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Letter to the Editor
Vaccination of patients with non-Hodgkin lymphoma under rituximab or other immunosuppressive drugs
Vacunación en el paciente con linfoma no hodgkiniano en tratamiento con rituximab u otros fármacos inmunodepresores
Juan Rodríguez-Garcíaa,
Corresponding author
juan.rodriguez@scsalud.es

Corresponding author.
, Rafael Fernández-Santosb, José Antonio García-Ercec
a Servicio de Medicina Preventiva, Calidad y Seguridad del paciente, Gerencia de Atención Especializada Áreas III y IV, Hospital de Sierrallana, Torrelavega, Cantabria, Spain
b Servicio de Medicina Preventiva, Hospital Obispo Polanco, Teruel, Spain
c Servicio de Hematología y Hemoterapia, Hospital San Jorge, Huesca, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Although pneumococcal vaccination is strongly recommended for patients who are immunosuppressed or patients with other high-risk medical conditions&#44; this important procedure is not commonly used in daily clinical practice&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> In addition&#44; since 2013&#44; all adult immunosuppressed patients in our country should receive the pneumococcal conjugate vaccine&#44; among others&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> We report the case of a patient diagnosed with non-Hodgkin&#39;s lymphoma &#40;NHL&#41; with other associated risk factors for invasive pneumococcal disease &#40;IPD&#41; who received several cycles of combination chemotherapy&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">52-year-old male patient diagnosed with nasopharyngeal BALT NHL in 1999&#46; He also had severe chronic obstructive pulmonary disease&#44; rheumatoid arthritis&#44; diabetes mellitus type 2 and moderate chronic renal failure&#46; He received 3 cycles of rituximab&#44; cyclophosphamide&#44; doxorubicin&#44; vincristine and prednisone &#40;R-CHOP&#41; every 2 months&#44; achieving the complete metabolic remission in 2004&#46; In 2006 he was diagnosed with gastric MALT NHL&#44; so 6 cycles of R-CHOP were scheduled&#46; In 2010 he showed haematological relapse&#44; which was subjected to another dosage schedule of 6 cycles of R-CHOP&#46; 7 days after completing the last cycle&#44; he developed pneumonia&#44; requiring hospitalization&#46; At 24 days of discharge&#44; he was readmitted due to a pneumonic process relapse&#46; Maintenance treatment with rituximab 375<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span> every 2 months was started&#44; for a 2-year period&#46; Again&#44; in July 2011&#44; the patient developed pneumonia&#44; finding <span class="elsevierStyleItalic">Haemophilus influenzae</span> type b &#40;Hib&#41; in sputum during admission&#46; In August 2011&#44; an anti-pneumococcal polysaccharide 23-valent vaccine was administered&#44; but in October&#44; 48 days after receiving the vaccine&#44; a new pneumonic condition required hospitalization&#46; <span class="elsevierStyleItalic">Streptococcus pneumoniae</span> was isolated in blood cultures&#46; Conjugate vaccines against Hib and meningococcal C were administered in November&#46; At 34 days of discharge&#44; he was readmitted with a diagnosis of pneumonia&#44; developing nephrotic syndrome during hospitalization&#44; which was considered secondary to pneumococcal infection&#46; In March 2013 he received a dose of Prevenar-13&#46; The patient was given an appointment for November 2014&#44; for a comprehensive examination&#46; His consent was requested and it became clear that there were no more infectious or pneumonic conditions&#44; neither moderate nor severe&#44; during the 3 years after the last admission&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">In reviewing the case&#44; some key elements in the patient&#39;s treatment regarding prevention through vaccination called our attention&#46; These relate to at least 2 of the episodes of severe pneumonia requiring hospitalization&#46; The patient was not vaccinated against pneumococcus or other encapsulated bacteria after initial diagnosis of hematologic malignancy despite its comorbidity&#44; neither was he when the need to use immunosuppressive therapy arose or after it was completed&#44; nor after the first episodes of severe pneumonia which required hospitalization&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Adults with one or more IPD risk conditions are 7&#46;4 times more likely to develop the disease than healthy subjects&#44; and those with 2 or more&#44; the risk is multiplied by 9&#46;6&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> In this case&#44; the risk of infection in patients treated with anti-CD20 is added to the increased risk associated with the patient diagnosis and comorbidity&#44; which is related to the number and time interval between cycles&#44; favouring a defect in humoral and cell immunity&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> The effect of treatment with rituximab alone or in combination chemotherapy has been studied in patients with NHL and other haematological malignancies&#44; observing an increased risk of leukopenia&#44; hypogammaglobulinemia and serious infections&#44; frequently including pneumonia and flu conditions&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4&#8211;6</span></a> However&#44; coverage against preventable diseases through more frequent vaccination in these patients&#44; such as influenza and pneumococcal disease&#44; remain low in patients under 65 years of age&#44; with 32&#37; and 19&#46;1&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> One of the main reasons given for non-vaccination of immunosuppressed patients is the lack of response&#44; however&#44; some studies have shown a response to the unconjugated polysaccharide vaccine of up to 45&#46;4&#37; in patients with NHL who had been splenectomized&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> In addition&#44; the new 13-valent conjugate vaccine is more immunogenic than the polysaccharide and is highly effective in preventing IPD caused by the 13 serotypes&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> in fact&#44; its administration has shown good immunogenicity in patients with NHL&#44; multiple myeloma or amyloidosis undergoing bone marrow transplant&#44; reaching protective titres in 78&#37; of patients compared with 61&#37; when the unconjugated polysaccharide vaccine was used&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> Despite this&#44; vaccine failures are possible&#44; especially when the preparation is administered during the period in which the patient&#39;s immune system remains impaired&#44; therefore&#44; in these cases&#44; revaccination is recommended at 3&#8211;6 months after the completion of the immunosuppressive therapy&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Although the risk of invasive disease and its complications is lower&#44; in addition to updating the patient&#39;s immunization schedule&#44; we must not forget influenza vaccination at the start of the season and vaccination against other bacteria capped as Hib and meningococcus -covering at least the type C and B in our environment-&#44; preferably at diagnosis or at least 15 days before the start of the cycles of treatment with immunosuppressive drugs&#44; whenever possible&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8&#44;10</span></a></p></span>"
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