A Case of X-Linked Moesin-Associated Immune Deficiency in a Pediatric Patient

Background: X-Linked Moesin-Associated Immune Deficiency (X-MAID) is a rare severe combined immunodeficiency (SCID) subtype that can present at any age due to its variability. Depending on severity, patients demonstrate failure to thrive, recurrent bacterial and viral infections, and increased susceptibility to varicella zoster. It has been characterized by marked lymphopenia with hypogammaglobulinemia and impaired T-cell migration and proliferation. Case Presentation: This is a report of a Cuban 7-year-old male with poor weight gain and facial dysmorphia. He had a history of recurrent bacterial gastrointestinal infections and pneumonia beginning at 4 months of age. He additionally had 4-6 upper respiratory tract and ear infections annually. While still living in Cuba, he was admitted for a profound EBV infection in the setting of significant leukopenia. A bone marrow biopsy confirmed no malignancy. After he moved to the United States, his laboratory work-up revealed marked leukopenia with low absolute neutrophil and lymphocyte count with low T and B cells, very low immunoglobulin levels IgG, IgA, and IgM, and poor vaccination responses to streptococcus pneumonia, varicella zoster, and SARS-CoV-2. Genetic testing revealed a missense pathogenic variant c.511C>T (p.Arg171Trp) in the moesin (MSN) gene associated with X-MAID. He was managed with Bactrim and acyclovir prophylaxis, and immunoglobulin replacement therapy, and considered for hematopoietic stem cell transplantation. Discussion(s): Diagnosis of X-MAID should be considered in patients with recurrent infections and profound lymphopenia. As with SCID, early diagnosis and intervention is of utmost importance to prevent morbidity and mortality. This case demonstrates the importance of genetic testing in identifying this disease as it may prompt an immunologist to consider HSCT if conservative management is suboptimal. In the current literature, HSCT appears promising, but the long-term outcomes have yet to be described.Copyright © 2023 Elsevier Inc.

Re-vaccination against SARS-COV2 in allogeneic HSCT patients: Repeated primary vaccines doses increases seroconversion rates

Patients undergoing treatment for haematological malignancies have been shown to have reduced antibody responses to vaccination against SARS-COV2. This is particularly important in patients who have undergone allogeneic haemopoietic stem cell transplantation (HSCT), in whom there is limited data about vaccine efficacy. In this retrospective single-centre analysis, we present data on serologic responses following one, two, three or four doses of either Pfizer-BioNTech (PB), AstraZeneca (AZ) or Moderna (MU) SARS-CoV- 2 vaccines from a series of 75 patients who have undergone allogeneic HSCT within 2 years from the time they were revaccinated. The seroconversion rates following post-HSCT vaccination were found to be 50.7%, 78%, 79% and 83% following the first, second, third and fourth primary post -HSCT vaccine doses, respectively. The median time from allograft to first revaccination was 145 days (range 79-700). Our findings suggest that failure to respond to the first SARS-CoV- 2 vaccine post-HSCT was associated with the presence of acute GVHD (p = 0.042) and treatment with rituximab within 12 months of vaccination (p = 0.019). A statistical trend was observed with the presence of chronic GVHD and failure to seroconvert following the second (p = 0.07) and third (p = 0.09) post-HSCT vaccine doses. Patients who had received one or more SARS-CoV- 2 vaccines prior to having an allogeneic stem cell transplant were more likely to demonstrate a positive antibody response following the first dose of revaccination against Sars-CoV- 2 (p = 0.019) and retained this seropositivity following subsequent doses. The incidence of confirmed COVID-19 diagnosis among this cohort at the time of analysis was 16%. 17% of these were hospitalised and there was one recorded death (8%) secondary to COVID-19 in a patient who was 15.7 months post allogeneic transplant. In summary, this study suggests that despite the initial low seroconversion rates observed postallogeneic transplant, increasing levels of antibody response are seen post the second primary vaccine dose. In addition, there seems to be lower risk of mortality secondary to COVID-19 in this vaccinated population, compared to what was reported in the earlier phases of the pandemic prior to use of SARS-COV2 vaccination. This adds support to the widely adopted policy of early full revaccination with repeat of primary vaccine doses and boosters post-HSCT to reduce mortality in this population. Finally, we have identified rituximab use and active GVHD as potential risk factors influencing serological responses to SARS-COV2 vaccination and further work should focus on further characterising this risk and optimum dosing schedule both pre-and post-transplant.

Celebrating the Sickle Cell Disease World Day on June 19th after Two Years of Pandemic: My Life with Scd, Patients' Perspective

Background: After two years of COVID in which activities were reduced due to the pandemic and each one's life was affected by restrictions and limitations, the Sickle Cell Disease (SCD) Association in Padova teamed up with the Sickle Cell Group at the Pediatric Hematology Oncology and Bone Marrow Transplant Unit to celebrate the Sickle Cell Disease world day by organizing an online meeting with children/youths and their families. Theme of the meeting was: "My Life with SCD: poems, pictures and writings express our view on disease and care". Aim(s): One of the goals of this meeting was to create an opportunity for individuals with SCD to meet and have a constructive discussion with each other about the disease and express their feelings after two years of pandemic. Method(s): One month before the meeting children, teenager and parents were asked to sharer with the organizing team any drawing, painting, poem, writing, that they felt could express their feelings or experience of the disease itself or how it affected their life, or their experience in the hospital. The materials received were organized in a power point presentation and At the meeting, families were able to see a PowerPoint presentation with the poems, drawings, writings. Each author had the choice to personally share their production or have it read out loud by a member of the team. Free time to comment or share experiences was given. Result(s): 20 children, teenagers and parents participated. Countries of origin (Nigeria, Ghana, Congo, Albania, Italy), religious background (catholic, muslim, no religion, other) were different as well as disease genotype (HbSS, HbSC, HbSBdegree), severity or treatment received (Hydroxyurea, transfusion, Hematopoietic stem cell transplantation -HSCT, none). Drawings and writings regarded experience with the disease (mechanism of action, admissions), feelings experienced (fear, hope, light at the end of the tunnel), aspirations (sports) and gratitude (to the social and medical team, to parents) (Figure 1). Surprisingly, families who had a child having undergone HSCT, reported on the need and importance to talk about this experience for years after the event and made a request of a support goup. Finally, all families underlined the need to meet again soon to discuss together issues related to personal experience with SCD, even via web. of discussion with each other and with the drepanocytosis group;and that throug the online telematics platform it is still possible to involve all families, listening and trying to comfort them on doubts and perplexities about the disease, In conclusion, it can be said that after two years of pandemic, in our setting, online meeting can help patients and families reconnect with each other and activities can be planned to aid experiences and feelings. Patients' associations and Health Care Teams can collaborate in this area.

COVID-19 pre-exposure prophylaxis with tixagevimab/cilgavimab in patients with haematological malignancy: A single-centre experience

Background: COVID-19 pandemic still pose a substantial threat worldwide despite increasing vaccine availability. Patients with haematological malignancies have been shown to have increased risk of contracting COVID-19 and are more susceptible to develop severe illness from SARS-CoV- 2 infection. The immune response to vaccines is impaired in patients with haematological malignancy due to underlying disease or antineoplastic therapies. The monoclonal-antibody combination, Evusheld is composed of tixagevimab and cilgavimab, two neutralising antibodies against SARS-CoV- 2. It has been shown to be safe and have efficacy for the prevention of COVID-19. Our aim of study is to describe the incidence and outcome of breakthrough COVID-19 infection among patients who received Evusheld in our centre and analyse the factors that possibly increase the risk of breakthrough infection. Material(s) and Method(s): A retrospective review of all adult patients with haematological malignancy who received tixagevimab/ cilgavimab 150/150 mg injection in Hospital Pulau Pinang from 1 July 2022 to 31 August 2022 with a follow-up period to 30 November 2022 was conducted. Demographic data, clinical characteristics and outcome will be retrieved from patient's medical records. Data were analysed using Statistical Package for Social Sciences software (version 21.0). Result(s): A total of 96 patients (50 males and 46 females) received tixagevimab/cilgavimab injection during the study period with a median age of 61 years (range 19-82). Majority of them were diagnosed with multiple myeloma (42.7%), followed by lymphoma (33.3%) and leukaemia (24%). One third of them had history of therapy with monoclonal antibody and 20% had haematopoietic stem cell transplantation. No major adverse effects of tixagevimab/cilgavimab injection were noted among the study population. Of the 12 patients (12.5%) who had COVID-19 infection, all of them had mild infection;three were asymptomatic and six patients received Paxlovid antiviral therapy. The median time from tixagevimab/cilgavimab to the onset of COVID-19 infection was 35 days (range 5-97 days). The mean age of patients with breakthrough COVID-19 infection were older compared to those without breakthrough infection but was not statistically significant. The incidence of breakthrough COVID-19 infection was not affected by type of haematological malignancy, history of monoclonal antibody therapy or COVID-19 vaccination. Discussion and Conclusion(s): Our findings showed that tixagevimab/cilgavimab was safe and effective in preventing COVID-19- related morbidity and mortality among patients with haematological malignancy during the study period. However, the limitation is the lack of access to whole genome sequencing for detection of resistant variants for breakthrough infections.

Anti-interferon-alpha autoantibodies in patients with inborn errors of Immunity and rheumatic diseases before and during the COVID-19 pandemic

Introduction: Type 1 interferon (IFN) autoantibodies, such as anti-IFNalpha, have pathogenic significance in life-threatening COVID-19 pneumonia. Ten to twenty percent of severe COVID cases are associated with type I IFN autoantibodies. These autoantibodies likely pre-exist while others arise de novo relative to SARS-CoV-2 infection. It is unclear to what extent type I anti-IFN autoantibodies are induced by SARS-CoV-2 infection and contribute to COVID-19 severity. We investigated these phenomena in those with inborn errors of immunity (IEI) and rheumatic disease (RHE). Aim(s): We aim to compare the prevalence and neutralization ability of anti-IFNalpha autoantibodies in IEI and RHE patients using archived blood samples before and after the COVID-19 pandemic began. Method(s): We determined the presence of autoantibodies against IFNalpha in plasma samples by enzyme linked immunosorbent assay in 453 patients with IEI or RHE who were testing either before or after the COVID-19 pandemic began in March 2020. Using flow cytometry, we determined the function of IFNalpha autoantibodies in plasma to block CD4T cell activation by inhibiting STAT-1 phosphorylation. Result(s): We found that 25 patients with IEI or RHE were positive for anti-IFNalpha autoantibodies. 10 out of 229 patient samples collected before the pandemic (4.2%) tested positive whereas 15 out of 224 patient samples collected after the pandemic began (7.0%) were positive. Seven of the 25 patients (28%) who tested positive had neutralizing antibodies in plasma, which prevented STAT-1 phosphorylation in CD4T cells;all of these patients had partial recombination activating gene deficiency (pRD) except for one patient with autoimmunity, leukemia and selective IgA deficiency. One pRD patient had anti-IFNalpha autoantibodies with neutralization capacity before the pandemic, which persisted after hematopoietic stem cell transplantation (HSCT) with full immune reconstitution. The patient was immunized for SARS-CoV-2 before and after HSCT and acquired COVID-19 infection a year after HSCT. The patient was symptomatic but never hospitalized and fully recovered despite having anti-IFNalpha autoantibodies. Conclusion(s): Anti-IFNalpha autoantibody levels were comparable before and after the start of the COVID-19 pandemic in IEI and RHE patients but only 28% of cases were neutralizing. The clinical implications of these autoantibodies are yet to be determined.Copyright © 2023 Elsevier Inc.

Clinical profile and outcomes of COVID-19 infection during the first wave in children with hematological illnesses and cancer: An observational study from a tertiary care center in North India

Background: Patients with cancer are at a higher risk of getting infected with the severe acute respiratory syndrome coronavirus 2 owing to their immunocompromised state. Providing care to these patients amidst the first wave of the coronavirus disease-2019 (COVID-19) pandemic was extremely challenging. Objective(s): This study was aimed at evaluating the clinical profile and disease-related outcomes of pediatric patients with hematological illnesses and cancer. Material(s) and Method(s): This retrospective study was conducted at a tertiary care center in North India during the first wave of the pandemic from March 2020 to December 2020. Children aged up to 18 years, who were treated for a hematological illness or malignancy or underwent hematopoietic stem cell transplantation (HSCT) and tested positive for COVID-19 regardless of symptoms were included in the study. Baseline demographic data related to the age, diagnosis, treatment status, and chemotherapy protocol used were collected. Outcomes including the cure rates, comorbidities, and sequelae were recorded. Result(s): A total of 650 tests for COVID-19 were performed for 181 children;22 patients were found to be COVID-19 positive. The most common diagnosis was acute leukemia (63.6%). None of the patients developed COVID-19 pneumonia. The majority of patients had asymptomatic infection and were managed at home. Among those with a symptomatic infection, the most common symptoms were fever and cough. A total of 3 (13.6%) patients needed oxygen therapy, one developed multisystem inflammatory syndrome of children leading to cardiogenic shock. Three patients required intensive care or respiratory support;all the patients had favorable clinical outcomes. The median time from the onset of COVID-19 to a negative result on the reverse transcription-polymerase chain reaction test was 21.3 days. Cancer treatment was modified in 15 patients (68.2%). Conclusion(s): Our results suggest that children with hemato-oncological illnesses rarely experience severe COVID-19 disease. The impact of the first wave of COVID-19 primarily manifested as disruptions in the logistic planning and administration of essential treatment to these children rather than COVID-19 sequelae.Copyright © 2021 Cancer Research, Statistics, and Treatment Published by Wolters Kluwer - Medknow.

Outcome of Haploidentical Hematopoietic Stem Cell Transplantation with a Donor and Recipient Infected with SARS-CoV-2 Infection

The current coronavirus disease 2019 (COVID 19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV 2), has impacted many facets of hematopoietic cell transplantation (HCT) in both developed and developing countries. The full impact of the COVID 19 pandemic, caused by the SARS CoV 2, on the field of hematopoietic cell transplantation (HCT) is unknown. Here, we report a rare case of a 21-year-old male patient known to have chronic myeloid leukemia (CML) with progression to T-cell lymphoblastic lymphoma as extramedullary blast crisis of CML. The patient was treated by pediatric chemotherapy regimen then. He underwent haploidentical stem cell transplantation. Posttransplantation, on day +7, he developed SARS-CoV-2 after receiving stem cell graft from a donor who was diagnosed with SARS-CoV-2 on the day of stem cells harvesting. The case elaborates complications and outcome of a patient receiving stem cell transplant from a donor with SARS-CoV-2 infection.Copyright © 2023 Journal of Applied Hematology Published by Wolters Kluwer - Medknow.

Check Point SOS! A Case of Cemiplimab-Associated Sinusoidal Obstruction Syndrome

Introduction: Hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS), is a clinical syndrome characterized by hepatomegaly, right-upper quadrant pain, and ascites that occurs most commonly in the setting of high-dose chemotherapy or hematopoietic stem cell transplantation (HSCT). The diagnosis can be confirmed on biopsy. Cemiplimab is an immune checkpoint inhibitor recently approved for the treatment of cutaneous squamous cell carcinoma. There are currently no known reports of immune checkpoint inhibitor-related VOD/SOS. Case Description/Methods: A 58-year-old female with a history of locally advanced basal cell carcinoma of the left eye treated with six months of Cemipilimab presented with ascites. On admission, labs were notable for a total bilirubin of 1.2, mildly elevated liver function tests, alkaline phosphatase 884, and international normalized ratio 2.1. A diagnostic tap revealed a high SAAG ascites that was negative for infection. A comprehensive serological workup for viral, metabolic and autoimmune causes was unrevealing. A transjugular liver biopsy demonstrated a hepatic venous pressure gradient of 18mmHg, nodular regenerative hyperplasia (NRH), and portal venopathy. The patient was discharged on steroids but returned one month later for recurrent ascites and worsening bilirubin to 12.6 (direct 7.3);COVID PCR was negative. A full rheumatologic and vasculitis workup was unremarkable. Repeat biopsy (Figure 1) demonstrated moderate NRH changes, prominent central vein sclerosis with fibrous obliteration, signs of SOS/ VOD and central venulitis with fibrotic changes with sinusoidal portal hypertension. Discussion(s): VOD occurs most often with hematopoietic stem cell transplantation, and chemotherapeutic agents. Here we present the first case of checkpoint inhibitor-induced VOD/SOS. Despite discontinuation of the offending agent and a trial of steroids, the patient's clinical course continued to deteriorate. She eventually developed refractory ascites and portosystemic encephalopathy. She was deemed not a candidate for liver transplant given her underlying malignancy. She was transitioned to home hospice before further treatment, such as Defibrotide could have been pursued. VOD associated with immune checkpoint inhibition should be considered in the differential of patients who develop new onset liver dysfunction and ascites while receiving these medications (Figure Presented).

Can You Spare 100 Days? The Allogeneic Hematopoietic Cell Transplant Caregiver Requirement

Allogeneic hematopoietic cell transplantation (alloHCT) is a potentially curative treatment for patients diagnosed with blood cancers (such as acute myeloid leukemia) and blood disorders (such as sickle cell disease). It is a resource-intensive treatment that generally requires a long hospital stay and recovery period. If continuous caregiver support is not available, alloHCT likely will not be a treatment option. To learn more about caregiver requirements and perspectives on those requirements, we conducted web-based focus groups with alloHCT social workers who worked with adult patients at United States (US) transplant centers (TCs) from May-July 2022. Web-based interviews with adult alloHCT recipients,caregivers of adult alloHCT recipients, and physicians/advanced practice professionals will also be conducted. Twenty-two social workers from TCs across the US (Midwest [n=8];West [n=5];Northeast: [n=5];South, [n=4]) and with varying volumes (median: 97 alloHCTs performed/year) participated. All noted their TC required a caregiver to proceed to alloHCT. However, there was variation across TCs in the length of time a recipient was required to have a caregiver, the distance/time needed to stay near the TC post-alloHCT, and COVID-19 vaccination requirements. The majority of participants also noted variance among the transplant team in allowing exceptions for caregiver requirements. All participants noted it would be helpful to have a 'gold standard' of requirements across TCs, though there was discussion about what such a standard would include, as well as the need for flexibility to account for different patient and TC needs. Social workers were also asked to identify patient barriers to meeting the caregiver requirement;common barriers included patients feeling they did not have anyone to ask to be a caregiver, the need to relocate closer to the TC, and financial barriers. The impact of the COVID-19 pandemic was also noted (e.g., vaccination requirements, and increased telework allowing more flexibility for caregivers). In analysis of the first of four populations interviewed in this study, social workers reported variation in caregiver requirements across TCs. Finding a caregiver is one of many barriers patients face in accessing alloHCT. Though this variation may allow for some flexibility, it may also contribute to access barriers. This study focused on those who received an alloHCT, but further research is needed to learn about barriers faced by those unable to access alloHCT. Results from this and other cohorts will describe current practices related to caregiver requirements and help inform the development of new programs to reduce caregiver-related barriers to alloHCT.Copyright © 2023 American Society for Transplantation and Cellular Therapy

Can You Spare 100 Days? Allogeneic Hematopoietic Cell Transplant Caregiver Requirements from the Perspective of Recipients and Caregivers

Allogeneic hematopoietic cell transplantation (alloHCT) is a potentially curative treatment for individuals diagnosed with blood cancers (e.g., acute myeloid leukemia) and blood disorders (e.g., sickle cell disease). Most transplant centers (TCs) require a caregiver to proceed with alloHCT. Caregiver requirements can be one of many barriers to alloHCT, as individuals without a caregiver can have limited or no access to this treatment. Few studies have described TC caregiver requirements, particularly from the perspective of recipients and caregivers. To learn more about alloHCT caregiver requirements and perspectives on those requirements, we conducted web-based interviews with adult alloHCT recipients and adult caregivers of adult alloHCT recipients in the United States (US) starting in May 2022. Recipients needed to be between 100 days and 1-year post-HCT and in remission;Table 1 describes participant demographics.(Table Presented)The majority of participants noted that their TC required a caregiver to proceed to alloHCT;however, there was variation in the length of time required to have a caregiver. When asked their perspective on the amount of time the TC required, the majority of participants noted that the actual length of time depended on the recipient's recovery (with some noting more time was needed and others noting less). Participants were also asked to share barriers they faced regarding the caregiver role. A common barrier included not fully understanding the specifics of the caregiver requirements, or what it would entail. Some recipients described being provided with too much information, making it difficult to sort through, while others reported feeling like they did not receive enough information. Other barriers identified by recipients included competing priorities of the caregiver (such as work/ home responsibilities and childcare), language barriers, and finances. Common barriers identified by caregivers included: feeling like they could not take time for themselves/their own health suffered and needing to be trained to perform medical tasks. Many recipients and caregivers also noted the impact of the COVID-19 pandemic (e.g., postponing alloHCT, trepidation about going to the TC, post-alloHCT housing restrictions, and increased telework for caregivers). Preliminary analysis of recipients and caregivers interviews showed variation in caregiver requirements across TCs. There is a need for clear, accessible information to help recipients and caregivers understand the caregiver role and requirements. This study included recipients and caregivers;further research is needed to identify barriers faced by individuals unable to access alloHCT. Results from this study will help facilitate the development of programs to help improve access to alloHCT.Copyright © 2023 American Society for Transplantation and Cellular Therapy

Developing Contemporary Survivorship Clinic for Recipients of Hematopoietic Cell Transplantation: A Single Center Experience

Introduction: Survival after hematopoietic cell transplantation (HCT) has improved tremendously over the last few decades. HCT survivors are at increased risk of long-term complications and secondary cancers. This poses unique challenges to the HCT-related healthcare system given the growing need for survivorship care. Developing a HCT survivorship program with a dedicated clinic to survivors ensures equitable access to care and ongoing patient education. Herein, we describe our program survivorship model and our initial experience. Method(s): The Moffitt Cancer Center (MCC) survivorship clinic (SC) planning committee was initiated in September 2019. The SC was launched in January 2021 with the mission to provide high-quality, comprehensive, and personalized survivorship care and to empower patients and community health care providers with education and a roadmap for screening for late effects. The SC initially focused on allogeneic (allo) HCT patients and later opened to autologous (auto) HCT recipients in February 2022. HCT patients are referred by primary HCT team after HCT with an emphasis on preferred timeframe of initial SC visit no earlier than 3 months but less than 12 months from HCT. SC is located at 2 physical locations: main campus and satellite, with virtual visit options to account for the distance from MCC and COVID considerations. SC applies a consultative model. SC is staffed by dedicated advanced practice professional (APP), supervised by SC faculty. The scope of SC care includes but is not limited to prevention of infections (education, vaccinations), surveillance of late effects (endocrine, pulmonary function, cardiac, bone health), and general cancer screenings (breast, colon, skin cancer). Patients' clinical data from SC inception to August 2022 were reviewed. Result(s): From January 2021 to August 2022, a total of 138 patients were seen in SC. The majority were seen in person (62% in clinic, 38% by virtual visit). Median age was 58 years (range, 19-82). Median time to first SC visit was 21 months (range, 3-1464) after HCT. Allo HCT was the most common type of HCT seen in clinic (87%, n=120). Most common diagnoses were acute myeloid leukemia (43%, n=59), myelodysplastic syndrome (17%, n=23), and acute lymphoblastic leukemia (10%, n=14). Only 17 patients (12%) were seen in 2021 but the volume increased significantly in 2022. Currently there are more than 10 patients seen in SC per month. Conclusion(s): We report successful experience in launching a contemporary HCT SC despite the challenges of an ongoing COVID pandemic. As a stand-alone cancer center, we serve a wide geographical location with subspecialty and primary care providers dispersed throughout the community. Our consultative model and experience could provide a useful guide for other programs. In 2023, we plan to expand our SC to a broader population of patients receiving other cellular immunotherapies.Copyright © 2023 American Society for Transplantation and Cellular Therapy

Cryopreservation of Unrelated Donor Stem Cell Grafts Is Associated with Lower Rates of Chronic Gvhd after Allogeneic Transplantation

Allogeneic hematopoietic stem cell transplantation (allo- HSCT) has traditionally involves administering fresh peripheral blood or bone marrow stem cells. At onset of the COVID-19 pandemic in March 2020, the National Marrow Donor Program (NDMP) mandated cryopreservation of all unrelated peripheral blood stem cell (PBSC) products to prevent interruptions in transplant plans by donor COVID-19 infection after recipient's start of conditioning chemotherapy. Since the lifting of this mandate, many centers have continued to cryopreserve grafts prior to initiation of conditioning, but the longer-term clinical outcomes of this practice including chronic graft versus host disease (cGVHD) rates of patients receiving cryopreserved stem cells have not been previously well described. Prior work has raised concern for a deleterious effect of cryopreservation on overall survival and non-relapse mortality (PMID: 33865804). However, heterogeneity in the patient population and reason for cryopreservation suggest that further study is needed to assess these outcomes. Here we report our single-institution experience of clinical outcomes using cryopreserved versus fresh URD PBSCs for allo-HSCT. We examined long-term outcomes in 387 patients who received unrelated donor (URD) PBSCs (136 cryopreserved, 251 fresh) between January 1, 2019 and July 31, 2021. The cohorts had similar baseline characteristics including donor/recipient age/sex, disease, conditioning regimen/intensity, and GVHD prophylaxis regimens. Two-year OS, PFS, relapse, NRM, and acute GVHD rates were not different between recipients of fresh versus cryopreserved PBSCs. Strikingly, 2-year incidence of cGVHD (28% vs 52%, p=0.00001) and moderate/severe cGVHD (9% vs 24%, p=0.00016) was substantially lower in recipients of cryopreserved PBSCs compared to fresh, respectively (Figure 1). This difference was only noted in patients receiving a GVHD prophylaxis regimen without post-transplantation cyclophosphamide (PTCY) (no PTCY 2-year cGVHD incidence cryopreserved vs fresh: 29% vs 57%, p=0.000016), moderate/severe cGVHD 16% vs 34%, p=0.0006) (Figure 2). For patients receiving a PTCY-containing GVHD prophylaxis regimen, there was no difference in cGVHD incidence (cGVHD cryopreserved vs fresh: 24% vs 27%, p=0.56, moderate/severe cGVHD 7% vs 9.3%, p=0.3, Figure 3). (Figure Presented) (Figure Presented) (Figure Presented) While survival and relapse rates are not different, cryopreservation is associated with a marked reduction in cGVHD rates in the setting of non-PTCy based GVHD prophylaxis. Larger multicenter or registry analyses are needed to confirm these observations and may prompt a re-assessment of the role of cryopreservation of stem cell products in clinical practice. If confirmed, it will be critical to understand the immunologic consequences of cryopreservation and how they might influence the clinical impact on chronic GVHDCopyright © 2023 American Society for Transplantation and Cellular Therapy

Why Are Patients Not Getting a Graft? An Intent-to-Transplant Analysis in the Times of Universal Coverage and Haploidentical Donors

Introduction: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a potentially curative option for patients with hematologic diseases. When considered candidates, patients face barriers to receive a transplant. Therefore, we aimed to analyze factors that limit or favor access to an alloHSCT in a population that has been HLA typed and therefore with a potential intent-to-transplant. Method(s): We retrospectively reviewed records from 2015 until the start of the COVID19 pandemic in two Mexican government- funded transplant centers and one private that have in-house HLA typing;in two of them, an outpatient transplant strategy is followed for most patients. HLA-typed patients who were potentially eligible for transplantation were included and their outcomes were assessed in an intent-to-transplant basis. We compared the outcomes of patients who underwent transplantation to those who did not and evaluated contributing barriers to access alloHSCT with multivariate logistic regression. Result(s): A total of n=374 patients were analyzed. The median age at HLA-typing was 35 years (IQR 23-47);59.3% had acute(Table Presented) leukemia, 17.4% bone marrow failure or myelodysplastic neoplasms, 13.1% lymphoma, 8% myeloproliferative neoplasms, 1.1% chronic lymphocytic leukemia and 1.1% multiple myeloma. Most patients (55.9%) had government insurance coverage. Median time from diagnosis to HLA-typing was 8 months (IQR 3-19). The majority had a potential donor (94.4%): 56.4% haploidentical, 37.4% a matched sibling donor and 0.5% an unrelated donor. Almost half of them received a transplant (n=185, 49.5%), the median time from HLA-typing to alloHSCT was 2 months (IQR 1-5.5). Disease activity or progression was the biggest barrier for transplantation;Table 1. Donor availability limited transplant access for 12.1% of patients. Access to transplantation was favored by private/out-of-pocket payment (OR 2.1 95% CI 1.3-3.4), and receiving care in the outpatient center (OR 6.4 95% CI 4-10.0), while HLA matching was not (OR 1.2 95% CI 0.8-1.8). Non-relapse mortality in alloHSCT was 21%. Median overall survival (OS) from the intent-to-transplant cohort was 16 months (CI 95% 12.4-19.6). An OS landmark analysis for patients alive at or beyond 2 months (the median time from HLA-typing to alloHSCT) showed prolonged survival in alloHSCT (30 vs 12 months, p <.001), Figure 1. By the time of the analysis 159 patients (42.5%) were still alive and 115 (30.7%) were event-free.(Figure Presented)Conclusion: The most frequent barrier to transplantation was the disease itself, followed by the transplant waitlist and comorbidities. Access to resources and an outpatient strategy or "center effect" favored alloHSCT. In the era of haploidentical transplantation, donor availability was a smaller issue. Efforts to improve timely referrals and access to effective pre-transplant therapies should be undertaken.Copyright © 2023 American Society for Transplantation and Cellular Therapy

Successful matched unrelated donor hematopoietic stem cell transplantation for infantile Wolman disease

Introduction: Wolman disease is a rare genetic disorder with an autosomal recessive inheritance. A mutation in the LIPA gene causes lysosomal acid lipase (LAL) deficiency results in lipid storage and adrenal insufficiency. Death in early infancy is due to liver failure. Patients and methods: We describe the clinical course of a three-month-old infant diagnosed with Wolman disease. A rapid mutational analysis confirmed a LIPA gene defect. Results: He underwent matched unrelated donor peripheral blood stem cell hematopoietic stem cell transplantation (HSCT) at 3 months of age, with a treosulfan-based conditioning, which resulted in engraftment with donor-derived hematopoietic cells. He required supportive care for sinusoidal obstruction syndrome and mucositis. He was administered low dose prednisolone for grade I skin graft versus host disease, and a complete donor chimerism was documented on several occasions. At one year post HSCT, his growth and development were optimal, and there was no hepatosplenomegaly. He is maintained on glucocorticoid and mineralocorticoid supplements for primary hypoaldosteronism. Conclusion: The case emphasizes the timely diagnosis and the potential for successful treatment of Wolman disease by HSCT. © 2022 Pediatric Hematology Oncology Chapter of Indian Academy of Pediatrics

Atypical Course of SarsCov-2 Infection in a Patient with Multiple Myeloma Treated with Autologous Stem Cell Transplantation

Covid-19 infection has more relevant consequences in frail and comorbid patients but little is known about its course in patients with hematologic malignancies. In this report we would like to present the case of a patient with multiple myeloma treated with recent autologous bone marrow stem cell transplantation and affected by Covid-19 pneumonia, presenting with a possible reinfection or an extremely long viral shedding.Copyright © 2023 Tehran University of Medical Sciences.

Challenges and Results of Haploidentical Stem Cell Transplantation for Adult Patients in Cuba

The Hermanos Ameijeiras Hospital (HAH) in Havana is the only center performing allogeneic hematopoietic stem cell transplantation (HSCT) in adult patients in Cuba. Because transplants from unrelated donors are not possible due to political restrictions and economic embargo, in 2016 HAH and University of Illinois at Chicago (UIC) started a collaboration to support the training of a physician, annual educational programs and exchange of guidelines and protocols to perform haploidentical transplants. The first haploidentical transplant was performed at HAH in 2016. Because of limited resources, disease risk stratification is based on morphologic assessment, as cytogenetic is tested on an irregular basis. Peripheral blood stem cells (PBSC) were infused based on total nucleated cell count (TNC) due to lack of reagents for flow cytometry. Posttransplant chimerism and CMV monitoring cannot be performed. Transplant activity was stopped in 2020 due to high expenses allocated for COVID19 pandemic in Cuba. From 2016 to 2020, 16 haploidentical HSCT in 15 patients (9 males/ 6 females) were completed at HAH. The median age of patients was 34 years (range:21-54). Diagnoses included: acute leukemia, n=12, myelodysplastic syndrome, n=1, Hodgkin disease, n=1, and severe aplastic anemia, n=1. At the time of transplant, 11 patients were in morphologic remission and 5 had active disease. Conditioning regimens utilized were myeloablative (Flu/Bu) in 10 cases and at reduced intensity (Flu/Cy/ TBI200 +/- ATG) in 6 cases, and GVHD prophylaxis was standard PTCy on D3 and 4, CsA and mycophenolate. The donors were mother (n=10), father (n=1), child (1), or sibling (n=3) and the median age was 48 years (range: 26-68). All patients received fresh stem cells from PBSC(n=13) or bone marrow (n=3). Median cell dose infused was 5.5x108 TNC/kg (range: 2.2-8). All patients but 1 engrafted and median time to neutrophil and platelet engraftment was 17 days (range:12-28) and 16 days (range:11-30), respectively. Acute graft-versus-host disease (GVHD) grade 2-3 occurred in 50% of patients and chronic GVHD in 2 out of 8 that were evaluable. Day 100 and 2-year overall survival rates were 73% and 40%, respectively. With a medium follow-up of 18.8 months (range: 0.3-64), 5 of 15 patients (30%) are alive and complete remission. Causes of death in the remaining 10 patients included relapse of original disease, n= 4;bacterial infection, n=2;brain hemorrhage, n=1;VOD, n=1;graft failure, n=1;and multi-organ failure, n=1. Despite significant difficulties, HAH implemented a haploidentical transplant program for adult patients in Cuba. Among future steps, improving access to molecular testing and using younger donors will be pursued to improve on the results. The partnership between HAH and UIC has been instrumental in building clinical and research capacity and continues to support HAH in its mission to provide care to patients in Cuba.(Figure Presented)Copyright © 2023 American Society for Transplantation and Cellular Therapy