Consistency Of RQ-PCR Analysis Results In Peripheral Blood and Bone Marrow Samples In Chronic Myeloid Leukemia Patients: Relevance From The Practical and Logistic Point Of View

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2592-2592
Author(s):  
Giovanna Rege-Cambrin ◽  
Carmen Fava ◽  
Enrico Gottardi ◽  
Filomena Daraio ◽  
Emilia Giugliano ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Wilcoxon Test ◽  
Molecular Response ◽  
Two Samples ◽  
The Mean

Abstract Background Consensus has been achieved that standardized molecular quantitative analysis (RQ-PCR) on peripheral blood (PB) is a suitable method for monitoring residual disease in chronic myeloid leukemia (CML). However, BM is still obtained at specific timepoints, and in a number of cases, only bone marrow (BM) sample collected for cytogenetic analysis is available. Being one of the laboratory involved in the standardization process of molecular monitoring for CML patients, we decided to perform a comparative analysis of BM and PB samples in order to evaluate the consistency of the results. Methods Between March 2009 and January 2013, 230 consecutive RQ-PCR tests to assess BCR-ABL transcript levels from simultaneously collected PB and BM samples were performed (for a total of 460 analysis) on 77 patients affected by Ph+ CML in chronic phase treated in our center. All samples were analyzed in the same laboratory following international guidelines (Cross N, Leukemia 2012) and results were expressed according to the International Scale; ABL1 was used as control gene. Time from blood-drawn to processing was within 3-4 hours. Results Among the 230 pairs, 3 were considered as not evaluable because of inadequate material; for the purpose of this study, the remaining 227 pairs were considered as “evaluable”. 204 pairs were classified as “fit” when both BM and PB ABL amplification resulted in more than 10.000 copies; 23 pairs were considered unfit for ABL1 <10.000 in either one of the two samples (21) or both (2). The mean number of ABL1 copies in all evaluable samples was 35.639 for BM (SD 21.465) and 30.958 for PB samples (SD 18.696). Correlation analysis was performed on the whole population and in 4 subgroups: No Complete Cytogenetic Response (CCyR, 22%), CCyR without Major Molecular Response (MMR), (21.6%), CCyR with MMR (excluding patients with MR4 or better,19.8%), and CCyR with MR4 – MR4.5 (32,6%). Cytogenetic response was not available in 9 BM samples (4%), not included in the subgroup analysis. Spearman correlation of BCR/ABL ratio values between PB versus BM paired samples resulted in a statistically significant correlation in all groups, both for evaluable and fit pairs. Correlation was stronger in samples that were not in MMR or better (table 1 and figure 1). The Wilcoxon test showed that the mean difference of BCR/ABL values between paired PB and BM samples was not significantly different from zero (in evaluable and fit pairs by considering the whole population). Concordance was further analyzed by the K test which resulted in a coefficient equal to 0.627, corresponding to a notable degree of concordance. For patients in CCyR, agreement on classification of response (MMR, MR4, MR4.5) between paired PB and BM samples was observed in 125/168 evaluable pairs; 22 out of the 43 evaluable cases of disagreement were due to technical failures (in 10 BM and 12 PB samples). In 14 of the remaining 21 cases, PB was more sensitive. Conclusions In a single center experience of molecular analysis, BCR/ABL ratio was highly consistent in BM and PB samples. In less than 10% of the cases a single test did not reach the required sensitivity of 10.000 ABL copies and the double testing allowed to obtain a valid result. This may be especially valuable in evaluating an early response (i.e. at 3 months), when the amount of disease has prognostic relevance. The analysis will be expanded to include samples coming from different centers to evaluate a possible role of timing and transport on data consistency. Disclosures: Saglio: Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; ARIAD: Consultancy, Honoraria; Celgene: Consultancy, Honoraria.

scholarly journals An Atypical Initial Presentation of Chronic Myeloid Leukemia with Central Nervous System and Lymph Node Blast Crises

2016 ◽  
Vol 9 (2) ◽  
pp. 415-421 ◽  
Author(s):  
Khadega A. Abuelgasim ◽  
Saeed Alshieban ◽  
Nada A. Almubayi ◽  
Ayman Alhejazi ◽  
Abdulrahman R. Jazieh
Keyword(s):  
Central Nervous System ◽  
Bone Marrow ◽  
Nervous System ◽  
Chronic Myeloid Leukemia ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Single Agent ◽  
Chronic Phase ◽  
Current Evidence ◽  
Molecular Response

We describe the case of a young man with therapy-naive chronic myeloid leukemia who did not initially have any peripheral blood or bone marrow excess blasts but presented with extramedullary myeloid blast crises involving the central nervous system and multiple lymph nodes. Conventional cytogenetic tests were positive for t(9;22)(q34:q11) as well as for trisomy 8, 14 and 21 and del(16q). The patient’s peripheral blood and bone marrow were positive for the BCR-ABL oncogene when analyzed by fluorescence in situ hybridization and polymerase chain reaction. He achieved good clinical, radiological, cytogenetic and molecular response to acute myeloid leukemia induction chemotherapy combined with 16 doses of triple intrathecal chemotherapy and oral dasatinib (second-generation tyrosine kinase inhibitor) treatment. Due to his poor general condition, he was treated with 24 Gy of whole-brain radiation therapy, as allogeneic stem cell transplantation was not feasible. Although extramedullary CNS blast crises are usually associated with a very poor outcome, our patient remains in complete cytogenetic and molecular remission, on single-agent dasatinib, 4 years after the diagnosis with no current evidence of active extramedullary disease. This suggests that dasatinib has a role in controlling not only chronic-phase chronic myeloid leukemia, but also its CNS blast crisis.

Real-Life Management of Children and Adolescents with Chronic Myeloid Leukemia: The Italian Experience

2018 ◽  
Vol 140 (2) ◽  
pp. 105-111 ◽  
Author(s):  
Fiorina Giona ◽  
Michelina Santopietro ◽  
Giuseppe Menna ◽  
Maria Caterina Putti ◽  
Concetta Micalizzi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Real Life ◽  
Chronic Phase ◽  
Optimal Management ◽  
Molecular Monitoring ◽  
Italian Experience ◽  
Adults And Children

Background: To date, no data on the adherence to specific guidelines for children with chronic myeloid leukemia (CML) in chronic phase (CP) have been reported. Methods: Since 2001, guidelines for treatment with imatinib mesylate (IM) and monitoring in patients younger than 18 years with CP-CML have been shared with 9 pediatric referral centers (P centers) and 4 reference centers for adults and children/adolescents (AP centers) in Italy. In this study, the adherence to these guidelines was analyzed. Results: Thirty-four patients with a median age of 11.4 years and 23 patients with a median age of 11.0 years were managed at 9 P and at 4 AP centers, respectively. Evaluations of bone marrow (BM) and/or peripheral blood (PB) were available for more than 90% of evaluable patients. Cytogenetics and molecular monitoring of PB were more consistently performed in AP centers, whereas molecular analysis of BM was carried out more frequently in P centers. Before 2009, some patients who responded to IM underwent a transplantation, contrary to the guidelines’ recommendations. Conclusions: Our experience shows that having specific guidelines is an important tool for an optimal management of childhood CP-CML, together with exchange of knowledge and proactive discussions within the network.

scholarly journals Nilotinib is effective in patients with chronic myeloid leukemia in chronic phase after imatinib resistance or intolerance: 24-month follow-up results

Blood ◽  
2011 ◽  
Vol 117 (4) ◽  
pp. 1141-1145 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Francis J. Giles ◽  
Kapil N. Bhalla ◽  
Javier Pinilla-Ibarz ◽  
Richard A. Larson ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Study Endpoint ◽  
Primary Study ◽  
Molecular Response ◽  
Open Label ◽  
Imatinib Resistance ◽  
Abl Tyrosine Kinase

Abstract Nilotinib is a potent selective inhibitor of the BCR-ABL tyrosine kinase approved for use in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP), and in CML-CP and CML-accelerated phase after imatinib failure. Nilotinib (400 mg twice daily) was approved on the basis of the initial results of this phase 2 open-label study. The primary study endpoint was the proportion of patients achieving major cytogenetic response (CyR). All patients were followed for ≥ 24 months or discontinued early. Of 321 patients, 124 (39%) continue on nilotinib treatment. Overall, 59% of patients achieved major CyR; this was complete CyR (CCyR) in 44%. Of patients achieving CCyR, 56% achieved major molecular response. CyRs were durable, with 84% of patients who achieved CCyR maintaining response at 24 months. The overall survival at 24 months was 87%. Adverse events were mostly mild to moderate, generally transient, and easily managed. This study indicates that nilotinib is effective, with a manageable safety profile, and can provide favorable long-term benefits for patients with CML-CP after imatinib failure. This trial was registered at www.clinicaltrials.gov as #NCT00109707.

Results of Imatinib Dose Escalation After 36 Months of Follow-up in Chronic Myeloid Leukemia Patients with Failure or Sub-Optimal Response According to 2006 EuropeanLeukemia Net (ELN) Criteria.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3302-3302
Author(s):  
Massimo Breccia ◽  
Fabio Stagno ◽  
Roberto Latagliata ◽  
Paolo Vigneri ◽  
Laura Cannella ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Dose Escalation ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Standard Dose ◽  
Acquired Resistance ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Molecular Response

Abstract Abstract 3302 Poster Board III-190 Introduction Imatinib mesylate (IM) given at a daily dose of 400 mg currently represents the gold standard of care for patients with chronic myeloid leukemia (CML) in chronic phase (CP). European LeukemiaNet (ELN) guidelines propose IM dose escalation to rescue those CML patients with either suboptimal response or drug resistance. We report on the long-term efficacy of IM dose escalation in 74 patients with CP-CML after suboptimal response or failure to IM conventional dose. Patients and methods Median age was 50 years (range 19-85), there were 52 males and 22 females. Thirteen patients were classified as hematologic failure (10 primary and 3 secondary), 57 patients as cytogenetic resistance (24 primary and 33 acquired). Three patients escalated the dose for cytogenetic suboptimal response and one patient for molecular suboptimal response at 18 months. Fifty-four received IM dose escalation from 400 to 600 mg and 20 patients from 400 to 800 mg. Results Overall, after a median follow-up of 36 months, 68/74 (91.8%) patients maintained or achieved a complete haematologic response (CHR); this was maintained in all patients who escalated the dose for cytogenetic failure or suboptimal response. A major cytogenetic response (MCyR) was achieved in 41 patients (72%) who escalated the dose for cytogenetic failure and in 6/13 (46%) patients who escalated imatinib for hematologic failure (p=0.002). Overall, complete cytogenetic responses (CCR) were achieved in 27 (37%) out of 74 CML patients: of the 13 hematologic failure patients, only 5 achieved CCyR: all patients had prior acquired resistance to imatinib. Of the 57 cytogenetic failure, 22 reached CCR: this response was obtained in 27% of the primary cytogenetic resistant, and in 50% of the acquired cytogenetic resistant patients (p=0.02). Three patients who escalated the dose for cytogenetic suboptimal response obtained CCR and complete molecular response (CMR), whereas one patient who escalated the dose for molecular suboptimal response at 18 months did not obtain CMR. Median time to cytogenetic response was 3.5 months. Cytogenetic responses occurred in 37/50 patients who escalated the dose to 600 mg and in 10/20 patients who escalated to 800 mg daily (p=0.234). CMR was obtained in 10 patients: in 7 patients who escalated the dose for cytogenetic failure and in 3 patients who escalated imatinib for suboptimal cytogenetic response. Estimated 2 year-progression free survival (PFS) and overall survival (OS) is 87% and 85% respectively. Sixteen patients (21.6%) experienced toxicities and had temporarily IM interruption. Conclusions Imatinib dose escalation can induce sustained responses in a subset of patients with cytogenetic resistance and a prior suboptimal cytogenetic response to standard-dose imatinib, whereas it appears less effective in haematologic failure patients or in molecular sub-optimal responders. The availability of second generation TKI should be taken into account in these letter categories of patients. Disclosures No relevant conflicts of interest to declare.

Clinical Efficacy and Safety Of Dasatinib For Newly Diagnosed Chronic Myeloid Leukemia In Chronic Phase In Japan

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1493-1493
Author(s):  
Kohei Yamaguchi ◽  
Kazunori Murai ◽  
Shigeki Ito ◽  
Tomoaki Akagi ◽  
Kazuei Ogawa ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Major Molecular Response ◽  
Once Daily

Abstract Background Dasatinib is a second-generation BCR-ABL inhibitor that has a 325-fold higher potency than imatinib and a 16-fold higher potency than nilotinib in vitro. The previous report from the global DASISION trial showed dasatinib resulted in significantly higher and faster rates of complete cytogenetic response (CCyR) and major molecular response (MMR) compared with imatinib. We conducted a phase II study to evaluate the efficacy and safety of dasatinib in patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP) in Japan. Methods Eighty newly diagnosed CML-CP patients were include in this study. Patients received dasatinib 100mg once daily. Treatment was continued until disease progression or unacceptable toxicity. Primary end point was the rate of major molecular response (MMR) by 12 months. MMR defined as a BCR-ABL transcript level of 0.1% or lower on the International scale by means of a real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in peripheral blood. Secondary end points were the rate of complete cytogenetic response (CCyR) by 12 months, the rate of MR4.5 (either (i) detectable disease with <0.0032% BCR-ABL1 IS or (ii) undetectable disease in cDNA with >32,000 ABL1 transcripts in the same volume of cDNA used to test for BCR-ABL1) by 12 months and adverse events of dasatinib (UMIN #000006358). Results Eighty newly diagnosed CML-CP patients were included in this study. All except one patient administered dasatinib 100 mg once daily. One patient was withdrawal before administration of dasatinib. So far, there were 71 patients with 6 months follow-up and 51 patients with 12 months follow-up. The estimated MMR rates were 69.5 % (95%CI, 58.7-80.3 %) by 6 months and 82.7% (95%CI, 73.0-92.4 %) by 12 months. The estimated MR4.5 rates were 27.1 % (95%CI, 16.7-37.5 %) by 6 months and 48.9% (95%CI, 36.0-61.7 %) by 12 months. Only 6 patients were withdrawal because of adverse event (5 patients) and ineffectiveness (1 patient). Conclusion Dasatinib treatment results in higher rates of molecular responses in newly diagnosed CML-CP patients in Japan. Dasatinib as the first-line agent might be acceptable for CML-CP patients because of better clinical efficacy and less toxicity. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Impact of Proteomic Profile of Peripheral Blood and Bone Marrow Sera on Molecular Response in Patients with Chronic Myeloid Leukemia: Preliminary Data

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5515-5515
Author(s):  
Nicola Sgherza ◽  
Vito Garrisi ◽  
Giacoma De Tullio ◽  
Simona Serratì ◽  
Angela Iacobazzi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Preliminary Data ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Differentially Expressed ◽  
Molecular Response ◽  
Proteomic Profile ◽  
Group A ◽  
Group B

Abstract BACKGROUND. Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm characterized by an aberrant protein (BCR–ABL) which is a constitutively active tyrosine kinase. According to the latest ELN recommendations for the management of CML, molecular response (MR) is best assessed according to the International Scale (IS) as the ratio of BCR-ABL1 transcripts to ABL1 transcripts, or other internationally recognized control transcripts. It is expressed and reported as BCR-ABL1% on a log scale where 10%, 1%, 0.1%, 0.01%, 0.0032%, and 0.001% correspond to a decrease of respectively 1 (MR1), 2 (MR2), 3 (MR3), 4 (MR4), 4.5 (MR4.5) logs below the standard baseline that was used in the IRIS study. Recent advances in the proteomic field have allowed us to better understand the biology of several cancer types and/or discover new candidate biomarkers, but very few data are available in CML. AIMS. The purpose of this study was to evaluate a possible correlation between depth of MR and proteomic profile in sera samples obtained from the peripheral blood and bone marrow of CML patients. PATIENTS AND METHODS Samples were consecutively and prospectively obtained from 20 CML patients observed between January and June 2014 at the Hematology Unit of the National Cancer Research Centre “Istituto Tumori Giovanni Paolo II” in Bari, Italy. Each individual involved in the study signed an informed consent form authorizing the Institute to utilize their biological tissues for research purposes. All patients at diagnosis displayed the classic t(9;22) Ph chromosome according to standard cytogenetics. The BCR/ABL transcript at RT-PCR was b3a2 in 13 patients and b2a2 in 7 patients. Peripheral blood and bone marrow samples were centrifuged within 30 minutes of sample taking. Serum specimens were immediately collected and frozen at −80°C. Twenty sera from peripheral blood were sampled from 5 patients in MR1 response, four in MR2, eight in MR3, two in MR4 and 1 patient at diagnosis; for eleven patients serum from bone marrow was also available; in particular 2 were sampled from patients in MR1, 3 in MR2, 4 in MR3, 1 in MR4 and 1 at diagnosis. Patients were grouped in two cohorts: the first comprised those with lower molecular response to MR3 (group A: 10 patients) and the second greater than or equal to MR3 (group B: 10 patients). The association of proteomic profile with molecular response was performed using the SELDI ToF Mass Spectrometry platform. Each specimen was spotted on an IMAC30 metal affinity protein-chip, prepared according to the manufacturer's instructions, and analyzed in duplicate. RESULTS Fourteen differentially expressed peaks were highlighted when comparing peripheral sera from group A and group B, but none was statistically significant. When comparing 11 available serum samples from the bone marrow of groups A (6) and B (5), four peaks (m/z 10629, m/z 3889, m/z 7772, m/z 7987) were reported as differentially expressed in a statistically significant way (p<0.05). Focusing the differential expression analysis in peripheral sera only on MR1 patients (including one patient at diagnosis) versus MR4 patients, one peak at m/z 11092 was identified as significantly and differentially expressed (p < 0.05) (Figure 1). Similarly, comparing bone marrow sera only from MR1 and MR4 patients respectively, 32 peaks were differentially expressed. Once again the peak at m/z 11092 resulted under expressed in MR1 patients, and interestingly the single patient at diagnosis had the lowest value. No statistical differences were evidenced when comparing peripheral blood and bone marrow sera obtained from b3a2 and b2a2 patients. CONCLUSIONS These preliminary data suggest that an over-expression of m/z 11092 in serum obtained from peripheral blood and bone marrow could be associated with a deeper molecular response; further investigations are needed on a larger number of patients in order to confirm or refute our results and, to definitively characterize the peak at m/z 11092. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Increased Expression of TIGIT/CD57 in Peripheral Blood/Bone Marrow NK Cells in Patients with Chronic Myeloid Leukemia

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Danlin Yao ◽  
Ling Xu ◽  
Lian Liu ◽  
Xiangbo Zeng ◽  
Juan Zhong ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Nk Cells ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Replicative Senescence ◽  
Cell Function ◽  
De Novo ◽  
Nk Cell ◽  
Molecular Response

The antitumor activity of NK cells in patients with chronic myeloid leukemia (CML) is inhibited by the leukemia microenvironment. Recent studies have identified that the expression of TIGIT, CD57, and KLRG1 is related to the function, maturation, and antitumor capabilities of NK cells. However, the characteristics of the expression of these genes in the peripheral blood (PB) and bone marrow (BM) from patients with CML remain unknown. In this study, we used multicolor flow cytometry to assay the quantity and phenotypic changes of NK cells in PB and BM from de novo CML (DN-CML) and CML patients acquiring molecular response (MR-CML). We found that the expression of TIGIT, which inhibits NK cell function, is increased on CD56+ and CD56dim NK cells in DN-CML PB compared with those in healthy individuals (HIs), and it is restored to normal in patients who achieve MR. We also found that the expression of CD57 on NK cells was approximately the same level in PB and BM from DN-CML patients, while decreased CD57 expression was found on CD56+ and CD56dim NK cells in HI BM compared with PB. Additionally, those two subsets were significantly increased in DN-CML BM compared to HI BM. The expression of CD57 correlates with replicative senescence and maturity for human NK cells; therefore, the increase in TIGIT on PB NK cells together with an increase in CD57 on BM NK cells may explain the subdued NK cell antileukemia capacity and proliferative ability in DN-CML patients. These results indicate that reversing the immune suppression of PB NK cells by blocking TIGIT while improving the proliferation of BM NK cells via targeting CD57 may be more effective in removing tumor cells.

scholarly journals Chronic myeloid leukemia (CML) with P190BCR-ABL: analysis of characteristics, outcomes, and prognostic significance

Blood ◽  
2009 ◽  
Vol 114 (11) ◽  
pp. 2232-2235 ◽  
Author(s):  
Dushyant Verma ◽  
Hagop M. Kantarjian ◽  
Dan Jones ◽  
Rajyalakshmi Luthra ◽  
Gautam Borthakur ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Prognostic Significance ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
Blast Phase ◽  
Complete Hematologic Response ◽  
Risk Patients

Abstract The most common BCR-ABL transcripts in chronic myeloid leukemia (CML) are e13a2(b2a2) and e14a2(b3a2). Other transcripts such as e1a2 are rare and their outcome with tyrosine kinase inhibitors (TKI) therapy is undefined. We analyzed 1292 CML patients and identified 14 with only e1a2 transcripts, 9 in chronic phase (CP), 1 in accelerated phase (AP), and 4 in blast phase (BP). Of the CP, 4 achieved complete hematologic response (CHR); 2, complete cytogenetic response (CCyR); 2, partial cytogenetic response (PCyR), and 1 did not respond to imatinib. Five patients progressed to myeloid BP (3), lymphoid BP (1), or AP (1). The AP patient received various TKIs sequentially and achieved only CHR. BP patients received hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, adriamycin, dexamethasone) plus imatinib/dasatinib or idarubicin plus cytarabine (Ara-C); 2 did not respond, 1 had CCyR, and 1 short-lasting complete molecular response (CMR). Overall, cytogenetic responses lasted 3 to 18 months; only 2 achieved major molecular response (MMR) on TKI. P190BCR-ABL CML is rare and is associated with an inferior outcome to therapy with TKI. These patients need to be identified as high-risk patients.

Prediction of Response to Imatinib by Prospective Quantitation of BCR-ABL Transcript in Late Chronic Phase Chronic Myeloid Leukemia PatientsBy GIMEMA Working Party on CML.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4672-4672
Author(s):  
Giovanni Martinelli ◽  
Gianantonio Rosti ◽  
Fabrizio Pane ◽  
Marilina Amabile ◽  
Simona Bassi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Working Party ◽  
Progression Free Survival ◽  
Prediction Of Response ◽  
Free Survival ◽  
Blood Samples

Abstract Imatinib mesylate (STI571), a specific Bcr-Abl inhibitor, has shown a potent antileukemic activity in clinical studies of chronic myeloid leukemia (CML) patients. Early prediction of response to imatinib cannot be anticipated. We used a standardized quantitative reverse-transcriptase polymerase chain reaction (QRT-PCR) for bcr-abl transcripts on 191 out of 200 late-chronic phase CML patients enrolled in a phase II clinical trial with imatinib 400 mg/day. Bone marrow samples were collected before treatment, after 3, 6 and 12 months or at the end of study treatment (12 months) while peripheral blood samples were obtained after 2, 3, 6, 10, 14, 20 and 52 weeks of therapy. The amount of Bcr-Abl transcript was expressed as the ratio of Bcr-Abl to β2-microglobulin (β2M). We show that, following initiation of imatinib, the early Bcr-Abl level trends in both bone marrow and peripheral blood samples made it possible to predict the subsequent cytogenetic outcome after 6 and 12 months of treatment, and that these early trends were also predictive of progression-free survival.

Better Molecular Response (MR) to Imatinib (IM) in Early Chronic Phase (CP) Versus Late CP Chronic Myeloid Leukemia (CML) Patients (pts) in Complete Cytogenetic Response (CCR): A Comparison at 24 Months of 2 Clinical Trials of the GIMEMA Working Party on CML on Behalf of the GIMEMA Working Party on Chronic Myeloid Leukemia (GIMEMA-CML).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1096-1096 ◽  
Author(s):  
Angela Poerio ◽  
Marilina Amabile ◽  
Ilaria Iacobucci ◽  
Simona Soverini ◽  
Sabrina Colarossi ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Nested Pcr ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Working Party ◽  
Cytogenetic Response ◽  
Interferon Α ◽  
Molecular Response ◽  
Front Line ◽  
Log Reduction

Abstract We sought to determine the differences in molecular response between early and late CP pts with CML who achieved a CCR after treatment with IM at the standard dose of 400mg/d. We studied 2 different cohorts of patients in CCR: 67/191 (35%) pts after α-Interferon (α-IFN) failure enrolled on the CML/002/STI571 protocol 53/76 (70%) pts treated front line with a combination of IM and pegilated IFN-α (PEG-IFN) enrolled on the CML/011/STI571 protocol Cytogenetic response was monitored on bone marrow (BM) metaphases and molecular response was assessed by real time RT-PCR (TaqMan) BM and peripheral blood (PB) samples, collected at baseline, 3, 6, 9 and 12 months during the first year, and every 6 months thereafter. Molecular response was expressed as the ratio between BCR/ABL and β2-microglobulin (β2-M) x100. The lowest level of detectability of the method was 10−5. Negative results (i.e. undetectable transcript) were confirmed by nested PCR performed 4 times (sensitivity 10−6). For the purpose of this analysis, a major molecular response (MMR) was defined as a BCR-ABL/β2M value &lt;0.0001%, which turned out to be roughly equivalent to a 3-log reduction and a complete molecular response (CMR) was defined as negative (undetectable) BCR/ABL levels confirmed by nested PCR. We observed a progressive decrease of the amount of BCR/ABL transcript in pts who achieved a CCR. At 24 months the median reduction in BCR/ABL transcript level was: a 3-log reduction in late CP pts a 4-log reduction in early CP pts In the latter group of pts MR was assessed also at 36 months. So we observed that 36 months after the first dose of IM and PEG-IFN pts who were still in CCR had the median value of BCR/ABL transcript of 0.00001% both in BM and PB. Therefore all these pts achieved a MMR. However only 8/53 (4%) pts were in CMR (undetectable BCR/ABL at least once as assessed by nested PCR). We conclude that front-line treatment with IM results in a better quality MR (4-log reduction in BCR/ABL transcript levels in early CP pts, as against a 3-log reduction in late CP pts). Figure Figure

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