TY - JOUR
T1 - Comparative study of FISH, PCR and cytogenetics on 25 patients submitted to bone marrow transplantation (BMT) for chronic myelogenous leukemia (CML); Which tests can we use in routine analysis post BMT?
AU - Palka, G.
AU - Lawler, M.
AU - Morizio, E.
AU - Gardiner, N.
AU - Stuppia, L.
AU - De Arce, M. A.
AU - Di Bartolomeo, P.
AU - Capodiffero, F.
AU - Sabatino, G.
AU - Gatta, V.
AU - Calabrese, G.
AU - McCann, S. R.
PY - 1998
Y1 - 1998
N2 - Chronic Myeloid Leukaemia (CML) shows an excellent response to allogeneic bone marrow transplantation (BMT) with a 60-80% long term disease free survival in recipients of unmanipulate marrow. The most frequent cause of treatment failure is leukaemic relapse, due to the re-emergence of malignant recipient clones. Clinical and haematological relapse is usually preceded by molecular evidence of relapse. Early detection of molecular relapse may allow intervention with immunotherapy such as donor lymphocyte infusions (DLI). This study was undertaken to compare results from two centres who employ either Fluorescent In Situ Hybridisation (FISH) or polymerase chain reaction (PCR) analysis of DNA polymorphisms as their routine method of detecting residual host cells following BMT for CML in order to establish (1) if these methods are equivalent for routine laboratory use in reporting of chimaerism results to the referring clinician, and (2) if these methods are beneficial for indicating new and early therapeutic strategies. FISH analyses for the X and Y chromosomes (in sex mismatched patients) and/or FISH for BCR and ABL loci were compared with short tandem repeat PCR (STR-PCR) and conventional karyotyping in serial analyses in 25 patients submitted to BMT for Philadelphia positive (Ph) CML. Comparison of all results on samples assessed between 1 and 13 years post BMT indicated that FISH and PCR, performed on the same bone marrow samples displayed similar results in more than 90% of patients in first 3 years after BMT which increased to a concordance rate of 100% in long term survivors. In contrast, comparison of FISH or PCR versus cytogenetic analysis indicated a low concordance rate, with less than 50% of samples showing similar results during all the follow-up period. Eighty percent of recipients (22 patients) had evidence of mixed chimaerism following BMT (initial level of positivity 1-6% recipient cells) during the follow-up period. This low percentage of recipient cells remained stable in 7 patients, while 9 patients reverted to a donor profile. All 16 patients are in haematological remission. In addition the 3 patients with complete donor chimaerism remain in remission. In the remaining 6 patients, a progressive increase in recipient cells occurred (progressive mixed chimaerism, PMC), and was followed by haematological relapse. We conclude that FISH and PCR can be used to monitor CML patients post BMT and transient or stable low level mixed chimaerism is not associated with leukaemia relapse, but PMC is predictive of imminent relapse and its detection may help to illucidate the timing of early intervention with donor lymphocyte infusion.
AB - Chronic Myeloid Leukaemia (CML) shows an excellent response to allogeneic bone marrow transplantation (BMT) with a 60-80% long term disease free survival in recipients of unmanipulate marrow. The most frequent cause of treatment failure is leukaemic relapse, due to the re-emergence of malignant recipient clones. Clinical and haematological relapse is usually preceded by molecular evidence of relapse. Early detection of molecular relapse may allow intervention with immunotherapy such as donor lymphocyte infusions (DLI). This study was undertaken to compare results from two centres who employ either Fluorescent In Situ Hybridisation (FISH) or polymerase chain reaction (PCR) analysis of DNA polymorphisms as their routine method of detecting residual host cells following BMT for CML in order to establish (1) if these methods are equivalent for routine laboratory use in reporting of chimaerism results to the referring clinician, and (2) if these methods are beneficial for indicating new and early therapeutic strategies. FISH analyses for the X and Y chromosomes (in sex mismatched patients) and/or FISH for BCR and ABL loci were compared with short tandem repeat PCR (STR-PCR) and conventional karyotyping in serial analyses in 25 patients submitted to BMT for Philadelphia positive (Ph) CML. Comparison of all results on samples assessed between 1 and 13 years post BMT indicated that FISH and PCR, performed on the same bone marrow samples displayed similar results in more than 90% of patients in first 3 years after BMT which increased to a concordance rate of 100% in long term survivors. In contrast, comparison of FISH or PCR versus cytogenetic analysis indicated a low concordance rate, with less than 50% of samples showing similar results during all the follow-up period. Eighty percent of recipients (22 patients) had evidence of mixed chimaerism following BMT (initial level of positivity 1-6% recipient cells) during the follow-up period. This low percentage of recipient cells remained stable in 7 patients, while 9 patients reverted to a donor profile. All 16 patients are in haematological remission. In addition the 3 patients with complete donor chimaerism remain in remission. In the remaining 6 patients, a progressive increase in recipient cells occurred (progressive mixed chimaerism, PMC), and was followed by haematological relapse. We conclude that FISH and PCR can be used to monitor CML patients post BMT and transient or stable low level mixed chimaerism is not associated with leukaemia relapse, but PMC is predictive of imminent relapse and its detection may help to illucidate the timing of early intervention with donor lymphocyte infusion.
KW - Allogeneic bone marrow transplantation (BMT)
KW - Chronic myeloid leukaemia
KW - Fluorescent in situ hybridisation (FISH)
KW - Haemopoietic chimaerism
KW - Polymerase chain reaction (PCR)
KW - Residual host cells
UR - http://www.scopus.com/inward/record.url?scp=0032407974&partnerID=8YFLogxK
U2 - 10.1080/10245332.1998.11746391
DO - 10.1080/10245332.1998.11746391
M3 - Article
AN - SCOPUS:0032407974
SN - 1024-5332
VL - 3
SP - 193
EP - 203
JO - Hematology
JF - Hematology
IS - 3
ER -