Case Report: Favorable outcome of allogeneic hematopoietic stem cell transplantation in SARSCoV2 positive recipient, risk-benefit balance between infection and leukemia.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in SARS-CoV-2 positive candidates is usually delayed until the clinical resolution of the infection's symptoms and a negative nasopharyngeal molecular test. However, prolonged SARS-CoV-2 positivity has been frequently observed in haematological malignancies, thus representing a challenge for the timing of transplant procedures. Here, we report on the case of a 34-year-old patient with recent pauci-symptomatic COVID-19 undergoing transplant for high-risk acute B-lymphoblastic leukemia before achieving viral clearance. Shortly before their scheduled allogeneic HSCT from a matched unrelated donor, the patient developed mild Omicron BA.5 infection receiving nirmatrelvir/ritonavir with fever resolution within 72 hours. Twenty-three days after COVID-19 diagnosis, because of increasing minimal residual disease values in the context of high-risk refractory leukemia and clinical resolution of SARS-2-CoV infection with reduction of viral load at surveillance nasopharyngeal swabs, it was decided not to delay further allo-HSCT. During myelo-ablative conditioning, the nasopharyngeal SARS-CoV-2 viral load increased while the patient remained asymptomatic. Consequently, two days before the transplant, intra-muscular tixagevimab/cilgavimab 300/300 mg and a 3-day course of intravenous remdesivir were administered. During the pre-engraftment phase, veno-occlusive disease (VOD) occurred at day +13, requiring defibrotide treatment to obtain a slow but complete recovery. The post-engraftment phase was characterized by mild COVID-19 at day +23 (cough, rhino-conjunctivitis, fever) that spontaneously resolved, achieving viral clearance at day +28. At day +32, she experienced grade I acute graft-versus host disease (a-GVHD, skin grade II) treated with steroids and photo-apheresis, without further complications during follow-up until day +180. Addressing the issue of allo-HSCT timing in patients recovering from SARS-CoV-2 infection with high-risk malignant diseases is challenging because of 1] the high risk of COVID-19 clinical progression, 2] the impact of transplant delay on leukemia prognosis and 3] the occurrence of endothelial complications such as VOD, a-GVHD, and transplant associated thrombotic micro-angiopathy. Our report describes the favourable outcome of allo-HSCT in a recipient with active SARS-CoV2 infection and high-risk leukemia thanks to timely anti-SARS-CoV-2 preventive therapies and prompt management of transplant-related complications.

Applications of virus-specific T cell therapies post-BMT.

Hematopoietic stem cell transplantation (HSCT) has been used as a curative standard of care for moderate to severe primary immunodeficiency disorders as well as relapsed hematologic malignancies for over 50 years [1,2]. However, chronic and refractory viral infections remain a leading cause of morbidity and mortality in the immune deficient period following HSCT, where use of available antiviral pharmacotherapies is limited by toxicity and emerging resistance [3]. Adoptive immunotherapy using virus-specific T cells (VSTs) has been explored for over 2 decades [4,5] in patients post-HSCT and has been shown prior phase I-II studies to be safe and effective for treatment or preventions of viral infections including cytomegalovirus, Epstein-Barr virus, BK virus, and adenovirus with minimal toxicity and low risk of graft vs host disease [6-9]. This review summarizes methodologies to generate VSTs the clinical results utilizing VST therapeutics and the challenges and future directions for the field.

A French single-center experience on allogeneic stem cell transplant cryopreservation during severe acute respiratory syndrome coronavirus 2 pandemic.

BACKGROUND AIMS: Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a curative treatment for chemo-resistant hematological malignancies. Because of transport restriction imposed by the coronavirus disease 2019 pandemic, regulatory bodies and societies recommended graft cryopreservation before recipient conditioning. However, the freezing and thawing processes, including washing steps, might impair CD34+ cell recovery and viability, thereby impacting the recipient engraftment. Over 1 year (between March 2020 and May 2021), we aimed to analyze the results of frozen/thawed peripheral blood stem cell allografts in terms of stem cell quality and clinical outcomes. METHODS: Transplant quality was evaluated by comparing total nucleated cells (TNCs), CD34+ cells and colony-forming unit-granulocyte/macrophage (CFU-GM)/kg numbers as well as TNC and CD34+ cell viabilities before and after thawing. Intrinsic biological parameters such as granulocyte, platelet and CD34+ cell concentrations were analyzed, as they might be responsible for a quality loss. The impact of the CD34+ cell richness of the graft on TNC and CD34 yields was evaluated by designing three groups of transplants based on their CD34 /kg value at collection: >8 × 10 6/kg, between 6 and 8 × 106/kg and <6 × 106/kg. The consequences of cryopreservation were compared in the fresh and thawed group by evaluating the main transplant outcomes. RESULTS: Over 1 year, 76 recipients were included in the study; 57 patients received a thawed and 19 patients a fresh allo-SCT. None received allo-SCT from a severe acute respiratory syndrome coronavirus 2-positive donor. The freezing of 57 transplants led to the storage of 309 bags, for a mean storage time (between freezing and thawing) of 14 days. For the fresh transplant group, only 41 bags were stored for potential future donor lymphocyte infusions. Regarding the graft characteristics at collection, median number of cryopreserved TNC and CD34+ cells/kg were greater than those for fresh infusions. After thawing, median yields were 74.0%, 69.0% and 48.0% for TNC, CD34+ cells and CFU-GM, respectively. The median TNC dose/kg obtained after thawing was 5.8 × 108, with a median viability of 76%. The median CD34+ cells/kg was 5 × 106, with a median viability of 87%. In the fresh transplant group, the median TNC/kg was 5.9 × 108/kg, and the median CD34+ cells/kg and CFU-GM/kg were 6 × 106/kg and 276.5 × 104/kg, respectively. Sixty-one percent of the thawed transplants were out of specifications regarding the CD34+ cells/ kg requested cell dose (6 × 106/kg) and 85% of them would have had this dose if their hematopoietic stem cell transplant had been infused fresh. Regarding fresh grafts, 15.8% contained less than 6 × 106 CD34+ cells /kg and came from peripheral blood stem cells that did not reach 6 × 106 CD34+ cells /kg at collection. Regarding the factor that impaired CD34 and TNC yield after thawing, no significant impact of the granulocyte count, the platelet count or the CD34+ cells concentration/µL was observed. However, grafts containing more than 8 × 10 6/kg at collection showed a significantly lower TNC and CD34 yield. CONCLUSIONS: Transplant outcomes (engraftment, graft-versus-host disease, infections, relapse or death) were not significantly different between the two groups.

Managing Survivorship after Hematopoietic Cell Transplantation.

PURPOSE OF REVIEW: With improvement in survival after hematopoietic cell transplantation (HCT), it has become important to focus on the late complications experienced by the survivors that may lead to late mortality and morbidity to be able to provide patient-centered care across the transplant continuum. The goals of this article are to describe the status of literature on late complications in HCT survivors; offer a brief overview of the status of the screening, prevention, and management of these complications; and identify opportunities for future practice and research. RECENT FINDINGS: This is an exciting time for the field with increasing awareness about survivorship issues. Studies are moving beyond description to examining pathogenesis of these late complications and identifying biomarkers. The eventual goal is to promote changes in our transplant techniques to decrease the incidence of these complications as well as help develop interventions targeting these late effects. There is also an emphasis on improving health care delivery models to provide optimal post-HCT management for medical and psychosocial complications through close coordination between multiple stakeholders and leveraging technology to help address the barriers in delivery of care to fulfill the unmet needs in this area. The increasing population of HCT survivors with their burden of late effects underscores the need for concerted efforts to improve long-term medical and psychosocial outcomes for this group.

Effects of extended transport on cryopreserved allogeneic hematopoietic progenitor cell (HPC) product quality and optimal methods to assess HPC stability.

BACKGROUND: Since the beginning of the COVID-19 pandemic, cryopreservation of hematopoietic progenitor cell (HPC) products has been increasingly used to ensure allogeneic donor graft availability prior to recipient conditioning for transplantation. However, in addition to variables such as graft transport duration and storage conditions, the cryopreservation process itself may adversely affect graft quality. Furthermore, the optimal methods to assess graft quality have not yet been determined. STUDY DESIGN AND METHODS: A retrospective review was performed on all cryopreserved HPCs processed and thawed at our facility from 2007 to 2020, including both those collected onsite and by the National Marrow Donor Program (NMDP). HPC viability studies were also performed on fresh products, retention vials, and corresponding final thawed products by staining for 7-AAD (flow cytometry), AO/PI (Cellometer), and trypan blue (manual microscopy). Comparisons were made using the Mann-Whitney test. RESULTS: For HPC products collected by apheresis (HPC(A)), pre-cryopreservation and post-thaw viabilities, as well as total nucleated cell recoveries were lower for products collected by the NMDP compared to those collected onsite. However, there were no differences seen in CD34+ cell recoveries. Greater variation in viability testing was observed using image-based assays compared to flow-based assays, and on cryo-thawed versus fresh samples. No significant differences were observed between viability measurements obtained on retention vials versus corresponding final thawed product bags. DISCUSSION: Our studies suggest extended transport may contribute to lower post-thaw viabilities, but without affecting CD34+ cell recoveries. To assess HPC viability prior to thaw, testing of retention vials offers predictive utility, particularly when automated analyzers are used.

The European landscape on allogeneic haematopoeietic cell transplantation in Chronic Lymphocytic Leukaemia between 2009 and 2019: a perspective from the Chronic Malignancies Working Party of the EBMT.

Allogeneic transplantation (allo-HCT) is a curative treatment in CLL whose efficacy including the most severe forms had led to the 2006 EBMT recommendations. The advent after 2014 of targeted therapies has revolutionized CLL management, allowing prolonged control to patients who have failed immunochemotherapy and/or have TP53 alterations. We analysed the pre COVID pandemic 2009-2019 EBMT registry. The yearly number of allo-HCT raised to 458 in 2011 yet dropped from 2013 onwards to an apparent plateau above 100. Within the 10 countries who were under the EMA for drug approval and performed 83.5% of those procedures, large initial differences were found but the annual number converged to 2-3 per 10 million inhabitants during the 3 most recent years suggesting that allo-HCT remains applied in selected patients. Long-term follow-up on targeted therapies shows that most patients relapse, some early, with risk factors and resistance mechanisms being described. The treatment of patients exposed to both BCL2 and BTK inhibitors and especially those with double refractory disease will become a challenge in which allo-HCT remains a solid option in competition with emerging therapies that have yet to demonstrate their long-term effectiveness.

Effect of the COVID-19 pandemic on allogeneic stem cell transplantation in Japan.

The coronavirus disease 2019 (COVID-19) pandemic affected healthcare quality and access worldwide and may also have negatively affected the frequency and outcomes of allogeneic hematopoietic stem cell transplantation (HSCT). We evaluated the effect of the pandemic on allogeneic HSCT in Japan. Our subjects were patients who received allogeneic HSCT during January 2018-December 2020 in Japan. We assessed differences in yearly number of allogeneic HSCTs and 1-year outcomes in 2020 versus both 2019 and 2018. The total number of patients who received allogeneic HSCT increased from 3621 patients in 2018 and 3708 patients in 2019 to 3865 patients in 2020. Some following changes in allogeneic HSCT methods were observed: patients were older, fewer patients received bone marrow transplantation, fewer patients received transplants from unrelated donors, fewer patients received transplants from matched donors, more patients received reduced-intensity conditioning, and fewer patients received anti-thymocyte globulin in 2020 compared with previous years. HSCT outcomes were not affected, as 1-year overall survival was not significantly different (65.8% in 2020, vs. 66.5% in 2019 and 66.4% in 2018). Our results suggest that we can maintain transplant care during the pandemic by controlling the spread of COVID-19 and modifying HSCT methods.

Allogeneic hematopoietic stem cell transplantation in the COVID-19 era.

Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) recipients are especially vulnerable to coronavirus disease 19 (COVID-19), because of their profound immunodeficiency. Indeed, the first pandemic wave was marked by a high mortality rate in this population. Factors increasing immunodepression such as older age, immunosuppressive treatments or a short delay between transplant and infection appear to worsen the prognosis. Many changes in clinical practice had to be implemented in order to limit this risk, including postponing of transplant for non-malignant diseases, preference for local rather than international donations and for peripheral blood as stem cell source, and the widespread use of cryopreservation. The great revolution in the COVID-19 pandemic came from the development of mRNA vaccines that have shown to be able to prevent severe forms of the disease. More than 75% of allo-HSCT recipients develop seroconversion after 2 doses of vaccine. Multiple studies have identified lymphopenia, exposure to immunosuppressive or anti-CD20 therapies, and a short post-transplant period as factors associated with a poor response to vaccination. The use of repeated injections of the vaccine, including a third dose, not only improves the seroconversion rate but also intensifies the immune response, both in B cells and T cells. Vaccines are an effective and well-tolerated method in this high-risk population. Some studies investigated the possibility of immune protection being transferred from a vaccinated donor to a recipient, with encouraging initial results. However, dynamic mutations and immune escape of the virus can lead to breakthrough infections with new variants in vaccinated individuals and still represent a threat of severe disease in allo-HSCT recipients. New challenges include the need to adapt vaccine protection to emerging variants.

Successful Autologous Bone Marrow Transplantation in Active COVID-19 Patients: Case Report.

BACKGROUND: Patients with hematologic malignancies are considered at high risk for COVID-19 infection either from the disease or the treatment. Hematopoietic stem cell transplantation, one of the approved therapies for hematologic malignancies, was performed worldwide during the COVID-19 era with some regulations, such as COVID-19 testing, before proceeding with transplantation or cellular therapy. To the authors' knowledge, none have reported the result of autologous hematopoietic stem cell transplantation in an active COVID-19 patient. CASE PRESENTATION: We describe a successful clinical course of autologous bone marrow transplantation for 2 lymphoma patients who tested positive for COVID-19. A thorough discussion was conducted between multidisciplinary hemato-oncology, intensive care, and infectious diseases teams. The decision was to proceed toward bone marrow transplantation with some modifications in the transplantation protocol and close patient monitoring. CONCLUSION: Our cases lend credence that successful autologous bone marrow transplantation is possible among active COVID-19 patients. The obstacles we faced could be overcome with collaboration between a highly qualified multidisciplinary team. Despite the potential complications, the benefits of bone marrow transplantation among patients with a high risk of relapse and who are still COVID-19-positive outweigh the risks. However, further studies are still recommended to support our inference.

A Phase I Trial of Allogeneic γδ T Lymphocytes From Haploidentical Donors in Patients With Refractory or Relapsed Acute Myeloid Leukemia.

Introduction We report the results of a phase I clinical trial NCT03790072 of an adoptive transfer of γδ T lymphocytes from haploidentical donors in patients with refractory/relapsed acute myeloid leukemia after lymphodepletion regimen. Patients and methods Healthy donor mononuclear cells collected by leukapheresis were consistently expanded to generate products of 109 to 1010 γδ T cells. Seven patients received donor-derived T cell product at doses of 106/kg (n = 3), 107/kg (n = 3), and 108/kg (n = 1). Results Four patients had bone marrow evaluation at day 28. One patient had a complete remission, one was classified as morphologic leukemia-free state, one had stable disease and one had no evidence of response. In one patient, there was evidence of disease control with repeat infusions up to 100 days after first dosing. There were no treatment-related serious adverse events or treatment-related Common Terminology Criteria for Adverse Events grade 3 or greater toxicities at any dose level. Allogeneic Vγ9Vδ2 T cell infusion was shown to be safe and feasible up to a cell dose of 108/kg. Discussion In agreement with previously published studies, the infusion of allogeneic Vγ9Vδ2 cells was safe. The contribution of lymphodepleting chemotherapy to responses seen cannot be ruled out. Main limitation of the study is the low number of patients and interruption due to COVID-19 pandemic. Conclusion These positive Phase 1 results support progression to phase II clinical trials.

Hematopoietic stem cell transplantation activity in Mexico during the COVID19 pandemic: on the way to recovery.

OBJECTIVE: To analyze the number of HSCTs performed in 2019 vs. 2020 and report the status of transplant centers (TCs) during and a year after the COVID-19 pandemic. METHODS: We performed a comprehensive cross-sectional nationwide study including active TCs interrogating HSCT activity from 2019 through September 2021. An electronic survey was sent to TCs and consisted of items regarding the number and characteristics of procedures performed and were compared yearly. Changes to their institutions' transplant policies and practices during the COVID19 pandemic were also documented. Fifty centers were invited to participate, 33 responded. RESULTS: Most TCs were part of the public health system (63.7%). Almost half are in the country's capital, Mexico City (45.5%). Most centers performed <10 procedures per year. The number of HSCTs decreased from 835 in 2019-505 in 2020 (p < .001), representing a 40% reduction in transplant activity. The monthly transplant rate in 2021 increased to 58.3, compared to 42 in 2020 and close to 69.5 in 2019 (p < .001). All types of HSCTs decreased excluding haploidentical transplants. All institutions treated patients with COVID19, and over two-thirds experienced some form of hospital reconversion. Transplant activity stopped completely in 23 TCs (70%) during the pandemic with a median closure duration of 9.9 months (range, 1-21). In 2021, 9.1% of TCs remained closed, all of them in the public setting. CONCLUSION(S): The limited transplant activity in Mexico decreased significantly during the pandemic but is recovering and nearly in pre-pandemic levels.

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.

[Multiple myeloma: response to treatment and survival of patients according to the interim analysis of the Russian observational, retrospective-prospective, multicenter cohort study (MULTISPECT)].

AIM: The primary objective of the interim analysis of the MULTISPECT study was to evaluate the short-term efficacy of the treatment and long-term outcomes in cohorts of primary and pretreated patients with multiple myeloma (MM) receiving treatment in actual clinical practice in various regions of the Russian Federation. Secondary objectives were a description of the main characteristics of patients; analysis of the most commonly used therapy regimens of the 1st and later lines and the sequence of their changes; evaluation of the response to therapy. Additional objectives included evaluation of the effect of the new COVID-19 coronavirus infection on the course of MM in patients. MATERIALS AND METHODS: The study is an observational retrospective-prospective multicenter cohort study. For its implementation, a structured database of patients with MM was used, provided by hematologists of the centers affiliated for the study. RESULTS: The study included 1,294 patients (cohort 1 806, cohort 2 488). In both cohorts, patients aged 6069 years were in the majority. 3 lines of therapy (L1, L2, L3) were used for cohort 1; in cohort 2, the 4th line of therapy was also used in 2 patients. The therapy regimens were analyzed for 290 (22.41%) of all patients in the study. Responses to therapy were analyzed for 214 patients of cohort 1 and 109 patients of cohort 2. Autologous and allogeneic hematopoietic stem cell transplantations were carried out for a limited proportion of patients in both cohorts. At the end of the study and upon presentation of its results, the status of patients was the following: 96% of patients in cohort 1 and 89% in cohort 2 were alive. The therapy regimens in both cohorts were characterized by variability. The most commonly used regimens in each of the lines of therapy have been identified. The most used therapy regimen in patients with MM of both cohorts was the VCD-regime. Rd-regime in cohort 1 and RD-regime in cohort 2 were the second most frequent used regimens. In patients of both cohorts, the therapy regimens including Bortezomib were most often used. CONCLUSION: The variety of therapy regimens used to treat MM in actual clinical practice may be due to the factors of availability of new medicines and updated recommendations for the treatment of the disease. Further, in the context of this study, a more detailed analysis of the efficacy of certain therapy regimens in the 1st and later lines on progression free survival and overall survival of MM patients should be carried out.

Strong SARS-CoV-2 T-Cell Responses after One or Two COVID-19 Vaccine Boosters in Allogeneic Hematopoietic Stem Cell Recipients.

A full exploration of immune responses is deserved after anti-SARS-CoV-2 vaccination and boosters, especially in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although several reports indicate successful humoral responses in such patients, the literature is scarce on cellular specific immunity. Here, both B- (antibodies) and T-cell responses were explored after one (V3 n = 40) or two (V4 n = 12) BNT162b2 mRNA vaccine boosters in 52 allo-HSCT recipients at a median of 755 days post-transplant (<1 year n = 9). Results were compared with those of 12 controls who had received only one booster (BNT162b2 n = 6; mRNA-1273 n = 6). All controls developed protective antibody levels (>250 BAU/mL) and anti-spike T-cell responses. Similarly, 81% of the patients developed protective antibody levels, without difference between V3 and V4 (82.5% vs. 75%, p = 0.63), and 85% displayed T-cell responses. The median frequency of anti-spike T cells did not differ either between controls or the whole cohort of patients, although it was significantly lower for V3 (but not V4) patients. COVID-19 infections were solely observed in individuals having received only one booster. These results indicate that four vaccine injections help to achieve a satisfactory level of both humoral and cellular immune protection in allo-HSCT patients.

Current status and prospects of hematopoietic stem cell transplantation in China.

ABSTRACT: Hematopoietic stem cell transplantation (HSCT) is a highly effective and unique medical procedure for the treatment of most hematological malignancies. The first allogeneic transplantation was performed by E. Donnall Thomas in 1957. Since then, the field has evolved and expanded worldwide. The first successful allogenic HSCT (allo-HSCT) in China was conducted in 1981. Although the development of allo-HSCT in China lagged, China has since made considerable contributions to the process of HSCT worldwide, with more than 10,000 HSCTs performed annually. In particular, haploid HSCT (haplo-HSCT) technology represented in the Beijing Protocol has demonstrated similar efficacy to human leukocyte antigen-matched HSCT and has gradually become the pre-dominant choice for allo-HSCT in China. Currently, the number of haplo-HSCT procedures exceeds 5000 per year, and the Beijing Protocol has been greatly improved by implementing updated individualized strategies for controlling complications, relapse, and infection management. In addition, innovative haplo-HSCT technologies developed by different medical transplantation centers, such as Soochow, Zhejiang, Fujian, Chongqing, and Anhui, have emerged, providing inspiration for the refinement of global practice. This review will focus on the current activity in this field and highlight important trends that are vital in China's allo-HSCT process, examining the current viewpoint and future directions.

Immune response to vaccination against SARS-CoV-2 in hematopoietic stem cell transplantation and CAR T-cell therapy recipients.

Recipients after hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T-cell (CAR-T) therapy are at increased risk for unfavorable outcomes after SARS-CoV-2 infection. The efficacy of COVID-19 vaccines remains undetermined in this vulnerable population, we therefore conducted a pooled analysis to evaluate the immune response after vaccination. A total of 46 studies were finally included, comprising 4757 HSCT and 174 CAR-T recipients. Our results indicated that HSCT and CAR-T recipients had an attenuated immune response to SARS-CoV-2 vaccination compared with healthy individuals, while time interval between transplant and vaccination, immunosuppressive therapy (IST) and lymphocyte counts at vaccination significantly affected the humoral response in HSCT recipients. In addition, seroconversion was significantly higher in patients with BCMA-based CAR-T than those with CD19-based CAR-T. Thus, an adapted vaccination strategy for HSCT and CAR-T recipients may be required, and further research on the effect of a booster dose of COVID-19 vaccine and the role of cellular response after vaccination is warranted.

Adaptation of the PERCEPT myeloma prehabilitation trial to virtual delivery: changes in response to the COVID-19 pandemic.

INTRODUCTION AND OBJECTIVE: Research activity was impacted by the novel COVID-19 pandemic, the PERCEPT myeloma trial was no exception. This pilot randomised trial delivered a face-to-face exercise intervention prior to and during autologous stem cell transplantation (ASCT) in myeloma patients, as a consequence of COVID-19 it required significant adaptions to continue. This brief communication describes how the previously published study protocol was adapted for virtual delivery. In addition, we highlight the challenge of continuing the study which was embedded within a clinical pathway also impacted by the pandemic. SUMMARY: The original trial protocol was amended and continued to recruit and deliver an exercise prehabilitation intervention virtually. Continued delivery of the intervention was deemed important to participants already enrolled within the trial and the adapted virtual version of the trial was acceptable to the research ethics committee as well as participants. Development of effective, remotely delivered rehabilitation and physical activity programmes are likely to benefit people living with myeloma. The COVID-19 pandemic provided an opportunity to explore the feasibility of a virtual programme for ASCT recipients, however, continued changes to the clinical pathway within which the study was embedded posed the greatest challenge and ultimately led to early termination of recruitment. TRIAL REGISTRATION NUMBER: ISRCTN15875290; pre-results.

B Cell Aplasia Is the Most Powerful Predictive Marker for Poor Humoral Response after BNT162b2 mRNA SARS-CoV-2 Vaccination in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation.

Little is known about the immune response to SARS-CoV-2 vaccination in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, several studies have reported that adequate protection could be provided to this population. The purpose of this study was to evaluate which factors can predict the efficacy of SARS-CoV-2 vaccination in these specifically immunosuppressed patients. Specific anti-Spike (S) antibody responses were assessed in a cohort of 117 allo-HSCT recipients after 2 injections of BNT162b2 mRNA SARS-CoV-2 vaccine (V1 and V2). Factors considered liable to influence the antibody response and analyzed in this series were the interval between allo-HSCT and V1, donor source, recipient and donor age, current immunosuppressive/chemotherapy (I/C) treatment, and levels of CD4+and CD8+ T cells, B cells, and natural killer cells at the time of V1. Overall, the S-antibody response rate, evaluated at a median of 35 days after V2, was 82.9% for the entire cohort, with 71 patients (61%) reaching the highest titer. In univariate analysis, a lower pre-V1 median total lymphocyte count, lower CD4+ T cell and B cell counts, ongoing I/C treatment, and a haploidentical donor were characteristic of nonhumoral responders. However, multiparameter analysis showed that B cell aplasia was the sole factor predicting the absence of a specific immune response (odds ratio, 0.01; 95% confidence interval, 0.00 to 0.10; P < 10-3). Indeed, the rate of humoral response was 9.1% in patients with B cell aplasia versus 95.9% in patients with a B cell count >0 (P < 10-9). These results advocate for the administration of anti-SARS-CoV-2 vaccination in allo-HSCT recipients as early as peripheral B cell levels can be detected, and also suggest the need for close monitoring of B-cell reconstitution after Allo-HSCT.

Evidence-Based Minireview: In young children with severe sickle cell disease, do the benefits of HLA-identical sibling donor HCT outweigh the risks?

In case 1, a 14-month-old male child with sickle cell disease (SCD) was referred for evaluation for an allogeneic hematopoietic stem cell transplant (HCT). The patient had a history of dactylitis 3 times in his first year of life and febrile episodes twice at the consult. His 4-year-old sister was found to be human leukocyte antigen (HLA) identical. The patient was started on hydroxyurea (HU) at 2.5 years of age. His parents again sought consultation when he was 5 years old because of concerns about his medical condition. At the time, the patient had experienced 2 vaso-occlusive pain episodes (VOEs) requiring hospitalization during the previous 2 years. He had also experienced intermittent pain crises requiring rest at home for 2 to 3 days. The child has not attended school in person due to the COVID-19 pandemic. The family is considering HCT but is ambivalent about it because of potential toxicity. In case 2, an 8-year-old female child is 3 years out from HCT for SCD from her HLA-identical sibling. Before HCT, despite receiving HU, she had experienced >5 VOEs requiring hospitalization and 2 episodes of acute chest syndromes in the previous 3 years. She had also been missing almost 50 days of school days each year. After HCT, she is now attending school regularly and participating in all normal age-appropriate activities. The parents believe that HCT has been transformative in their child's life.

Infectious complications and vaccines.

Infections are a major cause of morbidity and can result in mortality in long-term survivors after allogeneic hematopoietic cell transplantation. Chronic graft-versus-host disease and delayed immune reconstitution are recognized risk factors. Different strategies must be utilized depending on the individual patient's situation but include prolonged antimicrobial prophylaxis and vaccination. Some important infections due to pathogens preventable by vaccination are pneumococci, influenza, varicella-zoster virus, and SARS-CoV-2. Despite the fact that such recommendations have been in place for decades, implementation of these recommendations has been reported to be poor.