EBMT 2022 | MRD-driven HSCT for ALL
Arnon Nagler, MD, Chaim Sheba Medical Center, Tel-Aviv, Israel, discusses the role of measurable residual disease (MRD) in transplant decisions in acute lymphoblastic leukemia (ALL). Prof. Nagler first outlines the different methods to detect MRD, including multiparameter flow cytometry, PCR and next-generation sequencing (NGS), which is the most sensitive approach. Prof. Nagler further explains that a standard risk patient who is MRD-negative would not undergo stem cell transplantation (SCT), but if the patient is Philadelphia chromosome-positive (Ph+), then transplant may still go ahead. Moreover, patients who are MRD-positive pre-transplant are usually treated with blinatumomab, with the aim of obtaining MRD negativity. If a patient is MRD-positive post-transplant, they are given maintenance therapy due to the high risk of relapse. Finally, Prof. Nagler comments on the use of chimeric antigen receptor T-cell (CAR-T) therapy before SCT. This interview took place at the 48th Annual Meeting of the European Group for Blood and Marrow Transplantation (EBMT) 2022, which was held virtually.
Transcript (edited for clarity)
MRD was born in ALL, it was born in pediatric ALL, and also the means to detect MRD, there are three ways to detect MRD, multi-parameter flow cytometry, PCR, and next-generation sequencing. And the most sensitive way to detect MRD is by next-generation-sequencing. And if you have an MRD of 10 to the minus six, you are cured.
So by FACS or multi-parameter flow cytometry, the effects or the significance of MRD is the same if you do it by multi-parameter flow cytometry, or by PCR, or by next-generation sequencing...
MRD was born in ALL, it was born in pediatric ALL, and also the means to detect MRD, there are three ways to detect MRD, multi-parameter flow cytometry, PCR, and next-generation sequencing. And the most sensitive way to detect MRD is by next-generation-sequencing. And if you have an MRD of 10 to the minus six, you are cured.
So by FACS or multi-parameter flow cytometry, the effects or the significance of MRD is the same if you do it by multi-parameter flow cytometry, or by PCR, or by next-generation sequencing. And it’s also the same prognostic factor if you do it after induction, or after consolidation, or after maintenance. So again, first of all, the decision goal, to go or not to go to transplant in ALL is MRD-based. If you are standard risk ALL, and MRD negative, you don’t go to transplant. If you are standard risk and you go to transplant regardless of the MRD, it’s likely you are high-risk by cytogenetic or genetic factors. And then if you are Philadelphia-positive, then there is a question about if you go to transplant. But according to the EBMT recommendation, even if you are MRD negative and Philadelphia-positive, you go for transplantation, but this remain a hot debate to this day. And again, after transplantation, you have to give maintenance therapy if you are MRD-positive post-transplant, because of the high relapse rate and the reduction in leukemia-free survival and overall survival. But if you are MRD-negative post-transplant, then you can either monitor the patient and give the preemptive therapy, or you can decide if it’s high-risk to give prophylactic therapy.
So this is for the transplant, but in ALL, we have now monoclonal antibodies, blinatumomab. And in the Blood study, it was shown that you can convert a patient from MRD-positivity to negativity pre-transplant. And this is extremely important. So nowadays if you are MRD-positive, pre-transplant, you should get two to four courses of blinatumomab in order to convert you to MRD-negativity. And then go to transplant when you are MRD-negative. And also, we have CAR-T therapy, which can be given to patients that don’t undergo transplant, or before transplant. And MRD is also predicting the outcome of transplantation after CAR-Ts. So ALL was the first leukemia to show the importance of MRD, and detect the timeline of treatment of ALL today.
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