Cidofovir for BK Virus-Associated Hemorrhagic Cystitis: A Retrospective Study

Background.BK virus-associated hemorrhagic cystitis (BKV-HC) is a severe complication after allogeneic hematopoietic stem cell transplantation (HSCT), but antiviral treatment for this condition has not been evaluated. Methods.We conducted a retrospective survey on the safety and outcome of cidofovir treatment for patients with BKV-HC in centers affiliated with the European Group for Blood and Marrow Transplantation. Results.From 1 April 2004 to 31 December 2007, 62 patients received a diagnosis of BKV-HC after a median interval of 35 days after HSCT (range, 3-577 days). Fifty-seven patients (92%) received intravenous cidofovir, whereas 5 patients received cidofovir intravesically. Complete response (CR) was recorded in 38 (67%) of 57 patients with HC treated with intravenous cidofovir, whereas partial response (PR) was documented in 7 patients (12%). CR was documented in 3 patients and PR in 1 patient with HC treated with intravesical cidofovir. A reduction of 1-3 logs in BKV load was documented in 8 of the 10 patients achieving CR. Mild-to-moderate toxic effects were recorded in 18 of 57 patients who received intravenous cidofovir administration. In a multivariate analysis, the factors significantly associated with response to cidofovir were the stem cell source (P=.01) and the use of total body irradiation (P=.03). After a median follow-up of 287 days, overall survival and total treatment-related mortality rates were 63% and 40% for patients achieving CR, compared with 14% and 72% for patients with PR or no response to cidofovir, respectively (P<.001 and P=.001, respectively). Conclusions.Cidofovir may be a potentially effective therapy for BKV-HC, but evidence supporting its use requires randomized controlled trial

Could Immunophenotype Guide Molecular Analysis in Patients with Myeloid Malignancies?

Objective: Immunophenotype has been correlated with molecular aberrations in several studies. The aim of this study was the discovery of immunophenotypic features related to mutations in AML and MDS patients connected to prognostic factors. Moreover, an effort to evaluate a method for the detection of the most common NPM1 mutations of exon12 and Internal Tandem Duplications (ITD) mutations of FLT3 gene by flow cytometry was performed. Method: Patients with de novo myeloid neoplasms [ AML and MDS (AML-M3 patients were excluded)] were included. FLT3/ITD/TKD and NPM1 mutations were detected by PCR and fragment analysis. The immunophenotypic analysis was performed by multi-dimensional flow cytometry (FC) with a standardized panel of monoclonal antibodies on peripheral blood or bone marrow samples. Nucleophosmin Antibody and CD135 were used for the mutations immunophenotypic detection. Results: NPM1 and/or FLT3 mutations correlated with low or no expression of more immature cells markers such as CD34, CD117, HLADR, as well as higher expression of more mature markers such as CD11b. The higher expression of CD33 should be mentioned as well. The presence of NPM1mut and FLT3/ITD does not seem to be detectable by FC at least using these two monoclonal antibodies. The presence of CD7 aberrant lymphoid marker’s expression was associated with FLT3mut, NPM1wt genotype. CD56 or CD2 positivity was found only in patients’ samples negative for NPM1 and/or FLT3 mutations. Conclusions: Certain immunophenotype findings including the presence of aberrant lymphoid markers may be indicative of the presence of mutations in NPM1 and FLT3 linked to prognosis

Poor Neutralizing Antibody Responses in 132 Patients with CLL, NHL and HL after Vaccination against SARS-CoV-2: A Prospective Study

Emerging data suggest suboptimal antibody responses to COVID-19 vaccination in patients with hematological malignancies. We evaluated the humoral response following the BNT162b2 vaccine in patients with chronic lymphocytic leukemia (CLL), non-Hodgkin’s lymphoma (NHL), and Hodgkin’s lymphoma (HL). An FDA-approved, ELISA-based methodology was implemented to evaluate the titers of neutralizing antibodies (NAbs) against SARS-CoV-2 on day 1 of the first vaccine, and afterwards on day 22 and 50. One hundred and thirty-two patients with CLL/lymphomas and 214 healthy matched controls vaccinated during the same period, at the same center were enrolled in the study (NCT04743388). Vaccination with two doses of the BNT162b2 vaccine led to lower production of NAbs against SARS-CoV-2 in patients with CLL/lymphomas compared with controls both on day 22 and on day 50 (p &lt; 0.001 for all comparisons). Disease-related immune dysregulation and therapy-related immunosuppression are involved in the low humoral response. Importantly, active treatment with Rituximab, Bruton’s tyrosine kinase inhibitors, or chemotherapy was an independent prognostic factor for suboptimal antibody response. Patients with HL showed superior humoral responses to the NHL/CLL subgroups. In conclusion, patients with CLL/lymphomas have low humoral response following COVID-19 vaccination, underlining the need for timely vaccination ideally during a treatment-free period and for continuous vigilance on infection control measures

Poor Neutralizing Antibody Responses in 132 Patients with CLL, NHL and HL after Vaccination against SARS-CoV-2: A Prospective Study

Simple Summary The urgency of the COVID-19 pandemic has led to accelerated vaccine development within less than a year. Emerging data suggest that the ability of patients with hematological malignancies to form an adequate number of antibodies in response to vaccination for SARS-CoV-2 is suboptimal. In this context, we evaluated the ability of 132 patients with Chronic Lymphocytic Leukemia, Non-Hodgkin&apos;s Lymphoma and Hodgkin&apos;s Lymphoma to elicit an adequate immune response to the BNT162b2 vaccine. Vaccination with two doses of the BNT162b2 vaccine led to lower production of neutralizing antibodies against SARS-CoV-2 in these patients compared with healthy controls. Being on active treatment for the underlying disease was an independent prognostic factor for suboptimal antibody response. This finding underlines the need for timely vaccination ideally during a treatment-free period and for continuous vigilance on infection control measures. Emerging data suggest suboptimal antibody responses to COVID-19 vaccination in patients with hematological malignancies. We evaluated the humoral response following the BNT162b2 vaccine in patients with chronic lymphocytic leukemia (CLL), non-Hodgkin&apos;s lymphoma (NHL), and Hodgkin&apos;s lymphoma (HL). An FDA-approved, ELISA-based methodology was implemented to evaluate the titers of neutralizing antibodies (NAbs) against SARS-CoV-2 on day 1 of the first vaccine, and afterwards on day 22 and 50. One hundred and thirty-two patients with CLL/lymphomas and 214 healthy matched controls vaccinated during the same period, at the same center were enrolled in the study (NCT04743388). Vaccination with two doses of the BNT162b2 vaccine led to lower production of NAbs against SARS-CoV-2 in patients with CLL/lymphomas compared with controls both on day 22 and on day 50 (p &lt; 0.001 for all comparisons). Disease-related immune dysregulation and therapy-related immunosuppression are involved in the low humoral response. Importantly, active treatment with Rituximab, Bruton&apos;s tyrosine kinase inhibitors, or chemotherapy was an independent prognostic factor for suboptimal antibody response. Patients with HL showed superior humoral responses to the NHL/CLL subgroups. In conclusion, patients with CLL/lymphomas have low humoral response following COVID-19 vaccination, underlining the need for timely vaccination ideally during a treatment-free period and for continuous vigilance on infection control measures