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Molecular analysis of lineage-specific chimerism and minimal residual disease by RT-PCR of p210(BCR-ABL) and p190(BCR-ABL) after allogeneic bone marrow transplantation for chronic myeloid leukemia: increasing mixed myeloid chimerism and p190(BCR-ABL) detection precede cytogenetic relapse.
Blood. 2000 Apr 15; 95(8):2659-65.Blood

Abstract

We studied lineage-specific chimerism and minimal residual disease (MRD) in sequential posttransplant samples from 55 patients who underwent unmanipulated (n = 44) or partially T-cell-depleted (n = 11) allogeneic bone marrow transplantation (BMT) for chronic myeloid leukemia (CML). Chimerism was assessed by polymerase chain reaction (VNTR [variable number of tandem repeats]-PCR) analysis in highly purified CD19+, CD3+, CD15+, and CD56+ cell fractions, whereas MRD was investigated in whole blood by reverse transcriptase-PCR (RT-PCR) of both p210(BCR-ABL) and p190(BCR-ABL) hybrid transcripts. Of 55 patients, 14 (including 6 T-cell-depleted patients) had cytogenetic relapse at 5-80 months and progressed to hematologic relapse, while 41 patients remained in prolonged cytogenetic remission 12-107 months post-BMT. Before leukemia recurrence, patients in the relapse group showed a consistent evolution pattern sequentially featured by persistent p210(BCR-ABL) positivity, increasing mixed chimerism (MC) in myeloid cells, p190(BCR-ABL) positivity, and, finally, cytogenetic relapse. Myeloid MC preceded cytogenetic relapse by 2-12 months, whereas p190(BCR/ABL) was detected 1-6 months prior to cytogenetic relapse in 11 patients and concomitant with cytogenetic relapse in 3 patients. In the remission group, all patients invariably tested negative for p190(BCR-ABL); 10 patients tested positive for p210(BCR-ABL) at variable time-points but showed persistent full donor chimerism (DC), whereas 31 patients tested p210(BCR-ABL) negative and displayed full DC or transient MC due to the persistence of recipient T cells. Two patients in the relapse group were successfully reinduced into molecular remission with donor lymphocyte infusion. Sequential molecular analysis after such treatment showed the inverse pattern to that observed prior to relapse, ie, progressive disappearance of p190(BCR-ABL) transcripts, conversion of myeloid chimerism to donor type, and, finally, p210(BCR-ABL) negativity. We conclude that lineage-specific chimerism and p190(BCR-ABL) messenger RNA (mRNA) analyses contribute a better characterization of CML evolution after BMT and enable early identification of patients at the highest risk of relapse. (Blood. 2000;95:2659-2665)

Authors+Show Affiliations

Hematology Department of Reina Sofía Hospital, Córdoba, Spain. josefina.serrano@iname.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10753848

Citation

Serrano, J, et al. "Molecular Analysis of Lineage-specific Chimerism and Minimal Residual Disease By RT-PCR of p210(BCR-ABL) and p190(BCR-ABL) After Allogeneic Bone Marrow Transplantation for Chronic Myeloid Leukemia: Increasing Mixed Myeloid Chimerism and p190(BCR-ABL) Detection Precede Cytogenetic Relapse." Blood, vol. 95, no. 8, 2000, pp. 2659-65.
Serrano J, Roman J, Sanchez J, et al. Molecular analysis of lineage-specific chimerism and minimal residual disease by RT-PCR of p210(BCR-ABL) and p190(BCR-ABL) after allogeneic bone marrow transplantation for chronic myeloid leukemia: increasing mixed myeloid chimerism and p190(BCR-ABL) detection precede cytogenetic relapse. Blood. 2000;95(8):2659-65.
Serrano, J., Roman, J., Sanchez, J., Jimenez, A., Castillejo, J. A., Herrera, C., Gonzalez, M. G., Reina, L., Rodriguez, M. C., Alvarez, M. A., Maldonado, J., & Torres, A. (2000). Molecular analysis of lineage-specific chimerism and minimal residual disease by RT-PCR of p210(BCR-ABL) and p190(BCR-ABL) after allogeneic bone marrow transplantation for chronic myeloid leukemia: increasing mixed myeloid chimerism and p190(BCR-ABL) detection precede cytogenetic relapse. Blood, 95(8), 2659-65.
Serrano J, et al. Molecular Analysis of Lineage-specific Chimerism and Minimal Residual Disease By RT-PCR of p210(BCR-ABL) and p190(BCR-ABL) After Allogeneic Bone Marrow Transplantation for Chronic Myeloid Leukemia: Increasing Mixed Myeloid Chimerism and p190(BCR-ABL) Detection Precede Cytogenetic Relapse. Blood. 2000 Apr 15;95(8):2659-65. PubMed PMID: 10753848.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular analysis of lineage-specific chimerism and minimal residual disease by RT-PCR of p210(BCR-ABL) and p190(BCR-ABL) after allogeneic bone marrow transplantation for chronic myeloid leukemia: increasing mixed myeloid chimerism and p190(BCR-ABL) detection precede cytogenetic relapse. AU - Serrano,J, AU - Roman,J, AU - Sanchez,J, AU - Jimenez,A, AU - Castillejo,J A, AU - Herrera,C, AU - Gonzalez,M G, AU - Reina,L, AU - Rodriguez,M C, AU - Alvarez,M A, AU - Maldonado,J, AU - Torres,A, PY - 2001/2/7/pubmed PY - 2001/2/7/medline PY - 2001/2/7/entrez SP - 2659 EP - 65 JF - Blood JO - Blood VL - 95 IS - 8 N2 - We studied lineage-specific chimerism and minimal residual disease (MRD) in sequential posttransplant samples from 55 patients who underwent unmanipulated (n = 44) or partially T-cell-depleted (n = 11) allogeneic bone marrow transplantation (BMT) for chronic myeloid leukemia (CML). Chimerism was assessed by polymerase chain reaction (VNTR [variable number of tandem repeats]-PCR) analysis in highly purified CD19+, CD3+, CD15+, and CD56+ cell fractions, whereas MRD was investigated in whole blood by reverse transcriptase-PCR (RT-PCR) of both p210(BCR-ABL) and p190(BCR-ABL) hybrid transcripts. Of 55 patients, 14 (including 6 T-cell-depleted patients) had cytogenetic relapse at 5-80 months and progressed to hematologic relapse, while 41 patients remained in prolonged cytogenetic remission 12-107 months post-BMT. Before leukemia recurrence, patients in the relapse group showed a consistent evolution pattern sequentially featured by persistent p210(BCR-ABL) positivity, increasing mixed chimerism (MC) in myeloid cells, p190(BCR-ABL) positivity, and, finally, cytogenetic relapse. Myeloid MC preceded cytogenetic relapse by 2-12 months, whereas p190(BCR/ABL) was detected 1-6 months prior to cytogenetic relapse in 11 patients and concomitant with cytogenetic relapse in 3 patients. In the remission group, all patients invariably tested negative for p190(BCR-ABL); 10 patients tested positive for p210(BCR-ABL) at variable time-points but showed persistent full donor chimerism (DC), whereas 31 patients tested p210(BCR-ABL) negative and displayed full DC or transient MC due to the persistence of recipient T cells. Two patients in the relapse group were successfully reinduced into molecular remission with donor lymphocyte infusion. Sequential molecular analysis after such treatment showed the inverse pattern to that observed prior to relapse, ie, progressive disappearance of p190(BCR-ABL) transcripts, conversion of myeloid chimerism to donor type, and, finally, p210(BCR-ABL) negativity. We conclude that lineage-specific chimerism and p190(BCR-ABL) messenger RNA (mRNA) analyses contribute a better characterization of CML evolution after BMT and enable early identification of patients at the highest risk of relapse. (Blood. 2000;95:2659-2665) SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/10753848/Molecular_analysis_of_lineage_specific_chimerism_and_minimal_residual_disease_by_RT_PCR_of_p210_BCR_ABL__and_p190_BCR_ABL__after_allogeneic_bone_marrow_transplantation_for_chronic_myeloid_leukemia:_increasing_mixed_myeloid_chimerism_and_p190_BCR_ABL__detection_precede_cytogenetic_relapse_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-4971(20)64158-1 DB - PRIME DP - Unbound Medicine ER -