Adjuvanted recombinant zoster vaccine in adult autologous stem cell transplant recipients : polyfunctional immune responses and lessons for clinical practice

PLAIN LANGUAGE SUMMARY What is the context? After haematopoletic stem cell transplantation, patlents have impaired immunity from conditioning chemotherapy regimens, often exacerbated by underlying diseases, putting them at high risk of developing herpes zoster. In this population, antiviral prophylaxis is the current standard of care to reduce herpes zoster risk. Vaccination provides an additional means to prevent herpes zoster. Live-attenuated vaccines are generally contraindicated in immuonocompromised patients. A non-live, adjuvanted recombinant zoster vaccine (RZV, Shingrix, GSK), has been approved for use in adults 250 years of age in the European Union, United States, Canada, Australia, Japan, and China. This vaccine is highly efficacious at preventing herpes zoster in adults over 50 years of age, as demonstrated in large, placebo-controlled randomised trials. Importantly, Shingrix use is not contraindicated in immunocompromised conditions, and was found to be highly efficacious in adults who had recently undergone autologous haematopoleticstem cell transplant. What is new? In autologous haematopoietic stem cell transplant recipients in whom Shingrix has demonstrated efficacy, two doseselicited high and persistent immune responses. Date presented here further support our understanding of the impact of specific factors such as age or underlying diseases on the vaccine's effect in the population studies, as well as the characteristics of the elicited cell-mediated immune responses. What is the impact? These results indicate that Shingrix, given shortly after haematopoletic stem cell transplant, can induce robust immune responses and reduce the risk of herpes zoster, even in individuals with immunosuppression due to underlying disease and/or use of immunosuppressive therapies, regardless of age or underlying disease. Immunocompromised individuals, particularly autologous hematopoietic stem cell transplant (auHSCT) recipients, are at high risk for herpes zoster (HZ). We provide an in-depth description of humoral and cell-mediated immune (CMI) responses by age (protocol-defined) or underlying disease (post-hoc) as well as efficacy by underlying disease (post-hoc) of the adjuvanted recombinant zoster vaccine (RZV) in a randomized observer-blind phase III trial (ZOE-HSCT, NCT01610414). 1846 adult auHSCT recipients were randomized to receive a first dose of either RZV or placebo 50-70 days post-auHSCT, followed by the second dose at 1-2 months (M) later. In cohorts of 114-1721 participants, at 1 M post-second vaccine dose: Anti-gE antibody geometric mean concentrations (GMCs) and median gE-specific CD4[2+] T-cell frequencies (CD4 T cells expressing >= 2 of four assessed activation markers) were similar between 18-49 and >= 50-year-olds. Despite lower anti-gE antibody GMCs in non-Hodgkin B-cell lymphoma (NHBCL) patients, CD4[2+] T-cell frequencies were similar between NHBCL and other underlying diseases. The proportion of polyfunctional CD4 T cells increased over time, accounting for 79.6% of gE-specific CD4 T cells at 24 M post-dose two. Vaccine efficacy against HZ ranged between 42.5% and 82.5% across underlying diseases and was statistically significant in NHBCL and multiple myeloma patients. In conclusion, two RZV doses administered early post-auHSCT induced robust, persistent, and polyfunctional gE-specific immune responses. Efficacy against HZ was also high in NHBCL patients despite the lower humoral response.Peer reviewe

Acute Cholecystitis Is a Common Complication after Allogeneic Stem Cell Transplantation and Is Associated with the Use of Total Parenteral Nutrition

AbstractThe incidence and risk factors for acute cholecystitis after allogeneic hematopoietic stem cell transplantation (HSCT) are not well defined. Of 644 consecutive adult transplants performed at our institution between 2001 and 2011, acute cholecystitis occurred in the first year of transplant in 32 patients (5.0%). We conducted 2 retrospective case-control studies of this population to determine risk factors for cholecystitis after HSCT and to evaluate the performance of different methods of imaging to diagnosis cholecystitis in patients undergoing HSCT compared with non-HSCT patients. In the HSCT population, development of cholecystitis was associated with an increased 1-year overall mortality rate (62.5% versus 19.8%, P < .001). The risk of developing cholecystitis was higher in patients who received total parenteral nutrition (TPN) (adjusted odds ratio, 3.41; P = .009). There was a trend toward more equivocal abdominal ultrasound findings in HSCT recipients with acute cholecystitis compared with nontransplant patients (50.0% versus 30.6%, P = .06). However, hepatobiliary iminodiacetic acid (HIDA) scans were definitively positive for acute cholecystitis in most patients in both populations (80.0% of HSCT recipients versus 77.4% of control subjects, P = .82). In conclusion, acute cholecystitis is a common early complication of HSCT, the risk is increased in patients who receive TPN, and it is associated with high 1-year mortality. In HSCT recipients with findings suggestive of acute cholecystitis, especially those receiving TPN, early use of HIDA scan may be considered over ultrasound

Lenalidomide after Stem-Cell Transplantation for Multiple Myeloma

Data are lacking on whether lenalidomide maintenance therapy prolongs the time to disease progression after autologous hematopoietic stem-cell transplantation in patients with multiple myeloma