Alejandro Lazo-Langner

Inflammation markers and their trajectories after deep vein thrombosis in relation to risk of post-thrombotic syndrome

Post‐thrombotic syndrome (PTS) is a frequent chronic complication of deep vein thrombosis (DVT).

Patient preferences for stopping tyrosine kinase inhibitors in chronic myeloid leukemia

BACKGROUNDnWe used an interview-assisted survey of patients with chronic myeloid leukemia (cml) at a single tertiary care centre to explore patient reactions to and preferences for, and the risk-acceptability of, stopping tyrosine kinase inhibitor (tki) treatment.nnnMETHODSnThe study included patients with confirmed cml currently being treated with a tki. The survey was conducted by structured interview using a standard form. Patient preferences were explored in a case-based scenario using 0%-100% visual analog scales and 5-point Likert scales. Data were analyzed using proportions for dichotomous variables and medians and interquartile ranges for continuous variables.nnnRESULTSnOf 63 patients approached, 56 completed the survey. Participant responses suggest that the idea of stopping tki use is appealing to many patients if there is a chance of long-term stable disease and a high probability of response upon restarting a tki. Participants were more likely to stop their tki as the risk of relapse decreased. Participants reported loss of disease control and failure of disease to respond to treatment as important concerns if they chose to stop their tki.nnnCONCLUSIONSnGiven the current 60% estimated rate of relapse after discontinuation of tki therapy, most patients with cml chose to continue with tki. However, at the lower relapse rates reported with second-generation tkis, participants were more undecided, demonstrating a basic understanding of risk. Contrary to our hypothesis, neither compliance nor occurrence of side effects significantly affected patient willingness to stop their tki.

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light scattering versus microparticle size [1]. We are in essential agreement with the comments of both sets of authors that responded. We agree that some form of size calibration and standardization is needed to assure that results are comparable and reproducible between studies. As we indicated in our paper, the ISTH protocol is a crucial first step in this direction [2]. The important issues to consider, highlighted in our study and the comments from both groups, are that flow cytometer design can have a substantial impact on both the resolution of smaller microparticles and the relative intensity of what is termed forward scatter between different types of microspheres depending on the composition of the calibration microspheres used, the design of the flow cytometer, and the maintenance and alignment of individual instruments. Improved calibrators may need to have a refractive index similar to the particles being studied so that this is no longer a variable that can influence which particles are included in the analysis gate on different instruments. We did not intend to suggest that prior studies were primarily measuring platelets using theMegamix gate, but that there was some overlap between the platelet distribution and the large platelet microparticle distribution, the degree of overlap depending on the instrument used. As most prior studies have centrifuged samples to remove platelets and used annexin-V or other anionic lipid binding agents to define a population of particles from activated cells, these studies were likely to be measuring the larger end of the microparticle size distribution and not small platelets.

Response to "Need to minimize bias when surveying patient attitudes to stopping cml treatment".

The Editor, n nCurrent Oncology n nJune 23, 2014 n nWe thank Villemagne et al. for their comments, and we will address some of the issues that they raised. n nIt is important that clinicians understand patient concerns and values before key treatment decisions are made. Hypothetical scenarios such as “what if” or “when this occurs” are discussed routinely in close patient–physician relationships, and for that reason, we reject the assertion that our sample is not representative of patients with chronic myeloid leukemia (cml) who might be eligible for stopping tyrosine kinase inhibitors (tkis). We contend that it is not necessary for patients to have achieved a sustained deep molecular response (Bcr-Abl ≤ 0.0032%) to make informed responses to a hypothetical scenario. It is unknown whether a group of patients who have achieved a deep molecular response would respond differently than would patients whose molecular response might have not been optimal. n nFor the second point, consecutive patients with cml being treated by the investigators were approached for participation in the study during the study period. n nWe agree with the third comment that our single-centre study might have allowed for the opinion or influence of a small number of clinicians to have a significant impact on patient responses, which is explicitly stated in the Discussion section of the article. The reference cited by Villemagne et al. to support the statement that “studies of compliance in cml have shown a much more complex array of behaviours and choices” is also a single-centre study and subject to the same limitations1. n nIn response to the measurement tool, Villemagne et al. suggest that the first two measures of patient preference for relapse rates are confounded with willingness to stop treatment. Again, it is important to understand that the patient scenario is laid out with the remarks that the questions are hypothetical, that the response will not affect current clinical care, and that the very first question is asking about willingness to stop. There is no assumption of willingness to stop in the first question. It was not our intention to use only patients who are in deep molecular response and who are willing to stop to assess risk acceptability. Rather, we wanted to gauge the response of the general cml population who might or might not be faced with that decision. The visual analog scales were not modified from their original formats (with a 0 labelled the worst imaginable health state and a “sad face”). That presentation did cause some difficulty in interpretation of the question by the patients, but it was clarified by the interviewer in a standardized fashion. n nWe agree that patient compliance is complex, that our choices do not make a distinction between unintentional and deliberate noncompliance, and that self-reported measures of compliance are notoriously unreliable. The two references listed by Villemagne et al. as having validated measures for patient-reported outcomes of compliance and toxicity specific to cml have no documentation of the inclusion of cml patients in the studies2,3. The first study, by Morisky et al.2, dealt with adherence in hypertensive patients, and the second study, by Cleeland et al.3, categorized only 7 of 527 patients as having chronic leukemia in the outpatient setting, without clarifying the type of chronic leukemia. We agree that the evidence suggests that patients are more likely to misrepresent their treatment adherence in clinical settings; however, we conducted an interviewer-led study using an independent surveyor who had no involvement in patient care to minimize such bias. As discussed, conveying risk in treatment decisions is complex and is influenced by patient–physician communication and relationship4. Those interactions are also affected by physician beliefs about the quality of evidence, which influences how information about risk is conveyed to patients. Objective standardized patient education and decision tools can be useful adjuncts in such circumstances5. n nWe have outlined the various limitations of our study, but it nevertheless represents real-life discussions that can arise with patients who are generally well informed and interested in taking greater ownership of their health. Larger studies of stopping tkis are being done, and we anticipate that the question of stopping will arise for some patients. Our study offers a glimpse of how patients might approach this issue. Thus, the average patient with cml on a tki approaching this hypothetical question based on a personal opinion of “compliance” and a personal view of side effects might or might not be willing to stop. Larger multicentre studies can be performed, but ultimately each patient makes a personal decision based on their own perceptions of level of “compliance,” severity of side effects, and risk acceptability. The main message of the paper is that patients are capable of balancing risk, and the choice to stop a tki should involve shared decision-making between the patient and the clinician, which has been reported to be the approach preferred by most patients with cancer6.

Acute myeloid leukemia with promyelocytic morphology lacking RARA rearrangement and with double minutes, MYC deletion and 2 cell lines with amplification of MYC region: case report and literature review

Acute promyelocytic leukemia (APL) typically demonstrates the translocation t(15;17)(q24;q21) leading to PML-RARA fusion in ~92xa0% of the cases. The remaining t(15;17) negative APL-like cases may have other cytogenomic rearrangements, including cryptic PML-RARA fusion, translocation variants, or MYC gene amplification. The morphologic and cytogenetic profile of the APL-like cases with MYC amplification and the prognostic implications are largely unknown due to rarity of these cases. Here, we present a case of acute myeloid leukemia with promyelocytic morphology lacking the classic t(15;17) and RARA rearrangement, with der(5)t(5;17)(q13;21), MYC deletion, double minutes, and two cell lines with amplification of the MYC region. The two cell lines differed in contribution to the proportion of the cells and copy number of the amplified probes during the clinical course. This is likely the first case with such a complex molecular cytogenetic evolution detailed in the same patient. Literature review revealed that most of the APL-like cases with MYC amplification have no t(15;17) and PML-RARA (78.5xa0%; 7/8 cases) but a complex karyotype (75xa0%; 6/8 cases). Deletion 17p/monosomy 17 and deletion 9p/monosomy 9 are reported in ~40–50xa0% of the cases and are associated with poor prognosis. MYC amplification alone may not be a reliable prognostic indicator in APL-like cases. Our findings can be very helpful for clinicopathologic/cytogenetic correlation and potentially management of such rare but potentially unrecognized APL-like patients.