Immunogenicity of Haemophilus Influenza and Pneumococcal Vaccines in Related and Unrelated Transplant Recipients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 592-592 ◽  
Author(s):  
Mary K. Pao ◽  
Esperanza B. Papadopoulos ◽  
Nancy A. Kernan ◽  
Ann A. Jakubowski ◽  
James W. Young ◽  
...  
Keyword(s):  
Conjugate Vaccine ◽  
Pneumococcal Vaccine ◽  
Pneumococcal Vaccination ◽  
Healthy Children ◽  
Older Individuals ◽  
Transplant Recipients ◽  
Haemophilus Influenza ◽  
Post Transplant ◽  
Significant Difference ◽  
Invasive Infections

Abstract Despite advances in post transplant supportive care, invasive infections due to Haemophilus influenza and pneumococcus continue to result in significant morbidity and mortality long after successful HCT. Introduction of the protein-conjugated vaccines in healthy children has been associated with a reduction in invasive infections due to these organisms. Although current post transplant guidelines recommend immunization with the protein-conjugated H. flu vaccine, they still include the use of the 23-valent pure polysaccharide pneumococcal vaccine (PPV), a poor immunogen even in HLA matched sibling transplant recipients. There is limited data on the immunogenicity of any of these vaccines in recipients of an unrelated or T-cell depleted (TCD) HCT. In this study, we evaluated the responses of 270 allogeneic transplant patients who received the H flu conjugate vaccine and initial pneumococcal vaccination with either the 23-valent PPV (n=156) or a series of the protein-conjugated pneumococcal vaccine, Prevnar (n=114). The median age of the 270 patients at the time of HCT was 25.1 years (range, 0.2–69 years). Thirty-eight percent of the patients were children (<18 years of age). Donors were unrelated, HLA-mis-matched related or HLA matched related in 74, 22, and 174 cases, respectively. Seventy percent of patients underwent a TCD HCT. All vaccines were well tolerated. One child had a reversible allergic response to Prevnar. Eighty-seven percent of the patient population responded to the H flu conjugate vaccine, defined as a ≥3 fold rise in titer or seroconversion. Only 24% of patients responded to the 23-valent PPV. There was no significant difference between the response to PPV administered < or > 24 months post HCT (18% vs 28%, p=0.058), nor between children and adults (19% vs 25%, p=0.16). In contrast, 75% of patients were capable of responding to Prevnar, initiated at a median of 16 months post transplant. Response to Prevnar was significantly better in patients < 18 years of age compared to older individuals (85% vs 56%, respectively, p<0.001). There was no significant difference in the ability of children who received an unrelated or HLA matched related HCT to respond to Prevnar (85% vs 86%, p=0.385). In adults, 48% vs 69%, p=0.132) responded to Prevnar following an HLA-matched related or unrelated HCT, respect ively. Forty-one patients who failed to respond to the 23-valent PPV were subsequently immunized with a series of 3 doses of Prevnar administered 2 months apart, resulting in a 76% response rate. These data suggest that continued inclusion of the 23-valent PPV is inadequately protecting patients against a potentially preventable and often fatal disease. Consideration should be given to utilization of Prevnar in the upfront vaccination of children and adults following allogeneic HCT.

scholarly journals SUN-573 Use of PCSK9 Inhibitors Post-Transplant

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Juliana Matthews ◽  
Dustin Donald ◽  
Barbara Gisella Carranza-Leon
Keyword(s):  
Statin Therapy ◽  
Heart Transplant ◽  
Ldl Cholesterol ◽  
Case Series ◽  
Dose Titration ◽  
Transplant Recipients ◽  
Pcsk9 Inhibitors ◽  
Statin Intolerance ◽  
Post Transplant ◽  
Significant Difference

Abstract Background: Dyslipidemia is common in patients after transplant. While statins are the mainstay of therapy, interactions with immunosuppressants such as calcineurin inhibitors (CNIs) can limit dose titration or lead to intolerance of this important drug class. Withdrawal of statin therapy can precipitate hyperlipidemia and potentially accelerate cardiovascular disease in transplant recipients, including coronary allograft vasculopathy (CAV) in heart transplant (HT) patients. Proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9i) may provide a safe, effective option for such patients. PCSK9i profoundly reduce low-density lipoprotein (LDL) and subsequently the risk of cardiovascular events in nontransplant patients. Further, these novel agents have no known interactions with CNIs. There is a paucity of data describing PSCK9i use post-transplant, with only a few small case series reported in HT recipients. Here, we summarize our experience along with available literature on this topic. Methods: In this retrospective case series we investigated adult recipients of heart transplant who were treated with PCSK9 inhibitors from July 2015 to 2019 because of statin intolerance or refractory hyperlipidemia. We compared the data of patients at baseline and after various durations of therapy with the PSCK9i evolocumab and alirocumab using the median and interquartile range (IQR). Specifically, we evaluated PCSK9i efficacy, effect on immunosuppressant levels, cardiac function and adverse events. Results: Five patients (4 men; median age 54, IQR 52-60) underwent heart transplant an average of 7.4 years ago. Median treatment duration of evolocumab or alirocumab was 12 months (IQR 7-17). This led to a reduction of total cholesterol by 94 mg/dl (p=0.04) (47% decrease) and LDL cholesterol by 83 mg/dl (p=0.04) (69% decrease). No statistically significant difference in HDL cholesterol, triglycerides or liver function tests (LFTs) were observed. There were no episodes of rejection. Immunosuppressant levels remained at goal. One patient noted a few days of fatigue after alirocumab injections but otherwise no side effects were reported. Conclusion: The PCSK9 inhibitors evolocumab and alirocumab are promising alternatives to statin therapy in transplant recipients with statin intolerance or refractory hyperlipidemia. Our study showed their potential to significantly reduce LDL cholesterol in heart transplant patients without altering IST levels. No episodes of transplant rejection were noted. Further long-term studies to establish the safety and efficacy of PSCK9 inhibitors post-transplant are needed.

scholarly journals SP5.2.1 Renal Transplant Outcomes Through the COVID-19 Pandemic at a London Transplant Centre

2021 ◽  
Vol 108 (Supplement_7) ◽  
Author(s):  
Sara Mahdibeiraghdar ◽  
Abbas Ghazanfar ◽  
Sarah Heap ◽  
Abul Siddiky ◽  
Claire Fraser Taylor ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Graft Loss ◽  
Outcome Data ◽  
Adverse Outcomes ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Jugular Vein Thrombosis ◽  
Post Transplant ◽  
Significant Difference ◽  
The Impact

Abstract Aims The aim of this audit was to establish the impact of COVID-19 on the outcomes of renal transplant recipients in the post-transplant period at our centre, through the 2020 calendar year. Methods Living donor and deceased donor renal transplant recipients in the period of interest were identified and any complications or adverse outcomes were reviewed and compared to outcome data from the previous year. Results A total of 88 renal transplants were performed in 2020. Fifty-five cases were performed after reopening the Unit. Five patients tested positive for COVID-19 in the post-transplant period. One patient was admitted to the Intensive Care Unit and subsequently died from related complications. Another patient suffered from internal jugular vein thrombosis shortly after testing positive and could be attributed to the hypercoagulable state post-infection. A total of 4 deaths and 1 graft loss were recorded within 2020. This compares to 1 death, 2 graft losses and 1 primary non-function in 172 transplants in 2019. Of the 4 deaths, one was directly linked to COVID-19. The other 3 deaths could be indirectly linked to the disruptions that were made in the healthcare system during this period in adapting to the pandemic. Conclusions It was anticipated that COVID-19 will directly and indirectly affect patient outcomes from surgery during this period. This was clearly seen at this Unit, with mortality rates having increased almost eight-fold in the post-transplant period compared to the same period in the previous year. However, no significant difference was seen with graft losses.

scholarly journals Use of seven-valent pneumococcal conjugate vaccine (PCV7) in Europe, 2001-2007

2009 ◽  
Vol 14 (12) ◽  
Author(s):  
H De Carvalho Gomes ◽  
M Muscat ◽  
D L Monnet ◽  
J Giesecke ◽  
P L Lopalco
Keyword(s):  
Conjugate Vaccine ◽  
Vaccination Programme ◽  
Pneumococcal Vaccine ◽  
Age Groups ◽  
Pneumococcal Vaccination ◽  
European Countries ◽  
Vaccine Uptake ◽  
Childhood Vaccination ◽  
Vaccine Introduction ◽  
National Vaccination Programme

The first pneumococcal vaccine targeting the youngest age groups, a seven-valent conjugate vaccine (PCV7), was licensed in Europe in 2001. Since then several European countries have introduced PCV7 in their childhood vaccination schedules. Still, information on vaccination schemes, vaccine uptake and impact of vaccine introduction is scarce in Europe. The following article summarises the characteristics of national pneumococcal vaccination programmes for children in 32 European countries and provides an estimate of vaccine use based on sales data for 22 countries between 2001 and 2007. There were wide variations in the recommended PCV7 vaccination schemes and in PCV7 use. High vaccine uptake was not always related to the presence of a national vaccination programme.

scholarly journals High Incidence of Late, Sustained and Clinically Inconsequential Epstein Barr Virus (EBV) Reactivation Following Combined Unrelated Cord Blood and Haploidentical CD34+ Cell Transplantation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1180-1180
Author(s):  
Sneha Purvey ◽  
Enkhtsetseg Purev ◽  
Xin Tian ◽  
Jennifer Wilder ◽  
Lisa Cook ◽  
...  
Keyword(s):  
T Cells ◽  
Cord Blood ◽  
Cell Transplantation ◽  
Transplant Recipients ◽  
Post Transplant ◽  
Ebv Reactivation ◽  
Copy Numbers ◽  
Significant Difference ◽  
Unrelated Cord Blood ◽  
Matched Donor

Abstract Introduction: Unrelated cord blood (UCB) transplantation is a useful alternative for patients (pts) with malignant or non-malignant hematological disorders who lack an HLA matched donor. However, because UCB is devoid of memory T-cells, viral infections are more problematic following this transplant approach. EBV is a latent γ-herpesvirus that infects more than 90% of the world's population. Following UCB transplantation, early (<100 days) reactivation of latent EBV is common and is associated with a high risk of post-transplant lymphoproliferative disorder (PTLD). The likelihood of PTLD following late EBV reactivation (>100 days) is less well characterized. We investigated EBV reactivation and PTLD development in early vs late post-transplant periods in severe aplastic anemia (SAA) pts undergoing combined UCB and haploidentical CD34+ cell transplantation. Methods: Pts with SAA and life-threatening neutropenia (ANC <500/uL) refractory to ≥2 immunosuppressive agents were eligible for treatment if they lacked an HLA-matched donor. Conditioning consisted of cyclophosphamide (120 mg/kg), fludarabine (125 mg/m2), equine ATG (160 mg/kg) and a single dose of 200 cGy of total body irradiation. Graft-vs-host disease (GVHD) prophylaxis consisted of tacrolimus and mycophenolate mofetil. Pts received a single ³4/6 HLA antigen matched UCB unit co-infused with a G-CSF mobilized, T-cell depleted CD34+ selected (Miltenyi CliniMacs system) allograft collected by apheresis of a haploidentical relative. EBV copy numbers were measured weekly for the first six months post-transplant and thereafter as clinically warranted. Results: 18 pts with treatment refractory SAA (median age 18 years; range 4-30), including 4 with SAA evolved to myelodysplastic syndrome (MDS) were transplanted. All pts were platelet and RBC transfusion-dependent. 11 pts received a ≥4/6 HLA matched UCB unit and 7 received a 5/6 HLA-matched unit. UCB units contained a median 2.8 x 107 TNCs/kg (range 1.7- 5.2) and 2.1 x 105CD34+cells/kg (range 0.5- 4.7) and haploidentical peripheral blood grafts contained a median 3.2 x106 CD34+cells/kg (range 3- 4.1) and 2.3 x 103 CD3+cells/kg (range 0.8- 5). All 18 pts were EBV IgG seropositive pretransplant. With a median follow-up of 689 days (range 160-2022), 16 pts survive, all disease free and transfusion independent. 16/18 (89%) pts developed EBV reactivation (EBV copy number >1000 copies/ml of whole blood or >150 genome equivalents/million PBMC) at a median 42 days post-transplant (range 2-1165). 12 pts (67%) had EBV reactivation before transplant day 100 (defined as early reactivation). Among those with early reactivation, 10/12 (83%) were treated preemptively with rituximab while 2/12 (17%) did not receive treatment and cleared the EBV viremia without intervention. Late EBV reactivation (defined as reactivation occurring after day 100) occurred in 15/18 (83%) pts. Among those with late reactivation, 12/15 (80%) were not treated while 3/15 (20%) received rituximab, which was given preemptively for PTLD in 2 pts and used to treat biopsy-confirmed PTLD on day 343 in one pt. The median time to first rituximab use was 37 days (range 8-343). Among the 12 pts with late EBV reactivation not given treatment, 9 (50% of those transplanted) had sustained viremia of >1000 copies lasting >30 days (defined as late and sustained EBV reactivation). All pts with late and sustained EBV reactivation remained asymptomatic despite high viral copy numbers, including 4 who had peak EBV copy numbers >30,000 copies/ml (Figure). There was no statistically significant difference in immune reconstitution, as determined by quantitative serum IgG levels and absolute numbers of CD4+ and CD8+ T-cells on day 100, 6 months, 1 year and > 1 year post-transplant in those with vs without late and sustained EBV reactivation. Conclusion: We observed that late and sustained EBV reactivation occurs commonly following combined UCB/haploidentical selected CD34+ cell transplantation, even in pts off immunosuppressive therapy and without CD4 and/or CD8 lymphopenia. In most cases, it was clinically inconsequential, and did not require rituximab treatment. The factors contributing to late sustained EBV reactivation including potential defects in viral-specific immunity remain under investigation. Figure: Figure: Late and sustained EBV reactivation in 4 cord/haplo transplant recipients Figure:. Late and sustained EBV reactivation in 4 cord/haplo transplant recipients Disclosures No relevant conflicts of interest to declare.

scholarly journals MO987IMPACT OF POST-TRANSPLANT TUBERCULOSIS ON LIVE DONOR KIDNEY TRANSPLANT RECIPIENTS: RISK FACTORS AND OUTCOME

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Samar Elshahat ◽  
Salwa El wasif ◽  
Essam Lotfy Omar ◽  
Said M Al-Barshomy
Keyword(s):  
Kidney Transplant ◽  
Liver Enzymes ◽  
P Value ◽  
Study Group ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Cmv Infection ◽  
Statistical Significant Difference ◽  
Post Transplant ◽  
Significant Difference

Abstract Background and Aims TB is encountered worldwide more frequently among renal transplant recipients due to of the state of immunosuppression. Antituberculosis drugs cause CYP-450 enzyme induction that increase the metabolism of CNI and mTORi So, decreasing the plasma trough level which in turn expose the transplant recipient to the risk of rejection. Our study concerned with the impact of post-transplant TB on live donor kidney transplant recipients outcome. Method This is retrospective cohort study held in Urology and Nephrology Center, Mansoura University, Egypt. The study included 210 patients out of 3200 kidney transplant recipients (KTRs) who underwent renal transplantation at Mansoura urology and Nephrology Centre between March 1976 and December 2019. The patients were divided into 2 main groups according to history of post-transplant tuberculosis, a group of 70 kidney transplant recipients who developed tuberculosis after transplantation served as a study group and a matched group of 140 kidney transplant recipients who did not develop tuberculosis after transplantation served as control group. Study group was then subdivided into pulmonary and urinary TB groups. Results We found that patients with Low BMI are associated with higher incidence of post-transplant TB (p value: 0.023). While, post-transplant TB was associated with increased incidence of post-transplant DM, bacterial infection, CMV infection and surgical wound infection. Exposure to rejection episodes (either acute or chronic) is comparable among both groups. Post-transplant diabetes incidence was higher among TB group with statistical significant difference (p value: 0.01). Bacterial infection incidence including pneumonia, urinary tract infection and gastroenteritis were associated with higher incidence of TB with statistically significant difference (p value: 0.012). CMV infection incidence was significantly higher among TB group (p value: 0.02). Incidence of wound infection post-transplantation was higher among TB group with statistically significant difference (p value: 0.014). Both groups were comparable regarding creatinine and creatinine clearance at last follow-up (p value: 0.61, 0.51 respectively). Overall, there was no statistically significant difference among both groups regarding 5, 10 and 15 years graft and patient survival (p value: 0.54, 0.15 respectively). During treatment of TB in the study group, there was statistical significant difference regarding liver enzymes and CNI doses either before or during anti-tuberculous treatment as liver enzymes were elevated (p value: 0.023) and higher doses of CNI were required to achieve satisfactory trough level during antituberculus treatment (p value: 0.037). Liver enzymes dropped significantly and lower doses of CNI were used after cessation of anti-tuberculous treatment (p value: 0.041, 0.03 respectively). Study group was then subdivided into 2 main groups: pulmonary TB (42 KTRs) and Urinary TB (28 KTRs). There was no statistical significant difference among both groups regarding baseline data, transplantation data, post-transplant medical complication except that CMV infection incidence was higher among pulmonary TB group (p value: 0.012). Patient and graft survival were comparable. Conclusion Among renal transplant recipients, tuberculosis is a serious problem for both the disease itself and its treatment with anti-tuberculous medications. In our series the rejection was comparable in both groups (with or without tuberculosis) this may be explained by frequent monitoring of the immunosuppressive drug level.

Vaccine Reponses Following Unmodified or T Cell Depleted Unrelated and Mismatched Related HCT.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2226-2226 ◽  
Author(s):  
Trudy N. Small ◽  
Esperanza B. Papadopoulos ◽  
Farid Boulad ◽  
Nancy A. Kernan ◽  
Ruth Ford ◽  
...  
Keyword(s):  
T Cell ◽  
Red Blood Cells ◽  
Pneumococcal Vaccine ◽  
Blood Cells ◽  
Influenza B ◽  
Primary Immunization ◽  
Transplant Recipients ◽  
Post Transplant ◽  
Sheep Red Blood Cells ◽  
Fixed Times

Abstract Infection continues to contribute to morbidity and mortality late after hematopoietic stem cell transplant (HCT). The development of evidence-based guidelines for immunizing patients post HCT could substantially reduce this risk, particularly in view of the severity of many vaccine preventable infections in the naïve unimmunized host. The efficacy of current vaccine strategies, including the CDC guidelines, have not been tested in large numbers of patients, particularly following unrelated or HLA-mismatched related HCT. We retrospectively analyzed the pre and post vaccine titers of 103 patients transplanted from an unrelated (n=83) or HLA-mismatched (MM) donor (n=20) between 1/1/92 and 2/1/03. Thirty-three percent of the unrelated grafts were unmodified. The remainder were T cell depleted (TCD)using soybean agglutination followed by rosetting with sheep red blood cells (78%), CD34 selection followed by rosetting with sheep red blood cells (12%), or partial TCD using MoAb (12%). Of the 20 HLA-MM related grafts, 13 were TCD (SBA-E- BM, n=4, CD34+E-PBSC (n=9). Adults (>18 years) comprised 43 and 30% of the unrelated and MM-related groups, respectively. Patients were vaccinated according to guidelines recommended for previously unimmunized children, with the exception of live viral vaccines. Rather than vaccination at fixed times post transplant, the majority of patients were vaccinated when their CD4 cell counts were >200/ul and their T cell response to PHA was >75% of normal. Recipients of an unrelated or MM-related transplant were re-immunized starting a median (range) of 442 and 509 days post transplant, respectively. Seroconversion following a series of 3 tetanus and IPV vaccinations occurred in over 90% of patients regardless of transplant type. Following primary immunization with conjugated Haemophilus influenza B (Hib) vaccine, 21% of MM-related and 15% of unrelated HCT recipients failed to develop positive titers despite a series of 3 vaccinations. Sixty-six percent of MM-related and 75% of unrelated transplant recipients seroconverted following 3 recombinant HepB vaccinations. Less than 40% of unrelated transplant recipients responded to the 23-valent polysaccharide pneumococcal vaccine despite administration at a median of 2.5 years post transplant. In contrast 68% seroconverted following three immunizations with the 7-valent protein conjugated pneumococcal vaccine given 2 months apart. The majority of patients did not however seroconvert after only one dose of the 7-valent conjugated pneumococcal vaccine. Forty-six patients received an MMR vaccine. No unexpected toxicities were observed despite failure in 30 and 50% of unrelated and HLA-mismatched related transplant recipients, respectively. This data suggests that current immunization guidelines which recommend vaccination of all transplant recipients at fixed times post transplant (12 and 24 months) may not have adequately factored in the prolonged and variable immunodeficiency observed in unrelated and mis-matched related transplant recipients, that primary immunization against pneumococcus should consist of a series of the 7-valent conjugated pneumococcal vaccine, and that assessment of pre and post vaccination titers is essential to ensure protection against vaccine preventable diseases.

Initial Serological Response after Prime-boost Pneumococcal Vaccination in Rheumatoid Arthritis Patients: Results of a Randomized Controlled Trial

2017 ◽  
Vol 44 (12) ◽  
pp. 1794-1803 ◽  
Author(s):  
Mai T.T. Nguyen ◽  
Hanne Lindegaard ◽  
Oliver Hendricks ◽  
Charlotte Sværke Jørgensen ◽  
Bjørn Kantsø ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Single Dose ◽  
Primary Endpoint ◽  
Pneumococcal Vaccine ◽  
Controlled Trial ◽  
Pneumococcal Vaccination ◽  
Serological Response ◽  
Randomized Controlled ◽  
Significant Difference ◽  
Polysaccharide Pneumococcal Vaccine

Objective.To evaluate the initial serological responses to pneumococcal vaccination with the 13-valent protein-conjugated pneumococcal vaccine (PCV13) followed by the 23-valent polysaccharide pneumococcal vaccine (PPV23) among patients with rheumatoid arthritis (RA) treated with biological disease-modifying antirheumatic drugs (bDMARD) according to dosing and intervals between immunizations.Methods.Investigator-initiated clinical trial. Patients with RA receiving bDMARD were randomized (1:1:1) to immunization with single dose PCV13 followed by PPV23 after 16 or 24 weeks, or double dose PCV13 followed by PPV23 after 16 weeks. A comparison group of patients with RA treated with conventional synthetic (cs)DMARD received single dose PCV13 followed by PPV23 16 weeks later. Pneumococcal antibodies were collected before and 4 weeks after each vaccination. The primary endpoint was the proportion of participants responding to ≥ 6/12 pneumococcal serotypes 4 weeks after both vaccinations.Results.Sixty-five participants receiving bDMARD and 35 participants receiving csDMARD were included. After PPV23 vaccination, 87% (95% CI 0.76–0.94) and 94% (95% CI 0.77–0.99), respectively, of participants treated with bDMARD and csDMARD had reached the primary endpoint. There was no significant difference in primary endpoint between the 3 randomization arms. The response for rituximab-treated participants was 25% compared to ≥ 89% in participants treated with bDMARD with other mode of action.Conclusion.The early serological response to prime-boost vaccination with PCV13 followed by PPV23 was very similar among participants receiving bDMARD and csDMARD. However, notable differences in response were observed according to individual bDMARD. It is important to consider the RA treatment when planning pneumococcal vaccination in patients with RA.

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