Relationship between ABO Blood Group Distribution and COVID-19 Infection in Patients Admitted to the ICU: A Multicenter Observational Spanish Study.

Since the beginning of the COVID-19 pandemic in December 2019, a relationship between the ABO blood group type and the novel coronavirus SARS-CoV-2, the etiological agent of COVID-19, has been reported, noting that individuals with the O blood group are the least likely to be infected. Spain is one of the most badly affected countries worldwide, with high rates of patients diagnosed, hospitalized, and deceased due to COVID-19 infection. The present study aimed to analyze the possible relationship of ABO in COVID-19 patients hospitalized in different Spanish centers during the first wave of the COVID-19 pandemic, for which the ABO group was available. Physicians from the transfusion services of different Spanish hospitals, who have developed a multicenter retrospective observational study, were invited to participate voluntarily in the research and 12,115 patients with COVID-19 infection were admitted to the nine participating hospitals. The blood group was known in 1399 cases (11.5%), of which 365 (26.1%) were admitted to the ICU. Regarding the distribution of ABO blood groups, a significant increase in the non-O blood groups and reduction for the O blood group was observed in patients hospitalized due to COVID-19, compared to the reference general population. Among the patients admitted to the ICU, after multivariate analysis, adjusted for the rest of the confounding variables, patients with the O blood group presented a significantly lower risk for admission to the ICU. We conclude that an association was observed between patients with the O blood group and their lower susceptibility to SARS-CoV-2 infection, both for those admitted to the hospitalization ward and for those who required admission to the ICU.

Feasibility and efficacy of outpatient therapy with intermediate dose cytarabine, fludarabine and idarubicin for patients with acute myeloid leukaemia aged 70 or older.

OBJECTIVES: A multicentre prospective non-randomised study of de novo acute myeloid leukaemia (AML) in patients aged ≥70 yr was designed to reduce toxicity and achieve acceptable complete remission (CR) rates. METHODS: The outpatient treatment included induction with oral fludarabine, subcutaneous cytarabine and subcutaneous filgrastim (FAG). The patients received more induction cycles according to the response achieved. If there was no response to induction with FAG, the following induction cycle included oral idarubicin, subcutaneous cytarabine and subcutaneous filgrastim (IAG). Patients achieving CR received one intensification (FAG on response to previous FAG or alternatively IAG) and one consolidation cycle (IAG). RESULTS: Thirty patients were enrolled from April 2004 to June 2007. The median age was 73 yr (range 70-77). Fifteen patients (50%) achieved CR. The 2-yr DFS was 29% (95% CI, 5-47%), and the 2-yr OS was 23% (95% CI, 12-35%). Twenty-five of 69 cycles (36%) were managed on a completely outpatient basis. The median hospital stay per cycle was 10 d (95% CI, 3-25). CONCLUSIONS: This study demonstrates the tolerability and efficacy of a semi-intensive treatment in elderly de novo patients with AML managed on an outpatient basis, without substantial toxicity.

Predicting survival in adults with invasive aspergillosis during therapy for hematological malignancies or after hematopoietic stem cell transplantation: Single-center analysis and validation of the Seattle, French, and Strasbourg prognostic indexes.

In this retrospective monocenter study, we analyzed the outcomes of 130 adult hematological patients who developed a proven (n = 23), probable (n = 71), and possible (n = 36) invasive aspergillosis (IA) in a 13-year period. Forty-nine patients (38%) were recipients of an allogeneic hematopoietic stem cell transplantation (AlloHSCT). The main goal of the study was the identification of prognostic factors for 4-month aspergillosis free survival (AFS) and overall survival (OS). IA was identified as the main cause of death in 27/49 recipients of an AlloHSCT (55%) and 28/81 nontransplanted patients (35%). Diagnosis of IA at or before 2000 had a negative impact in both 4-month AFS and 4-month OS in the entire group. In multivariate analysis performed separately for nontransplanted and allo-HSCT patients, five variables (excluding the year of diagnosis) decreased 4-month AFS: (i) impairment of one organ function (OF), (ii) impairment of two or more OFs (two points), (iii) disseminated IA, (iv) neutropenia lasting more than 10 days (non-AlloHSCT group only) or monocytopenia (<0.1 x 10(9)/l) [AlloHSCT group only], and (v) high-dose steroids (non-AlloHSCT group only) or an alternative donor (AlloHSCT group only). According to the number of adverse risk factors, three prognostic subgroups were defined in non-transplanted and alloHSCT patients with good (97% and 78% AFS), intermediate (73% and 32% AFS) and poor prognosis (20% and 11% AFS) of IA [P < 0.01]. In addition, we validated the French and Seattle prognostic indexes for allo-HSCT recipients and the Strasbourg model for all hematological patients with IA.

Efficacy and toxicity of intermediate-dose amphotericin B lipid complex as a primary or salvage treatment of fungal infections in patients with hematological malignancies.

We treated 74 adults with a hematological malignancy and documented or suspected invasive fungal infection (IFI) with amphotericin B lipid complex (ABLC) at 3 mg/kg/day. Forty-five patients (61%) received upfront therapy and 29 patients (39%) received salvage therapy for their IFI. Forty-eight of 71 evaluable patients responded [complete responses in 40 (56%) and partial responses in 8 (11%)] and 15 (21%) died as a consequence of the IFI. Response rates in invasive aspergillosis were 33 out of 49 (67%) for probable/definite cases and 6 out of 11 (55%) for invasive candidiasis. In 40 patients with neutropenia-associated IFI, rapid neutropenic recovery ( < 10 days from study entry) was essential for response to therapy (90% vs. 32%, P < 0.01). Treatment was well tolerated, with 15% infusions followed by infusion-related adverse events, nephrotoxicity in 7% of patients and 11% of withdrawals due to toxicity. These data suggest that intermediate-doses of ABLC may be of similar efficacy than higher doses with less toxicity, making it a cost-effective alternative worthy of study in future trials.

Low-dose amphotericin B lipid complex vs. conventional amphotericin B for empirical antifungal therapy of neutropenic fever in patients with hematologic malignancies--a randomized, controlled trial.

BACKGROUND: Conventional amphotericin B (c-AmB) remains the empirical antifungal treatment of choice for neutropenic patients with persistent fever of unknown origin (FUO). Unfortunately, empirical treatment with c-AmB is hampered by its safety profile, with frequent infusion-related adverse events (IRAEs) and renal toxicity. Amphotericin B lipid complex (ABLC) has been investigated for this indication due to its low toxicity profile. The recommended dose of ABLC is 5 mg/kg/d, which is five to seven times higher than the recommended dose of c-AmB. METHODS: This randomized, controlled trial includes 105 adult patients with hematologic malignancies and with FUO after receiving chemotherapy or autologous stem cell transplantation. Patients were randomly allocated to receive ABLC at 1 mg/kg/d or c-AmB at 0.6 mg/kg/d for empirical antifungal therapy. RESULTS: The incidence of renal toxicity was significantly lower in the ABLC group, compared with c-AmB group: 8% vs. 32%, respectively (P = 0.003). The rates of IRAEs were similar in both groups (73% for ABLC vs. 77% for c-AmB). The overall response rate was 72% for ABLC compared with 48% for c-AmB (P = 0.018). This difference was mainly due to the significantly higher renal toxicity in the c-AmB group. The number of emergent fungal infections and overall mortality were similar in both groups. CONCLUSIONS: This randomized trial suggests that ABLC at 1 mg/kg/d produces less nephrotoxicity than c-AmB, without differences in the incidence of IRAEs and with similar efficacy.

Strategies to reduce transplant-related mortality after allogeneic stem cell transplantation in elderly patients: Comparison of reduced-intensity conditioning and unmanipulated peripheral blood stem cells vs a myeloablative regimen and CD34+ cell selection.

OBJECTIVES: The aim of this study was to compare two approaches used to reduce transplant-related mortality (TRM) after allogeneic peripheral blood stem cell transplantation (allo-PBSCT) in elderly patients. PATIENTS AND METHODS: Data from 50 patients, 45 years of age or older, consecutively treated with an HLA-identical sibling allo-PBSCT at the Hospital de Sant Pau were analyzed. We have compared the outcome of patients treated with conventional myeloablative regimens and CD34(+)-selected cells (CD34(+) group; n=23) with those receiving reduced-intensity conditioning regimens, consisting of fludarabine (150 mg/m(2)) plus an alkylating agent, followed by unmanipulated grafts (RIC group; n=27). Patient characteristics were well balanced between the two groups, although patients in the RIC group were slightly older. RESULTS: The incidence of acute graft-vs-host disease (GVHD) was similar in both groups. The 1-year cumulative incidence of extensive chronic GVHD was 38% in the RIC group and 17% in the CD34(+) group (p=0.2). After a median follow-up of 28 months, there were no differences in the relapse rate. Patients in the RIC group had a lower TRM, with a cumulative incidence of 7% vs 30% at 6 months and 15% vs 39% at 1 year (p=0.05). The Kaplan-Meier estimates of PFS at 2 years was 67% in the RIC group and 43% in the CD34(+) group (p=0.09) and the OS was 69% vs 43% (p=0.05), respectively. CONCLUSION: CD34(+) cell selection reduced the risk of extensive cGVHD but was associated with a higher TRM. Although the number of patients is limited, our study suggests that this approach should be restricted to relatively young patients, as better outcomes can be achieved in elderly patients using RIC strategies.

Invasive pulmonary aspergillosis in patients with hematologic malignancies: survival and prognostic factors.

BACKGROUND AND OBJECTIVES: Despite improvements made in its early diagnosis and effective treatment, invasive pulmonary aspergillosis (IPA) remains a devastating opportunistic infection. In this retrospective study we have reviewed all consecutive cases of IPA diagnosed in adult patients with hematologic malignancies in our center from 1995 to 2000 to determine survival and prognostic factors. DESIGN AND METHODS: Forty-one patients were included in the study. Ante-mortem classification of cases of IPA were: 4 definite, 10 highly probable, 19 probable and 8 possible cases; all these last eight patients were later upgraded to definite IPA at post-mortem examination. Clinical charts were reviewed and factors possibly affecting the outcome of IPA were analyzed. RESULTS: All but two patients received chemotherapy and/or immunosuppresive therapy before the onset of IPA (conventional chemotherapy = 24, allogeneic stem cell transplantation [SCT] = 12, autologous SCT = 3). At IPA diagnosis 28 patients were neutropenic (< 0.5 x 10(9)/L) for a median of 25 days (range 7-135), and 10 allogeneic SCT patients were receiving corticosteroids for graft-versus-host-disease. All but two patients received antifungal treatment for IPA. The median delay from diagnosis to start of therapy was two days (range 0-20). The median follow-up after the first symptom or sign of IPA was 42 days with a maximum follow-up of 61 months. The actuarial 4-month infection-free survival was 40% (95% CI 25% to 55%). Thirty-three patients died during follow-up and IPA was implicated in the patients' death in 24 cases (75%). In multivariate analysis prolonged survival was associated with recovery of neutropenia during treatment (p = 0.001) and not having received an allogeneic SCT (p = 0.003). INTERPRETATION AND CONCLUSIONS: Despite prompt initiation of antifungal therapy, survival of patients with a hematologic malignancy and IPA is currently low. Perhaps the introduction of more sensitive diagnostic methods will allow the onset of intensive therapy prior to the appearance of more advanced clinical symptoms and/or radiological signs, and the time will come to test whether earlier and more intensive therapy will improve survival.

Invasive fungal infections after allogeneic peripheral blood stem cell transplantation: incidence and risk factors in 395 patients.

We have analysed the incidence and risk factors for the occurrence of invasive fungal infections (IFI) among 395 recipients of an allogeneic peripheral blood stem cell transplantation (PBSCT) from a human leucocyte antigen (HLA)-identical sibling. IFI (n = 50) occurred in 46 patients, giving an overall probability of 14%. There were 12 cases of invasive candidiasis (3%), with only one death. Non-Candida IFI occurred in 37 patients (12% probability), mostly invasive aspergillosis (n = 32). In multivariate analysis the only two significant variables associated with a higher risk of developing a non-Candida IFI were the development of moderate-to-severe graft-versus-host disease (GvHD, P < 0.0001; OR 4.6) and having received steroid prophylaxis for GvHD (P = 0.04; OR 2.1). In multivariate analysis the variables associated with a lower overall survival after PBSCT were development of a non-Candida IFI (P < 0.0001; OR 5.6), non-early disease phase (P = 0.0001; OR 1.9), steroid prophylaxis (P = 0.02; OR 1.4), moderate-to-severe GvHD (P = 0.01; OR 1.6) and cytomegalovirus infection post transplant (P = 0.001; OR 1.8). Our results show that non-Candida IFI (in particular aspergillosis) was an important cause of infectious morbidity and mortality after an HLA-identical sibling PBSCT, while invasive candidiasis was rare. Use of steroid prophylaxis and, in particular, the development of moderate-to-severe GvHD post transplant were risk factors for non-Candida IFI. Prophylactic strategies for these infections should thus take into account these risk factors.