Late Effects of the Immune System

Spleen
Immune System

Surgical or functional splenectomy increases risk of life-threatening invasive bacterial infection.[1] Although staging laparotomy is no longer standard practice for pediatric Hodgkin lymphoma, patients from earlier time periods have ongoing risks.[2,3] In addition, children may be rendered asplenic by radiation therapy to the spleen in doses greater than 30 Gy.[4,5] Low-dose involved-field radiation (21 Gy) combined with multiagent chemotherapy did not appear to adversely affect splenic function as measured by pitted red blood cell assays.[5] No other studies of immune status after radiation therapy are available. Functional asplenia (with Howell Jolly bodies, reduced splenic size and blood flow) after bone marrow transplantation has been attributed to graft-versus-host disease (GVHD).

A pneumococcal vaccine booster is recommended for patients aged 10 years and older and more than 5 years after previous dose.[6] Asplenic patients should also be immunized against Neisseria meningitidis and Haemophilus influenzae type B and should receive antibiotic prophylaxis for dental work.

Prophylactic antibiotics (penicillin or similar broad-spectrum agent) have been recommended for at least 2 to 3 years after splenectomy and until at least 5 years of age for young children.[7] Randomized studies that address the benefit of daily prophylactic antibiotics have not been conducted in a pediatric oncology population; thus, these recommendations are based on extrapolated study data derived from other populations with asplenia.[8-11] The benefit of prolonged antibiotic prophylaxis is also unknown. Many patients, over time, discontinue use of penicillin; consideration should be given to ensuring availability of appropriate antibiotics for use at the first onset of febrile illness in patients who are not on daily prophylaxis. Medical care should be sought promptly for fevers higher than 38.5°C.

Refer to the Centers for Disease Control and Prevention (CDC) Guidelines for Preventing Opportunistic Infections Among Hematopoietic Stem Cell Transplant Recipients for more information on posttransplant immunization.

Although the immune system appears to recover from the effects of active chemotherapy and radiation, there is some evidence that lymphoid subsets may not always normalize. Innate immunity, thymopoiesis, and DNA damage responses to radiation were shown to be abnormal in survivors of childhood leukemia.[12] Antibody levels to previous vaccinations are also reduced in patients off therapy for acute lymphoblastic leukemia for at least one year,[13,14] suggesting persistence of abnormal humoral immunity [15] and a need for revaccination in such children. Immune status is also compromised after stem cell transplantation, particularly in association with GVHD.[16] In a prospective, longitudinal study of 210 survivors treated with allogeneic hematopoietic cell transplantation, antibody responses lasting for more than 5 years after immunization were observed in most patients for tetanus (95.7%), rubella (92.3%), poliovirus (97.9%), and, in diphtheria-tetanus-acellular pertussis (DTaP) recipients, diphtheria (100%) . However, responses to pertussis (25.0%), measles (66.7%), mumps (61.5%), hepatitis B (72.9%), and diphtheria in tetanus-diphtheria (Td) recipients (48.6%) were less favorable. Factors associated with vaccine failure include older age at immunization; lower CD3, CD4, or CD19 count; higher immunoglobulin M concentration; positive recipient cytomegalovirus serology; negative titer before immunization; history of acute or chronic GVHD; and radiation conditioning.[17]

Follow-up recommendations for transplant recipients have been published by the major North American and European transplant groups, the Centers for Disease Control and Prevention (CDC), and the Infectious Diseases Society of America.[18,19]

Refer to the Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers for immune system late effects information including risk factors, evaluation, and health counseling.

1. Pickering LK, Peter G, Baker CJ, eds.: 2000 Red Book: Report of the Committee on Infectious Diseases. 25th ed. Elk Grove Village, Ill: American Academy of Pediatrics, 2000. 
   
   
2. Kaiser CW: Complications from staging laparotomy for Hodgkin disease. J Surg Oncol 16 (4): 319-25, 1981.  [PUBMED Abstract]
   
   
3. Jockovich M, Mendenhall NP, Sombeck MD, et al.: Long-term complications of laparotomy in Hodgkin's disease. Ann Surg 219 (6): 615-21; discussion 621-4, 1994.  [PUBMED Abstract]
   
   
4. Coleman CN, McDougall IR, Dailey MO, et al.: Functional hyposplenia after splenic irradiation for Hodgkin's disease. Ann Intern Med 96 (1): 44-7, 1982.  [PUBMED Abstract]
   
   
5. Weiner MA, Landmann RG, DeParedes L, et al.: Vesiculated erythrocytes as a determination of splenic reticuloendothelial function in pediatric patients with Hodgkin's disease. J Pediatr Hematol Oncol 17 (4): 338-41, 1995.  [PUBMED Abstract]
   
   
6. Immunocompromised children. In: Pickering LK, Baker CJ, Kimberlin DW, et al., eds.: 2009 Red Book: Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, Il: American Academy of Pediatrics, 2009, pp 72-86. 
   
   
7. Spelman D, Buttery J, Daley A, et al.: Guidelines for the prevention of sepsis in asplenic and hyposplenic patients. Intern Med J 38 (5): 349-56, 2008.  [PUBMED Abstract]
   
   
8. Waghorn DJ, Mayon-White RT: A study of 42 episodes of overwhelming post-splenectomy infection: is current guidance for asplenic individuals being followed? J Infect 35 (3): 289-94, 1997.  [PUBMED Abstract]
   
   
9. Ejstrud P, Kristensen B, Hansen JB, et al.: Risk and patterns of bacteraemia after splenectomy: a population-based study. Scand J Infect Dis 32 (5): 521-5, 2000.  [PUBMED Abstract]
   
   
10. Bisharat N, Omari H, Lavi I, et al.: Risk of infection and death among post-splenectomy patients. J Infect 43 (3): 182-6, 2001.  [PUBMED Abstract]
    
    
11. Davidson RN, Wall RA: Prevention and management of infections in patients without a spleen. Clin Microbiol Infect 7 (12): 657-60, 2001.  [PUBMED Abstract]
    
    
12. Schwartz C L, Hobbie WL, Constine LS, et al., eds.: Survivors of Childhood Cancer: Assessment and Management. St. Louis, Mo: Mosby, 1994. 
    
    
13. Leung W, Neale G, Behm F, et al.: Deficient innate immunity, thymopoiesis, and gene expression response to radiation in survivors of childhood acute lymphoblastic leukemia. Cancer Epidemiol 34 (3): 303-8, 2010.  [PUBMED Abstract]
    
    
14. Aytac S, Yalcin SS, Cetin M, et al.: Measles, mumps, and rubella antibody status and response to immunization in children after therapy for acute lymphoblastic leukemia. Pediatr Hematol Oncol 27 (5): 333-43, 2010.  [PUBMED Abstract]
    
    
15. Brodtman DH, Rosenthal DW, Redner A, et al.: Immunodeficiency in children with acute lymphoblastic leukemia after completion of modern aggressive chemotherapeutic regimens. J Pediatr 146 (5): 654-61, 2005.  [PUBMED Abstract]
    
    
16. Olkinuora HA, Taskinen MH, Saarinen-Pihkala UM, et al.: Multiple viral infections post-hematopoietic stem cell transplantation are linked to the appearance of chronic GVHD among pediatric recipients of allogeneic grafts. Pediatr Transplant 14 (2): 242-8, 2010.  [PUBMED Abstract]
    
    
17. Inaba H, Hartford CM, Pei D, et al.: Longitudinal analysis of antibody response to immunization in paediatric survivors after allogeneic haematopoietic stem cell transplantation. Br J Haematol 156 (1): 109-17, 2012.  [PUBMED Abstract]
    
    
18. Rizzo JD, Wingard JR, Tichelli A, et al.: Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation: joint recommendations of the European Group for Blood and Marrow Transplantation, Center for International Blood and Marrow Transplant Research, and the American Society for Blood and Marrow Transplantation (EBMT/CIBMTR/ASBMT). Bone Marrow Transplant 37 (3): 249-61, 2006.  [PUBMED Abstract]
    
    
19. Tomblyn M, Chiller T, Einsele H, et al.: Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant 15 (10): 1143-238, 2009.  [PUBMED Abstract]