher in the ATG group than in the tATG group (OR=1.339, p=0.70). However, the proportion of acute GVHD is significantly higher in the tATG group than the ATG group (73.68% vs 31.58%, p=0.022). Also, the proportion of higher grade acute GVHD is significantly higher in the tATG group than the ATG group (31.58% vs 0%, p=0.020). RFS is longer in the tATG group than the ATG group, tending statistical significance (p=0.063). However, there is no difference in OS between study arms (p=0.645). [Figures 1 and 2] In a multivariable-adjusted logistic regression, adjusting for age at HCT, diagnosis, disease status at HCT, prior lines of therapy, and stem cell source, no confounder was found to be significantly associated with GVHD. Conclusion: Individualized targeted dosing of ATG (tATG), based on weight, recipient lymphocyte counts and stem cell source, increases the risk of acute GVHD when compared to standard fixed-dosing method, however, it improves RFS, implying possibly better immune reconstitution providing improved graft versus leukemia effect. Disclosures No relevant conflicts of interest to declare.

Infused Autograft-Absolute Lymphocyte Count Predicts Superior Survival in Diffuse Large B-Cell Lymphoma Patients Post-Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation: A Matched-Control Study

Introduction Day 15 absolute lymphocyte count (ALC-15) recovery after autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT) is recognized as a prognostic factor for survival. ALC-15 recovery is directly dependent on the amount of collected and infused autograft-absolute lymphocyte count (A-ALC). Our group published a double-blind phase III study which showed that patients infused with an A-ALC ≥ 0.5 x 109 cells/kg experienced superior survival post-APBHSCT. Based on the results from our phase III study, on April 1, 2017, our Bone Marrow Transplant Program changed our standard clinical practice to collect an A-ALC ≥ 0.5 x 109 cells/kg in addition to stem cells for lymphoma patients undergoing APBHSCT. To continue to assess the prognostic ability of A-ALC, we evaluated the overall survival (OS) and progression-free survival (PFS) of diffuse large B-cell lymphoma (DLBCL) patients that underwent APBHSCT after April 1, 2017 compared with a matched-control group in a 1:1:1 ratio with DLBCL patients infused with an A-ALC &amp;lt; 0.5 x 109 cells/kg or an A-ALC ≥ 0.5 x 109 cells/kg prior to April 1, 2017. Methods Eight-five consecutive DLBCL patients after our practice changed on April 1, 2017 received an A-ALC ≥ 0.5 x 109 cells/kg. For each DLBCL patient infused with an A-ALC ≥ 0.5 x 109 cells/kg after April 1, 2017, the set of potential controls was restricted to those DLBCL patients infused with an A-ALC &amp;lt; 0.5 x 109 cells/kg and an A-ALC ≥ 0.5 x 109 cells/kg prior to April 1 2017 . Within this group of potential controls, the subjects were chosen who best matched for the cases in terms of clinical risk variables, including gender, age, stage, lactate dehydrogenase (LDH), performance status, extra-nodal disease, International prognostic index (IPI), and disease status prior to APBHSCT (complete or partial response), using the GREEDY algorithm. Cases were defined as DLBCL patients infused with an A-ALC ≥ 0.5 x 109 cells/kg starting from April 1 2017. Control 1 was defined as DLBCL patients infused with an A-ALC &amp;lt; 0.5 x 109 cells/kg prior to April 1 2017. Control 2 was defined as DLBCL patients infused with an A-ALC ≥ 0.5 x 109 cells/kg prior to April 1 2017. We truncated the survival follow-up to 3 years starting from the date of transplant to match follow-up time between cases and controls. Both matched cases and control groups patients received BEAM conditioning. This retrospective study was approved by the Mayo Clinic Institutional Review Board according to the regulation of the Declaration of Helsinki. Results Cases, control 1 and control 2 were balanced to the clinical risk variables; age (p = 0.8); gender (p = 0.9); LDH (p = 0.6); stage (p = 0.3); performance status (p = 0.5); extra-nodal disease (p = 0.2); IPI (p = 0.6); and clinical status prior to transplant (p = 0.2). Figure 1A showed the OS and figure 1B the PFS. Both the cases and control 2 showed superior OS and PFS in comparison to control 1. Cases and control 2 showed overall similar OS and PFS. Multivariate analysis including all patients continue to depict the A-ALC ≥ 0.5 x 109 cells/kg as an independent predictor for OS (HR = 0.382, 95%CI=0.241-0.605, p &amp;lt; 0.0001) and PFS (HR = 0.437, 95%CI = 0.279-0.629, p &amp;lt;0.0001). Subgroup analysis, including all patients, shows superior OS and PFS for patients infused with an A-ALC ≥ 0.5 x 109 cells/kg for each of the following clinical variables: age [&amp;gt; 60 years: OS (p &amp;lt;0.0001); PFS (p &amp;lt;0.0001) or ≤ 60 years: OS (p &amp;lt;0.01); PFS (p , 0.02)]; extra-nodal disease [&amp;gt; 1: OS (p &amp;lt;0.008); PFS (p &amp;lt;0.01) or ≤1: OS (p &amp;lt; 0.001): PFS (p &amp;lt;0.0005)]; IPI [&amp;gt; 2: OS (p &amp;lt;0.01); PFS (p &amp;lt;0.02) or ≤ 2: OS (p &amp;lt;0.0008); PFS (p &amp;lt;0.0006)]; LDH [abnormal: OS (p &amp;lt;0.006); PFS (p &amp;lt;0.005) or normal: OS (p &amp;lt;0.002); PFS (p &amp;lt;0.002)]; performance status [&amp;gt; 1: OS (p &amp;lt;0.04); PFS (p &amp;lt;0.03) or ≤ 1: OS (p &amp;lt;0.0001); PFS (p &amp;lt;0.0001)]; stage [I/II: OS (p &amp;lt;0.006); PFS (p &amp;lt;0.006) or III/IV: OS (p &amp;lt;0.002); PFS (p &amp;lt;0.001)]; response prior to transplant [complete response: OS (p &amp;lt;0.0007); PFS (p &amp;lt;0.0001) or partial response: OS (p &amp;lt;0.01); PFS (p &amp;lt;0.02)]. Conclusion Our match-control study continues to support the results of our Phase III study showing that the infusion of A-ALC is a prognostic factor for survival of DLBCL patients undergoing APBHSCT. Our studies support the practice of not only collecting enough stem cells (i.e., CD34) for hematologic engraftment, but also enough immune effector cells (i.e., A-ALC) to improve clinical outcomes in DLBCL patients post-APBHSCT. Figure 1 Disclosures Ansell: Regeneron: Research Funding; Bristol Myers Squibb: Research Funding; Trillium: Research Funding; ADC Therapeutics: Research Funding; Takeda: Research Funding; AI Therapeutics: Research Funding; Affimed: Research Funding; Seattle Genetics: Research Funding.