BACKGROUND: Blinatumomab has demonstrated encouraging activity in relapsed/refractory (r/r) and minimal residual disease-positive (MRD+) acute lymphoblastic leukemia (ALL). Extramedullary disease (EMD) relapse or relapse with CD19-disease has been observed after blinatumomab therapy in patients with r/r or MRD+ ALL. However, the pathophysiology and risk factors of treatment failure are not fully understood. METHODS: This study retrospectively reviewed the outcomes of adult patients with B-cell ALL treated with blinatumomab (n = 132) for either r/r (n = 103) or MRD+ disease (n = 29) at the authors' center (2013-2021) and analyzed factors associated with treatment response and EMD failure. RESULTS: The overall response rate was 64%. A lower marrow blast burden before blinatumomab (P = .049) and no history of previous EMD (P = .019) were significantly associated with a higher response. Among the patients who responded to blinatumomab, 56% underwent consolidation with allogeneic transplantation. Blinatumomab failure was observed in 89 patients; 43% of these patients (n = 38) either progressed or relapsed at extramedullary sites. A history of extramedullary involvement (53% vs 24%; P = .005) and retention of CD19 expression at the time of relapse/progression (97% vs 74%; P = .012) were associated with a higher risk for extramedullary failure. Central nervous system (CNS) failure after blinatumomab was encountered in 39% of the patients with EMD. CONCLUSIONS: A history of EMD predicted an inferior response to blinatumomab therapy with a higher risk for relapse/ progression at extramedullary sites (particularly CNS). Consolidation with allogenic transplantation in patients who primarily responded to blinatumomab did not abrogate the risk of extramedullary relapse. The incorporation of extramedullary assessment and the intensification of CNS prophylaxis may help in addressing extramedullary failure.

Donor-specific anti-HLA antibodies (DSA) are a major cause of engraftment failure in patients receiving haploidentical stem cell transplantation (HaploSCT). Effective treatments are needed for these patients who often have no other donor options and/or are in need to proceed urgently to transplantation. We studied a multimodality treatment with alternate day plasma exchange, rituximab, intravenous gamma globulin (IvIg) and an irradiated donor buffy coat for patients with DSA at two institutions. Thirty-seven patients with a median age of 51 years were treated with this desensitization protocol. Treatment outcomes were compared with a control group of HaploSCT patients without DSA (N=345). Majority of patients in the DSA group were females (83.8% vs. 37.1% in controls, p<0.001) and received stem cells from a child as donor (67.6% vs. 44.1%, p=0.002). Mean DSA level before and after desensitization was 10,198 and 5,937 MFI, respectively with mean differences of 4,030 MFI. Fourteen of 30 tested patients (46.7%) had C1q positivity while 8 of 29 tested patients (27.6%) remained positive after desensitization. In multivariable analysis, patients with initial DSA >20,000 MFI and with persistent C1q+ after desensitization had a significantly lower engraftment rate, resulted in a significantly higher non-relapse mortality (NRM) and worse overall survival (OS) than controls whereas graft outcome and survivals of patients with initial DSA <20,000 MFI and those with negative C1q after treatment were comparable with controls. In conclusion, treatment with plasma exchange, rituximab, IvIg and donor buffy coat is effective in promoting engraftment in patients with DSA up to 20,000 MFI.

No abstract

No abstract

Immunocompromised recipients of allogeneic hematopoietic stem cell transplant (HCT) are at increased risk of severe COVID-19. 1 During the first year of a successful HCT, circulating T-cells arise from donor CD34 + cells and can react to antigens exposed to the donor through natural infection or vaccination before transplantation. Therefore, donor pathogen exposure or vaccination pre-graft can be beneficial to the recipient when mounting cellular and humoral response to augment immune reconstitution and control post-HCT natural infection or increase vaccination responses. 2 Here, we present evidence of transfer and expansion of SARS-CoV-2-specific adaptive immunity from three matched unrelated donors (MUDs), vaccinated with licensed COVID-19 vaccines to unvaccinated and vaccinated recipients. The 10/10 matched (with permissive HLA-DPB1 locus mismatch) MUDs and their recipients did not have COVID-19 history nor developed active infection through study completion (d + 180). All three recipients engrafted and achieved full donor chimerism (>95%) 3 by d + 30.The patient from MUD/R1 pair (Table 1S) was a 29-year-old Hispanic male, with body mass index of 40.07 kg/m 2 , hypertension, diabetes, diagnosed with Philadelphia like B-cell acute lymphoblastic leukemia, with cytokine receptor-like factor 2 rearrangement. The mRNA-1273 vaccinated MUD donor was a 33-year-old male. The recipient underwent a myeloablative HCT soon after CD-19 CAR T-cell therapy, while in second complete remission (CR2) with negative measurable residual disease (MRD), using fractionated total body irradiation with etoposide. He received GVHD prophylaxis of tacrolimus and sirolimus (tacro/siro). He developed grade 1 skin GVHD around d + 24, which resolved with topical therapy. He did not receive a COVID-19 vaccine because prior to HCT, the patient was unstable and not ambulatory.Patient from MUD/R2 pair was a 74-year-old Caucasian male with history of hypertension, diagnosed with acute myeloid leukemia with deletion Y and SRSF2 mutation, who was in CR1 with negative MRD after receiving hypomethylating agent and venetoclax. The BNT162b2 mRNA vaccinated MUD donor was a 30-year-old female.The recipient underwent reduced intensity HCT using fludarabine and melphalan conditioning (FM), with tacro/siro GVHD prophylaxis in combination with itacitinib JAK-1 inhibitor (NCT04339101). He devel-