RT-PCR evaluation of peripheral blood, bone marrow and peripheral blood stem cells in children and adolescents undergoing VACIME chemotherapy for Ewing's sarcoma and alveolar rhabdomyosarcoma

Peripheral blood stem cell support allows dose intensification of multiple cycle chemotherapy for metastatic tumors, including pediatric sarcomas. The VACIME protocol (vincristine, adriamycin, cyclophosphamide, ifosfamide, mesna and etoposide) utilizes peripheral blood stem cells (PBSC) collected fo...

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Veröffentlicht in:Bone marrow transplantation (Basingstoke) 1999-09, Vol.24 (5), p.527-533
Hauptverfasser: THOMSON, B, HAWKINS, D, FELGENHAUER, J, RADICH, J. P
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HAWKINS, D
FELGENHAUER, J
RADICH, J. P
description Peripheral blood stem cell support allows dose intensification of multiple cycle chemotherapy for metastatic tumors, including pediatric sarcomas. The VACIME protocol (vincristine, adriamycin, cyclophosphamide, ifosfamide, mesna and etoposide) utilizes peripheral blood stem cells (PBSC) collected following the treatment cycle as support for subsequent dose- and time-intensive chemotherapy. A critical assumption is that PBSC collected in this manner will be purged of residual tumor cells in vivo. We tested this assumption using sensitive reverse-transcriptase polymerase chain reaction (RT-PCR) to assess the presence of the characteristic translocations of the Ewing's sarcoma family of tumors (ESFT) and alveolar rhabdomyosarcoma (ARMS), t(11;22), and t(2;13), respectively. We used RT-PCR to evaluate 122 samples of peripheral blood (PB), bone marrow (BM) and PBSC collected from 12 pediatric patients with metastatic ESFT and ARMS. The samples included pre-therapy BM and PB, as well as BM, PB, and PBSC collections at various times in the VACIME treatment course. Molecular evidence of tumor contamination was detected in 1/40 PBSC collections from 12 patients. In all patients, we documented clearance of disease by RT-PCR in peripheral blood and bone marrow by week 9 of the VACIME protocol. In vivo purging in combination with the intensive VACIME regime appears to be effective in removing tumor cells from PBSC, bone marrow, and peripheral blood as detected by RT-PCR.
doi_str_mv 10.1038/sj.bmt.1701939
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P</creator><creatorcontrib>THOMSON, B ; HAWKINS, D ; FELGENHAUER, J ; RADICH, J. P</creatorcontrib><description>Peripheral blood stem cell support allows dose intensification of multiple cycle chemotherapy for metastatic tumors, including pediatric sarcomas. The VACIME protocol (vincristine, adriamycin, cyclophosphamide, ifosfamide, mesna and etoposide) utilizes peripheral blood stem cells (PBSC) collected following the treatment cycle as support for subsequent dose- and time-intensive chemotherapy. A critical assumption is that PBSC collected in this manner will be purged of residual tumor cells in vivo. We tested this assumption using sensitive reverse-transcriptase polymerase chain reaction (RT-PCR) to assess the presence of the characteristic translocations of the Ewing's sarcoma family of tumors (ESFT) and alveolar rhabdomyosarcoma (ARMS), t(11;22), and t(2;13), respectively. 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Graft versus host reaction ; Bone Neoplasms - blood ; Bone Neoplasms - drug therapy ; Bone Neoplasms - genetics ; Bone tumors ; Chemotherapy ; Child ; Children ; Chromosomes, Human, Pair 11 - genetics ; Chromosomes, Human, Pair 11 - ultrastructure ; Chromosomes, Human, Pair 13 - genetics ; Chromosomes, Human, Pair 13 - ultrastructure ; Chromosomes, Human, Pair 2 - genetics ; Chromosomes, Human, Pair 2 - ultrastructure ; Chromosomes, Human, Pair 22 - genetics ; Chromosomes, Human, Pair 22 - ultrastructure ; Combined Modality Therapy ; Contamination ; Cyclophosphamide ; Cyclophosphamide - administration & dosage ; Cyclophosphamide - adverse effects ; DNA-Binding Proteins - genetics ; Doxorubicin - administration & dosage ; Doxorubicin - adverse effects ; Etoposide ; Etoposide - administration & dosage ; Etoposide - adverse effects ; Evaluation ; Ewings sarcoma ; Female ; Forkhead Box Protein O1 ; Forkhead Transcription Factors ; Hematopoietic Stem Cell Transplantation ; Hematopoietic stem cells ; Hematopoietic Stem Cells - drug effects ; Humans ; Ifosfamide ; Ifosfamide - administration & dosage ; Ifosfamide - adverse effects ; Male ; Medical sciences ; Mesna - administration & dosage ; Mesna - adverse effects ; Metastases ; Metastasis ; Neoplasm Proteins - genetics ; Neoplastic Cells, Circulating ; Oncogene Proteins, Fusion - genetics ; Paired Box Transcription Factors ; Patients ; PAX3 Transcription Factor ; Pediatrics ; Peripheral blood ; Polymerase chain reaction ; Proto-Oncogene Protein c-fli-1 ; Purging ; Reverse Transcriptase Polymerase Chain Reaction ; Rhabdomyosarcoma ; Rhabdomyosarcoma, Alveolar - blood ; Rhabdomyosarcoma, Alveolar - drug therapy ; Rhabdomyosarcoma, Alveolar - genetics ; RNA-Binding Protein EWS ; Sarcoma ; Sarcoma, Ewing - blood ; Sarcoma, Ewing - drug therapy ; Sarcoma, Ewing - genetics ; Sensitivity and Specificity ; Soft Tissue Neoplasms - blood ; Soft Tissue Neoplasms - drug therapy ; Soft Tissue Neoplasms - genetics ; Stem cell transplantation ; Stem cells ; Transcription Factors - genetics ; Transfusions. 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P</creatorcontrib><title>RT-PCR evaluation of peripheral blood, bone marrow and peripheral blood stem cells in children and adolescents undergoing VACIME chemotherapy for Ewing's sarcoma and alveolar rhabdomyosarcoma</title><title>Bone marrow transplantation (Basingstoke)</title><addtitle>Bone Marrow Transplant</addtitle><description>Peripheral blood stem cell support allows dose intensification of multiple cycle chemotherapy for metastatic tumors, including pediatric sarcomas. The VACIME protocol (vincristine, adriamycin, cyclophosphamide, ifosfamide, mesna and etoposide) utilizes peripheral blood stem cells (PBSC) collected following the treatment cycle as support for subsequent dose- and time-intensive chemotherapy. A critical assumption is that PBSC collected in this manner will be purged of residual tumor cells in vivo. We tested this assumption using sensitive reverse-transcriptase polymerase chain reaction (RT-PCR) to assess the presence of the characteristic translocations of the Ewing's sarcoma family of tumors (ESFT) and alveolar rhabdomyosarcoma (ARMS), t(11;22), and t(2;13), respectively. We used RT-PCR to evaluate 122 samples of peripheral blood (PB), bone marrow (BM) and PBSC collected from 12 pediatric patients with metastatic ESFT and ARMS. The samples included pre-therapy BM and PB, as well as BM, PB, and PBSC collections at various times in the VACIME treatment course. Molecular evidence of tumor contamination was detected in 1/40 PBSC collections from 12 patients. In all patients, we documented clearance of disease by RT-PCR in peripheral blood and bone marrow by week 9 of the VACIME protocol. 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Graft versus host reaction</subject><subject>Bone Neoplasms - blood</subject><subject>Bone Neoplasms - drug therapy</subject><subject>Bone Neoplasms - genetics</subject><subject>Bone tumors</subject><subject>Chemotherapy</subject><subject>Child</subject><subject>Children</subject><subject>Chromosomes, Human, Pair 11 - genetics</subject><subject>Chromosomes, Human, Pair 11 - ultrastructure</subject><subject>Chromosomes, Human, Pair 13 - genetics</subject><subject>Chromosomes, Human, Pair 13 - ultrastructure</subject><subject>Chromosomes, Human, Pair 2 - genetics</subject><subject>Chromosomes, Human, Pair 2 - ultrastructure</subject><subject>Chromosomes, Human, Pair 22 - genetics</subject><subject>Chromosomes, Human, Pair 22 - ultrastructure</subject><subject>Combined Modality Therapy</subject><subject>Contamination</subject><subject>Cyclophosphamide</subject><subject>Cyclophosphamide - administration &amp; dosage</subject><subject>Cyclophosphamide - adverse effects</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Doxorubicin - administration &amp; dosage</subject><subject>Doxorubicin - adverse effects</subject><subject>Etoposide</subject><subject>Etoposide - administration &amp; dosage</subject><subject>Etoposide - adverse effects</subject><subject>Evaluation</subject><subject>Ewings sarcoma</subject><subject>Female</subject><subject>Forkhead Box Protein O1</subject><subject>Forkhead Transcription Factors</subject><subject>Hematopoietic Stem Cell Transplantation</subject><subject>Hematopoietic stem cells</subject><subject>Hematopoietic Stem Cells - drug effects</subject><subject>Humans</subject><subject>Ifosfamide</subject><subject>Ifosfamide - administration &amp; dosage</subject><subject>Ifosfamide - adverse effects</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mesna - administration &amp; dosage</subject><subject>Mesna - adverse effects</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplastic Cells, Circulating</subject><subject>Oncogene Proteins, Fusion - genetics</subject><subject>Paired Box Transcription Factors</subject><subject>Patients</subject><subject>PAX3 Transcription Factor</subject><subject>Pediatrics</subject><subject>Peripheral blood</subject><subject>Polymerase chain reaction</subject><subject>Proto-Oncogene Protein c-fli-1</subject><subject>Purging</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Rhabdomyosarcoma</subject><subject>Rhabdomyosarcoma, Alveolar - blood</subject><subject>Rhabdomyosarcoma, Alveolar - drug therapy</subject><subject>Rhabdomyosarcoma, Alveolar - genetics</subject><subject>RNA-Binding Protein EWS</subject><subject>Sarcoma</subject><subject>Sarcoma, Ewing - blood</subject><subject>Sarcoma, Ewing - drug therapy</subject><subject>Sarcoma, Ewing - genetics</subject><subject>Sensitivity and Specificity</subject><subject>Soft Tissue Neoplasms - blood</subject><subject>Soft Tissue Neoplasms - drug therapy</subject><subject>Soft Tissue Neoplasms - genetics</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Transcription Factors - genetics</subject><subject>Transfusions. 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P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c454t-30464e4b52a6afd92c26a64e164bef2cd7a2cee09444c4ae41cf93759dd616843</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Adolescent</topic><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Antineoplastic Combined Chemotherapy Protocols - adverse effects</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Blood</topic><topic>Bone marrow</topic><topic>Bone Marrow - pathology</topic><topic>Bone Marrow Purging</topic><topic>Bone marrow, stem cells transplantation. Graft versus host reaction</topic><topic>Bone Neoplasms - blood</topic><topic>Bone Neoplasms - drug therapy</topic><topic>Bone Neoplasms - genetics</topic><topic>Bone tumors</topic><topic>Chemotherapy</topic><topic>Child</topic><topic>Children</topic><topic>Chromosomes, Human, Pair 11 - genetics</topic><topic>Chromosomes, Human, Pair 11 - ultrastructure</topic><topic>Chromosomes, Human, Pair 13 - genetics</topic><topic>Chromosomes, Human, Pair 13 - ultrastructure</topic><topic>Chromosomes, Human, Pair 2 - genetics</topic><topic>Chromosomes, Human, Pair 2 - ultrastructure</topic><topic>Chromosomes, Human, Pair 22 - genetics</topic><topic>Chromosomes, Human, Pair 22 - ultrastructure</topic><topic>Combined Modality Therapy</topic><topic>Contamination</topic><topic>Cyclophosphamide</topic><topic>Cyclophosphamide - administration &amp; dosage</topic><topic>Cyclophosphamide - adverse effects</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Doxorubicin - administration &amp; dosage</topic><topic>Doxorubicin - adverse effects</topic><topic>Etoposide</topic><topic>Etoposide - administration &amp; dosage</topic><topic>Etoposide - adverse effects</topic><topic>Evaluation</topic><topic>Ewings sarcoma</topic><topic>Female</topic><topic>Forkhead Box Protein O1</topic><topic>Forkhead Transcription Factors</topic><topic>Hematopoietic Stem Cell Transplantation</topic><topic>Hematopoietic stem cells</topic><topic>Hematopoietic Stem Cells - drug effects</topic><topic>Humans</topic><topic>Ifosfamide</topic><topic>Ifosfamide - administration &amp; dosage</topic><topic>Ifosfamide - adverse effects</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mesna - administration &amp; dosage</topic><topic>Mesna - adverse effects</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neoplastic Cells, Circulating</topic><topic>Oncogene Proteins, Fusion - genetics</topic><topic>Paired Box Transcription Factors</topic><topic>Patients</topic><topic>PAX3 Transcription Factor</topic><topic>Pediatrics</topic><topic>Peripheral blood</topic><topic>Polymerase chain reaction</topic><topic>Proto-Oncogene Protein c-fli-1</topic><topic>Purging</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Rhabdomyosarcoma</topic><topic>Rhabdomyosarcoma, Alveolar - blood</topic><topic>Rhabdomyosarcoma, Alveolar - drug therapy</topic><topic>Rhabdomyosarcoma, Alveolar - genetics</topic><topic>RNA-Binding Protein EWS</topic><topic>Sarcoma</topic><topic>Sarcoma, Ewing - blood</topic><topic>Sarcoma, Ewing - drug therapy</topic><topic>Sarcoma, Ewing - genetics</topic><topic>Sensitivity and Specificity</topic><topic>Soft Tissue Neoplasms - blood</topic><topic>Soft Tissue Neoplasms - drug therapy</topic><topic>Soft Tissue Neoplasms - genetics</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Transcription Factors - genetics</topic><topic>Transfusions. 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P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>RT-PCR evaluation of peripheral blood, bone marrow and peripheral blood stem cells in children and adolescents undergoing VACIME chemotherapy for Ewing's sarcoma and alveolar rhabdomyosarcoma</atitle><jtitle>Bone marrow transplantation (Basingstoke)</jtitle><addtitle>Bone Marrow Transplant</addtitle><date>1999-09-01</date><risdate>1999</risdate><volume>24</volume><issue>5</issue><spage>527</spage><epage>533</epage><pages>527-533</pages><issn>0268-3369</issn><eissn>1476-5365</eissn><coden>BMTRE9</coden><abstract>Peripheral blood stem cell support allows dose intensification of multiple cycle chemotherapy for metastatic tumors, including pediatric sarcomas. The VACIME protocol (vincristine, adriamycin, cyclophosphamide, ifosfamide, mesna and etoposide) utilizes peripheral blood stem cells (PBSC) collected following the treatment cycle as support for subsequent dose- and time-intensive chemotherapy. A critical assumption is that PBSC collected in this manner will be purged of residual tumor cells in vivo. We tested this assumption using sensitive reverse-transcriptase polymerase chain reaction (RT-PCR) to assess the presence of the characteristic translocations of the Ewing's sarcoma family of tumors (ESFT) and alveolar rhabdomyosarcoma (ARMS), t(11;22), and t(2;13), respectively. We used RT-PCR to evaluate 122 samples of peripheral blood (PB), bone marrow (BM) and PBSC collected from 12 pediatric patients with metastatic ESFT and ARMS. The samples included pre-therapy BM and PB, as well as BM, PB, and PBSC collections at various times in the VACIME treatment course. Molecular evidence of tumor contamination was detected in 1/40 PBSC collections from 12 patients. In all patients, we documented clearance of disease by RT-PCR in peripheral blood and bone marrow by week 9 of the VACIME protocol. In vivo purging in combination with the intensive VACIME regime appears to be effective in removing tumor cells from PBSC, bone marrow, and peripheral blood as detected by RT-PCR.</abstract><cop>Basingstoke</cop><pub>Nature Publishing Group</pub><pmid>10482938</pmid><doi>10.1038/sj.bmt.1701939</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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subjects Adolescent
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Antineoplastic Combined Chemotherapy Protocols - adverse effects
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biological and medical sciences
Blood
Bone marrow
Bone Marrow - pathology
Bone Marrow Purging
Bone marrow, stem cells transplantation. Graft versus host reaction
Bone Neoplasms - blood
Bone Neoplasms - drug therapy
Bone Neoplasms - genetics
Bone tumors
Chemotherapy
Child
Children
Chromosomes, Human, Pair 11 - genetics
Chromosomes, Human, Pair 11 - ultrastructure
Chromosomes, Human, Pair 13 - genetics
Chromosomes, Human, Pair 13 - ultrastructure
Chromosomes, Human, Pair 2 - genetics
Chromosomes, Human, Pair 2 - ultrastructure
Chromosomes, Human, Pair 22 - genetics
Chromosomes, Human, Pair 22 - ultrastructure
Combined Modality Therapy
Contamination
Cyclophosphamide
Cyclophosphamide - administration & dosage
Cyclophosphamide - adverse effects
DNA-Binding Proteins - genetics
Doxorubicin - administration & dosage
Doxorubicin - adverse effects
Etoposide
Etoposide - administration & dosage
Etoposide - adverse effects
Evaluation
Ewings sarcoma
Female
Forkhead Box Protein O1
Forkhead Transcription Factors
Hematopoietic Stem Cell Transplantation
Hematopoietic stem cells
Hematopoietic Stem Cells - drug effects
Humans
Ifosfamide
Ifosfamide - administration & dosage
Ifosfamide - adverse effects
Male
Medical sciences
Mesna - administration & dosage
Mesna - adverse effects
Metastases
Metastasis
Neoplasm Proteins - genetics
Neoplastic Cells, Circulating
Oncogene Proteins, Fusion - genetics
Paired Box Transcription Factors
Patients
PAX3 Transcription Factor
Pediatrics
Peripheral blood
Polymerase chain reaction
Proto-Oncogene Protein c-fli-1
Purging
Reverse Transcriptase Polymerase Chain Reaction
Rhabdomyosarcoma
Rhabdomyosarcoma, Alveolar - blood
Rhabdomyosarcoma, Alveolar - drug therapy
Rhabdomyosarcoma, Alveolar - genetics
RNA-Binding Protein EWS
Sarcoma
Sarcoma, Ewing - blood
Sarcoma, Ewing - drug therapy
Sarcoma, Ewing - genetics
Sensitivity and Specificity
Soft Tissue Neoplasms - blood
Soft Tissue Neoplasms - drug therapy
Soft Tissue Neoplasms - genetics
Stem cell transplantation
Stem cells
Transcription Factors - genetics
Transfusions. Complications. Transfusion reactions. Cell and gene therapy
Translocation
Translocation, Genetic
Tumor cells
Tumors
Vincristine
Vincristine - administration & dosage
Vincristine - adverse effects
title RT-PCR evaluation of peripheral blood, bone marrow and peripheral blood stem cells in children and adolescents undergoing VACIME chemotherapy for Ewing's sarcoma and alveolar rhabdomyosarcoma
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