Cultural factors related to adherence to imatinib in CML: a Mexican perspective.
Hematology. 2015 Mar;20(2):72-6
Authors: Cantú-Rodríguez OG, Sánchez-Cárdenas M, Gutiérrez-Aguirre CH, Jaime-Pérez JC, Mancias-Guerra C, González-Llano O, Gómez-Almaguer D
INTRODUCTION: The advent of imatinib as a therapeutic option of chronic myeloid leukemia (CML) has transformed this previously highly resistant disease into one that is susceptible to management with oral drugs that now offer high long-term survival rates. However, achieving an adequate adherence to treatment regimes is of critical importance. The characteristics of treatment compliance in Mexican patients have not been determined.
METHODS: We evaluated 38 CML patients, members of the Glivec(®) International Patient Assistance Program (GIPAP). A bimonthly simplified medication adherence questionnaire was applied and the adherence rate was calculated by direct tablet counting.
RESULTS: Two groups, one of local patients and another of out-of-town patients, were studied using an 85% adherence rate as a cut-off. The overall adherence rate was 85.9%. Fifteen patients were considered non-adherent (39.5%). The group of out-of-town patients presented a higher adherence rate of 92.8% in contrast with 76.3% in the local population (P = 0.021). The probability of achieving a complete cytogenetic response at some point of evolution after 8 years of follow-up was 93% in the adherent group vs. 58% in the group with an adherence rate <85% (P = 0.008). In patients with imatinib failure, the adherence rate was 75.8% compared to 95.5% (P = 0.008) in the optimal response group.
CONCLUSIONS: In Mexican patients with CML, non-adherence to treatment is a cause of the failure to achieve remission or the subsequent loss of a complete cytogenetic and major molecular response.
PMID: 25034734 [PubMed - indexed for MEDLINE]
Detection of BCR-ABL1 mutations that confer tyrosine kinase inhibitor resistance using massively parallel, next generation sequencing.
Ann Hematol. 2015 Nov 10;
Authors: Szankasi P, Schumacher JA, Kelley TW
Detection of BCR-ABL1 mutations that confer resistance to tyrosine kinase inhibitors is important for management of patients with t(9;22);BCR-ABL1-positive (Ph+) leukemias. Testing is often performed using Sanger sequencing (SS) which has relatively poor sensitivity. Given the widespread adoption of next generation sequencing (NGS), we sought to reevaluate the testing in the context of NGS methods. We developed an NGS-based BCR-ABL1 mutation test on the Ion Torrent Personal Genome Machine (PGM) to test for resistance mutations, primarily in the kinase domain in BCR-ABL1. We analyzed 508 clinical samples from patients with Ph+ leukemias. In a subset of these samples (n?=?97), we conducted a comparison of the NGS results to a classical SS-based test. NGS facilitated detection of low-level mutations (<20 % allele frequency) that were not detectable by SS. In a subset of cases with multiple mutations, NGS was also able to determine if two mutations were on the same molecule (compound) or on separate molecules (polyclonal) but this was limited by the distance between mutated positions and by the effects of apparent distance-dependent PCR recombination. We found 22 compound mutations that centered on one or two key residues including two novel compound mutants: Q252H/Y253H and F311Y/F359I. The advantages of NGS make it a superior method for inventorying BCR-ABL1 resistance mutations. However, data analysis may be complicated by short read lengths and the effects of PCR recombination.
PMID: 26555285 [PubMed - as supplied by publisher]
Sudden sensorineural hearing loss as the first manifestation of chronic myeloid leukaemia: case report.
J Laryngol Otol. 2014 Nov;128(11):1015-7
Authors: Diao M, Tian F, Sun J
BACKGROUND: Sudden sensorineural hearing loss rarely occurs in patients with chronic myeloid leukaemia.
CASE REPORT: We present a case report of a patient who presented with sudden sensorineural hearing loss as the first manifestation of chronic myeloid leukaemia, and review the mechanisms responsible for sudden sensorineural hearing loss in leukaemic patients.
RESULTS: A 31-year-old female presented to our clinic with unilateral sudden sensorineural hearing loss and tinnitus. Pure tone audiometry revealed profound sensorineural hearing loss in the left ear at all frequencies. During an investigation into her hearing loss, the patient was found to have chronic myeloid leukaemia.
CONCLUSION: Every case of sudden sensorineural hearing loss must be carefully evaluated, and haematological disorders must be considered in the differential diagnosis of sudden hearing loss.
PMID: 25399829 [PubMed - indexed for MEDLINE]
Analysis of microRNA and gene networks in human chronic myelogenous leukemia.
Mol Med Rep. 2015 Nov 5;
Authors: Wang K, Xu Z, Wang N, Tian Y, Sun X, Ma Y
Molecular biologists have identified a number of genes and microRNAs (miRs) associated with chronic myelogenous leukemia (CML). However, their underlying mechanisms in CML remain unclear. In the present study, three regulatory networks of genes and miRs were constructed to elucidate the underlying mechanisms of CML. The first network was the experimentally validated network of miRs and genes. The second was the dysregulatory network of CML, consisting of dysregulated genes and miRs, contributing to the pathogenesis of CML. The third was the CML?associated network, consisting of CML?associated genes and miRs. In addition to dysregulated genes and miRs, the associated network includes non?dysregulated genes and miRs that contribute to prevention, diagnosis, metastasis and therapy of CML. Key pathways were extracted and compared to distinguish the similarities and differences between dysregulatory nodes among the three networks. V-myb avian myeloblastosis viral oncogene homolog and miR?155 were observed to form a feedback loop module in the dysregulatory network. Regulation of the dysregulatory network may present as a strategy for gene therapy of CML. The current study provides an improved understanding of the molecular mechanisms of, and a potential treatment strategy for, CML.
PMID: 26548770 [PubMed - as supplied by publisher]
Hydroxyurea-induced oral ulceration.
Oral Surg Oral Med Oral Pathol Oral Radiol. 2015 Dec;120(6):e232-4
Authors: Badawi M, Almazrooa S, Azher F, Alsayes F
Hydroxyurea is an antimetabolite that is widely used in the treatment of many benign and malignant conditions. This drug is usually well tolerated but has a number of side effects that vary in incidence. In cases of clinically significant adverse events, hydroxyurea is usually discontinued either temporarily or permanently, depending on treatment need versus harm caused by side effects. Here, we report a case of oral ulceration associated with hydroxyurea treatment in a patient who had chronic myelogenous leukemia. The patient rapidly developed an oral ulcer 12 days after administration of the drug. Hydroxyurea was discontinued, and the oral lesion appreciably decreased in size and severity. Physicians and dentists should be aware of the association between hydroxyurea and oral lesions.
PMID: 26548732 [PubMed - in process]
[Isolation of Neisseria elongata subsp. elongata Isolated from an Acute Myelogenous Leukemia Patient].
Kansenshogaku Zasshi. 2015 Jan;89(1):10-5
Authors: Kubota H, Okuno R, Hatakeyama K, Sadamasu K, Hidai H, Fujita A, Kai A
Gram-negative cocci with a rod-like shape were isolated from a blood sample of a patient with acute myelogenous leukemia (AML). The 16S rRNA sequence of the isolate was similar to that of Neisseria elongata. Because previous reports about N. elongata as a pathogen have been extremely rare, more reliable identification seemed to be needed. We thus additionally performed a Multilocus Sequencing Analysis (MLSA) based on another four regions (argF, rho, recA, glnA), and confirmed the identification of N. elongata. The results from the MLSA identified the species; however, we could not identify the isolates into subspecies from the sequences. Three subspecies of N. elongata (N. elongata subsp. elongata, N. elongata subsp. glycolytica and N. elongata subsp. nitroreducens) were classified based on three definitive characteristics (catalase possession, nitrite reducibility, and acid from glucose). The results of the tests of three characteristics supported the identification of the isolate as N. elongata subsp. elongata. Therefore we determined the isolate from the AML patient to be N. elongata subsp. elongata.
PMID: 26548291 [PubMed - in process]
Background differences in baseline and stimulated MMP levels influence abdominal aortic aneurysm susceptibility.
Atherosclerosis. 2015 Oct 8;243(2):621-629
Authors: Dale MA, Suh MK, Zhao S, Meisinger T, Gu L, Swier VJ, Agrawal DK, Greiner TC, Carson JS, Baxter BT, Xiong W
OBJECTIVE: Evidence has demonstrated profound influence of genetic background on cardiovascular phenotypes. Murine models in Marfan syndrome (MFS) have shown that genetic background-related variations affect thoracic aortic aneurysm formation, rupture, and lifespan of mice. MFS mice with C57Bl/6 genetic background are less susceptible to aneurysm formation compared to the 129/SvEv genetic background. In this study, we hypothesize that susceptibility to abdominal aortic aneurysm (AAA) will be increased in 129/SvEv mice versus C57Bl/6 mice. We tested this hypothesis by assessing differences in aneurysm size, tissue properties, immune response, and MMP expression.
METHODS: Mice of C57Bl/6 or 129/SvEv background underwent AAA induction by periaortic application of CaCl2. Baseline aortic diameters, tissue properties and MMP levels were measured. After aneurysm induction, diameters, MMP expression, and immune response (macrophage infiltration and bone marrow transplantation) were measured.
RESULTS: Aneurysms were larger in 129/SvEv mice than C57Bl/6 mice (83.0% ± 13.6 increase compared to 57.8% ± 6.4). The aorta was stiffer in the 129/SvEv mice compared to C57Bl/6 mice (952.5 kPa ± 93.6 versus 621.4 kPa ± 84.2). Baseline MMP-2 and post-aneurysm MMP-2 and -9 levels were higher in 129/SvEv aortas compared to C57Bl/6 aortas. Elastic lamella disruption/fragmentation and macrophage infiltration were increased in 129/SvEv mice. Myelogenous cell reversal by bone marrow transplantation did not affect aneurysm size.
CONCLUSIONS: These data demonstrate that 129/SvEv mice are more susceptible to AAA compared to C57Bl/6 mice. Intrinsic properties of the aorta between the two strains of mice, including baseline expression of MMP-2, influence susceptibility to AAA.
PMID: 26546710 [PubMed - as supplied by publisher]
An Efficient Method for Electroporation of Small Interfering RNAs into ENCODE Project Tier 1 GM12878 and K562 Cell Lines.
J Biomol Tech. 2015 Oct 29;
Authors: Muller RY, Hammond MC, Rio DC, Lee YJ
The Encyclopedia of DNA Elements (ENCODE) Project aims to identify all functional sequence elements in the human genome sequence by use of high-throughput DNA/cDNA sequencing approaches. To aid the standardization, comparison, and integration of data sets produced from different technologies and platforms, the ENCODE Consortium selected several standard human cell lines to be used by the ENCODE Projects. The Tier 1 ENCODE cell lines include GM12878, K562, and H1 human embryonic stem cell lines. GM12878 is a lymphoblastoid cell line, transformed with the Epstein-Barr virus, that was selected by the International HapMap Project for whole genome and transcriptome sequencing by use of the Illumina platform. K562 is an immortalized myelogenous leukemia cell line. The GM12878 cell line is attractive for the ENCODE Projects, as it offers potential synergy with the International HapMap Project. Despite the vast amount of sequencing data available on the GM12878 cell line through the ENCODE Project, including transcriptome, chromatin immunoprecipitation-sequencing for histone marks, and transcription factors, no small interfering siRNA-mediated knockdown studies have been performed in the GM12878 cell line, as cationic lipid-mediated transfection methods are inefficient for lymphoid cell lines. Here, we present an efficient and reproducible method for transfection of a variety of siRNAs into the GM12878 and K562 cell lines, which subsequently results in targeted protein depletion.
PMID: 26543439 [PubMed - as supplied by publisher]
Persistent clonal chromosomal abnormalities in a chronic myeloid leukemia patient.
Pediatr Int. 2015 Nov 5;
Authors: Muraoka M, Washio K, Kanamitu K, Kanazawa Y, Ishida T, Miyamura T, Chayama K, Nishiuchi R, Oda M, Shimada A
Clonal cytogenetic abnormalities (CCA) in Philadelphia chromosome (Ph)-negative cells have been reported in a small population of adult chronic myelogenous leukemia (CML) patients during the clinical course, but CCA in pediatric CML patients are rarely reported. We herein report the case of an 8-year-old boy from the onset of CML. Although he had relapse after unrelated bone marrow transplantation when 9?years old, he has since been in complete molecular response on imatinib mesylate treatment. Surprisingly, various CCA have been observed in this patient, including several reciprocal chromosomal translocations in Ph-negative cells for >12?years. Although dysplasia in the bone marrow cells was identified, no overt transformation to myelodysplastic syndrome or acute myeloid leukemia has been observed. The cause of the CCA remains unknown in this patient, and careful observation is required.
PMID: 26542480 [PubMed - as supplied by publisher]
Influence of Fucoidans and Their Derivatives on Antitumor and Phagocytic Activity of Human Blood Leucocytes.
Biochemistry (Mosc). 2015 Jul;80(7):925-33
Authors: Anisimova NY, Ustyuzhanina NE, Donenko FV, Bilan MI, Ushakova NA, Usov AI, Nifantiev NE, Kiselevskiy MV
The immunotropic activity of structurally different fucoidans and their derivatives towards isolated immune blood cells, effectors of innate immune system, was studied. The most potent effect was observed for high molecular weight fucoidan CF from the alga Chordaria flagelliformis, whose backbone is built of (1?3)-linked units of ?-L-fucopyranose, and branches included residues of ?-D-glucuronic acid and ?-L-fucofuranose. This compound at the concentration of 0.05 mg/ml potentiated phagocytosis of Saccharomyces cerevisiae and Lactobacillus acidophilus by neutrophils, increasing relative quantity of phagocytes as well as their effectiveness. Along with this, 14% increase in the concentration of membrane-bound integrin CD11c molecules was observed. The systemic effect of CF at the dose of 0.01 mg/mouse i.p. led to potentiation of cytotoxic activity of spleen mononuclear leucocytes towards melanoma cells of line B16 by 1.9-fold and towards chronic myelogenous leukemia cells of line K-562 by 1.7-fold. These results indicate that fucoidan CF can stimulate anti-infective and antitumor activity of effectors of the innate immune system via CD11c integrins.
PMID: 26542005 [PubMed - in process]
[Development of Ph negative acute myeloid leukemia in a patient with minor-BCR/ABL positive chronic myeloid leukemia achieving a partial cytogenetic response during tyrosine kinase inhibitor treatment].
Rinsho Ketsueki. 2015 Jun;56(6):681-6
Authors: Fujii S, Miura I, Tanaka H
A 78-year-old male, who had CKD and chronic heart failure, was referred to our hospital for evaluation of leukocytosis. His bone marrow contained 12% blast cells and chromosome analysis showed the Ph chromosome as well as other changes. The patient was diagnosed with the accelerated-phase CML because FISH and RT-PCR disclosed BCR/ABL fusion signals and minor BCR/ABL, respectively. Imatinib was administered, but the CML was resistant to this treatment. We gave him nilotinib employing a reduced and intermittent administration protocol because of the progression of anemia and heart failure. The patient achieved PCyR in 8 months, but, 12 months later, his WBC count increased and 83% of the cells were blasts. Because the probable diagnosis was the blast crisis of CML, we switched from nilotinib to dasatinib. However, leukocytosis worsened and he died of pneumonia. It was later revealed that he had a normal karyotype and both FISH and RT-PCR analysis of BCR/ABL were negative. His final diagnosis was Ph negative AML developing from Ph positive CML in PCyR. Since there were no dysplastic changes indicative of MDS, it was assumed that the AML was not secondary leukemia caused by the tyrosine kinase inhibitor but, rather, de novo AML.
PMID: 26256879 [PubMed - indexed for MEDLINE]
Comparison of molecular responses based on BCR-ABL1% (IS) results from an in-house TaqMan-based qPCR versus Xpert(®) assay in CML patients on tyrosine kinase inhibitor therapy.
Acta Clin Belg. 2015 Aug;70(4):237-43
Authors: Boeckx N, Laer CV, Roover JD, Wilmsen B, Bruyninckx K, Pauwels S
OBJECTIVES: Tyrosine kinase inhibitors (TKIs) have drastically changed the prospects for chronic myeloid leukemia (CML) patients. The European LeukemiaNet (ELN) recommends molecular monitoring of BCR-ABL1 mRNA levels at distinct time points to define an optimal response, warning, or failure of treatment.
METHODS: Sixty-four follow-up peripheral blood samples from CML patients on TKI were tested by two methods. Molecular responses based on BCR-ABL1% (IS) from an Xpert(®) BCR-ABL1 Monitor assay were compared with TaqMan-based qPCR.
RESULTS: Seven samples showed ‘molecularly undetectable leukaemia’ by both methods (11%). In-house qPCR showed 57 BCR-ABL1+ samples; 45/57 samples (79%) were concordant for ‘major molecular response’ (MMR, n?=?32) and ‘no MMR’ (n?=?13) by both assays, whereas nine were BCR-ABL1 negative by Xpert(®). Identical molecular responses (i.e. ‘optimal’) were defined in 41 samples. Discordances seen in patients <?10 months on TKI (n?=?2) had no impact on clinical management, whereas for patients >12 months on TKI, a different molecular response was defined (‘warning’ versus ‘optimal’). Thirteen samples had ‘no MMR’ by both methods. 10/13 showed identical intervals (>10%(IS), 1-10%(IS) or 0·1-1%(IS)), corresponding to seven ‘failures’ and three ‘warnings’. Discordant intervals were seen in 3/13 samples (all defined as ‘failures’). Deep molecular responses (MR(4·0) or MR(5·0)) with detectable BCR-ABL1 showed some fluctuations between both methods, nevertheless, all had ‘optimal’ responses. ‘Molecularly undetectable leukaemia’ was observed more frequently by Xpert(®) (n = 16) as by our in-house assay (n?=?7).
DISCUSSION: Based on current ELN recommendations, Xpert(®) BCR-ABL1 assay defines identical molecular responses as TaqMan-based qPCR BCR-ABL1% (IS) data in 98% (63/64) of samples.
PMID: 26166681 [PubMed - indexed for MEDLINE]
Dimers of melampomagnolide B exhibit potent anticancer activity against hematological and solid tumor cells.
J Med Chem. 2015 Nov 5;
Authors: Crooks PA, Janganati V, Ponder J, Jordan CT, Borrelli MJ, Penthala NR
Novel carbamate (7a-7h) and carbonate (7i, 7j and 8) dimers of melampomagnolide B have been synthesized by reaction of the melampomagnolide-B-triazole carbamate synthon 6 with various terminal diamino- and dihydroxyalkanes. Dimeric carbamate products 7b, 7c and 7f exhibited potent growth inhibition (GI50 = 0.16-0.99 µM) against the majority of cell lines in the NCI panel of 60 human hematological and solid tumor cell line. Compound 7f and 8 exhibited anticancer activity that was 300-fold and 1 x 106-fold more cytotoxic, respectively, than DMAPT at a concentration of 10 µM against rat 9L-SF gliosarcoma cells. Compounds 7a-7j and 8 were also screened against M9-ENL1 and acute myelogenous leukemia (AML) primary cell lines and exhibited two- to ten-fold more potent antileukemic activity against M9-ENL1 cells (EC50 = 0.57-2.90 µM) when compared to parthenolide (EC50 = 6.0), and showed potent anti-leukemic activity against five primary AML cell lines (EC50 = 0.76-7.3 µM).
PMID: 26540463 [PubMed - as supplied by publisher]
CBL controls a tyrosine kinase network involving AXL, SYK and LYN in nilotinib-resistant chronic myeloid leukaemia.
J Pathol. 2015 Sep;237(1):14-24
Authors: Gioia R, Trégoat C, Dumas PY, Lagarde V, Prouzet-Mauléon V, Desplat V, Sirvent A, Praloran V, Lippert E, Villacreces A, Leconet W, Robert B, Vigon I, Roche S, Mahon FX, Pasquet JM
A tyrosine kinase network composed of the TAM receptor AXL and the cytoplasmic kinases LYN and SYK is involved in nilotinib-resistance of chronic myeloid leukaemia (CML) cells. Here, we show that the E3-ubiquitin ligase CBL down-regulation occurring during prolonged drug treatment plays a critical role in this process. Depletion of CBL in K562 cells increases AXL and LYN protein levels, promoting cell resistance to nilotinib. Conversely, forced expression of CBL in nilotinib-resistant K562 cells (K562-rn) dramatically reduces AXL and LYN expression and resensitizes K562-rn cells to nilotinib. A similar mechanism was found to operate in primary CML CD34(+) cells. Mechanistically, the E3-ligase CBL counteracts AXL/SYK signalling, promoting LYN transcription by controlling AXL protein stability. Surprisingly, the role of AXL in resistance was independent of its ligand GAS6 binding and its TK activity, in accordance with a scaffold activity for this receptor being involved in this cellular process. Collectively, our results demonstrate a pivotal role for CBL in the control of a tyrosine kinase network mediating resistance to nilotinib treatment in CML cells.
PMID: 25965880 [PubMed - indexed for MEDLINE]
A coiled-coil mimetic intercepts BCR-ABL1 dimerization in native and kinase-mutant chronic myeloid leukemia.
Leukemia. 2015 Aug;29(8):1668-75
Authors: Woessner DW, Eiring AM, Bruno BJ, Zabriskie MS, Reynolds KR, Miller GD, O’Hare T, Deininger MW, Lim CS
Targeted therapy of chronic myeloid leukemia (CML) is currently based on small-molecule inhibitors that directly bind the tyrosine kinase domain of BCR-ABL1. This strategy has generally been successful, but is subject to drug resistance because of point mutations in the kinase domain. Kinase activity requires transactivation of BCR-ABL1 following an oligomerization event, which is mediated by the coiled-coil (CC) domain at the N terminus of the protein. Here, we describe a rationally engineered mutant version of the CC domain, called CC(mut3), which interferes with BCR-ABL1 oligomerization and promotes apoptosis in BCR-ABL1-expressing cells, regardless of kinase domain mutation status. CC(mut3) exhibits strong proapoptotic and antiproliferative activity in cell lines expressing native BCR-ABL1, single kinase domain mutant BCR-ABL1 (E255V and T315I) or compound-mutant BCR-ABL1 (E255V/T315I). Moreover, CC(mut3) inhibits colony formation by primary CML CD34(+) cells ex vivo, including a sample expressing the T315I mutant. These data suggest that targeting BCR-ABL1 with CC mutants may provide a novel alternative strategy for treating patients with resistance to current targeted therapies.
PMID: 25721898 [PubMed - indexed for MEDLINE]
Ponatinib is not transported by ABCB1, ABCG2 or OCT-1 in CML cells.
Leukemia. 2015 Aug;29(8):1792-4
Authors: Lu L, Saunders VA, Leclercq TM, Hughes TP, White DL
PMID: 25676419 [PubMed - indexed for MEDLINE]
Avascular necrosis of femoral head as the initial manifestation of CML.
Pediatr Hematol Oncol. 2014 Sep;31(6):568-73
Authors: Kumar S, Bansal D, Prakash M, Sharma P
A 12-year-old female is reported who presented with right hip pain for 6 months. With massive splenohepatomegaly and leukocytosis, CML was suspected and confirmed on bone-marrow examination and cytogenetics. Further investigations confirmed avascular necrosis (AVN) of the right femoral head. CML was treated by hydroxyurea, followed by imatinib. AVN was managed conservatively; patient demonstrated progressive improvement, though a mild limp in the gait was persisting at 22 months. AVN as the initial manifestation of CML is a rarity. Leukostasis is considered to be the pathophysiological mechanism. In view of the rarity, a case is reported, along with compilation of previously reported cases.
PMID: 24087840 [PubMed - indexed for MEDLINE]
Budget Impact Analysis of Dasatinib as a Second-Line Therapy in Patients with Chronic Myelogenous Leukemia (Cml) in the Russian Federation.
Value Health. 2015 Nov;18(7):A441-2
Authors: Kulikov A, Yagudina R, Protsenko MV
PMID: 26532483 [PubMed - in process]
Relationship between obesity and clinical outcome in adults with acute myeloid leukemia: A pooled analysis from four CALGB (Alliance) clinical trials.
Am J Hematol. 2015 Nov 3;
Authors: Castillo JJ, Mulkey F, Geyer S, Kolitz JE, Blum W, Powell BL, George SL, Larson RA, Stone RM
Obesity has been previously suggested as an adverse prognostic marker in patients with acute leukemia. To evaluate the relationship between obesity and clinical outcome, disease-free survival (DFS) and overall survival (OS), in patients with acute myelogenous leukemia (AML), including acute promyelocytic leukemia (APL), we performed a pooled analysis of four CALGB (Alliance) clinical trials. Our study included 446 patients with APL from CALGB 9710, and 1,648 patients between 18 and 60 years of age with non-APL AML from CALGB 9621, 10503, and 19808. Obesity was defined as BMI ?30 kg/m(2) . Multivariate Cox proportional-hazard regression models were fitted for DFS and OS. Obesity was seen in 50% and 38% of APL and non-APL AML patients, respectively. In APL patients, obesity was associated with worse DFS (HR 1.53, 95% CI 1.03-2.27; p=0.04) and OS (HR 1.72, 95% CI 1.15-2.58; p=0.01) after adjusting for age, sex, performance status, race, ethnicity, treatment arm and baseline white blood cell count. Obesity was not significantly associated with DFS or OS in the non-APL AML patients. In conclusion, our study indicates that obesity has significant prognostic value for DFS and OS in APL patients, but not for non-APL AML patients. This article is protected by copyright. All rights reserved.
PMID: 26526191 [PubMed - as supplied by publisher]
Prognostic significance of early molecular response in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors.
Hematology Am Soc Hematol Educ Program. 2014 Dec 5;2014(1):240-3
Authors: Yeung DT, Mauro MJ
A 55-year-old man presented with splenomegaly (10 cm below left costal margin) and leucocytosis (145 × 10(9)/L). Differential showed neutrophilia with increased basophils (2%), eosinophils (1.5%), and left shift including myeloblasts (3%). A diagnosis of chronic myeloid leukemia in chronic phase was established after marrow cytogenetics demonstrated the Philadelphia chromosome. Molecular studies showed a BCR-ABL1 qPCR result of 65% on the International Scale. Imatinib therapy at 400 mg daily was initiated due to patient preference, with achievement of complete hematological response after 4 weeks of therapy. BCR-ABL1 at 1 and 3 months after starting therapy was 37% and 13%, respectively (all reported on International Scale). Is this considered an adequate molecular response?
PMID: 25696861 [PubMed - indexed for MEDLINE]