There are limited data on outcomes of allogeneic hematopoietic stem cell transplantation (allo‐HSCT) in recipients with prior COVID‐19 infection. This single‐center retrospective study included 54 ...adult patients who received allo‐HSCT from July 2020 to September 2021 after previous COVID‐19 infection and 122 control group patients without a history of COVID‐19 who underwent HSCT during the same period, with a median follow‐up of 17 months. Median time from COVID‐19 to allo‐HSCT was 211 days. The incidence of main complications in the post‐transplant period was not significantly different between the two groups: deep vein thrombosis (p = .85), TMA (p = .8), VOD (p = .25), bloodstream infections (p = .21), pneumonia of any etiology (p = .41), viral infections (p = .85), invasive fungal disease (p = .08). The 2‐year non‐relapse mortality, relapse incidence, overall survival, and progression‐free survival also were comparable in the study and the control groups: 22% (95% CI 10.5–36.2) versus 26.3% (95% CI 18.7–34.6) p = .4; 15.6% (95% CI 7.3–26.9) versus 23.6% (95% CI 16.0–32.3) p = .39; 67.9% (95% CI 50.4–80.3) versus 59.8% (95% CI 50.2–68.1) p = .24 and 62.3% (95% CI 45.5–75.3) versus 49.9% (95% CI 40.0–59.1) p = .18, respectively. The history of previous COVID‐19 infection did not affect the results of allo‐HSCT.
Ravulizumab, a novel long‐acting complement component 5 (C5) inhibitor administered every 8 weeks (q8w), was non‐inferior to eculizumab for all efficacy outcomes in two randomised, open‐label, phase ...3 trials in C5 inhibitor‐naïve (Study 301) and eculizumab‐experienced (Study 302) adult patients with paroxysmal nocturnal haemoglobinuria (PNH). This pre‐specified analysis characterised ravulizumab pharmacokinetics (PK), pharmacodynamics (PD; free C5 levels), and PD differences between medications (Study 301, n = 246; Study 302, n = 195). Ravulizumab PK parameters were determined using non‐compartmental analysis. Serum free C5 was quantified with a Gyros‐based fluorescence assay (ravulizumab) and an electrochemiluminescence ligand‐binding assay (eculizumab). Ravulizumab PK parameters were numerically comparable in both studies; the median time to maximum concentrations ranged from 2·3 to 2·8 and 2·3 to 2·6 h in studies 301 and 302, respectively. Ravulizumab steady‐state serum concentrations were achieved immediately after the first dose and sustained throughout treatment. For ravulizumab, the mean (SD) post hoc terminal elimination half‐life was 49·7 (8·9) days. Serum free C5 concentrations <0·5 µg/ml were achieved after the first ravulizumab dose and sustained throughout treatment in both studies. In a minority of patients, free C5 concentrations <0·5 µg/ml were not consistently achieved with eculizumab in either study. Ravulizumab q8w was more consistent in providing immediate, complete, sustained C5 inhibition than eculizumab every‐2‐weeks in patients with PNH.
For patients with acute myeloid and lymphoblastic leukaemia (AML/ALL) lacking a matched sibling or unrelated donor, haploidentical stem cell transplantation (HAPLO-SCT) is increasingly used. However, ...available data on the treatment of relapse after HAPLO-SCT, including feasibility and efficacy of a second HAPLO-SCT (HAPLO-SCT2), is scarce. Hence, adults with AML/ALL, that had undergone HAPLO-SCT2 without ex-vivo manipulation after haematologic relapse from HAPLO-SCT1 were selected for a retrospective registry analysis. Eighty-two patients (AML, n = 63, ALL, n = 19, median follow-up: 33 months) were identified. Engraftment rate was 87%. At day +180, cumulative incidences of acute GvHD II-IV°/chronic GvHD were 23.9%/22.6%, respectively. Two-year overall survival/leukaemia-free survival (OS/LFS) were 34.3%/25.4%; 2-year non-relapse mortality (NRM) and relapse incidence (RI) were 17.6% and 57%. Leukaemia was the most frequent cause of death. Separated by disease, 2-year OS/LFS/NRM/RI were 28.7%/22.3%/16.2%/61.6% in AML, and 55.3%/38.4%/23.5%/38.2% in ALL patients. In a risk-factor analysis among patients with AML, stage at HAPLO-SCT1 and HAPLO-SCT2, and interval from HAPLO-SCT1 to relapse significantly influenced outcome. Our data demonstrate that HAPLO-SCT2 is a viable option in acute leukaemia relapse after HAPLO-SCT1. Engraftment, toxicity, risk factors and long-term outcome are comparable to data reported after allo-SCT2 in a matched donor setting.
Background
The effects of eculizumab treatment in paroxysmal nocturnal hemoglobinuria (PNH) patients with or without high‐disease activity (HDA), defined by LDH ≥ 1.5 × ULN and history of major ...adverse vascular events (MAVEs; including thrombotic events TEs); anemia; and/or physician‐reported abdominal pain, dyspnea, dysphagia, erectile dysfunction, fatigue, and/or hemoglobinuria, in the International PNH Registry were evaluated.
Methods
Registry patients were stratified by baseline HDA and eculizumab‐treatment status. Longitudinal changes in laboratory and clinical PNH‐related endpoints were evaluated using linear mixed models (continuous variables) or Poisson regression (incidence rates).
Results
As of May 1, 2017, 3009 patients (HDA/eculizumab‐treated, n = 913; HDA/never‐treated, n = 651; no‐HDA/eculizumab‐treated, n = 173; no‐HDA/never‐treated, n = 1272) were analyzed. Higher proportions of eculizumab‐treated patients had HDA and history of MAVEs. In patients with and without HDA, respectively, eculizumab treatment resulted in reductions from baseline for (1) LDH ratio (mean SD: −5.3 4.0 and −2.3 3.8); (2) incidence rate ratio (IRR) for MAVEs (−80% and −70%); (3) IRR for TEs (−80% for both); and (4) units of red blood cell transfusions per year (from 6.8 to 2.8 and 3.6 to 2.5 units).
Conclusions
Eculizumab treatment in a real‐world setting improved outcomes, including substantial decreases in hemolysis, MAVE rates, TEs, and transfusions in PNH patients regardless of HDA.
Background. Pregnancy in paroxysmal nocturnal hemoglobinuria (PNH) patients has historically been a high-risk situation. The combination of chronic complement-mediated hemolysis caused by the disease ...and physiological activation of the complement system during pregnancy, significantly worsened the prognosis for the life. For a long time, there were no effective methods for the PNH treatment, and pregnancy in patients seemed to be extremely risky, as it significantly increased the risk of life-threatening complications. The advent of targeted therapy with eculizumab turned the prognosis of this disease upside down: patients began not only to survive, but also to live comparable to healthy people. A comparative analysis of the course and outcomes of pregnancy in patients with PNH treated with eculizumab and in patients without targeted therapy was carried out.
Aim. The study was to evaluate the course and outcomes of pregnancy in patients with PNH, depending on the therapeutic approach.
Materials and methods. We analyzed data from 57 pregnancies in 49 women (31 used eculizumab, 26 with supportive care only) observed at the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology or with remote consultation (23 clinics from 19 cities of Russia).
Results. The high probability of pregnancy complications and its adverse outcomes outside of targeted therapy indicates the vital need for its use: all observations were accompanied by complications of varying severity. The course of pregnancy with the eculizumab is generally more favorable: an apparently higher rate of live births and a lower likelihood of complications are registered. Without increasing the incidence of complications, eculizumab significantly improves pregnancy outcomes for both mother and fetus, and does not adversely affect the health of newborns.
Conclusion. Thus, eculizumab allows not only to increase the survival rate of patients with PNH, but also to comprehensively improve their quality of life, including the possibility of safe childbirth.
Objectives
Therapy of patients with relapsed and refractory classic Hodgkin lymphoma (r/r cHL) after PD-1 inhibitors failure remains an unresolved issue. The aim of this study was to evaluate the ...efficacy and safety of the combination of nivolumab with brentuximab vedotin (Nivo + BV) after nivolumab monotherapy failure.
Methods
This study retrospectively analyzed 21 patients with r/r cHL who were treated with the combination of Nivo + BV after Nivo failure. The response was evaluated by PET–CT scan according to the LYRIC criteria. Adverse events (AEs) were assessed according to NCI CTCAE v.4.03.
Results
Median follow-up was 19 (9–47) months. The ORR was 57%. The median OS was not reached, 24 month OS was 80% (95% CI 50–93%). Median PFS was 12 months with 24 month PFS of 31% (95% CI 12–53%). Any grade AEs were observed in 12 patients (63%), 3–4 grade AEs in 2 patients (10%). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) after Nivo + BV was performed in 8 (38%) patients. The median time between Nivo + BV and allo-HSCT was 8 (5–21) months.
Conclusions
Combination of Nivo + BV in r/r cHL after nivolumab monotherapy failure is potentially an effective and safe approach.
Currently, eculizumab is the main effective treatment for paroxysmal nocturnal hemoglobinuria (PNH). The aim of this randomized multicenter noninferiority study was to evaluate the efficacy and ...safety of the Biosimilar (Elizaria) in comparison with the Originator (Soliris) in patients with PNH. Biosimilar and Originator were administered at a dose of 600 mg weekly for 4 weeks at the initial stage in naive patients, as well as for maintenance therapy at a dose of 900 mg every 2 weeks in all patients. The primary endpoint was a comparative assessment of hemolytic activity based on the area under the lactate dehydrogenase (LDH) concentration–time curve during the maintenance therapy. Thirty-two (32) patients were randomized for therapy with Biosimilar (
n
= 16) or Originator (
n
= 16). The mean values of LDH concentration–time curve were similar in both treatment groups without statistically significant differences (
p
> 0.05). Evaluation of secondary endpoints has shown no statistically significant differences between the groups. Safety values were comparable in both treatment groups. The data obtained confirm that the Biosimilar is not inferior to the Originator in terms of the main efficacy parameter, and is also comparable with it in terms of safety and additional efficacy parameters. Clinicaltrials.gov identifier: NCT04463056
Intestinal complications are common after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, only scarce data concern herpesvirus incidence in the colonic mucosa post-HSCT. Our ...purpose was to assess the frequency and clinical significance of cytomegalovirus (CMV), Epstein−Barr virus (EBV), human herpesvirus type 6 (HHV6), and herpes simplex virus (HSV) in the colonic mucosa post-HSCT. The study group included 119 patients of different ages, mostly with leukemias and lymphomas, subjected to allo-HSCT from haploidentical related (48%) or HLA-compatible donors (52%). In total, 155 forceps biopsies of the colonic mucosa were taken in cases of severe therapy-resistant intestinal syndrome post-HSCT. Most samples were taken from the descending, sigmoid, and transverse colon. Intestinal GVHD or local infections were assessed clinically and by histology. EBV, CMV, HSV, and HHV6 were tested in colonic mucosal lysates with commercial PCR assays. HSV was found in <8% of colonic samples, along with high HHV6 and CMV positivity (up to 62% and 35%, respectively) and a higher EBV incidence at 5−6 months post-HSCT (35%). For CMV and EBV, significant correlations were revealed between their rates of detection in blood and colonic mucosa (r = 0.489 and r = 0.583; p < 0.05). No significant relationships were found between the presence of herpesviruses and most patients’ characteristics. EBV positivity in colonic samples was correlated with delayed leukocyte and platelet recovery post-HSCT. Higher EBV frequency in the colonic mucosa was found in deceased patients (56% versus 21%, p = 0.02). The correlations among EBV positivity in the colon, lethality rates and delayed hematopoietic reconstitution suggest some relationship with systemic and local EBV reactivation post-transplant.
The pilot clinical study presented demonstrates the possibility, safety, and effectiveness of oral microbiota transplantation from a healthy donor to a patient with neuroblastoma to prevent ...chemotherapy-induced oral mucositis. A 6-month-old patient with a diagnosis of retroperitoneal neuroblastoma was treated according to the NB 2004 protocol. Due to the development of severe oral mucositis, it was decided to perform oral microbiota transplantation. During the next 3 chemotherapy cycles and conditioning regimen before autologous hematopoietic cell transplantation (auto-HCT), the patient was repeatedly injected per os with donor saliva from her healthy mother. Oral microbiota transplantation was shown to effectively prevent the development of oral mucositis after chemotherapy, and only grade 1 oral mucositis developed after auto-HCT. In all loci of the oral cavity, there was a decreased abundance of bacteria from the Staphylococcaceae, Micrococcaceae, and Xanthomonadaceae families. Conversely, there was an increase in the relative abundance of Streptococcaceae and certain other bacterial taxa. In conclusion, the transplantation of maternal saliva in this patient prevented severe mucositis and was accompanied by a compositional change of the patient’s oral microbiota. No adverse events due to the transplantation of maternal saliva were noted.
Dose-intensive cytostatic therapy and antibiotic treatment in allogeneic hematopoietic stem cell transplantation (allo-HSCT) cause severe abnormalities in a composition of gut microbiota as well as ...the emergence of antibiotic resistance. The data on the longitudinal recovery of major bacterial phyla and the expansion of genes associated with antibiotic resistance are limited. We collected regular stool samples during the first year after allo-HSCT from 12 adult patients with oncohematological disorders after allo-HSCT and performed 16SrRNA sequencing, multiplex PCR, conventional bacteriology and CHROMagar testing. We observed a decline in Shannon microbiota diversity index as early as day 0 of allo-HSCT (p = 0.034) before any administration of antibiotics, which persisted up to 1 year after transplantation, when the Shannon index returned to pre-transplant levels (p = 0.91). The study confirmed the previously shown decline in Bacillota (Firmicutes) genera and the expansion of E. coli/Shigella, Klebsiella and Enterococci. The recovery of Firmicutes was slower than that of other phyla and occurred only a year post-transplant. A positive correlation was observed between the expansion of E. coli/Shigella genera and blaKPC, blaCTX-M-1 and blaTEM (p < 0.001), Klebsiella spp. and blaOXA-48-like, blaNDM, blaCTX-M-1, blaTEM, and blaSHV (p < 0.001), Pseudomonas spp. and blaNDM (p = 0.002), Enterococcus spp. and blaOXA-48-like, blaNDM, blaCTX-M-1, blaSHV (p < 0.01). The correlation was observed between the expansion of Enterobacterales and and carbapenemase-positive CHROMagar samples (p < 0.001). Samples positive for carbapenem-resitant bacteria were at their maximum levels on day +30, and were gradually diminishing one year after allo-HSCT. From day +30 to +60, all isolated K. pneumoniae strains in fecal samples proved to be resistant to the main antibiotic groups (carbapenems, aminoglycosides, fluoroquinolones, third-generation cephalosporins). One year after HSCT, we documented the spontaneous decolonization of K. pneumoniae. The sensitivity of molecular biology techniques in the search for total and antibiotic-resistant Klebsiella seems to be superior to common bacteriological cultures. Future studies should be focused on searching for novel approaches to the efficient reconstitution and/or maintenance of strictly anaerobic microbiota in oncological patients.
PDF
