scholarly journals Minimal residual disease-based effect and long-term outcome of first-line dasatinib combined with chemotherapy for adult Philadelphia chromosome-positive acute lymphoblastic leukemia

2016 ◽  
Vol 27 (6) ◽  
pp. 1081-1088 ◽  
Author(s):  
J.-H. Yoon ◽  
H.-Y. Yhim ◽  
J.-Y. Kwak ◽  
J.-S. Ahn ◽  
D.-H. Yang ◽  
...  
PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256801
Author(s):  
Wanhua Zhang ◽  
Erguai Jang

Minimal residual disease (MRD) appeared to be a potent prognostic indicator in patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL), with potential value in informing individualized treatment decisions. Hence, we performed herein a systemic literature review and meta-analysis to comprehensively address the prognostic value of MRD in Ph+ ALL. Systematic literature review was conducted in PubMed, Embase, and Cochrane databases with the data access date up to September 23, 2020. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated with fixed-effects or random-effects models. Furthermore, subgroup analyses were performed to assess the robustness of the associations. 27 studies with a total number of 3289 patients were eligible for this meta-analysis. Combined HRs suggested that MRD positivity was associated with inferior event-free survival (EFS) (HR = 2.00, 95% CI 1.77–2.26) and overall survival (OS) (HR = 2.34, 95% CI 1.86–2.95). The associations remained statistically significant in subgroup analyses including age group, MRD timing, disease status at MRD, MRD cutoff level, et al. Our findings suggested MRD as a potent clinical tool for assessing the prognosis of Ph+ ALL. Further studies using MRD-based risk stratification might help optimize individualized treatment strategies for Ph+ ALL patients.


Blood ◽  
1992 ◽  
Vol 79 (5) ◽  
pp. 1366-1370 ◽  
Author(s):  
K Miyamura ◽  
M Tanimoto ◽  
Y Morishima ◽  
K Horibe ◽  
K Yamamoto ◽  
...  

Abstract Minimal residual disease (MRD) in patients with Philadelphia chromosome- positive acute lymphoblastic leukemia (Ph1 ALL) who received allogeneic (n = 9) or autologous (n = 6) bone marrow transplantation (BMT) was evaluated by the polymerase chain reaction (PCR) for the bcr-abl transcript. Twelve patients received BMT at the time of hematologic and cytogenetic remission. However, MRD was detected in 8 of 10 patients evaluated. Seven patients, including three who had MRD before BMT, continue to have a disease-free survival 5 to 64 months after BMT. Twenty-one specimens obtained from these patients at various times after BMT did not show MRD. In three patients, MRD detected just before BMT seems to be eradicated by BMT protocol. The other eight patients developed cytogenetic or hematologic relapses 2 to 8 months after BMT. Seven of 14 samples from these patients demonstrated MRD, which preceded clinical relapse by 3 to 9 weeks. Thus, this technique for the detection of MRD appears to be useful for the more precise assessment of various antileukemia therapies and for early detection of leukemia recurrence.


2010 ◽  
Vol 28 (22) ◽  
pp. 3644-3652 ◽  
Author(s):  
Renato Bassan ◽  
Giuseppe Rossi ◽  
Enrico M. Pogliani ◽  
Eros Di Bona ◽  
Emanuele Angelucci ◽  
...  

Purpose Short imatinib pulses were added to chemotherapy to improve the long-term survival of adult patients with Philadelphia chromosome (Ph) –positive acute lymphoblastic leukemia (ALL), to optimize complete remission (CR) and stem-cell transplantation (SCT) rates. Patients and Methods Of 94 total patients (age range, 19 to 66 years), 35 represented the control cohort (ie, imatinib-negative [IM-negative] group), and 59 received imatinib 600 mg/d orally for 7 consecutive days (ie, imatinib-positive [IM-positive] group), starting from day 15 of chemotherapy course 1 and from 3 days before chemotherapy during courses 2 to 8. Patients in CR were eligible for allogeneic SCT or, alternatively, for high-dose therapy with autologous SCT followed by long-term maintenance with intermittent imatinib. Results CR and SCT rates were greater in the IM-positive group (CR: 92% v 80.5%; P = .08; allogeneic SCT: 63% v 39%; P = .041). At a median observation time of 5 years (range, 0.6 to 9.2 years), 22 patients in the IM-positive group versus five patients in the IM-negative group were alive in first CR (P = .037). Patients in the IM-positive group had significantly greater overall and disease-free survival probabilities (overall: 0.38 v 0.23; P = .009; disease free: 0.39 v 0.25; P = .044) and a lower incidence of relapse (P = .005). SCT-related mortality was 28% (ie, 15 of 54 patients), and postgraft survival probability was 0.46 overall. Conclusion This imatinib-based protocol improved long-term outcome of adult patients with Ph-positive ALL. With SCT, post-transplantation mortality and relapse remain the major hindrance to additional therapeutic improvement. Additional intensification of imatinib therapy should warrant a better molecular response and clinical outcome, both in patients selected for SCT and in those unable to undergo this procedure.


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