Autologous hematopoietic cell transplantation (AHCT) is a standard of care in multiple myeloma (MM) patients aged <65 years. To understand age-related trends in utilisation and outcome of AHCT, we ...analysed 53 675 MM patients who underwent a first AHCT in 31 European countries between 1991 and 2010. The number of patients undergoing AHCT increased for all age groups (<40, 40-49, 50-59, 60-64, 65-69 and ⩾70 years) throughout the observation period. The highest increase was observed for patients aged ⩾65 years, who accounted for 3% of AHCTs in 1991-1995 and for 18.8% of AHCTs in 2006-2010. Risk factors associated with survival over the entire observation period (P<0.001) were calendar period, remission status at AHCT, gender, disease duration before AHCT and age. Survival improved considerably more in older than in younger patients in recent years. In 2006-2010, median 2- and 5-year post-transplant survival ranged from 85.9 and 61.5% in patients <40 years to 80.2 and 49.7% in those ⩾70 years. All-cause day-100 mortality decreased throughout the observation period to ⩽2.4% for all age groups in 2006-2010. The results of this study demonstrate increased utilisation and safety of AHCT with improved post-transplant survival particularly in elderly MM patients in recent years in Europe.
The optimal choice for mesh fixation in laparoscopic inguinal hernia repair (LIHR) has not been well established. This review compared the effects of glue versus mechanical mesh fixation in LIHR on ...incidence of chronic postoperative inguinal pain (CPIP) and other secondary outcomes, including acute pain, seroma, haematoma, hernia recurrence and other postoperative complications.
A systematic review of English/non-English studies using MEDLINE, the Cochrane Library, OpenGrey, OpenThesis and Web of Science, and searching bibliographies of included studies was completed. Search terms included laparoscopic, hernia, fibrin glue, Tisseel, Tissucol, cyanoacrylate, Glubran and Liquiband. Only RCTs comparing mechanical with glue-based fixation in adult patients (aged over 18 years) that examined CPIP were included. Two authors independently completed risk-of-bias assessment and data extraction against predefined data fields. All pooled analyses were computed using a random-effects model.
Fifteen RCTs met the inclusion criteria; 2777 hernias among 2109 patients were assessed. The incidence of CPIP was reduced with use of glue-based fixation (risk ratio (RR) 0.36, 95 per cent c.i. 0.19 to 0.69; P = 0.002), with moderate heterogeneity that disappeared with sensitivity analysis (8 d.f.) for patient-blinded studies (RR 0.43, 0.27 to 0.86). Trial sequential analysis provided evidence for a relative risk reduction of at least 25 per cent. The incidence of haeamtoma was reduced by using glue-based fixation (RR 0.29, 0.10 to 0.82; P = 0.02) with no significant effects on seroma formation or hernia recurrence (RR 1.07, 0.46 to 2.47; P = 0.88).
Glue-based mesh fixation appears to reduce the incidence of CPIP and haematoma after LIHR compared with mechanical fixation, with comparable recurrence rates.
Advanced stage (IIB-IVB) Mycosis Fungoides (MF) and Sezary Syndrome (SS) have a poor prognosis with median survival <5 years. We report long-term outcomes of a non-myeloablative allogeneic stem cell ...transplantation regimen consisting of total skin electron beam therapy, total lymphoid irradiation and antithymocyte globulin. Our prospective cohort consisted of 41 patients with a higher proportion of MF (34MF, 7SS). Acute GVHD Grade 2 to 4 was seen in 31.7% and chronic GVHD Grade 2 to 4 in 24%. The cumulative incidence of non-relapse mortality was 9.8% at 1 year and 12.6% at 2 years. At Day +90 post-transplant 66% of patients had a complete response (CR). With a median post-transplant follow up of 5.27 years, the 5-year overall survival rate was 37.7% (MF 36.7%, SS 57.1%). The 5-year cumulative incidence of progressive disease or relapse was 52.7% in all patients but only 20.8% in those with CR at transplant compared to 70.6% in those not in CR at transplant (p = 0.006). Long term survival is possible in advanced MF and SS with non-myeloablative transplantation and outcomes are improved in patients with CR at transplant.
Introduction
Thrombosis and bleeding are major complications in patients supported with left ventricular assist devices (LVADs). We aimed to assess the incidence of bleeding and thrombosis in ...patients supported with a HeartWare left ventricular assist device (HVAD), their predictive factors and their impact on mortality.
Methods
A single centre retrospective observational study of patients supported with HVAD over 5 years from January 2015 to October 2020.
Results
A total 139 patients (median age 52.5, 72.1% male) were included for analysis. The probability of 1-year survival was 73.1%. Advanced age (>60 years) and EuroSCORE II score (>20%) were independently associated with reduced survival. Major bleeding and thrombosis occurred in 46.8% and 35.3% respectively. Secondary mechanical circulatory support (MCS) increased likelihood of experiencing major bleeding (HR: 2.76, 95%1.65–4.62, p < 0.0001) whilst patients receiving aspirin were protected from bleeding and thrombosis (HR: 0.34 95% CI 0.19–0.58, p < 0.001). Pre-operative anaemia (HR: 3.02, 95% CI: 1.6–5.7, p = 0.014) and use of a secondary MCS device (HR: 2.78, 95% CI: 1.2–6.3, p = 0.001) were associated with an increased risk of thrombosis. Patients with any major bleeding (with or without thrombosis) had a 7.68-fold (95% CI 3.5–16.8) increased risk of death compared to those without. In contrast, ‘thrombosis only’ patients had 4.23-fold (95% CI 1.8–10.2) increased risk of death compared to those without thrombosis. The risk of mortality was increased in patients with any thrombosis and the risk of death was highest in patients with major bleeding and thrombosis (HR: 16.49 95% CI 7.7–35.3).
Conclusions
Major bleeding and thrombosis significantly increase the 1-year mortality. Optimal perioperative haemostasis and anticoagulation remains crucial in patients supported with HVAD.
Some patients treated by transplantation of haemopoietic stem cells (peripheral blood or bone marrow) become permanently infertile, but others retain or recover fertility. We assessed the outcome of ...conception in women, and partners of men previously treated by autologous or allogeneic stem cell transplantation (SCT).
We sent questionnaires to 229 centres of the European Group for Blood and Marrow Transplantation. We sought details about the original disease, transplant procedure, and outcome of conception for both male and female patients.
199 centres gave information relating to 19 412 allogeneic and 17 950 autologous transplant patients. 232 (0·6%) patients conceived after SCT. Crude annual birth rate for 4-month survivors of SCT was lower than the national average for England and Wales at 1·7 per 1000 patients. 312 conceptions were reported in 113 patients (74 allograft) and partners of 119 patients (93 allograft). Most pregnancies were uncomplicated and resulted in 271 livebirths. 28 (42%) of 67 allograft recipients had caesarean section compared with 16% in the normal population (difference=26% 95% CI 15–38), 12 (20%) of 59 had preterm delivery compared with a normal rate of 6% (14% 4–24), and 12 (23%) of 52 had low birthweight singleton offspring compared with a normal rate of 6% (17% 6–29).
Pregnancy after SCT is likely to have a successful outcome. Pregnancies in allograft patients who have received total body irradiation should be treated as high risk for maternal and fetal complications.
Improving haematopoietic cell transplantation outcomes by selection of an HLA-matched unrelated donor is best practice; however, donor selection by secondary characteristics is controversial. We ...studied 1271 recipients with haematological malignancies who underwent T-cell-depleted allografts and had complete data on HLA-matching status for six loci (HLA-A, -B, -C, -DRB1, -DQB1, -DPB1) and clinical outcome data. Five-year overall survival was 40.6%. HLA mismatching (at HLA-A, -B, -C, -DRB1, -DQB1) relative risk (RR) 1.22, 95% confidence interval (CI) 1.2-1.5, P=0.033 for 1 mismatch and RR 1.46, 95% CI 1.1-1.9, P=0.009 for >1 mismatch) and CMV mismatching (RR 1.37, 95% CI 1.2-1.6, P<0.001) were significantly associated with inferior survival. Donors aged <30 years showed a trend towards better survival. The multivariate model for mortality, combining CMV and HLA-match status, found an RR of 1.36 (95% CI 1.1-1.7, P=0.003) for HLA matched/CMV mismatched, an RR of 1.22 (95% CI 0.99-1.5, P=0.062) for HLA mismatched/CMV matched and an RR of 1.81 (95% CI 1.4-2.3, P=<0.001) for HLA/ CMV mismatched, compared with the HLA/CMV-matched recipients. These data suggest that HLA and CMV matching status should be considered when selecting unrelated donors and that CMV matching may abrogate the effect of an HLA mismatch.
In 2009 the declaration by the World Health Organization of a global pandemic of influenza-H1N1 virus led to a vaccination campaign to ensure protection for immunocompromised patients. The goal of ...this study was to determine the efficacy of the 2009 H1N1 vaccine in patients with hematologic malignancies.
We evaluated humoral and cellular immune responses to 2009 H1N1 vaccine in 97 adults with hematologic malignancies and compared these responses with those in 25 adult controls. Patients received two injections of vaccine 21 days apart and the controls received one dose. Antibody titers were measured using a hemagglutination-inhibition assay on days 0, 21 and 49 after injection of the first dose. Cellular immune responses to H1N1 were determined on days 0 and 49.
By day 21 post-vaccination, protective antibody titers of 1:32 or more were seen in 100% of controls compared to 39% of patients with B-cell malignancies (P<0.001), 46% of allogeneic stem cell transplant recipients (P<0.001) and 85% of patients with chronic myeloid leukemia (P=0.086). After a second dose, seroprotection rates increased to 68%, (P=0.008), 73%, (P=0.031), and 95% (P=0.5) in patients with B-cell malignancies, after allogeneic stem cell transplantation and with chronic myeloid leukemia, respectively. On the other hand, T-cell responses to H1N1 vaccine were not significantly different between patients and controls.
These data demonstrate the efficacy of H1N1 vaccine in most patients with hematologic malignancies and support the recommendation for the administration of two doses of vaccine in immunocompromised patients. These results may contribute towards the development of evidence-based guidelines for influenza vaccination in such patients in the future.
Granulocyte-Colony-Stimulating factor (G-CSF) is currently the standard mobilising agent for peripheral blood stem cell (PBSC) donation. Concerns that it may trigger chromosome aberrations similar to ...those observed in leukaemia patients were refuted but long-term effects of G-CSF mobilisation on genome integrity remains unclear. In the setting of a multi-centre clinical trial we screened blood samples from 50 PBSC donors at cellular and gene level for aberrations common in haematological malignancies using fluorescence in situ hybridisation (FISH) and next generation sequencing (NGS) assays. Analysis of samples collected before, on the day of donation, 90 and 180 days after G-CSF admission confirmed the absence of short-term effects in PBSC donors on both quiescent and dividing cells. This data did not differ from the results of 50 individuals tested 3-5 years after bone marrow donation and 50 healthy persons. NGS using a panel targeting 54 genes recurrently affected in myeloid disorders (TruSight Myeloid panel, Illumina) showed that the gene profiles of samples from 48 PBSC donors remained stable throughout the study period. These data strongly indicate absence of detrimental effects on the genome integrity caused by PBSC donation.
Outcomes and prognostic factors of reduced intensity-conditioned allo-SCT (RIC allo-SCT) for multiple myeloma (MM) relapsing or progressing after prior autologous (auto)-SCT are not well defined. We ...performed an analysis of 413 MM patients who received a related or unrelated RIC allo-SCT for the treatment of relapse/progression after prior auto-SCT. Median age at RIC allo-SCT was 54.1 years, and 44.6% of patients had undergone two or more prior auto-SCTs. Median OS and PFS from the time of RIC allo-SCT for the entire population were 24.7 and 9.6 months, respectively. Cumulative non-relapse mortality (NRM) at 1 year was 21.5%. In multivariate analysis, CMV seronegativity of both patient and donor was associated with significantly better PFS, OS and NRM. Patient-donor gender mismatch was associated with better PFS, fewer than two prior auto-SCT was associated with better OS, and shorter time from the first auto-SCT to the RIC allo-SCT was associated with lower NRM. The results of this study identify patient and donor CMV seronegativity as the key prognostic factor for outcome after RIC allo-SCT for MM relapsing or progressing after prior auto-SCT.
PDF
