Sex: F
Vaccine: HIBV, PPV
Symptoms: Intensive care, Lymphocyte count abnormal, Lymphocyte count normal, Neutropenia, Neutrophil count normal
Clinical narrative: negative IgG titers to diphtheria and Haemophilus influenza type B vaccine/ patient has immune dysfunction/did not result in any functional IgG production again pneumococcus; This literature marketed report has been received from the authors of a published literature article, titled as stated below and refers to a female patient of unknown age. The patient was born via donor embryo to a 46-year-old woman, who had been diagnosed with preB-cell acute lymphoblastic leukemia during her 18th week of pregnancy. The mother received 3 cycles of chemotherapy with cyclophosphamide, doxorubicin, vincristine, dexamethasone, and 5 cycles of rituximab. A bone marrow biopsy at 21 weeks gestation demonstrated leukemia remission. The last chemotherapy cycle was completed by 28 weeks, the last dose of rituximab was completed at 27 weeks. The mother had complete blood count recovery before the planned cesarean section at 30 weeks gestational age. The newborn patient had a relatively uncomplicated neonatal intensive care unit course, she did not require intubation or ventilator support, and was able to be discharged by 7 weeks of life. The infant did not receive maternal breast milk to minimize any potential for further rituximab exposure. Her complete blood count (CBC) at delivery was within normal limits: white blood cell count 12.1×10^3/mcL, absolute lymphocyte count (ALC) was 1600/mcL (normal 29 to 31 weeks gestational age ALC: 3219/mcL [800 to 5800]), absolute neutrophil count (ANC) 9922/mcL (normal 29 to 31 wk gestational age ANC: 12000/mcL [7800 to 14500]), hemoglobin 11.4 g/dL, and platelets 447×10^3/mcL. Despite this severe lymphopenia, a repeat CBC on day of life 2 revealed improved ALC of 2530 mcL. She received 1 red blood cell transfusion for a drop in hemoglobin to 9.8 g/dL at day 3 of life. The infant had 2 normal newborn screens.   On unknown dates, she was vaccinated with haemophilus b conjugate vaccine (meningococcal protein conjugate)(manufacturer unknown) and pneumococcal vaccine, polyvalent (23-valent) (manufacturer unknown) for prophylaxis (dose #, exact doses, routes, anatomical locations, lot # and expiration dates were not reported). Other vaccines included: tetanus, hepatitis B, polio strain 1 and diphtheria.  At 10 weeks of life during a scheduled follow-up, the patient was found to be severely neutropenic with an ANC of 0 in addition to severe hypogammaglobulinemia with immunoglobulin (Ig)G of 62mg/dL (normal: 206 to 601; 95% confidence interval, for age 2mo). Because of fever following her 2 months immunizations, the patient was admitted and was treated with intravenous immunoglobulin (IVIG)×2 doses which resulted in the improvement of her ANC to 528. A neutrophil antibody screening test was not done at this time but based on improvement of ANC following IVIG infusion. With concern for recurrent neutropenia, the decision was made to give her intermittent granulocyte colony stimulation factor 5mcg/kg with gradual return of her ANC to normal levels without granulocyte colony stimulation factor by 9 months of age, where it has remained. However, the patient has continued to have severe hypogammaglobulinemia requiring IVIG every 4 to 8 weeks to maintain IgG> 400 mg/dL. At 10 months of life she demonstrated improvement in IgM levels but continued to have a severe deficiency in IgG and IgA. Lymphocyte subset analysis by flow cytometry at 10 and 15 months of age demonstrated a grossly normal number of B cells: 1410 and 1797 cells/µL, respectfully (normal range of 600 to 2700 cells/µL); her IgM levels were close to normal at 10 months (patient: 30 mg/dL, normal 82 mg/dL (41 to 149 mg/dL) and in the normal range at 15 months of age (patient: 61 mg/dL, normal 93 mg/dL [43 to 173 mg/dL]); however, she remains profoundly deficient in IgG with nadirs below 300. At 19 months of age, further evaluation by flow cytometry revealed this B-cell population consisted of IgM-only memory B cells, with no evidence of the next stage in development of the B cell to an IgG antibody secreting, class switched B cell. Repeat B-cell phenotyping at 24 months of age continued to demonstrate a complete absence of class switched B cells and the patient remains on IVIG infusions to maintain IgG levels >400 mg/dL. The patient is currently 4 years of age. Attempts at weaning off the IVIG have failed thus far. Spacing IVIG to 6-week intervals (~2 half lifes) resulted in IgG levels <300 mg/dL (normal, 728 mg/dL [441 to 1135 mg/dL]) and a recurrent stye. Given her frequent IVIG infusions, it is difficult to interpret vaccine response, the patient has demonstrated variable response to protein antigen vaccines. She had potential positive response to tetanus, hepatitis B, polio strain 1 vaccines, with unknown longevity of the response. She had negative IgG titers to diphtheria and Haemophilus influenza type B vaccine suggesting that positive antibody titers to other vaccines may not be real. Remarkably, the patient has had few infections despite her immunologic dysfunction. The outcome of the event was unknown. Multiple attempts at giving the patient other vaccines such as pneumococcal polysaccharide vaccine combined with spreading IVIG out up to 3 months did not result in any functional IgG production again pneumococcus suggesting continued immune dysregulation in this patient.  The reporter considered the event to be related to suspect vaccines.   A copy of the published article is attached as further documentation of the patient's experience.