COVID-19-related mortality among hematopoietic stem cell transplantation (HSCT) recipients in the pre-vaccine era ranged between 22 and 33%. The Pfizer/BioNTech BNT162b2 vaccine demonstrated significant immunogenicity and efficacy in the healthy population; however, its long-term effects on allogeneic HSCT recipients remained unclear. Our study longitudinally evaluated humoral and cellular responses to the BNT162b2 vaccine in adult allogeneic HSCT patients. A positive response was defined as antibody titers ≥ 150 AU/mL post-second vaccination. Among 77 included patients, 51 (66.2%) responded to vaccination. Response-associated factors were female gender, recent anti-CD20 therapy, and a longer interval between transplant and vaccination. Response rates reached 83.7% in patients vaccinated >12 months post-transplant. At 6 months post-second vaccination, antibody titers dropped, but were significantly increased with the booster dose. Moreover, 43% (6/14) of non-responders to the second vaccination acquired sufficient antibody titers after booster administration, resulting in an overall response rate of 79.5% for the entire cohort. The BNT162b2 vaccine was effective in allogeneic transplant recipients. Although antibody titers decreased with time, the third vaccination led to their significant elevation, with 93% of third-dose responders maintaining titers above 150 AU/mL at 3 months post-administration.

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Introduction: Acute undifferentiated leukemia (AUL), also referred to as ambiguous lineage leukemia, has been recognized as a unique entity by the WHO classification of myeloid neoplasms since 2008, and is considered a rare subtype. It is characterized by lacking expression of markers diagnostic of myeloid or lymphoid lineages, and encompasses the provisional entity of myeloid/natural killer (NK) leukemia, which also expresses CD56 and other immature T-cell markers. Small studies have reported that AUL is associated with a poor prognosis; however, cytogenetic and molecular characterization of this subgroup of patients is lacking, as are the long-term outcomes of induction therapy and stem cell transplantation (SCT). The goal of this study was to assess clinical and laboratory data of patients diagnosed with AUL at our institution, focusing on its unique characteristics and response to initial therapy. Methods: Parameters assessed at diagnosis included: initial blood counts, bone marrow (BM) blast cell percentage by morphology, specific phenotypic characteristics of BM blasts, molecular mutations and translocations, as well as cytogenetic abnormalities. Immunophenotyping of BM cells at diagnosis was performed using eight-color flow cytometry. Multi-parameter Cytognos acute orientation tube (ALOT) and the combination of the following antigens were used: CD34/CD117/CD14/CD56/CD36/CD123/HLA-DR/CD45/CD64/CD11c. Data were acquired with FACSCanto II flow cytometer and analyzed with Infinicyt software. Myeloperoxidase staining by fluorescence-activated cell sorting (FACS) was considered negative if <3% of blast population stained positive. Data on BM response to initial therapy, based on morphology, immunophenotyping and biopsy, as well as the 18-month outcome following the diagnosis of the first patient in this cohort were assessed. Results: One hundred and sixteen cases of acute myeloid leukemia were diagnosed at the Rambam Health Care Campus between 11/2016 and 5/2018; 16 (1.4%) of them were defined as AUL, since they did not qualify for myeloid, B- or T-cell lineage according to the WHO classification. CD56 positivity was demonstrated in 8 (50%) cases, 5 of which were also CD7 positive. Patient median age was 63 years, 56% were men. None of the patients was found positive for either NPM1 or FLT3 mutations. Likewise, no core binding leukemias were diagnosed in this cohort. Sixty six percent (10/15) of the BM samples demonstrated cytogenetic and/or FISH abnormalities, with 26% complex karyotype cases, and 20% chromosome 7 aberrancies. All but two patients were treated with AML-oriented therapies. None of the patients achieved remission with induction therapy regardless of whether it included a chemotherapy backbone (82% of patients) or a hypomethylating agent. Seven patients have undergone allogeneic SCT, 4 of whom are in remission to date. Two of the remaining transplanted patients died of progressive disease and one developed extramedullary relapse 6 months post-transplant. While 8/16 (50%) patients are alive at 18-month follow-up, only 4 of them (25%) are in remission. Notably, all of the latter patients are SCT recipients. Six out of 8 CD56-positive patients have died of progressive disease, and the remaining two have not achieved remission. Conclusions: The present study, while confirming the poor prognosis of AUL patients, also suggests that a certain subset of such individuals could benefit from an allogeneic SCT. The high percentage of complex karyotype abnormalities, the lack of NPM1 mutations, and the expression of T/NK cell immaturity markers could partly account for the established poor outcome. However, since other molecular abnormalities described in the AML mutational landscape may be involved in AUL initiation/progression, extensive molecular sequencing of this patient population is required. A better understanding of the unique characteristics of this leukemia subtype is also crucial for the design of potentially improved treatment strategies for AUL patients. Disclosures No relevant conflicts of interest to declare.

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Background:Background: In most individuals, protective humoral and cellular immunity develops after two doses of the BNT162b2 Pfizer vaccine. In patients with lymphoma, humoral response is weaker and almost universally abrogated in patients who received anti-CD20 monoclonal antibodies. Whether cellular immune response is also abrogated is unknown.