Reply to U. Dührsen et al

Abstract

In their letter, Duhrsen et al disagree with our conclusion that in patients with relapsed or refractory follicular lymphoma, the presence of tumor cells in blood or bone marrow, as detected by BCL2/IgH major break point region (MBR) polymerase chain reaction (PCR) at the end of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone induction therapy, is not predictive of progression-free survival (PFS). Their major argument is that we have compared inappropriate groups because the BCL2/IgH MBR–negative group might have contained patients with tumor cells in blood or bone marrow that have escaped detection because they have t(14;18) with a break point outside the MBR. On the basis of cited literature, they mention that up to 50% of t(14;18) patients have break points outside the MBR, whereas in fact, this figure is 32%. Nevertheless, regardless of the exact frequency of BCL2/ IgHMBRpositivityamongpatientswitht(14;18), intheDiscussionofour article, we already have addressed rather extensively the issue raised by Duhrsen et al. At present, we are in the process of performing an additional minor break point region PCR analysis to further corroborate our conclusions. However, when we restricted our analysis to the group with initial BCL2/IgH MBR–positive results in blood and/or bone marrow, we found no difference in PFS between patients who converted from PCR positive to PCR negative and patients who remained PCR positive. This was true for both bone marrow and peripheral blood. This observation, which was mentioned in our article under Results, strongly supports the conclusion that in patients with relapsed or refractory follicular lymphoma, the BCL2/IgH status in peripheral blood and bone marrow at the end of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone induction therapy is not predictive for PFS.