Search

Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only known curative therapy for chronic myeloid leukemia (CML); however, it is rarely utilized given the excellent long-term results with tyrosine kinase inhibitor (TKI) treatment. The purpose of this study is to examine HSCT outcomes for patients with CML who failed TKI therapy or presented in advanced phase and to identify predictors of survival, relapse, and nonrelapse mortality (NRM). Fifty-one patients with CML underwent HSCT for advanced disease at diagnosis (n = 15), TKI resistance as defined by the European LeukemiaNet guidelines (n = 30), TKI intolerance (n = 2), or physician preference (n = 4). At a median follow-up of 71.9 months, the 8-year overall survival (OS), event-free survival (EFS), relapse, and NRM were 68%, 46%, 41%, and 23%, respectively. In univariate analysis, predictors of OS included first chronic phase (CP1) disease status at HSCT ( P = .0005), European Society for Blood and Marrow Transplantation score 1 to 4 ( P = .04), and complete molecular response (CMR) to HSCT ( P < .0001). Donor (female) to patient (male) gender combination ( P = .02) and CMR to HSCT ( P < .0001) predicted lower relapse. In multivariate analysis, CMR to HSCT remained an independent predictor of OS (odds ratio [OR], 43), EFS (OR, 56) and relapse (OR, 29). This report indicates that the outlook is excellent for those patients who remain in CP1 at the time of HSCT and achieve a CMR after HSCT. However, only approximately 50% of those in advanced phase at HSCT are long-term survivors. This highlights the ongoing need to try to identify patients earlier, before disease progression, who are destined to fail this treatment to optimize transplantation outcomes. [ABSTRACT FROM AUTHOR]

Tyrosine kinase inhibitors (TKI) have been used to treat relapse of chronic myelogenous leukemia (CML) after allogeneic stem cell transplant (HSCT), with responses seen predominantly in chronic phase (CP) patients. This study aimed to analyze the response to TKI therapy and overall survival for patients relapsing predominantly in advanced phase. We retrospectively reviewed 22 patients treated with imatinib (n=20) and/or dasatinib (n=6) for relapsed CML after HSCT; 8 patients were in CP, and 14 patients had advanced disease. Seven patients also received donor lymphocyte infusions. Hematologic, cytogenetic, and molecular responses were analyzed. Nineteen patients (86%) achieved complete hematologic response (CHR), 17 patients (77%) achieved complete cytogenetic response (CCR), and 14 patients (64%) achieved complete molecular response (CMR). In advanced phase patients, 11 (79%) achieved CHR, 10 (71%) CCR, and 8 (57%) achieved CMR. Grade 3 or 4 cytopenias occurred in 10 cases. With median follow-up of 31.5 months from relapse, 14 (64%) patients remain alive, 13 in CMR. In multivariate analysis, the achievement of CMR was significantly correlated with OS with an odds ratio of 20.5 (95% confidence interval 2.3-182) P =.007. TKI therapy is capable of inducing durable molecular responses for CML relapsing after HSCT, both in chronic and advanced phases. The achievement of CMR appears to be crucial in providing long-term disease control for these patients. [Copyright &y& Elsevier]

Abstract: Cytogenetic and molecular responses to standard-dose imatinib (IM) were correlated with trough IM plasma levels for 78 patients with chronic myeloid leukemia (CML) after a minimum of 12 months of IM therapy. The mean trough IM plasma level was 1065ng/ml (range, 203–2910). There was no correlation of mean plasma trough IM levels and complete cytogenetic response (CCR) at 1 year (CCR 1010ng/ml vs no CCR 1175ng/ml P =.29) or major molecular response (MMR) (MMR1067ng/ml vs no MMR 1063ng/ml P =.74) after a median of 1298 days of IM therapy. CCR and MMR did correlate with Sokal risk scores with the odds of achieving CCR or MMR for a low risk vs high risk score of 10.8 (95% CI 2.2–53.5) and 6.4 (95% CI 1.4–29.4), respectively. Furthermore, a longer duration of IM therapy also was associated with a greater likelihood of achieving MMR (P =.02). [Copyright &y& Elsevier]