Differential depth of treatment response required for optimal outcome in patients with blast phase versus chronic phase of chronic myeloid leukemia

Chen, Z; Medeiros, L. Jeffrey; Kantajian, H M; Zheng, Lan; Gong, Zimu; Patel, Keyur P.; Xiong, Hong; Wang, W; Cortes, Jorge; Hu, Shimin

doi:10.1038/bcj.2017.4

Cited by 10 publications

(16 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The study showed no lower cut off point for survival benefit per log reduction in MRD, and speculated that more sensitive approaches are likely to yield even better prediction of outcome. Further studies have shown that very deep response correlates with better survival in PCM patients (7,29), in line with other types of hematological malignancy (30). Therefore, our study has shown that standardized FC approaches can aid such studies and improve patient outcomes.…”

Section: Discussionsupporting

confidence: 70%

Assessment of plasma cell myeloma minimal residual disease testing by flow cytometry in an international inter‐laboratory study: Is it ready for primetime use?

Scott

Fletcher

Whitehouse

et al. 2018

Cytometry Part B Clinical

View full text Add to dashboard Cite

Background Minimal/measurable residual disease (MRD) testing by flow cytometry (FC) has been proposed as a potential surrogate clinical endpoint in plasma cell myeloma (PCM) clinical trials. As a result, effort has gone into standardizing this approach on PCM patients. Aims To assess inter‐laboratory variation in FC MRD testing of PCM patients in an independent inter‐laboratory study. Methods A dilution series of five stabilized bone marrow samples manufactured to contain 0%, 0.1%, 0.01%, 0.001%, and 0.0001% neoplastic plasma cells (PCs) were tested blind, using standardized FC PCM MRD assays by 10 international laboratories. Results Laboratories' assays broadly adhered to the consensus guidelines; however, some deviations were identified in panel design, fluorochrome conjugates, and lysis reagents. Despite this, all laboratories that returned results detected neoplastic PCs down to 0.001% of leucocytes. 6/8 laboratories detected neoplastic PCs at a level of 0.0001%. Quantitative data returned by laboratories showed good consensus and linearity with increasing variation at lower levels of MRD. However, examples of analytical and post analytical error were identified. Summary/Conclusion Broadly standardized PCM MRD FC assays can attain the lower limit of detection (LOD) required by current and future clinical trials, an important consideration in establishing PCM MRD testing as a surrogate clinical marker in PCM clinical trials. Laboratories' assays showed good linearity, encouraging the prediction of survival based on log reduction in neoplastic PC populations in future clinical trials. However, the deviations from consensus guidelines identified in this study would suggest that if PCM MRD assays are further standardized interlaboratory variation could be reduced. © 2018 International Clinical Cytometry Society

show abstract

Section: Discussionsupporting

confidence: 70%

Assessment of plasma cell myeloma minimal residual disease testing by flow cytometry in an international inter‐laboratory study: Is it ready for primetime use?

Scott

Fletcher

Whitehouse

et al. 2018

Cytometry Part B Clinical

View full text Add to dashboard Cite

show abstract

“…Patients who achieved molecular undetectable leukemia status had a better survival than those who achieved MMR. The results are similar for patients with myeloid BP and for patients with lymphoid BP 28…”

Section: Assessment Of Responses To Treatmentsupporting

confidence: 56%

<p>Chronic myelogenous leukemia, a still unsolved problem: pitfalls and new therapeutic possibilities</p>

Flis¹,

Chojnacki²

2019

DDDT

View full text Add to dashboard Cite

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of hematopoietic stem cells. At the molecular level, the disorder results from t(9;22)(q34;q11) reciprocal translocation between chromosomes, which leads to the formation of an oncogenic BCR–ABL gene fusion. Instead of progress in the understanding of the molecular etiology of CML and the development of novel therapeutic strategies, clinicians still face many challenges in the effective treatment of patients. In this review, we discuss the pathways of diagnosis and treatment of patients, as well as the problems appearing in the course of disease development. We also briefly refer to several aspects regarding the current knowledge on the molecular basis of CML and new potential therapeutic targets.

show abstract

“…In earlier trials, it was observed that rates of MCyR often exceeded those of CHR in BP-CML patients (Tables 4, 5) and it was suggested that achievement of MCyR without CHR was associated to inferior survival (151). More recently, a direct correlation between the depth of response and survival was seen in a cohort of 386 patients with BP-CML: 5-year OS rates were 72, 34, 12, and 11% for patients with complete molecular response (CMR), MMR but not CMR, CCyR but not MMR, and HR only, respectively (152). Interestingly, no differences in survival were seen between patients who underwent or not to allogeneic SCT once they had obtained a CMR, reinforcing the concept that rapid kinetics of response to TKI therapy could allow long-term disease control even without transplant.…”

Section: Open Questions and Perspectivesmentioning

confidence: 99%

Management of Chronic Myeloid Leukemia in Advanced Phase

et al. 2019

View full text Add to dashboard Cite

Management of chronic myeloid leukemia (CML) in advanced phases remains a challenge also in the era of tyrosine kinase inhibitors (TKIs) treatment. Cytogenetic clonal evolution and development of resistant mutations represent crucial events that limit the benefit of subsequent therapies in these patients. CML is diagnosed in accelerated (AP) or blast phase (BP) in <5% of patients, and the availability of effective treatments for chronic phase (CP) has dramatically reduced progressions on therapy. Due to smaller number of patients, few randomized studies are available in this setting and evidences are limited. Nevertheless, three main scenarios may be drawn: (a) patients diagnosed in AP are at higher risk of failure as compared to CP patients, but if they achieve optimal responses with frontline TKI treatment their outcome may be similarly favorable; (b) patients diagnosed in BP may be treated with TKI alone or with TKI together with conventional chemotherapy regimens, and subsequent transplant decisions should rely on kinetics of response and individual transplant risk; (c) patients in CP progressing under TKI treatment represent the most challenging population and they should be treated with alternative TKI according to the mutational profile, optional chemotherapy in BP patients, and transplant should be considered in suitable cases after return to second CP. Due to lack of validated and reliable markers to predict blast crisis and the still unsatisfactory results of treatments in this setting, prevention of progression by careful selection of frontline treatment in CP and early treatment intensification in non-optimal responders remains the main goal. Personalized evaluation of response kinetics could help in identifying patients at risk for progression.

show abstract

Differential depth of treatment response required for optimal outcome in patients with blast phase versus chronic phase of chronic myeloid leukemia

Cited by 10 publications

References 15 publications

Assessment of plasma cell myeloma minimal residual disease testing by flow cytometry in an international inter‐laboratory study: Is it ready for primetime use?

Assessment of plasma cell myeloma minimal residual disease testing by flow cytometry in an international inter‐laboratory study: Is it ready for primetime use?

<p>Chronic myelogenous leukemia, a still unsolved problem: pitfalls and new therapeutic possibilities</p>

Management of Chronic Myeloid Leukemia in Advanced Phase

Contact Info

Product

Resources

About