B cell haematological malignancies (HMs) have been described as the worst cancer type for concomitant COVID‐19 in terms of mortality, with rates up to 65%. This risk factor for COVID‐19 cannot only ...be explained by comorbidities and advanced age of patients, but aggravated by secondary immunodeficiency (SID). We aimed at evaluating the impact of COVID‐19 on 86 HM patients with concomitant SID from a single centre. Only 14 HM patients of 86 (16.28%) patients suffered COVID‐19, with mortality rate of 7%. When we considered patients according to B‐cell defect only or multiple immune defect overlap (B‐T‐cell/NK cells/complement), patients with immune defect overlap presented 5.30‐fold higher risk of COVID‐19 than only B cell defect (95% CI, 1.67–17.0) (p = 0.004). Seven (50%) patients were on active IgRT; while five (36%) had received prior mucosal vaccines for respiratory infections. Our results show that modelling SID in HM may contribute to better prediction of infectious risk and to prompt more targeted and timely preventive therapies.
This is the first report of the health economic benefits derived from preventing infections through Immunoglobulin Replacement Therapy (IgRT) in patients with secondary immunodeficiency due to ...hematological malignancies. We conducted a retrospective population-based cohort study using patient medical history and pharmacy data from the Hospital Clínico San Carlos for 21 patients between 2011 and 2020. The pharmacoeconomic impact of using prophylactic IgRT was assessed by comparing characteristics of the SID patients 1 year before and after initiating IgRT measured by direct medical and tangible indirect costs. Results indicate a marked reduction in hospitalization days following IgRT initiation, decreasing from an average of 13.9 to 6.1 days per patient, with the elimination of ICU admissions. While emergency department visits decreased significantly, the number of routine consultations remained unchanged. Notably, absenteeism from work dropped substantially. The financial analysis revealed significant reductions in medication use and fewer ancillary tests, resulting in considerable cost savings. Specifically, total expenditure dropped from €405,088.18 pre-IgRT to €295,804.42 post-IgRT—including the cost of IgRT itself at €156,309.60. Overall, the annual savings amounted to €109,283.84, validating the cost-effectiveness of IgRT in managing SID in patients with hematological cancers.
Infectious complications are a major cause of morbidity and mortality in B-cell hematological malignancies (HM). Prophylaxis for recurrent infections in HM patients with antibody deficiency consists ...of first-line antibiotics and when unsuccessful, gammaglobulin replacement therapy (IgRT). Recent knowledge of trained immunity-based vaccines (TIbV), such as the sublingual polybacterial formulation MV130, has shown a promising strategy in the management of patients with recurrent infections. We sought to determine the clinical benefit of MV130 in a cohort of HM patients with recurrent respiratory tract infections (RRTIs) who underwent immunization with MV130 for 3 months. Clinical information included the frequency of infections, antibiotic use, number of visits to the GP and hospitalizations previous and after MV130 immunotherapy. Improvement on infection rate was classified as: clear (>60% reduction of infection), partial (26%-60%) and low (≤25%) improvement. Fifteen HM patients (aged 42 to 80 years; nine females) were included in the study. All patients reduced their infection rate. Analysis of paired data revealed that the median (range, min - max) of respiratory infectious rate significantly decreased from 4.0 (8.0-3.0) to 2.0 (4.0-0.0) (
<0.001) at 12 months of MV130. A clear clinical improvement was observed in 53% (n = 8) of patients, partial improvement in 40% (n = 6) and low improvement in 7% (n = 1). These data correlated with a decrease on antibiotic consumption from 3.0 (8.0-1.0) to 1.0 (2.0-0.0) (
= 0.002) during 12 months after initiation of treatment with MV130. The number of infectious-related GP or emergency room visits declined from 4.0 (8.0-2.0) to 2.0 (3.0-0.0) (
<0.001), in parallel with a reduction in hospital admissions due to infections (
= 0.032). Regarding safety, no adverse events were observed. On the other hand, immunological assessment of serum IgA and IgG levels demonstrated an increase in specific antibodies to MV130-contained bacteria following MV130 immunotherapy. In conclusion, MV130 may add clinical benefit reducing the rate of infections and enhancing humoral immune responses in these vulnerable patients.
Hemato-oncologic patients with chemotherapy-induced thrombocytopenia are one of the populations receiving platelet transfusions. The general practice with these patients is to give prophylactic ...platelet transfusions when platelet counts fall below 10×109PLT/L. However, in more than 40% of these patients, platelet transfusion does not prevent bleeding. The reason of the low efficacy of platelet transfusion in the context of chemotherapy patients is not entirely understood.
We therefore aimed at immunophenotyping the expression of platelet surface and activation markers and thrombopoietin levels from hemato-oncologic patients before and after transfusion. A more detailed follow-up was performed in three patients that underwent autologous bone marrow transplantation.
As previously reported, basal platelet activation was observed in hemato-oncologic patients. Based on flow cytometry parameters, i.e. the percentage of positivity and mean fluorescence intensity (MFI) distribution, our data provide an additional interpretation of platelet acquired qualitative changes in the hemato-oncologic patient. From our results we propose: first, the underlying activation of platelets in the hemato-oncologic patient is accompanied by loss of expression of the platelet receptors that are susceptible to protease-mediated shedding; second, soon after transfusion, the newly circulating donor platelets show additional activation, which may result in subsequent platelet receptor recycling and potential accelerated clearance of these activated platelets.
In conclusion, the immunophenotype of circulating platelets changes after prophylactic platelet transfusion. Next to platelet count increment, exploration of this immunophenotype might help to explain transfusion refractory bleeding in hemato-oncologic patients. Eventually this may lead to personalization and improvement of the present platelet transfusion support regime.
B cell chronic lymphoproliferative diseases (B-CLPD) are associated with secondary antibody deficiency and other innate and adaptive immune defects, whose impact on infectious risk has not been ...systematically addressed. We performed an immunological analysis of a cohort of 83 B-CLPD patients with recurrent and/or severe infections to ascertain the clinical relevance of the immune deficiency expression. B-cell defects were present in all patients. Patients with combined immune defect had a 3.69-fold higher risk for severe infection (p = 0.001) than those with predominantly antibody defect. Interestingly, by Kaplan–Meier analysis, combined immune defect showed an earlier progression of cancer with a hazard ratio of 3.21, than predominantly antibody defect (p = 0.005). When B-CLPD were classified in low-degree, high-degree, and plasma cell dyscrasias, risk of severe disease and cancer progression significantly diverged in combined immune defect, compared with predominantly antibody defect (p = 0.001). Remarkably, an underlying primary immunodeficiency (PID) was suspected in 12 patients (14%), due to prior history of infections, autoimmune and granulomatous conditions, atypical or variegated course and compatible biological data. This first proposed SID classification might have relevant clinical implications, in terms of predicting severe infections and cancer progression, and might be applied to different B-CLPD entities.
Acute promyelocytic leukemia (APL) has become a highly curable malignant disease after the introduction of all transretinoic acid (ATRA) to chemotherapy treatment. However, the risk to develop ...therapy-related myeloid neoplasms (t-MN) has become a matter of concern, as APL patients are otherwise expected to have a good prognosis. We report a patient with APL who achieved complete remission after chemotherapy induction with anthracycline and ATRA, followed by consolidation and maintenance chemotherapy. Two years later, the patient developed t-AML, with MLL rearrangements, without any evidence of relapse of the APL original clone. The increasing incidence of t-MN in oncohematological patients is partly due to the development of safer, more efficient or targeted therapies, which allow better outcomes and lengthened survival amongst treated patients. The identification of genetic factors, mechanisms or prognostic biomarkers in t-MN might open new windows for the development of personalized targeted therapy regimes in this underserved patient population.
An increasing healthcare challenge in the management of hematological malignancy (HM) is secondary immunodeficiency (SID), either caused by the underlying malignancy or by treatments, including ...B-cell-targeting therapies. From January 2019, the EMA (European Medicines Agency) included the evaluation of specific antibody (Ab) responses to better select patients for immunoglobulin replacement therapy (IgRT). Antibody response to polysaccharide immunizations is primordial in the immunological evaluation of the patients and it is thought to be the first Ab response to be lost in the rising of an immunodeficiency. Clinically, an impaired polysaccharide response means that the patient may not be protected to new encounters with encapsulated bacteria, having therefore higher risk of severe or recurrent infections. We evaluated Ab responses to pneumococcal (PPV) and Salmonella typhi (TV) pure polysaccharide immunization in a cohort of 42 HM patients and 24 healthy controls. Pre-post specific Ab serum concentrations were measured by ELISA (Binding Site, UK), before immunizations and at 4 weeks. Globally, the prevalence of TV titers pre-immunization was lower (9%) compared to PPV pre-immunization titers (76%) (p<0.001). There were more HM patients' non-responders for TV (88%, unable to mount a >3-fold increase in TV titers) than PPV non-responders (62%) (p<0.0001), and no-response to TV correlated better to infectious history. By ROC analysis, pre-post 5-fold TV increase was the best cut-off to discriminate HM with recurrent infections and controls (sensitivity 91%, specificity 100%). TV Ab responses were superior to PPV to identify SID and defective primary responses, notably in patients with high PPV baseline titers in the conjugate vaccine era, therefore overcoming the limitations in identifying patients with impaired polysaccharide responses after pneumococcal conjugate vaccine immunizations. Our results suggest that specific Ab response to S typhi polysaccharide is a useful complementary assay in the diagnosis and management decision of SID to HM, that may help to predict patients more prone to infections and guide a more risk-adapted infection-prophylaxis.
No relevant conflicts of interest to declare.
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