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PEDIATRICS Vol. 109 No. 6 January 2002, pp. e91

ELECTRONIC ARTICLE

Current Chemotherapy Protocols for Childhood Acute Lymphoblastic Leukemia Induce Loss of Humoral Immunity to Viral Vaccination Antigens

Anna Nilsson, MD*,{ddagger}, Angelo De Milito, MS{ddagger}, Pär Engström, MS{ddagger}, Margareta Nordin, MD§, Mitsuo Narita, MD||, Lena Grillner, MD, PhD{ddagger},§, Francesca Chiodi, PhD{ddagger} and Olle Björk, MD, PhD*

* Pediatric Cancer Research Unit, Astrid Lindgren Children Hospital, Stockholm, Sweden
{ddagger} Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden
§ Department of Clinical Microbiology, Karolinska Hospital, Stockholm, Sweden
|| Department of Pediatrics, Hokkaido University, Sapporo, Japan

--> Objective. To evaluate viral vaccination immunity and booster responses in children treated successfully for acute lymphoblastic leukemia by chemotherapy and to study the response to treatment of antibody-producing plasma cells that are important for persistence of humoral immunity.

Methods. Forty-three children who were in continuous first remission for a median of 5 years (range: 2–12 years) were studied. Before the leukemia was diagnosed, all children had been immunized against measles, mumps, and rubella according to the Swedish National immunization program. We analyzed levels of serum antibodies against measles and rubella by enzyme immunoassays. Avidity tests for measles antibodies were concomitantly performed by enzyme-linked immunosorbent assay for measles virus immunoglobulin G detection. The proportion of plasma cells in bone marrow was studied by flow cytometry at different times during treatment and follow-up. Children who lacked protective levels of antibodies to vaccination antigens were reimmunized. Serum was collected 3 months after immunization to assess vaccination responses.

Results. After completion of the treatment, only 26 of the 43 children (60%) were found to be immune against measles and 31 (72%) against rubella. The proportion of bone marrow plasma cells decreased during treatment but returned to normal after 6 months. Revaccination caused both primary and secondary immune responses. Six of the 14 children without immunity failed to achieve protective levels of specific antibodies against measles and 3 against rubella.

Conclusions. Our finding of loss of antibodies against measles and rubella in children treated with intensive chemotherapy suggests that reimmunization of these patients is necessary after completion of the treatment. To determine reimmunization schedules for children treated with chemotherapy, vaccination responses need to be studied further.

Key Words: children • acute leukemia • humoral immunity • immunization

Abbreviations: ALL, acute lymphoblastic leukemia • Ig, immunoglobulin • BM, bone marrow • MMR, measles, mumps, and rubella • SR, standard risk • IR, intermediate risk • HR, high risk • PBS, phosphate-buffered saline

Received for publication Dec 19, 2001; Accepted May 5, 2002.




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