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

Abstract

ABSTRACT. 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. A n increasing number of children survive leukemia as a result of improved and more intense chemotherapy. Other factors that influence outcome are improved supportive care including platelet transfusions, treatment with growth factors such as granulocyte colony-stimulating factor, and prophylactic antibiotic treatment. 1,2 Few studies have focused on potential long-term immunologic consequences of chemotherapy in survivors of childhood leukemia. Short-term (Ͻ2 years) effects of chemotherapy on immune function have previously been documented in children who were treated for malignancies, including acute lymphoblastic leukemia (ALL). 3,4 In those children, severe Band T-cell depletion results in clinical complications related to immune incompetence, 5,6 although the total B-and T-cell counts resolve quantitatively 6 months to 1 year after cessation of therapy. [7][8][9][10] In earlier studies, children who were treated with chemotherapy had lower levels of antibodies against common viral vaccination antigens such as measles, mumps, rubella, and polio. 11 The clinical implications, if any, of this finding are not completely und...

Humoral immunity to diphtheria, tetanus, measles, and hemophilus influenzae type b in children with acute lymphoblastic leukemia and response to re‐vaccination

“…We agree with the recommendation of many others that ALL patients should be re-vaccinated following completion of chemotherapy [3,6,21,24]. Only Fioredda et al [23] considered administration of another complete vaccination schedule to each ALL subject over treatment taking into account the economical aspect of vaccines and laboratory kits.…”

“…In Ercan et al's [17] study from our country only 29% of the patients had protective levels after chemotherapy. In Nilsson et al's [6] study of 43 ALL patients 60% were immune for measles after chemotherapy. Measles antibodies were measured in 16 of these patients at diagnosis and levels were significantly higher than post-chemotherapy levels.…”

“…In Ercan et al's [17] study similar seroconversion rates were achieved. In Nilsson et al's [6] study 14 ALL patients without immunity against measles were re-vaccinated after chemotherapy and only 8 patients (57%) responded. Patel et al [21] reported higher re-vaccination responses (94%) in patients with ALL and AML.…”

“…In the United Kingdom a booster of each vaccine 6 months after completion of chemotherapy was recommended [25]. Underestimation of re-vaccination may contribute to the spread of viral infections such as measles in the society [6].…”

“…Resolution of any immune defect in children who are disease-free occurs within 6 months to 1 year [1]. Previous studies described immune abnormalities after the completion of chemotherapy [4][5][6], suggesting a persistent immunodeficiency in these children. However, other studies have provided conflicting evidence of normal [7] or abnormal [8] immune responses in these children, although all these studies were conducted during or immediately after the completion of chemotherapy.…”