Evaluation of pandemic H1N1 (2009) influenza vaccine in adults with solid tumor and hematological malignancies on active systemic treatment

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Abstract

Background

Over 85% of healthy individuals vaccinated with the pandemic H1N1 (pH1N1) vaccine achieve seroprotection.

Objectives

We evaluated the safety and immunogenicity of pH1N1 vaccine in patients undergoing chemotherapy for hematological and solid tumor malignancies.

Study design

Adult patients, receiving chemotherapy undergoing pH1N1 vaccination at our institution had blood samples drawn for CBC (baseline only) and serology prior to and ≥21 days post vaccination. HAI antibody testing was performed for pH1N1 (A/California/7/2009 strain) and seasonal H1 (A/Brisbane/59/07 strain). Seroprotection was defined as a pH1N1 antibody titre ≥1:40 and seroconversion as an antibody titre >4× baseline. Patients completed a symptom diary card.

Results

Paired samples were available for 46 patients (20 solid tumor, 26 hematological), median age 56 (range 23–76) years. The seroprotective rate post-vaccination for solid tumors was 50% compared to 27% for hematological malignancy (p = 0.11), respective seroconversion rates were 45% and 19% (p = 0.06). In patients with solid tumors vaccination mid cycle resulted in the highest pH1N1 titres, although timing and blood count were not associated with seroconversion or seroprotection. For hematological patients, a normal leukocyte count and vaccination at the beginning of a cycle were associated with higher rates of seroconversion (p  0.05). Addition of rituximab to chemotherapy resulted in a failure to seroconvert (p = 0.05). Vaccination was well tolerated by all patients.

Conclusions

Although well tolerated, the seroprotection rate following pH1N1 vaccination is lower than that would be expected. Further investigation into immunization strategies in patients receiving chemotherapy is required.

Introduction

Patients undergoing chemotherapy are reported to be at increased risk of contracting, suffering complications and dying from seasonal influenza.1, 2, 3 The Centers for Disease Control and Prevention (CDC) recommends annual vaccination for patients on chemotherapy.4 However, limited and conflicting data exists to inform the clinician on the efficacy of vaccination programs in this patient population.5, 6, 7, 8, 9, 10 As a result, despite recommendations, less than half of patients on chemotherapy undergo vaccination.11, 12 Dialogue between patients and oncologists is variable, one study suggesting it may occur in as few as 7% of cases.13

In March of 2009, an influenza A H1N1 virus – H1N1 (2009) – was linked to an outbreak of respiratory infections in Mexico, launching a worldwide pandemic.14, 15 A subunit inactivated monovalent vaccine – the H1N1 (2009) pandemic vaccine – was generated from the influenza A/California/7/2009 viral strain and made available through public vaccination programs. Vaccination dosing and schedule for the pandemic vaccine were developed using healthy individuals.16, 17

Section snippets

Objectives

To evaluate rates of seroprotection and seroconversion following H1N1 (2009) vaccination in two patient populations receiving cytotoxic chemotherapy: patients with solid tumors; and those with hematological malignancies. Secondary aims included providing safety data on the vaccine and exploring physicians’ attitudes to vaccination.

Design

Patients actively receiving cytotoxic chemotherapy for solid tumor and hematological malignancy in ambulatory clinics at the Princess Margaret Hospital, Toronto, Canada were approached to participate in this study assessing serological response to ASO 3-adjuvanated H1N1 pandemic influenza vaccine Arepanrix™ (GlaxoSmithKline). The study was approved by the Local Research Ethics Board. All patients signed written informed consent prior to study entry. A separate survey of clinician attitudes to

Results

A total of 46 patients, median age was 56 years, had paired sera available for analysis. 50% of patients had undergone seasonal flu vaccination in previous seasons (no patient had undergone 2009 seasonal flu vaccination); additional characteristics are shown in Table 1. Amongst the solid tumor patients 12 were receiving a platinum based combination chemotherapy and seven single agent treatment. The most common co morbidities were hypertensions, hyperlipidaemia and type 2 diabetes. Concurrent

Discussion

Studies measuring immunogenicity following vaccination with a single dose of pH1N1 vaccine in the general population have shown seroprotection rates over 85%.16, 17, 21 To the best of our knowledge, this represents the first report on the effect of pH1N1 vaccination in patients undergoing chemotherapy. Although well tolerated, we observed lower rates of seroprotection (37%) and serconversion (30%) than would be expected in the general population. Rates were lowest in patients with hematological

Funding

Medical Gynecology Research Fund, PMH Foundation.

Conflict of interest

No conflict of interest to declare.

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