Vaccines against SARS-CoV-2 have shown remarkable efficacy and thus constitute an important preventive option against coronavirus disease 2019 (COVID-19), especially in fragile patients. We aimed to ...systematically analyze the outcomes of patients with hematological malignancies who received vaccination and to identify specific groups with differences in outcomes. The primary end point was antibody response after full vaccination (2 doses of mRNA or one dose of vectorbased vaccines). We identified 49 studies comprising 11,086 individuals. Overall risk of bias was low. The pooled response for hematological malignancies was 64% (95% confidence interval CI: 59-69; I²=93%) versus 96% (95% CI: 92-97; I²=44%) for solid cancer and 98% (95% CI: 96-99; I²=55%) for healthy controls (P<0.001). Outcome was different across hematological malignancies (P<0.001). The pooled response was 50% (95% CI: 43-57; I²=84%) for chronic lymphocytic leukemia, 76% (95% CI: 67-83; I²=92%) for multiple myeloma, 83% (95% CI: 69-91; I²=85%) for myeloproliferative neoplasms, 91% (95% CI: 82-96; I²=12%) for Hodgkin lymphoma, and 58% (95% CI: 44-70; I²=84%) for aggressive and 61% (95% CI: 48-72; I²=85%) for indolent non-Hodgkin lymphoma. The pooled response for allogeneic and autologous hematopoietic cell transplantation was 82% and 83%, respectively. Being in remission and prior COVID-19 showed significantly higher responses. Low pooled response was identified for active treatment (35%), anti-CD20 therapy ≤1 year (15%), Bruton kinase inhibition (23%), venetoclax (26%), ruxolitinib (42%), and chimeric antigen receptor T-cell therapy (42%). Studies on timing, value of boosters, and long-term efficacy are needed. This study is registered with PROSPERO (clinicaltrials gov. Identifier: CRD42021279051).
Hepatitis E virus is increasingly being reported to cause chronic infection in immunocompromised patients. However, less is known about patients with an underlying hematologic disease. In particular, ...the impact of hepatitis E infection on oncological therapy has been poorly described. In this retrospective single-center study, we analyzed 35 hematologic patients with hepatitis E, including 20 patients under active oncological treatment and 15 patients who were in the posttreatment follow-up or under active surveillance. The primary aim was to describe the clinical courses with particular focus on any hepatitis E-related therapy modifications of cancer-directed therapy. In the majority (60%) of patients who were under active oncological treatment, hepatitis E-related therapy modifications were made, and 25% of deaths were due to progression of the hematologic disease. In patients receiving concomitant oncological treatment, no hepatitis Erelated deaths occurred. In contrast, two patients in the follow-up group died from hepatitis E-associated acute-onchronic liver failure. Chronic hepatitis E was observed in 34% of all cases and 43% received ribavirin therapy; of those, 27% achieved a sustained virological response. CD20-directed therapy was the only independent risk factor for developing chronic hepatitis E. We conclude that CD20-directed treatment at any time point is a risk factor for developing chronic hepatitis E. Nevertheless, since mortality from the progression of hematologic disease was higher than hepatitis E-related mortality, we suggest careful case-by-case decisions on modifications of cancer treatment. Patients in the posttreatment follow-up phase may also suffer from severe courses and hepatitis E chronicity occurs as frequently as in patients undergoing active therapy.
Hematologic patients requiring abdominal emergency surgery are considered to be a high-risk population based on disease- and treatment-related immunosuppression. However, the optimal surgical therapy ...and perioperative management of patients with abdominal emergency surgery in patients with coexisting hematological malignancies remain unclear.
We here report a single-center retrospective analysis aimed to investigate the impact of abdominal emergency surgery due to clinically suspected gastrointestinal perforation (group A), intestinal obstruction (group B), or acute cholecystitis (group C) on mortality and morbidity of patients with coexisting hematological malignancies. All patients included in this retrospective single-center study were identified by screening for the ICD 10 diagnostic codes for gastrointestinal perforation, intestinal obstruction, and ischemia and acute cholecystitis. In addition, a keyword search was performed in the database of all pathology reports in the given time frame.
A total of 56 patients were included in this study. Gastrointestinal perforation and intestinal obstruction occurred in 26 and 13 patients, respectively. Of those, 21 patients received a primary gastrointestinal anastomosis, and anastomotic leakage (AL) occurred in 33.3% and resulted in an AL-related 30-day mortality rate of 80%. The only factor associated with higher rates of AL was sepsis before surgery. In patients with suspected acute cholecystitis, postoperative bleeding events requiring abdominal packing occurred in three patients and lead to overall perioperative morbidity of 17.6% and surgery-related 30-day mortality of 5.9%.
In patients with known or suspected hematologic malignancies who require emergency abdominal surgery due to gastrointestinal perforation or intestinal obstruction, a temporary or permanent stoma might be preferred to a primary intestinal anastomosis.
Donor lymphocyte infusions (DLIs) are used for adoptive immunotherapy to prevent or treat relapse and infectious complications after allogeneic hematopoietic stem cell transplantation (HSCT). ...Unmanipulated DLIs are associated with a risk of graft-versus-host disease (GVHD), probably related to CD8+ T cell activity. We investigated an automated clinical-scale human-CD4+ -cell purification method to deplete CD8+ cells. Twenty-four stem cell recipients received a total of 24 leukapheresis products being enriched for CD4+ cells using magnetic associated cell sorting (MACS) with an automated device (CliniMACS® ) before DLIs. MACS resulted in a mean CD4+ cell count of 16 × 106 /kg bw corresponding to 3.4-fold CD4+ cell enrichment. Mean yield and purity of CD45+ CD3+ CD4+ CD14− 7AAD− were 74% ± 23% and 82% ± 11%, respectively. Median initial dose of DLIs was 1.1 × 106 CD4+ /kg. During a median follow-up of 25 months, 7 (30%) patients experienced GVHD (acute II-IV: n = 4, 17%; acute III-IV: n = 2, 8%; chronic limited: n = 2, 8%; chronic extensive: n = 1, 4%). Thirteen of 21 further evaluable patients (62%) showed measurable clinical response, 2 patients with therapy refractory infectious complications (HSV) showed remarkable immunologic improvement. Automated enrichment of CD4+ by magnetic cell sorting provides an efficient and rapid method for processing donor lymphocytes. Additional studies should further investigate this approach in terms of efficacy and the risk of GVHD.
Daratumumab is a human monoclonal antibody that targets CD38, a cell surface protein that is overexpressed on multiple myeloma cells. Some clinical studies have shown encouraging efficacy and ...acceptable safety profile of daratumumab, so that the drug became the first monoclonal antibody as single agent therapy approved by the FDA for the treatment of multiple myeloma. The role of allo-SCT in myeloma patients remains unclear; nevertheless, the registry study of European Society for Blood and Marrow Transplantation (EBMT) suggests an increasing rate of allografts in Europe in last years. Despite the potentially curative potential of this approach, the increased relapse rate and low PFS remain a central clinical problem. In this single center retrospective analysis, we report on our experience on the use of daratumumab in relapsed/refractory myeloma patients after allo-SCT.
A total of 10 patients (male, n=5) with median age of 59 years (range, 37-69) relapsing after allo-SCTs that had been performed during a period 2008-2015 at the University of Hamburg and received daratumumab as single agent salvage therapy. Before allografting 8 patients received one and 2 patients ≥2 autografts, respectively. All but one patient received at least 1 salvage therapy line prior to the allo-SCT. The allografts were performed from unrelated donors (MUD, n=5; MMUD, n=3) or matched related donors (MRD, n=2). Five patients experienced early relapses (≤12 months) after allo-SCT. The median number of salvage lines post-transplant and prior to first daratumumab infusion was 3 (range, 1-4). The salvage regimens included bortezomib, lenalidomide, pomalidomide and carfilzomib. Daratumumab infusions were started at a median of 21 months (range, 2-30) after relapse/progress. The median number of infusions was 6 (range, 2-12). A total of 10 and 9 patients were available to safety and efficacy evaluation, respectively. The safety was assessed according to the Common Toxicity Criteria (CTC).
A total of 14 adverse events were observed in 9 patients: dyspnea (CTC1, n=2; CTC2, n=1), bronchospasm (CTC2, n=1) shivering (CTC1, n=3), cough (CTC1, n=1; CTC2, n=1), musculoskeletal pain (CTC1, n=2), acute coronary syndrome (CTC3, n=1), skin rush (CTC2, n=1), pressure on eyes (n=1). There were no cases of hematologic toxicity. There were no cases of GvHD. The adverse events appeared in all patients after the first infusion, with improved tolerance of following infusions. There were no cases, where the therapy had to be stopped due to adverse events.
Within a median follow-up of 25 months (range, 3-38) from the relapse/progression 9 of 10 patients remain alive. One patient died due to severe infection after progress of myeloma. A total of 5 of 9 evaluable patients responded (56%), of those 3 of 5 patients with early relapses (PR, n=2; vgPR, n=1). The responses (decrease of paraprotein and/or free light chains; reduction of extramedullary tumor in 1 patient) occurred at a median of 7 days (range, 7-22) after the first administration of daratumumab. The median response duration is 35 days (range, 7-84). All responding and 2 non-responding patients showed clinical improvement of constitutional symptoms. No patients required blood or platelets transfusions during and after the therapy. All responding patients maintain their responses 7, 14, 35, 54 and 84 days after the first administration of daratumumab.
Daratumumab demonstrated encouraging efficacy in relapsed/refractory patients with myeloma after allo-SCT. The administrations of the drug in these heavily pre-treated patients were associated with good safety profile and development in majority of cases non-severe adverse events mostly after the first infusion. Further studies on the use of daratumumab in post-transplant setting are warranted.
Kröger:Neovii: Honoraria, Research Funding; Riemser: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding.
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