Candidates For Bone Marrow Transplantation Research Articles

Evaluation of Staphylococcus Aureus and Pseudomonas Aeruginosa in Saliva of Patients with Acute Myeloid Leukemia.

Patients with leukemia are prone to infectious and often life-threatening complications. Evidence suggests that a specific oral microbiota may contribute to septicemia, which can delay antineoplastic treatment, compromise treatment efficacy, or even endanger patients' lives. This study investigated the prevalence of Staphylococcus aureus and Pseudomonas aeruginosa in the saliva of patients with acute myeloid leukemia who were candidates for bone marrow transplantation. This cross-sectional study was conducted in 2019 in the Hematology-Oncology Department of Namazi Hospital, Shiraz University of Medical Sciences. The study included 28 patients with acute myeloid leukemia eligible for bone marrow transplantation as the case group and age- and sex-matched healthy individuals as the control group. Unstimulated saliva samples were collected to determine the frequency of Staphylococcus aureus and Pseudomonas aeruginosa. Data were analyzed using SPSS version 18, the chi-square test, and the independent t-test. In the patients with acute myeloid leukemia, 26 (86%) were positive for Staph-ylococcus aureus and 18 (60%) were positive for Pseudomonas aeruginosa. In the healthy group, 11 (22.9%) were positive for Staphylococcus aureus and 3 (6.2%) were positive for Pseudomonas aeruginosa. The frequency of Pseudomonas aeruginosa and Staphylococcus aureus in the saliva samples of patients with acute myeloid leukemia was significantly higher than in the healthy control subjects (p value < 0.05). Chi-square test showed no significant association between age and the frequency of bacteria (p value= 0.27). In the current study, the frequency of Staphylococcus aureus and Pseudomonas aeruginosa in the saliva of patients with acute myeloid leukemia was higher than in the healthy control group.

Lower uric acid and adequate hydration are associated with lower risk of febrile neutropenia following autologous bone marrow transplantation in patients with lymphoma

Background. Despite the promising results of autologous bone marrow transplantation (BMT) in patients with lymphoma, infectious complications limit its positive outcomes. This study evaluated the incidence and associated factors of febrile neutropenia (FN) following BMT in patients with lymphoma. Materials and methods. The study consecutively included 147 patients with lymphoma who were candidates for BMT. Clinical and laboratory results were recorded, and after BMT, the occurrence of FN was investigated through the daily evaluation of neutrophil count and body temperature. Results. On average, FN occurred in 91 patients (61.9%) after 12.77 ± 2.45 days after BMT. Lower fluid balance was associated with a higher risk of FN (lowest adjusted odds ratio [OR] at day -2 = 0.602, 95% confidence interval [CI] = 0.299 – 0.870, p-value = 0.007). The higher uric acid level was associated with a higher risk of FN (highest adjusted OR at day -10 = 1.617, 95% CI = 1.328 – 1.963, p-value = 0.035). LDH was also positively correlated with FN (highest adjusted OR at day 0 = 1.501, 95% CI = 1.198 – 2.104, p-value = 0.004). Conclusions. Adequate hydration of the patients is of paramount importance for preventing FN in patients who receive BMT. Furthermore, uric acid and LDH could be considered in future studies for the risk stratification of FN.

The Effects of Premedication with Desipramine on Bone Marrow Mobilization for Autologous Bone Marrow Transplantation in Multiple Myeloma

Background: Multiple myeloma (MM) management includes primary chemotherapy, followed by autologous bone marrow transplantation (ABMT) if the bone marrow gets cleared of cancerous cells. In some cases disease relapse may occur disease relapse may occur if complete clearance is not achieved. Transplantation was primarily performed through the bone marrow; however, peripheral blood has become more favored due to its safety and convenient collection in case of appropriate bone marrow mobilization which is a challenging issue. Objectives: The current study was aimed to investigate the effectiveness of desipramine application for bone marrow mobilization in multiple myeloma (MM) who were candidate for autologous bone marrow transplantation (ABMT). Methods: The current randomized clinical trial involved 122 MM patients who were candidate for ABMT. The participants were divided into two intervention groups: the first group (n = 63) received G-CSF only treatment, while the second group (n = 59) received a similar G-CSF treatment plus desipramine. The first group received 30 microgram intravenous G-CSF for five days and the second one was treated with G-CSF with similar pattern in combination with daily 100 mg desipramine initiated within three days before G-CSF treatment and continued until the last dose of G-CSF. CD34+ cells and complete blood cells and differentiation were assessed by the end of the interventions. Results: The findings of the study show that the number of CD34+ cells, white blood cells (WBC) and platelet (PLT) count were remarkably higher among the patients receiving the combination therapy compared to the G-CSF only treated group (P-value &lt; 0.001) within 5 days after the interventions; however, no significant differences were observed between the two groups when considering the stage of the disease and the frequency of chemotherapy sessions (P-value &gt; 0.05). Conclusions: Desipramine application led to significantly increased levels of CD34+ cells as the representatives of bone marrow mobilization. Besides, the patients treated with this regimen had higher serum levels of WBC and PLT; however, the disease stage and the number of chemotherapy sessions did not affect the response to the treatment.

Multitracer PET/CT with [18F]Fluorodeoxiglucose and [18F]Fluorocholine in the Initial Staging of Multiple Myeloma Patients Applying the IMPeTus Criteria: A Pilot Study.

Initial staging of patients diagnosed with multiple myeloma (MM) can lead to negative results using conventional diagnostic imaging workup, including [18F]Fluorodesoxiglucose ([18F]FDG) PET/CT. The aim of this prospective pilot study was to evaluate the diagnostic efficacy of [18F]Fluorocholine ([18F]FCH) PET/CT in the initial staging of MM patients who were candidates for autologous bone marrow transplant. Materials and Methods: The inclusion criteria of our study were: (a) patients diagnosed with MM; (b) candidates for autologous bone marrow transplant (AT); and (c) studied with [18F]FCH PET/CT and [18F]FDG PET/CT for initial staging less than 4 weeks apart. Imaging analysis included the presence of: bone marrow infiltration, focal bone lesions, and para-medullary or extra-medullary disease, according to the proposed IMPeTus criteria. The analysis was performed per lesion, per patient, and per location. Results: The study population included ten patients. Globally, [18F]FCH PET/CT showed bone marrow uptake in all the patients and visualised 16 more focal lesions than [18F]FDG PET/CT. One patient presented a plasmacytoma, detected by both tracers. Extra-medullary and para-medullary disease was identified with different degrees of uptake by both tracers. In summary, [18F]FCH PET seemed to be superior to [18F]FDG PET/CT in detecting focal bone lesions. SUVmax values were slightly higher in [18F]FCH PET/CT than in [18F]FDG PET/CT. Conclusions: Taking into account the small study population, according to our results, [18F]FCH PET/CT could be a useful tool for staging MM patients.

A case of a Young Multiple Myeloma Patient With Poor Prognostic Cytogenetics

Multiple myeloma is a hematologic malignancy and a subtype of plasma cell dyscrasias, which accounts for 13% of all hematologic malignancies. It mainly affects older adults and is diagnosed in only 2% of the young population under the age of 40 years. This report presents a 33-year-old man diagnosed with Multiple myeloma with 4 poor prognostic specifications consisting of amplification of the 1q21, Translocation of t(4;14), deletion of the 6q21 and 13q14, along with decreased chromosome count to 44, X,-Y. Even though the combination of 4 poor prognostic cytogenetics in young patients is rare, he responded significantly to the Bortezomib regimen. He was selected as a candidate for bone marrow transplantation. The treatments get interrupted 2 days after the first session of the fifth cycle due to an undesirable COVID-19 infection. After 20 days, the symptoms return, and paraclinical findings show signs of MM relapse.

Estimation of glomerular filtration rate in a pediatric population using non-contrast kidney phase contrast magnetic resonance imaging.

Glomerular filtration rate (GFR) is a key measure of kidney function but often inaccurately ascertained by serum creatinine and cystatin C in pediatrics. In this pilot trial, we evaluated the relationship between GFR calculated by using phase-contrast MRI (PC-MRI) biomarkers and GFR by 125I-iothalamate clearance in youth undergoing bone marrow transplantation (BMT). A total of twenty-one pediatric BMT candidates (8-21years of age) were recruited for a research kidney PC-MRI. After completion of 125I-iothalamate clearance, same-day PC-MRI measurements were completed of the kidney circulation without a gadolinium-based contrast agent. MRI included a non-contrast balanced-SSFP-triggered angiography to position ECG-gated breath-held 2D PC-MRI flow measurements (1.2 × 1.2 × 6 mm3). A multivariate model of MRI biomarkers estimating GFR (GFR-MRI) was selected using the elastic net approach. The GFR-MRI variables selected by elastic net included average heart rate during imaging (bpm), peak aorta flow below the kidney artery take-offs (ml/s), average kidney artery blood flow, average peak kidney vein blood flow, and average kidney vein blood flow (ml/s). The GFR-MRI model demonstrated strong agreement with GFR by 125I-iothalamate (R2 = 0.65), which was stronger than what was observed with eGFR by the full age spectrum and Chronic Kidney Disease in Children under 25 (CKiD U25) approaches. In this pilot study, noninvasive GFR-MRI showed strong agreement with gold standard GFR in youth scheduled for BMT. Further work is needed to evaluate whether non-contrast GFR-MRI holds promise to become a superior alternative to eGFR and GFR by clearance techniques. A higher resolution version of the Graphical abstract is available as Supplementary information.

Periodontal condition of candidates for bone marrow, liver and kidney transplantation: a retrospective observational study

OBJECTIVE: Th e aim of this retrospective observational study was to evaluate the periodontal condition of bone marrow, liver and kidney candidates transplantation. METHODS: Th e sample consisted of individuals candidates for bone marrow, liver and kidney transplants, who underwent dental care at the dental assistance program for transplant patients at the university, between 2014 and 2018. Data collection was carried out based on medical records. Periodontal condition was assessed by analyzing the Community Periodontal Index and/or periodontogram in the medical record. Periodontitis was classifi ed according to stage and extension. RESULTS: Medical records of 46 pre-liver transplant patients, 35 pre-bone marrow transplant patients and 18 pre-kidney transplant patients were analyzed, totaling 99 patients. Th e average age of the sample was 46.6 years and 62.6% of the individuals were male. Th e prevalence of periodontitis in the sample was high. Individuals who are candidates for liver transplantation had a higher percentage of sites with bleeding, a higher percentage of sites with deeper pockets and a higher percentage of periodontitis among the groups evaluated. CONCLUSION: Individuals who are candidates for bone marrow, liver and kidney transplants have a high prevalence of periodontal changes and a signifi cant need for dental treatment to reduce the risk of infections.

Marrow aplasia congenital red series: Diamond Blackfan Anemia. About a case

Pure red cell aplasia medullary is a disorder characterized by anemia with almost complete absence of red cell precursors in the bone marrow, with leukocyte count and platelets. The Diamond-Blackfan anemia is a failure syndrome characterized by bone marrow anemia, reticulocytopenia and decreased erythroid precursors in the bone marrow. the case of an infant under 2 months of age presented no family or perinatal history major, whose mother progressive skin pallor evidence mucosa associated with hyporexia; go to health center where they perform paraclinical reporting hemoglobin 1.7 g / dL. peripheral blood smear where erythroid frankly affected with normal megakaryocytic granulocytic count shown is made; It biopsied and bone marrow aspirate concluding marrow red cell aplasia; possible anemia Diamond-Blackfan in light of other clinical findings arises. It stays with glucocorticoid treatment, however insufficient response, begins erythropoietin dose progressively increasing, despite it, warrants blood transfusions on a regular basis; compatibility studies performed with first-degree resulting positive, currently a candidate for allogeneic bone marrow transplantation. It is concluded that despite being a rare syndrome should be suspected in severe anemia where there is acute blood loss, ruling out other etiologies; also timely initiation of treatment is critical to the survival of these patients.

Azacitidine Maintenance Versus No Maintenance after Standard Therapy in Patientswith Acute Myeloid Leukemia, a Mexican Center Experience

INTRODUCTION Achieving complete remission (CR) is an important goal for patients with acute myeloid leukemia (AML)undergoing treatment with the intent to cure. However, even after consolidation and/or hematopoieticcell transplantation (HCT), many patients will experience disease recurrence. Because of this there has long been an interest in the use of maintenance therapies after the intensive treatment phase to prolong the duration of remission and improve survival and the likelihood of cure. Although the concept of maintenance therapy in AML has been present since the 1960s, it is still a matter of controversy.Azacitidine (AZA) is a hypomethylating agent that acts by incorporating itself into DNA, reversiblyinhibiting DNA methyltransferase, thereby blocking its methylation and activating silenced tumor suppressor genes, resulting in an antitumor effect.Maintenance chemotherapy had not been able to demonstrate improvement in survival. However, in the results of the HOVON-97, Huls et al. showed a 12-month progression free survival (PFS) in 64% of older AML patients who received AZA as maintenance therapy for a maximum of 12 cycles, thus opening the door for new research in this field. OBJECTIVE To know if there is an impact of maintenance treatment with 5-Azacitidine on disease-free survival and progression-free survival, in Acute Myeloid Leukemia in complete remission, in patients who are and are not candidates for bone marrow transplant. PATIENTS AND METHODS We conducted a longitudinal, cohort, analytical, descriptive and single-center study, in the time period between January 2016 and December 2019 (designated the AZA group). Data obtained from patients receiving maintenance was compared with a historic patient cohort (designates as the no-AZA group).This study was approved by the ethics committee of CMN 20 de Noviembre. RESULTS A total of 21 patients were analyzed in the AZA group, of which 53% (n = 12) were women and 37% (n =9) were men, the median age was 54 years with a range of 19 to 65. The median of leukocytes,hemoglobin and platelets of the AZA-group at diagnosis was 22.8x109, 9.3 g/dL, and 44,000 mm3, respectively. Thirty percent had an intermediate cytogenetic risk. In the no-AZA group a total of 18 patients were analyzed, of which 73% (n=11) were female and 26% (n=7) were male, the median age was 57 years with a range of 18 to 64. The median of leukocytes, hemoglobin and platelets at diagnosis was 29.5 x109, 9.5 g/dL, and 57,000 mm3, respectively. In the no-AZA group 8% and 22% had intermediate and high cytogenetic risk, respectively. The median follow up in the no-AZA group was 32 months (10-96). The median of cycles of maintenance with AZA was 12 cycles (1-24); the follow up median, in months, was 19 (range 7-59). The response to maintenance therapy was evaluated after the completion of the first 6 treatment cycles, in which 71.4% maintained a negative minimal residual disease (MRD), and 23.8% experienced a relapse. In the no-AZA group the median time to progression was approximately 8 months, with a PFS median of 15 months; time to progression in the AZA group was approximately 15 months. At the closing of this study the AZA group has not reached the median for PFS (p=0.011) (Figure 1); 42.8% are still in maintenance therapy and in remission, 19% received a bone marrow transplant and are still in remission, 14.4% experienced relapse, 4.8% are in elective suspension of treatment and continue in remission, 9.5% are in observation and palliative care respectively CONCLUSIONS Azacitidine used as maintenance treatment in Acute Myeloid Leukemia can extend progression free survival. Disclosures De La Peña: Janssen:Speakers Bureau;Novartis:Speakers Bureau;Amgen:Speakers Bureau.Alvarez:Amgen:Speakers Bureau;Roche:Speakers Bureau;Celgene:Speakers Bureau;Novartis:Speakers Bureau;Janssen:Speakers Bureau.Perez:Novartis:Speakers Bureau;Roche:Speakers Bureau;Celgene:Speakers Bureau.Alvarado:Novartis:Speakers Bureau;Amgen:Speakers Bureau;Celgene:Speakers Bureau;Alexion:Speakers Bureau;Roche:Speakers Bureau. OffLabel Disclosure: azacitidine as maintenance for AML it is not approved yet in Mexico

Nosso Desafio no Coração do Brasil

Faced with the major health crisis of the century – Coronavirus Disease (COVID19) Pandemic, we could see two waves installing in society: incredulity and fear. This issue was politicized several times and the vast amount of scientific publications made the discussion very controversial and consequently society became more and more confused and insecure.&#x0D; Brasilia - the Capital of Brazil, is the heart of the country, it is centrally located and therefore politically strategic. It was one of the first places in Brazil to spread, under public decree, radical measures of social isolation (such as closing schools, colleges, commerce, and other public places) in mid March / 2020. Only the so-called “essential activities” continued working. When such measures were adopted, the city had just over 50 confirmed cases of COVID19.&#x0D; Concerns about the pandemic moved the entire local health care assistance, with homeric financial investments by hospitals with massive testing for Coronavirus and a reduction in the number of elective surgeries (important profit providers).&#x0D; The Bone Marrow Transplant (BMT) Unit, traditionally considered to be a very vulnerable space, gained special focus and numerous efforts were designed to make it virtually a COVID19 free area. The view of doctors during this period was also very heterogeneous, and it varied between fearlessness and major worry. Finding a balance and offering a safe environment for carrying out the procedures proved to be a great challenge, whose building still occurs daily until today.&#x0D; Despite being a hard social, political and economic moment, it would not be appropriate to shoot all over the place like a war. The elaboration of new protocols, periodically reviewed and modified, was carried out based on intense involvement and collaborative works by the Hospital Coordination, the Infectious Diseases Specialists, doctors and multidisciplinary team. The Good Practices policies published periodically by the Medical Societies of Infectious Diseases and Bone Marrow Transplant guided our local protocols.&#x0D; Among the main measures adopted are the testing of patients and caregivers with PCR lab test to check the coronavirus infection before hospitalization, the prohibition of visitors and the use of reverse vestments (use of cloaks, gloves, caps and masks), which although controversial, was used to potentially reduce the risk of coronavirus transmission by asymptomatic health professionals. In addition, daily screening of respiratory symptoms was applied to all caregivers and employees of the unit, in order to identify suspected cases and keep them away before contact with patients. Such measures were crucial to the excellent results achieved and to strengthen the medical teams trust in the hospital logistic and support.&#x0D; According to data published by the Brazilian Organ Transplant Association - ABTO, in the first half of 2020, 31 transplants were performed in two institutions that predominantly receive public institutions patients (3 allogeneic and 28 autologous) and 23 transplants in the private services (18 autologous and 5 allogeneic) - represented by two private hospitals in Brasília1. The peak of the pandemic occurred in July and August 2020, with periods of significant overload in the hospital structure in the public and private sectors. The depletion of resources caused by the pandemic associated with previous institutional issues have compromised the care of adult patients who are candidates for BMT from public services. This fact generated an important patient demand for centers in other regions of the country associated with an increase in the obstacles of moving and welcoming these patients in the pandemic scenario.&#x0D; In private practice, there was a strong and well-structured work-ethic, which allowed the program to continue without impairing the quality of care or the expected outcomes. To date, we have had no cases of death by COVID19 in the scenario of bone marrow transplantation in Brasília, reflecting the efforts and protocols previously mentioned.&#x0D; At this moment, we are experiencing a significant reduction in the number of COVID19 cases in Brasilia, making it possible to observe an increase in the number of patients undergoing transplant procedures. This fact reflects the postponement of treatment of non-urgent cases in the previous three months.&#x0D; After six months of Pandemic, it is essential to recognize the strong presence of the spirit of cooperation, tolerance and patience that has been installed in all the scenarios that permeate the BMT, associated with the relevant growth of all involved. The “new normal” is uncomfortable because it is characterized by restrictions imposed by the pandemic and not by our choices and preferences, but above all it symbolizes our ability to adapt and to have resilience. We are important characters in this memorable historical period, and we carry the desire to continue pulsating in the heart of Brazil.

Existe beneficio en la adición de Trasplante de Progenitores Hematopoyéticos a pacientes con Mieloma Múltiple que reciben Lenalidomida en la fase de mantenimiento?

Introducción: La controversia en el beneficio de la adición de trasplante de progenitores hematopoyéticos a pacientes que reciben Lenalidomida en la fase de mantenimiento de pacientes con Mieloma Múltiple está en pleno debate en la comunidad científica por lo que el objetivo del presente estudio fue medir la supervivencia en un grupo de pacientes en estas condiciones.&#x0D; Métodos: El estudio tipo observacional analítico realizado con pacientes oncológicos ingresados en el Hospital SOLCA durante el periodo de enero del 2014- mayo del 2018. Con una muestra no probabilística se seleccionaron pacientes con Mieloma Múltiple, mayores de 18 años en cuyo tratamiento se incluye Lenalidomida. Grupo 1 (G1): pacientes con trasplante de médula ósea, Grupo 2: pacientes no candidatos a trasplante de médula ósea. Las variables demográficas, clínicas descriptivas (ISS, ECOG), supervivencia como variable principal y efectos secundarios. se realizó el análisis de sobrevida de Kaplan-Meyer.&#x0D; Resultados: Se incluyeron 23 casos en G1y 26 casos en G2. La edad en G1 53 años (Rango 38-70), en G2: 65 años (Rango 46-85) P=0.13. En G1 fueron 12/23 (52%) hombres, en G2 fueron 15/26 (57%) P=0.93. ISS grado II 11/23(48%) en G1 y 10/26(38%) en G2 P=0.51. ECOG 2 en G1: 12/23(52%) y en G2 16/26 (32%) en G2 P=0.51. La supervivencia Libre de progresión en el Grupo 1-TPH a los 24 meses de seguimiento fue del 98%, en el Grupo 2 no Candidato a TPH a los 24 meses de seguimiento fue de 82%, Logrank test P=0.023. X2=5.192. La supervivencia global en el Grupo 1-TPH a los 24 meses de seguimiento fue del 100%, en el Grupo 2 no Candidato a TPH a los 24 meses de seguimiento fue de 90%, Logrank test P=0.17. X2=1.846.&#x0D; Conclusión: En el presente estudio se demostró que la sobrevida libre de progresión es mayor en el grupo de pacientes con Mieloma Múltiple sometidos a Trasplante de Progenitores Hematopoyéticos versus el grupo de pacientes con Mieloma Múltiple que no son candidatos a Trasplante. La sobrevida global es igual en ambos grupos.

Mesenchymal stem cell and hematopoietic stem cell transplantation for vasculitis

Vasculitis poses a great therapeutic challenge to the treating physician. Steroids remain the mainstay of the treatment and biologics are emerging as popular agents. Similar to other immune-mediated diseases, refractory vasculitis seems to be a suitable candidate for bone marrow and mesenchymal stem cell transplantation. Preliminary data show stem cell-based therapies are feasible and effective in severe, treatment-resistant forms of several types of vasculitis. However, due to the fact that patients are rare, clinical data are sparse. Further prospective studies are needed to confirm these preliminary results. In addition, mostly partial remissions are achieved after stem cell transplantation; thus optimization of the therapeutical regimens is necessary through international cooperation.

Subtypes of Blastocystis sp. isolated in fecal samples from transplant candidates in São Paulo, Brazil

Blastocystis sp. is an intestinal protozoan commonly found in fecal samples of many animal species, including humans, but poorly studied in transplant candidates. The aim of this study was to evaluate the occurrence and molecular identification of Blastocystis sp. in fecal samples from transplant candidates. A polymerase chain reaction was performed using specific primers for Blastocystis ribosomal DNA. The DNA sequences obtained were aligned and compared with other sequences from the GenBank and MLST databases. The analyzed samples showed a positivity of 16% (24 of 150) for Blastocystis sp. The highest occurrence was observed in renal transplant candidates (31.4%), followed by hepatic transplant candidates (10.4%) and candidates for bone marrow transplantation (5.9%). Subtype (ST) 3 (45.8%) was the most prevalent among the isolates, followed by ST1 (37.5%), ST2 (12.5%), and ST7 (4.2%). This is the first study of molecular identification Blastocystis sp. in transplant candidates. Our results confirmed that ST3 was the most common subtype in transplant candidates and reinforce the importance of new studies to investigate of Blastocystis sp. in these patients.

HLA analysis of Mexican candidates for bone marrow transplantation and probability of finding compatible related donors

IntroductionOncohematological disorders are the main cause of morbidity in the Mexican population from 1 to 19 years old, where megakaryoblastic and promyelocitic leukemias are more frequent. Considering that the success of a transplant is multifactorial, the criterion of compatibility in the HLA system is crucial and even more so when the source of HSC is bone marrow. ObjectiveTo determine the frequency of the HLA genotype in Mexican candidates who require a bone marrow transplant from related donors and the probability to find donors. Materials and methodsOne hundred twenty-six candidates for bone marrow transplant and related donors were tested for HLA class I (–A*, −B* alleles) and class II (–DRB1* allele) in intermediate–resolution, as the first phase in the choice of the possible donor. The criteria to identify donors were determined by antigen–matched in each HLA haplotype as follows: 4/6, 5/6 and 6/6 at the HLA–A*, HLA–B*, and HLA–DRB1* alleles. ResultsOf all the candidates analyzed, 57.93%, at least one bone marrow donor was identified; in 53 cases, no donor was found. The average size of the families was 4.79 ± 1.06 members. A higher percentage of compatibility with grade 6/6 (31.6%) was identified with brothers, followed by sisters in 25.3%. The probability to find at least one compatible potential donor was 1.51 ± 0.92 donors. ConclusionIn the first phase to select donors, Mexican patients studied in this work, have a compatible donor, however the grade of resolution test influenced in the probability identified.

The changing landscape of gene editing in hematopoietic stem cells: a step towards Cas9 clinical translation.

Since the discovery two decades ago that programmable endonucleases can be engineered to modify human cells at single nucleotide resolution, the concept of genome editing was born. Now these technologies are being applied to therapeutically relevant cell types, including hematopoietic stem cells (HSC), which possess the power to repopulate an entire blood and immune system. The purpose of this review is to discuss the changing landscape of genome editing in hematopoietic stem cells (GE-HSC) from the discovery stage to the preclinical stage, with the imminent goal of clinical translation for the treatment of serious genetic diseases of the blood and immune system. With the discovery that the RNA-programmable (sgRNA) clustered regularly interspace short palindromic repeats (CRISPR)-Cas9 nuclease (Cas9/sgRNA) systems can be easily used to precisely modify the human genome in 2012, a genome-editing revolution of hematopoietic stem cells (HSC) has bloomed. We have observed that over the last 2 years, academic institutions and small biotech companies are developing HSC-based Cas9/sgRNA genome-editing curative strategies to treat monogenic disorders, including β-hemoglobinopathies and primary immunodeficiencies. We will focus on recent publications (within the past 2 years) that employ different genome-editing strategies to 'hijack' the cell's endogenous double-strand repair pathways to confer a disease-specific therapeutic advantage. The number of genome-editing strategies in HSCs that could offer therapeutic potential for diseases of the blood and immune system have dramatically risen over the past 2 years. The HSC-based genome-editing field is primed to enter clinical trials in the subsequent years. We will summarize the major advancements for the development of novel autologous GE-HSC cell and gene therapy strategies for hematopoietic diseases that are candidates for curative allogeneic bone marrow transplantation.

EXPERIENCE WITH IBRUTINIB IN PATIENTS WITH REFRACTORY AND RECURRENT B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA

Purpose of the study . To obtain experience with ibrutinib in patients with chronic lymphocytic leukemia (CLL) in everyday clinical practice. Material and methods. 20 patients with refractory or relapsed CLL were included in the study during the period from October 2015 to January 2016. Immunophenotyping, cytogenetic and molecular tests of peripheral blood samples were performed for all patients. Patients took ibrutinib at dose of 420 mg once daily for a year or until progression. The effectiveness of treatment was assessed by overall response rate, complete response and overall survival. Results. The overall response rate was 100%. The overall survival rate at 14 months was 80%. The complete response rate at 14 months after initiation of therapy was 60%. The primary effect was observed in lymph nodes, while changes in the hemogram occurred later. The medicine was well tolerated. Patients who stopped ibrutinib therapy therapy due to complications, restarted treatment at full dose after resolving. Conclusion . Ibrutinib is a highly effective medicine for patients with refractory or relapsed CLL, including those from the highrisk group, but it is not a «salvage therapy» and is not effective at terminal states. Ibrutinib can be considered as a «bridge» for young patients who are candidates for allogeneic bone marrow transplantation.

Qualitative polymerase chain reaction versus quantitative polymerase chain reaction for the detection of minimal residual disease in children with acute lymphoblastic leukemia.

In acute lymphoblastic leukemia (ALL), remission is classically defined as the reestablishment of normal hematopoiesis and the presence of less than 5% of the nucleated blast cell population found by conventional microscopy; this is used in older protocols to assess treatment response. Morphological analysis, although useful and applicable at any center, has proven to be of limited sensitivity, subjective and imprecise to study early response to treatment and this technique does not appear to be sufficient to identify patients at true risk of relapse who might benefit from the intensification of treatment.1,2 For this reason, cytomorphological analysis has been replaced by minimal residual disease (MRD) monitoring in several treatment protocols and new definitions of remission and relapse in childhood ALL have been proposed.3 The analysis of MRD has proved to be the strongest independent prognostic factor in all studies analyzing large series of patients with B-lineage and T-cell ALL, and specific molecular subgroups such as patients with the BCR-ABL fusion gene and ALL patients with MLL gene rearrangements. This analysis allows more accurate risk group assignment and tailoring the intensity of treatment, permitting reduction or intensification at the different treatment time points according to the MRD level.4–9 MRD monitoring can also guide treatment decisions in relapsed patients and those who are candidates for bone marrow transplantation.4,5,10,11

Immunofluorescence assay for diagnosis of strongyloidiasis in immunocompromised patients

Background: Strongyloides stercoralis is a parasite that causes human strongyloidiasis. The disease ranges from asymptomatic to severe forms, which are often fatal in immunocompromised individuals. Laboratory diagnosis is challenging owing to limitations in the use of conventional parasitological techniques. The present study aimed to evaluate the indirect immunofluorescence assay (IFA) using infective larvae of S. venezuelensis as an antigen for the immunodiagnosis of human strongyloidiasis in immunocompromised patients. Methods: Serum and stool samples from 200 immunocompromised patients (HIV-positive, HTLV-1-positive, and renal, liver, and/or bone marrow transplantation candidates) were used. Stool samples were examined using three parasitological methods: Lutz, Rugai, and culture agar plate. IFA was performed using sections of infective larvae of S. venezuelensis as antigens, and showed 95.4% sensitivity and 95.8% and specificity. Results: Among the 200 patients, 17 (8.5%) were positive for S. stercoralis by at least one parasitological method, and 43 (21.5%) were positive by IFA. Conclusions: IFA can be used as a screening method for the detection of S. stercoralis in immunocompromised patients.

DI-066 Analysis of the profile of candidates for bone marrow transplant and respective conditioning chemotherapy

BackgroundBone marrow transplant (BMT) involves intravenous transference of haematopoietic stem cells (HSC) from a donor to a recipient after the administration of chemotherapy, possibly in association with radiotherapy. The HSC...

Ventilation Heterogeneity Of Peripheral Airways (Sacin*VT) Assessed By Nitrogen Multiple Breath Washout (N2-MBW) Is An Accurate and Sensitive Marker Of Bronchiolitis Obliterans Following Haematopoietic Stem Cell Transplantation Recipients

Bronchiolitis Obliterans (BO) initially affects terminal and respiratory bronchioles, a region of the lung largely unexplored by spirometry, which is only altered in advanced disease. In contrast, the Impulse Oscillation System (IOS) and the nitrogen multiple breath washout (N2-MBW) are techniques characterized by a high sensitivity to peripheral airway changes and potentially more suited to early detection of small airways disease. In a cross sectional study, a total of 161 patients, divided into 4 groups: healthy controls (n=41), bone marrow transplant candidates (n=47), haematopoietic stem cell transplantation (HSCT) recipients (n=65) and patients with chronic obstructive pulmonary disease (COPD; n=8), were assessed by IOS, N2-MBW, spirometry, body plethysmography and diffusing capacity for carbon monoxide (DLCO) in order to describe respiratory function changes in post-transplant patients without pulmonary graft versus host disease (GVHD) and in order to characterize the pattern of peripheral airway changes in BO. All subjects were able to perform IOS and N2-MBW without difficulty. Significant variables are illustrated in the table.ControlNo BOSpBOSpMSDMSDMSDRV/TLC %9714109240.04414422&lt;0.001DLCO %96880160.0024911&lt;0.001Scond* VT [l]0.020.010.030.02&lt;0.0010.020.01&lt;0.001Sacin* VT [l]0.050.020.130.09&lt;0.0010.370.20&lt;0.001Z5Hz [cmH2O/(l/s)]3.070.673.491.29NS4.932.460.017DR5-20Hz [cmH2O/(l/s)]0.300.230.560.68NS1.250.960.016X5Hz [cmH2O/(l/s)]-0.950.21-1.130.77NS-2.271.980.002fR [1/s)]10.632.5413.194.86NS20.346.39&lt;0.001Rperipheral [cmH2O/(l/s)]1.770.802.091.46NS3.703.060.026 Stem cell transplantation, even without respiratory complications, does not affect spirometry but appears to cause an increase in air trapping, a reduction in DLCO and enhanced ventilation inhomogeneity both in conductive (Scond*VT) and acinar (Sacin*VT) airways. Patients with BO (n=8) were characterized by further DLCO reduction, increase in oscillometric indices sensible to peripheral airways involvement (Z5Hz, DR5-20Hz, X5Hz, Resonant frequency and Rperipheral) and a further three-fold increase in Sacin* VT. Compared to patients with BO, COPD patients with the same degree of spirometric obstruction (FEV1/FVC&lt; 0.7, FEV1 50% predicted) showed only half the increase in predicted Sacin*VT (p= 0.03). At a cut off of 321% of predicted value, Sacin* VT could distinguish the subjects with BO from recipients, with good accuracy (87%), sensibility (87.5%) and specificity (89.5%). We conclude that IOS and N2-MBW are simple tests able to detect changes following HSCT as well as those specific to Bronchiolitis Obliterans. Disclosures: No relevant conflicts of interest to declare.