Sars-CoV-2 in critical immunocompromised patients. Evolution and prognosis

Introduction: In this study, we share the results of immunosuppressed patients who suffered from acute respiratory distress syndrome (ARDS) secondary to COVID-19 pneumonia managed in our ICU. Method(s): We tracked all patients admitted to ICU of a Tertiary Hospital diagnosed with severe SARS-COV2 pneumonia from March 1, 2020 to January 31, 2022. The definition of Immunocompromised patient is based on history of transplantation, active neoplasia, autoimmune diseases or HIV. Collected data includes: sex, age, type of immunosuppression, vaccination, mechanical ventilation, ECMO VV, incidence of superinfections and mortality. Result(s): From a cohort of 425 patients, 55 met the inclusion criteria. 33% were women and 67% male. The average age was 58 years for women and 62 years for men. Out of these patients, 27% had solid organ transplants. 40% suffered from neoplasic disease. 27% had autoimmune diseases and were under treatment with immunosuppressants. 3 had HIV. Only the 29% had received at least 1 dose of COVID 19 vaccine. 80% required orotracheal intubation. 3.64% (2) required Veno-Venous ECMO. 61% presented bacterial superinfection, with the most frequent germs being Pseudomonas aeruginosa and Enterococcus. 36% had viral superinfection, being cytomegalovirus the most frequent one. 32% had fungal superinfection, mainly by Aspergillus fumigatus. 27% did not suffer any superinfection. 40% of the total sample died. After logistic regression, in our model (AUC 83,4% (Se 57.1%, Sp 87.9%), we identified need of intubation as independent variable of mortality (OR 27,06 IC95% 1.76-415.55, p = 0.018). Conclusion(s): Immunocompromised patients with ARDS secondary to COVID-19 pneumonia present high mortality, with statistically significant difference when mechanical ventilation is needed. The most frequently isolated germs causing superinfection in this group of patients are bacterias. We believe that this group of patients require special care in our ICU units and an in-depth analysis and study to optimize their prognosis.

Outcomes and Complications of Covid-19 in Pediatric Solid Organ Transplant Patients

Purpose: The purpose of the study was to examine the clinical course, outcomes, and complications of COVID-19 in pediatric solid organ transplant patients from a single institution, with special attention to thrombotic complications, multiple inflammatory syndrome in children (MIS-C), and new rejection. Method(s): The medical record at our institution was retrospectively queried for all solid organ transplant patients up to 21 years old diagnosed with COVID-19 from March 2020 to September 2021. This cohort was compared in a 1:1 fashion with age, sex, and ethnicity-matched controls with COVID-19 infection, but no history of transplant. Categorical variables were analyzed with Chi-square or Fisher's exact test, and continuous variables were analyzed with Mann-Whitney test. Result(s): 44 solid organ transplant patients met study inclusion criteria. Six patients were excluded from analysis due to insufficient documentation of COVID-19 diagnosis or course. The cohort was composed of 17 kidney, 11 heart, six liver, two lung, one liver-kidney, and one multivisceral transplant patients. Median age at COVID-19 diagnosis was 15 years (IQR 9). Median time from transplant to COVID-19 diagnosis was 2.5 years (IQR 3.4). Of the 38 patients, 17 were white non-Hispanic/Latino (44.7%), 12 were Hispanic/Latino (31.6%), three were Black (7.9%), two were Asian (5.3%), three were other (7.9%), and one was unknown (2.6%). 19 patients (50%) were male. 12 transplant patients were asymptomatic (31.6%), compared to five controls (13.2%, p=0.054). Of the symptomatic patients, the most common symptoms in the solid organ transplant group were fever (26.3%) and headache (18.4%), with few patients experiencing shortness of breath (5.3%). Hospital (15.8%) and ICU (5.3%) admission rates were equal in both groups, with a median length of stay of 4.5 days for the transplant group (IQR 5.25) versus 4 days (IQR 5.75) for controls (p=0.59). 32 patients in each group received supportive care as outpatients (84.2%). A minority of transplant patients received monoclonal antibody (6.3%), convalescent plasma (6.3%), steroids (6.3%), and remdesivir (3.1%). There was one case of MIS-C in the transplant group (2.6%) versus three in the control group (7.9%) (p=0.62). One transplant patient developed COVID-associated microangiopathy (2.6%), but there were no thrombotic complications among controls (p > 0.99). There were no new cases of cellular or antibody-mediated rejection following COVID-19. There was one death in the transplant cohort, but no deaths in the control group. Conclusion(s): We report the largest multi-organ cohort of pediatric solid organ transplant recipients with COVID-19 to date. Our findings suggest pediatric solid organ transplant patients fare similarly to healthy children, without elevated risk of complications.

Barriers to Completing the Transplant Evaluation Process: A Mixed- Methods Study

Purpose: Little is known about patient-reported factors affecting patients' access to the kidney transplant waitlist after starting evaluation. We qualitatively assessed patients' perceived barriers to completing kidney transplant evaluation. Method(s): We conducted semi-structured telephone interviews with patients undergoing kidney transplant evaluation at 1 transplant program. Transcripts were analyzed by thematic analysis. Result(s): 26 patients participated (26% participation rate), identifying as Black (46%), White (39%), or Hispanic (15%), who underwent evaluation for a mean (SD) of 12 (23) months [range: 1-120]. Critical barriers to completing transplant evaluation reported based on experiences at prior transplant programs and/or the current program were poor communication with the transplant team, negative interactions with the transplant team, and difficulties scheduling transplant tests. Due to inconsistent and unclear communication with the transplant team, patients reported they had "[no] clue about what's going on." The lack of follow-up from the team contributed to patients feeling a loss of control over their health. Patients did not know their waitlist status or what medical exams they needed to complete and reported repeated attempts to contact the team for information. Patients perceived the transplant team as "cold" and "uncaring" and reported feeling as if "nobody gives a damn about [them]." Seven (27%) patients reported that structural racism affected their transplant evaluation process. Transplant team interactions made Black patients feel less than human. One patient perceived that the team thought their transplant did not matter because "Black people don't usually do what they are supposed to do" compared to White patients. Black patients perceived the transplant evaluation process as "tough" for Black individuals, emphasizing the importance of having a transplant team who have "some cultural background in dealing with" minoritized patients. Black patients reported feeling as if the transplant team feared them and reported experiencing unfair treatment due to their race, prompting them to seek treatment elsewhere. Overall, patients reported difficulties scheduling and completing medical exams due to conflicts with their work and dialysis schedules. Patients experienced challenges with identifying hospitals that provided required clinical exams during the Covid-19 pandemic. Conclusion(s): Preliminary findings suggest that communication and structural barriers impede progression through the transplant evaluation process. Interventions are needed to redress these barriers. Further analysis will assess whether racial/ ethnic minorities experience barriers differently as a source of disparities in access to the transplant waitlist.

Evolution of Cellular and Humoral Immunity During and After a Three Doses-Course of mRNA-1273 COVID-19 Vaccine in Kidney Transplant Recipients

Purpose: Seroconversion after a 2 doses of mRNA COVID-19 vaccine in kidney transplant recipients (KTR) ranges between 30 and 50% in different series. We previously demonstrated that a substantial proportion of KTRs (35%) without a humoral response, develops a cellular response after the second dose assessed by the ELISpot technique. We aim to study the evolution of both humoral and cellular response in the same cohort before and 1 month after the administration of the third dose of mRNA-1273 COVID-19 vaccine. Method(s): We included in the final analysis KTRs without evidence of previous exposure to COVID-19 and who were not infected during the course of the study and with complete data in all the time-points (n=105). The four time-points studied were at baseline before the first dose (T1), after the second dose (T2, 2 months) and before (T3, 6 months) and after (T4, 7 months) the administration of the third dose of 100mcg mRNA-1273 COVID-19 vaccine. In all the time points, IgG and IgM titre against protein S assessed by Luminex technique and cellular immunity assessed by N- and S-protein specific ELISpot were studied. Result(s): The percentage of patients with a positive humoral or cellular immunity against the S-protein were 24.8% and 51.4% after the second dose (T2). This percentages changed to 54.3% and 48.6% at 6 months (T3), respectively for IgG and S-ELISpot, in the absence of proven COVID-19. After the administration of the 3rd dose (T4) these percentages increased to 75.2% for IgG and 61.0% of S-ELISpot respectively. At multivariate analysis, the only factor that was positively associated with IgG development at T4 was S-ELIspot positivity after the 2nd dose (T2) [OR(CI) 3.14[1.10-8.96], p=0.032). Factors negatively associated with seroconversion were being transplanted during the last year [OR(CI) 0.23[0.07-0.80], P=0.021] and previous transplantation [OR(CI) 0.22[0.06-0.78], P=0.020). Conclusion(s): After a 3 doses-course of mRNA-1273 COVID-19 vaccine, three quarters of kidney transplant recipients developed finally IgG against protein S. Developing a cellular response after the second dose was positively associated with the final seroconversion, while being transplanted previously or being vaccinated during the first year after KT impacted negatively on the vaccine outcome.

ARE ABO INCOMPATIBLE KIDNEY TRANSPLANT RECIPIENTS AT HIGHER RISK OF INFECTIONS?-A SINGLE CENTER EXPERIENCE

Introduction: Because of the limited donor pool, transplants are being done across the blood group and even HLA incompatibility barriers. But this comes at the cost of increased immunosuppression and the side effects. Effect of this intensified immunosuppression on the incidence of post transplant infections and the type of infection has not been studied extensively. Methods: We retrospectively analysed the incidence of infection in ABO incompatible transplants (ABOi) and compared it with propensity matched cohort of ABO compatible transplants(ABOc) over the same timeframe i.e. 2011 to April 2019. using hospital eHIS record system. Patients were matched with 1:2 ratio (ABOi: ABOc) for age (<60yr, >60yrs),sex, number of previous transplants, pretransplant infections, history of prior immunosuppression, diabetic status, NODAT, and induction agent used. Desensitization protocol for ABO incompatible transplant includes rituximab with double filtration plasmapheresis, plasmapharesis or immunoadsorption to target anti blood group titre of 8. Patient with high immunological risk (e.g.second transplant, HLA incompatible) receive ATG induction while others receive basiliximab induction. Valganciclovir prophylaxis was given only in patients with ATG induction. Results: [Formula presented] [Formula presented] During the study period 89 patients underwent ABOi transplants which were compared with 178 ABOc transplants. (Table1)Mean follow up duration was 50.45months (SD 26.8) in ABOi group and 49.47months (SD28.7) in ABOc group. 17% patients lost to follow up with their last follow up being more than 2 years before. Incidence of overall infections was similar in both the groups (59% (43/89) Vs 44.3% (79/178);p=0.6). (Table2) Incidence of urinary tract infections(UTI)was significantly more in ABOi group vs ABOc group.(23.5% (21/89) vs 11.79% (21/178);p=0.019). Cytomegalovirus infections (CMV) were significantly more in ABOi group 12.3% (11/89) as compared to ABOc group 5% (9/187) (p=0.04). All the patients with CMV infection were CMV IgG positive pretransplant except 2, one from ABOc group who was CMV IgG negative and another from ABOi group who’s pretransplant CMV serology was unavailable. There was no significant difference in incidence of fungal infection, pneumocystis infection, diarrheal infections (other than CMV),pneumonia (other than CMV, PCP, fungal), Herpes, BKV infection. Incidence of post-transplant tuberculosis (3.3% (3/89) Vs 2.8% (5/178);p=1.0) and SARS COV2 infections (12.3% (11/89) vs 9% (16/178);p=0.39 was similar in both the groups. Patient survival was similar in both the groups i.e.95.5% but death censored graft loss was significantly more in ABOi group 0.9% (8/89) as compared ABOc group 0.3% (5/178) p=0.03. Reason of graft loss in all the patients was immunological and not infection. Infection was cause for death in three ABOi patients and four ABOc patients. Conclusions: Overall incidence of infections in ABOi transplants was similar to Abo compatible transplant. Incidence of UTIs and CMV infections were significantly higher in ABOi group. No conflict of interest

MULTIFOCAL BONE INFARCT AS A LATE SIDE EFFECT OF STEROID IN A PATIENT WITH BILATERAL LUNG TRANSPLANTATION SECONDARY TO COVID-19 PNEUMONIA/ARDS

CASE: A 37-year-old Hispanic female was referred to a tertiary center nine months status-post lung transplant secondary to post-COVID ARDS for evaluation of constant, dull, aching, gradually progressive pain in her bilateral lower extremities that was insidious in onset. Lab work was notable for persistently elevated alkaline phosphatase. 12 months prior to this admission, the patient was admitted for COVID-19 pneumonia for a week of ongoing fever, shortness of breath, and chest discomfort. Her hospital course was complicated by PE, ARDS, pneumothorax, required chest tube placement, intubation and ECMO. She was treated with dexamethasone, remdesivir, ceftriaxone, azithromycin, and convalescent plasma. Unfortunately, the patient developed post-ARDS pulmonary fibrosis and she was unable to wean off ECMO. Three months later, she underwent lung transplantation for postCOVID ARDS. Post- operative course was significant for profound shock intraoperatively, acute blood loss with delayed chest closure, Grade 3 primary graft dysfunction (PGD), critical illness myopathy, AKI with a need for continuous renal replacement therapy (CRRT) / hemodialysis, and Aspergillus pneumonia. She received two doses of COVID-19 vaccination. The patient underwent a bone scan that showed asymmetrically increased uptake in the bilateral femoral metadiaphysis, metaphysis, and proximal tibial metaphysis. There was questionable increased uptake in the humeral heads. MRI of the tibia showed bilateral distal tibial metaphysis/epiphysis heterogeneous T1 and T2 signal intensity lesions compatible with intramedullary infarct. There was no evidence of acute fracture or dislocation. Overall, the findings were consistent with multifocal osteonecrosis secondary to corticosteroid treatment. She is currently managed with analgesics in view of a nonsurgical approach as advised by the orthopedic team. IMPACT/DISCUSSION: Coronavirus disease 2019 (COVID-19) pandemic continues to present critical challenges for public health and medical communities globally. Its manifestations are predominantly respiratory, with multiorgan dysfunction in severe cases. Skeletal involvement is uncommon. Systemic corticosteroids such as dexamethasone are frequently used as the standard of care for critically ill COVID-19 patients to alleviate the hyperinflammatory response and reduce the need for mechanical ventilation. However, long-term treatment with dexamethasone can increase the risk of the development of osteonecrosis. In this case report, to our knowledge, we describe the first case of multifocal bone infarction in a patient treated with corticosteroids status-post lung transplant secondary to COVID-19 pneumonia. CONCLUSION: Recognizing clinical features of multifocal bone infarct as a late effect of corticosteroid treatment may be challenging given a complicated history of transplant and COVID-19. However, it may be prudent to consider osteonecrosis when a patient with prior steroid treatment history presents with musculoskeletal complaints.

Interest of a Third Dose of BNT162b2 Anti- Sars-Cov-2 mRNA Vaccine in Allogeneic Hematopoietic Stem-Cells Recipients

Introduction In a previous observational study of 117 allogeneic hematopoietic stem cell transplant (Allo-HSCT) recipients, we found that 83 % of them achieved a specific humoral response after two doses (V1 and V2) of BNT162b2 anti-SARS-CoV-2 messenger RNA vaccine (Pfizer BioNTech). However, although 61.5% of the patients achieved the highest detectable IgG titers, this proportion remained significantly lower than what was observed in healthy controls, where 100% reached these highest antibody titers. Here, we investigated whether a third dose of vaccine would improve the anti- SARS-CoV-2 response in Allo-HSCT recipients. Methods This monocentric retrospective study aimed at evaluating the efficacy of a third vaccine (V3) of BNT162b2 in a cohort of Allo-HSCT adult recipients. Patients with previous clinical or asymptomatic biological COVID-19 infection at V1 were excluded from the study. A cohort of healthy volunteers (caregivers from the Clinical Hematology Department) who had also already received V1 and V2 was considered as controls. All participants were vaccinated between January 20 and June 1, 2021. Analyses were performed in July 2021. Antibody response to the SARS-CoV-2 spike protein receptor-binding domain was tested after V2 for all subjects (Serology post V2, SpV2) using the Roche Elecsys® assay. All subjects benefited later from another evaluation of specific serum antibodies as monitoring (Serology post V2+, SpV2+) or after V3 (Serology post V3, SpV3). Various serological methods were used for these later assays because performed outside of our hospital for some patients. Considering thresholds of negativity and positivity as well as highest values for each test, we were able nevertheless to distinguish 4 sub-groups: i) negativity at both SpV2 & SpV2+/SpV3, ii) increase of the IgG titer between SpV2 & SpV2+/SpV3, including patients showing seroconversion, iii) decreased or stable IgG titer between SpV2 & SpV2+/SpV3 and iv) highest IgG titers at both SpV2 and SpV2+/SpV3. Results A cohort of 25 controls and 114 patients, including 91 who received V3 (V3+) and 23 who did not (V3-) was considered for the purpose of this study. The characteristics of participants and delays from SpV2 to SpV2+ or SpV2 to SpV3 are reported in Tables 1 and 2. The serological methods used for the latest assays are reported in Table 2 with criteria of negativity, positivity and highest IgG titer values. V3- patients were younger, with less myeloid disease than V3+ cases and had not received myeloablative conditioning. However, both V3+ and V3- groups shared similar median intervals between Allo-HSCT and V1, incidence of previous graft versus host disease (GVHD), proportions of patients under chemotherapy or immunosuppressive drugs and median lymphocyte counts at V1, suggesting similar immune status. The reasons for not receiving V3 were forgetting, refusal or surveillance after detection of the highest IgG titer at SV2. Samples from controls, all evaluated by Roche Elecsys®, showed the highest anti-spike antibody value (>250U/mL) at both SpV2 and SpV2+, suggesting a persistent response without the need of a third vaccine in this healthy population. The proportion of patients still negative at SpV2+/SpV3 was similar between V3- and V3+ patients (17% vs 12%, p=0.74). However, the proportion of patients showing a decreased/stable IgG titer between SpV2 and SpV2+/SpV3 was significantly higher for V3- cases (35% vs 4%, p=0.0001) (Table 2). Moreover, the proportion of patients with the highest IgG titer at SpV2+/SpV3 was significantly higher in the V3+ sub-group (80% vs 43%, p=0.001), even if it remained significantly lower than in controls (p=0.03). The proportion of patients showing an IgG titer increase between SpV2 and SpV2+/SpV3 was higher in V3+ vs V3- patients (24% vs 4%, p=0.06). The difference was not significant as surprisingly one V3- case showed a seroconversion without any argument for SARS-CoV-2 infection between SpV2 and SpV2+. Three patients out of 14 (21%), with a negative SpV2, showed a seroconversion after V3. Fi ally, with a median follow up from V1 of 106 days in V3+ patients, 138 days in V3- patients and 154 days in controls, no COVID-19 infection was documented in any participant. Conclusion This study shows the interest of a third dose of BNT162b2 anti-SARS-CoV-2 messenger RNA vaccine after allograft as more patients are documented with less decrease of IgG titers and the highest IgG values after V3. [Formula presented] Disclosures: Moreau: Abbvie: Honoraria;Amgen: Honoraria;Janssen: Honoraria;Sanofi: Honoraria;Celgene BMS: Honoraria;Oncopeptides: Honoraria.

Implementation of Inpatient Palliative Care Consultation Triggers and Its Impact on Healthcare Use in Patients with Relapsed/Refractory Acute Myeloid Leukemia

Background: Patients with relapsed/refractory acute myeloid leukemia (AML) have poor outcomes and high levels of healthcare utilization at end of life. Palliative care remains underused in this population despite the high symptom burden. Questions remain regarding how best to integrate palliative care for high risk hematology patients. Prior implementation of standardized palliative care consultation triggers on an inpatient solid tumor service led to increased palliative care consultations and decreased healthcare utilization (Adelson et al, JOP 2017). We conducted a prospective cohort study evaluating standardized palliative care consultation triggers for patients admitted to a tertiary academic center with advanced AML. Method: Trigger criteria were developed for hospitalized patients with hematologic malignancies on the inpatient hematology floors at Smilow Cancer Hospital and included: 1) persistent disease after ≥ 2 lines of therapy, 2) length of stay (LOS) >7 days for symptom management, 3) Eastern Cooperative Oncology Group (ECOG) performance status > 2, and 4) refractory graft versus host disease (GVHD) after ≥ 3 lines of therapy. Patients with relapsed/refractory AML were included if they met criteria #1. A palliative care nurse coordinator performed chart review of admitted patients 1-2 times per week from June to December 2020 and contacted the primary team when a patient met eligibility. Patient characteristics and healthcare outcomes were compared with patients with AML meeting criteria #1 admitted pre-intervention (June to December 2019) using Fisher t-tests. Results: A total of 110 admitted patients with advanced AML met eligibility criteria #1 (64 pre-intervention and 46 post-intervention). Baseline patient and disease characteristics were similar, including mean age at admission (60.4 vs 60.9 years, p=0.848), gender (64% vs 59% male, p=0.691), prior transplant (56% vs 52%, p=0.702), and AML risk stratification (67% vs 78% adverse risk, p=0.283). In the post-intervention group, 61% of eligible patients were screened. Of the screened patients, 54% received a palliative care consult, 18% were declined by the primary team, 14% were marked as not eligible, and 14% did not have a palliative care consult with reason unspecified. Within the same admission, there was a significant increase in advance care planning and/or advanced directive documentation post-intervention (13% vs 28%, p=0.049). There was no differences in pre- and post-intervention groups in time to palliative care consult from admission (7.2 vs 4.9 days, p=0.245), LOS (12.13 vs 12.33 days, p=0.941), 30-day readmissions (52% vs 39%, p=0.246), critical/intermediate care escalation (22% vs 13%, p=0.318) during the same admission. By July 2021, 92% of the pre-intervention patients and 57% of the post-intervention patients were deceased. Of the deceased patients, there was no differences in pre- and post-intervention groups in blood transfusions (100% vs 96%, p=0.306) or hospice enrollment (46% vs 62%, p=0.157) within 14 days of death. There was also no significant differences in pre- and post-intervention groups in non-palliative anti-neoplastic therapy use (37% vs 38%, p=0.999), hospital admissions (95% vs 88% p=0.364), or critical/intermediate care escalation (51% vs 38%, p=0.350) within 30 days of death. Conclusion: A trigger-based palliative care referral intervention is feasible and doubled palliative care use in patients with relapsed/refractory AML. Our intervention was associated with increased advance care planning documentation during the admission. There were directional changes in other healthcare measures, including decreased time to palliative care consult and escalation of care, as well as increased hospice enrollment. These differences, however, were not statistically significant due to the small sample size. The significant healthcare use likely reflected high symptom burden at end of life, associated with transfusions and admissions for infection and symptom management. More research is needed to determine how best to sup ort these patients at end of life. Of note, our intervention period occurred during the COVID-19 pandemic, which may have impacted threshold for inpatient admissions and the inpatient census. Disclosures: Adelson: Carrum Health: Other: Stock;Abbvie: Consultancy;Roche/Genentech: Consultancy, Honoraria, Patents & Royalties, Research Funding;Heron: Consultancy;Celgene: Consultancy. Prebet: BMS: Research Funding;BMS, Curios, Daichi: Consultancy.

Profound B-Cell Lymphopenia Is a Major Factor Predicting Poor Humoral Response after BNT162b2 mRNA Sars-Cov-2 Vaccines in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation

Background Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection results in poor outcome in patients with hematologic malignancies. Moreover, the efficacy of anti-SARS-CoV-2 mRNA vaccines appears lower in immunocompromised patients, including recipients of allogeneic stem cell transplantation (Allo-HSCT). In this population, data are scarce regarding factors predicting the response to mRNA vaccines. Methods This retrospective study aimed to decipher which factors, including immune status at time of vaccine and recipient/donor blood groups, might influence the antibody response after two injections (V1 and V2) of BNT162b2 (Pfizer-BioNTech) vaccine in a cohort of allografted patients with no previous symptomatic nor asymptomatic COVID-19 infection. Possible previous asymptomatic COVID-19 infection was investigated in pre-V1 samples by testing for anti-nucleocapsid (N) antibodies (anti-SARS-CoV-2 immunoassay, Roche Elecsys®, Rotkreuz, Switzerland). Antibody response to the SARS-CoV-2 spike protein receptor-binding domain was tested post-V2 (Roche Elecsys®). As recommended by the manufacturer, titers ≥0.8 U/mL were considered positive, the highest value being >250 U/mL. Blood samples were also collected before V1 and at distance from V2 to evaluate, by flow cytometry, total lymphocyte (Ly) counts and quantitative Ly subsets (CD3, CD4 and CD8 T cells, B and NK cells). Statistical analyses were performed on R (version 4.0.3). Patient characteristics were compared by using the Χ² test for discrete variables and the Wilcoxon test for continuous variables. Generalized linear models were used to conduct multivariate analyses. Results Samples were available from 117 Allo-HSCT patients who had been vaccinated between January 20 and April 17, 2021. Patient characteristics are provided in Table 1. The average interval from Allo-HSCT day 0 (D0) to V1 (D0-V1) was 654 (IQR: 372-1367) days (d). S-antibody response rate post-V2 was 82.9% for the entire cohort. Non-humoral responders (NHR) post-V2 (n = 20) had a lower D0-V1 interval (median 271 vs 914 d, p <10 -5) and a lower pre-V1 median total Ly count (0.62 vs 1.61x10 9/L, p < 10 -4). Lymphocyte subsets possibly predictive of antibody response were then investigated. NHR were associated with lower median CD3 (0.39 vs 0.97 x10 9/L, p = 0.01), CD4 (0.13 vs 0.35 x10 9/L, p=<10 -3), and B-cell (0.00 vs 0.28 G/L, p <10 -6) counts. NK and T CD8 counts were not statistically different between NHR and HR (respectively p=0.14 and p=0.06). No influence either was observed when considering the age of donors (p=0.39) or recipients (p=0.55), underlying disease (p=1), Allo-HSCT conditioning (p=0.11), blood groups (donor, p=0.55;receiver, p=0.39) or a previous history of graft versus host disease (GVHD;83.1 vs 83.6%, p=1). Conversely, ongoing immunosuppressive (IS)/chemotherapy treatment and a haploidentical source of graft were associated with lower responses to vaccination (respectively 62.5 vs 90.5%, p<10 -3, and 69.4 vs 88.6% for patients with matched donors, p=0.02). In multivariate analysis (Fig.1) also including D0-V1 interval, donor source, current IS/chemotherapy treatment and TCD4 Ly count, only B cell aplasia remained statistically associated with lack of antibody response after two vaccine injections (OR 0.01, 95%CI [0.00 - 0.10], p <10 -3). The possible modification in terms of lymphocyte counts between pre-V1 and post-V2 times has been also investigated showing that only CD4 lymphocytes counts improved significantly (0.31 vs 0.34 x10 9/L, p=0.01) between this interval. Conclusion B cell aplasia appears as a major predictor of anti SARS-CoV-2 mRNA vaccine failure after Allo-HSCT. It may be suggested from this result that a close immune monitoring should be proposed after allotransplant to propose the vaccine at the most appropriate time, meaning after of B cell detection, regardless of the delay from Allo-SCT or the presence of an IS/chemotherapy treatment. The possibility for these patients to have mounted a cellular response should also be considered, which was not investigated here. [Formula presented] Disclosures: Moreau: Celgene BMS: Honoraria;Sanofi: Honoraria;Abbvie: Honoraria;Oncopeptides: Honoraria;Amgen: Honoraria;Janssen: Honoraria.