ABSTRACT
INTRODUCTION: We previously reported an interim analysis of the DADI (dasatinib discontinuation) trial. The results showed that 48% of patients with chronic myeloid leukemia in the chronic phase who maintained a deep molecular response (DMR) for ≥ 1 year could discontinue second- or subsequent-line dasatinib treatment safely at a median follow-up of 20 months. However, the results from longer follow-up periods would be much more useful from a clinical perspective. PATIENTS AND METHODS: The DADI trial was a prospective, multicenter trial conducted in Japan. After confirming a stable DMR for ≥ 1 year, dasatinib treatment subsequent to imatinib or nilotinib was discontinued. After discontinuation, the loss of DMR (even of 1 point) was defined as stringent molecular relapse, thereby triggering therapy resumption. The predictive factors of treatment-free remission (TFR) were analyzed. RESULTS: The median follow-up period was 44.0 months (interquartile range, 40.5-48.0 months). The estimated overall TFR rate at 36 months was 44.4% (95% confidence interval, 32.0%-56.2%). Only 2 patients developed a molecular relapse after the 1-year cutoff point. The presence of imatinib resistance was a significant risk factor for molecular relapse. Moreover, high natural killer cell and low γδ+ T-cell and CD4+ regulatory T-cell (CD25+CD127low) counts before discontinuation correlated significantly with successful therapy discontinuation. CONCLUSION: These findings suggest that discontinuation of second- or subsequent-line dasatinib after a sustained DMR of ≥ 1 year is feasible, especially for patients with no history of imatinib resistance. In addition, the natural killer cell count was associated with the TFR.
Subject(s)
Antineoplastic Agents/therapeutic use , Dasatinib/therapeutic use , Deprescriptions , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Protein Kinase Inhibitors/therapeutic use , Female , Follow-Up Studies , Fusion Proteins, bcr-abl/genetics , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/blood , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Male , Middle Aged , Recurrence , Remission Induction , Risk Factors , Treatment OutcomeABSTRACT
Contraception is recommended during imatinib therapy based on the teratogenicity data in rats. However, patients may become pregnant and here we describe a successful pregnancy and labor without any congenital anomaly in a patient with chronic myeloid leukemia (CML) under treatment with imatinib. The patient had received imatinib for 53 months before she became pregnant, with a complete cytogenetic response achieved after 6 months of therapy and a major molecular response (MMR) after 28 months. CML was in MMR at discovery of pregnancy and the fetus had been exposed to imatinib for 5 weeks. Treatment was discontinued, but MMR persisted during gestation.
Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Piperazines/therapeutic use , Pregnancy Complications, Neoplastic/drug therapy , Pyrimidines/therapeutic use , Benzamides , Female , Humans , Imatinib Mesylate , Infant, Newborn , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Male , Piperazines/adverse effects , Pregnancy , Pregnancy Complications, Neoplastic/diagnosis , Pyrimidines/adverse effects , Remission Induction/methods , Treatment Outcome , Young AdultABSTRACT
We report here a very rare case of chronic myeloid leukemia (CML) following long-term chemotherapy with 5'-deoxy-5-fluorouridine (5'-DFUR) for gastric cancer. A 69-year-old man was diagnosed with the chronic phase of CML. Six years previously, he underwent radical subtotal gastrectomy for gastric cancer, and was subsequently treated with oral anti-metabolite 5'-DFUR as adjuvant chemotherapy for 6 years. He was placed on imatinib therapy, and achieved a major molecular response 10 months after the initiation of therapy. This is the first reported case of therapy-related CML following 5'-DFUR treatment.
