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Objective: Rare coexistence of disease or pathology. Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the presence of the Philadelphia (Ph) chromosome, which results from the fusion of the translocation of the ABL1 gene from chromosome 9 to the BCR gene located in chromosome 22, forming the BCR-ABL gene on chromosome number 22, which accounts for approximately 95% of CML cases. Complex translocation involving other chromosomes can occur. Case Report: We present a rare case of CML with a variant Ph chromosome, in which chromosome 16 was involved with the usual translocation. A 34-year-old woman presented with a history of left upper quadrant pain and excessive sweating, with no hepatosplenomegaly on examination. She was found to have leukocytosis, with elevated neutrophils (34 000/mm3), basophils (1460/mm3), and eosinophils (2650/mm3). Karyotyping showed a translocation (16;22) (q24,q11.2), and FISH analysis showed BCR-ABL fusion as a result of (9,22) translocation, with a third chromosome (chromosome 16) involved and fused with chromosome 22, with a different breakpoint, which has never been reported in the literature, affecting the long arm of chromosome 16. The patient was treated with a first-generation tyrosine kinase inhibitor (imatinib) and achieved a deep molecular remission. The repeated FISH analysis confirmed the disappearance of both translocations (9,22) and (16,22). Conclusions: The impact of the additional chromosomal aberration in CML is widely heterogeneous, and the outcome is dependent on multiple factors. Larger studies are needed to clarify the outcome in CML with variant Ph chromosomes, as most of the available data come from reported cases. [ABSTRACT FROM AUTHOR]

Background: Barely two per million Belgian children/adolescents are diagnosed with chronic myeloid leukemia (CML) annually. In this retrospective study, we aimed to investigate the diagnostic features, clinical and laboratory characteristics, and treatment outcome of this rare entity. Methods: Medical records of all pediatric CML patients (age ≤ 17 years) diagnosed at the University Hospitals Leuven between 1986 and 2021 were reviewed. Results: Fourteen patients (median age at diagnosis 12.5 years) were included, all presenting in chronic phase. Five patients were diagnosed before 2003; main therapy included hydroxyurea (n = 5/5), interferon‐alfa (n = 3/5) and allogeneic hematopoietic stem cell transplantation (allo‐Tx) (n = 3/5). Complete hematologic response (CHR), complete cytogenetic response (CCyR) and major molecular response (MMR) was reached in resp. 4/5, 4/5 and in 2/3 of evaluable patients. Three patients progressed to accelerated/blast phase (median time 19 months) and 1/5 is alive and disease‐free at last follow‐up. Nine patients were diagnosed after 2003 and were treated with first generation (1°G) tyrosine kinase inhibitors (TKI): 3/9 subsequently underwent an allo‐Tx, 4/9 were switched to 2°G TKI, one patient was additionally switched to 3°G TKI. CHR, CCyR and MMR was reached in 9/9, 9/9 and 8/9 of these patients. No progression to accelerated/blast phase was observed and none of these patients deceased. At last follow‐up, 7/9 patients were in MMR or disease free, the two remaining patients did not reach or lost MMR, both related to compliance issues. Conclusion: Our study confirmed that TKI significantly improved the prognosis of pediatric CML. However, drug compliance poses a considerable challenge. [ABSTRACT FROM AUTHOR]

Introduction. Extramedullary sites of leukemic proliferation, harboring an adverse outcome, are rare and usually found in the blastic phase of chronic myeloid leukemia. We report a case of a newly diagnosed patient with chronic myeloid leukemia in the chronic phase, with leukemic infiltration of the right ovary on disease presentation. Case report. The patient presented with abdominal pain, leukocytosis, and anemia. A peripheral blood smear indicated chronic myeloid leukemia, and cytoreductive treatment was started. Due to the worsening of the abdominal pain, computed tomography was done. It revealed a cystic tumor of the r ight o vary. T he t umor w as s urgically r emoved. B one marrow examination confirmed the diagnosis of chronic myeloid leukemia in the chronic phase. Immunohistochemical analysis of the ovarian tumor showed leukemic infiltration with 5% of blasts. The patient was treated with imatinib for one year. Due to treatment failure, imatinib was switched to nilotinib. Allogeneic stem cell transplantation was considered. Conclusion. This case highlights the critical role of the multidisciplinary team approach and close treatment monitoring to achieve the best possible outcome in these patients. [ABSTRACT FROM AUTHOR]

The BCR-ABL oncogene is a tyrosine kinase gene that is over-expressed in CML. It inhibits the TGF-β1 signaling pathway. Due to resistance of cells to the tyrosine kinase inhibitor, STI-571, the combined effect of STI-571 and TGF-β1 on K562 cells was studied in the present research. Results revealed that the TGF-β1 cell signaling pathway, which is activated in K562 cells treated with TGF-β1, activates collective cell signaling pathways involved in survival and apoptosis.

Objectives: This study aimed to assess the quantitative real-time RT-PCR (QRT-PCR) technique as a diagnostic tool for molecular surveillance of the BCR-ABL duplicate in Chronic Myelogenous Leukemia (CML) using both peripheral blood (PB) and bone marrow (BM) samples. Methods: Prospective analysis has been conducted a by quantitative real-time RT-PCR (QRT-PCR) for both PB and BM specimens, from 25 patients with untreated CML. QRT-PCR investigation was carried out previous and during treatment with Imatinib for untreated CML. Statistical examinations showed useful agreement of PB and BM pre- treatment specimens. Nevertheless, using the SPSS statistical method that estimates the agreement between PB and BM data. Results: This study showed low correspond of BCR-ABL measurements in PB and BM for specimens acquired through treatment. PB values tended to be lower than the conformable BM values [average difference = -0.37 (P < 0.001) in 36 coupled samples] and the 95% limits of agreement ranged from -1.23 to 0.48. Nevertheless, the present study showed that BM and PB QRT-PCR values followed a similar direction during treatment (Spearman correlation coefficient, 0.83; 95% CI, 0.70, 0.96). Conclusion: Our findings imply that PB and BM measures of BCR-ABL are frequently quantitatively different. The most accurate way to determine whether there is minimal residual disease is through BM sampling because BM results tend to be greater than PB values (MRD). Based on these findings, we advise avoiding switching BM and PB sampling for MRD monitoring during CML treatment because doing so could result in incorrect interpretation of treatment outcomes. [ABSTRACT FROM AUTHOR]

BackgroundPulmonary hypertension (PH) is a rare but life-threatening adverse event (AE) of dasatinib, but the associated variables are not clear. This study aimed to explore the variables associated with PH by echocardiography in patients with chronic myeloid leukemia in the chronic phase (CML-CP) receiving dasatinib therapy.MethodsEchocardiography was performed to estimate the probability of PH and pulmonary artery systolic pressure (PASP). Binary logistic analysis and Fine–Gray hazard model were used to identify the variables associated with PH by using cross-sectional and longitudinal data.ResultsAmong the 243 patients in the cross-sectional dataset, with a median dasatinib therapy duration of 27 months, 30 (12.3%) were classified as having a high probability of PH. Increasing age (OR = 1.7, p = 0.002; OR = 1.5, p = 0.003) and pericardial effusion (OR = 4.3, p = 0.004; OR = 3.2, p = 0.014) were significantly associated with a high probability of PH and PASP ≥ 40 mmHg, respectively. Among the 161 patients in the longitudinal dataset, the 3-year cumulative incidences of a high probability of PH and PASP ≥ 40 mmHg were 9.3% and 22.1%, respectively. Pericardial effusion (HR = 3.8, p = 0.005) and cardiopulmonary comorbidities (HR = 3.2, p = 0.021) were significantly associated with a high probability of PH; increasing age (HR = 1.5, p < 0.001) and dasatinib as ≥ 3rd-line therapy (p = 0.032; 2nd-line vs. 1st-line, HR = 2.0, p = 0.200; ≥ 3rd-line vs. 1st-line, HR = 3.4, p = 0.047) were significantly associated with PASP ≥ 40 mmHg.ConclusionIncreasing age, pericardial effusion, cardiopulmonary comorbidities, and dasatinib as ≥ 3rd-line TKI therapy were associated with PH in the patients with CML-CP on dasatinib therapy.

Background: Chronic myelogenous leukemia (CML) is a malignant myeloproliferative neoplasm of pluripotent stem cell origin. Ophthalmic manifestation as an initial presentation in cases of CML is extremely rare. Frequently, ocular lesions in CML are asymptomatic. However, vitreous or foveal involvement can result in a symptomatic visual loss and earlier presentation. Here, we report a rare case of monocular vision loss due to subhyaloid hemorrhage in a case of CML. Case Report: A 19-year-old healthy woman presented to the Emergency Department with sudden painless decrease in vision in her left eye for 1 day. Fundus examination revealed multiple intraretinal hemorrhages with some whitecentered hemorrhages in 4 quadrants in both eyes, and subhyaloid hemorrhage involving the fovea in the left eye. Complete blood count and peripheral blood smear were consistent with the diagnosis of chronic myeloid leukemia. After referral to the hematology service, the diagnosis was confirmed based on bone marrow aspiration and chromosomal analysis. The patient then received the appropriate management and continued to follow up with the hematology service. Conclusions: This case report highlights the rarity of ocular involvement as an initial manifestation of chronic myeloid leukemia, and the importance of systemic work-up for the diagnosis of this entity. A multidisciplinary team approach involving ophthalmologists, hematologists, and oncologists is paramount for the diagnosis and management of CML. [ABSTRACT FROM AUTHOR]

We report the case of a patient who was initially presented with ischemic priapism to the emergency department. He was treated with adrenaline intracavernous injections and aspiration with irrigation of the corpora cavernosa and distal shunt. In the postoperative period, anemia, basophilia, eosinophilia, thrombocytosis and hyperleukocytosis were detected. The patient was subsequently diagnosed with chronic myeloid leukemia. Priapism is a rare manifestation of chronic myeloid leukemia (≤ 3%) and occurs mostly due to hyperleukocytosis, resulting in thrombus formation and corporal venous outflow obstruction. Priapism occurring in any setting is considered as a medical emergency that requires immediate local therapy because of resulting irreversible cell damage and fibrosis if not treated within the first 24–48 h. [ABSTRACT FROM AUTHOR]

Abstract We report the case of a patient who was initially presented with ischemic priapism to the emergency department. He was treated with adrenaline intracavernous injections and aspiration with irrigation of the corpora cavernosa and distal shunt. In the postoperative period, anemia, basophilia, eosinophilia, thrombocytosis and hyperleukocytosis were detected. The patient was subsequently diagnosed with chronic myeloid leukemia. Priapism is a rare manifestation of chronic myeloid leukemia (≤ 3%) and occurs mostly due to hyperleukocytosis, resulting in thrombus formation and corporal venous outflow obstruction. Priapism occurring in any setting is considered as a medical emergency that requires immediate local therapy because of resulting irreversible cell damage and fibrosis if not treated within the first 24–48 h.

Chronic myeloid leukemia (CML) is a rare disease among children. A retrospective study was conducted from November 2002 to March 2019 at a single institution in China. A total of 36 pediatric CML patients (25 male and 11 female) were enrolled. Median follow-up time was 51 months (range 8–144), and 5-year overall survival and event-free survival were 95.5 ± 4.4% and 88.9 ± 6.0%, respectively. Among the 25 patients whose response to imatinib mesylate (IM) was regularly monitored, 92.0% achieved complete hematologic response at 3 months, 80.0% achieved complete cytogenetic response at 12 months, and 64.0% achieved major molecular response at 18 months after IM therapy. A higher WBC count at diagnosis was associated with failure to achieve early molecular response (EMR). Height standard deviation score after long-term treatment was significantly and positively correlated with age at diagnosis and at the start of IM therapy. Overall, IM therapy was effective in treating pediatric CML, and WBC count at diagnosis might be an ideal predictor of EMR. Moreover, retardation of height and weight growth due to IM tended to affect patients younger than 9 years old at diagnosis, and longitudinal growth might normalize further into treatment. [ABSTRACT FROM AUTHOR]

Introduction. Additional karyotype abnormalities in the Philadelphia-positive (Ph+) clone can emerge during the progression of chronic myeloid leukemia (CML) and are often associated with the resistance to treatment with tyrosine kinase inhibitors (TKI). Sometimes, during the TKI treatment, karyotype abnormalities can appear in the Philadelphia-negative (Ph-) cells as well but do not seem to adversely affect the outcome except for chromosome 7 abnormalities. Case report. The patient presented was in the chronic phase of Ph+ CML with highly diverse karyotype abnormalities. The abnormalities appeared in three unrelated clones during the TKIs treatment, followed by the evolution of the disease into acute myeloid leukemia (AML). The primary Ph+ clone was revealed during the chronic phase of CML, and therapy with imatinib mesylate was commenced. After a three-year hematologic and cytogenetic remission period, the evolution of the primary clone was noticed. Nilotinib was introduced, leading to a good molecular response and the disappearance/loss of the Ph+ clone with additional abnormalities but with the appearance of the Ph- clone with trisomy 8. Finally, after 5.5 years of nilotinib therapy, the Ph- clone with monosomy 7 occurred during the deep molecular response for BCR-ABL. At that time, the FISH analysis for trisomy 8 was negative, but the rise in blast count was noticed in the bone marrow, and the diagnosis of the secondary AML was established soon after. Conclusion. The achievement of the deep molecular response in CML patients does not rule out regular cytogenetic testing of their bone marrow. This is of crucial importance for detecting adverse karyotype abnormalities leading to the development of the myelodysplastic syndrome and AML. [ABSTRACT FROM AUTHOR]

Objective: Unusual clinical course Background: Although the V617F mutation in the Janus kinase 2 (JAK2) gene and the breakpoint cluster region-abl1 (BCRABL1) oncogene fusion have been considered mutually exclusive in most myeloproliferative neoplasms (MPNs), many recent studies have described patients with both. This report describes a patient with chronic myelogenous leukemia (CML) and the unusual JAK2 R795S mutation and reviews 23 additional patients with JAK2 gene mutations coexisting with myelofibrosis (MF) and CML. Case Report: A 50-year-old woman with MF experienced rapid disease progression 3 weeks later, accompanied by severe abdominal pain and a white blood cell count of 257.45x109/l. Karyotype analysis indicated that she was 46, XY, Philadelphia (Ph) (+) and BCR-ABL1 positive. Bone marrow aspiration after 1 cycle of chemotherapy and treatment with dasatinib showed that her marrow was hypercellular, with an increased number of megakaryocytes and 48.5% myeloblasts expressing the myeloid antigens CD33, CD13, CD34, CD117, and CD71. Next-generation sequencing identified a rare JAK2 R795S mutation. She was diagnosed with CML in blast phase, and was successfully treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Conclusions: JAK2 gene mutations, including the rare JAK2 R795S mutation, can coexist with BCR-ABL1 in patients with MPNs. The clinical course of MPN in patients with both BCR-ABL1 and JAK2 mutations may be different from that in patients with classical MPNs. [ABSTRACT FROM AUTHOR]

Until recently, the main goal of chronic myeloid leukemia therapy was disease control with the best overall survival, which required lifelong treatment. However, currently, the treatment-free remission concept is becoming an important goal in clinical practice, and several tyrosine kinase inhibitors discontinuation studies have shown that round 50% of patients with a durable deep molecular response beyond major molecular response successfully interrupt tyrosine kinase inhibitors for at least three years without loss of molecular response. However, and regardless of the existing evidence, the exact conditions for attempting treatment-free remission remain poorly defined. Different authors tried to guide the clinical decision regarding this topic but there are some points that differ, namely with respect to the recommended duration of tyrosine kinase inhibitors therapy and the appropriate molecular response prior to treatment-free remission. The goal of this article is to propose an algorithm to guide clinical practice in Portugal concerning chronic phase-chronic myeloid leukemia patients who wish to attempt treatment-free remission, since there are no national guidelines.

We report the occurrence of leukaemic infiltration of cervical spinal cord secondary to chronic myeloid leukaemia (CML) in a 31-year-old male patient. He presented with left upper limb monoplegia. On examination he had asymmetric quadriparesis, graded sensory loss and urinary retention. Diagnosis was suggested by magnetic resonance imaging. He responded dramatically to radiotherapy and corticosteroids treatment. Infiltration of the cervical spinal cord in a patient with CML has seldom been reported in literature till date, and hence we are reporting this case.

Background: Chronic myeloid leukemia is a myeloproliferative disorder characterized by the Philadelphia chromosome or t(9;22)(q34.1;q11.2), resulting in the break-point cluster regionAbelson tyrosine kinase fusion gene, which encodes a constitutively active tyrosine kinase protein. The Philadelphia chromosome is detected by karyotyping in around 90% of chronic myeloid leukemia patients, but 5-10% may have variant types. Variant Philadelphia chromosomes are characterized by the involvement of another chromosome in addition to chromosome 9 or 22. It can be a simple type of variant when one other chromosome is involved, or complex, in which two or more chromosomes take part in the translocation. Few studies have reported the incidence of variant Philadelphia chromosomes or the breakpoints involved among Brazilian chronic myeloid leukemia patients. Objective: The aim of this report is to describe the diversity of the variant Philadelphia chromosomes found and highlight some interesting breakpoint candidates for further studies. Methods: the Cytogenetics Section Database was searched for all cases with diagnoses of chronic myeloid leukemia during a 12-year period and all the variant Philadelphia chromosomes were listed. Results: Fifty (5.17%) cases out of 1071 Philadelphia-positive chronic myeloid leukemia were variants. The most frequently involved chromosome was 17, followed by chromosomes: 1, 20, 6, 11, 2, 10, 12 and 15. Conclusion: Among all the breakpoints seen in this survey, six had previously been described: 11p15, 14q32, 15q11.2, 16p13.1, 17p13 and 17q21. The fact that some regions get more fre- quently involved in such rare rearrangements calls attention to possible predisposition that should be further studied. Nevertheless, the pathological implication of these variants remains unclear.

Chronic myeloid leukemia (CML) has evolved into a chronic disease that is managed with tyrosine kinase inhibitor therapy. Now that long-term survival has been achieved in patients with CML, the focus of treatment has shifted to dose optimization, with the goal of maintaining response while improving quality of life. In this review, the authors discuss optimizing the dose of the second-generation tyrosine kinase inhibitor dasatinib. Once-daily dosing regimens for dasatinib in the first and later lines of treatment were established through long-term (5-year and 7-year) trials. Recently published data have indicated that further dose optimization may maintain efficacy while minimizing adverse events. Results obtained from dose optimization and discontinuation trials currently in progress will help practitioners determine the best dose and duration of dasatinib for patients with CML, because treatment decisions will be made through continued discussions between physicians and patients. Cancer 2018;124:1660-72. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. [ABSTRACT FROM AUTHOR]

Background Chronic myeloid leukemia (CML) has a low incidence but a high burden of disease, and is treated with high-cost tyrosine kinase inhibitors (TKI). Objective To determine the time from the start of a first-line TKI until it passes to second-line, and to establish the reasons for the change of therapy time. Setting Patients with Philadelphia-positive CML treated with some TKI. Methods Retrospective cohort study, between January 1 2007 and July 31 2015, with information obtained from medical records, the time to change initial drugs to secondline therapy, and the reasons for change, were identified. Kaplan-Meier survival analysis was carried out. Main outcome measure A change in therapy to the secondline TKI and the final reason for the change of therapy. Results A total of 247 patients treated were found in 22 cities in Colombia with a mean age of 53.2 ± 15.2 years. The drug most used as initial therapy was imatinib; 53.8% of cases had to change to another TKI. 50% of patients changed therapy in 42 months, men in 24 and women in 67 months (95% CI 14.314-33.686; p = 0.001). Being male (OR 2.23; 95% CI 1.291-3.854; p = 0.004) and receiving hydroxyurea (OR 3.65; 95% CI 1.601-8.326; p = 0.002) were associated with a higher probability of switching to nilotinib or dasatinib, while receiving a new-generation TKI (OR 0.15; 95% CI 0.071-0.341; p < 0.001) reduced this risk. Conclusions A high proportion of patients needed to change to a second line with nilotinib and dasatinib management. It is necessary to obtain more real world evidence, to improve the effectiveness, adherence and safety of the treatment. [ABSTRACT FROM AUTHOR]

Objective: Rare co-existance of disease or pathology Background: CML presenting with a variant Philadelphia translocation, atypical BCR-ABL transcript, additional chromosomal aberrations, and evolving MDS is uncommon and therapeutically challenging. The prognostic significance of these genetic findings is uncertain, even as singular aberrations, with nearly no data on management and outcome when they coexist. MDS evolving during the course of CML may be either treatment-associated or an independently coexisting disease, and is generally considered to have an inferior prognosis. Tyrosine kinase inhibitors (TKI) directed against BCR-ABL are the mainstay of treatment for CML, whereas treatment modalities that may be utilized for MDS and CML include allogeneic stem cell transplant and - at least conceptually - hypomethylating agents. Case Report: Here, we describe the clinical course of such a patient, demonstrating that long-term combined treatment with dasatinib and azacitidine for coexisting CML and MDS is feasible and well tolerated, and may be capable of slowing disease progression. This combination therapy had no deleterious effect on subsequent potentially curative haploidentical bone marrow transplantation. Conclusions: The different prognostic implications of this unusual case and new therapeutic options in CML are discussed, together with a review of the current literature on CML presenting with different types of genomic aberrations and the coincident development of MDS. Additionally, this case gives an example of long-term combined treatment of tyrosine kinase inhibitors and hypomethylating agents, which could be pioneering in CML treatment. [ABSTRACT FROM AUTHOR]

Objective: Rare co-existance of disease or pathology Background: Hypercalcemia associated with chronic myeloid leukemia (CML) is an ominous sign. Although rare, several cases have been reported and multiple pathophysiologic mechanisms have been independently proposed. We present a patient case and a literature review of the clinical presentation and mechanisms of CML-associated hypercalcemia. Case Report: A 58-year-old male with a past medical history of CML diagnosed six years earlier, presented to the emergency department with one week of acute confusion, disorientation, polyuria, and polydipsia. On physical examination, we observed tachycardia, altered mental status, and dehydration. Blood analysis revealed leukocytosis, thrombocytosis, and marked hypercalcemia (18.6 mg/dL). His chest CT scan showed diffuse lytic lesions and bone destruction concerning for diffuse bone marrow involvement. The patient was diagnosed with hypercalcemia in the context of a CML blast phase. Treatment with hydration, calcitonin, and zoledronic acid lead to control of his symptoms and normalization of his serum calcium levels. After discharged, the patient was maintained on palliative treatment and zoledronic acid management without new episodes of hypercalcemia. However, eight months later, the patient died. Conclusions: Evidence from the literature demonstrates a highly variable clinical presentation of CML-associated hypercalcemia, commonly occurring during an accelerated or a blast phase, and associated with poor survival. Multiple mechanisms could be involved and are not exclusive of each other. Better understanding of the pathophysiologic mechanisms involved in CML-associated hypercalcemia could lead to improvement in clinical and laboratory evaluation of these patients and be the foundation for the development of better management strategies and possibly target-directed therapy to positively improve prognosis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The goal of this study was to monitor imatinib mesylate therapeutically in the Tumor Biology Laboratory, Department of Hematology and Hemotherapy, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (USP). A simple and sensitive method to quantify imatinib and its metabolite (CGP74588) in human serum was developed and fully validated in order to monitor treatment compliance. METHODS: The method used to quantify these compounds in serum included protein precipitation extraction followed by instrumental analysis using high performance liquid chromatography coupled with mass spectrometry. The method was validated for several parameters, including selectivity, precision, accuracy, recovery and linearity. RESULTS: The parameters evaluated during the validation stage exhibited satisfactory results based on the Food and Drug Administration and the Brazilian Health Surveillance Agency (ANVISA) guidelines for validating bioanalytical methods. These parameters also showed a linear correlation greater than 0.99 for the concentration range between 0.500 µg/mL and 10.0 µg/mL and a total analysis time of 13 minutes per sample. This study includes results (imatinib serum concentrations) for 308 samples from patients being treated with imatinib mesylate. CONCLUSION: The method developed in this study was successfully validated and is being efficiently used to measure imatinib concentrations in samples from chronic myeloid leukemia patients to check treatment compliance. The imatinib serum levels of patients achieving a major molecular response were significantly higher than those of patients who did not achieve this result. These results are thus consistent with published reports concerning other populations.

BACKGROUND: Chronic myeloid leukemia is a neoplasm characterized by clonal expansion of hematopoietic progenitor cells resulting from the (9:22)(q34,11) translocation. The tyrosine kinase abl fusion protein,the initial leukemogenic event in chronic myeloid leukemia, is constitutively activated thus inducing the production of reactive oxygen species. Of particular relevance is the fact that an increase in reactive oxygen species can facilitate genomic instability and may contribute to disease progression. OBJETIVE: To evaluate oxidative stress by determining the levels of malondialdehyde and nitrite in chronic myeloid leukemia patients under treatment with 1st and 2nd generation tyrosine kinase inhibitors monitored at a referral hospital in Fortaleza, Ceará. METHODS: A cross-sectional study was performed of 64 male and female adults. Patients were stratified according to treatment. The levels of malondialdehyde and nitrite were determined by spectrophotometry. Statistical differences between groups were observed using the Student t-test and Fisher's exact test. The results are expressed as mean ± standard error of mean. The significance level was set for a p-value < 0.05 in all analyses. RESULTS: The results show significantly higher mean concentrations of nitrite and malondialdehyde in chronic myeloid leukemia patients using second-generation tyrosine kinase inhibitors compared to patients on imatinib. Conclusion: It follows that chronic myeloid leukemia patients present higher oxidative activity and that the increases in oxidative damage markers can indicate resistance to 1st generation tyrosine kinase inhibitors.

The discovery of the Philadelphia chromosome in 1960, and of theBCR-ABL oncogene in 1984, enabled the development in subsequentyears of a targeted therapy that revolutionized the treatment of chronic myeloid leukemia, thus changing its natural history. The use of imatinib resulted in a significant improvement of the prognosis and outcome of patients with chronic myeloid leukemia. However, the occurrence of mechanisms of resistance or intolerance precludes the eradication of the disease in some of the patients. Second-generation tyrosinekinase inhibitors are efficient in most of these patients, except for those with T315I mutation. We present an overall review of chronic myeloid leukemia, with emphasis on the progress in its treatment.

Background: To evaluate prognostic effect of submicroscopic deletions involving breakage and fusion points of the derivative chromosome 9 and 22 in chronic myeloid leukemia in untreated patients and their follow up samples to correlate with disease outcome. Methods: The study included 78 pretreatment (PT) samples from CML patients and 90 follow-up samples, classified as complete responders (CR, n=33), nonresponders (NR, n =54), and partial responder (PR, n=3) depending on the treatment status of the follow-up samples. Karyotype analysis was performed on metaphases obtained through short term cultures of bone marrow and blood. Detection of BCR-ABL fusion gene was performed using dual color dual fusion (D-FISH) translocation probes. Results: BCR-ABL fusion gene detection by D-FISH showed ABL-BCR deletion on derivative 9 in 47.8% of nonresponders which was higher as compared to pretreatment (11%). Mix D-FISH signal pattern was found in around 20% of pretreatment and non-responder samples. Average interval from chronic phase to blast crisis and accelerated phase was respectively 3.5 and 18 months and accelerated to blast crisis was 16.5 months from the time of diagnosis. The follow-up duration of 31 patients responded to therapy was significantly higher (p=0.0001) as compared to 45 patients who did not respond to therapy. Variant D-FISH signal pattern was seen at the time of diagnosis in patient who responded to therapy as well as those patients who did not respond to therapy. Conclusion: This is the first study from India reporting deletion in ABL, BCR, or ABL-BCR on derivative 9 did not correlate with response to therapy.

Objective: Several studies quantitatively described patients with Chronic Myeloid Leukemia on active treatment with tyrosine kinase inhibitors, however there are few qualitative studies that focus their results on how to accompany patients in the course of the disease over time. The objective of this review is to find out what are the expectations, information needs and experiences that determine adherence to treatment with tyrosine kinase inhibitors in patients with Chronic Myeloid Leukemia in qualitative research articles published in the scientific literature., Methods: A systematic review of qualitative research articles published between 2003-2021 was carried out in PubMed/Medline, Web of Science and Embase databases. Main keywords used were: "Leukemia, Myeloid" and "Qualitative Research". Articles on the acute phase or blast phase were excluded., Results: 184 publications were located. After elimination of duplicates, 6 (3%) were included and 176 (97%) publications were excluded. Studies show that the illness is a turning point in patients' lives, and they develop their own strategies for managing the adverse effects. The factors that determine medication experiences with tyrosine kinase inhibitors should be addressed by implementing personalized strategies: this would result in early detection of problems, reinforce education at each stage and promote open discussion about complex causes underlying the treatment failure., Conclusions: This systematic review provides evidence that implementation personalized strategies must be done to adress the factors that determine the illness experience with Chronic Myeloid Leukemia and receiving treatment with tyrosine kinase inhibitors., Competing Interests: Conflict of interest The authors have declared to have no conflict of interest in connection with this article., (Copyright © 2022 Sociedad Española de Farmacia Hospitalaria (S.E.F.H). Publicado por Elsevier España, S.L.U. All rights reserved.)

Context: Chronic myelogenous leukemia (CML) is a chronic malignancy of myeloid linage associated with a significant increase in granulocytes in bone marrow and peripheral blood. CML diagnosis is based on detection of Philadelphia chromosome and "Abelson murine leukemia viral oncogene homolog" (ABL)-"breakpoint cluster region protein" fusions (ABL-BCR fusions). Aims: In this study, patients with CML morphology were studied according to ABL-BCR fusions and the relationship between the fusions and peripheral blood cell changes was examined. Materials and Methods: All patients suspected to chronic myeloproliferative disorders in Lorestan Province visiting subspecialist hematology clinics who were confirmed by oncologist were studied over a period of 5 years. After completing basic data questionnaire, blood samples were obtained with informed consent from the patients. Blood cell count and morphology were investigated and RNA was extracted from blood samples. cDNA was synthesized from RNA and ABL-BCR fusions including b3a2 and b2a2 (protein 210 kd or p210), e1a2 (protein 190 kdor p190), and e19a2 (protein 230 kdor p230) were studied by multiplex reverse transcription polymerase chain reaction method. Coexistence of e1a2 and b2a2 (p210/p190) fusions was also studied. The prevalence of mutations and their correlation with the blood parameters were statistically analyzed. Results: Of 58 patients positive for ABL-BCR fusion, 18 (30.5%) had b2a2 fusion, 37 (62.71%) had b3a2 fusion and three (3.08%) had e1a2 fusion. Coexistence of e1a2 and b2a2 (p210/p190) was not observed. There was no significant correlation between ABL-BCR fusions and white blood cell count, platelet count, and hemoglobin concentration. Conclusions: The ABL-BCR fusions in Lorestan Province were similar to other studies in Iran, and b3a2 fusion had the highest prevalence in the studied patients studied. [ABSTRACT FROM AUTHOR]

Extramedullary leukemia (EM AML), also known as myeloid sarcoma, is a rare manifestation of acute myelogenous leukemia and often accompanies bone marrow involvement. EM AML is diagnosed based on H&E stains with ancillary studies including flow cytometry and cytogenetics. Isolated EM AML is often misdiagnosed as large cell lymphoma or other lymphoproliferative disorder. The clinical presentation is often dictated by the mass effect and the location of the tumor. The optimal treatment remains unclear. High-dose chemotherapy, radiation, surgical resection, and allogeneic stem cell transplantation are all modalities that can be incorporated into the therapy of EM AML. Cytarabine-based remission induction regimens have been the most commonly used in the upfront setting. There are limited data about the optimal consolidation. Transplantation is ideally offered for high risk disease or in the relapsed setting. In this manuscript, we will review the recent literature about EM AML, focusing on therapy and proposing a treatment algorithm for managing this rare form of leukemia. Further studies addressing risk stratification, role of molecular and genetic aberrations, and optimal treatment strategies are warranted. [ABSTRACT FROM AUTHOR]

We report the occurrence of leukaemic infiltration of cervical spinal cord secondary to chronic myeloid leukaemia (CML) in a 31-year-old male patient. He presented with left upper limb monoplegia. On examination he had asymmetric quadriparesis, graded sensory loss and urinary retention. Diagnosis was suggested by magnetic resonance imaging. He responded dramatically to radiotherapy and corticosteroids treatment. Infiltration of the cervical spinal cord in a patient with CML has seldom been reported in literature till date, and hence we are reporting this case. [ABSTRACT FROM AUTHOR]