Longitudinal Analysis of Antibody Response to Immunization in Pediatric Survivors After Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 795-795
Author(s):  
Hiroto Inaba ◽  
Meredith Posner ◽  
Christine Hartford ◽  
Jie Yang ◽  
Deqing Pei ◽  
...  

Abstract Abstract 795 Re-immunization is a common practice after allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the optimal vaccine schedule and long-term response have not been established. We prospectively and longitudinally evaluated the antibody response to childhood vaccines in 210 survivors after allo-HSCT. Positive titer lasting for 5 years or more after immunization was observed more often for diphtheria (98.1%), tetanus (96.1%), rubella (92.9%), and polio vaccines (96.2% for type 1; 98.1% for type 2 and 3), but less often for pertussis (25.0%), measles (65.4%), mumps (64.3%), and hepatitis B (75.0%). As shown in the table below, vaccine failure was associated with patients who were older at the time of re-immunization, received a T cell depleted graft, had a high-risk hematological malignancy, lower IgG levels, higher IgM levels, chronic GvHD, positive recipient CMV status, and negative titers prior to immunization. These clinical factors are useful to formulate immunization and monitoring strategies for survivors after allo-HSCT. Patients at risk for vaccine failure should be monitored closely during long-term follow-up, and booster immunizations should be considered when there is no seroconversion.Table.Factors associated with negative titers after re-immunizationVaccineFactorOdds ratio95% confidence intervalp value DiphteriaT cell depleted graft5.521.14-26.820.034 TetanusOlder age at immunization1.541.05-2.220.026 Lower IgG level*1.031.00-1.050.033 MeaslesLower IgG level*1.011.00-1.020.022 MumpsHigh risk vs. standard risk2.631.02-6.670.045 RubellaHigher IgM level*1.121.03-1.230.012 High risk vs. standard risk16.71.56-100.000.02 PoliovirusType 1Older age at immunization1.431.05-1.920.021 Positive recipeint CMV titer3.181.58-6.410.001 Higher IgM level*1.081.01-1.150.027 Negative titer before immunization8.332.17-33.330.002 Type 2Older age at immunization1.411.04-1.920.027 Positive recipeint CMV titer2.651.36-5.200.004 Higher IgM level*1.061.00-1.140.04 Negative titer before immunization14.34.55-50.00<0.001 Type 3Older age at immunization1.411.04-1.890.027 Positive recipient CMV titer3.111.67-5.80<0.001 Higher IgM level*1.061.00-1.120.035 Chronic GVHD2.71.05-6.950.04 Negative titer before immunization5.881.92-20.000.002*Total IgG and IgM, not disease specific Ig levels Disclosures: No relevant conflicts of interest to declare.

Blood ◽  
2010 ◽  
Vol 116 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Victoria Bordon ◽  
Andrew R. Gennery ◽  
Mary A. Slatter ◽  
Els Vandecruys ◽  
Genevieve Laureys ◽  
...  

Abstract Cartilage-hair hypoplasia (CHH) is a rare autosomal recessive disease caused by mutations in the RMRP gene. Beside dwarfism, CHH has a wide spectrum of clinical manifestations including variable grades of combined immunodeficiency, autoimmune complications, and malignancies. Previous reports in single CHH patients with significant immunodeficiencies have demonstrated that allogeneic hematopoietic stem cell transplantation (HSCT) is an effective treatment for the severe immunodeficiency, while growth failure remains unaffected. Because long-term experience in larger cohorts of CHH patients after HSCT is currently unreported, we performed a European collaborative survey reporting on 16 patients with CHH and immunodeficiency who underwent HSCT. Immune dysregulation, lymphoid malignancy, and autoimmunity were important features in this cohort. Thirteen patients were transplanted in early childhood (∼ 2.5 years). The other 3 patients were transplanted at adolescent age. Of 16 patients, 10 (62.5%) were long-term survivors, with a median follow-up of 7 years. T-lymphocyte numbers and function have normalized, and autoimmunity has resolved in all survivors. HSCT should be considered in CHH patients with severe immunodeficiency/autoimmunity, before the development of severe infections, major organ damage, or malignancy might jeopardize the outcome of HSCT and the quality of life in these patients.


Blood ◽  
2008 ◽  
Vol 111 (1) ◽  
pp. 439-445 ◽  
Author(s):  
Hulya Ozsahin ◽  
Marina Cavazzana-Calvo ◽  
Luigi D. Notarangelo ◽  
Ansgar Schulz ◽  
Adrian J. Thrasher ◽  
...  

Wiskott-Aldrich syndrome (WAS) is a rare X-linked immunodeficiency with microthrombocytopenia, eczema, recurrent infections, autoimmune disorders, and malignancies that are life-threatening in the majority of patients. In this long-term, retrospective, multicenter study, we analyzed events that occurred in 96 WAS patients who received transplants between 1979 and 2001 who survived at least 2 years following hematopoietic stem-cell transplantation (HSCT). Events included chronic graft-versus-host disease (cGVHD), autoimmunity, infections, and sequelae of before or after HSCT complications. Three patients (3%) died 2.1 to 21 years following HSCT. Overall 7-year event-free survival rate was 75%. It was lower in recipients of mismatched related donors, also in relation with an older age at HSCT and disease severity. The most striking finding was the observation of cGVHD-independent autoimmunity in 20% of patients strongly associated with a mixed/split chimerism status (P < .001), suggesting that residual-host lymphocytes can mediate autoimmune disease despite the coexistence of donor lymphocytes. Infectious complications (6%) related to splenectomy were also significant and may warrant a more restrictive approach to performing splenectomy in WAS patients. Overall, this study provides the basis for a prospective, standardized, and more in-depth detailed analysis of chimerism and events in long-term follow-up of WAS patients who receive transplants to design better-adapted therapeutic strategies.


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