Outcomes of Telerehabilitation Versus In-Office Training With Magnification Devices for Low Vision: A Randomized Controlled Trial.

Purpose: An evidence basis is lacking but needed to compare reading ability outcomes after magnification device training remotely via telerehabilitation versus in office. Methods: A multicenter randomized controlled trial at academic centers and vision rehabilitation private practices randomized 61 visually impaired adults to telerehabilitation or in-office training 1 to 4 months after dispensing new portable electronic, hand-held, or stand optical magnifiers. Telerehabilitation included loaner equipment for Zoom videoconferencing with remote control access software. Using a multilevel regression model, changes in Activity Inventory responses using Rasch analysis estimated reading ability in dimensionless log odds units (logits) (0.14-logit change corresponds with ability change expected from a one-line change in visual acuity). Results: Across 47 participants who completed the trial, reading ability with new magnifiers improved significantly by 0.61 logits on average (95% confidence interval [CI], 0.36-0.86; P < 0.001) from baseline to 1 month, and by an additional 0.44 logits on average (95% CI, 0.19-0.69; P < 0.001) from 1 to 4months (i.e., after magnifier training), with very similar significant findings for both telerehabilitation (n = 29; mean improvement = 0.44 logits; 95% CI, 0.08-0.80; P = 0.018) and in-office training (n = 18; mean improvement = 0.43 logits; 95% CI, 0.15-0.71; P = .003), and no significant difference between randomized groups across both follow-ups (95% CI, -0.43 to 0.61; P = .73). Vision, demographics, and health factors were nonsignificantly related to reading ability changes from 1 to 4 months. Conclusions: Reading ability improved after the provision of newly dispensed magnifiers, with further improvements following additional magnifier training via either telerehabilitation or in-office usual care. Translational Relevance: These findings provide support for the use of telerehabilitation to enhance reading ability with newly prescribed magnifiers as an alternative modality of care delivery.

Value of Handheld Optical Illuminated Magnifiers for Sustained Silent Reading by Visually Impaired Adults.

SIGNIFICANCE: Vision rehabilitation providers tend to recommend handheld, illuminated optical magnifiers for short-duration spot reading tasks, but this study indicates that they are also a viable option to improve sustained, continuous text reading (e.g., books or magazines), especially for visually impaired adults who read slowly with only spectacle-based near correction. PURPOSE: The utility of handheld optical magnifiers for sustained silent reading tasks involving normal-sized continuous text could be a valuable indication that is not recognized by vision rehabilitation providers and patients. METHODS: Handheld, illuminated optical magnifiers were dispensed to 29 visually impaired adults who completed the sustained silent reading test by phone at baseline without the new magnifier and 1 month after using the magnifier. Reading speed in words per minute (wpm) was calculated from the time to read each page and then averaged across up to 10 pages or determined for the fastest read page (maximum). RESULTS: From baseline without the magnifier to 1 month with the magnifier, there was a significant improvement in mean reading speed by 14 wpm (95% confidence interval [CI], 2.6 to 24; P = .02) and for maximum reading speed by 18 wpm (95% CI, 5.4 to 30; P = .005) on average across participants. Participants who had slower baseline reading speeds without the magnifier demonstrated significantly greater improvements in mean and maximum reading speeds on average with the magnifier (95% CI, 8 to 32 [ P = .003]; 95% CI, 4 to 36 [ P = .02]). A significantly greater number of pages were read with the new magnifier than without it (Wilcoxon z = -2.5; P = .01). A significantly greater number of pages were read with the magnifier by participants who read fewer pages at baseline (95% CI, 0.57 to 5.6; P = .02) or had greater improvements in mean reading speed (95% CI, 0.57 to 5.6; P = .007). CONCLUSIONS: Many visually impaired adults read more quickly and/or read a greater number of pages after using a new magnifier for a month than compared to without it. The largest gains occurred among those with more difficulty at baseline, indicating the potential to improve reading rates with magnifiers for those with greater deficits.

Telerehabilitation Training to Facilitate Improved Reading Ability with New Magnification Devices for Low Vision.

SIGNIFICANCE: This pilot study provides some insight about the potential benefits of telerehabilitation training to improve the reading ability of adults with low vision using magnifiers, to spur future work with larger groups. Telerehabilitation services can be implemented clinically to facilitate access to follow-up care for low vision. PURPOSE: A recent Cochrane systematic review revealed that there are no published visual function outcomes for telerehabilitation with handheld magnification devices for low vision; thus, this study aimed to provide evidence for its preliminary efficacy. METHODS: One to 4 months after receiving a new magnification device (i.e., handheld or stand optical magnifier or portable electronic magnifier), 14 adult low vision patients (with any visual acuity level or ocular diagnosis) received two training sessions at home via telerehabilitation with their vision rehabilitation provider located remotely in-office. Telerehabilitation included a loaner smartphone for Zoom videoconferencing with remote control access software. The Minnesota Low-Vision Reading Test was administered during each of the telerehabilitation sessions to assess near reading (acuity and speed) with the new magnifier. RESULTS: Mean reading acuity with the magnifier was 0.17 logMAR across subjects before training at telerehabilitation session 1, which significantly improved to 0.09 on average a few weeks later at telerehabilitation session 2 (95%confidence interval, -0.001 to -0.16; P = .047). Logarithm reading speed with the magnifier for the reading acuity level at session 1 improved significantly by 0.18 log words per minute on average for the same text size at session 2 (95% confidence interval, 0.06 to 0.29; P = .002). With the magnifier at session 2, 71% of participants gained at least 0.1 log unit in reading acuity, and half improved by >0.01 in log reading speed; all participants with increased reading speed also improved in reading acuity ( P = .02). CONCLUSIONS: These preliminary data support that telerehabilitation can enhance reading ability and efficiency with newly prescribed magnifiers as an alternative option to in-office vision rehabilitation.

Acceptability of Telerehabilitation for Magnification Devices for the Visually Impaired Using Various Approaches to Facilitate Accessibility.

Purpose: We examined different methods to reduce the burden of accessing technology for videoconferencing during telerehabilitation for magnification devices for the visually impaired. Methods: During telerehabilitation studies over the past 5 years, vision rehabilitation providers assessed and gave training to visually impaired participants with newly dispensed magnification devices at home who connected to Zoom videoconferencing via loaner tablets or smartphones with assistance from (phase 1; n = 10) investigators by phone, (phase 2; n = 11) local Lions Club volunteers in participants' homes, or (phase 3; n = 24) remote access control software in a randomized controlled trial with 13 usual care controls who received in-office training. All participants completed the same post-telerehabilitation phone survey. Results: A significantly greater proportion of phase 3 subjects indicated they strongly or mostly agreed that the technology did not interfere with the session (96%) compared to phase 1 (60%; 95% confidence interval [CI], 1.2-12.5; P = 0.03) or phase 2 (55%; 95% CI, 1.8-188; P = 0.01). The majority indicated telerehabilitation was as accurate as in person (68%), they were comfortable with telerehabilitation (91%) and interested in a future session (83%), and their magnifier use improved (79%), with no significant differences in these responses between phases (all P > 0.10), including comparisons of participants randomized to telerehabilitation or in-office training in phase 3 who reported similar overall satisfaction levels (P = 0.84). Conclusions: Participants across all phases reported high levels of acceptance for telerehabilitation, with least interference from technology using remote access control in phase 3. Translational Relevance: With accommodations for accessibility to videoconferencing technology, telerehabilitation for magnification devices can be a feasible, acceptable, and valuable option in countries with resources to support the technology.

Feasibility of Telerehabilitation for Low Vision: Satisfaction Ratings by Providers and Patients.

SIGNIFICANCE: This pilot study demonstrated feasibility and acceptability of telerehabilitation between a provider in-office and a low vision patient at home as an approach to provide follow-up care to improve reading ability with magnification devices and that would help overcome barriers related to transportation and paucity of providers. PURPOSE: A recent systematic review found no publications with results on the topic of telerehabilitation for low vision. Our goal was to perform the initial steps to develop, administer, refine, and evaluate components required to deliver follow-up low vision telerehabilitation services. METHODS: Three low vision providers (ophthalmic technician or optometrist) conducted telerehabilitation sessions from their office with 10 visually impaired older adults in their homes, who recently received a handheld magnification device for reading and self-reported difficulty with returning for follow-up training at their provider's office. All except one participant had never used videoconferencing before our study, and three had never used the Internet. Participants and providers rated the use of loaner hardware devices (i.e., tablets, MiFi mobile hotspot) and Health Insurance Portability and Accountability Act-compliant, secure videoconference services during telerehabilitation sessions at which participants read MNREAD cards and received feedback on magnifier use. RESULTS: Providers reported little to no difficulty with evaluating participants' reading speed, reading accuracy, and working distance with their magnifier. Both providers and participants rated video quality as excellent to good. Audio quality ratings were variable, generally related to signal strength or technical issues during some sessions. All participants agreed that they were satisfied and comfortable receiving telerehabilitation and evaluation via videoconferencing. Eight of 10 reported that their magnifier use improved after telerehabilitation. All except one reported that they were very interested in receiving telerehabilitation services again if their visual needs change. CONCLUSIONS: Positive feedback from both participants and providers in this pilot study supports the feasibility, acceptability, and potential value of low vision telerehabilitation.

Gemcitabine, dexamethasone, and cisplatin (GDP) is an effective and well-tolerated salvage therapy for relapsed/refractory diffuse large B-cell lymphoma and Hodgkin lymphoma.

The optimal choice of salvage therapy for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma (HL) remains unknown. Based on promising results of phase II trials, the preferred salvage regimen in British Columbia since 2002 has been the out-patient regimen, gemcitabine, dexamethasone, and cisplatin (GDP). We conducted a retrospective analysis including all patients with relapsed/refractory DLBCL or HL who received GDP as salvage therapy between September 2002 and June 2010. We identified 235 patients: 152 DLBCL, 83 HL. Overall response rates were 49% and 71% for patients with DLBCL and HL, respectively. Within the transplant-eligible population, 52% of patients with DLBCL and 96% of patients with HL proceeded to stem cell transplantation. The 2-year progression-free survival and overall survival were 21% and 28% in the DLBCL cohort, and 58% and 85% in the HL group. GDP is an effective and well-tolerated out-patient salvage regimen for relapsed/refractory DLBCL and HL.

Outcome of Patients With Non-Hodgkin Lymphomas With Concurrent MYC and BCL2 Rearrangements Treated With CODOX-M/IVAC With Rituximab Followed by Hematopoietic Stem Cell Transplantation.

BACKGROUND: Double-hit lymphoma is characterized by the presence of concurrent MYC (myelocytomatosis oncogene) and BCL2 (B-cell lymphoma 2) gene rearrangements. Prognosis is poor with standard chemoimmunotherapy. Since 2003, the British Columbia Cancer Agency has used CODOX-M/IVAC+R (cyclophosphamide, vincristine, doxorubicin, methotrexate, cytarabine, ifosfamide, and etoposide, combined with rituximab) followed by consolidative hematopoietic cell transplantation as definitive treatment for double-hit lymphoma. PATIENTS AND METHODS: A retrospective review of the survival outcomes of patients with double-hit lymphoma treated at our institution was conducted. Thirty-two patients diagnosed with non-Hodgkin lymphoma with concurrent MYC and BCL2 translocations from 2003 to 2013 were identified. Cases with MYC or BCL2 amplification and those with overexpression in immunohistochemistry analysis were excluded. RESULTS: Median age at diagnosis was 53.0 years (range, 35.5-70.9 years), 23 (72%) were male, and 30 (94%) had stage III to IV disease. CODOX-M/IVAC+R was administered in 25 (78%) patients and 20 (80%) achieved a partial remission or better, of which 9 (36%) had a complete remission. Nineteen of the 32 (59%) patients underwent upfront hematopoietic cell transplantation. At a median follow-up of living patients of 26.4 months, 14 (44%) were alive in remission, 15 (47%) died, and 3 (9%) were alive in relapse. The 2-year progression-free survival (PFS) and overall survival (OS) of all patients were 41% and 53%, respectively. The sixteen patients treated with CODOX-M/IVAC+R followed by hematopoietic cell transplantation had a 2-year PFS of 60% and 2-year OS of 82%. CONCLUSION: Patients with double-hit lymphoma treated with CODOX-M/IVAC+R followed by hematopoietic cell transplantation can achieve durable remissions, although disease progression before transplantation remains a significant problem.

Normal karyotype CALLA-positive adult pre-B ALL: dismal outcome with chemotherapy for patients with loss/gain of ABL1 and/or BCR FISH signals.

BACKGROUND: Diagnostic karyotype and molecular studies represent the most powerful prognostic indicators in acute myeloid leukemia and provide the framework for risk stratification. Risk stratification in ALL has also a vital role in predicting outcome and identifying patients at higher risk of relapse with multiagent chemotherapy, but the role of diagnostic karyotype and molecular markers in adult ALL is limited to few well recognized cytogenetic abnormalities. PATIENTS AND METHODS: We report a case series of 6 adult ALL patients with a characteristic molecular abnormality that have done poorly with chemotherapy. Between April 2004 and November 2009, 72 adult ALL patients (Pre-B-cell 61; T-cell 11) were referred to and treated at the Leukemia/BMT Program of BC in Vancouver, Canada. FISH for BCR-ABL fusion was positive in 12 of 61 Pre-B cell ALL patients. An additional 6 patients were negative for this typical fusion but had FISH abnormalities related to BCR and/or ABL1. RESULTS: In this report, we describe the clinical and hematopathologic characteristics of these 6 patients and their poor outcome. We review the literature where only 2 similar cases with normal karyotype Pre-B ALL and associated FISH BCR/ABL1 numerical abnormalities were found. CONCLUSION: We recommend screening all adult pre-B ALL patients with normal karyotype for this clonal abnormality and suggest classifying these ALL patients into the high-risk category.

SCI-U: e-learning for patient education in spinal cord injury rehabilitation.

BACKGROUND/OBJECTIVES: To develop an online patient education resource for use in spinal cord injury rehabilitation. PARTICIPANTS: The development process involved more than 100 subject-matter experts (SMEs) (rehabilitation professionals and consumers) from across Canada. Preliminary evaluation was conducted with 25 end-users. METHODS: An iterative development process was coordinated by a project team; SMEs (including patients) developed the content in working groups using wiki-based tools. Multiple rounds of feedback based on early prototypes helped improve the courses during development. RESULTS: Five courses were created, each featuring more than 45 minutes of video content and hundreds of media assets. Preliminary evaluation results indicate that users were satisfied by the courses and perceived them to be effective. CONCLUSIONS: This is an effective process for developing multimedia patient education resources; the involvement of patients in all parts of the process was particularly helpful. Future work will focus on implementation, integration into clinical practice and other delivery formats (smart phones, tablets).

Allogeneic haematopoietic stem cell transplantation for chronic lymphocytic leukaemia: outcome in a 20-year cohort.

The curative potential of allogeneic haematopoietic stem cell transplant (allo HSCT) in chronic lymphocytic leukaemia CLL is established, with a demonstrated role for graft-versus-leukaemia and less certainty for other factors in determining outcome. The first two decades of CLL patients proceeding to allo HSCT at the Leukaemia/Bone Marrow Transplant Program of British Columbia (n = 49 consecutive, 1991-2009) were studied to clarify factors predicting outcome. The donor was related in 29 (59%) and unrelated in 20 (41%). Conditioning was reduced-intensity in 27 (55%) and myeloablative in 22 (45%). Thirty-one of 49 patients survive with median follow-up of 5 years (0·2-15). Cumulative incidence of non-relapse mortality; complete remission (CR); clearance of fluorescence in situ hybridization (FISH) abnormality and progression at 10 years was 36%; 69%; 55% and 22%. Overall survival (OS) was 63% at 2 years; 55% at 5 years and beyond. Factors predicting OS (P value by log rank <0·05) were: comorbidity index <3, FISH rank (Dohner) and 17p deletion, alemtuzumab pre-HSCT, achievement of CR post-HSCT, donor chimerism >90%, clearance of FISH abnormality post-HSCT and absence of high-grade (3-4) graft-versus-host disease. Results from this province-wide, two-decade cohort demonstrated that a substantial proportion of patients with high-risk CLL become long term disease-free survivors.

Long-term follow-up of patients with chronic myeloid leukemia in chronic phase developing sudden blast phase on imatinib therapy.

Sudden blast phase (SBP) is a rare event that occurs in an unpredictable fashion amongst patients with chronic myeloid leukemia (CML) who otherwise appear to be responding satisfactorily to imatinib (IM) treatment. We investigated the incidence, clinical characteristics, treatment outcome and long-term follow-up of 213 patients with chronic phase CML treated with IM according to the European LeukemiaNet guidelines. Nine patients, eight of whom received IM as first-line therapy, developed SBP (4.2% of the total). They tended to have low or intermediate risk Sokal scores at diagnosis, a predominance of the lymphoid phenotype and a short interval from "optimal" response to the development of BP. Five of the nine patients with SBP are alive in complete molecular remission; however, all of them underwent allogeneic hematopoietic stem cell transplant. The cumulative incidence of SBP for the patients who received IM as first-line therapy was 5.9% and the 2-year overall survival of the nine patients who developed SBP was 56%. Despite the improved outcome for patients with SBP receiving tyrosine kinase inhibitors (TKIs) and transplant, many of these patients are not salvaged with these therapies. This illustrates the need to develop predictive models to identify patients early whose response to TKI therapy will not be durable and hopefully prevent the transformation to advanced disease.

Novel agents improve survival of transplant patients with multiple myeloma including those with high-risk disease defined by early relapse (<12 months).

The treatment of multiple myeloma (MM) has changed with the advent of thalidomide, bortezomib, and lenalidomide, the so-called novel agents (NAs). Given the complexity of MM therapy in the NA era we pursued a population based study to assess for improvements in survival as well as to characterize the relevance of early relapse (within 12 months) and the International Staging System in this clinical setting. We reviewed our experience with 460 patients with MM treated with autologous stem cell transplant (ASCT) between 1988 and 2008, of whom 306 had relapsed. The cohort was divided into two groups based upon relapse pre-2004 and relapse during/after 2004 (2004+), which correlated to availability of bortezomib and lenalidomide. Improvements in both overall survival (OS) (median 32.0 months vs. 71.8 months; p < 0.001) and post-relapse survival (PRS) (median 15.2 months vs. 42.8 months; p < 0.001) correlated with the NA era. Exposure to NAs conferred a better PRS (median 35.7 months vs. 9.1 months; p < 0.001). Although all patients had improvements in survival, those who relapsed late continued to do better. Lastly, in the NA era, the ISS remains an important prognostic tool in relapse, but only in the late relapsing cohort.

Response to tyrosine kinase inhibitor therapy in patients with chronic myelogenous leukemia relapsing in chronic and advanced phase following allogeneic hematopoietic stem cell transplantation.

Tyrosine kinase inhibitors (TKI) have been used to treat relapse of chronic myelogenous leukemia (CML) after allogeneic stem cell transplant (HSCT), with responses seen predominantly in chronic phase (CP) patients. This study aimed to analyze the response to TKI therapy and overall survival for patients relapsing predominantly in advanced phase. We retrospectively reviewed 22 patients treated with imatinib (n=20) and/or dasatinib (n=6) for relapsed CML after HSCT; 8 patients were in CP, and 14 patients had advanced disease. Seven patients also received donor lymphocyte infusions. Hematologic, cytogenetic, and molecular responses were analyzed. Nineteen patients (86%) achieved complete hematologic response (CHR), 17 patients (77%) achieved complete cytogenetic response (CCR), and 14 patients (64%) achieved complete molecular response (CMR). In advanced phase patients, 11 (79%) achieved CHR, 10 (71%) CCR, and 8 (57%) achieved CMR. Grade 3 or 4 cytopenias occurred in 10 cases. With median follow-up of 31.5 months from relapse, 14 (64%) patients remain alive, 13 in CMR. In multivariate analysis, the achievement of CMR was significantly correlated with OS with an odds ratio of 20.5 (95% confidence interval 2.3-182) P=.007. TKI therapy is capable of inducing durable molecular responses for CML relapsing after HSCT, both in chronic and advanced phases. The achievement of CMR appears to be crucial in providing long-term disease control for these patients.

IPSS poor-risk karyotype as a predictor of outcome for patients with myelodysplastic syndrome following myeloablative stem cell transplantation.

The optimal therapy for myelodysplastic syndrome (MDS) is allogeneic bone marrow (BM) or blood (BSC) stem cell transplantation (SCT), although outcomes are limited by nonrelapse mortality (NRM) and relapse. A retrospective review was performed of 156 patients who underwent SCT (114 BM, 42 BSC) for MDS or secondary acute myelogenous leukemia (sAML) at our institution. Fifty-five patients remain in continuous complete remission: 35 BM recipients and 20 BSC recipients (median follow-up 139 and 89 months, respectively). Estimated 7-year event-free survival (EFS), NRM, and risk of relapse (ROR) are 33% (95% confidence intervals [CI] 25%-43%), 42% (CI 33%-51%), and 25% (CI 17%-33%) for the BM cohort and 45% (CI 32%-64%, P= .07), 32% (CI 18%-47%, P= .15), and 23% (CI 11%-37%, P= .79) for the BSC cohort. Multivariate analysis showed IPSS poor-risk cytogenetics (P< .001), time from diagnosis to SCT (P< .001), FAB subgroup (P= .001), recipients not in complete remission (CR1) at SCT (P= .005), and the development of acute graft-versus-host disease (aGVHD) (P= .04) were all predictive of an inferior EFS. The FAB subgroup (P= .002), poor-risk karyotype (P= .004), and non-CR1 status also correlated with ROR in multivariate analysis. EFS for poor-risk karyotype patients was superior after receiving BSC compared to BM (39% versus 6%, P< .001). SCT outcomes in MDS/sAML are strongly associated with the IPSS cytogenetic risk group, although the use of BSC in poor-risk karyotype patients may lead to a more favorable long-term EFS.

Cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia are correlated with Sokal risk scores and duration of therapy but not trough imatinib plasma levels.

Cytogenetic and molecular responses to standard-dose imatinib (IM) were correlated with trough IM plasma levels for 78 patients with chronic myeloid leukemia (CML) after a minimum of 12 months of IM therapy. The mean trough IM plasma level was 1065 ng/ml (range, 203-2910). There was no correlation of mean plasma trough IM levels and complete cytogenetic response (CCR) at 1 year (CCR 1010 ng/ml vs no CCR 1175 ng/ml P=.29) or major molecular response (MMR) (MMR1067 ng/ml vs no MMR 1063 ng/ml P=.74) after a median of 1298 days of IM therapy. CCR and MMR did correlate with Sokal risk scores with the odds of achieving CCR or MMR for a low risk vs high risk score of 10.8 (95% CI 2.2-53.5) and 6.4 (95% CI 1.4-29.4), respectively. Furthermore, a longer duration of IM therapy also was associated with a greater likelihood of achieving MMR (P=.02).

Long-term outcome of myeloablative allogeneic stem cell transplantation for multiple myeloma.

Allogeneic stem cell transplantation (alloSCT) has been used in the hopes of harnessing the curative potential of the graft-versus-myeloma effect. This study examines the long-term outcomes of a large cohort of patients with myeloma who were treated with myeloablative alloSCT at a single center. Comparisons are made with those who were treated with autologous stem cell transplantation (ASCT). Between January 1989 and February 2002, 158 patients age10 years post myeloablative alloSCT, similarly there are long-term survivors post-ASCT. Myeloablative alloSCT should not be considered standard treatment, and should only be considered in the context of a clinical trial.

Philadelphia-negative clonal hematopoiesis following imatinib therapy in patients with chronic myeloid leukemia: a report of nine cases and analysis of predictive factors.

There are increasing reports of Philadelphia-negative (Ph-negative) clonal hematopoiesis developing among patients with chronic myeloid leukemia (CML) treated with imatinib mesylate (IM). To establish the incidence and significance of these chromosomal abnormalities, we analyzed data on 141 consecutive patients with CML treated with IM at the British Columbia Cancer Agency and Vancouver General Hospital from 1999 to 2004. The cumulative incidence of developing a Ph-negative clone three years from the start of IM was 8.7% at a median of 13.3 months. The Ph-negative clonal abnormalities included monosomy 7 and/or trisomy 8 (seven patients), monosomy for chromosomes X and 22 (one patient), and a (12;16) translocation (one patient). Two of the patients presented with the same chromosomal abnormality in both Ph-negative and Ph-positive cells. None of the Ph-negative clonal abnormalities was associated with myelodysplasia. In a multivariate analysis, an interval from diagnosis to initiation of IM of 1 year or less was associated with an increased risk of developing a Ph-negative clone (relative risk = 20.2; P = 0.025). There was no difference, however, in event-free survival between patients who did and did not develop Ph-negative clones. Therefore, while the development of Ph-negative clonal hematopoiesis in patients with CML treated with IM is uncommon, it appears to be more frequent than that previously seen with IFN, but it does not seem to confer a worse prognosis.