COVID-19 pandemic: how can the lessons learnt contribute to the digital transformation of schools of tomorrow?

The Coronavirus disease 2019 (COVID-19) pandemic may have had less effect on the lives of people in the Global south, but its negative impact on society is massive, especially in the area of education. To help manage the pandemic, social gatherings and other related activities, such as schools, were halted. While a few schools in the Global south have managed to continue their academic activities, the majority have struggled to migrate their teaching and learning online. This situation highlights the fact that the perceived diffusion of educational technologies was scarcely used for the intended purpose as many students and staff have struggled to cope. This study critically reviews Literature on COVID-19 pandemic from diverse information sources. These sources include research articles and other sources such as the World Health Organisation and public media platforms. The analysis of the disruption that the pandemic has caused identifies and manifests the latent use of digital technologies in the educational arena. Guidelines for rethinking the schools of tomorrow are proposed. Policymakers and educational practitioners could make use of the proposed guidelines for transformative digital initiatives of the schools of tomorrow in the Global south.

Impact of COVID-19 Pandemic on Global Unrelated Stem Cell Donations in 2020 - Report from World Marrow Donor Association

Introduction: World Marrow Donor Association (WMDA) promotes global collaboration for the benefit of stem cell donors and transplant patients. WMDA activities include recording the number of unrelated hematopoietic stem cell (HSC) donations globally. Because the COVID-19 pandemic also has an impact on the treatment of patients with other diseases, we hypothesise that it also impacted the practice of unrelated hematopoietic stem cell transplantation (HSCT). We used the 2020 WMDA data to examine the trends in unrelated HSC donations during the COVID-19 pandemic globally, per continent and per country/region. Methods: Donor registries (DRs) and cord blood banks (CBBs) from 61 countries participated in the 2020 survey, compared to 59 countries in the 2019. Slight differences in participation between the data sets of 2019 and 2020 do not explain the trends we observe in HSC donations. Country/region-specific COVID-19 data on cases and deaths were obtained from the data repository operated by the Johns Hopkins University Center for Systems Science and Engineering(https://github.com/CSSEGISandData/COVID-19, accessed July 12, 2021);and population data were retrieved from the Worldometer website(https://www.worldometers.info/, accessed July 12, 2021). Results: HSC donations from unrelated donors (peripheral blood stem cells (PBSC) and bone marrow (BM)) decreased from 20,330 in 2019 to 19,623 in 2020 (-3.5%), compared to an average annual growth rate of 3.9% from 2015 to 2019 (figure 1). The 3.5% decrease is composed of a 29.0% decrease for BM and a 2.6% increase for PBSC, resulting in a drop in the BM share of unrelated HSC donations from 19.3% in 2019 to 14.2% in 2020. The number of cord blood unit (CBU) shipments globally decreased with 3.5% from 2,851 to 2,750. The percentage of national use of HSC products (PBSC and BM) increased from 51.2% to 53.5%. When considering the continent on which the patient is transplanted (table 1), the change rate of use of HSC donated products in 2020 vs. 2019 ranged from -28.0% in South America to +18.2% in Africa. In absolute numbers, the largest decrease of HSC donations occurred for patients in Asia (n=-485) followed by Europe (n=-205), and the largest increase occurred in North America (n=+88) followed by Oceania (n=+25). The share of HSC donations requiring intercontinental transport decreased from 24.6% in 2019 to 21.9% in 2020. In terms of the country/region of transplant (table 2), the largest percentage decrease occurred in Colombia (-90,5%) followed by Russia (-55,5%). In absolute numbers, the largest decrease occurred in Turkey (-147), with Japan following (-128, although Japan saw an increase of CBU use of +106). The highest growth rate was observed in Iran (+28,7%), followed by South Africa (+28,2%). In absolute figures, the greatest increase occurred in Italy (+67). The two countries receiving the largest HSC donation numbers showed no major changes versus the previous year: USA: +0.6% (although a decrease for CBU of -21,0% was observed) and Germany: -2.4%. We did not find any significant correlation between the numbers of COVID-19 cases or COVID-19-related deaths per 1 million inhabitants with the HSC donation numbers (Spearman's r=0.05 for cases and =0.08 for deaths). Discussion: The decline in the number of unrelated HSC donations in 2020 suggests an impact of the COVID-19 pandemic on HSC donation and unrelated HSCT. The significant decrease in BM collections and intercontinental/cross-border shipments can be explained by logistically complex processes, as well the increased risk to the donor of being exposed to an operative procedure. CBU as a stem cell source potentially circumvents these logistical complications. However, on a global scale our data does not show increased use of CBU suggesting that decisions to use CBU as a stem cell source did not change in the pandemic. We were unable to demonstrate a correlation between country/region-specific severity of the pandemic and HSC donation numbers. We suspect this is due to the data quality of reported number of COVID-1 cases and COVID-19-related deaths. Also, we did not gather monthly data and therefore could not specify pandemic waves. In conclusion, we would like to point out the fact that global exchanges of HSC products continued and only decreased slightly is an extraordinary achievement of DRs, CBBs and their donors and is a testament to the importance of international collaborations in the WMDA. [Formula presented] Disclosures: Devine: Orca Bio: Consultancy, Research Funding;Johnsonand Johnson: Consultancy, Research Funding;Sanofi: Consultancy, Research Funding;Magenta Therapeutics: Current Employment, Research Funding;Tmunity: Current Employment, Research Funding;Vor Bio: Research Funding;Kiadis: Consultancy, Research Funding;Be the Match: Current Employment. Shaw: Orca bio: Consultancy;mallinkrodt: Other: payments. 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.

Cryopreservation of Allogeneic Hematopoietic Cell Grafts Did Not Adversely Affect Early Post-Transplant Survival during the First Six Months of the COVID-19 Pandemic

[Formula presented] Introduction: During the COVID-19 pandemic, concerns regarding travel logistics and donor safety necessitated a substantial increase in the use of cryopreserved hematopoietic stem cell (HSC) grafts from both related (RD) and unrelated donors (URD) to ensure patients have a graft available prior to the start of conditioning for hematopoietic cell transplantation (HCT). However, pre-pandemic data beyond single center or small multi-center reports are lacking to reassure clinicians that cryopreservation of allogeneic grafts does not adversely impact post-HCT outcomes including hematopoietic engraftment and overall survival (OS). The Center for International Blood and Marrow Transplant Research (CIBMTR) has recently published three retrospective analyses of outcomes in recipients of cryopreserved compared to fresh grafts administered prior to the pandemic. Results have been conflicting and reasons for receipt of cryopreserved grafts were not routinely collected, rendering interpretation of the impact of cryopreservation on clinical outcomes problematic. Since the pandemic provided a unifying rationale (including mandatory cryopreservation required by the National Marrow Donor Program (NMDP) and other major registries) for the majority of patients to receive cryopreserved allografts, we sought to evaluate early post-HCT clinical outcomes in patients reported to the CIBMTR database who received a first allogeneic HCT using cryopreserved grafts from March through August 2020. Methods: Key study endpoints were hematopoietic engraftment and overall survival (OS). We compared these outcomes to those in patients allografted using fresh products transplanted between March through August 2019. Additional patient selection criteria included: 1) recipients in US only, 2) peripheral blood stem cell (PBSC) or bone marrow (BM) grafts, 3) consented to research, and 4) availability of both CIBMTR product infusion and post-HCT day 100 (D100) follow-up form. The Pearson chi-square test was used for comparing discrete variables;the Kruskal-Wallis test was used for comparing continuous variables. Multivariate analysis (MVA) using a Cox proportional hazards model was performed for OS after adjusting for confounders and testing the proportional hazards assumption. Neutrophil engraftment by D28 and platelet engraftment by D100 were analyzed using multivariate logistic regression. Results: This study included 959 and 2,499 recipients of cryopreserved and fresh products, respectively. Patient characteristics are presented in Table 1. Recipients of cryopreserved grafts were older, more likely to receive URD grafts, PBSC as the graft source and post-transplant cyclophosphamide (PTCy) for graft versus host disease (GVHD) prophylaxis. They received lower infused PBSC and BM cell doses. Due to differences in duration of follow-up between the cohorts, follow up for the OS analysis was censored at Days 100 and 180. MVA results are presented in Table 2. No impact of cryopreservation on OS at either D100 (HR 0.93, p=0.72) or D180 (HR 1.10, p=0.34) post HCT was detected (see also Figure 1). When we performed the MVA for OS limiting the analysis to URD recipients only, the results were unchanged. Median time to neutrophil and platelet engraftment were both delayed by 1 day in recipients of cryopreserved grafts (16 vs. 15 days and 21 vs. 20 days, respectively) but there was no difference in the risk of primary graft failure by D28 (OR 1.38, p=0.96). Some delay in D100 platelet engraftment was observed in recipients of cryopreserved grafts (OR 0.67, p<0.005). There were no interactions identified between donor or graft type for OS or engraftment. Other important clinical outcomes such as secondary graft failure, acute GVHD, and early relapse are being analyzed and will be included at the time of presentation. Conclusion: The shift in clinical practice to cryopreserved products necessitated during the pandemic did not adversely impact early post HCT OS or risk of primary graft failure. We caution that follow up is short and it ill be critical to follow this cohort and subsequent recipients of cryopreserved grafts for much longer periods to determine the ultimate impact of cryopreservation on outcomes. Nevertheless, this large multi-center study will be useful to inform clinical decision making both during and following the pandemic. [Formula presented] Disclosures: Devine: Sanofi: Consultancy, Research Funding;Magenta Therapeutics: Current Employment, Research Funding;Tmunity: Current Employment, Research Funding;Vor Bio: Research Funding;Kiadis: Consultancy, Research Funding;Johnsonand Johnson: Consultancy, Research Funding;Orca Bio: Consultancy, Research Funding;Be the Match: Current Employment. Stefanski: Novartis: Honoraria. Shaw: mallinkrodt: Other: payments;Orca bio: Consultancy.

Neither COVID-19, Nor Cryopreservation, Prevented Allogeneic Product Infusion: A Report from the National Marrow Donor Program

The COVID-19 pandemic posed numerous logistical challenges in the way that the National Marrow Donor Program (NMDP) delivered allogeneic products to patients undergoing hematopoietic cell transplant (HCT). Prior to COVID-19, fresh bone marrow (BM) and peripheral blood stem cell (PBSC) grafts were infused into patients at the time of transplant in more than 90% of cases. Due to the pandemic, graft products could no longer be reliably delivered fresh and required cryopreservation given patient safety issues as well as logistical issues in ensuring timely delivery of a fresh product. Given these challenges, the NMDP as well as other donor registries pivoted to providing cryopreserved products. We sought to evaluate the effect of cryopreservation on the infusion of allogeneic products, analyzing all allogeneic products collected from March 17, 2020 through June 30, 2021. A total of 9294 products were collected from both related donors (RDs) and unrelated donors (URDs). Of these, a total of 8702 products were infused both domestically and internationally: 476 were RDs and 8226 were URDs. One main difference between fresh and cryopreserved products is that transplant centers (TCs) can wait to infuse the product depending on the status of the patient, patient's preference of when to receive HCT, and other factors. Moreover, TCs also can assess the product quality both at the time of product receipt and after cryopreservation thaw, thereby allowing the TC to determine if they will infuse a patient based on product quality. Due to this nuance for cryopreservation, 370 products are pending infusion. Over the last 18 months, only 222 products were not infused for a variety of reasons including patient death, patient choice, poor product quality (low cell counts, clumps in the product, viability or a positive culture) or unknown reasons. The number of products collected and infused on average per month was 544, while the number of products that were not infused each month averaged 14. Figure 1 shows the number of products infused, pending and not infused each month. We hypothesized that as TCs and apheresis centers became more adept at cryopreservation and infusing cryopreserved products, fewer products not infused would decrease. To determine if there was a difference in the number of products that were not infused in the first half of the pandemic compared to the latter half of the pandemic, we compared the first 5 months (March-July 2020) to the last 5 months (March-July 2021) using the Kruskal-Wallis test to compare the two timeframes. As shown in Figure 2, a significant downward trend (p<0.04) was noted in non-infused products by domestic TCs (p<0.02), but not international TCs, most likely reflecting low volume from the international TCs. In the study cohort, we were also able to analyze the effect of COVID-19 on product infusion. Since March 2020, a total of 34 COVID-19 positive cases were noted with 33 being PCR positive and one being antibody positive. In the PCR positive cases, 16 had a donor that tested positive for COVID-19 post-donation: 12 products were infused and 4 were not infused based on the TC's preference. Thirteen (13) had a donor with COVID-19 concerns that caused the collection to be stopped and 4 were uncharacterized. In the patients that had products infused, there were no known infections of COVID-19 or deleterious effects on engraftment. Taken together this analysis demonstrates that despite cryopreservation, a surprisingly low number of products were not infused. Moreover, patients that received products from a COVID-19 positive donor did not become infected with COVID-19 nor suffered deleterious effects. This preliminary data may help inform donors to aid them in making choices about donation as well as guide TCs and donor centers in future crises or instances when a donor's allogeneic products need to be cryopreserved [Formula presented] Disclosures: Stefanski: Novartis: Honoraria. Devine: Magenta Therapeutics: Current Employment, Research Funding;Tmunity: Current Employment, Research Funding;S nofi: Consultancy, Research Funding;Johnsonand Johnson: Consultancy, Research Funding;Orca Bio: Consultancy, Research Funding;Be the Match: Current Employment;Vor Bio: Research Funding;Kiadis: Consultancy, Research Funding.

A Phase I Study of the IDH2 Inhibitor Enasidenib As Maintenance Therapy for IDH2-Mutant Myeloid Neoplasms Following Hematopoietic Cell Transplantation

Characterization of molecular alterations in acute myeloid leukemia (AML) has led to development of targeted therapies, including FLT3 and IDH1/2 inhibitors. Maintenance therapy following hematopoietic cell transplantation (HCT) has shown substantial promise. Enasidenib (ENA), a selective IDH2 inhibitor, was associated with impressive rates of response in relapsed/refractory (R/R) AML and is now FDA-approved for this indication. We sought to assess the tolerability and define the maximum tolerated dose (MTD) of ENA as maintenance following HCT for IDH2-mutated myeloid malignancy. HCT-eligible patients (pts) ≥ 18 years with AML in remission, or myelodysplastic syndrome (MDS) with <5% marrow blasts, were enrolled. There were no restrictions on conditioning or donor type. A 2-step registration process was utilized;1 before HCT and 1 before ENA initiation. Before HCT, pts were required to have normal organ and recovered marrow function (neutrophils > 1000/µL and platelets > 50000/µL). Those with prior HCT, active disease, QTc ≥450ms, and active infections were excluded. ENA was initiated between day 30 and 90 after HCT, at which time the following were required: chimerism ≥70% of donor origin among blood/marrow cells, no acute graft versus host disease (aGVHD) requiring ≥0.5mg/kg/day prednisone or equivalent, and no relapse. ENA was taken orally (po) daily (qd) in 28-day cycles. The period for dose-limiting toxicity (DLT) evaluation was the first cycle, escalation to successive levels was guided by DLT incidence, and 2 levels (50mg,100mg) were studied. Following establishment of MTD or recommended phase 2 dose (RP2D), 10 pts would be enrolled in an expansion cohort. Pts were monitored for relapse and toxicity and continued until disease progression, intolerable toxicity, or receipt of 12 cycles. Nineteen pts have been registered prior to HCT at 3 sites, Massachusetts General Hospital, Dana Farber Cancer Institute, and Johns Hopkins Hospital. Three pts could not initiate ENA following HCT;2 due to logistic challenges of the COVID pandemic and 1 due to relapse. The remaining 16 pts initiated ENA treatment. The median age was 61 years (range 31-76);12 (75%) were male, and 13 (81%) were Caucasian. Fourteen (88%) had AML, of which 6 were AML with MDS related changes and 2 had antecedent myeloproliferative neoplasm. Two pts (13%) had MDS. Among these 16 pts, 9 (56%) had IDH2 R140, and 5 (25%) had IDH2 R172 mutations. IDH2 subtype data was unavailable for 2 pts. Of 15 pts with available data from time of diagnosis, 11 (73%) had intermediate-risk and 4 (27%) had adverse-risk cytogenetics. Among these 15 pts, common concurrent mutations were DNMT3A (47%), SRSF2 (33%), and RUNX1 (33%). Eleven AML pts (85%) received intensive versus non-intensive therapies (15%) prior to HCT, and among all pts, 7 (44%) had received ENA prior to HCT. HCT data was available for all 16 pts;4 pts (25%) received myeloablative, and 12 (75%) received reduced-intensity conditioning. Nine pts (56%) had a matched unrelated, 6 (38%) had haploidentical, and 1 (6%) had a matched related donor HCT. Three pts were enrolled at the 50mg dose level, 6 pts at 100mg, and after no DLTs were detected, the remaining were enrolled in an expansion cohort at 100mg qd. Median follow-up (F/U) for surviving patients is currently 11.7 months (range 1.5-18.9). 2 pts (13%) have relapsed during F/U, at 96 and 364 days post HCT. Additional ≥grade (G) 3 toxicities detected during treatment, possibly or probably related to ENA, included neutropenia, anemia, and bilirubinemia. Six pts (38%) required dose interruptions lasting a median 19 days (range 7-25), 4 required a dose reduction to 50mg, and 1 stopped treatment due to G3 bilirubinemia. In total, 3 pts (18%) discontinued study treatment, 1 for aforementioned G3 bilirubinemia, 1 to pursue a GVHD trial, and 1 for relapse. Six pts have completed the 12-month f/u without relapse, and 7 remain on study. 15 of 16 pts remain alive. Thus far, 3 pts have experienced ≥ G2 aGVHD, and 4 had moderate chronic GVHD. Serial me surement of 2HG is being conducted on samples, and these will be reported. Enasidenib is well-tolerated as post-HCT maintenance therapy for myeloid malignancy at the RP2D of 100mg qd. No DLTs have been detected, and a low rate of post-HCT relapse has been identified to date, although longer f/u is needed. Larger, randomized studies of ENA in the post-SCT setting would determine the true efficacy of this agent as maintenance therapy. Disclosures: Fathi: Blueprint: Consultancy;Jazz: Consultancy;Amgen: Consultancy;Newlink Genetics: Consultancy;Pfizer: Consultancy;Abbvie: Consultancy;Seattle Genetics: Consultancy, Research Funding;Agios: Consultancy, Research Funding;PTC Therapeutics: Consultancy;Takeda: Consultancy, Research Funding;Boston Biomedical: Consultancy;Amphivena: Consultancy;BMS/Celgene: Consultancy, Research Funding;Kite: Consultancy;Trovagene: Consultancy;Forty Seven: Consultancy;Novartis: Consultancy;Daiichi Sankyo: Consultancy;Astellas: Consultancy;Trillium: Consultancy;Kura Oncology: Consultancy. Soiffer: Gilead: Consultancy;Novartis: Consultancy;Juno: Membership on an entity's Board of Directors or advisory committees;Celgene: Membership on an entity's Board of Directors or advisory committees;VOR Biopharma: Consultancy;alexion: Consultancy;Rheos Therapeutics: Consultancy;Cugene: Consultancy;Precision Bioscience: Consultancy;Be the Match/ National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees;Kiadis: Membership on an entity's Board of Directors or advisory committees;Mana Therapeutics: Consultancy. Levis: Menarini: Honoraria;Amgen: Honoraria;FujiFilm: Honoraria, Research Funding;Astellas: Honoraria, Research Funding;Daiichi-Sankyo: Honoraria. Mims: Novartis: Speakers Bureau;Kura Oncology: Membership on an entity's Board of Directors or advisory committees;Leukemia and Lymphoma Society: Other: Senior Medical Director for Beat AML Study;Agios: Consultancy;Syndax Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees;Jazz Pharmaceuticals: Other: Data Safety Monitoring Board;Abbvie: Membership on an entity's Board of Directors or advisory committees. Devine: Magenta Therapeutics: Consultancy. Defilipp: Incyte: Research Funding;Regimmune: Research Funding;Syndax Pharmaceuticals: Consultancy. Spitzer: Jazz Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees;Bluebird Bio: Membership on an entity's Board of Directors or advisory committees. Frigault: Celgene: Consultancy;Arcellx: Consultancy;Novartis: Consultancy, Research Funding;Gilead/Kite: Consultancy, Research Funding. Amrein: Amgen: Research Funding;AstraZeneca: Consultancy, Research Funding;Takeda: Research Funding. Hobbs: Incyte: Research Funding;Merck: Research Funding;Bayer: Research Funding;Constellation: Honoraria, Research Funding;Jazz: Honoraria;Celgene/BMS: Honoraria;Novartis: Honoraria. Brunner: Janssen: Research Funding;Acceleron Pharma Inc.: Consultancy;GSK: Research Funding;Xcenda: Consultancy;Takeda: Consultancy, Research Funding;Novartis: Consultancy, Research Funding;Jazz Pharma: Consultancy;Forty Seven, Inc: Consultancy;Celgene/BMS: Consultancy, Research Funding;Biogen: Consultancy;Astra Zeneca: Research Funding. Narayan: Genentech: Other: Prior Spouse employment within 24 months and prior spouse equity divested within past 24 months;Takeda: Other: Prior Spouse employment within 24 months;Sanofi-Genzyme: Other: Current Spouse employment. Chen: AbbVie: Other: Data and Safety Monitoring Board Member;Incyte Corporation: Consultancy;Takeda: Consultancy;Actinium: Other: Data and Safety Monitoring Board Member;Equillium: Other: Data and Safety Monitoring Board Member;Magenta: Consultancy;Kiadis: Consultancy. OffLabel Disclosure: Enasidenib as post-transplant maintenance therapy