Timing of last COVID-19 vaccine dose and SARS-CoV-2 breakthrough infections in fully (boosted) vaccinated healthcare personnel.

AIM: To estimate the incidence, timing and severity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) breakthrough infections in fully vaccinated healthcare personnel (HCP). METHODS: In total, 6496 fully vaccinated HCP were analysed prospectively from 15th November 2021 to 17th April 2022. Full coronavirus disease 2019 (COVID-19) vaccination was defined as a complete primary vaccination series followed by a booster dose at least 6 months later. RESULTS: Overall, 1845 SARS-CoV-2 breakthrough infections occurred (28.4 episodes per 100 HCP), of which 1493 (80.9%) were COVID-19 cases and 352 (19.1%) were asymptomatic infections. Of the 1493 HCP with COVID-19, four were hospitalized for 3-6 days (hospitalization rate among HCP with COVID-19: 0.3%). No intubations or deaths occurred. SARS-CoV-2 breakthrough infections occurred at a mean of 16.2 weeks after the last vaccine dose. Multi-variable regression analyses showed that among the 1845 HCP with a breakthrough infection, the administration of a COVID-19 vaccine dose ≥16.2 weeks before the infection was associated with increased likelihood of developing COVID-19 rather than asymptomatic SARS-CoV-2 infection [odds ratio (OR) 1.58, 95% confidence interval (CI) 1.01-2.46; P=0.045] compared with administering a vaccine dose later. The likelihood of developing COVID-19 compared with asymptomatic infection increased by 7% weekly after the last COVID-19 vaccine dose (OR 1.07, 95% CI 1.03-1.11; P=0.001). CONCLUSION: SARS-CoV-2 breakthrough infections are common among fully (boosted) vaccinated HCP. However, full COVID-19 vaccination offered considerable protection against hospitalization. These findings may contribute to defining the optimal timing for booster vaccinations. More efficient COVID-19 vaccines that will also confer protection against SARS-CoV-2 infection are needed urgently.

Presence of human herpes virus-8 in saliva and non-lesional oral mucosa in HIV-infected and oncologic immunocompromised patients.

BACKGROUND/AIM: Human Herpes Virus-8 (HHV-8) is a recently identified virus etiologically associated with Kaposi's sarcoma. Studies regarding its presence in the oral cavity have given variable results. This study attempted to determine the oral presence of HHV-8 in an area where classic Kaposi's sarcoma is primarily found such as Greece. METHODS: Three groups of patients were studied: 10 immunocompromised with hematologic malignancies, 10 immunocompromised with HIV infection and 20 immunocompetent as controls. Whole unstimulated saliva and scrapes from the lingual and the buccal mucosa were collected and polymerase chain reaction was applied to amplify HHV-8 DNA. RESULTS: None of the patients in any group had oral lesions. In the control group, all samples tested negative (0/60). HHV-8 DNA was detected in 5/30 (17%) of all samples from HIV-positive patients (the mean value of their CD4+ T-lymphocytes being 385/mm3) and in 13/30 (43%) of all samples from oncologic patients (mean CD4+ T-lymphocytes 51/mm3). HHV-8 DNA was found in 10% of saliva samples and 40% of lingual and buccal scrapes both of HIV-infected and of oncologic patients. CONCLUSION: HHV-8 is present in the saliva and the non-lesional oral mucosa (not simultaneously) of patients with impaired immunity, with or without HIV co-infection. The oral epithelium seems to represent an independent location of viral residency and may be of viral replication; the clinical implications need further clarification.

Predictive factors affecting mobilization and peripheral blood stem cell (PBSC) collection using single apheresis (SA) for rescuing patients after high-dose chemotherapy (HD.CHE) in various malignancies.

We have investigated factors that affect the efficiency of single apheresis (SA) before transplant and define groups of patients that may require more than one collection for hematologic support. A consecutive series of 56 patients with hematologic malignancies and solid tumours had peripheral blood stem cells (PBSC) collected following mobilization with colony-stimulating factors (CSF) alone or after conventional chemotherapy (CHE) or high-dose cytoxan (HD.CY) followed by CSF. The efficiency of SA was assessed by total mononuclear cell number (MNC) in the harvest, CD34+ cells and colony-forming units (CFU). Linear regression analysis was performed to determine factors that affect SA yield as assessed by the above parameters. Thirty-five patients were mobilized once, 13 patients twice, six patients required three, one required four and one required five aphereses. Suboptimal mobilization and collection by SA occurred in patients with extended previous radiotherapy (RT) and patients older than 50 years. The number of CHE cycles given in the past also had an adverse effect on SA efficiency. In contrast, disease status, bone marrow infiltration by malignant cells, type of CHE, time since last CHE and mobilization regimen used were not significantly related to the collection efficiency by SA. Age, extent of previous RT and amount of CHE given prior to mobilization define the patients who require more than one SA course for support regardless of the underlying disease, BM status or mobilization regimen used. In such patients a plan for multiple aphereses should be scheduled in advance.

Peripheral blood progenitor cell (PBPC) transplantation with a single apheresis in patients with lymphoma, myeloma and solid tumors.

The aim of this study was to investigate if a single apheresis after peripheral blood progenitor cell (PBPC) mobilization can be used to rescue patients receiving high dose chemotherapy (HD.CHE) as treatment for an underlying malignancy. Eighteen consecutive patients who were admitted to the transplant unit for treatment were leukapheresed following mobilization with one of the following protocols: group I: rHuG-CSF alone, group II: conventional chemotherapy (C.CHE) + rHuG-CSF or rHuGM-CSF and group III: high dose cytoxan (HD.CTX) + rHuG-CSF. The optimal day for leukapheresis was determined by following white blood cell counts (WBC), mononuclear cell counts (MNC) and CD34+ cell counts daily. Granulocyte-macrophage colony-forming cells (GM-CFC) assay was performed at the leukapheresis product and prior to reinfusion. All patients proceeded directly to ablative therapy according to their underlying malignancy. PBPC from single apheresis were reinfused to all patients and cytokines started 24 h after infusion. Hematologic recovery after HD.CHE was the parameter used to ensure successful engraftment. We have been able to recover adequate number of PBPC for transplantation with a single apheresis in all patients. The number of infused cells were for groups I, II and III: (1) median number of MNC 4.7, 3.58 and 2.79 x 10(8)/kg, respectively (2); median number of CD34+ cells 4.4, 2.8, 2.7 x 10(6)/kg, respectively. The median apheresis day was 6, 16 and 16, respectively. Recovery times to granulocyte count > 0.5 x 10(9)/ L was 9 d (range 9-12) and to platelets > 20 x 10(9)/L was 12 d (range 1-135); 17/18 patients have engrafted successfully independent of the mobilization method used. These data suggest that sufficient PBPC can be harvested at a single leukapheresis for hemopoietic rescue after myeloablative therapy. Rapid hematologic recovery occurs when cytokines alone after conventional or HD.CHE are used for mobilization. Results of collection products and hematopoietic recovery are independent of the mobilization technique used.

Maintenance therapy with interferon-alpha (IFN-alpha) versus IFN-alpha plus chemotherapy in multiple myeloma (MM). The Greek Myeloma Study Group.

Results of studies using IFN-alpha treatment for maintaining remission and prolonging survival in multiple myeloma (MM) are in conflict and trials seeking optimum use for this biological response modifier are continuing. Between 1989 and 1993 a prospective randomized multicentre trial was undertaken to evaluate the role of the combination of IFN-alpha with chemotherapy (CT) in maintenance treatment of MM. For remission induction, in patients 65 yr or younger, we used VAD (group A) and for the remaining Melphalan and Prednisone (MP) (group B). For maintenance, patients were randomized to receive IFN-alpha 3 x 10(6) i.u. s.c. t.i.w. (group I) or alternating monthly cycles of IFN-alpha and CT. The CT cycles were also alternated (VAD, MP, CP) in an effort to prevent the development of multidrug resistance. Median survival of the two maintenance groups from randomization (36 months for group I and 31 months for group II, p = 0.3) as well as response duration (13 months in group I and 15 months in group II, p = 0.95) were similar. Toxicities were more pronounced both with VAD induction and in the combination maintenance arm. The addition of chemotherapy to the IFN maintenance regimen in MM did not have an advantage over IFN alone.

Relation between hematological recovery and number of transplanted mononuclear cells in patients after high dose chemotherapy with peripheral blood stem cell rescue.

The aim of the study is to investigate the relation between the hematological recovery in patients after high dose chemotherapy and peripheral blood stem cell (PBSC) rescue and the number of reinfused previously collected stem cells assessed by the number of mononuclear cells (MNCs), CFU-GMs and CD34(+) cells in th harvest. Forty nine patients mobilized with different techniques were transplanted. Our data indicate that the number of reinfused MNCs and CFU-GMS has a statistical significant relationship with the duration of leukopenia and thrombocytopenia following high dose chemotherapy and PBSC rescue in patients with various malignancies.

Recurrence of acute leukemia in donor cells after bone marrow transplantation: documentation by in situ DNA hybridization.

Donor cell leukemia after BMT has been documented in a small number of cases mainly by cytogenetic studies. We describe a case of leukemia relapse in a 16-year-old girl 1 year after BMT from her histocompatible brother. Relapse in donor cells was initially suspected on the basis of cytogenetic analysis and confirmed by DNA in situ hybridization in blast cells using a Y chromosome-specific probe.

Intermediate dose of intravenous melphalan in advanced multiple myeloma.

Eighteen patients with advanced multiple myeloma resistant to VAD chemotherapy (vincristine, Adriamycin, dexamethasone) were treated with intravenous melphalan in a single-pulse dose of 50-70 mg/m2. Objective response (greater than or equal to 50% reduction of the monoclonal protein) was observed in 9 patients. The median duration of remission in the responding patients was 6 months and the median survival 11.5 months. The main toxicity noted was bone marrow suppression. We conclude that intermediate doses of intravenous melphalan are a useful therapeutic modality in refractory or relapsing myeloma patients.