CAR-T Meeting 2021 | Impact of spleen size and splenectomy on outcomes of allo-HSCT for myelofibrosis

Massive splenomegaly before there’s any transplantation for patients with myelofibrosis it’s a very difficult problem. We don’t know what to do because there is some concerns regarding the toxicity of the operation splenectomy itself. For instance, can we do this before transplantation or not? On the other hand, we have some concerns because we know that patients transplanted with massive splenomegaly had less advantage results, outcome after transplantation. So to try to solve this problem, first of all, we conducted two studies. The first of all, it was a French national-wide study.

Actually, we compared patients with clear indication for allogeneic transplantation for myelofibrosis. Some of them were transplanted others not, and some of them were splenectomized before transplantation, other not. So we looked at the impact of a splenectomy before transplantation on the probability to being transplanted. Actually in this study, and the first time I would say, we demonstrated that there is no impact. So once you have the indication for splenectomy before transplantation, you can do it.

I would say you can do it without any risk to prevent patients to undergo transplantations. This was the first part of the question. So can we do splenectomy safely before transplantation? The answer is yes. At least I would say, there’s no statistical differences regarding patient who’s splenectomized or not, regarding being transplanted or not. The second part, it was the other study. It’s the impact of spleen size on outcomes. Of course, we demonstrated that patients with small spleen at transplantation or those who were splenectomized did better than those with massive splenomegaly before transplantation.

So I think with these two studies, we can answer the question regarding the management of a splenomegaly before allogeneic transplantation for patients with myelofibrosis you would say. Now how to place a splenectomy before transplantation or how to manage splenomegaly in those patients. Of course, now we have the JAK2 inhibitors and we have first-generation, second-generation and so on. I would say in patients responding to JAK2 inhibitors, especially in terms of splenomegaly, so you can go to transplantation without no concerns.

We have at the EBMT a third study, which has been just submitted for publication. Actually demonstrating that people responding to JAK2 inhibitor did better than the others after transplantations. However, the problem is still concerning regarding patients who failed JAK2 inhibitors. So the question is what to do? Do we need to offer them the second generation of JAK2 inhibitors? The question, it’s not clear, the answer is not near right now. Or can we offer them a splenectomy before transplantation? I would say today I would go for a splenectomy before transplantation in those patients. But many investigations are ongoing to try to answer second-generation JAK2 inhibitors or splenectomy before transplantation.