The Majority of Patients Receiving Donor Lymphocyte Infusions for Relapsed Chronic Myeloid Leukemia Remain PCR Positive Despite Maintaining Long-Term Remission,
Authors: Innes Andrew J , Lurkins James , Szydlo Richard M , Guerra Andrea , Milojkovic Dragana , Pavlu Jiri , Kanfer Edward J , Marin David , MacDonald Donald , Rahemtulla Amin , Loaiza Sandra , Kirschke Stephanie , Rezvani Katayoun , Goldman John , Apperley Jane F , Dazzi Francesco 
Published: October 2019

Abstract
Abstract 4103
Donor 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.Figure 1.The probability of molecular relapse following complete molecular remission is low and not significantly different between those who are persistently negative, fluctuating low-level positive or persistently positive.Figure 1. The probability of molecular relapse following complete molecular remission is low and not significantly different between those who are persistently negative, fluctuating low-level positive or persistently positive.Figure 2.Patients who achieve a major molecular remission but not a complete molecular remission have non-inferior survival to those who do achieve a complete molecular remission, which is significantly better than those who do not achieve either of these.Figure 2. Patients who achieve a major molecular remission but not a complete molecular remission have non-inferior survival to those who do achieve a complete molecular remission, which is significantly better than those who do not achieve either of these.

Disclosures:
No relevant conflicts of interest to declare.