Exacerbation of autoimmune hemolytic anemia associated with pure red cell aplasia after COVID-19: A case report.

Autoimmune hemolytic anemia (AIHA) and pure red cell aplasia (PRCA) are rare complications of coronavirus disease 2019 (COVID-19). Herein, we report the case of a 28-year-old Japanese man who showed severe AIHA exacerbation associated with PRCA after COVID-19. AIHA was diagnosed and maintained for 5 years. Approximately 4 weeks after COVID-19, the patient developed severe anemia (hemoglobin level, 3.4 g/dL). Laboratory test results confirmed hemolytic exacerbation of IgG-mediated warm-type AIHA. Despite the hemolysis phase, the bone marrow revealed extreme hypoplasia of erythroblasts with a decreased reticulocyte count, similar to that observed in patients with PRCA. During oral prednisolone treatment, the patient recovered from anemia and showed increased reticulocyte count and reduced hypoplasia of marrow erythroblasts. Exacerbation of AIHA and PRCA was triggered by COVID-19 because other causes were ruled out. Although this case report highlights that COVID-19 could lead to hematological complications such as AIHA and PRCA, the exact mechanisms remain unclear.

Prevalence of phalangeal bone marrow edema on MRI before and during the COVID-19 pandemic and correlation with chilblain skin lesions.

OBJECTIVE: The purpose of this study is to establish the prevalence bone marrow edema of the phalanges of the feet and hands before and during the COVID-19 pandemic on MRI studies and correlate with clinically chilblain skin lesions and epidemiological data. METHODS: This observational retrospective study. In patients with confirmed bone marrow edema of the phalanges, epidemiological data and clinical findings were collected, including the history of current or remote COVID-19 infection and vaccination status. The two-proportion test was used to compare the frequency of bone marrow edema in the phalanges before and during the pandemic, and the comparison between the categories variables was performed using the one-proportion test. RESULTS: Of the total of 7215 patients, only 20 presented isolated bone marrow edema of the digits in MRI studies; 2 (0.05%) were found two years before the pandemic's beginning, and 18 (0.64%) after the pandemic's onset, demonstrating an increase of 13-fold in this period. 16 were women with a mean age of 40.3 years and 4 were men with a mean age of 53.5 years. The most frequently reported clinical symptoms by the patients were pain (85.0%), and erythema of the skin (45.0%). Of the 18 patients found after the pandemic's onset, only 27.8% had COVID-19 infections confirmed by RT-PCR before the imaging study, and all cases were mild. CONCLUSION: This study demonstrated a significant increase in the prevalence of bone marrow edema of the phalanges after the onset of the COVID-19 pandemic, particularly in middle-aged and younger women.

Molecular Markers of Blood Cell Populations Can Help Estimate Aging of the Immune System.

Aging of the immune system involves functional changes in individual cell populations, in hematopoietic tissues and at the systemic level. They are mediated by factors produced by circulating cells, niche cells, and at the systemic level. Age-related alterations in the microenvironment of the bone marrow and thymus cause a decrease in the production of naive immune cells and functional immunodeficiencies. Another result of aging and reduced tissue immune surveillance is the accumulation of senescent cells. Some viral infections deplete adaptive immune cells, increasing the risk of autoimmune and immunodeficiency conditions, leading to a general degradation in the specificity and effectiveness of the immune system in old age. During the COVID-19 pandemic, the state-of-the-art application of mass spectrometry, multichannel flow cytometry, and single-cell genetic analysis have provided vast data on the mechanisms of aging of the immune system. These data require systematic analysis and functional verification. In addition, the prediction of age-related complications is a priority task of modern medicine in the context of the increase in the aged population and the risk of premature death during epidemics. In this review, based on the latest data, we discuss the mechanisms of immune aging and highlight some cellular markers as indicators of age-related immune disbalance that increase the risk of senile diseases and infectious complications.

Haemophagocytic lymphohistiocytosis following a COVID-19 infection: case report.

The case of a 57-year-old male patient with jaundice, high-grade fever, and upper abdominal pain who was recovering from a mild coronavirus disease-19 (COVID-19) infection is reported. Laboratory analysis showed liver injury with high levels of AST and ALT, as well as an elevated serum ferritin level. The patient underwent a bone marrow biopsy which showed features of hemophagocytic lymphohistiocytosis (HLH), a systemic syndrome caused by immune activation. The patient was successfully treated with etoposide and dexamethasone and kept on maintenance therapy with cyclosporine, with resolution of the HLH. The discussion highlights that COVID-19 infection may cause liver injury, and in severe cases, patients may develop HLH as a cause for liver injury. The incidence of HLH in adults with severe COVID-19 infection is estimated to be lower than 5%. The association between HLH and COVID-19 infection has been studied due to immunological hyperactivation. Signs such as persistent high fever, hepatosplenomegaly, and progressive pancytopenia should raise suspicion for the diagnosis of overlapping HLH. A specific approach using steroids and etoposide, followed by maintenance therapy with cyclosporine, is proposed in the HLH-94 protocol as the mainstay of treatment. It is suggested that HLH should be suspected in patients with laboratory signs of liver injury following COVID-19 infection, especially in patients with high-grade fever and a history of rheumatic conditions.

Risk factors for a severe disease course in children with SARS-COV-2 infection following hematopoietic cell transplantation in the pre-Omicron period: a prospective multinational Infectious Disease Working Party from the European Society for Blood and Marrow Transplantation group (EBMT) and the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH) study.

Risk factors for severe SARS-Cov-2 infection course are poorly described in children following hematopoietic cell transplantation (HCT). In this international study, we analyzed factors associated with a severe course (intensive care unit (ICU) admission and/or mortality) in post-HCT children. Eighty-nine children (58% male; median age 9 years (min-max 1-18)) who received an allogeneic (85; 96%) or an autologous (4; 4%) HCT were reported from 28 centers (18 countries). Median time from HCT to SARS-Cov-2 infection was 7 months (min-max 0-181). The most common clinical manifestations included fever (37; 42%) and cough (26; 29%); 37 (42%) were asymptomatic. Nine (10%) children following allo-HCT required ICU care. Seven children (8%) following allo-HCT, died at a median of 22 days after SARS-Cov-2 diagnosis. In a univariate analysis, the probability of a severe disease course was higher in allo-HCT children with chronic GVHD, non-malignant disease, immune suppressive treatment (specifically, mycophenolate), moderate immunodeficiency score, low Lansky score, fever, cough, coinfection, pulmonary radiological findings, and high C-reactive protein. In conclusion, SARS-Cov-2 infection in children following HCT was frequently asymptomatic. Despite this, 10% needed ICU admission and 8% died in our cohort. Certain HCT, underlying disease, and SARS-Cov-2 related factors were associated with a severe disease course.

Improved outcomes over time and higher mortality in CMV seropositive allogeneic stem cell transplantation patients with COVID-19; An infectious disease working party study from the European Society for Blood and Marrow Transplantation registry.

Introduction: COVID-19 has been associated with high morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. Methods: This study reports on 986 patients reported to the EBMT registry during the first 29 months of the pandemic. Results: The median age was 50.3 years (min - max; 1.0 - 80.7). The median time from most recent HCT to diagnosis of COVID-19 was 20 months (min - max; 0.0 - 383.9). The median time was 19.3 (0.0 - 287.6) months during 2020, 21.2 (0.1 - 324.5) months during 2021, and 19.7 (0.1 - 383.9) months during 2022 (p = NS). 145/986 (14.7%) patients died; 124 (12.6%) due to COVID-19 and 21 of other causes. Only 2/204 (1%) fully vaccinated patients died from COVID-19. There was a successive improvement in overall survival over time. In multivariate analysis, increasing age (p<.0001), worse performance status (p<.0001), contracting COVID-19 within the first 30 days (p<.0001) or 30 - 100 days after HCT (p=.003), ongoing immunosuppression (p=.004), pre-existing lung disease (p=.003), and recipient CMV seropositivity (p=.004) had negative impact on overall survival while patients contracting COVID-19 in 2020 (p<.0001) or 2021 (p=.027) had worse overall survival than patients with COVID-19 diagnosed in 2022. Discussion: Although the outcome of COVID-19 has improved, patients having risk factors were still at risk for severe COVID-19 including death.

Risk of COVID-19 infection in long-term survivors of blood or marrow transplantation: a BMTSS report.

There is limited information regarding COVID-19 in long-term blood or marrow transplant (BMT) survivors. We leveraged the BMT Survivor Study (BMTSS) to address this gap. BMTSS included patients who underwent BMT at 1 of 3 sites in the United States between 1974 and 2014 and survived ≥2 years after BMT. A sibling cohort serves as a non-BMT comparison group. Participants (2430 BMT survivors; 780 non-BMT participants) completed the BMTSS survey between October 2020 and November 2021 about COVID-19 testing, risk mitigation behaviors, morbidity, and health care use. Median age at BMT was 46 years (range, 0-78 years) and median follow-up since BMT was 14 years (6-46 years); 76% were non-Hispanic White, 54% had received allogeneic BMT. The risk of COVID-19 infection was comparable for BMT survivors vs non-BMT participants (15-month cumulative incidence, 6.5% vs 8.1%; adjusted odd ratio [aOR] = 0.93; 95% confidence interval [CI], 0.65-1.33; P = .68). Among survivors, being unemployed (aOR 1.90; 95% CI, 1.12-3.23; P = .02; reference: retired) increased the odds of infection; always wearing a mask in public was protective (aOR = 0.49; 95% CI, 0.31-0.77; P = .002; reference: not always masking). When compared with COVID-positive non-BMT participants, COVID-positive BMT survivors had higher odds of hospitalization (aOR = 2.23; 95% CI, 0.99-5.05; P = .05); however, the odds of emergency department visits were comparable (aOR = 1.60; 95% CI = 0.71-3.58; P = .25). COVID-19 infection status did not increase the odds of hospitalization among BMT survivors (aOR = 1.32; 95% CI = 0.89-1.95; P = .17) but did increase the odds of emergency department visits (aOR = 2.63; 95% CI, 1.74-3.98; P <.0001). These findings inform health care providers about the management of care for long-term BMT survivors during the ongoing pandemic.

A fatal SARS-coronavirus-2 induced bone marrow aplasia complicated with invasive fungal infection and severe neutropenic enterocolitis.

BACKGROUND: Immunization against the coronavirus disease 2019 (COVID-19) began in January 2021 in Iran; nonetheless, due to a lack of vaccination among children under 12, this age group is still at risk of SARS-CoV-2 infection and its complications. CASE PRESENTATION: SARS-CoV-2 infection was diagnosed in a 6-year-old girl who had previously been healthy but had developed a fever and pancytopenia. The bone marrow aspiration/biopsy demonstrated just hypocellular marrow without signs of leukemia. She was worked up for primary and secondary causes of pancytopenia. Except for a repeated reactive HIV antibody/Ag P24 assay, all test results were inconclusive. After a thorough diagnostic investigation, the cross-reactivity of the HIV antibody/Ag P24 test with SARS-CoV-2 antibodies was confirmed. The patient did not develop any COVID-19-related signs and symptoms, but she did get a severe invasive fungal infection and neutropenic enterocolitis. She died as a result of disseminated intravascular coagulopathy. CONCLUSION: It is critical to recognize children infected with SARS-CoV-2 who exhibit atypical clinical manifestations of COVID-19, such as persistent pancytopenia. SARS-CoV-2 infection can cause severe and deadly consequences in children; thus, pediatricians should be aware of COVID-19's unusual signs and symptoms mimicking other conditions such as aplastic anemia.

Enteropathy and bone marrow hypoplasia associated with presumptive albendazole toxicosis in a juvenile Boer goat.

Albendazole is a widely used anthelmintic drug that is labeled for the treatment of specific nematodes and flukes in ruminants. Albendazole is approved for the treatment of liver flukes in goats (10 mg/kg PO for a single dose), but is commonly used extra-label in situations in which parasite resistance is an issue. Albendazole toxicosis has been reported in pigeons, doves, alpacas, humans, dogs, and cats. Here we report an adverse event in a 6-mo-old goat associated with extra-label use of albendazole (35.7 mg/kg PO daily for 3 d). Clinicopathologic findings included severe diarrhea and death, with small intestinal crypt necrosis and dysplasia, and severe bone marrow hypoplasia. Microbial and molecular testing and transmission electron microscopy ruled out infectious organisms. The described pathologic changes are similar to those reported in other species that have experienced toxicosis associated with albendazole. To our knowledge, bone marrow and intestinal lesions associated with albendazole use in the goat have not been reported previously. Veterinarians should be aware of potential adverse events and toxicoses associated with anthelmintic drugs, especially as parasite resistance increases, and extra-label usage, and the use of such drugs without veterinary supervision, becomes more common.

A ubiquitous bone marrow reservoir of preexisting SARS-CoV-2-reactive memory CD4+ T lymphocytes in unexposed individuals.

Circulating, blood-borne SARS-CoV-2-reactive memory T cells in persons so far unexposed to SARS-CoV-2 or the vaccines have been described in 20-100% of the adult population. They are credited with determining the efficacy of the immune response in COVID-19. Here, we demonstrate the presence of preexisting memory CD4+ T cells reacting to peptides of the spike, membrane, or nucleocapsid proteins of SARS-CoV-2 in the bone marrow of all 17 persons investigated that had previously not been exposed to SARS-CoV-2 or one of the vaccines targeting it, with only 15 of these persons also having such cells detectable circulating in the blood. The preexisting SARS-CoV-2-reactive memory CD4+ T cells of the bone marrow are abundant and polyfunctional, with the phenotype of central memory T cells. They are tissue-resident, at least in those persons who do not have such cells in the blood, and about 30% of them express CD69. Bone marrow resident SARS-CoV-2-reactive memory CD4+ memory T cells are also abundant in vaccinated persons analyzed 10-168 days after 1°-4° vaccination. Apart from securing the bone marrow, preexisting cross-reactive memory CD4+ T cells may play an important role in shaping the systemic immune response to SARS-CoV-2 and the vaccines, and contribute essentially to the rapid establishment of long-lasting immunity provided by memory plasma cells, already upon primary infection.

Severe Pancytopenia After COVID-19 Revealing a Case of Primary Bone Marrow Diffuse Large B Cell Lymphoma.

BACKGROUND Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL). While bone marrow (BM) involvement is common in lymphoma, primary bone marrow (PBM) DLBCL is extremely rare. We present a case of PBM DLBCL discovered in a patient with COVID-19. CASE REPORT An 80-year-old man presented with generalized abdominal pain, weight loss, fever, fatigue, anorexia, and watery diarrhea over a 3-month period. Physical examination was unremarkable. Laboratory workup revealed anemia, thrombocytopenia, and elevated inflammation markers. SARS-COV-2 PCR was positive, while blood cultures were negative. A rapid decline in the white blood cell count in the following days prompted a BM biopsy, confirming the diagnosis of PBM DLBCL. Computed tomography (CT) did not show thoracic or abdominal lymphadenopathy. The patient received packed red blood cell and platelet transfusions, granulocyte colony-stimulating factor (G-CSF) for pancytopenia, and empirical antibiotics for suspected infection. Due to active COVID-19 and advanced age, cytotoxic chemotherapy was delayed. Rituximab and prednisone were initiated on day 9, followed by an infusion reaction, which led to treatment discontinuation. He died 2 days later. CONCLUSIONS Diagnosing PBM malignancy is challenging, especially with coexisting infection. It is essential to suspect underlying BM malignancy in patients with clinical deterioration and worsening pancytopenia despite adequate treatment. The diagnosis of PBM DLBCL requires the absence of lymphadenopathy, and the presence of histologically confirmed DLBCL. Prompt management with combination chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with/without hematopoietic stem cell transplant can improve the prognosis.

Laboratory Perspective of Concurrent Acute Myeloid Leukemia and COVID-19: a Case Report and Review of Literature.

BACKGROUND: Whether the diagnosis and treatment of coronavirus disease 2019 (COVID-19) affect the clinical course of patients with hematologic malignancies has been of interest during the COVID-19 pandemic. METHODS: We describe a 47-year-old female who was concurrently diagnosed with COVID-19 and acute myeloid leukemia (AML). RESULTS: She developed COVID-19 pneumonia which required treatment with remdesivir and dexamethasone, and induction therapy for t-AML was delayed. After her COVID-19 was resolved and isolation ended, follow-up bone marrow examination showed decreased leukemic burden. CONCLUSIONS: This case describes possible effects of COVID-19 treatment on the clinical course of patients with AML from a laboratory perspective.

Neither COVID-19, nor cryopreservation, prevented allogeneic product infusion: A report from the National Marrow Donor Program.

Background: The Coronavirus Disease 2019 (COVID-19) pandemic in early 2020 has resulted in an unprecedented level of uncertainty and challenge for the stem cell donor registries. To address these challenges, rapid strategies were implemented by the National Marrow Donor Registry (NMDP) and its network partners. Herein, we aim to report the impact of the COVID-19 pandemic on the collection, utilization of grafts, and short-term outcomes of patients who received stem cell products from COVID-19-positive donors. Methods: NMDP data during the early phase (1 March 2020 through 1 May 2020) of the pandemic were compared to the later phase (1 March 2021 through 1 May 2021). Odds ratios were calculated to determine the impact of the pandemic on graft sources requested by transplant centers (TCs). The Kruskal-Wallis test was used to test the effect of the pandemic on the disease indication, volume of searches, and number of products not infused. Results: Although there was an initial decline in overall donor searches during the early phase of the pandemic, these numbers increased reaching pre-pandemic levels during the later phase. Urgent malignant diseases remained the most common indication for transplant in 2021. The pandemic necessitated cryopreservation of stem cell products due to transportation restrictions as well as clinical uncertainties in managing the virus. Cryopreserved grafts remained the most common requested grafts throughout the pandemic. In the later phase of the pandemic, the total numbers of requests for fresh grafts increased, mostly due to the increase in requests for fresh bone marrow (BM) grafts. As the pandemic continued, TCs became more accepting of cryopreservation, resulting in a reduction in the number of products not infused. Lastly, no short-term deleterious outcomes were noted among the patients who had stem cell products infused from a SARS-CoV-2-positive donor. Conclusion: Throughout the pandemic, the NMDP and TCs worked tirelessly to ensure that patients would receive lifesaving grafts when needed. The data reported here, although limited by small numbers, illustrate that transplantation from donors with COVID-19 is feasible and safe.

Immune Transcriptome and Secretome Differ between Human CD71+ Erythroid Cells from Adult Bone Marrow and Fetal Liver Parenchyma.

CD71+ erythroid cells (CECs) were only known as erythrocyte progenitors not so long ago. In present times, however, they have been shown to be active players in immune regulation, especially in immunosuppression by the means of ROS, arginase-1 and arginase-2 production. Here, we uncover organ-of-origin differences in cytokine gene expression using NanoString and protein production using Bio-Plex between CECs from healthy human adult bone marrow and from human fetal liver parenchyma. Namely, healthy human adult bone marrow CECs both expressed and produced IFN-a, IL-1b, IL-8, IL-18 and MIF mRNA and protein, while human fetal liver parenchymaCECs expressed and produced IFN-a, IL15, IL18 and TNF-b mRNA and protein. We also detected TLR2 and TLR9 gene expression in both varieties of CECs and TLR1 and NOD2 gene expression in human fetal liver parenchymaCECs only. These observations suggest that there might be undiscovered roles in immune response for CECs.

Bone Marrow-Derived Mesenchymal Stromal Cell Therapy in Severe COVID-19: Preliminary Results of a Phase I/II Clinical Trial.

Background: Treatment of acute respiratory distress syndrome (ARDS) associated with COronaVIrus Disease-2019 (COVID-19) currently relies on dexamethasone and supportive mechanical ventilation, and remains associated with high mortality. Given their ability to limit inflammation, induce immune cells into a regulatory phenotype and stimulate tissue repair, mesenchymal stromal cells (MSCs) represent a promising therapy for severe and critical COVID-19 disease, which is associated with an uncontrolled immune-mediated inflammatory response. Methods: In this phase I-II trial, we aimed to evaluate the safety and efficacy of 3 intravenous infusions of bone marrow (BM)-derived MSCs at 3-day intervals in patients with severe COVID-19. All patients also received dexamethasone and standard supportive therapy. Between June 2020 and September 2021, 8 intensive care unit patients requiring supplemental oxygen (high-flow nasal oxygen in 7 patients, invasive mechanical ventilation in 1 patient) were treated with BM-MSCs. We retrospectively compared the outcomes of these MSC-treated patients with those of 24 matched control patients. Groups were compared by paired statistical tests. Results: MSC infusions were well tolerated, and no adverse effect related to MSC infusions were reported (one patient had an ischemic stroke related to aortic endocarditis). Overall, 3 patients required invasive mechanical ventilation, including one who required extracorporeal membrane oxygenation, but all patients ultimately had a favorable outcome. Survival was significantly higher in the MSC group, both at 28 and 60 days (100% vs 79.2%, p = 0.025 and 100% vs 70.8%, p = 0.0082, respectively), while no significant difference was observed in the need for mechanical ventilation nor in the number of invasive ventilation-free days, high flow nasal oxygenation-free days, oxygen support-free days and ICU-free days. MSC-treated patients also had a significantly lower day-7 D-dimer value compared to control patients (median 821.0 µg/L [IQR 362.0-1305.0] vs 3553 µg/L [IQR 1155.0-6433.5], p = 0.0085). Conclusions: BM-MSC therapy is safe and shows very promising efficacy in severe COVID-19, with a higher survival in our MSC cohort compared to matched control patients. These observations need to be confirmed in a randomized controlled trial designed to demonstrate the efficacy of BM-MSCs in COVID-19 ARDS. Clinical Trial Registration: (www.ClinicalTrials.gov), identifier NCT04445454.

Common bone marrow signature in COVID-19-associated multisystem inflammatory syndrome in children: A first-wave small case series experience.

The hyper-inflammatory response, also known as multisystem inflammatory syndrome in children (MIS-C), represents a major concern in children with SARS-CoV-2 infection. We report bone marrow features of three patients with MIS-C who were diagnosed during the first wave of the SARS-CoV-2 pandemic. A bone marrow evaluation was performed at onset of the inflammatory condition in order to exclude secondary hemophagocytic lymphohistiocytosis (sHLH). The bone marrows of the patients presented common features: the erythroid and megakaryocytic lineages were prominently affected and hemophagocytosis was moderately increased, differently than observed in sHLH. Megakaryocytopoiesis was increased, representing a peculiar feature of MIS-C differing from sHLH. SARS-CoV-2 RT-PCR and viral panel were studied in bone marrow aspiration samples. MIS-C is a rare complication of SARS-CoV-2 infections in children. An immuno-dysregulation considering both innate and adaptive immunity together with vascular inflammation and endothelial dysfunction play a major role. Our observations, although limited due to the small sample size, suggest that there are unique features in the bone marrow of patients with MIS-C that are likely secondary to immuno-dysregulation, and there are notable differences in bone marrow features compared to those reported in sHLH.

SOCS1 Haploinsufficiency Presenting as Severe Enthesitis, Bone Marrow Hypocellularity, and Refractory Thrombocytopenia in a Pediatric Patient with Subsequent Response to JAK Inhibition.

Haploinsufficiency of suppressor of cytokine signaling 1 (SOCS1) is a recently discovered autoinflammatory disorder with significant rheumatologic, immunologic, and hematologic manifestations. Here we report a case of SOCS1 haploinsufficiency in a 5-year-old child with profound arthralgias and immune-mediated thrombocytopenia unmasked by SARS-CoV-2 infection. Her clinical manifestations were accompanied by excessive B cell activity, eosinophilia, and elevated IgE levels. Uniquely, this is the first report of SOCS1 haploinsufficiency in the setting of a chromosomal deletion resulting in complete loss of a single SOCS1 gene with additional clinical findings of bone marrow hypocellularity and radiologic evidence of severe enthesitis. Immunologic profiling showed a prominent interferon signature in the patient's peripheral blood mononuclear cells, which were also hypersensitive to stimulation by type I and type II interferons. The patient showed excellent clinical and functional laboratory response to tofacitinib, a Janus kinase inhibitor that disrupts interferon signaling. Our case highlights the need to utilize a multidisciplinary diagnostic approach and consider a comprehensive genetic evaluation for inborn errors of immunity in patients with an atypical immune-mediated thrombocytopenia phenotype.

Effect of Cryopreservation in Unrelated Bone Marrow and Peripheral Blood Stem Cell Transplantation in the Era of the COVID-19 Pandemic: An Update from the Japan Marrow Donor Program.

During the COVID-19 pandemic, donor grafts are frequently cryopreserved to ensure that a graft is available before starting a conditioning regimen. However, there have been conflicting reports on the effect of cryopreservation on transplantation outcomes. Also, the impact of cryopreservation may differ in bone marrow (BM) transplantation (BMT) and peripheral blood stem cell (PBSC) transplantation (PBSCT). In this retrospective study, we analyzed the clinical data of both cryopreserved unrelated BMTs (n = 235) and PBSCTs (n = 118) and compared these with data from a large control cohort without cryopreservation including 4133 BMTs and 720 PBSCTs. Among the patients with cryopreserved grafts, 10 BMT recipients (4.3%) and 3 PBSCT recipients (2.5%) did not achieve neutrophil engraftment after transplantation, including 4 of the former and all 3 of the latter who died early before engraftment. In a multivariate analysis, cryopreservation was not associated with neutrophil engraftment in BMT but significantly delayed neutrophil engraftment in PBSCT (hazard ratio [HR], .82; 95% confidence interval [CI], .69 to .97; P = .023). There was an interaction with borderline significance between cryopreservation and the stem cell source (P = .067). Platelet engraftment was delayed by cryopreservation after both BMT and PBSCT. Only 2 cryopreserved grafts (<1%) were unused during the study period. The cryopreservation of unrelated donor BM and PBSC grafts is associated with a slight delay in neutrophil and platelet engraftment but an acceptable rate of graft failure. PBSC grafts may be more sensitive to cryopreservation than BM grafts. Cryopreservation is a reasonable option during COVID-19 pandemic, provided that the apheresis and transplantation centers are adept at cryopreservation. © 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Haematopoietic ageing through the lens of single-cell technologies.

Human lifespan is now longer than ever and, as a result, modern society is getting older. Despite that, the detailed mechanisms behind the ageing process and its impact on various tissues and organs remain obscure. In general, changes in DNA, RNA and protein structure throughout life impair their function. Haematopoietic ageing refers to the age-related changes affecting a haematopoietic system. Aged blood cells display different functional aberrations depending on their cell type, which might lead to the development of haematologic disorders, including leukaemias, anaemia or declining immunity. In contrast to traditional bulk assays, which are not suitable to dissect cell-to-cell variation, single-cell-level analysis provides unprecedented insight into the dynamics of age-associated changes in blood. In this Review, we summarise recent studies that dissect haematopoietic ageing at the single-cell level. We discuss what cellular changes occur during haematopoietic ageing at the genomic, transcriptomic, epigenomic and metabolomic level, and provide an overview of the benefits of investigating those changes with single-cell precision. We conclude by considering the potential clinical applications of single-cell techniques in geriatric haematology, focusing on the impact on haematopoietic stem cell transplantation in the elderly and infection studies, including recent COVID-19 research.