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Blood, Vol. 95 No. 8 (April 15), 2000:
pp. 2659-2665
Molecular analysis of lineage-specific chimerism and minimal
residual disease by RT-PCR of p210BCR-ABL and
p190BCR-ABL after allogeneic bone marrow transplantation
for chronic myeloid leukemia: increasing mixed myeloid chimerism and
p190BCR-ABL detection precede cytogenetic relapse
Josefina Serrano,
Jose Roman,
Joaquin Sanchez,
Antonio Jimenez,
Juan A. Castillejo,
Concepcion Herrera,
Maria Gracia Gonzalez,
Luisa Reina,
Maria del Carmen Rodriguez,
Miguel A. Alvarez,
Juan Maldonado, and
Antonio Torres
From the Hematology Department of Reina Sofía Hospital,
Córdoba, Spain, and the Hematology Department of Carlos Haya
Hospital, Malaga, Spain.
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
p210BCR-ABL and p190BCR-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 p210BCR-ABL positivity, increasing
mixed chimerism (MC) in myeloid cells, p190BCR-ABL positivity, and, finally, cytogenetic
relapse. Myeloid MC preceded cytogenetic relapse by 2-12 months,
whereas p190BCR/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 p190BCR-ABL; 10 patients tested
positive for p210BCR-ABL at variable time-points but showed
persistent full donor chimerism (DC), whereas 31 patients tested
p210BCR-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 p190BCR-ABL transcripts,
conversion of myeloid chimerism to donor type, and, finally,
p210BCR-ABL negativity. We conclude that lineage-specific
chimerism and p190BCR-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.
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