Scan factors and practices associated with radiation doses for chest CT: current Brazilian scenario.

The main purpose of this study was to compare the parameters of computed tomography (CT) and the corresponding patient doses undergoing chest CT scan examinations in different regions of Brazil, providing the current scenario of how these procedures are being carried out in the country as well as the patient dose distribution. Thirty institutions, across 17 states and the Federal District, participated in the survey. The evaluation included 30 multislice CTs of seven different models, manufactured by General Electric (GE) Healthcare. For each institution, data from 10 adult chest CT examinations, performed without contrast, were collected remotely. The analysis of the results showed a significant difference of the CTDIvolvalues, ranging from 1.1 mGy to 46.6 mGy in seven institutions. The mean value of CTDIvolwas higher than values found in the literature and the UK Reference Levels. It was also observed that, regardless of the region of the country, for the same CT model, different scanning parameters were used, which resulted in CTDIvolup to 5 times higher in some institutions. Repetitions of CT acquisitions and scouts with radiation field dimensions larger than the region of interest were found in 25% of chest examinations, resulting in higher absorbed doses. The results of this work show a mapping of the chest CT procedures, which enables the establishment of strategic plans for the country. In addition, each institution will be able to implement an appropriate optimization program and establish institutional reference levels.

First Latin American and Caribbean interlaboratory comparison exercise for SSDLs on reference irradiation capabilities in personal dose equivalent.

A comparison exercise of Latin American and Caribbean Secondary Standards Dosimetry Laboratories (SSDLs) was jointly organized by the International Atomic Energy Agency (IAEA) and the Ionizing Radiation Metrology Laboratory at the Federal University of Pernambuco (LMRI-DEN/UFPE). This exercise was organized during an IAEA regional meeting on the review and update of calibration capabilities in Latin America, held in Recife, during the period from 23 to 27 April 2018 under the technical cooperation project ME-RLA 9085-170572. Fifteen participating SSDLs were required to irradiate optically stimulated personal dosimeters in terms of the personal dose equivalent Hp(10) in137Cs radiation quality. In addition, the IAEA Dosimetry Laboratory in Seibersdorf, Austria, and the National Physical Laboratory in Teddington, Middlesex, UK participated in this exercise as reference institutes. Each participant received 10 dosimeters that were hand-carried directly to the SSDL. Two nominal dose values of 2 mSv and 4 mSv were selected for this exercise. The participants irradiated the dosimeters using the setup and the procedures which are normally used in their standard laboratory for Hp(10) dosimeter irradiations. The dosimeters were evaluated as they were received by the coordinating laboratory, using a single BeOSL Reader. The results show that, except for one laboratory, the differences between the dosimeter reading and the assigned values were within 10%; this is consistent with the expanded uncertainty. The results indicate that most of the participant laboratories have a good capability to irradiate personal dosimeters in the quantity Hp(10).

Evaluation of a 3D printed OSL eye lens dosimeter for photon dosimetry.

This work demonstrates the use of high-resolution 3D printing to fine-tune the low energy dependence of an eye lens dosimeter holder associated to a BeO OSL detector element (ezClip). Five geometries of the denominated iBe dosimeter were developed, three with a variation in the thickness of the wall in front of the sensitive element that tailor the response at low radiation energies; and three with variations of width and curvature in order to vary the angular response of the dosimeter badges. Additive manufacturing was accomplished using stereolithography which gave a high degree of accuracy and precision. The optimised dosimeter badges showed a low energy and angular dependence, within -20% to +20% in the energy range of 24 keV to 662 keV and from 0 to 60° incidence; and within -10% to +10% in the energy range of 24 keV to 164 keV and from 0 to 60° incidence. In contrast to other dosimeters with higher effective atomic numbers, the use of BeO as the sensitive element resulted in a flat energy and angular dependence response at low energies. A significant reduction in the measurement uncertainty in the diagnostic radiology energy range was achieved.

A phase 1 trial of itacitinib, a selective JAK1 inhibitor, in patients with acute graft-versus-host disease.

Acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic cell transplantation (HCT) is a primary cause of nonrelapse mortality and a major barrier to successful transplant outcomes. Itacitinib is a Janus kinase (JAK)1-selective inhibitor that has demonstrated efficacy in preclinical models of aGVHD. We report results from the first registered study of a JAK inhibitor in patients with aGVHD. This was an open-label phase 1 study enrolling patients aged ≥18 years with first HCT from any source who developed grade IIB to IVD aGVHD. Patients with steroid-naive or steroid-refractory aGVHD were randomized 1:1 to itacitinib 200 mg or 300 mg once daily plus corticosteroids. The primary endpoint was safety and tolerability; day 28 overall response rate (ORR) was the main secondary endpoint. Twenty-nine patients (200 mg, n = 14; 300 mg, n = 15) received ≥1 dose of itacitinib and were included in safety and efficacy assessments. One dose-limiting toxicity was reported (grade 3 thrombocytopenia attributed to GVHD progression in a patient receiving 300 mg itacitinib with preexisting thrombocytopenia). The most common nonhematologic treatment-emergent adverse event was diarrhea (48.3%, n = 14); anemia occurred in 11 patients (38%). ORR on day 28 for all patients in the 200-mg and 300-mg groups was 78.6% and 66.7%, respectively. Day 28 ORR was 75.0% for patients with treatment-naive aGVHD and 70.6% in those with steroid-refractory aGVHD. All patients receiving itacitinib decreased corticosteroid use over time. In summary, itacitinib was well tolerated and demonstrated encouraging efficacy in patients with steroid-naive or steroid-refractory aGVHD, warranting continued clinical investigations. This trial was registered at www.clinicaltrials.gov as #NCT02614612.

Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial.

Patients who develop steroid-refractory acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation have poor prognosis, highlighting an unmet therapeutic need. In this open-label phase 2 study (ClinicalTrials.gov identifier: NCT02953678), patients aged at least 12 years with grades II to IV steroid-refractory aGVHD were eligible to receive ruxolitinib orally, starting at 5 mg twice daily plus corticosteroids, until treatment failure, unacceptable toxicity, or death. The primary end point was overall response rate (ORR) at day 28; the key secondary end point was duration of response (DOR) at 6 months. As of 2 July 2018, 71 patients received at least 1 dose of ruxolitinib. Forty-eight of those patients (67.6%) had grade III/IV aGVHD at enrollment. At day 28, 39 patients (54.9%; 95% confidence interval, 42.7%-66.8%) had an overall response, including 19 (26.8%) with complete responses. Best ORR at any time was 73.2% (complete response, 56.3%). Responses were observed across skin (61.1%), upper (45.5%) and lower (46.0%) gastrointestinal tract, and liver (26.7%). Median DOR was 345 days. Overall survival estimate at 6 months was 51.0%. At day 28, 24 (55.8%) of 43 patients receiving ruxolitinib and corticosteroids had a 50% or greater corticosteroid dose reduction from baseline. The most common treatment-emergent adverse events were anemia (64.8%), thrombocytopenia (62.0%), hypokalemia (49.3%), neutropenia (47.9%), and peripheral edema (45.1%). Ruxolitinib produced durable responses and encouraging survival compared with historical data in patients with steroid-refractory aGVHD who otherwise have dismal outcomes. The safety profile was consistent with expectations for ruxolitinib and this patient population.

Evaluation of the MOSkin dosimeter for diagnostic X-ray CT beams.

The aim of the present study was to evaluate the response of the MOSkin MOSFET dosimeter for X-ray diagnostic CT beams. Experiments were performed to investigate the sensitivity, energy dependence, reproducibility, fading and angular dependence of the dose response for the device. The dosimeter's performance was evaluated for the standard radiation qualities RQT 8, RQT 9 and RQT 10 in a metrology laboratory. In a CT scanner, the MOSkin was used to assess the air kerma profile and the dose profile in a phantom. The integral of the dose profile was compared to the CPMMA,100 measured with a pencil ionization chamber. The results showed that the MOSkin response was linear and reproducible with doses in the CT range. Energy dependence varied up to a factor of 1.19 among the tested X-ray energies. Angular dependence of the response was not greater than 7.8% within the angle range from 0 to 90 degrees. Signal fading within 3 min was negligible. Additionally, the MOSkin was able to accurately assess the air kerma profile and the integral of the dose profile in a CT scanner. The integral of the dose profile in a phantom was in agreement with the CPMMA,100. The presented results demonstrated the potential of the MOSkin for application in CT dosimetry.

REDUCTION OF STAFF RADIATION DOSE IN PROSTATIC ARTERY EMBOLISATION.

Prostatic artery embolisation (PAE) is used to treat patients with benign prostatic hyperplasia and with lower urinary obstructive tract symptoms. It is an interventional procedure which uses fluoroscopy equipment and can result in exposure to high doses of radiation in patients and staff. We aimed to demonstrate the reduction of radiation doses received by staff during PAE by implementing an optimised protocol called Radiation Exposure Curtailment for Embolisation (RECiFE). This protocol was implemented in cooperation with the medical team and technical team using Siemens Combined Applications to Reduce Exposure (CARE) protocol. The results showed approximately 83% reduction in the radiation doses received by the main physician during PAE. Thus, by adjusting the acquisition parameters of the angiographic equipment and implementing the RECiFE protocol, it is possible to optimise the PAE procedure and reduce the staff radiation dose.

RADIATION DOSES TO ANAESTHETISTS DURING PROSTATIC ARTERY EMBOLIZATION INTERVENTIONAL PROCEDURES.

The objective of this study was to assess the radiation doses received by anaesthetists from prostatic artery embolization (PAE) procedures. Ten PAE procedures conducted in a reference hospital in the city of Recife, Brazil were investigated. Occupational dosimetry was performed using thermoluminescent dosemeters which were located next to the eyes, close to the thyroid (over the shielding), on the thorax (under the apron), on the wrist and on the feet of the physician's body. The results showed that the anaesthetist's feet received the highest doses followed by the eyes and the hands. In some complex PAE procedures the doses received by anaesthetists on the lens of the eyes and the effective dose were higher than those received by the main operator due to the anaesthetist's close position to the patient's table and the use of oblique projections. The personal dose equivalent Hp(3) per procedure for the anaesthetist's right eyebrow ranged from 20.2 µSv to 568.3 µSv. This result shows that anaesthetists assisting PAE procedures can exceeds the annual eye lens dose limit of 20 mSv recommended by the ICRP with only one procedure per week if radiation protection measures are not implemented during procedures.

PERFORMANCE OF THE INSTADOSETM DOSEMETER FOR INTERVENTIONAL RADIOLOGY AND CARDIOLOGY APPLICATION.

The aim of this article was to verify the performance of the Mirion InstadoseTM dosemeter under clinical conditions and to compare its response in typical X-ray fields used during interventional and cardiology procedures with the TLD-100, usually used for radiation dosimetry. It was also objective of this study to verify the feasibility of using the InstadoseTM dosemeter response at the chest level for estimation of occupational eye lens dose in cardiology and interventional radiology. Initially the response of the dosemeter was tested using continuous X-ray beams and the results showed that the Instadose dosemeter present a satisfactory behavior of the most important dosimetric properties based on the tests as described in the IEC 62387 standard. The measurements performed in clinical conditions showed that the InstadoseTM dosemeter response was comparable to that of TL dosemeters used in interventional radiology and cardiology procedures and there is a correlation between the eye lens doses and the chest doses measured with the InstadoseTM. Based on the results obtained, we recommend the use of the InstadoseTM dosemeter for purposes of occupational whole-body monitoring of medical staff in interventional radiology and cardiology procedures.

Development of a realistic 3D printed eye lens dosemeter using CAD integrated with Monte Carlo simulation.

Recent epidemiological studies suggested to lower the threshold dose for radiation induced cataract in the eye lens. Therefore, eye lens radiation protection became to play a more important role in personal dosimetry. The main objective of this work is to propose a new methodology for prototyping and benchmarking of an eye lens dosimter based on the equivalent dose to the sensitive part of the eye lens, using CAD Software and Geant4 Monte Carlo simulations with mesh modelling and 3D printing. A 3D printed dosemeter was type tested based on IEC 62387:2012, in terms of energy and angular dependence for the measurements of Hp(3). The results show that the methodology employed is suitable for the development of new eye lens dosemeters.

Myeloablative vs reduced-intensity conditioning allogeneic hematopoietic cell transplantation for chronic myeloid leukemia.

Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment of chronic myeloid leukemia (CML). Optimal conditioning intensity for allo-HCT for CML in the era of tyrosine kinase inhibitors (TKIs) is unknown. Using the Center for International Blood and Marrow Transplant Research database, we sought to determine whether reduced-intensity/nonmyeloablative conditioning (RIC) allo-HCT and myeloablative conditioning (MAC) result in similar outcomes in CML patients. We evaluated 1395 CML allo-HCT recipients between the ages of 18 and 60 years. The disease status at transplant was divided into the following categories: chronic phase 1, chronic phase 2 or greater, and accelerated phase. Patients in blast phase at transplant and alternative donor transplants were excluded. The primary outcome was overall survival (OS) after allo-HCT. MAC (n = 1204) and RIC allo-HCT recipients (n = 191) from 2007 to 2014 were included. Patient, disease, and transplantation characteristics were similar, with a few exceptions. Multivariable analysis showed no significant difference in OS between MAC and RIC groups. In addition, leukemia-free survival and nonrelapse mortality did not differ significantly between the 2 groups. Compared with MAC, the RIC group had a higher risk of early relapse after allo-HCT (hazard ratio [HR], 1.85; P = .001). The cumulative incidence of chronic graft-versus-host disease (cGVHD) was lower with RIC than with MAC (HR, 0.77; P = .02). RIC provides similar survival and lower cGVHD compared with MAC and therefore may be a reasonable alternative to MAC for CML patients in the TKI era.

The performance of a multi guard ring (MGR) diode for clinical electron beams dosimetry.

The dosimetric response of a multi guard ring structure (MGR) diode has been studied with clinical electron beam energies from 5 MeV to 15 MeV. The results showed that the MGR dose response is linear in the range of 5-320 cGy and presents reproducibility with variation coefficients less than 0.4%. The field output factors measured with the MGR agreed within 2% with those measured with an ionization chamber. This study evidences that this diode can be used for clinical electron beam dosimetry.

Safety and efficacy of second-line bosutinib for chronic phase chronic myeloid leukemia over a five-year period: final results of a phase I/II study.

Bosutinib is a Src/Abl tyrosine kinase inhibitor indicated for adults with newly-diagnosed Philadelphia positive chronic myeloid leukemia or with resistant/intolerant disease. We report the final results of a phase I/II study of second-line bosutinib in chronic phase chronic myeloid leukemia patients after imatinib failure (n=284). Median follow up and treatment durations were 54.8 (range 0.6-96.3) and 25.6 (0.2-96.3) months, respectively. At years 2 and 5, 54% and 40% of patients, respectively, remained on bosutinib. Cumulative major cytogenetic response and complete cytogenetic response rates (newly-attained or maintained from baseline) were 58% and 46%, respectively, by year 2 and 60% and 50% by year 5. Kaplan-Meier probability of maintaining major and complete cytogenetic response was 76% and 78%, respectively, at year 2 and 71% and 69% at year 5. Cumulative incidence of on-treatment disease progression/death was similar at years 5 (19%) and 2 (15%); Kaplan-Meier overall survival was 91% at year 2 and 84% at year 5. Of 169 patients who had discontinued bosutinib by year 5, 38 did so after year 2, most commonly for disease progression (n=11). Most adverse events initially occurred within two years. Overall, gastrointestinal events were the most common (diarrhea 86%, nausea 46%, vomiting 37%); the most common grade 3/4 toxicity was thrombocytopenia (25%). None of the 4 on-treatment deaths in years 3-5 were related to bosutinib. Bosutinib demonstrated durable efficacy and manageable toxicity through year 5 confirming its importance in the treatment of chronic phase chronic myeloid leukemia patients resistant/intolerant to prior imatinib. This trial was registered at clinicaltrials.gov identifier: 00261846.

Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial.

Ponatinib has potent activity against native and mutant BCR-ABL1, including BCR-ABL1T315I The pivotal phase 2 Ponatinib Ph+ ALL and CML Evaluation (PACE) trial evaluated efficacy and safety of ponatinib at a starting dose of 45 mg once daily in 449 patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) resistant/intolerant to dasatinib or nilotinib, or with BCR-ABL1T315I This analysis focuses on chronic-phase CML (CP-CML) patients (n = 270) with 56.8-month median follow-up. Among 267 evaluable patients, 60%, 40%, and 24% achieved major cytogenetic response (MCyR), major molecular response (MMR), and 4.5-log molecular response, respectively. The probability of maintaining MCyR for 5 years was 82% among responders. Dose reductions were implemented in October 2013 to decrease the risk of arterial occlusive events (AOEs); ≥90% of CP-CML patients who had achieved MCyR or MMR maintained response 40 months after elective dose reductions. Estimated 5-year overall survival was 73%. In CP-CML patients, the most common treatment-emergent adverse events were rash (47%), abdominal pain (46%), thrombocytopenia (46%), headache (43%), dry skin (42%), and constipation (41%). The cumulative incidence of AOEs in CP-CML patients increased over time to 31%, while the exposure-adjusted incidence of new AOEs (15.8 and 4.9 per 100 patient-years in years 1 and 5, respectively) did not increase over time. These final PACE results demonstrate ponatinib provides durable and clinically meaningful responses, irrespective of dose reductions, in this population of heavily pretreated CP-CML patients. This trial was registered at www.clinicaltrials.gov as #NCT01207440.

Recent advances in the genomics and therapy of BCR/ABL1-positive and -negative chronic myeloproliferative neoplasms.

This review is based on the presentations and deliberations at the 7th John Goldman Chronic Myeloid Leukemia (CML) and Myeloproliferative Neoplasms (MPN) Colloquium which took place in Estoril, Portugal on the 15th October 2017, and the 11th post-ASH International Workshop on CML and MPN which took place on the 6th-7th December 2016, immediately after the 58th American Society of Hematology Annual Meeting. Rather than present a resume of the proceedings, we have elected to address some of the topical translational research and clinically relevant topics in greater detail. We address recent updates in the genetics and epigenetics of MPN, the mechanisms of transformation by mutant calreticulin, advances in the biology and therapy of systemic mastocytosis, clinical updates on JAK2 inhibitors and other therapeutic approaches for patients with MPNs, cardiovascular toxicity related to tyrosine kinase inhibitors and the concept of treatment-free remission for patients with CML.

Practical management of toxicities associated with bosutinib in patients with Philadelphia chromosome-positive chronic myeloid leukemia.

Bosutinib (SKI-606) is an oral, dual Src/Abl tyrosine kinase inhibitor (TKI) approved for treatment of patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) that is resistant or intolerant to prior TKI therapy or for whom other TKIs are not appropriate choices. The objective of this review is to provide a longitudinal summary of toxicities that may arise during treatment with second-line or later bosutinib in patients with Ph+ chronic phase CML and to provide strategies for managing these toxicities. As bosutinib is not currently indicated for newly diagnosed CML, toxicities associated with first-line treatment are not reviewed. Recognition and optimal management of these toxicities can facilitate patient compliance and affect treatment outcomes.

Peritransplantation Red Blood Cell Transfusion Is Associated with Increased Risk of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.

More than 90% of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients receive red blood cell (RBC) or platelet transfusions in the peritransplantation period. We tested the hypothesis that transfusions are associated with the development of severe (grade III-IV) acute graft-versus-host disease (aGVHD) or mortality after allo-HSCT in a retrospective study of 322 consecutive patients receiving an allogeneic bone marrow or granulocyte colony-stimulating factor-mobilized blood stem cell graft for a hematologic malignancy. Counting transfused RBC and platelet units between day -7 pretransplantation and day +27 post-transplantation, but excluding transfusions administered after a diagnosis of aGVHD, yielded medians of 5 RBC units and 2 platelet units transfused. Sixty-three patients (20%) developed a maximal grade III-IV aGVHD with onset up to day +150 post-transplantation (median aGVHD onset of 28 days). HLA mismatch (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.2 to 4.7; P = .01), and transfusion of more than the median number of RBC units (HR, 2.1; 95% CI, 1.1 to 3.7; P = .02) were independently associated with greater risk of grade III-IV aGVHD in a multivariable analysis model. Disease risk strata (HR, 1.7; 95% CI, 1.2 to 2.4 for high risk versus low risk; P = .005) and transfusion of more than the median number of RBC units (HR, 1.4; 95% CI, 1.0 to 2.0; P = .054) were independently associated with inferior overall survival. These data support our hypothesis that peritransplantation RBC transfusions are associated with the risk of developing severe aGVHD and worse overall survival following allo-HSCT, and suggest that strategies to reduce routine RBC transfusion may favorably reduce the incidence and severity of GVHD.

Intravenous Busulfan Compared with Total Body Irradiation Pretransplant Conditioning for Adults with Acute Lymphoblastic Leukemia.

Total body irradiation (TBI) has been included in standard conditioning for acute lymphoblastic leukemia (ALL) before hematopoietic cell transplantation (HCT). Non-TBI regimens have incorporated busulfan (Bu) to decrease toxicity. This retrospective study analyzed TBI and Bu on outcomes of ALL patients 18-60 years old, in first or second complete remission (CR), undergoing HLA-compatible sibling, related, or unrelated donor HCT, who reported to the Center for International Blood and Marrow Transplant Research from 2005 to 2014. TBI plus etoposide (25%) or cyclophosphamide (75%) was used in 819 patients, and intravenous Bu plus fludarabine (41%), clofarabine (30%), cyclophosphamide (15%), or melphalan (13%) was used in 299 patients. Bu-containing regimens were analyzed together, since no significant differences for patient outcomes were noted between them. Bu patients were older, with better performance status; took longer to achieve first CR and receive HCT; were treated more recently; and were more likely to receive peripheral blood grafts, antithymocyte globulin, or tyrosine kinase inhibitors. With median follow-up of 3.6 years for Bu and 5.3 years for TBI, adjusted 3-year outcomes showed treatment-related mortality Bu 19% versus TBI 25% (P = .04); relapse Bu 37% versus TBI 28% (P = .007); disease-free survival (DFS) Bu 45% versus TBI 48% (P = .35); and overall survival (OS) Bu 57% versus TBI 53% (P = .35). In multivariate analysis, Bu patients had higher risk of relapse (relative risk, 1.46; 95% confidence interval, 1.15 to 1.85; P = .002) compared with TBI patients. Despite the higher relapse, Bu-containing conditioning led to similar OS and DFS following HCT for ALL.

Pretransplant Consolidation Is Not Beneficial for Adults with ALL Undergoing Myeloablative Allogeneic Transplantation.

Allogeneic hematopoietic cell transplantation (alloHCT) is curative for patients with acute lymphoblastic leukemia (ALL) who achieve complete remission (CR1) with chemotherapy. However, the benefit of consolidation chemotherapy remains uncertain in patients undergoing alloHCT. We compared clinical outcomes of 524 adult patients with ALL in CR1 who received ≥2 (n = 109), 1 (n = 93), or 0 cycles (n = 322) of consolidation before myeloablative alloHCT from 2008 to 2012. As expected, time to alloHCT was longer with increasing cycles of consolidation. Patients receiving ≥2, 1, or 0 cycles of consolidation had an adjusted 3-year cumulative incidence of relapse of 20%, 27%, and 22%; 1-year transplant-related mortality (TRM) of 16%, 18%, and 23%; adjusted 3-year leukemia-free survival (LFS) of 54%, 48%, and 47%; and 3-year overall survival (OS) of 63%, 59%, and 54% (all P values >.40). Multivariable analysis confirmed that consolidation was not prognostic for LFS (relative risk, 1.20, 95% confidence interval, .86 to 1.67; P = .28 for no consolidation; RR, 1.18, 95% confidence interval, .79 to 1.76; P = .41 for 1 cycle versus ≥2 cycles = reference). Similarly, consolidation was not associated with OS, relapse, TRM, or graft-versus-host disease. We conclude that consolidation chemotherapy does not appear to provide added benefit in adult ALL patients with available donors who undergo myeloablative alloHCT in CR1.

Outcomes of Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia Following an Elective Switch From Second-Generation Tyrosine Kinase Inhibitor to Imatinib.

The second-generation tyrosine kinase inhibitors (TKIs) (2G-TKIs) dasatinib (DAS) and nilotinib (NIL) yield faster responses in newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML) as compared with imatinib (IM); however, long-term safety of these agents is a growing concern. We identified 20 patients with CP-CML diagnosed between August 2013 and October 2016 who initiated 2G-TKIs and were then switched after optimal response at 3 months to IM. Second-generation TKIs initiated were DAS (n = 15), NIL (n = 3), or both sequentially due to intolerance (n = 1). One other patient initiated therapy with ponatinib on trial. Response was assessed by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) for BCR-ABL1 levels every 3 months and in patients with qRT-PCR values less than 10% at 3 months, IM was started at 400 mg/d. IM was well tolerated except in 2 patients who required dose-reduction and discontinuation due to grade 2 skin rash (1) and grade 2 anxiety (1). After initiation of IM therapy, the BCR-ABL1 qRT-PCR levels trended down as expected. At 12 months 16 (84.2%) of 19 evaluable patients showed a 3 log (major molecular remission) or better reduction in their PCR levels. In conclusion, this retrospective analysis shows that IM can be safely and effectively administered following optimal response to 2G-TKIs. A prospective trial exploring this approach is currently enrolling and will be needed to confirm the safety and efficacy of this therapeutic approach.