Treatment of Relapsing Ph+ Acute Lymphoblastic Leukemia with Donor Leukocyte Infusion Followed by Quantitative Monitoring of Residual Disease

Abstract

The case of a 34-year-old man with relapsing Ph+ acute lymphoblastic leukemia (ALL), which occurred five months after allogeneic bone marrow transplantation, is described. He was originally treated with aggressive chemotherapy, which put him in hematological remission, and he subsequently received donor leukocyte infusion (DLI) form the original donor. To assess the efficacy of this adoptive immunotherapy, we monitored minor-BCR/ABL (m-BCR/ABL) mRNA levels using the recently established real-time quantitative RT-PCR (RQ-PCR) assay. The results were compared with those obtained using conventional qualitative RT-PCR assays run in parallel. RQ-PCR, but not RT-PCR-based, minimum residual disease (MRD) detection showed a good correlation with the rapid changes documented during the post-DLI clinical course. Currently, six months after DLI, the patient continues to be in remission, which is consistent with the undetectable levels of m-BCR/ABL mRNA in the leukemic clone using RQ-PCR found in this study. Thus, monitoring of m-bcr/abl transcripts using RQ-PCR provides more useful information on a clinical assessment of MRD.

Granulocyte Colony-Stimulating Factor-Primed Donor Lymphocyte Infusion after Salvage Chemotherapy for Treatment of Relapsed Acute Leukemia after Allogeneic Stem Cell Transplantation

“…After completion of this chemotherapy regimen, the patient achieved a hematologic remission. The patient was then treated with DLI from the original donor, as previously described [5]. Despite these aggressive interventions, which resulted in temporary molecular remission [5], the patient again relapsed at day 561.…”

“…The patient was then treated with DLI from the original donor, as previously described [5]. Despite these aggressive interventions, which resulted in temporary molecular remission [5], the patient again relapsed at day 561. The patient received the same therapeutic strategy applied at the initial relapse.…”

Serial monitoring of T315I BCR-ABL mutation by Invader assay combined with RT-PCR

“…Among these, 33 patients remained in molecular remission, while the remaining 14 patients were identified as being positive for minimal residual disease (i.e., more than 50 copies of b2a3 major-bcr/abl/1 lg total RNA [13]), despite undergoing at least 6 months oral administration of imatinib, and then underwent serial T315I mutation analyses for studying kinetics of the emergence of this mutated clone. A further 1 patient with Philadelphia (Ph) chromosome-positive acute lymphoid leukemia (Ph?…”