The Majority of Patients Receiving Donor Lymphocyte Infusions for Relapsed Chronic Myeloid Leukemia Remain PCR Positive Despite Maintaining Long-Term Remission,

Abstract

Abstract 4103Donor lymphocyte infusions (DLI) produce molecular remission in the large majority of chronic myeloid leukaemia (CML) patients who relapse after allografting. Although response to DLI is associated with long-term clinical remissions, we asked whether minimal residual disease could still be detected. We identified 116 patients who had received escalating doses of donor lymphocytes between 1995 and 2010 for molecular, cytogenetic or haematological relapse following allogeneic hematopoietic stem cell transplantation for CML. These patients had serial monitoring of their response by quantitative reverse transcriptase–polymerase chain reaction (RT-PCR). 84 patients had achieved a complete molecular remission (CMR) (defined by 2 consecutive negative PCR), however 79 (94%) of these subsequently became positive again. All patients who achieved a complete molecular remission were allocated to 3 categories: (1) “persistently negative” or a single low level positive result (n=15 (18%); (2) “fluctuating low-level positive”, who had multiple positive results, but never more than 2 consecutive positive results (n=34 (40%)); and (3) “persistently low-level positive” (n=35(42%)), and the rates of relapse were compared in the three groups. The overall probability of relapse (defined by the initial molecular relapse criteria) at 10 years was low in all three groups (6.7%), and there was no significant difference in each category: 0%, 4.2% and 10.3% respectively (P=0.372) (figure 1), with no survival difference in the three groups. Furthermore, of the 32 patients who did not achieve a CMR, 11 achieved a fall in PCR to <0.1 (major molecular remission (MMR)) following completion of their DLI protocol and had a non-inferior survival to those who achieve a CMR, in contrast to those who did not satisfy either of these criteria, and had a significantly inferior survival (p<0.01) (figure 2). We conclude that the majority of patients who respond to DLI do not remain PCR negative, but low-level positive results do not predict relapse. This suggests that, although DLI does not completely eradicate the disease, it exerts a highly effective long-term disease control. The data presented also raises the question of whether persistent PCR negativity should be unequivocally pursued, or whether a threshold of MMR may be adequate. [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.