bcr/abl chimeric transcript in patients in remission after marrow transplantation for chronic myeloid leukemia: Higher frequency of detection and slower clearance in patients grafted in advanced disease as compared to patients grafted in chronic phase

F. Frassoni, G. Martinelli, G. Saglio, M. Sessarego, M. Podesta, G. Piaggio, P. Farabegoli, A. Zaccaria, N. Testoni, C. Remiddi, A. Bacigalupo, P. Di Bartolomeo, F. Angrilli, M. Falda, F. Locatelli, T. Izzi, E. Gottardi, A. Guerrasio

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Abstract

The polymerase chain reaction (PCR) was used to amplify the bcr/abl transcript as a marker of minimal residual disease (MRD) in 76 patients with chronic myeloid leukemia (CML) subjected to allogeneic BMT and in complete hematological remission. We examined 56 patients transplanted in chronic phase (CP) and 20 in advanced phase (AD), including 16 in accelerated phase and four in blastic transformation. A total of 135 samples collected between 4 and 105 months from BMT were analyzed and the PCR analysis was positive in 33 (24%) samples from 20 patients. The bcr/abl chimeric transcript was detected in 7/13 (54%) patients analyzed within 1 year and in 21/88 (23%) beyond 1 year from BMT. Fluctuation of the residual disease at the molecular level in individual patients was recorded. The results have been correlated with a number of clinical parameters obtained before and after BMT; among the tested variables only the phase of the disease at BMT was associated with higher frequency of PCR positivity after BMT. The probability of finding persisting disease 1 year beyond BMT was significantly higher (P = 0.00005) in patients allografted in AD (14/26, 54%) as compared to patients grafted in CP (7/62, 11%). At any interval from BMT the difference between the two groups remained statistically significant: the bcr/abl transcript was present in 5/31 patients transplanted in CP compared to 9/15 patients transplanted in AD (P = 0.003) between 12 and 36 months from BMT, and in 2/31 CP vs 5/11 AD patients (P = 0.008) beyond 36 months from BMT. This indicates that the clearance of the residual disease is slower in patients allografted in AD and could reflect the diminished capability of allogeneic BMT in controlling and eradicated a Ph chromosome-positive clone with different biological characteristics. Nevertheless, in spite of the persistence of leukemic cells, most patients remain in clinical and cytogenetic remission. However, the three relapses that occurred in this series took place in patients persistently PCR-positive, and therefore the PCR analysis may identify a group of patients with an increased risk of relapse and may be useful for early therapeutic intervention.

Original languageEnglish
Pages (from-to)595-601
Number of pages7
JournalBone Marrow Transplantation
Volume16
Issue number4
Publication statusPublished - 1995

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Transplantation
Bone Marrow
Polymerase Chain Reaction
Recurrence
Residual Neoplasm
Cytogenetics
Clone Cells
Chromosomes

Keywords

  • bcr/abl transcripts
  • CML
  • PCR

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

bcr/abl chimeric transcript in patients in remission after marrow transplantation for chronic myeloid leukemia : Higher frequency of detection and slower clearance in patients grafted in advanced disease as compared to patients grafted in chronic phase. / Frassoni, F.; Martinelli, G.; Saglio, G.; Sessarego, M.; Podesta, M.; Piaggio, G.; Farabegoli, P.; Zaccaria, A.; Testoni, N.; Remiddi, C.; Bacigalupo, A.; Di Bartolomeo, P.; Angrilli, F.; Falda, M.; Locatelli, F.; Izzi, T.; Gottardi, E.; Guerrasio, A.

In: Bone Marrow Transplantation, Vol. 16, No. 4, 1995, p. 595-601.

Research output: Contribution to journalArticle

Frassoni, F, Martinelli, G, Saglio, G, Sessarego, M, Podesta, M, Piaggio, G, Farabegoli, P, Zaccaria, A, Testoni, N, Remiddi, C, Bacigalupo, A, Di Bartolomeo, P, Angrilli, F, Falda, M, Locatelli, F, Izzi, T, Gottardi, E & Guerrasio, A 1995, 'bcr/abl chimeric transcript in patients in remission after marrow transplantation for chronic myeloid leukemia: Higher frequency of detection and slower clearance in patients grafted in advanced disease as compared to patients grafted in chronic phase', Bone Marrow Transplantation, vol. 16, no. 4, pp. 595-601.
Frassoni, F. ; Martinelli, G. ; Saglio, G. ; Sessarego, M. ; Podesta, M. ; Piaggio, G. ; Farabegoli, P. ; Zaccaria, A. ; Testoni, N. ; Remiddi, C. ; Bacigalupo, A. ; Di Bartolomeo, P. ; Angrilli, F. ; Falda, M. ; Locatelli, F. ; Izzi, T. ; Gottardi, E. ; Guerrasio, A. / bcr/abl chimeric transcript in patients in remission after marrow transplantation for chronic myeloid leukemia : Higher frequency of detection and slower clearance in patients grafted in advanced disease as compared to patients grafted in chronic phase. In: Bone Marrow Transplantation. 1995 ; Vol. 16, No. 4. pp. 595-601.
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abstract = "The polymerase chain reaction (PCR) was used to amplify the bcr/abl transcript as a marker of minimal residual disease (MRD) in 76 patients with chronic myeloid leukemia (CML) subjected to allogeneic BMT and in complete hematological remission. We examined 56 patients transplanted in chronic phase (CP) and 20 in advanced phase (AD), including 16 in accelerated phase and four in blastic transformation. A total of 135 samples collected between 4 and 105 months from BMT were analyzed and the PCR analysis was positive in 33 (24{\%}) samples from 20 patients. The bcr/abl chimeric transcript was detected in 7/13 (54{\%}) patients analyzed within 1 year and in 21/88 (23{\%}) beyond 1 year from BMT. Fluctuation of the residual disease at the molecular level in individual patients was recorded. The results have been correlated with a number of clinical parameters obtained before and after BMT; among the tested variables only the phase of the disease at BMT was associated with higher frequency of PCR positivity after BMT. The probability of finding persisting disease 1 year beyond BMT was significantly higher (P = 0.00005) in patients allografted in AD (14/26, 54{\%}) as compared to patients grafted in CP (7/62, 11{\%}). At any interval from BMT the difference between the two groups remained statistically significant: the bcr/abl transcript was present in 5/31 patients transplanted in CP compared to 9/15 patients transplanted in AD (P = 0.003) between 12 and 36 months from BMT, and in 2/31 CP vs 5/11 AD patients (P = 0.008) beyond 36 months from BMT. This indicates that the clearance of the residual disease is slower in patients allografted in AD and could reflect the diminished capability of allogeneic BMT in controlling and eradicated a Ph chromosome-positive clone with different biological characteristics. Nevertheless, in spite of the persistence of leukemic cells, most patients remain in clinical and cytogenetic remission. However, the three relapses that occurred in this series took place in patients persistently PCR-positive, and therefore the PCR analysis may identify a group of patients with an increased risk of relapse and may be useful for early therapeutic intervention.",
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AU - Martinelli, G.

AU - Saglio, G.

AU - Sessarego, M.

AU - Podesta, M.

AU - Piaggio, G.

AU - Farabegoli, P.

AU - Zaccaria, A.

AU - Testoni, N.

AU - Remiddi, C.

AU - Bacigalupo, A.

AU - Di Bartolomeo, P.

AU - Angrilli, F.

AU - Falda, M.

AU - Locatelli, F.

AU - Izzi, T.

AU - Gottardi, E.

AU - Guerrasio, A.

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N2 - The polymerase chain reaction (PCR) was used to amplify the bcr/abl transcript as a marker of minimal residual disease (MRD) in 76 patients with chronic myeloid leukemia (CML) subjected to allogeneic BMT and in complete hematological remission. We examined 56 patients transplanted in chronic phase (CP) and 20 in advanced phase (AD), including 16 in accelerated phase and four in blastic transformation. A total of 135 samples collected between 4 and 105 months from BMT were analyzed and the PCR analysis was positive in 33 (24%) samples from 20 patients. The bcr/abl chimeric transcript was detected in 7/13 (54%) patients analyzed within 1 year and in 21/88 (23%) beyond 1 year from BMT. Fluctuation of the residual disease at the molecular level in individual patients was recorded. The results have been correlated with a number of clinical parameters obtained before and after BMT; among the tested variables only the phase of the disease at BMT was associated with higher frequency of PCR positivity after BMT. The probability of finding persisting disease 1 year beyond BMT was significantly higher (P = 0.00005) in patients allografted in AD (14/26, 54%) as compared to patients grafted in CP (7/62, 11%). At any interval from BMT the difference between the two groups remained statistically significant: the bcr/abl transcript was present in 5/31 patients transplanted in CP compared to 9/15 patients transplanted in AD (P = 0.003) between 12 and 36 months from BMT, and in 2/31 CP vs 5/11 AD patients (P = 0.008) beyond 36 months from BMT. This indicates that the clearance of the residual disease is slower in patients allografted in AD and could reflect the diminished capability of allogeneic BMT in controlling and eradicated a Ph chromosome-positive clone with different biological characteristics. Nevertheless, in spite of the persistence of leukemic cells, most patients remain in clinical and cytogenetic remission. However, the three relapses that occurred in this series took place in patients persistently PCR-positive, and therefore the PCR analysis may identify a group of patients with an increased risk of relapse and may be useful for early therapeutic intervention.

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