Vaccinations in patients with hematological malignancies

doi:10.1016/j.blre.2015.10.001

Blood Reviews

Volume 30, Issue 2, March 2016, Pages 139-147

https://doi.org/10.1016/j.blre.2015.10.001 Get rights and content

Abstract

Patients with hematological malignancies are at risk for a number of infections that are potentially preventable by vaccinations such as pneumococcal infections and influenza. Treatment, especially with anti-B-cell antibodies and hematopoietic stem cell transplantation (HSCT), negatively impacts the response to vaccination for several months. It is therefore recommended that patients be vaccinated before initiating immunosuppressive therapy if possible. The risk of side-effects with inactivated vaccines is low, but care has to be taken with live vaccines, such as varicella-zoster virus vaccine, since severe and fatal complications have been reported. HSCT patients require repeated doses of most vaccines to achieve long-lasting immune responses. New therapeutic options for patients with hematological malignancies that are rapidly being introduced into clinical practice will require additional research regarding the efficacy of vaccinations. New vaccines are also in development that will require well-designed studies to ascertain efficacy and safety.

Introduction

Over the past several decades, the number of immunocompromised patients has rapidly increased. These patients are vulnerable to numerous infections against which vaccines exist. The 2009 H1N1 influenza A pandemic illustrated the importance of rapid design and implementation of vaccination strategies for patients with hematological malignancies including hematopoietic stem cell transplant (HSCT) recipients. Immunosuppressed patients were recognized early during the pandemic to be at increased risk for severe complications and vaccines were rapidly tested in these patient groups [1], [2], [3], [4], [5], [6]. Safety of vaccines is also an important issue since severe and life-threatening complications can develop from live attenuated vaccines [7].

Vaccination in patients with hematological malignancies is complex as the background and characteristics of immunosuppressed states differ between different patient categories. Patients undergoing allogeneic HSCT are the most deeply immunocompromised and new transplant techniques are constantly developing that are challenging the knowledge regarding the immune responses to vaccination collected from earlier studies. Therapy for hematological malignancies has also changed substantially during the last decade with the introduction of drugs having different modes of action, including monoclonal antibodies, drugs with immunomodulatory effects such as lenalidomide, and targeted drugs such as thyrosine kinase inhibitors. Therefore prior vaccination studies might not accurately represent the current risks and benefits of vaccinations. In general, almost all vaccination studies have assessed surrogate endpoints, namely immune responses, since true efficacy studies are difficult to perform due to the number of patients required to assess prevention of infection or disease.

Section snippets

When is it meaningful to start vaccinations?

Since all types of immunosuppressive therapy, including transplantation, are likely to suppress the response to vaccination, it might be beneficial to administer vaccines before the start of therapy for hematological malignancies or before HSCT. Recovery of immune function after cessation of immunosuppressive therapy is an important factor that impacts the development of an adequate response to vaccination. Furthermore, vaccine safety has to be considered. The optimal time to administer

Should we vaccinate all HSCT patients according to the same schedule?

HSCT recipients may be immunosuppressed from their underlying disease, pre-transplant treatments of the disease, immunosuppressive medications given either as pre-transplant conditioning or post-transplant immunosuppression, or GVHD. Current recommendations do not differ for different categories of HSCT recipients, although it is obvious that the mechanisms behind patient's immunosuppressed states vary between autologous and allogeneic HSCT recipients. Current recommendations also do not take

What data do we have regarding uptake of vaccination recommendations?

A number of recommendations regarding vaccination of hematology and transplant patients have been published [39], [40]. Most recently, the Infectious Diseases Society of America (IDSA) in collaboration with other organizations published recommendations regarding vaccinations in the immunocompromised host [8], [15]. Despite the availability of guidelines, surveys of immunization practices in patients with hematological malignancies over the past 2 decades have shown that immunizations are

Pneumococcal conjugate and polysaccharide vaccines

Pneumococci are important causes of infection in patients with hematological malignancies. Risk factors include poor B-cell function such as in patients with CLL and multiple myeloma and HSCT recipients, especially those with chronic GVHD. There are two types of pneumococcal vaccines available. The first vaccine developed was the 23-valent pneumococcal polysaccharide vaccine (PPSV23), which is T-cell independent and therefore unable to create an immunological memory, but has the advantage of

Influenza

The morbidity of influenza is increased in patients with cancer. For example, patients with malignancies were more likely to die during hospitalization for influenza [69]. Influenza might also interrupt scheduled chemotherapy with a negative impact on disease outcome. HSCT patients infected with the 2009 pandemic H1N1 virus were at high risk for pneumonia, frequently required mechanical ventilation, and had high mortality despite oseltamivir therapy [2], [6]. There is also significant morbidity

Conflict of interest

Constantine Tsigelis has no conflicts to declare. Per Ljungman has received research grants from Pfizer and Merck and been a member of an advisory board for Astellas and Vical.

Research Agenda

•
The rapid development of treatments for both hematologic malignancies and HSCT patients challenges current vaccination recommendations since studies including patients treated with these new modalities are lacking.
•
The optimal schedules for PCV and influenza vaccination are not well-defined and require

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ReviewVaccinations in patients with hematological malignancies

Abstract

Introduction

Section snippets

When is it meaningful to start vaccinations?

Should we vaccinate all HSCT patients according to the same schedule?

What data do we have regarding uptake of vaccination recommendations?

Pneumococcal conjugate and polysaccharide vaccines

Influenza

Conflict of interest

Vaccine

Blood

Blood

Leuk Res

Vaccine

Biol Blood Marrow Transplant

Biol Blood Marrow Transplant

Blood

Biol Blood Marrow Transplant

Blood

Blood

Vaccine

Vaccine

J Pediatr

Blood

Blood

Vaccine

Eur J Intern Med

Blood

Biol Blood Marrow Transplant

Lancet

Biol Blood Marrow Transplant

Vaccine

Semin Hematol

Biol Blood Marrow Transplant

Travel Med Infect Dis

Travel Med Infect Dis

2009 Pandemic influenza A (H1N1) virus infection in pediatric oncology and hematopoietic stem cell transplantation patients

Pediatr Blood Cancer

Outcome of pandemic H1N1 infections in hematopoietic stem cell transplant recipients

Haematologica

Respiratory failure caused by 2009 novel influenza A/H1N1 in a hematopoietic stem-cell transplant recipient: detection of extrapulmonary H1N1 RNA and use of intravenous peramivir

Ann Intern Med

Oseltamivir resistance in adult oncology and hematology patients infected with pandemic (H1N1) 2009 virus

Australia Emerg Infect Dis

Disseminated, persistent, and fatal infection due to the vaccine strain of varicella-zoster virus in an adult following stem cell transplantation

Clin Infect Dis

2013 IDSA clinical practice guideline for vaccination of the immunocompromised host

Clin Infect Dis

Vaccination of hematopoietic cell transplant recipients

Bone Marrow Transplant

Recovery of blood B-lymphocytes and serum immunoglobulins after chemotherapy for childhood acute lymphoblastic leukemia

Cancer

Immune recovery in children with malignancy after cessation of chemotherapy

J Pediatr Hematol Oncol

Response to immunization against polio after allogeneic marrow transplantation

Bone Marrow Transplant

Response to tetanus toxoid immunization after allogeneic bone marrow transplantation

J Infect Dis

2013 IDSA clinical practice guideline for vaccination of the immunocompromised host

Clin Infect Dis

Response to pneumococcal polysaccharide vaccine in patients with untreated Hodgkin's disease

Children's Cancer Study Group Report Lancet

Antibody response to pneumococcal vaccine in patients with early stage Hodgkin's disease

Eur J Haematol

Revaccination of children after completion of standard chemotherapy for acute leukemia

Clin Infect Dis

Humoral immunity to diphtheria, tetanus, measles, and hemophilus influenzae type b in children with acute lymphoblastic leukemia and response to re-vaccination

Pediatr Blood Cancer

Active immunization of children with leukemias and lymphomas against infection by hepatitis B virus

Acta Paediatr Jpn

Immune response to conjugated meningococcal C vaccine in pediatric oncology patients

Pediatr Blood Cancer

Vaccination of patients with haematological malignancies with one or two doses of influenza vaccine: a randomised study

Br J Haematol

Pretransplant vaccinations in allogeneic stem cell transplantation donors and recipients: an often-missed opportunity for immunoprotection?

Bone Marrow Transplant

Randomized study of early versus late immunization with pneumococcal conjugate vaccine after allogeneic stem cell transplantation

Clin Infect Dis

The influence of graft versus host reaction on the response to pneumococcal vaccination in bone marrow transplant patients

Review
Vaccinations in patients with hematological malignancies