Response: CNS prophylaxis in MCL

We thank Dr Gatt and Dr Grisaro for raising the issue of central nervous system (CNS) prophylaxis in mantle cell lymphoma (MCL), which we admit having addressed only indirectly in our review.¹  We agree with most of the content of their letter, in particular the fact that the true incidence of CNS involvement in MCL is unknown, that most CNS involvements are part of a systemic relapse and therefore the role of primary prophylaxis is probably limited, and, finally, that it is controversial whether prophylaxis can really prevent CNS relapse.

Basically, as there are no data allowing clear recommendations to be made, each center is left to make up its own policy. The available data would support the concept that initial treatments including CNS-penetrating agents at high-dose (with or without intrathecal therapy) may provide sufficient prophylaxis, at least in the younger patients²  and in our center the treatment of patients younger than 65 years of age is Hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternated with high doses of methotrexate and cytarabine (Hyper-CVAD/HD-MTX-AraC); therefore, we are left with the question of what to do with elderly patients and with those who are unfit for aggressive treatment. For these patients, based on the uncertainities mentioned above, we think that the cost-benefit ratio of routine CNS prophylaxis is unfavorable, and therefore we do not propose it. Because of the same uncertainities, on the other hand, it may not be wrong to offer CNS prophylaxis (as suggested by Gatt and Grisaro) to the patients supposed to be at higher risk.

It should be noted, however, that the definition of patients at risk for CNS relapse is still controversial even in the most common setting of diffuse large B-cell lymphoma (DLBCL),³  and that, perhaps with the exception of raised lactate dehydrogenase, the prognostic indicators for MCL²  may not necessarily be the same described in DLBCL.