Age: 7.0
Sex: M
Vaccine: DTP, HEP, HIBV, IPV, MMR, VARCEL, DTAP, HEP, HIBV, IPV, MMR, VARCEL
Symptoms: Bone marrow oedema, C-reactive protein increased, CD4 lymphocytes, CD8 lymphocytes, Clostridium test negative
Clinical narrative: This literature marketed report was received from a physician concerning to a 7 year old male patient with a history of recurrent acute lymphoblastic leukemia (ALL) which was initially diagnosed at the age of 2 years and was treated per chemotherapy protocol COG-AALL0331. He was then in remission for more than 1 year until he relapsed at 4 years of age and received treatment per chemotherapy protocol COG-AALL02P2. The medical history of the patient included femur fracture that healed after closed reduction and casting and insertion and subsequent removal of a port-a-cath. Family history is noncontributory. There was no recent history of nausea, vomiting, diarrhea, cough, ear pain, dysuria, weakness, malaise, confusion, or syncope. In addition, there was no recent history of travel or camping, no known sick contacts, and no known trauma. The patient had received all recommended vaccines up to 18 months of age according to the Centers for Disease Control and Preventions Advisory Committee on Immunization Practices recommended schedule. On an unknown date, the patient was vaccinated with MMR (manufacturer unknown) 1 dose (lot number, expiry date, dose and route unspecified), Hib (manufacturer unknown) 4 doses (lot number, expiry date, dose and route unspecified), varicella virus vaccine live (manufacturer unknown) 1 dose (lot number, expiry date, dose and route unspecified) and Hep B Vaccine (manufacturer unknown) 3 doses (lot number, expiry date, dose and route unspecified). Concomitant therapies included DTP (manufacturer unknown) 4 doses, IPV (manufacturer unknown) 3 doses. All the vaccines were given more than 6 month before his diagnosis of ALL. Varicella-Zoster Virus (VZV) immunity was documented before initiation of chemotherapy, although anti-Hib antibody testing was not performed before chemotherapy. On an unknown date, the patient presented to his primary care pediatrician clinic with a 2-day history of worsening right hip pain with weight-bearing activities. 6 days previously, the patient had a single elevated temperature of 100.2 degree Fahrenheit (F), which resolved the same day and he had since remained afebrile. The patient was transferred to the hospital for admission and started on intravenous (IV) antibiotics for Gram-negative diplococci revealed by blood cultures. On physical examination the patient was afebrile with normal vital signs. The physical examination was unremarkable except for tenderness to palpation in the right groin without warmth, swelling or erythema. Range of motion at the hip was normal, although there was discomfort with extension and abduction of the right leg. The gait was antalgic, favoring the left side. The complete blood count and manual differential were within normal limits. The urine analysis was normal and patient's serum C-reactive protein was elevated at 7.0 mg/dl. Magnetic resonance imaging (MRI) of right hip showed a large right hip joint effusion and bone marrow edema of the femoral neck that was interpreted as suspicious for osteomyelitis and septic arthritis. Arthrocentesis of the right hip and bone biopsy of the femoral neck revealed no pathologic evidence of malignancy and minimally inflammatory joint fluid (3100 white blood cells per cubic millimeter). Although cultures (after initiation of antibiotics) were negative, osteomyelitis was presumed to be the cause of bone marrow edema. After 6 days of improvement in the patient's symptoms and a decrease in his C-reactive protein, the patient was discharged to home to complete 10 days of IV antibiotic therapy followed by another 32 days of oral therapy. The pathogen on the initial blood cultures was identified as Hib. The patient returned to clinic, and titers were drawn to assess his immunity to previous vaccinations. The patient had negative serum IgG for varicella zoster virus (VZV), measles, hepatitis B, tetanus, pertussis, and diphtheria, although he did still retain evidence of immunity to polio, with titers of 1:8 (polio 1), 1:64 (polio 2), and 1:128 (polio 3). He also had detectable Hib antibodies 4 weeks after his initial presentation. Subsequent immune workup revealed normal quantitative immunoglobulins, normal lymphocyte subsets (normal CD3, CD4, CD8, and CD19, according to Harriet Lane normal values; and normal CD2, natural killer cells, CD45RA, and CD45RO according to reference laboratory standards and normal lymphocyte proliferation in response to mitogens with absent quantitative response to tetanus antigen. A complete reimmunization schedule was undertaken. Pathogen-specific antibody testing revealed detectable antibodies to polio but not measles, mumps, rubella, varicella-zoster virus, tetanus, diphtheria, pertussis, or hepatitis B. This loss of immunologic memory appears to be a rarely described side effect of ALL chemotherapy and osteomyelitis caused by Haemophilus influenzae type b (Hib), for which he had been vaccinated. The mechanisms of defects after chemotherapy may include a deficiency of both naive and memory T-helper cells, as well as a lack of circulating antibodies. The intensity of chemotherapy also seems to be an important factor in loss of immune memory. The author concluded that we present the first case we are aware of in which a fully vaccinated ALL relapse survivor presented with invasive Hib. Additional information has been requested.