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  • 1
    Publication Date: 2019-11-13
    Description: Introduction Patients with AML are inmmunocompromised because of the disease itself and the use of chemotherapy, increasing endemic opportunistic infections. The main complication is secondary infectious diseases, which we have to consider TB. In cancer patients infected with TB frequently manifest more atypical. Clinical signs and symptoms include lung disease which is still the most commonly involved site, extra pulmonary tuberculosis is not uncommon. Even that we're in an endemic country we still have some delay in the diagnosis of such disease. Objective To characterize the clinical and factors that contributes to the delay on the diagnosis of tuberculosis in patients with AML. Methods We did a chart review of patients with the diagnosis of TB and AML in the Instituto Nacional de Cancerologia, Mexico City, from January 2014 to July 2019. We analyze the clinical presentation of and the time to diagnosis TB in those patients. Results We analyze a cohort of 5 patients, three male and two female with a median age of 44 years old. The majority of patients were on induction chemotherapy. The main clinical presentation was persistent fever that begins in the nadir of chemotherapy. We observed a median of days for the diagnosis of tuberculosis of 37 days (9-82), the diagnosis was made by histopathology supported by special stains, and were required at least two biopsies for the diagnosis. One patient has pulmonary tuberculosis, one nodal presentation, two have a hepatosplenic presentation, and in the last patient was conclude latent TB. Just in one patient was available the microbiological identification, Mycobaterium bovis. Four patients started the approved treatment in Mexico, intensive phase with rifampicin, pyrazinamide, ethambutol and isoniazid. One patient develop Drug induce liver injury (DILI) so she couldn't continue the first line treatment and have to receive the second line which it is not standardize. After the initiation of the treatment, patients went out of fever and improve their condition. The patients were followed during the maintenance phase with rifampicin, and isoniazid. All of the patients are alive at the moment of the study. Conclusion: Febril neutropenia is a common complication in patients with AML, and in patients with persistent fever, tuberculosis should be include in the differential diagnosis. In México we have limited access to all the diagnostic tools available in our center. Culture is not always a way to identify TB, most of our patients were diagnosed by biopsy, median number of procedures were 3. Patient number 5 was followed by the infectology service after the whole protocol of culturing TB were concluded with no evidence of the disease and they decide to stop the treatment, and they manage the patient as latent TB. The availability of the techniques is the main factor which contributes to the diagnosis delay of TB. After the treatment was started, patients have a significant clinical improvement. Disclosures No relevant conflicts of interest to declare.
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  • 2
    Publication Date: 2015-12-03
    Description: Introduction. Autologous stem cell transplant is considered the standard of care in young (
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  • 3
    Publication Date: 2018-11-29
    Description: Introduction: Acute Myeloid Leukemia is a clonal heterogeneous disease, where age is an important risk factor to develop theses disease, PCR studies and next generation sequence have proven the diversity of these disease. A lot of genes mutations have been identifying to play a role in the DNA metilation, epigenetics a transcription. We initiate a screening to all acute myeloid leukemias that where the novo or relapse with a 28 gene panel of HEMAVISION a 28q; DNA diagnostic, for the detection al ARN gene fusion and alternatives of the: PML-RAR ALFA (bcr2,V), CBF-MYH11, RUNX1-RUNX1T1, PML-RAR alfa(bcr1,L), KMT2A-MLT3, PML-RAR alfa (bcr3,S), KMT2A-ELL, FUS-ERG, ETV6-MN1, DEK-NUP214, KMT2A-EPS15, KMT2A-AFDN, TCF3-PBX1, ETV6-RUNX1, KMT2A-MLLT1, KMT2A-AFF1, TCF3-HLF, STIL-TAL1, BCR/ABL(p190), SET-NUP214, BCR/ABL(p210), BCR/ABL(p230), ZBTB16-RARalfa, ETV6-ABL1, ETV6-PDGFRB, KMT2A-MLLT10, KMT2A-MLLT11,KMT2A-FOXO4, KMT2A-MLLT6, RUNX1-MECON, NPM1-RAR alfa, NMP1-MLF1, RUNX1-MECON. FLT3 ITD mutation and D385 by PCR electrophoresis by Invivoscribe was also perform. And the regular cytogenetics and FISH mutations for BCR/ABL, PML/RAR alfa, Inv16, MLL, +8, ETO, BCR, ABL, monosomy 7, monosomy8 Objectives The main objective is the know the mutation in the Mexican population and the prognostic in these group of patients Results These study was perform at Instituto Nacional de Cancerologia, Mexico, randomized patient from 2016-2018 where screen. A total of 70 patients, 37 females and 33 males, ages from 18-85years old, 54 patients where newly diagnosis of acute myeloid leukemia, 4 where relapses and 12 where secondary leukemias, the most frequent FAB morphologic classification where M4:22 cases, M2:15 cases, M3:8 cases, M1:4cases, M0 and M5:3 cases each. Of the 70 patients: 56 patients where negative to all of the panel screen, FLT3 where only perform in 14 patients 12 where negative and 2 where insufficient to perform the test, the most common FISH translocation was PML/RAR alfa, follow by MLL, ETO and +8. For the cytogenetics we had 21 cases that didn´t have enough metaphases, 7 normal, 28 cases with more than 2 cytogenetics alterations and 9 with only 1. With a Cytogenetics risk: high risk 44, intermedium:10 and low12. Of the 70 patient, 14 have some genes mutations +: t(9;11)(p22;q23) KMT2A-MLLT3, t(6;11)(q27;q23) KMT2A-AFDN, t(5;12)(q33;p13) ETV6-PDGFRB, t(8;21)(q22;q22) RUNX1RUNX1T1, inv16(p13q;22q) CBFB-MYH11, t(6;11)(q27;q23) KMT2A-AFDN, t(3;21)(q26:q22) RUNX1-MECOM, inv16(p13q;22q) CBFB-MYH11, t(15;17)(q24;q21) PML-RARA (bcr2,V) t(15;17)(q24;q21) PML-RARA (bcr1,L) t(15;17)(q24;q21) PML-RARA (bcr3,S), t(8;21)(q22;q22) RUNX1RUNX1T1, t(8;21)(q22;q22) RUNX1RUNX1T1, t(15;17)(q24;q21) PML-RARA (bcr3,S) Out of 70 patients: 38 receive 7+3 (cytarabine + Daunorubicin) for first line of treatment, 41 received high doses of cytarabine at 3g /m2. Our first option for relapse treatment is MEC (mitoxantrone, cytarabine and etoposide) because of costs and the second line of rescued treatment is Flag- Ida (idarubicin, fludarabine and cytarabine) and not all patient can afford it. For the elderly patients the first line of treatment is low dose of cytarabine and only in those who can pay azacytidine it is use. The correlation between high risk cytogenetics with mortality is 12 cases out 70. And genes with morality only 4 patients with: t(9;11)(p22;q23) KMT2A-MLLT3, t(6;11)(q27;q23) KMT2A-AFDN, t(5;12)(q33;p13) ETV6-PDGFRB, t(6;11)(q27;q23) KMT2A-AFDN Conclusion We need to know our population characteristics, we don´t have the incidence and prevalence of the gene mutation in the Mexican population. In the market there are several screening panels with different genes. We need to have more genes and more patient to be analyzed to learn our molecular risk, to have a better approach to these patients and better techniques. There is no paper publish with the genetics and gene alteration in the Mexican Population, it is important to continuing working and to use panels with genes as ASXL1, FLT-TKD, CEBPA, KIT, KRAS, IDH1,2, TET2 and others. And other important issue that we found is the high number of patient that abandon treatment 4 cases, because of money issues. And the time of these population 24 patient where death. The incidence of FLT3 mutation ITD and D385 is low in theses population but it was performed only 14/70 patients, we need a large number of patient to know the real incidence. Table. Table. Disclosures No relevant conflicts of interest to declare.
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  • 4
    Publication Date: 2015-12-03
    Description: Infectious complications are a major cause of morbidity and mortality in hematologic patients with acute leukemia. In this paper we address the mayor infectious complications, at the Leukemia Clinic (LC) in the Instituto Nacional de Cancerologia (INCan) Material and Methods. This is a retrospective, observational study, carried on at INCan. We included all patients that attended the LC and died of an infectious complication between January 2012 and December 2014, regardless of status (new case/relapsed) at diagnosis, we included patients with Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML), Acute Biphenotypic Leukemia (ABL) and Acute Promyelocytic Leukemia (APML). The main objective of the study was to determine the most frequent causes of infectious complications in the treatment of acute leukemias. Results. We included 240 patients that were admitted to the LC between the study dates. 12 patients were excluded since they were later diagnosed with another hematologic malignancy rather than leukemia. 228 patients were analyzed. 132 males, 96 females, 36 years was the median age (14-85 years). 126 patients were new cases and 102 patients were treated for relapse. AML 69 patients, ALL 140 patients, ABL 9 patients, and APML 10 patients. We revised the data of all the deaths that occurred in the period of time. 100 cases were included in the study, of those, 30 that were not infectious related and were excluded. Of the 40 patients included, 41 were males and 29 females, with a mean age of 36.8 years (16-72). 44 ALL patients, 18 AML patients, 7 ABL patients and 1 APML patient. 32 patients were new cases and 38 were relapses. The media number of relapses was 1 (1-3). Septic Shock was stated as the cause of death on all electronic files, with Pneumonia as the most common cause of infection origin with 47 patients. As for determining the causal agent of the infection, we used the last positive culture 5 days prior to the death, we found a causal agent in only 47 patients; the most frequent agents involved were: Escherichia coli BLEE with 13 patients, Enterococus faecium with 6 patients, we also report 1 H1N1 and 1 H3N2 influenza infections. 14 patients did not received intensive chemotherapy prior to death, 11 were on supportive care, and 3 of them did not consent treatment. HyperCVAD was the most frequent regimen administered prior to death, with 13 patients, 7+3 followed with 11 patients. POMP in the setting of palliative regimen was also prevalent with 12 patients. 52% of the patients were in nadir of chemotherapy, with a mean of days of 19 (3-64). All patients that received intensive chemotherapy received GSFC and meropenem/vancomycin regimen once septic shock was diagnosed according to the data in the electronic file. All patients received treatment in the beginning, of the 70 patients only 19 were treated in the intensive care unit (ICU). Conclusions. We addressed the most frequent causes of infectious complications at the Acute Leukemia Clinic, as we thought, E. coli BLEE was the most frequent agent involved, perhaps diverting from reports in the literature, we have a low prevalence of gram positive cocci. Pneumonia is the most frequent site of infection, all our patients are admitted to for chemotherapy, hence all the pneumonia cases are hospital acquired. POMP is a prevalent regimen reported, since we use this regimen for palliative care we could relate mortality to relapse/refractory disease more than to toxicity itself. No maintenance regimens were reported in the results. Our study has certain limitations, no mycotic infections could be reported as the electronic file lacks reliable information. Disclosures No relevant conflicts of interest to declare.
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  • 5
    Publication Date: 2016-12-02
    Description: Objectives: To evaluate the therapeutic response to treatment with transcriptional therapy that combines hydralazine / valproate(Transkrip) in cancer patients with cutaneous T-cell lymphoma Determine toxicity, duration of response and time to progression of epigenetic therapy with hydralazine / valproate in patients with T-cell lymphomas Material and methods an open-label, phase II, prospective and longitudinal in the National Cancer Institute of Mexico was carried out, recruiting patients diagnosed with Cutaneous T based on WHO classification 2008, newly diagnosed untreated, demographic data were analyzed and vital and somatometry signs, assessment of efficacy was established according to the therapeutic response in lymphomas measured at each visit at the affected sites for each patient, using the m-SWAT system sorted in complete response (CR), partial response (PR ), stable disease (SD) and progression (PE) and is considered response to patients with complete or partial response, these data were collected in the form of case report at baseline in the first consultation, during treatment and at the end the study at each visit to the doctor. Statistical analysis was performed with SPSS version 13.0 software. results 16 patients were selected with diagnosis of cutaneous T-cell lymphoma, one patients discontinued the study at baseline and 4 patients had disease progression during the first months of the study, a total of 10 patients who completed 18 months of study continuing the compassionate use treatment. The median age of patients was 45.8 years analyzed (18-83 years) of which 8 are women (53%) and 7 men (47%) with an ECOG 1 in 93.3% of patients, with an average weight of 72.5 ± 15.99 kg, height 1.6 ± 0.1 m, body mass index 28.3 ± 5.7 kg / m2, 46.7% of overweight patients, systolic blood pressure an average of 116.2 ± 14.3 mmHg and diastolic 75.1 ± 11.04 mmHg with respiratory rate 19.43 ± 1.74 resp / min and 77.8 ± 12.3 cardiac beats / min. Of the 10 patients who completed the study, 100% had complete or partial response itching to 6 month continuing unchanged at month 18, the dream as an adverse event occurred in 33% of patients, this being more frequent, adverse events attributed to the drug were known, expected and mild. From 6 months of treatment, the percentage of partial response and complete response of m-SWAT and pruritus were greater than 90% of patients. conclusions: Hydralazine/Valproate (Transkrip) is a medication that offers patients with cutaneous T-cell lymphoma, both first-line and refractory, a therapeutic alternative with high efficiency and good safety profile. Disclosures No relevant conflicts of interest to declare.
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  • 6
    Publication Date: 2016-12-02
    Description: Multiple myeloma a plasmatic cell disorder, characterized by bone marrow infiltration of clonal plasmatic cells, monoclonal immunoglobulin production and end stage organ damage. This disease has a wide range of clinical manifestations, including solitary disease or plasmacytoma. It´s the second most common hematologic disease just behind Non Hodgkin Lymphoma. More than 60% of de novo MM patients present vertebral involvement. 80% of MM patients refer pain as the first symptom of the disease, and this often leads to opioid abuse and adverse effects related to pain medication. Plasmocytoma is one of the three neoplastic lesions of the vertebra that can be susceptible of percutaneous vertebroplasty. The preferred method of treatment is a percutaneous vertebroplasty (PV), a radiologic invasive treatment that can treat multiple pathologies, and is now widely used for treatment of osteoporosis vertebral fractures. For the purpose of the study we aimed to assess functional status and reincorporation to daily living, we used the Karnofsky Performance Status; and the Barthel index. For pain improvement we used the Visual Analog Scale. The Likert satisfaction scale (introduced in 1932) measures patient satisfaction in an analog scale. The main objective of the study was to assess the repercussion of the PV in pain score modification and improvement of functional scores in patients with MM at the Pain Clinic of the Instituto Nacional de Cancerología (INCan) in Mexico City. We carried out the study between January 2004 and October 2015. We compared VP treatment to bisphosphonate (BP) and radiotherapy (RT) according to the visual analog scale; and according to Karnofsky and Barthel scales, we determined the reincorporation to daily activities. We included 119 new cases con MM, of this only 64 were included in the study. Of this 54 were female, and 65 were male with a mean age of 59 years (28-87). 88% of patients referred pain as their main symptom, and 70% presented with a vertebral fracture. 26.9% had an ECOG of 3 or more. 96% (114) received RT and 99% (118) BP. 64 (54%) of patients were treated with VP. Of this, 67% referred a VAS of 4 or more (moderate to severe pain). And 92% of the patients achieved a VAS of 4 or less. As for the Karnofsky we assessed an improvement of 50/80 points pre VP to 80/90 post VP. The same result was assessed in the Barthel scale, with an improvement of 50/80 points pre VP to 80/100 post VP. This data provides solid evidence of the importance of multidisciplinary approach, and that VP is a safe and effective treatment, coupled of course with BP and RT. Disclosures No relevant conflicts of interest to declare.
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  • 7
    Publication Date: 2016-12-02
    Description: Azacitidine, a pyrimidine nucleoside analog of cytidine, causes hypomethilation of DNA. Currently FDA approved for treatment of low and intermediate MDS with complete responses around 50%. And Acute myeloid leukemia (AML) in the eldery In the CALGB studies, the usual dose is 75mg/m2 in 28 day cycles, with dose modifications according to toxicity. In low income countries such as Mexico, one course of Azacitidine is around 500 dollars, median income in Mexico is 4,910 PPP (purchasing power parity); vs 30,616 in the USA. So, azacitidine treatment is far from reach for most of the common population, particularly those who do not have insurance. This is a retrospective observational study, of a compassionate use program of a fixed dose of Aza at 100mg. We analyzed data from patients that were treated with Aza between 2012 and 2016, and collected data in 2016. The aim of the study was to assess the effectivity of the fixed dose. For that purpose, we collected information from the physical and electronic file. We analyzed: Hemoglobin level before and after treatment, independence of transfusion, ANC recovery, number of courses, and overall survival. We conducted our research in a public institution in Mexico (Instituto Nacional de Cancerología) and a private institution (Medica Sur). We included acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients, regardless of age, previous treatment and comorbidities (we included patients with renal failure, hypertension etc.) We included 8 patients in our study, 6 males and 2 females, with a mean age of 69.9 years (49-87). We had 2 AML and 6 MDS. We had 2 high risk AML and according to IPSS-R: 1 very low, 2 low, 1 intermediate, 1 high and 1 very high risk MDS. As for the Karyotype we had 1 complex KT, 4 normal KT and 1 Del 7q Del 5q +8. All patients received at least one dose of Aza, with mean number of cycles of 4. We have a mean survival of 439 days (110-1385). 6/8 patients achieved transfusion independency within 3 doses of Aza. 6/8 patients achieved ANC but lost eventually lost response. 5/8 patients are alive in follow up. 3 patients died of infectious complications. 2 patients never achieved transfusion independence or ANC. The information recovered suggests that a fixed dose of 100mg is as feasible as a higher dose, at least when no other treatment or higher dose can be administered. We still are analyzing the survival data in order to find other bad prognosis factor within this population. Disclosures No relevant conflicts of interest to declare.
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  • 8
    Publication Date: 2019-11-13
    Description: INTRODUCTION Secondary Acute Myeloid Leukemia (s-AML) evolves from a previous hematopoietic clonal disease such as Myelodysplastic Syndromes (MDS/AML), myeloproliferative neoplasia (NPM/AML), medullary insufficiencies - aplastic anemia - (AA/AML) or exposure to chemo or radiotherapy (t-AML). The objective of this work is to describe and highlight the demographic, pathophysiologic and clinical-therapeutic characteristics of s-AML patients compared with p-AML. METHODS This is a retrospective cohort study based on the casuistry from 34 reference centers in Latin America during a period of 10 years (JAN10'-MAY19'). Patients ≥18 years old with primary AML, excluding the promyelocytic subtype (p-AML), and s-AML were admitted. Age, gender, performance status, comorbidity, cytogenetics, mutations, AML subtypes, extramedullary compromise, treatments and overall survival (OS) were analyzed. Statistically, Graph Pad Prism version 5.00 and, SPSS version 17 were used. RESULTS One thousand eleven patients with newly diagnosed AML were recruited, 693 (68.5%) corresponded to p-AML and 318 (31.5%) to s-AML. The demographic differences between p-AML and s-AML are shown on Table 1. Subtypes of s-AML: t-AML (18.5%), MDS/AML (58.2%), NMP/AML (13.5%), AA/AML (5.7%) and others s-AML (4.1%). Global median age was 58 years (R 18-93) and male 52%. Extramedullary compromise in CNS (3.2%) and other organs (5.5%). Seven hundred ninety-three cytogenetic studies were evaluable (based on MRC classification): High (22.3%), Intermediate (68.3%) and Low Risk (9.3%). FLT3 mutation was more frequently found in p-AML. In s-AML, the multivariate study showed short overall survival associated with ECOG ≥2 (HR:2.0), white blood count ≥ 50x109/L at diagnosis (HR:1.9), poor risk karyotype (HR:1.6) and age over 60 years (HR:1.5). At least, 883 patients received treatment (Table 2). During this study period, 211 patients (21%) were transplanted; 49 (23%) were s-AML; histoidentical related donor (46%), haploidentical (39%), non-related (8%) and autologous (7%). The median survival for all AML was 11.0 months with a statistically significant difference in favor of the p-AML (Figure 1). CONCLUSION Performance status (by ECOG ≥2), age ≥60, level of leukocytes a ≥50x109/L, poor risk karyotype and s-AML subtype at diagnosis had a significant worse impact on overall survival. Most patients with s-AML came from MDS, they were older and their incidence increased as the population aged. They presented more comorbidities and worse performance status. Undoubtedly, our findings showed that s-AML is a distinct high risk subset of myeloid disorder with adverse prognosis and represents a therapeutic challenge. Disclosures No relevant conflicts of interest to declare.
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