Minimal residual disease quantification in ovarian tissue collected from patients in complete remission of acute leukemia

Abstract

Ovarian tissue cryopreservation (OTC) is offered to women treated for acute leukemia to preserve their fertility before hematopoietic stem cell transplantation. The risk of leukemic infiltration in ovarian samples harvested before administration of chemotherapy limits ovarian tissue transplantations. We assessed the minimal residual disease (MRD) by sensitive quantitative polymerase chain reaction in cryopreserved ovarian cortex and medulla samples harvested from 30 patients in complete remission of acute leukemia, including 60 % with negative bone marrow MRD at the time of OTC. Ovarian MRD was undetectable in 21 patients (70%), detectable below 10-4 in 8 patients (27%) and between 10-3 and 10-4 in 1 patient (3%). Twenty patients (67%) had concordant MRD between bone marrow and ovarian samples. Interestingly 4 patients had positive MRD in ovarian samples while undetectable in bone marrow. Our results underline the importance of reaching the best control of the disease with undetectable or low MRD levels before OTC to minimize the risk of ovarian leukemic infiltration. The discordant results between ovarian samples and bone marrow require to test the more ovarian samples available before considering ovarian tissue transplantation.

Minimal residual disease detection by multicolor flow cytometry in cryopreserved ovarian tissue from leukemia patients

“…However, molecular analysis could be performed just before autotransplantation of ovarian cortex to con rm MFC results, as was done in patient 2, for example. The ndings presented in this study are congruent with previous reports from other teams [34,35,38,40].…”

“…MRD evaluation in the residual medulla, when available, is recommended by ESHRE [22]. In our study, MRD results for the cortex and medulla were concordant in 3 patients, and in line with a recent study where 20/24 MRD results were concordant [40].…”

“…In hematology laboratories, two methods are currently used for MRD monitoring in blood or bone marrow, namely polymerase chain reaction (PCR) ampli cation of speci c transcripts or Ig gene rearrangements, and detection of leukemia-associated immunophenotype by multicolor ow cytometry (MFC) [28][29][30]. Some studies have investigated the detection of minimal residual disease (MRD) in cryopreserved ovarian tissue using molecular techniques [31][32][33][34][35][36][37][38][39][40], xenograft of cryopreserved ovarian tissue in immunode cient mice [34,35,39,41] and next-generation sequencing [41] to highlight the presence of malignant cells. To detect MRD in ovarian tissue by MFC, it is necessary to identify markers that enable the differentiation of leukemic cells from viable ovarian cells by the use of leukemia-associated immunophenotypes (LAIP).…”

Successful pregnancies after transplantation of ovarian tissue retrieved and cryopreserved at time of childhood acute lymphoblastic leukemia – A case report

“…Importantly, studies have shown that OTC retrieved after the patient has achieved complete remission in the bone marrow in most cases also is negative for leukemia markers in the cryopreserved ovarian tissue (8,13,14) and OTCs that scored negative for molecular leukemic markers did not transfer leukemia to the recipient mice (13). In a recent study Chevillon and coworkers investigated the presence of minimal residual disease (MRD) in OTC harvested from acute leukemia patients that achieved complete remission and showed significant concordance between bone marrow and OT; however, 4/9 discordant patients had undetectable MRD in the bone marrow while positive in the OT (15).…”

“… 13 In a recent study Chevillon and co-workers investigated the presence of minimal residual disease (MRD) in OTC harvested from acute leukemia patients that achieved complete remission and showed significant concordance between bone marrow and OT; however, four of nine discordant patients had undetectable MRD in the bone marrow while positive in the OT. 15 …”