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Polymerase chain reaction for detection of residual leukaemia
G J Morgan1, T Hughes, J W Janssen
1Leukaemia Research Fund Centre, Institute of Cancer Research, London.
Abstract:
The occasional finding of cells positive for the Philadelphia (Ph) chromosome months or years after bone-marrow transplantation for chronic myeloid leukaemia raises the possibility that the Ph-positive clone may never be eradicated. The polymerase chain reaction with probes able to detect the transcript of the bcr/abl hybrid gene at very low levels was used to study marrow cells from seven patients in continuing haematological and cytogenetic remission 5-7 years after allogeneic bone-marrow transplantation for chronic myeloid leukaemia. No evidence of the leukaemic mRNA was found. Thus, it seems that all leukaemic cells were eradicated in these patients and that they are truly cured.
Insights
Philadelphia chromosome-positive cells may persist after bone-marrow transplants for chronic myeloid leukaemia. However, sensitive PCR testing found no evidence of leukaemic cells, suggesting a true cure in these patients.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- The Philadelphia chromosome (Ph) is a hallmark of chronic myeloid leukaemia (CML).
- Bone marrow transplantation (BMT) is a curative therapy for CML, but residual Ph-positive cells can sometimes be detected post-transplant, raising concerns about cure.
- The persistence of minimal residual disease after BMT for CML requires sensitive detection methods.
Purpose of the Study:
- To investigate the potential eradication of leukaemic cells in patients with chronic myeloid leukaemia (CML) after allogeneic bone marrow transplantation (BMT).
- To determine if the Philadelphia chromosome (Ph)-positive clone is completely eliminated post-BMT using sensitive molecular techniques.
- To assess the long-term cure status in CML patients achieving haematological and cytogenetic remission after BMT.
Main Methods:
- Study included seven patients with chronic myeloid leukaemia (CML) in complete remission 5-7 years post-allogeneic bone marrow transplantation (BMT).
- Bone marrow cells were analyzed using the polymerase chain reaction (PCR) technique.
- PCR assays were designed with probes to detect the bcr/abl hybrid gene transcript at very low levels, indicating the presence of Ph-positive leukaemic cells.
Main Results:
- No evidence of leukaemic messenger RNA (mRNA) for the bcr/abl hybrid gene was detected in the bone marrow cells of any of the seven patients studied.
- All patients had maintained haematological and cytogenetic remission for 5-7 years following allogeneic bone marrow transplantation.
- The sensitive PCR method did not identify any residual leukaemic cells.
Conclusions:
- The complete eradication of leukaemic cells appears to have been achieved in these patients following allogeneic bone marrow transplantation for chronic myeloid leukaemia (CML).
- The findings suggest that patients in long-term remission after BMT for CML may be considered truly cured.
- Sensitive molecular detection methods like PCR are crucial for confirming the absence of minimal residual disease and assessing cure.