Rosario Salazar-Riojas

Intracoronary infusion of CD133+ endothelial progenitor cells improves heart function and quality of life in patients with chronic post-infarct heart insufficiency

AIM To assess the safety and efficacy of the intracoronary infusion of CD133+ hematopoietic stem cells to improve ventricular function and quality of life in candidates for heart transplantation due to post-infarct chronic heart failure. METHODS We selected seven candidates for heart transplantation (six males/one female, age range 44-65 years) in whom all treatment alternatives were exhausted (angioplasty/stent and bypass surgery). These subjects had a symptomatic New York Heart Association (NYHA) scale of at least II and ejection fractions (EFs) below 35%. After obtaining informed consent, CD133+ cells were obtained by stimulation with granulocyte-colony stimulating factor, apheresis, and separation with magnetic beads. Stem cells were implanted in the infarcted zone via intracoronary percutaneous angiography. Evaluations (NYHA scale classification, plasma concentration of pro-B-natriuretic-peptide and the risk of sudden death, echocardiography, cardiac magnetic resonance, and gated-SPECT with MIBI) were performed at baseline and at 3, 6, 12, and 24 months after cell infusion. RESULTS Stem cell isolation was efficient and safe (around 10(7) cells/patient and >92% CD133+ viable cells). Two patients died during observation due to noncardiac conditions. In the five remaining subjects, the NYHA scale improved and no accounts of hospital admissions for heart failure were documented. Plasma concentrations of pro-B-natriuretic peptide and the risk of sudden death clearly decreased, while the EF increased significantly to 35% and 40% by echocardiography and cardiac MRI, respectively (P=.013 and .009, respectively) 24 months after treatment. No other major adverse events were noticed. CONCLUSIONS The intracoronary inoculation of CD133+ stem cells was safe and effective to improve ventricular contraction and symptomatic class function in patients with refractory post-infarct heart failure.

Circulating microRNA expression profile in B-cell acute lymphoblastic leukemia

BACKGROUND Acute lymphoblastic leukemia (ALL) is a highly diverse disease characterized by cytogenetic and molecular abnormalities, including altered microRNA (miRNA) expression signatures. AIM We perform and validate a plasma miRNA expression profiling to identify potential miRNA involved in leukemogenesis METHODS MiRNA expression profiling assay was realized in 39 B-ALL and 7 normal control plasma samples using TaqMan Low Density Array (TLDA) plates on Applied Biosystems 7900 HT Fast Real-Time PCR System. MiRNA validation was done for six miRNA differentially expressed by quantitative real-time PCR. RESULTS Seventy-seven circulating miRNA differentially expressed: hsa-miR-511, -222, and -34a were overexpressed, whereas hsa-miR-199a-3p, -223, -221, and -26a were underexpressed (p values < 0.005 for both sets). According to operating characteristic curve analysis, hsa-miR-511 was the most valuable biomarker for distinguishing B-ALL from normal controls, with an area under curve value of 1 and 100% for sensitivity, and specificity respectively. CONCLUSIONS Measuring circulating levels of specific miRNA implicated in regulation of cell differentiation and/or cell proliferation such as hsa-miRNA-511, offers high sensitivity and specificity in B-ALL detection and may be potentially useful for detection of disease progression, as indicator of therapeutic response, and in the assessment of biological and/or therapeutic targets for patients with B-ALL.

Higher doses of CD34+ progenitors are associated with improved overall survival without increasing GVHD in reduced intensity conditioning allogeneic transplant recipients with clinically advanced disease

The influence of CD34+ cell dose on the outcome of allogeneic peripheral blood stem cell (PBSC) transplantation after reduced intensity conditioning (RIC) remains controversial. The impact of the number of CD34+ hematoprogenitors infused on transplant outcome and on the incidence of graft versus host disease (GVHD) was analyzed.

Non-myeloablative hematopoietic stem cell transplantation is of limited value in advanced or refractory acute myeloblastic leukemia. The Mexican experience †

Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective strategy for preventing relapse of acute myelogenous leukemia (AML). We analyzed the outcome of 31 primary AML patients who received a reduced-intensity conditioning regimen for allogeneic HSCT in first or second remission. Thirty-one AML patients, 20 in first complete remission (FCR), 8 in second complete remission (SCR) and 3 in a partial remission (SPR) were included. All received busulfan 4 mg/kg/d/2 days, fludarabine 30 mg/m2/d/3 days and cyclophosphamide 350 mg/m2/d/3 days as conditioning regimen. The median number of CD34+ cells infused was 5.6 × 106/kg and 5.2 × 106 in FCR and SCR group, respectively. All patients received cyclosporine-A (CsA) and methotrexate as graft vs. host disease (GvHD) prophylaxis. All patients showed myeloid engraftment (neutrophils >0.5 × 109/l) after a median of 13 days in FCR group and 15 days in SCR group. Platelet recovery >20 × 109/l was achieved after a median of 13 days in both groups. Relapse for 20 patients in FCR was 35% compared to 91% for 11 in SCR/SPR (p < 0.05). Conclusions. Reduced-intensity conditioning followed by allogeneic HSCT can induce stable remission in primary AML patients transplanted in FCR. A high relapse rate was documented in patients with refractory or relapsed AML.

Effective collection of peripheral blood stem cells in children weighing 20 kilogram or less in a single large-volume apheresis procedure

Introduction: Peripheral blood stem cell (PBSC) transplantation has become a routine procedure in pediatric oncology. A special group of PBSC donors are children weighing 20 kg or less. Limited vascular access and low blood volume puts them at a higher risk. Central line placement and a priming apheresis machine are recommended to avoid these complications. Patients and Methods: PBSC collections performed from July 2006 to May 2013 in children weighing less than 20 kg were included. All donors had a central venous catheter (CVC). An apheresis machine was primed with packet red blood cells. Results: Twenty‐seven PBSC collections were performed in 22 children weighing 20 kg or less, 14 for allogeneic and 8 for autologous transplantation, in order to collect at least 2 × 106 CD34+ cells/kg. In the allogeneic group, median age and weight were 3 years (0.8–7) and 15.5 kg (8–20). In the autologous group, median age and weight were 3 years (2–7) and 15.35 kg (12.5–19.5). A single large‐volume apheresis was sufficient to obtain the CD34+ cells needed in 78.5% and 75% of the allogeneic and autologous groups, respectively, with a median 11.84 × 106 and 5.79 × 106 CD34+ cells collected per kilogram of weight of the recipient. No serious complications related to the apheresis procedure or CVC placement occurred. Conclusion: PBSC collection in a single large‐volume apheresis for allogeneic and autologous transplants in children weighing 20 kg or less is a safe and effective procedure when based on standardized protocols. J. Clin. Apheresis 30:281–287, 2015.

Assessment of immune reconstitution status in recipients of a successful hematopoietic stem cell transplant from peripheral blood after reduced intensity conditioning.

OBJECTIVE To document immune reconstitution status after hematopoietic stem cell transplantation (HSCT) for malignant hematologic diseases. METHODS Hematology patients who received a reduced intensity conditioning (RIC) were followed after successful allogeneic or autologous HSCT. Patients had at least 100days post-transplant. T, B and NK cells in peripheral blood (PB), and CD34+, CD133+ progenitor cells in bone marrow (BM) and peripheral blood (PB) were determined by flow cytometry. RESULTS Twenty-seven HSCT recipients, 19 allogeneic and 8 autologous, were studied at a median 155 (100-721) days post-transplant. In the whole group the median value of CD34+ cells was 1.03% in the bone marrow and 0.04% in PB, whereas values for CD133+ cells were 0.39% and 0.13%, respectively, without statistical differences between autologous and allogeneic recipients. Significantly more B cells (CD3-/CD56-/CD19+) were found in the autologous compared to the allogeneic group, 12.6 vs. 5.01, p=0.04. An increased number of CD8+ lymphocytes with a 0.63 CD4:CD8 relationship was documented in PB. CONCLUSION In clinically recovered autologous and allogeneic HSCT recipients BM and PB CD34+/CD133+ hematoprogenitor homeostasis is maintained within normal ranges, with better B-cell reconstitution in the autologous group.

Identification of Differentially Expressed Genes Associated with Prognosis of B Acute Lymphoblastic Leukemia

Background. Acute lymphoblastic leukemia type B (B-ALL) is a neoplastic disorder with high mortality rates. The aim of this study was to validate the expression profile of 45 genes associated with signaling pathways involved in leukemia and to evaluate their association with the prognosis of B-ALL. Methods. 219 samples of peripheral blood mononuclear cells obtained from 73 B-ALL patients were studied at diagnosis, four, and eight weeks after starting treatment. Gene expression was analyzed by quantitative real-time polymerase chain reaction. Results. Normalized delta Cq values of 23 genes showed differences between B-ALL and controls at diagnosis time (P values < 0.05). There were significant associations between B-ALL patients relapse/death and the expression levels of IL2RA, SORT1, DEFA1, and FLT3 genes at least in one of the times evaluated (P values < 0.05 and odds ratio ranges: 3.73–27). The association between FLT3 deregulation and relapse/death was a constant in the times studied and their overexpression significantly increased the odds of relapse/death in a range of 3.73 and 6.05 among study population (P values < 0.05). Conclusions. Overexpression of FLT3 and DEFA1 genes retained independent prognostic significance for B-ALL outcome, reflected as increased risks of relapse/death among the study population.

Lower than expected cytogenetic and molecular response to imatinib in Mexican patients with chronic myelogenous leukemia.

Abstract Imatinib has been considered as the gold standard for drug therapy of chronic myelogenous leukemia (CML) because it offers higher cytogenetic response and better quality of life than traditional drugs. In this study we applied the standard 400 mg dose of imatinib in 37 CML Ph (+) Mexican patients, monitoring their cytogenetic response using fluorescent in situ hybridization and carrying out molecular analyses using reverse transcription polymerase chain reaction. The study included 19 male and 18 female patients with a median age of 41 years. The median follow-up time from diagnosis was 56 months. Thirty-six patients (97%) achieved complete hematologic response in a median time of 29 days. Complete cytogenetic response and complete molecular remission was observed in only five (13%) and three (8.1%) patients, respectively, less than the expected rate (50–90%) reported in other studies.

Moderate hyperprolactinemia is associated with survival in patients with acute graft-versus-host disease after allogeneic stem cell transplantation

Abstract Fasting serum prolactin (PRL) levels in response to metoclopramide (MCP) and lymphocyte cytokine profiles was studied in patients given allografts and their donors. Thirty normoprolactinemic volunteers (12–59 years) were studied: group 1, 10 healthy men; group 2, 8 males and 2 females with various hematologic diseases; and group 3, 3 males and 7 females HLA-identical sibling donors: PRL and cytokines were measured. Four surviving recipients developed acute graft-versus-host disease (GVHD) (+), and six did not. Before transplant Fasting PRL concentrations were higher in ‘future’ GVHD(+) recipients than in their donors (P < 0.001). The opposite was seen in response to MCP (P = 0.01). Donors had a predominant T-helper type 1 (Th1) cytokine profile compared with recipients (P ≤ 0.02), and GVHD(+) recipients had a greater tumor necrosis factor (TNF) value than GVHD(−) (P = 0.05). After transplant On days +30 and +100, a mild sustained rise in fasting PRL levels occurred only in GVHD(+) recipients (P ≤ 0.05) simultaneously with a transient rise in Th1 cytokines. GVHD(−) recipients had no changes. Donors with a Th1 cytokine profile might be more prone to induce GVHD in their recipients, and a mild sustained rise in PRL concentrations after transplantation in recipients GVHD(+) might participate in the amelioration of the severity of GVHD.

Comparative analysis of iron status and other hematological parameters in preeclampsia

ABSTRACT Objective: To compare serum ferritin (SF) concentrations and other hematological parameters between patients with preeclampsia (PE) and normal pregnant women of the same gestational period who received supplemental iron during pregnancy. Methods: Prospective, comparative, observational pilot study that included 31 women with PE and 30 healthy pregnant women, at 20 weeks’ of gestation. Ferritin, iron and complete blood cell count were compared between groups. Results: In comparison with controls, preeclamptic patients had a higher weight, body mass index, and arterial pressure. Serum ferritin and serum iron were higher in patients with PE (median: 36.5 μg/l vs. 20.9 μg/l and 103.9 μg/dl vs. 90.8 μg/dl) with a significant difference (P = 0.019 and P = 0.345). SF values >40 μg/l correlated with PE (r = 0.281; P = 0.032). A platelet count less than 100 × 109/l was higher in the PE group than in the control group (13% vs. 3%, P = 0.354). Conclusion: Higher SF levels, despite being within normal range, were associated with PE. The incidence of thrombocytopenia was higher in preeclamptic women, however, the remaining hematological parameters were similar in both groups.