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

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

COVID-19 infection in hematopoietic stem cell transplant recipients.

Objective. To assess the course and outcomes of COVID-19 in recipients of allogeneic and autologous hematopoietic stem cell transplant (HSCT). Materials and methods. The retrospective study included 44 adult recipients (allogeneic - 33 [75%] and autologous - 11 [25%] of HSCT who diagnosed with COVID-19 after transplantation. Group mostly represented by acute leukemia - 18 (41%) and lymphoma - 10 (22.7%). The median follow-up time since the development of COVID-19 was 231 days (1-818 days), after HSCT - 507.5 days (14-3723 days). Overall and progression-free survival was assessed using the Kaplan-Meier and Log-Rank method. We also evaluated the characteristics of the course of a new coronavirus infection. Results. Median time for the development of COVID-19 from the moment of HSCT was 122.5 days (-1-3490 days). Twelve patients (27.2%) were in grade 3-4 neutropenia at the time of COVID-19 diagnosis, 16 (36.4%) patients were in grade 1-2 neutropenia. Sixteen (48.4%) allo-HSCT recipients had active graft-versus-host disease (GVHD) at the time of COVID-19 development. Disease severity was mild in 19 (43.2%) and moderate in 13 (29.5%) patients. Overall, 200-day survival from the onset of COVID-19 was 78.8% (95% CI [63.1-88.4]). Anemia (p = 0.02) and thrombocytopenia (p = 0.01) significantly decrease OS in patients with COVID-19 after HSCT. Patients with GVHD at the time of COVID-19 onset had a better survival rate (p = 0.02). The timing of COVID-19 development after HSCT did not affect outcomes. Conclusions. The key points of the course of COVID-19 in HSCT recipients are the presence of cytopenia and graft-versus-host disease. Overall survival was 78.8%.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

Prolonged SARS-CoV-2 infection during autologous hematopoietic stem cell transplantation from Hodgkin's lymphoma: a case report.

Autologous hematopoietic stem cell transplantation (HSCT) for relapsed Hodgkin's lymphoma increases the risk of infection by using intensive chemotherapy. This risk is obviously ongoing given the increased virulence of severe COVID-19. We report a case of a young man with Hodgkin's lymphoma who received conditioning chemotherapy followed by autologous HSCT and tested positive for SARS-CoV-2 by polymerase chain reaction (PCR) during the early phase of aplasia with persistence of COVID-19 beyond 30 days with favorable follow-up and clinical improvement on treatment. For this type of patient with hematologic malignancy, viral infection can be fatal and strict medical precautions with isolation rules must be maintained, especially for SARS-CoV-2.

Impact of Covid-19 in Patients with Multiple Myeloma Who Are Candidates for Autologous Hematopoietic Stem Cell Transplantation

Introduction: Recent studies have shown an increased risk of covid infections in patients with multiple myeloma (MM) compared to patients withoutMM, a reduction in the number of new diagnoses ofMMin 2020 compared to 2019 as well as a decrease in the survival of newly diagnoses patients. The general objective of this study was to analyze the possible impact of covid-19 pandemic in the treatment plan for patients withMM who are candidates for autologous hematopoietic stem cell transplantation (HSCT). Material(s) and Method(s): All patients with MM who received autologous HSCT in our hospital between March 2020 and October 2021 has been included in the study. This period coincides with the beginning of the confinement for covid-19 in our country and the date of which 88,4% of the population over 12 years of age had received the complete vaccination schedule at that time according to official data. Patient demographics, disease-related variables were obtained from the patient's medical record. On the other hand, treatment-related variables were collected from the eprescription program. Results and discussion: A total of 13 patients were undergoing induction treatment or underwent autologous HSCT during the study period, 62% were men. The median age of the patients was 55 years (30-69). Almost all patients (92,3%) were affected in some way the planned treatment. The reasons were the following: the induction treatment had to be prolonged in 5 patients (increase in the number of cycles due to the impossibility of performing the HSCT), in 4 patients the induction treatment had to be changed (bortezomib/lenalidomide/dexamethasone for bortezomib/ thalidomide/dexamethasone) due to the impossibility of performing apheresis as planned after the third cycle, 2 patients had delay in starting second-line treatment after disease relapse or in starting consolidation treatment and 1 patient suffered a delay in the diagnosis of relapse (delay in the planned CT scan confirming progression). Conclusion(s): Although we cannot yet know the impact on survival, the covid-19 pandemic has meant an alteration in the treatment plan of practically all myeloma patients who are candidates for HSCT and who were receiving anti-myeloma therapy in our hospital in the first 18 months after the declaration of the pandemic in our country.

Impact of Covid 19 pandemic on hematopoietic stem cell transplantation activities: Report from a single center.

The current COVID-19 pandemic has placed unprecedented stress on the healthcare system, including HSCT. Several international organizations have created guidelines for managing different aspects of HSCT in the context of the pandemic. Comparing 2019 and 2020, our transplant center performed the same number of transplants. In both periods, transplants were mainly for patients with acute leukemia; thus, the urgency criteria was respected in light of pandemic restraints. Transplants by sibling donors and cord blood units remained the same, while transplants by unrelated donors were increased, in particular from European registries, and transplants by haploidentical donors were decreased. This change was made in light of the necessity of cryopreserving all apheresis products. We decided against cryopreserving bone marrow products due to the greater risk of drastic reduction in CD34 + cell count during the process. For urgent cases with only a haploidentical donor available, we opted for the use of PBSC following stimulation with G-CSF. GvHD prophylaxis was performed with PTCY on days + 3 + 5, cyclosporine with tapering from day + 100, and mycophenolic acid until day + 90 post-HSCT. Post-transplant outcomes such as graft failure, sepsis, and GVHD were not affected by the changes implemented. As a result of logistic difficulties, we halted our Car-T program from the start of the lockdown in March 2020 until September 2020. In accord with international guidelines, we were able to continue our HSCT program in the order to ensure a lifesaving treatment for patients with hematologic diseases for whom this procedure cannot be postponed.

No evidence of excess mortality in the winter season in hematopoietic stem cell transplant recipients-a Swiss multi-center study

Introduction: In winter, mortality in the elderly general population is increased. Among other causes, this is due to infections from seasonal respiratory viruses and pneumonia. Patients afer hematopoietic stem cell transplantation (HSCT) frequently experience such infections. We therefore hypothesized that HSCT recipients experience excess mortality during winter. Method(s): This is a retrospective cohort study using the SBST database to assess the proportion of HSCT-patients who died during winter defned as from October to March as compared to the summer half of the year. Histograms depict distribution of dates of death. Univariate analyses for death afer allogeneic and autologous HSCT of factors potentially associated with higher risks of winter deaths such as patient age, disease, disease stage, presence of GvHD and treatment center were done by chi-squared tests. Multivariable logistic regression was done separately for all patients and those surviving less and more than 100 days and more than one year to separately evaluate early and late deaths. Result(s): Between 1997 and 2019 12'412 patients received HSCT (8107 auto, 4305 allo). 4904 patients died (3218 auto, 1686 allo). Overall, 2517 patients (51.3%) of those died in the winter season, 2387 (48.7%) in summer (fgure 1). The proportion of patients with deaths in winter did not difer by type of HSCT, age, disease or disease stage at the time of transplant. Excluding patients dying in the first 100 days and in the first year afer transplant or those dying without relapsed disease did not change these results. Only deaths in the first 100 days afer autologous HSCT had a higher number of events in winter but this did not reach statistical signifcance (p=0.17). Of particular interest, in patients afer allogeneic HSCT the proportion of deaths occurring in winter was 48%, 49%, 52% and 51% in patients with a transplant age less than 20, 20-40, 40-65 and >65 (p=0.61). Conclusion(s): Contrary to our assumption, no higher mortality in winter was found in HSCT patients pointing to no increased death rate due to respiratory viruses. Additional data will be analyzed once the Covid-19 pandemic is over. [Figure Presented].

SARS-CoV-2-infection in the setting of autotransplants for multiple sclerosis.

The severe adult respiratory syndrome virus type 2 (SARS-CoV-2) related acute respiratory distress syndrome (ARDS) has a strong immunological and inflammatory component; accordingly investigators are employing monoclonal antibodies to ameliorate the virus-induced cytokine storm such as antibodies against interleukin 6 (IL-6), tumor necrosis factors alpha (TNF-alpha) and CC chemokine receptor 5 (CCR5) (1). Cyclophosphamide (Cy) has proven its role in various settings including autoimmune diseases, and in the post-haploidentical stem cell transplant setting; Cy depletes cytotoxic and effector T cell populations while relatively sparing the regulatory T cells (Tregs) and could tip the balance away from the overtly pro-inflammatory setting (1). We present here the cases of three persons who were infected by the SARS-CoV-2 virus during the Cy-induced pancytopenia of an autologous hematopoietic stem cell transplantation (HSCT), aimed to down-regulate the immune response in multiple sclerosis (MS) (2). The surprisingly benign course of the COVID-19 in the three cases suggest that the Cy could have had a role in abrogating the inflammatory response in these persons.

Immunochemotherapy of refractory classical Hodgkin's lymphoma with high-dose consolidation and autologous hematopoietic stem cell transplantation complicated by a new coronavirus infection

Classical Hodgkin's lymphoma is one of the most treatable lymphoproliferative diseases with current chemotherapy regimens. The 5-year overall survival rate among patients after initial chemotherapy reaches 95 %, however, despite the significant success achieved, the problem of refractoriness/relapse remains very relevant. A standard approach to the treatment of refractory/recurrent Hodgkin's lymphoma among young patients with preserved general status and chemoresponsive to salvage therapy tumor is high-dose consolidation chemotherapy followed by transplantation of autologous hematopoietic stem cells. The intensification of chemotherapy regimens is highly difficult task for a doctor during the COVID-19 pandemic, which requires careful assessment of a risk-benefit ratio. In current conditions, new targeted and immune drugs are used to overcome resistance and reduce toxicity among pretreated patients, which allows not only to improve the results of a treatment, but also to preserve the high quality of life among patients with extremely unfavorable prognosis. we show our experience of using a checkpoint inhibitor in combination with a dose-intensive regimen of DHAp (dexamethasone, cytarabine, cisplatin) in the treatment of a refractory classical Hodgkin's lymphoma followed by high-dose consolidation chemotherapy and allogeneic hematopoietic stem cells transplantation, among patients complicated with a new coronavirus infection in the post-transplant period. Copyright © 2022 ABV-Press Publishing House. All rights reserved.

A changing target-adapting ongoing autologous haematopoietic stem cell transplantation clinical trials to evolving clinical practice in the treatment of highly active relapsing remitting multiple sclerosis

Background: Autologous hematopoietic stem cell transplantation (aHSCT) is an effective and safe treatment resulting in suppression of disease activity and delay of disease progression in patients with highly active relapsing remitting multiple sclerosis (RRMS) who failed first line disease modifying treatments (DMT) (Burt et al. 2019). However, its safety and effectiveness compared to high efficacy DMTs remains undetermined. Around 4-14% RRMS patients present with an aggressive clinical course (Lacobaeus et al. 2020). There is no unanimous definition of aggressive MS but rapidly evolving severe MS (RES-MS) is defined as patients with >=2 disabling relapses in 1 year, and >=1 gadoliniumenhancing lesions or a significant increase in T2 lesion load on brain magnetic resonance imaging (MRI). High efficacy DMTs are usually a first line treatment to prevent long term disability (Laffaldano et al. 2021). In a retrospective study Das et al. (2021) demonstrated no evidence of disease activity in 100% of patients with treatment naive aggressive RRMS treated with aHSCT. Method(s): Star-MS, ISRCTN88667898, is a multicentre parallelgroup rater-blinded randomised controlled trial of aHSCT versus high efficacy DMT (alemtuzumab, cladribine, ocrelizumab and ofatumumab) of 198 RRMS patients in the United Kingdom. aHSCT is delivered using non-myeloablative conditioning with a cyclophosphamide/anti-thymocyte globulin regimen followed by an unselected autologous graft. Eligibility was based on clinical practice at the time the trial was conceived in 2019 and included patients with >=2 relapses, or 1 relapse and evidence of MRI disease activity >3 months before or after its onset, in the last 12 months despite use of a DMT (but not a comparator DMT). Star-MS opened recruitment in September 2021 following an 18 month delay due to COVID. Changes to clinical practice, namely early use of high efficacy treatment, no longer aligned with trial design, reducing the pool of eligible patients, resulting in slower than expected recruitment. Trial protocol was revised to include active RRMS, defined as >=1 relapse or evidence of MRI disease activity in last 12 months use of a DMT, or RES-MS in treatment naive patients. Here we describe the positive impact of utilising adaptations to study design to keep clinical trials aligned with clinical practice. Conclusion(s): Clinical trials must be responsive to changing clinical practice to ensure success and relevance to the target patient population.

Implications of Pre-Transplant (tx) COVID-19 on SOT or HCT: A Multicenter Study

Purpose: Describe outcomes of patients (pt) with pre-tx COVID-19. Method(s): Multicenter study of SOT/HCT candidates who had a positive (pos) SARS-CoV-2 PCR pre-tx. Result(s): Pre-tx: Of 208 pt, median age was 56 (range 3-76). 87.8% were SOT candidates (40.5% kidney, 40.5% liver, 9.8% lung, 6.9% heart, 2.3% pancreas) and 13.9% were HCT candidates (54.2% allo, 45.8% auto). Pt underwent a median of 2 tests (range 1 - 14). In 41% of pt, > 1 neg PCR was required by the tx center before reactivation. Neg PCR was documented in 67.4% of pt at a median of 41 days (18-68) after pos PCR. Waitlist mortality was 11.0%;deaths were due to COVID-19 in 60% (12/20). Post-tx (all pt): 78 pt underwent tx at a median of 65.5 days (range 17-324) from COVID-19;71/78 have completed 4-weeks of follow-up. 24/78 (30.7%) pt were still PCR pos at time of tx (details below). 54/78 (69.2%) pt underwent routine PCR testing post-tx;62% were tested regularly for 8 weeks. Only 1 pt, who remained asymptomatic, developed recurrent pos PCR on surveillance testing 18 days post-tx. 1 pt had graft loss. There were no deaths at 4 weeks post-tx. Pt transplanted without a negative PCR: 24 pt with COVID-19 did not have neg PCR at time of tx: 9 (37.5%) kidney, 9 (37.5%) liver, 2 (8.3%) SLK, 1 (4.2%) lung, 1 heart (4.2%), 2 auto-HSCT (8.3%), 2 allo-HSCT (8.3%). Of 24 pt who were reactivated at a median of 21 days (range 8 - 38) from COVID-19 diagnosis, 7 underwent tx emergently (5 liver, 1 lung, 1 heart). 20/24 completed 4-weeks of follow-up;all were alive. PCR Cycle thresholds (Ct) increased over time, suggesting a reduction in SARS-CoV-2 viral loads with time elapsed since COVID-19 diagnosis. Conclusion(s): Short-term outcomes of transplantation in SOT/HCT candidates with prior COVID-19 were promising in this small cohort, even with a positive PCR going into transplant. Whether documentation of a negative PCR should be required for all tx candidates with a history of COVID-19 prior to transplantation should be investigated further, particularly among lung tx candidates. For certain tx candidates with COVID-19, relying time-based strategy instead of a test-based strategy may be 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.

RADIOIMMUNOTHERAPY (RIT) VERSUS AUTOLOGOUS HEMATOPOIETIC STEM-CELL TRANSPLANTATION (ASCT) IN RELAPSED/REFRACTORY (R/R) FOLLICULAR LYMPHOMA: A FONDAZIONE ITALIANA LINFOMI (FIL) PHASE III TRIAL

Background: Optimal consolidation for young R/R FL in the rituximab age remains uncertain and the benefit of ASCT is not clearly established. Aims: The FIL FLAZ12 trial (NCT01827605) is a prospective, multicenter, randomized, phase 3 trial, comparing RIT versus ASCT, as consolidation after chemoimmunotherapy, both followed by R maintenance in R/R FL. Methods: Pts aged 18-65 yrs, with R/R FL after 1 or 2 lines of chemoimmunotherapy, without significant comorbidities were enrolled. Patients received 3 courses of therapy chosen by the investigator among RCHOP, R-DHAP, R-FM, R-ICE, R-IEV or R-B. Pts achieving at least PR (according to Cheson et al. 2007) were randomized 1:1 to either RIT or ASCT before CD34+ collection. Conditioning for ASCT was BEAM or TEAM. RIT was given as previously described (Morschhauser et al., 2008). After consolidation, pts received R maintenance every 3 months for eight courses. Primary endpoint was PFS. Considering ASCT toxicity, it was hypothesized to be a superior choice, if capable of increasing 3-years PFS from 40% to 60% (two-side log-rank test with alpha of 5% and a power of 85%). Clinical secondary endpoints were ORR, CRR, OS, EFS and TTF. Results: Between Aug 2012, and Sep 2019, 164 pts were screened and 159 enrolled by 38 FIL Centers (enrolled population). Unfortunately, the study was prematurely closed due to low accrual. The data were analyzed on an ITT basis on May 2, 2021 with a median follow-up (mFU) from enrollment of 43 months and 75 PFS events. The two arms were clinically well balanced, with median age of 57 yrs (IQR 49-62), 55% male, 57% stage IV, 20% bulky disease. Tumor re-biopsy was performed in 79% pts. POD-24, retrospectively assessed was observed in 32% of pts. Two pts (1%) did not start treatment (non-confirmed histology and withdrawal). Sixteen (10%) pts discontinued before randomization (7 SD, 3 PD, 3 AE, 1 withdrawal, 2 poor compliance) and 141 (89%) were randomized to either RIT (71) or ASCT (70) (randomized population). Of these 19 (13%) (RIT 8, ASCT 11) did not receive the planned consolidation due to 7 PD, 4 AE, 1 medical decision, 2 poor mobilization, 2 withdrawals, 1 poor compliance, 2 protocol breaches, while 63 (89%) received RIT and 59 (84%) ASCT. After RIT, 61% of pts achieved CR and 23% PR, while after ASCT these were 70% and 9%. Estimated PFS at 3 yrs was 60% (95% CI: 46%-71%) in the RIT arm vs. 59% (95% CI:45%-70%) in the ASCT arm, p = 0.8613 (HR 0.96, 95%CI: 0.57,1.59). (Figure 1) 3yrs-OS was again superimposable in the two arms: 83% (95%CI: 69%-91%) in the RIT vs 85% (95% CI: 72%-91%) in the ASCT, p = 0.8310 (HR 1.10, 95%CI: 0.45,2.72). Grade ≥ 3 hematological toxicity was 46% in the RIT vs 94% in the ASCT arm (p < 0.001). For ASCT vs RIT grade ≥3 neutropenia occurred in 94% vs 41% of pts (p < 0.001). During follow-up, 4 pts died in remission: 1 AML (RIT), 2 SARS-COV2 infections (RIT) and 1 pneumonia (ASCT). Second cancers occurred in 3 pts after RIT and 7 after ASCT (p = 0.480). Multivariable analysis for PFS indicated POD-24, male sex, LDH and refractory disease as adverse parameters. Subgroup analysis for PFS including gender, age, LDH, POD-24 and extranodal disease show no subgroup favoring RIT nor ASCT. Image: Summary/Conclusion: Even if prematurely interrupted, our study demonstrated no meaningful difference in efficacy between ASCT and RIT, but ASCT was more toxic and more demanding for pts and health service. Both strategies induced a similar and favorable long-term outcome suggesting that consolidation programs milder than ASCT require further investigation in R/R FL.

Safety and cost effectiveness of outpatient autologous hematopoietic stem cell transplantation for multiple myeloma - Single-center experience of a pilot Early Discharge Program

Introduction: Multiple myeloma (MM) is the leading indication for autologous stem cell transplantation (ASCT), with over 12,000 transplants per year in Europe. Due to low toxicity, an entirely outpatient procedure or an early discharge after ASCT can be considered as alternatives to inpatient transplantation. Thus, we launched an Early Discharge Program (EDP) for patients qualified for ASCT due to MM who were under 60 years of age, without significant comorbidities, who had a caregiver available 24/7, and who lived within a 60-minute drive of our hospital. Material and methods: Patients spent 72 hours in the hospital being administered melphalan 200 mg/m2 intravenous followed by an infusion of hematopoietic stem cells. They were eventually discharged and remained under outpatient care. The program was launched in September 2019 and was temporarily halted due to the coronavirus disease 19 (COVID-19) pandemic in early 2020. Five patients were enrolled to the EDP. Results: Non-hematological toxicity was mild and manageable in an outpatient setting. Only one patient was readmitted due to exacerbation of ulcerative colitis that was probably not related to ASCT. We observed neither infections nor bleeding. Due to hematological toxicity, three of the five patients received platelet transfusion on the 6th day after ASCT as outpatients. No packed erythrocytes were transfused. The EDP demonstrated lower costs compared to an inpatient approach. Conclusions: We believe that early discharge, which is an intermediate step to full at-home transplantation due to patients' wellbeing, reduction of infections caused by resistant microorganisms, and costs, will eventually replace a full inpatient procedure for a significant population of patients suffering from multiple myeloma and indeed other diseases.

Allogeneic and Autologous Hematopoietic Transplants Can be Safely Performed after COVID-19 Infections

We are in the midst of a pandemic with the COVID-19 virus, a pathogen with potential severe manifestations. A major clinical question is whether it is safe to undergo hematopoietic stem cell transplantation (HSCT) shortly after COVID-19 infection. A total of 21 patients received HSCT following a diagnosis of COVID-19 infection at our institution between 7/30/2020 and 4/14/2021. The majority (n=13, 62%) received an allogeneic (ALLO) HSCT from an HLA-matched related (n=5), -matched unrelated (n=6), or haploidentical (n=2) donor. The remaining 8 patients received autologous (AUTO) HSCT. Among ALLO-HSCT recipients, 4 (31%), 5 (38%), 3 (23%), and 1 (8%) patients had grade 1, 2, 3, and 4, manifestations respectively, scored according to the WHO COVID-19 infection severity grading system. Among AUTO-HSCT recipients, 5 (62%), 1 (12%), and 2 (25%) patients had grade 0, 1, and 2 manifestations, respectively. All patients had resolution of COVID-19 symptoms before HSCT. In recipients of ALLO-SCT, the median time from diagnosis of the COVID infection to HSCT was 134 (range: 55-311) days. Median age of recipients was 53 (range: 17-71) years and the majority (69%) of patients were male. Only one patient was <18 years old, and 38% were >60 years. Patients received ALLO-HSCT for treatment of acute myeloid leukemia or myelodysplastic syndrome (n=7, 54%), acute lymphoblastic leukemia (n=2, 15%), chronic lymphoblastic leukemia (n=2, 15%), and Hodgkin's (n=1, 8%) or non-Hodgkin's lymphoma (n=1, 15%). Most (62%) patients were not in remission at the time of HSCT. The median hematopoietic cell transplant-co-morbidity index (HCT-CI) score was 3 (range 0-6);one patient had a history of diabetes and another of hypertension before HSCT. Conditioning regimen was myeloablative in 61%, and stem cell source was peripheral blood (PB) in 92% of transplants. Median time to neutrophils engraftment was 15 (range: 10-20) days. With a median follow-up of 3.5 (range: 0.4-8) months since ALLO-HSCT, two patients died and another two experienced progression of the underlying malignancy. Three patients were diagnosed with grade 2 and none with grade 3 or 4 acute graft-versus-host disease (GvHD). The deaths occurred among patients with COVID-19 infection grade 2 and 3. The primary cause of death was attributed to alveolar hemorrhage/pneumonitis (no organism identified) and acute GvHD, respectively. Overall survival was 89% (95% confidence interval [CI]:43-98) and 76% (95% CI 33-93) at 3 and 6 months, respectively. In recipients of AUTO-HSCT, the median time from diagnosis of the COVID-19 infection to HSCT was 55 (range: 20-157) days. Median age of recipients was 55 (range: 34-75) years, and the majority (62%) of patients were male. One (12%) patient was >60 years. Patients received AUTO-HSCT for treatment of Hodgkin's (n=1, 15%) or non-Hodgkin's (n=4, 50%) lymphoma, or multiple myeloma (n=3, 37%). Six (75%) patients were in remission at the time of HSCT. The median HCT-CI score was 2 (range 0-6). None of the patients had a history of diabetes or hypertension before transplant. Conditioning regimen was myeloablative and stem cell source was PB for all patients. Median time to neutrophils engraftment was 10 (range: 9-13) days. With a median follow-up of 4 (range: 0.8-9) months since AUTO-HSCT, one patient with grade 1 COVID infection died as a result of a candida/cytomegalovirus infection, and none of the patients experienced progression of the underlying malignancy. Overall survival was 100% and 75% (95% CI 13-96) at 3 and 6 months respectively. After HSCT, one ALLO and two AUTO asymptomatic patients had a positive nasal swab COVID-19 PCR assay possibly due to delayed shedding of the virus. None of the 21 patients developed active COVID infections post-transplant. In conclusion, allogeneic and autologous hematopoietic transplantation can be performed in patients after COVID-19 infection. Two of 13 allogeneic and one of 8 autologous recipients experienced non-relapse mortality, none directly related to COVID-19 infection. Patients recovering from COVID-19 in ection should be considered eligible for hematopoietic transplantation as clinically indicated. Disclosures: Shpall: Magenta: Honoraria;Affimed: Patents & Royalties;Novartis: Honoraria;Navan: Consultancy;Magenta: Consultancy;Axio: Consultancy;Adaptimmune: Consultancy;Bayer HealthCare Pharmaceuticals: Honoraria;Novartis: Consultancy;Takeda: Patents & Royalties. Chemaly: Other: Other: Compensation: I am a consultant and advisor on companies who are developing new agents such as Merck, Ansun, and Janssen.

Characterization of the Humoral and Cellular Immune Response Against the Natural Infection By Sars-Cov-2 in Oncohematological Patients with Post-COVID19 Autologous Transplantation

Background: Oncohematological patients may have a lower immune response against SARS-CoV-2, both to natural infection and to vaccines. Most studies have focused on the analysis of the humoral response, which means that the information available on the cellular response against SARS-CoV-2 in these patients is limited. Current recommendations include vaccination against SARS-CoV-2 in patients undergoing autologous hematopoietic stem cell transplantation (AHSTC), regardless of whether they have been previously exposed to the virus. These recommendations are based on previous studies with other vaccines. Therefore, it is necessary to analyze the immune response that is developed in these patients in order to make specific recommendations for COVID-19 vaccination. Objective: To study the humoral and cellular immune response before and after AHSTC in patients with oncohematological neoplasms who were exposed to SARS-CoV-2 before the transplantation. Materials & methods: Nine patients with previous exposure to SARS-CoV-2 who underwent AHSTC (Table 1) and 8 healthy donors who recovered from mild COVID-19 were recruited from Hospital Ramón y Cajal and Primary Healthcare Center Pedro Laín Entralgo (Madrid, Spain), respectively. Specific direct cellular cytotoxicity (DCC) of PBMCs from these patients against Vero E6 cells infected with pseudotyped SARS-CoV-2 was determined. The activation of caspase-3 in Vero cells was measured after 1 hour of co-culture with PBMCs, in which cytotoxic cell populations were analyzed by flow cytometry. Antibody-dependent cellular cytotoxicity (ADCC) was analyzed by quantifying the binding of Annexin V to rituximab-coated Raji cells as targets of PBMCs. Results: 1) 66% of AHSTC patients did not develop detectable levels of IgGs against SARS-CoV-2 (Fig. 1). In 33% of these patients with detectable IgG, the titers decreased after AHSTC, as well as their neutralizing capacity (Fig. 1B and C). 2) AHSTC patients showed increased levels of immature B cells (9.5-fold;p=0.0586) and plasmablasts (28.8-fold), in comparison with healthy donors who had mild COVID-19, while naive and resting memory B cells decreased 1.7- and 6.9-fold, respectively. 3) Specific DCC against SARS-CoV-2-infected cells increased 1.5-fold in comparison with healthy donors (Fig. 2A). Cytotoxic populations with NK phenotypes (CD3-CD56+CD16+), NKT (CD3+CD56+CD16+), and CD8+ T cells (CD3+CD8+TCRγδ+) increased 1.9- (p=0.0311), 1.9- (p=0.0592), and 1.6-fold, respectively (Fig. 2B). ADCC increased 2.1-fold in PBMCs from AHSTC patients in comparison with healthy donors (p = 0.0592). Conclusions: Our data show for the first time how the humoral and cellular immune response against the natural infection by SARS-Cov-2 may be modified in patients who were subsequently subjected to AHSTC. Although the humoral response may be reduced after AHSTC, the specific cellular response showed an increased cytotoxic activity. These results could be extrapolated to patients who were vaccinated against COVID-19 prior to AHSTC. Therefore, this information could be useful to define the recommendations for COVID-19 vaccination after AHSTC. [Formula presented] Disclosures: Garcia-Gutiérrez: Pfizer: Research Funding;Incyte: Consultancy;Novartis: Consultancy;Bristol-Myers Squibb: Consultancy.

Serological Response Following BNT162b2 Anti-Sars-Cov-2 mRNA Vaccination in Hematopoietic Stem Cell Transplantation Patients

Patients with hematological malignancies (HM) undergoing hematopoietic stem cell transplantation (HSCT) have an increased vulnerability to SARS-Cov-2 (Sharma et al, Lancet Haematology 2020;Ljungman et al, Leukemia 2021), the reason why international guidelines strongly support the need for a protective vaccination for these subjects. The most relevant data currently available on the response to a complete anti-SARS-Cov-2 vaccination cycle in HM patients after HSCT refer to 314 patients reported in a Lithuanian national survey (Maneikis et al, Lancet Haematol 2021). In this study, the median titers of antibodies against SARS-Cov-2, determined 7-21 days after the second vaccination, were comparable to that of healthy controls (HC) in both autologous and allogeneic groups, with no patient found below the protective threshold of 50 arbitrary units (AU)/ml. Notably, the large majority of patients had received the transplant more than 1 year before vaccination. In a prospective, cohort study, we compared 114 patients, who had received an autologous or allogeneic HSCT at least three months before the first dose of vaccination, to 107 HC, matched for age and sex. Study population and HC received two doses of BNT162b2 anti-SARS-Cov-2 mRNA vaccine on days 1 and 21, between April and May 2021. Serological tests were performed by a commercially available immunoassay for the quantitative determination of anti-spike IgG antibodies to SARS-Cov-2. The cut-off for defining responders was 50 or greater AU/ml. Patients and HC samples were collected four weeks after the second dose of the vaccine. Table 1 reports the main clinical characteristics of patients and HC. Eighteen of 114 patients (16%) did not respond (24% in the allogeneic group, 6% in autologous recipients). Overall, median antibodies titers did not differ between HC and the entire cohort of transplanted patients, recipients of allogeneic HSCT, all patients responding to the vaccine or responders in the autologous subgroup (Figure 1A). All autologous HSCT recipients had significantly lower titers of antibodies than HC, while higher levels were found in responders who had received allogeneic HSCT (Figure 1A). Responders in the allogeneic subgroup showed antibodies titers significantly higher than responders in the autologous subgroup (Figure 1B). We further stratified patients in three groups, according to the time elapsed from transplant to vaccination: G1:<1 year;G2:1-5 years;G3:>5 years. Higher antibodies titers were observed in HC compared to all transplanted patients in G1 (Figure 1C), including both allogeneic (Figure 1D) and autologous (Figure 1E) HSCT recipients. No differences emerged in G2 between HC and all patients (Figure 1C), allogeneic (Figure 1D) or autologous (Figure 1E) HSCT recipients. Finally, no differences were found in G3 when comparing HC with all patients (Figure 1C) or allogeneic recipients (Figure 1D), whereas patients in the autologous subgroup showed significantly lower titers than HC (Figure 1E). Myeloma patients with controlled disease showed higher titers than patients with active disease (Figure 1F). According to median age, autologous HSCT recipients older than 57 years had significantly lower antibody levels than younger patients (Figure 1G). Autologous vs allogeneic HSCT, age of all patients and of allogeneic HSCT recipients, sex, type of allogeneic HSCT, conditioning regimen, age and sex of donor, occurrence of GVHD, disease type and single vs double autologous HSCT did not significantly impact on antibody levels (data not shown). No relevant side effects were recorded after vaccination. With a median follow up of 12 weeks, no case of COVID19 occurred among vaccinated patients. In our single center study, patients with a previous history of HSCT tolerated well BNT162b2 vaccine and mounted a potentially protective immune response in the majority of cases one month after two doses of vaccine. However, lack of response was not rare, especially in the allogeneic setting. The main factor associated with the quality of response was the tim from HSCT, with lower responses within the first year from transplant and differences between autologous and allogeneic groups transplanted more than five years before vaccination. Here, a consolidated, complete immune reconstitution in allogeneic HSCT recipients, as well as age and a still active disease in the autologous setting, could have played opposite pivotal roles. [Formula presented] Disclosures: Delia: Gilead: Consultancy;Amgen: Consultancy;abbvie: Consultancy;Jazz pharmaceuticals: Consultancy.

COVID-19 in Children Following Hematopoietic Cell Transplantation: A Multinational Study of the European Bone Marrow Transplantation Society (EBMT) and the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH)

Introduction COVID-19 is usually a mild disease in immunocompetent children, with ~1% requiring intensive care unit (ICU) admission and <0.1% mortality. Data on its course in children following hematopoietic cell transplantation (HCT) is limited. Methods Data on children following HCT who developed COVID-19 (diagnosed by positive SARS-CoV-2 PCR on respiratory tract samples) during 3.2020-4.2021 were prospectively collected by EBMT and GETH, including demography, HCT data, COVID-related manifestations, ICU admission and mortality. Factors associated with worse outcomes (ICU admission or mortality) were characterized. Results Sixty-two children (34 boys;median age 9;min-max;0.7-17 years) were reported from 27 centers, 16 countries;57 (92%) following allogeneic and 5 (8%) following autologous HCT. Underlying diseases were acute leukemia (23;37%), inherited disorders (9;15%), hemoglobinopathies (7;11%), solid tumor (6;10%), bone marrow failure (5;8%), other malignant (8;13%) and non-malignant (4;6%) diseases. Five (8%) children had high blood pressure;6 (10%) had underlying lung pathology. The median time from the most recent HCT to COVID was 5 months (min-max;0-169). The stem cell source was bone marrow (33);peripheral (22) or cord blood (1). Among the patients with information available, 34 (62%) underwent in-vivo T cell depletion, 20 (33%) received corticosteroids, and 36 (60%) other immunosuppressant drugs(s) within two months prior to and after the COVID-19 episode. The presence of acute grade 2-4 or chronic graft versus host disease (GVHD) was reported in 12/54 (23%) and 8/51 (16%) children, respectively. Clinical presentation (n=57) included fever (28;49%), cough (18;32%), diarrhea (8;14%), upper respiratory tract disease (as rhinorrhea, sinusitis, otitis, or pharyngitis;12;21%);six (10%) required oxygen to maintain oxygen saturation above 92%;20 children (35%) were asymptomatic. The median time from symptoms onset to COVID diagnosis was 1 day (-43-40). Sixty-three percent of patients were hospitalized;43% due to COVID. The proportion of children with neutropenia or lymphocytopenia (<500 cells/mm 3) was 75% and 73%, respectively. Sixteen children (26%) had evidence of viral (n=10), bacterial (n=6) or fungal (n=2) coinfections. The median time from COVID diagnosis to the last follow-up in alive patients was 69 days (min-max;2 - 294). Six (10%) children who developed COVID at a median 6.5 (min-max;2- 16) months following allo-HCT (median age 6 years;5 boys) required ICU care within a median 6 (min-max;-5-15) days after diagnosis. All of them were neutropenic, received steroids, and other immunosuppressive drugs at COVID diagnosis;5 had undergone in-vivo T cell depletion;5 were lymphocytopenic, 5 had GVHD (2 acute and 3 chronic);3 received non-invasive and 2 invasive ventilation. Three children had viral or bacterial coinfections. Three children died. Six (10%) children (5 boys, median age 10.5 years;min-max;4-13) who developed COVID at median 2 (min-max;0-147) months following allo-HCT died within median 35 days (min-max;5-54) after diagnosis. One had high blood pressure, and none suffered from underlying lung pathology. At the time of COVID, 3 were neutropenic, 2 lymphocytopenic;4 had GVHD (2 acute, 2 chronic);3 received steroids and 4 immunosuppressive drugs. Two had viral or bacterial coinfections. Five had positive SARS-CoV-2 PCR at the time of death. In 3, COVID was the primary cause of death. We compared nine children with the worse outcomes to 53 children with benign course. Among patients alive at 100-day post HCT, the probability of worse outcomes was higher in patients with vs. without chronic GVHD (Figure). No other significant differences were observed in demographic, underlying disease, and HCT-related characteristics. Compared to adults following HCT (Ljungman, Leukemia 2021), children had: - Shorter median time from HCT to COVID diagnosis, 5 vs 18 months;- Higher proportion of asymptomatic infections, 35% vs 9%;- Lower proportion of those who required oxygen, 10% vs 35%;- Lower all-cause mortality, 10% vs 29%. Conclusions Children following HCT with COVID-19 have a higher risk of ICU admission and mortality compared to immune competent children. The presence of chronic GVHD at COVID diagnosis was associated with worse outcomes. COVID course following HCT is milder in children compared to adults. [Formula presented] Disclosures: Averbuch: Takeda: Consultancy;Pfizer: Consultancy;GSK: Speakers Bureau. De La Camara: Roche: Consultancy;IQONE: Consultancy. Corbacioglu: Gentium/Jazz Pharmaceuticals: Consultancy, Honoraria. Mikulska: Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Gilead: Speakers Bureau;MSD: Speakers Bureau;Janssen: Speakers Bureau;Biotest: Speakers Bureau. Kulagin: Roche: Speakers Bureau;Sanofi: Speakers Bureau;Generium: Speakers Bureau;Biocad: Research Funding;Apellis: Research Funding;Alexion: Research Funding;X4 Pharmaceuticals: Research Funding;Novartis: Speakers Bureau;Johnson & Johnson: Speakers Bureau;Pfizer: Speakers Bureau. Cesaro: Sobi: Membership on an entity's Board of Directors or advisory committees;Gilead: Speakers Bureau. Lawson: Alexion: Honoraria. Kroeger: Neovii: Honoraria, Research Funding;Sanofi: Honoraria;Jazz: Honoraria, Research Funding;Celgene: Honoraria, Research Funding;Riemser: Honoraria, Research Funding;Gilead/Kite: Honoraria;AOP Pharma: Honoraria;Novartis: Honoraria. Styczynski: MSD, Pfizer, Giled, TEVA, Jazz, Novartis: Honoraria, Speakers Bureau. Ljungman: Takeda: Consultancy, Other: Endpoint committee, speaker;Enanta: Other: DSMB;Janssen: Other: Investigator;OctaPharma: Other: DSMB;Merck: Other: Investigator, speaker;AiCuris: Consultancy.

Safety, Feasibility and Healthcare Cost Differences between Inpatient and Outpatient Mobilization Chemotherapy for Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma: A Single Center Experience

Introduction The standard of care for patients with multiple myeloma (MM) involves autologous hematopoietic stem cell transplantation (ASCT). Pre-ASCT mobilization chemotherapy for MM, vinorelbine and high dose cyclophosphamide (VC), has been historically given in the inpatient (IP) setting. Due to rising bed occupancy rates and patients' preferences for treatment in the ambulatory setting, our team has offered eligible patients an option to receive VC outpatient (OP) since 2018. Our study aims to audit the feasibility and safety of this initiative, and review potential healthcare-related cost savings. Methods Eligibility criteria for OP chemotherapy were developed by a multidisciplinary team based on patients' age, functional status, medical comorbidities and social factors (Figure 1). The chemotherapy regimen was modified for an OP setting (Figure 2), of which the main alteration involved changing the route of administration of intravenous (IV) mesna to a combination of IV and oral. A retrospective review was conducted for 35 MM patients (18 IP and 17 OP) who received VC for mobilisation at our center from 2018 to 2019. The patient characteristics were similar between the two groups (Table 1). Patient data were analyzed from the day of admission for VC (IP) or day 1 of VC (OP), to the day before admission for stem cell harvesting. Clinical charts were reviewed for unexpected complications and unplanned admissions. Costs incurred were calculated using the value-driven-outcome (VDO) informatics analysis of the hospital. Results There were no unexpected clinical complications or unplanned admissions in both groups. The median length of hospital stay for the IP cohort was 3 days, amounting to a saving of 51 hospital days over 2 years in the OP cohort. Median costs were 73% lower in the OP cohort (Figure 3). The difference was mainly due to certain costs not incurred in the OP setting. These included room charges and daily treatment fees (which accounted for an average of 46% and 19% of IP charges respectively). Investigation costs were also 55% lower in the OP cohort, which could be attributed to more investigations being performed in the IP setting such as screening for methicillin-resistant Staphylococcus aureus and nonurgent radiographs ordered after hours by the on-call physician upon admission. Conclusions Our findings show that OP mobilization chemotherapy for MM is safe, feasible and associated with improved bed utilization and cost savings. Other components of the stem cell transplantation process are also increasingly being transitioned from the IP to OP setting in our center as part of an ongoing paradigm shift in right-siting treatment services, which has been accelerated by the COVID-19 pandemic's strain on inpatient capacity. These results provide an affirmation of our efforts to optimize the utilization of healthcare resources. [Formula presented] Disclosures: Chng: Takeda: Consultancy;GlaxoSmithKline: Consultancy;Johnson & Johnson: Consultancy, Research Funding;Aslan: Research Funding;Antengene: Consultancy;Abbvie: Consultancy;Pfizer: Consultancy;Novartis: Research Funding;Sanofi: Consultancy;Amgen: Consultancy;BMS/Celgene: Consultancy, Research Funding.

Use of Monoclonal Antibody Therapy in Hematologic Patients with Mild-to-Moderate COVID-19: A Retrospective Single-Center Experience

Background: In November 2020, the U.S. Food and Drug Administration (FDA) issued emergency use authorization (EUA) for monoclonal antibody (mAb) therapy in patients with mild to moderate COVID-19 who are at high risk for disease progression. These mAbs reduce the risk of hospitalization in the general population. However, its efficacy and safety in immunocompromised hematology patients are not known. Methods: From November 9th, 2020, until February 28th, 2021, all adult hematology patients with mild to moderate COVID-19 disease who received monoclonal antibodies within 10 days of symptoms onset were included. Patients who were asymptomatic, had severe or critical COVID-19 disease, or were hospitalized at the time of COVID-19 diagnosis were excluded. Baseline demographic, clinical outcomes, and hematologic-related data were extracted. All statistical analysis was performed using SAS statistical software. Results: Thirty-eight hematology patients with mild to moderate COVID-19 disease who received mAb therapy under EUA were included in this study. Thirty (79%) patients received bamlanivimab and 8 (21%) casirivimab-imdevimab. Baseline characteristics prior to mAB administration include: 53% female, median age of 51 years (range: 21-80), with 18% above 65 years old. Twenty-eight (74%) patients received cellular therapy: 18 (47%) had undergone allogeneic hematopoietic cell transplantation (HCT), 9 (24%) autologous HCT, and 1 (3%) chimeric antigen receptor T-cell (CAR T) therapy. Among the 17 patients who had COVID-19 disease after HCT, the median time to COVID-19 diagnosis was 22.8 months (range: 2.6-274.4) from HCT to COVID-19 diagnosis. Twelve out of 17 (71%) alloHCT patients were being managed for active graft-vs-host disease (GvHD) at the time of COVID-19 diagnosis (chronic GVHD: n=11 [mild: 4, moderate: 4, severe: 3], acute GVHD (grade 2): n=1). Ten (59%) alloHCT patients were on immunosuppressant therapy at the time of COVID-19 diagnosis. Fifteen (39%) patients were on active treatment for their hematologic malignancy (HM) at the time of COVID-19 diagnosis with a mean of 3 previous lines of treatment (range: 1-6). Additional patient characteristics are shown in Table 1. mAb therapy under EUA was well tolerated in this patient population with only 1 (3%) patient having experienced an adverse reaction characterized as headache. Four (11%) patients were hospitalized due to COVID-19, and 2 (5%) progressed to severe disease. All four patients had received bamlanivimab. The median time for hospitalization from diagnosis of COVID-19 to admission date was 8 days (range: 1-20) while median time from mAB infusion to hospitalization was 7.5 days (range: 0-17). One patient (3%) died within 30 days of COVID-19 diagnosis;the cause of death was COVID-19 disease. Most patients (n=34, 89%) ultimately tested negative for SARS-CoV-2 by PCR after mAb infusion. 34% of patients (n=13) cleared the virus within 2 weeks of receiving mAb infsuion. The median time to clearance of viral shedding was 25.5 days (range: 7-138). After mAb infusion, most patients (10/15;67%) who were previously on active treatment for HM prior to diagnosis of COVID-19 resumed therapy for their HM with a median delay of 21.5 days (range: 12-42). We observed a significant difference in hospitalization was amongst patients who received a HCT vs. non-HCT (0%, 0/26 and 36%, 4/11 respectively;p<0.01). None of the other patient characteristics, which included: gender, ethnicity, age, BMI, smoking, obesity, chronic kidney disease, diabetes mellitus, hypertension, coronary vascular disease, and lung disease, were associated with significantly increased rate of hospitalization. Conclusion: This study demonstrates that SARS-COV2 specific mAb use in malignant hematology patients under EUA was safe and may reduce hospitalization as reported in the literature amongst those at high risk for disease progression. Thus, the access to SARS-COV2 mAb in this population who is at increased risk for complications from SARS-COV2 infection is critical in reducing progression to severe COVID-19 disease and hospitalization. [Formula presented] Disclosures: Ali: Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;CTI BioPharma: Membership on an entity's Board of Directors or advisory committees;BMS: Speakers Bureau. Aribi: Seagen: Consultancy. Artz: Radiology Partners: Other: Spouse has equity interest in Radiology Partners, a private radiology physician practice. Koller: Novartis: Consultancy. Nikolaenko: Rafael Pharmaceuticals: Research Funding;Pfizer: Research Funding. Shouse: Beigene: Honoraria;Kite Pharma: Speakers Bureau. Stein: Amgen: Consultancy, Speakers Bureau;Celgene: Speakers Bureau;Stemline: Speakers Bureau. Marcucci: Abbvie: Other: Speaker and advisory scientific board meetings;Novartis: Other: Speaker and advisory scientific board meetings;Agios: Other: Speaker and advisory scientific board meetings. Forman: Mustang Bio: Consultancy, Current holder of individual stocks in a privately-held company;Lixte Biotechnology: Consultancy, Current holder of individual stocks in a privately-held company;Allogene: Consultancy. Dadwal: AlloVir: Research Funding;Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Astellas: Speakers Bureau;Shire/Takeda: Research Funding;Aseptiscope: Consultancy;Janssen: Other: Investigator;Karius: Other: Investigator. Al Malki: CareDx: Consultancy;Rigel Pharma: Consultancy;Jazz Pharmaceuticals, Inc.: Consultancy;Neximmune: Consultancy;Hansa Biopharma: Consultancy.

COVID-19 vaccine in hematologic patients: Preliminary safety and effectiveness results

Background: From March to May of the current year, the Department of onco-hematology of “Guglielmo da Saliceto” hospital of Piacenza vaccinated 108 haematological patients with a m-RNA vaccine, either Pfizer- BionNTech or Moderna. The aim of this study is to investigate the efficacy and safety of COVID-19 vaccine Materials and methods: This is an observational study. We analyzed the humoral immune response by antibody titer (IgG) at baseline (T0) and 4-6 weeks after the first dose of vaccine (T1). We evaluated whether age, sex, hematologic disease, previous bone marrow transplant, past COVID-19 infection and antitumor treatments interfere with the development of the humoral immune response evaluated with an anti-SARS-CoV-2 IgG ChemiLuminescent ImmunoAssay (LIAISON SARS-CoV2 S1/S2 IgGDIASORIN Inc.) measured in AU/ml. An antibody level 315 AU/ml was considered relevant. Results: From the 108 patients enrolled, 87 patients with median age of 65 years (IQR 58-71) have T1 IgG determination available of which 51 patients (58,62%) seroconverted, with IgG median value of 254 AU/ml (IQR 98,1-385 AU/ml), whereas 36 patients (41,38%) did not, with IgG median value of 3.8 AU/ml (IQR 3.8-4,5 AU/ml). Being on active anticancer treatment at the time of vaccination (p 0,03), especially on anti-CD20 monoclonal therapy (p 0.001), showed a statistically significant effect on seroconversion in univariate analysis, while age over 60 years and sex (male vs female) are near to be significant (respectively p 0.05 and p 0.06). Hematologic disease and previous bone marrow transplant (without differentiate between allo-HSCT and auto-HSCT) seem not to influence the immune response. In multivariate analysis, only anti-CD20 monoclonal therapy deeply reduces the probability of seroconversion (99,97%, p 0.003). The latter does not seem to be influenced by age, sex and active therapy (including all the remaining immunomodulant or immunosuppressor treatments). None of the patients had adverse reactions to vaccine, neither allergic nor immunological. Conclusions: More than half of the patients seroconverted. Active antitumor therapy, especially anti-CD20 monoclonal antibody, seems to have a negative effect on seroconversion. We are actually testing the cell-mediated immune response to prove the efficacy of COVID vaccination also in those immunocompromised subjects who did not seroconverted. The m-RNA vaccines seem to be safe in patients with immune deficiency.