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Mariemadeleine Dolmans - One of the best experts on this subject based on the ideXlab platform.
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evaluation of minimal Disseminated Disease in cryopreserved ovarian tissue from bone and soft tissue sarcoma patients
Human Reproduction, 2016Co-Authors: Mariemadeleine Dolmans, Yuki Iwahara, Jacques Donnez, Michelle Soares, Jeanluc Vaerman, Christiani Andrade Amorim, Helene PoirelAbstract:STUDY QUESTION What is the risk of finding malignant cells in cryopreserved ovarian tissue from sarcoma patients? SUMMARY ANSWER Minimal Disseminated Disease (MDD) was not detected in frozen-thawed ovarian tissue from 26 patients by any of the sensitive methods applied. WHAT IS KNOWN ALREADY In case of leukemia, the risk of malignant cell transmission through the graft is well known and widely documented. However, for bone cancer, like Ewing sarcoma or osteosarcoma, only a small number of case reports, have been published. These cancers often affect prepubertal girls, in whom ovarian tissue cryopreservation and transplantation is the only option to preserve fertility. STUDY DESIGN, SIZE, DURATION The presence of malignant cells in cryopreserved ovarian tissue from patients with bone/soft tissue sarcoma was investigated with Disease-specific markers for each patient, using immunohistochemistry (IHC), FISH and real-time quantitative RT-PCR (qPCR), with the original tumor serving as a positive control. PARTICIPANTS/MATERIALS, SETTING, METHODS Forty-eight sarcoma patients were enrolled in the study, 12 of whom subsequently died. In each case, tissue from the primary tumor was investigated in order to identify markers (immunohistochemical and/or molecular) to analyze the ovarian tissue case by case. Ovarian tissue from osteosarcoma (n = 15), liposarcoma (n = 1) and undifferentiated sarcoma (n = 5) patients could not be evaluated, as no specific markers were detected by FISH or sensitive IHC in any of their primary tumoral tissue. One patient with Li-Fraumeni syndrome was also excluded from the study. IHC analyses were therefore performed on ovarian tissue from 26 patients and qPCR on 19. The primary tumors involved were Ewing sarcoma family of tumors (n = 14), rhabdomyosarcoma (n = 7), synovial sarcoma (n = 2), clear cell sarcoma (n = 2) and a malignant peripheral nerve sheath tumor (n = 1). MAIN RESULTS AND THE ROLE OF CHANCE MDD was not detected in any of the 26 analyzed samples using sensitive techniques in this largest reported series, even from patients who subsequently died and/or those who presented with metastasis (11/26), hence the most aggressive forms of bone cancer. Indeed, anti-CD99 IHC and PCR performed on patients presenting with Ewing sarcoma family of tumors (n = 14) was negative in all cases. In patients with soft tissue sarcoma (n = 12) primitive tumor markers were detected by IHC and were negative in ovarian tissue. PCR could only be performed in 6/12 of these patients, again proving negative. LIMITATIONS, REASONS FOR CAUTION Cryopreserved ovarian fragments to be transplanted cannot be tested, so this analysis of malignant cells cannot guarantee that all cryopreserved fragments will not contain any Disseminated Disease. Moreover, molecular markers are not readily available for all types of tumors. WIDER IMPLICATIONS OF THE FINDINGS These results are reassuring regarding the risk of malignant cells in the ovary for transplantation, as the study involves a large series including different types of sarcomas. We believe this will help clinicians in their patient counseling for fertility preservation and restoration. STUDY FUNDING/COMPETING INTERESTS This work was supported by the Fonds National de la Recherche Scientifique de Belgique-FNRS under Grants Nos 7.4578.14 (Televie to MS) and 5/4/150/5 to MMD. The authors declare no competing financial interests.
Helene Poirel - One of the best experts on this subject based on the ideXlab platform.
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evaluation of minimal Disseminated Disease in cryopreserved ovarian tissue from bone and soft tissue sarcoma patients
Human Reproduction, 2016Co-Authors: Mariemadeleine Dolmans, Yuki Iwahara, Jacques Donnez, Michelle Soares, Jeanluc Vaerman, Christiani Andrade Amorim, Helene PoirelAbstract:STUDY QUESTION What is the risk of finding malignant cells in cryopreserved ovarian tissue from sarcoma patients? SUMMARY ANSWER Minimal Disseminated Disease (MDD) was not detected in frozen-thawed ovarian tissue from 26 patients by any of the sensitive methods applied. WHAT IS KNOWN ALREADY In case of leukemia, the risk of malignant cell transmission through the graft is well known and widely documented. However, for bone cancer, like Ewing sarcoma or osteosarcoma, only a small number of case reports, have been published. These cancers often affect prepubertal girls, in whom ovarian tissue cryopreservation and transplantation is the only option to preserve fertility. STUDY DESIGN, SIZE, DURATION The presence of malignant cells in cryopreserved ovarian tissue from patients with bone/soft tissue sarcoma was investigated with Disease-specific markers for each patient, using immunohistochemistry (IHC), FISH and real-time quantitative RT-PCR (qPCR), with the original tumor serving as a positive control. PARTICIPANTS/MATERIALS, SETTING, METHODS Forty-eight sarcoma patients were enrolled in the study, 12 of whom subsequently died. In each case, tissue from the primary tumor was investigated in order to identify markers (immunohistochemical and/or molecular) to analyze the ovarian tissue case by case. Ovarian tissue from osteosarcoma (n = 15), liposarcoma (n = 1) and undifferentiated sarcoma (n = 5) patients could not be evaluated, as no specific markers were detected by FISH or sensitive IHC in any of their primary tumoral tissue. One patient with Li-Fraumeni syndrome was also excluded from the study. IHC analyses were therefore performed on ovarian tissue from 26 patients and qPCR on 19. The primary tumors involved were Ewing sarcoma family of tumors (n = 14), rhabdomyosarcoma (n = 7), synovial sarcoma (n = 2), clear cell sarcoma (n = 2) and a malignant peripheral nerve sheath tumor (n = 1). MAIN RESULTS AND THE ROLE OF CHANCE MDD was not detected in any of the 26 analyzed samples using sensitive techniques in this largest reported series, even from patients who subsequently died and/or those who presented with metastasis (11/26), hence the most aggressive forms of bone cancer. Indeed, anti-CD99 IHC and PCR performed on patients presenting with Ewing sarcoma family of tumors (n = 14) was negative in all cases. In patients with soft tissue sarcoma (n = 12) primitive tumor markers were detected by IHC and were negative in ovarian tissue. PCR could only be performed in 6/12 of these patients, again proving negative. LIMITATIONS, REASONS FOR CAUTION Cryopreserved ovarian fragments to be transplanted cannot be tested, so this analysis of malignant cells cannot guarantee that all cryopreserved fragments will not contain any Disseminated Disease. Moreover, molecular markers are not readily available for all types of tumors. WIDER IMPLICATIONS OF THE FINDINGS These results are reassuring regarding the risk of malignant cells in the ovary for transplantation, as the study involves a large series including different types of sarcomas. We believe this will help clinicians in their patient counseling for fertility preservation and restoration. STUDY FUNDING/COMPETING INTERESTS This work was supported by the Fonds National de la Recherche Scientifique de Belgique-FNRS under Grants Nos 7.4578.14 (Televie to MS) and 5/4/150/5 to MMD. The authors declare no competing financial interests.
Angelo Rosolen - One of the best experts on this subject based on the ideXlab platform.
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use of minimal Disseminated Disease and immunity to npm alk antigen to stratify alk positive alcl patients with different prognosis
Leukemia, 2013Co-Authors: Lara Mussolin, Marta Pillon, Angelo Rosolen, Christine Dammwelk, Martin Zimmermann, Genny Franceschetto, Karen Pulford, Alfred Reiter, Willi WoessmannAbstract:We studied the prognostic value of minimal Disseminated Disease (MDD) and anti-ALK immune response in children with NPM-ALK-positive anaplastic-large cell lymphoma (ALCL) and evaluated their potential for risk stratification. NPM-ALK transcripts were analyzed by RT-PCR in bone marrow/peripheral blood of 128 ALCL patients at diagnosis, whereas ALK antibody titers in plasma were assessed using an immunocytochemical approach. MDD was positive in 59% of patients and 96% showed an anti-ALK response. Using MDD and antibody titer results, patients could be divided into three biological risk groups (bRG) with different prognosis: high risk (bHR): MDD-positive and antibody titer ≤ 1/750, 26/128 (20%); low risk (bLR): MDD negative and antibody titer >1/750, 40/128 (31%); intermediate risk (bIR): all remaining patients, 62/128 (48%). Progression-free survival was 28% (s.e., 9%), 68% (s.e., 6%) and 93% (s.e., 4%) for bHR, bIR and bLR, respectively (P<0.0001). Survival was 71% (s.e., 9%), 83% (s.e., 5%) and 98% (s.e., 2%) for bHR, bIR and bLR (P=0.02). Only bHR and histology other than common type were predictive of higher risk of failure (hazard ratio 4.9 and 2.7, respectively) in multivariate analysis. Stratification of ALCL patients based on MDD and anti-ALK titer should be considered in future ALCL trials to optimize treatment.
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minimal Disseminated Disease in high risk burkitt s lymphoma identifies patients with different prognosis
Journal of Clinical Oncology, 2011Co-Authors: Lara Mussolin, Marta Pillon, Emanuele S G Damore, Valentino Conter, M Piglione, Luca Lo Nigro, Alberto Garaventa, Salvatore Buffardi, Maurizio Arico, Angelo RosolenAbstract:Purpose To study minimal Disseminated Disease (MDD) in children with Burkitt's lymphoma (BL) and to determine its impact on prognosis. Patients and Methods We established a simplified long-distance polymerase chain reaction (LD-PCR) assay that can amplify up to 15 to 20 Kb of DNA sequence, making it possible to detect the t(8;14) at the genomic level with sensitivity of 10−4. We prospectively studied diagnostic biopsies and bone marrow aspirates from 134 patients affected by BL. Results A specific LD-PCR product was detected in 96 (72%) of 134 BL biopsies. Among 84 patients with t(8;14) positivity on tumor biopsy and bone marrow (BM), 26 (31%) had LD-PCR–positive BM, and 15 (18%) were positive at standard morphologic analysis. Twenty (85%) of 26 MDD-positive patients belonged to the R4 risk group, according to Berlin-Frankfurt-Munster definition. The 3-year progression-free survival was 68% (SE, 10%) in MDD-positive patients in R4 compared with 93% (SE, 5%) in MDD-negative patients in R4 (P = .03). By mul...
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minimal Disseminated Disease in high risk burkitt s lymphoma identifies patients with different prognosis
Journal of Clinical Oncology, 2011Co-Authors: Lara Mussolin, Marta Pillon, Emanuele S G Damore, Valentino Conter, M Piglione, Luca Lo Nigro, Alberto Garaventa, Salvatore Buffardi, Maurizio Arico, Angelo RosolenAbstract:Purpose To study minimal Disseminated Disease (MDD) in children with Burkitt’s lymphoma (BL) and to determine its impact on prognosis. Patients and Methods We established a simplified long-distance polymerase chain reaction (LD-PCR) assay that can amplify up to 15 to 20 Kb of DNA sequence, making it possible to detect the t(8;14) at the genomic level with sensitivity of 10 4 . We prospectively studied diagnostic biopsies and bone marrow aspirates from 134 patients affected by BL. Results A specific LD-PCR product was detected in 96 (72%) of 134 BL biopsies. Among 84 patients with t(8;14) positivity on tumor biopsy and bone marrow (BM), 26 (31%) had LD-PCR–positive BM, and 15 (18%) were positive at standard morphologic analysis. Twenty (85%) of 26 MDD-positive patients belonged to the R4 risk group, according to Berlin-Frankfurt-Munster definition. The 3-year progressionfree survival was 68% (SE, 10%) in MDD-positive patients in R4 compared with 93% (SE, 5%) in MDD-negative patients in R4 (P .03). By multivariate analysis (including MDD, sex, lactate dehydrogenase, CNS involvement), only MDD was predictive of higher risk of failure (hazard ratio, 4.7; P .04). Conclusion MDD identifies a poor-prognosis subgroup among children with high-risk BL. To improve Disease control in these patients, a more effective risk-adapted therapy, possibly including anti-CD20 monoclonal antibody, should be considered. J Clin Oncol 29:1779-1784. © 2011 by American Society of Clinical Oncology
Yuki Iwahara - One of the best experts on this subject based on the ideXlab platform.
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evaluation of minimal Disseminated Disease in cryopreserved ovarian tissue from bone and soft tissue sarcoma patients
Human Reproduction, 2016Co-Authors: Mariemadeleine Dolmans, Yuki Iwahara, Jacques Donnez, Michelle Soares, Jeanluc Vaerman, Christiani Andrade Amorim, Helene PoirelAbstract:STUDY QUESTION What is the risk of finding malignant cells in cryopreserved ovarian tissue from sarcoma patients? SUMMARY ANSWER Minimal Disseminated Disease (MDD) was not detected in frozen-thawed ovarian tissue from 26 patients by any of the sensitive methods applied. WHAT IS KNOWN ALREADY In case of leukemia, the risk of malignant cell transmission through the graft is well known and widely documented. However, for bone cancer, like Ewing sarcoma or osteosarcoma, only a small number of case reports, have been published. These cancers often affect prepubertal girls, in whom ovarian tissue cryopreservation and transplantation is the only option to preserve fertility. STUDY DESIGN, SIZE, DURATION The presence of malignant cells in cryopreserved ovarian tissue from patients with bone/soft tissue sarcoma was investigated with Disease-specific markers for each patient, using immunohistochemistry (IHC), FISH and real-time quantitative RT-PCR (qPCR), with the original tumor serving as a positive control. PARTICIPANTS/MATERIALS, SETTING, METHODS Forty-eight sarcoma patients were enrolled in the study, 12 of whom subsequently died. In each case, tissue from the primary tumor was investigated in order to identify markers (immunohistochemical and/or molecular) to analyze the ovarian tissue case by case. Ovarian tissue from osteosarcoma (n = 15), liposarcoma (n = 1) and undifferentiated sarcoma (n = 5) patients could not be evaluated, as no specific markers were detected by FISH or sensitive IHC in any of their primary tumoral tissue. One patient with Li-Fraumeni syndrome was also excluded from the study. IHC analyses were therefore performed on ovarian tissue from 26 patients and qPCR on 19. The primary tumors involved were Ewing sarcoma family of tumors (n = 14), rhabdomyosarcoma (n = 7), synovial sarcoma (n = 2), clear cell sarcoma (n = 2) and a malignant peripheral nerve sheath tumor (n = 1). MAIN RESULTS AND THE ROLE OF CHANCE MDD was not detected in any of the 26 analyzed samples using sensitive techniques in this largest reported series, even from patients who subsequently died and/or those who presented with metastasis (11/26), hence the most aggressive forms of bone cancer. Indeed, anti-CD99 IHC and PCR performed on patients presenting with Ewing sarcoma family of tumors (n = 14) was negative in all cases. In patients with soft tissue sarcoma (n = 12) primitive tumor markers were detected by IHC and were negative in ovarian tissue. PCR could only be performed in 6/12 of these patients, again proving negative. LIMITATIONS, REASONS FOR CAUTION Cryopreserved ovarian fragments to be transplanted cannot be tested, so this analysis of malignant cells cannot guarantee that all cryopreserved fragments will not contain any Disseminated Disease. Moreover, molecular markers are not readily available for all types of tumors. WIDER IMPLICATIONS OF THE FINDINGS These results are reassuring regarding the risk of malignant cells in the ovary for transplantation, as the study involves a large series including different types of sarcomas. We believe this will help clinicians in their patient counseling for fertility preservation and restoration. STUDY FUNDING/COMPETING INTERESTS This work was supported by the Fonds National de la Recherche Scientifique de Belgique-FNRS under Grants Nos 7.4578.14 (Televie to MS) and 5/4/150/5 to MMD. The authors declare no competing financial interests.
Jacques Donnez - One of the best experts on this subject based on the ideXlab platform.
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evaluation of minimal Disseminated Disease in cryopreserved ovarian tissue from bone and soft tissue sarcoma patients
Human Reproduction, 2016Co-Authors: Mariemadeleine Dolmans, Yuki Iwahara, Jacques Donnez, Michelle Soares, Jeanluc Vaerman, Christiani Andrade Amorim, Helene PoirelAbstract:STUDY QUESTION What is the risk of finding malignant cells in cryopreserved ovarian tissue from sarcoma patients? SUMMARY ANSWER Minimal Disseminated Disease (MDD) was not detected in frozen-thawed ovarian tissue from 26 patients by any of the sensitive methods applied. WHAT IS KNOWN ALREADY In case of leukemia, the risk of malignant cell transmission through the graft is well known and widely documented. However, for bone cancer, like Ewing sarcoma or osteosarcoma, only a small number of case reports, have been published. These cancers often affect prepubertal girls, in whom ovarian tissue cryopreservation and transplantation is the only option to preserve fertility. STUDY DESIGN, SIZE, DURATION The presence of malignant cells in cryopreserved ovarian tissue from patients with bone/soft tissue sarcoma was investigated with Disease-specific markers for each patient, using immunohistochemistry (IHC), FISH and real-time quantitative RT-PCR (qPCR), with the original tumor serving as a positive control. PARTICIPANTS/MATERIALS, SETTING, METHODS Forty-eight sarcoma patients were enrolled in the study, 12 of whom subsequently died. In each case, tissue from the primary tumor was investigated in order to identify markers (immunohistochemical and/or molecular) to analyze the ovarian tissue case by case. Ovarian tissue from osteosarcoma (n = 15), liposarcoma (n = 1) and undifferentiated sarcoma (n = 5) patients could not be evaluated, as no specific markers were detected by FISH or sensitive IHC in any of their primary tumoral tissue. One patient with Li-Fraumeni syndrome was also excluded from the study. IHC analyses were therefore performed on ovarian tissue from 26 patients and qPCR on 19. The primary tumors involved were Ewing sarcoma family of tumors (n = 14), rhabdomyosarcoma (n = 7), synovial sarcoma (n = 2), clear cell sarcoma (n = 2) and a malignant peripheral nerve sheath tumor (n = 1). MAIN RESULTS AND THE ROLE OF CHANCE MDD was not detected in any of the 26 analyzed samples using sensitive techniques in this largest reported series, even from patients who subsequently died and/or those who presented with metastasis (11/26), hence the most aggressive forms of bone cancer. Indeed, anti-CD99 IHC and PCR performed on patients presenting with Ewing sarcoma family of tumors (n = 14) was negative in all cases. In patients with soft tissue sarcoma (n = 12) primitive tumor markers were detected by IHC and were negative in ovarian tissue. PCR could only be performed in 6/12 of these patients, again proving negative. LIMITATIONS, REASONS FOR CAUTION Cryopreserved ovarian fragments to be transplanted cannot be tested, so this analysis of malignant cells cannot guarantee that all cryopreserved fragments will not contain any Disseminated Disease. Moreover, molecular markers are not readily available for all types of tumors. WIDER IMPLICATIONS OF THE FINDINGS These results are reassuring regarding the risk of malignant cells in the ovary for transplantation, as the study involves a large series including different types of sarcomas. We believe this will help clinicians in their patient counseling for fertility preservation and restoration. STUDY FUNDING/COMPETING INTERESTS This work was supported by the Fonds National de la Recherche Scientifique de Belgique-FNRS under Grants Nos 7.4578.14 (Televie to MS) and 5/4/150/5 to MMD. The authors declare no competing financial interests.