Dexamethasone does not prevent malignant cell reintroduction in leukemia patients undergoing ovarian transplant: risk assessment of leukemic cell transmission by a xenograft model.

STUDY QUESTION: Does dexamethasone (DXM) incubation avoid the reintroduction of leukemic malignant cells after ovarian tissue retransplantation in vivo? SUMMARY ANSWER: DXM incubation prior to retransplantation of ovarian tissue does not prevent reintroduction of leukemic cells. WHAT IS KNOWN ALREADY: Retransplantation of cryopreserved ovarian cortex from patients diagnosed with acute lymphoblastic leukemia (ALL) involves a risk of reintroducing malignant cells. DXM treatment is effective at inducing leukemic cell death in vitro. STUDY DESIGN, SIZE, DURATION: This was an experimental study where ovarian cortex fragments from patients with ALL were randomly allocated to incubation with or without DXM (n = 11/group) and grafted to 22 immunodeficient mice for 6 months. In a parallel experiment, 22 immunodeficient mice were injected i.p. with varying amounts of RCH-ACV ALL cells (human leukemia cell line) and maintained for 4 months. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cryopreserved ovarian fragments from patients with ALL were exposed in vitro to 0.4 µM DXM or basal media (control) prior to xenograft into ovariectomized severe combined immunodeficiency (SCID) mice (experiment 1). After 6 months of monitoring, leukemia cell contamination was assessed in ovarian grafts and mouse organs by histology, PCR (presence of mouse mtDNA and absence of p53 were together considered a negative result for the presence of human cells) and detection of immunoglobulin monoclonality and specific ALL markers if present in the patient.In experiment 2, a series of 22 immunodeficient female mice was injected with specific doses of the leukemia cell line RCH-ACV (103 - 5 × 106, n = 4/group) to assess the engraftment competence of the SCID model. MAIN RESULTS AND THE ROLE OF CHANCE: ALL metastatic cells were detected, by PCR, in five DXM-treated and one control human ovarian tissue graft as well as in a control mouse liver, although malignant cell infiltration was not detected by histology in any sample after 6 months. In total, minimal residual disease was present in three DXM-treated and three control mice.RCH-ACV cells were detected in liver and spleen samples after the injection of as little as 103 cells, although only animals receiving 5 × 106 cells developed clinical signs of disease and metastases. LIMITATIONS, REASONS FOR CAUTION: This is an experimental study where the malignant potential of leukemic cells contained in human ovarian tissues has been assessed in immunodeficient mice. WIDER IMPLICATIONS OF THE FINDINGS: These results indicate that DXM incubation prior to retransplantation of ovarian tissue does not prevent reintroduction of leukemic cells. Therefore, caution should be taken in retransplanting ovarian tissue from patients with leukemia until safer systems are developed, as leukemic cells present in ovarian grafts were able to survive, proliferate and migrate after cryopreservation and xenograft. STUDY FUNDING/COMPETING INTEREST(S): Funded by the Regional Valencian Ministry of Education (PROMETEO/2018/137) and by the Spanish Ministry of Economy and Competitiveness (PI16/FIS PI16/01664 and PTQ-16-08222 for S.H. participation). There are no competing interests.

Childhood cancer: improved prospects for survival but is prevention possible?

With optimum treatment 65-70% of children diagnosed with cancer should be long term survivors and probably cured. Prevention is better than cure. Recent studies into the causes of childhood malignancy are reviewed. The incidence of childhood acute lymphoblastic leukaemia (ALL) is steadily increasing. The cause for this may be increasing social and economic development. Exposure to electromagnetic fields has been a cause of concern for almost 20 years. A recent large case control study has shown no increased risk of cancer or leukaemia in those who have measurably increased exposure to electromagnetic fields. Leukaemia which has the cytogenetic abnormality 11q23 or MLL gene rearrangement characteristically occurs as a second malignancy after exposure to epipodophyllotoxins which act by inhibiting topoisomerase. Infant leukaemia has the same cytogenetic profile. Mothers of babies who develop infant leukaemia have high exposure to potential dietary inhibitors of topoisomerase during pregnancy. Clusters of leukaemia can probably best be accounted for by population mixing. There may be an increased risk of ALL following vitamin K given to newborns.