A case study of double cord persistence: Everyone wins

Abstract

Double cord (DC) transplants (txp) as a treatment of choice for hematologic malignancies are much less frequently utilized when compared to MUD stem cell therapies. The vast majority of stem cell recipients (recip) receiving DC txp transition from 100% recip to 100% single cord blood unit (CBU), as usually one CBU “wins” and persists alone. This occurs within a few weeks to a few months post-txp. We present a case study in which neither cord is eliminated, but rather, long term engraftment of both CBUs persists. A 26 y/o, Caucasian, male with CML was conditioned for DC txp with busulfan, thiotepa and fludarabine due to lack of 10/10 MUDs and presence of inhibitor-resistant T315I mutation. DC txp is a low relapse option for CML patients who cannot be treated with the standard inhibitor therapies due to presence of T315I mutation. Engraftment monitoring (EM) analysis was performed by qPCR on day 18, revealing 0% recip, 86% CBU #1 and 14% CBU #2. These unexpected results, and the potential for artifacts of the newer qPCR method led us to confirm EM by qPCR in peripheral blood and bone marrow samples by standard STR analysis. The presence of both CBUs has persisted to 115 days post-txp at 83% CBU #1 and 17% CBU #2, contrary to the more common instance of single CBU engraftment. Both CBUs are a 5/6 antigen match to the recip. Coincidentally, both CBU were typed as HLA-A3; the only mismatched antigen. No anti-HLA antibodies were detected in the recip against this single HLA-A antigen mismatch. The recip and the dominant CBU #1 are blood type O-positive. The minor cord (CBU #2) is B-positive. CML patients are a small fraction of hematologic malignancy cases, and even further represent a very small % of DC recips; the majority being patients diagnosed with AML. The instance of the mixed DC chimerism described here is rare, especially compared to the mixed chimerism of recip and donor commonly seen in pediatric cases of single cord txp. This case is unique in the feature of total absence of recip and a mixture of 2 CBUs persisting in an adult double cord recip. CBUs’ mixed chimerism in adults txp with DCs is considered by some to be a negative prognostic predictor. In the case we present here, the recip is in clinically good condition and currently free of disease. This is a rare case of successful CML therapy upon DC txp in an adult with mixed donor chimerism persistence.