Allogenic stem cell transplantation in elderly patients with acute lymphoblastic leukaemia is clearly a very hot topic in 2017. This is due to several reasons because, first of all, we know that a prognosis of elderly ALL is still dismal despite all the advances we have seen over the last ten years or so. Also we should be reminded that the biology of the disease in older patients is definitely different compared to the younger population. Also we should not forget that the feasibility, safety and tolerance of a given protocol for ALL will be different when we consider the older patients who, besides their age, have some comorbidities and will face more toxicities. This is the reason why there is still room to perform allogenic stem cell transplantation in older patients with ALL.

Actually when it comes to donors it’s not a major limitation these days because, thanks to the advent of haploidentical donors, it’s becoming more and more easy to find these donors. Also the development of the so-called reduced intensity conditioning regimens prior to transplant is allowing to perform these procedures safely. Today we can achieve a relatively very low non-relapse mortality incidence.

So in terms of feasibility, allotransplant for elderly ALL is definitely feasible. The major challenge we will be facing in the near future is going to be the disease status, first of all before going to transplant but also what to do after transplant. In order to achieve the optimum results for an allogenic stem cell transplant in elderly ALL we need to perform the transplant in the situation of the best disease control. Ideally we would like to achieve the deepest MRD negativity. I must confess this is not always easy to achieve and we should always balance efficacy with toxicity. In other words, we should not continuously hammer the patient with therapy before transplant because we will generate more toxicities that will either preclude the use of transplant or will negatively impact transplant. But in all cases whenever it is feasible we should take advantage of the novel treatment options that are now being developed, I’m thinking mainly about the monoclonal antibodies, whether the conjugated monoclonal antibodies directed against CD22 or whether talking about the bispecific monoclonal antibodies directed against CD3 and CD19. In all cases these options can allow to deepen the response prior to proceeding to transplant.

Once we have performed the transplant itself we really need to have a very close and careful monitoring of MRD and to be ready to start pre-emptive or maintenance therapy. So if we are considering Philadelphia positive ALL we have to consider the TKI options, tyrosine kinase inhibitors. The choice will depend on the drugs that were received prior to transplant but also on the safety profile in a given patient. In Philadelphia negative B-cell ALL definitely the use of bi-clonal antibodies directed against CD3, CD19 can be of great value, especially for example in case of positive MRD. So from some experiences, some cases reported here or there, we know that these antibodies can be used after transplant safely and can allow to achieve MRD negativity. We still don’t know how many cycles should we give after achieving negative MRD, should we repeat them on a regular basis, what to do after finishing the treatment, all of these are open questions that need to be investigated.

In the situation of disease relapse post-allo, whether the bi-clonal antibodies or the conjugated antibody against CD22 can be also a very good option to try again to achieve disease control. Once you are able to achieve disease control it will be again an open case because the question will be should we use DLI to consolidate the results, donor lymphocyte infusion, should we do some form of maintenance, and what is the optimal choice, or should we go to a second allotransplant using a different donor? All of these are open questions, I don’t think we will be able to find the right answer to all of them because this has to be tailored to the needs and to the situation of the patient at a given time with a given disease status but also, most importantly, tailored to the general status comorbidities of the patient. But also we have to take into account patient wishes.