Reimplantation of cryopreserved ovarian tissue from patients with acute lymphoblastic leukemia is potentially unsafe

Abstract

Ovarian tissue cryopreservation is currently proposed to young cancer patients to preserve their fertility before radiochemotherapy. The potential risk is that the tissue might harbor malignant cells that could induce disease recurrence. We therefore decided to evaluate the presence of leukemic cells in cryopreserved ovarian tissue from 18 leukemic patients: 6 with chronic myeloid leukemia (CML) and 12 with acute lymphoblastic leukemia (ALL). In each case, histology, quantitative reverse-transcribed polymerase chain reaction (RT-PCR) and long-term (6 months) xenografting to immunodeficient mice were used. Histology did not identify any malignant cells in the ovarian tissue. By quantitative RT-PCR, 2 of 6 CML patients were positive for BCR-ABL in their ovarian tissue. Among the 12 ALL patients, 7 of the 10 with available molecular markers showed positive leukemic markers in their ovarian tissue (translocations or rearrangement genes). Four mice grafted with ovarian tissue from ALL patients developed intraperitoneal leukemic masses. In conclusion, this study demonstrates, by quantitative RT-PCR, ovarian contamination by malignant cells in acute as well as chronic leukemia, whereas histology fails to do so. Moreover, chemotherapy before ovarian cryopreservation does not exclude malignant contamination. Finally, reimplantation of cryopreserved ovarian tissue from ALL and CML patients puts them at risk of disease recurrence.

Is transplantation of cryopreserved ovarian tissue from patients with advanced-stage breast cancer safe? A pilot study

“…Breast tumor tissue (infiltrating ductal carcinoma) was grafted to an additional SCID mouse as a positive control for long-term xenografting. The grafting protocol used in this study was the same as previously described [11]. Briefly, a small median slit was made in the abdomen and peritoneum of the animals, and human ovarian tissue strips were fixed to the inner side of the peritoneum with one or two stitches of 6-0 Prolene (Fig.…”

“…Morphological and immunohistochemical studies may not be sensitive or specific enough to identify malignant microinvasion of ovarian tissue, and more sensitive methods such as long-term xenografting and qPCR analyses are mandatory. These techniques were used to detect leukemic cells in cryopreserved ovarian tissue [11], with qPCR proving positive in 9 out of 16 ovarian tissue samples from leukemia patients. After xenografting, 4 out of 12 mice presented with malignant invasion.…”

“…Indeed, it is impossible to find a PCR marker which is 100 % sensitive and specific for breast cancer cells. Ideally, a disease-specific marker should be identified for each patient, but it is not always available [9][10][11]. In our study, we selected the MGB2 gene as one of the most specific markers to detect malignant breast cells, but because of the limited quantity of ovarian tissue available for this study, we were able to assess the presence of only one gene.…”

Is transplantation of a few leukemic cells inside an artificial ovary able to induce leukemia in an experimental model?

“…Several studies have identified malignant cells in cryopreserved ovarian tissue of leukemia patients by sensitive PCR [17][18][19] and flow cytometry [20] analysis. In one study, the tumor-inducing potential of leukemic cells present in ovarian tissue was demonstrated in a xenografting model [18].…”

“…Several studies have identified malignant cells in cryopreserved ovarian tissue of leukemia patients by sensitive PCR [17][18][19] and flow cytometry [20] analysis. In one study, the tumor-inducing potential of leukemic cells present in ovarian tissue was demonstrated in a xenografting model [18]. In another study, however, ovarian tissue from patients in complete remission did not appear to contain any viable malignant cells; although PCR results were positive, none of the grafted mice developed the disease [21].…”