Stable non-transforming minimal residual disease in Philadelphia chromosome positive acute lymphoblastic leukemia after autologous transplantation: origin from neoplastic yet ‘pre-leukemic’ stem cells?

2011 ◽  
Vol 52 (5) ◽  
pp. 842-848 ◽  
Author(s):  
Alexandra Böhm ◽  
Harald Herrmann ◽  
Gerlinde Mitterbauer-Hohendanner ◽  
Alexander W Hauswirth ◽  
Werner Rabitsch ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Autologous Transplantation ◽  
Philadelphia Chromosome ◽  
Leukemic Stem Cells ◽  
Minimal Residual ◽  
Philadelphia Chromosome Positive

scholarly journals Dasatinib for a child with Philadelphia chromosome–positive acute lymphoblastic leukemia and persistently elevated minimal residual disease during imatinib therapy

2015 ◽  
Vol 22 (4) ◽  
pp. 303 ◽  
Author(s):  
K.H. Wu ◽  
H.P. Wu ◽  
T. Weng ◽  
C.T. Peng ◽  
Y.H Chao
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Intensive Chemotherapy ◽  
Molecular Remission ◽  
Allogeneic Hsct ◽  
Minimal Residual ◽  
Philadelphia Chromosome Positive

Imatinib has improved outcomes in patients with Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (all). Minimal residual disease (mrd) is a useful tool for predicting leukemia relapse. However, there is no consensus on how to treat children with elevation of BCR-ABL transcripts but no evidence of hematologic relapse during chemotherapy combined with imatinib. Here, we report the case of a child with Ph+ all who had persistent elevation of mrd, but no evidence of hematologic relapse while receiving imatinib plus intensive chemotherapy. Dasatinib was substituted for imatinib because no suitable donor for allogeneic hematopoietic stem-cell transplantation (hsct) was available. Less-intensive chemotherapy with methotrexate and 6-mercaptopurine was administered concomitantly. No serious adverse events were encountered. With continuous dasatinib combined with chemotherapy, but no allogeneic hsct, our patient reached complete molecular remission and has been in complete molecular remission for more than 13 months. This report is the first about the long-term use of dasatinib in patients with Ph+ all and mrd elevation but hematologic remission during imatinib chemotherapy. In a similar situation, chemotherapy combined with dasatinib instead of allogeneic hsct could be considered to avoid hsct-related mortality and morbidity. Clinical trials are needed.

Early Intervention in Minimal Residual Disease after Allogeneic Transplant for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Prolonged Survival by Imatinib.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4581-4581
Author(s):  
Koichi Miyamura ◽  
Kodera Yoshihisa ◽  
Satoshi Skamaki ◽  
Shinji Nakao ◽  
Satoshi Sasaki ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Group A ◽  
Group B ◽  
Minimal Residual ◽  
Philadelphia Chromosome Positive

Abstract Minimal residual disease (MRD) was examined using quantitative polymerase chain reaction in 34 patients with Philadelphia chromosome- positive acute lymphoblastic leukemia (Ph+ ALL) who received allogeneic hematopoietic stem cell transplantation (HSCT). Patients were divided into two groups according to the time of transplant (Group A; n=17, – 2000 and Group B; n=17, 2001-). Group B had a significantly higher overall survival rate than Group B (74.2% vs 29.4%, P<0.01). In Group A, MRD+ after HSCT indicated imminent hematological relapse with subsequent death. On the contrary, in Group B, 8 patients showed MRD after HSCT. However, only one died of leukemia during the observation. Among the MRD+ patients after HSCT, the probability of hematological relapse was higher in group A than in group B (100% vs 20%, P<0.05). MRD-based clinical interventions such as Imatinib administration, donor lymphocyte infusion, or second HSCT may contribute to longer survival. In particular, imatinib introduce MRD-negativity in most patients, resulting better performance status and time for preparing next strategies. Two patients who became MRD-negative after imatinib treatment developed molecular relapse after imatinib discontinuation. Thus, Imatinib may contribute to the improvement of overall survival, however, an allogeneic power may be required for the cure of leukemia.

scholarly journals Association of minimal residual disease with clinical outcomes in Philadelphia chromosome positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era: A systemic literature review and meta-analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256801
Author(s):  
Wanhua Zhang ◽  
Erguai Jang
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Literature Review ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Meta Analysis ◽  
Philadelphia Chromosome ◽  
Individualized Treatment ◽  
Subgroup Analyses ◽  
Minimal Residual

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.

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