On December 27, 2021, two patients were admitted to our ward for high-dose chemotherapy (HDT) and ASCT. They shared a two-bed positive-pressure isolation room with high-efficiency particulate air filters and both had a negative molecular NPS the day before admission.

Patient 1 (the index case), was a 31-year-old male with relapsed Hodgkin lymphoma. He was not yet vaccinated due to former COVID-19 pneumonia, sustained by the SARS-CoV-2 VUI202012/01 GRY alpha variant (B.1.1.7), which occurred one year before (December 2020). He had recovered from pneumonia after 25 days with negative serial NPSs starting from 35 days after the first COVID-19 diagnosis. Pre-transplant salvage chemotherapy was administered without problems and the patient displayed a sequence of negative NPSs throughout treatment.

Patient 2, was a 61-year-old male with MM who had received two doses of the BNT162b2 mRNA vaccine on October 22 and November 12, 2021. He was given induction with bortezomib, thalidomide, cyclophosphamide and dexamethasone, which resulted in a stringent complete remission. He was a poor mobilizer with a total stem cell harvest of 2 × 106 CD34 + /Kg.

The case index was planned to initiate HDT on January 3, 2022, while the MM patient received HDT (melphalan 200 mg/m2; 400 mg total dose) on December 31, 2021 (day-2). Since per internal procedures we screen all inpatients for SARS-CoV-2-RNA every 3–4 days, both patients underwent a further NPS on December 30, 2021. Results, forwarded on December 31, evidenced that while the MM case (patient 2) had a negative NPS, the case index (patient 1) tested positive. Upon further questioning, the patient disclosed that, in contrast with the information provided at admission, he had unprotected contact at home with his brother. The latter was found positive at a molecular NPS performed on December 29, 2021, due to unremitting fever, headache, and pharyngodynia.

The index case (patient 1) not having yet started HDT was moved to an academic infectious diseases Unit, for sequencing of the viral isolate and anti-viral treatment. The analysis of the SARS-CoV-2 RNA isolated from his NPS showed the presence of VOC-21NOV-01 (B.1.1.529) viral variant, named Omicron variant. Therefore, the patient was treated with intravenous sotrovimab (500 mg flat dose) on day + 3 from infection and with remdesivir on days + 3–5 (200 mg on the first day and 100 mg on the second and third day). On day + 9, the index case achieved a negative NPS and was discharged.

Unfortunately, the MM case (patient 2) fulfilled all the CDC close contact criteria with the index patient (patient 1) with whom he had shared a positive air pressure room for four days and had several risk factors for severe COVID-19 [4,5,6, 8, 9]. In addition, despite two doses of BNT162b2 mRNA vaccine, the patients lacked neutralizing antibodies [4]. Based on these considerations, we decided to administer post-exposure prophylaxis with sotrovimab despite the patient having already received ASCT and was in the pre-engraftment phase. We opted for sotrovimab due to its capacity, at variance with antibody cocktails, such as casirivimab and imdevimab or etesevimab and bamlanivimab, to recognize a viral epitope not substantially altered by the mutations typically found in the Omicron spike proteins [1, 10,11,12,13].

Therefore, on January 5, 2022 (day + 2 from ASCT and day + 5 from the last close contact with the Omicron-positive index case), the patient, after signing informed consent, was given intravenous sotrovimab (500 mg). At the time of infusion, his hemogram showed an absolute neutrophil count (ANC) of 4.9 × 109/L, an absolute lymphocyte count (ALC) of 0.3 × 109/L, platelets 216 × 109/L, and hemoglobin of 12.7 g/dL. From December 29, 2021 (day-5), he was given prophylactic levofloxacin, fluconazole, and acyclovir plus sinusoidal obstruction syndrome prevention with heparin (100 IU/kg/day as a 24-h infusion). On January 7 (day + 4) the patient received subcutaneous peg-filgrastim (6 mg). Two irradiated platelet units were infused on January 11 and 12 (days + 8 and + 9) while he never necessitated RBC support. His clinical course was uneventful, without febrile episodes or hepatic and renal toxicities; mucositis and nausea/vomiting were never higher than grade 1. Daily NPSs were negative up to discharge and engraftment times were as follows: ANC > 500 and > 1000 × 109/L (10 and 11 days, respectively), platelets > 20.000 and > 50.000 × 109/L (11 and 13 days, respectively), and ALC > 1000 × 109/L (12 days). Repeated post-discharge bi-weekly NPSs were constantly negative and symptoms possibly related to SARS-CoV-2 infection never manifested up to the last follow up (day + 30) post-transplant.

The case timeline as compared to the last 15 MM patients who received ASCT with the same conditioning at our Center is illustrated in Fig. 1. Clinical and transplant-related features of these patients were fully comparable with those of the sotrovimab-treated patient, including the total dose of melphalan receveid during high-dose conditioning and the total dose of CD34+ cells reinfused (Table 1). As shown in Fig. 1, no significant differences in engraftment kinetics emerged as a consequence of sotrovimab administration. Nadir peaks for ANC, platelets, and ALC were fully comparable (Fig. 1), as well as, the median times to engraftment for ANC > 500 and > 1000 × 109/L (10 ± 1 days for both outcomes), platelets > 20.000 and > 50.000 × 109/L (12 ± 1 and 13 ± 2 days, respectively) and ALC > 1000 × 109/L (18 ± 4 days). Similarly, the incidence and grading of transplant-related toxicities and the required hemocomponents support were superimposable (Table 1).

Visual clinical timeline including treatments and engraftment kinetics of a MM patient (patient 2) treated with sotrovimab during the pre-engraftment phase of autologous stem cell transplant (ASCT) in comparison with data from the last 15 MM patients who underwent the same procedure at our institution in the preceding four months. Blue lines represent median values (± SD) for absolute neutrophil count (ANC), absolute lymphocyte count (ALC) and platelets counts obtained from the last 15 MM patients who received high-dose melphalan (200 mg/m2) and autologous stem cell transplant (ASCT) before patient 2 at our Center. The red lines indicate ANC, ALC and platelet counts for a MM patient (Patient 2) given high-dose melphalan (200 mg/m2) and single-agent sotrovimab (500 mg flat dose), two days after ASCT