Anti-Hla Donor-Specific Antibodies Are Associated to Infection and Not to the Engraftment Rate in Outpatient Haploidentical Hematopoietic Cell Transplantation.

Background: Recipients of a related haploidentical stem cell transplant (haplo-SCT) can have preformed antibodies to HLA donor's antigens. Objective: The aim of the study was to evaluate the engraftment rate and major clinical associations of anti-HLA donor-specific antibodies (DSA) at two mean fluorescence intensity (MFI) thresholds in recipients of an outpatient haplo-SCT. Methods: Seventy haplo-HCT recipients were analyzed. A virtual crossmatch was performed using the donor HLA typing and the recipient's anti-HLA DSA test results. Data for anti-HLA-A, -B, -C, and -DR were analyzed. Recipients with DSA ≥ 500 MFI were considered positive, and those with < 500 were considered negative; the same was adopted for MFI ≥ 1000. Results: Post-transplant infection was higher in recipients with DSA ≥ 500 MFI (84.6%, p = 0.041). First-year mortality was higher in DSA-positive patients ≥ 500 MFI, p = 0.004, and DSA ≥ 1000 MFI, p = 0.022, than in DSA-negative recipients. Graft failure in the first 100 days was not associated with DSA ≥ 500 or ≥ 1000 MFI. There was no difference in acute (a-GVHD) or chronic (c-GVHD) graft versus host disease between DSA-positive and negative patients. Conclusions: There was no association of anti-HLA DSA at MFI ≥ 500 and ≥ 1000 with graft failure, however, increased infection and 1st-year mortality were documented in related haplo-HCT at the MFI cutoffs studied.

Assessing the Efficacy of Mitoxantrone and Doxorubicin as Frontline Anthracyclines During Induction Therapy of Newly Diagnosed Acute Promyelocytic Leukemia.

BACKGROUND: Therapeutic advances in acute promyelocytic leukemia (APL) have transformed it into today's most curable form of leukemia. However, recommended agents, including arsenic trioxide, idarubicin, or daunorubicin, are not easily available in low-middle-income countries, where outcomes remain suboptimal. We aimed to assess the efficacy and safety of more accessible anthracyclines. METHODS: We conducted a retrospective cohort study including sixty-one patients diagnosed with APL over a 15-year period. Patients received low-dose all-trans retinoic acid (ATRA, 25 mg/m2) with mitoxantrone or doxorubicin as an induction to remission therapy. Groups were compared using the χ2 and Student's t-tests. Kaplan-Meier analysis was used for survival analyses. RESULTS: Thirty (49.18%) patients received mitoxantrone, and 31 (50.82%) received doxorubicin. The median follow-up was 24.6 months (1-146). Twenty-eight (93.3%) patients achieved complete remission (CR) in the mitoxantrone group and 28 (87.1%) in the doxorubicin group (p=0.103), and the median time to CR was 40 and 31 days, respectively. Mitoxantrone had a 6.7% early mortality rate and a 16.7% relapse rate compared with doxorubicin (3.2% and 32.3%, respectively). No differences were found in survival (p = 0.795), hospitalization days (p = 0.261), or adverse events (p = 0.554). CONCLUSIONS: Using mitoxantrone or doxorubicin as induction therapy in newly diagnosed APL is a safe and adequate alternative with comparable outcomes to first-line agents in scenarios where the latter might not be readily available, such as in low-middle-income countries.

Alternatives for managing patients with newly diagnosed immune thrombocytopenia: a narrative review.

INTRODUCTION: Primary immune thrombocytopenia (ITP) is an acquired bleeding disorder. Conventionally, first-line ITP therapy aims to obtain a rapid response and stop or decrease the risk of bleeding by increasing the platelet count. At this point, the duration of the response, the tolerability, and the long-term safety of pharmacologic interventions are considered less of a priority. Combination treatments that simultaneously address multiple disease mechanisms are an attractive strategy to increase efficacy in acute ITP therapy. In this review, we discuss the treatment of newly diagnosed ITP patients, emphasizing the use of new combinations to benefit from their synergy. AREAS COVERED: This article summarizes conventional treatment, recent and novel combinations, and COVID-19 management recommendations of newly diagnosed ITP patients. EXPERT OPINION: The key areas for improvement consider the long-term effects of conventional first-line therapy, reducing relapse rates, and extending responses to achieve long-term remission. Although corticosteroids remain a first-line therapy, restricting their use to avoid toxicity and the increasing use of rituximab and TPO-RAs in the first three months after diagnosis open the landscape for future interventions in frontline therapy for ITP. First-line therapy intensification or synergistic drug combination offers a potential and realistic shift in future treatment guidelines.

A Method for the Elution of Anti-CD20 With an EDTA/Glycine Acid Solution for Accurate Immunophenotyping of B Lymphocytes Sensitized With Rituximab.

OBJECTIVES: To assess the efficacy of a method to circumvent CD20-positive antigen masking by rituximab for flow cytometry analysis of B-cell malignancies in hematology patients. METHODS: Mononuclear cells (MNCs) from 10 healthy individuals and 5 untreated patients with B-cell malignancies were sensitized with rituximab. Patients' diagnoses included chronic lymphocytic leukemia, hairy cell leukemia, and follicular lymphoma. MNCs were isolated by gradient density centrifugation. An EDTA/glycine acid (EGA) elution method was used to dissociate CD20-rituximab complexes; afterwards, CD20-positive immunoreactivity was assessed by flow cytometry. A saturation curve was built based on serial dilutions of rituximab. Median fluorescent intensities of CD20-positive signals were obtained before sensitization with rituximab and after its elution with EGA. RESULTS: CD20-positive signals were not detectable by flow cytometry after rituximab sensitization of B cells. CD20-sensitized vs CD20-unsensitized, CD20-sensitized vs CD20-eluted, and CD20-eluted vs CD20-negative control (NC) MNC populations exhibited statistical differences (P = .001), while CD20-sensitized vs CD20-NC populations did not (P = .499), confirming CD20 antigen masking by rituximab. CONCLUSIONS: Rituximab interfered with the flow cytometry protocol for CD20 determination on normal and neoplastic B cells. The EGA method efficiently eluted rituximab, allowing for accurate identification of CD20-positive B cells.

The Influence of Nutritional Status at Diagnosis of Childhood B-Cell Acute Lymphoblastic Leukemia on Survival Rates: Data from a Hispanic Cohort.

The impact of nutritional status at diagnosis of childhood acute lymphoblastic leukemia (ALL) on survival rates was assessed in a Hispanic cohort. Children <16 years with newly diagnosed ALL-B from 2011 to 2019 were studied. Overweight and obesity were classified by body mass index (BMI) and Z-score according to WHO and CDC criteria. BMI, weight percentiles for age and Z-Score were assessed using the WHO Anthro (0-5 years) and AnthroPlus (5-19 years) programs. Cox model was used to estimate risk factors for relapse and death; differences between groups were assessed with Student's T test for parametric and Mann-Whitney U test for non-parametric variables. Disease-free survival (DFS) and overall survival (OS) were determined by the Kaplan-Meier method, calculating time, status, cumulative survival and standard error with a 95% confidence interval. Equal data distribution was estimated with the log-rank test. One-hundred and seventy-two B-ALL children were studied. The overweight-obese group had a non-significant lower DFS (CDC: 54% vs. 60%, p = 0.80; WHO: 57% vs. 64%, p = 0.89) and OS rate (CDC:76% vs. 82%, p = 0.38; WHO:65% vs. 81%, p = 0.13). An association between nutritional status determined by CDC and WHO criteria at diagnosis of B-cell ALL and survival rates was not documented.

Assessing the performance of a plateletpheresis unit at a tertiary-care academic medical center in Mexico: A 6-year experience.

BACKGROUND: Optimization of platelet (PLT) apheresis collection is a priority to satisfy the increasing demand of hemato-oncology patients. We assessed the performance of a plateletpheresis unit supporting hematology patients. STUDY DESIGN AND METHODS: This descriptive retrospective study included 561 plateletpheresis collections from 2013 to 2018. For data analysis, descriptive statistics and receiver operating characteristic (ROC) curve were used. A 5-item satisfaction questionnaire was analyzed. RESULTS: Ninety percent of the donors were males. The median plateletpheresis time was 89 minutes; its success rate was 92.5%; median donor PLT count was 232 × 109 /L, women median PLT count was 247 × 109 /L vs 231x109 /L in men (P = .017). Seventy-seven percent donors were candidates for a double product and 24.5% were processed; 20.8% of these donors had a weight ≤75 and 79.2% >75 kg, P = .003, and 6.6% were women and 93.4% men, P = .161. Thirty-six of donors had ≥250 × 109 /L and 16.8% was processed as a triple product. ROC analysis showed that with donor PLT counts ≥200 × 109 /L the sensitivity for obtaining double products was 0.981 and specificity 0.714, with an area under the curve (AUC) = 0.877. The adverse effect rate was 4.3%. Of the potential donors, 6.3% were rejected. The cost of processing single or double products was 430 USD. Comfort and time spent during plateletpheresis were areas for improvement. CONCLUSION: Platelet count and donor weight predicted PLT yield and obtaining double products. Women had higher PLT counts, but no significant difference was found between donor gender and processed products. Assessment of the apheresis unit can help to improve its performance.

Moral Distress: Its Manifestations in Healthy Donors during Peripheral Blood Hematopoietic Stem Cell Harvesting.

Hematopoietic stem cell donors (HSCDs) may have ambivalent feelings about donation. These feelings are related to moral obligation to help a sick relative and/or fear about the donation procedure. This ambivalence can produce moral distress (MD) and anxiety, which are usually unnoticed by the treating physician. The aim of this study was to evaluate the incidence of MD and anxiety in a group of related HSCDs for allogeneic transplantation. In this prospective observational study, to assess MD and anxiety, we applied 3 self-answered questionnaires-a questionnaire developed to assess MD (MDQ), State Trait Anxiety Index (STAI), and Edmonton Symptom Assessment System (ESAS)-before, during, and after hematopoietic stem cell donation. A total of 60 consecutive related HSCDs with a mean age of 38.2 years were included. Thirty-six were male. Hematopoietic stem cell collections were done by apheresis, performed as an outpatient process in all cases. The incidence of MD during the donation process was 56%. The proportion of HSCDs with moderate to high state anxiety decreased significantly from before donation (63%) to after donation (30%). Higher scores for MD correlated with higher scores on the STAI questionnaire (r = 0.448; P < .005). Thirty-seven donors (62%) had at least 1 physical symptom even before the stem cell mobilization process started, mainly anxiety (33%), difficulty sleeping (33%), and fatigue (30%). The number of symptomatic donors increased during donation (100%) and decreased after the procedure (80%). We conclude that MD and anxiety symptoms experienced by HSCDs are very common and can be explained by mixed feelings about the donation process. Providing comprehensive psychological support before starting the donation process and guaranteeing respect for the donor's autonomy are needed to decrease the negative impact of the donation experience.

Contributions to the American Society of Hematology Meeting From Low- and Middle-Income Countries: An In-Depth Analysis and Call to Action.

PURPOSE: Establishing research capacity in low- and middle-income countries (LMICs) is key for improving the outcomes of patients with hematologic diseases globally. Few studies have analyzed the contributions of LMICs to global hematology. The American Society of Hematology Meeting (ASH) is the largest international academic event where peer-reviewed contributions in our field are presented. METHODS: In this cross-sectional analysis, all abstracts accepted to ASH 2018 selected for a poster or oral presentation were reviewed. Those that had a contributing author from an LMIC were identified. The proportion of LMIC abstracts across categories was analyzed. Country of origin, high-income country participation, the presence of a conflict of interest (COI), and sponsorship were determined. RESULTS: From 4,871 abstracts reviewed, 506 had a contributing author from an LMIC (10.4%), with 277 (54.7%) contributions in partnership with a high-income country. LMIC-independent contributions corresponded to 19 of 1,026 oral abstracts (1.9%) and 209 of 3,845 posters (5.4%). Most abstracts from LMICs were clinical (n = 311; 61.5%) and multicentric in nature (n = 353; 69.8%). COI statements with the pharmaceutical industry were common (n = 214; 42.3%). Collaboration between LMICs was infrequent (n = 33; 6.5%). Upper-middle-income countries had 466 participations (81.5%), in comparison with 96 (16.8%) in low-middle-income and 10 (1.7%) in low-income countries. CONCLUSION: LMICs were responsible for a small fraction of abstracts at ASH18; low-income countries were practically absent. Almost half of accepted works represented a form of international collaboration, with clinical, multicenter studies predominating and COI disclosures a frequent and unexpected feature, reflecting the instrumental nature of LMIC participation and a lack of independent, robust, locally developed hematology research.

Diagnoses, outcomes, and chronicity predictors of patients with secondary immune thrombocytopenia: ten-year data from a hematology referral center

ABSTRACT Background: Secondary immune thrombocytopenia (ITP) is a heterogeneous and unpredictable disease associated with various underlying conditions. Objective: The objective of the study was to investigate clinical evolution and chronicity predictors in secondary ITP. Methods: Patients treated at an academic medical center during 2008-2019 were stratified by age as children <16 years and adults >16 years. Responses to steroids, intravenous immunoglobulin G (IVIG), rituximab, and eltrombopag were classified as response (R) and complete response (CR). Risk factors for chronic ITP were determined by multiple regression with uni- and multi-variate analysis. Results: Eighty-three patients were included, 37 children and 46 adults. The most frequent associated conditions were infections 53%, systemic lupus erythematosus (SLE) 24%, thyroid disease 9.6%, and Evans syndrome 3.6%. Response to first-line treatment in the whole cohort was 94%; CR 45.7%; and R 50.6%. Initial response to steroids alone was 91.3% (n = 21/23), rituximab plus high-dose dexamethasone (HDD) 93.3% (n = 14/15); children receiving IVIG alone 100% (n=12/12); and eltrombopag in adults 100% (n = 3/3). Relapse was documented in 19.4% of children and 34% of adults, at a median time of 15 and 2 months, respectively; 30.4% of adults (15.2% from the miscellaneous group, 10.9% SLE-associated, and 4.3% infection-associated) and 18.9% of children followed a chronic course; age ≥10 years and platelets ≥20 × 109/L were risk factors for chronic ITP in children. Conclusion: Evolution was heterogeneous: a better and more sustained response was documented in the infections group compared to SLE or the miscellaneous group. (REV INVEST CLIN. 2021;73(1):31-8)

Results of a completely outpatient autologous stem cell transplant program for lymphoma patients receiving reduced-intensity conditioning.

Autologous stem cell transplantation (ASCT) is commonly an in-patient procedure. However, outpatient ASCT grows as a cost-effective and feasible option for patients with lymphoma and reports assessing it after reduced-intensity conditioning (RIC) are sparse. We report the outcome of 102 patients with lymphoma who underwent ASCT on a full outpatient basis in a single-center transplant program between 2010 and 2020. Forty-two percent of the cohort required transfusion support, 36.3% experienced a neutropenic fever episode, 25.5% mucositis, and 9.8% developed severe infection. At a median time of 5 days (range 1-28), only 22.5% of the cohort required admission within the first 100 days after the autograft, median length of hospital stay was 0 days (range 0-14) and neutropenic fever was the most common reason for hospitalization. Non-relapse mortality at 1 year was 5%. ASCT in a completely outpatient setting is feasible, safe, and highly effective to treat lymphoma patients.

An audit of platelet transfusion indications in acute leukaemia patients: six-year experience at an Academic Centre.

BACKGROUND: Platelet transfusion plays a critical role in the supportive treatment of acute leukaemia patients who receive chemotherapy and haematopoietic stem cell transplantation (HSCT). There are few studies assessing appropriateness of platelet transfusion in this population. An audit was conducted to determine how appropriately platelets are transfused in acute leukaemia patients at a tertiary care health institution. MATERIALS AND METHODS: A six-year retrospective audit was conducted in acute lymphoblastic (ALL) and acute myeloid leukaemia (AML) patients in an Academic Centre. Episodes were assessed as either appropriate or inappropriate based on guidelines from the British Society for Haematology (BSH). Pre-transfusion platelet count, transfusion indication, World Health Organization (WHO) bleeding score, and antibiotic use were all documented. RESULTS: Overall, 745 platelet transfusion episodes in 154 patients were audited. The proportion of episodes appropriately indicated according to BSH guidelines was 75.3%. Paediatrics and Internal Medicine had the lowest and highest proportion of appropriateness by department at 63.9% and 86.8%, respectively. The best alignment to guidelines was found on the wards (82.3%). Inpatient cases were significantly better indicated (p=0.002), whereas therapeutic and HSCT-related transfusions were not. The majority of inappropriate transfusions had a pre-transfusion count >20×109/L without a valid justification (45.1%), whereas appropriate episodes were mainly accounted for by a pre-transfusion count <10×109/L (69%). DISCUSSION: The 25% rate of inappropriate platelet transfusion in acute leukaemia patients underscores the learning needs of physicians, particularly those in training, regarding adequate use of platelets in haematologic malignancies to optimise its utilisation and patient outcome.

Diagnoses, Outcomes, and Chronicity Predictors of Patients with Secondary Immune Thrombocytopenia: Ten-Year Data from a Hematology Referral Center.

BACKGROUND: Secondary immune thrombocytopenia (ITP) is a heterogeneous and unpredictable disease associated with various underlying conditions. OBJECTIVE: The objective of the study was to investigate clinical evolution and chronicity predictors in secondary ITP. METHODS: Patients treated at an academic medical center during 2008-2019 were stratified by age as children <16 years and adults <16 years. Responses to steroids, intravenous immunoglobulin G (IVIG), rituximab, and eltrombopag were classified as response (R) and complete response (CR). Risk factors for chronic ITP were determined by multiple regression with uni- and multi-variate analysis. RESULTS: Eighty-three patients were included, 37 children and 46 adults. The most frequent associated conditions were infections 53%, systemic lupus erythematosus (SLE) 24%, thyroid disease 9.6%, and Evans syndrome 3.6%. Response to first-line treatment in the whole cohort was 94%; CR 45.7%; and R 50.6%. Initial response to steroids alone was 91.3% (n = 21/23), rituximab plus high-dose dexamethasone (HDD) 93.3% (n = 14/15); children receiving IVIG alone 100% (n=12/12); and eltrombopag in adults 100% (n = 3/3). Relapse was documented in 19.4% of children and 34% of adults, at a median time of 15 and 2 months, respectively; 30.4% of adults (15.2% from the miscellaneous group, 10.9% SLE-associated, and 4.3% infection-associated) and 18.9% of children followed a chronic course; age ≥10 years and platelets ≥20 × 109/L were risk factors for chronic ITP in children. CONCLUSION: Evolution was heterogeneous: a better and more sustained response was documented in the infections group compared to SLE or the miscellaneous group.

Early changes in IL-21, IL-22, CCL2, and CCL4 serum cytokines after outpatient autologous transplantation for multiple sclerosis: A proof of concept study.

Changes in serum cytokines after autologous hematopoietic stem cell transplantation (AHSCT) in multiple sclerosis (MS) patients were documented. Thirty-six consecutive MS patients who had their Expanded Disability Status Scale (EDSS) scored before AHSCT were prospectively enrolled. Cyclophosphamide (Cy) was infused at 200 mg/kg in two administrations given 10 days apart: the first dose for mobilization, the second as the conditioning regimen. Patients were mobilized with 10 µg/kg/day subcutaneous G-CSF. Serum was collected 14 days before and 14 after AHSCT. IL-6, IL-9, IL-10, IL 17-A, IL-21, IL-22, IL-23, TNF-A, CCL2, CCL3, and CCL4 were measured by magnetic bead-based immunoassay. t Test and Wilcoxon test were used to compare cytokine levels before and after AHSCT. There were 28 women and 8 men with a median age of 46 (15-62) years, median duration of MS was 9.5 (1-32) years, and EDSS score was 5.7 (1.5-8.0). Patients had a decrement of pro-inflammatory IL-21 and IL-22 (p = .003 and p = .028) and an increment of anti-inflammatory CCL2 and CCL4 (p < .001 and p = .039) after AHSCT. Decrease of IL-21 and IL-22 coupled with an increment of CCL2 and CCL4 could reflect the immunomodulatory effect of auto-HSCT and be an early indicator of its efficacy.

IMPACT OF HLA-DPB1 MATCHING ON CLINICAL OUTCOMES AFTER HAPLOIDENTICAL-RELATED HEMATOPOIETIC STEM CELL TRANSPLANTATION.

BACKGROUND: The impact of HLA-DPB1 compatibility and its role as a transplantation antigen in haploidentical-related hematopoietic stem cell transplant (haplo-R-HSCT) have not been established, and a negative effect on survival has been suggested. OBJECTIVE: The objective of the determine was to study the frequency and clinical effects of incompatibility at the HLA-DPB1 locus in the haplo-R-HSCT setting. METHODS: Clinical records and electronic files of 91 patients with a hematological disease who underwent haplo-HSCT from January 2009 to October 2017 in a university medical center were scrutinized. Overall survival (OS) was estimated by the Kaplan-Meier method; the cumulative incidence of transplant-related mortality (TRM) and relapse rates was determined. Acute graft-versus-host disease was assessed by binary logistic regression. Cox regression model with a 95% confidence interval was used to examine the association between the different variables and their effect on OS. RESULTS: Of the 91 donor-recipient pairs, 24 (26.37%) shared complete DPB1 identity, 60 (65.93%) had a mismatch at one allele, and 7 (7.70%) were mismatched at two alleles. Twenty-four different HLA-DPB1 alleles were found; the most frequent were DPB1*04:01 (34.1%) and DPB1*04:02 (27.5%). Two-year OS, the cumulative incidence of TRM and relapse was 51.3 ± 6.8%, 28 ± 6% and 60 ± 7.8% for all haplo-related transplants, respectively, with no statistical difference between HLA-DPB1 matched and partially matched patients. In Cox regression analysis, no risk factors associated with OS, TRM, or relapses were identified. CONCLUSION: HLA-DPB1 mismatching in the haplo-R-HSCT setting did not influence transplant outcomes and was clinically tolerable. A high degree of homozygosity was found.

Impact of hHLA-DPB1 matching on clinical outcomes after haploidentical-related hematopoietic stem cell transplantation

ABSTRACT Background: The impact of HLA-DPB1 compatibility and its role as a transplantation antigen in haploidentical-related hematopoietic stem cell transplant (haplo-R-HSCT) have not been established, and a negative effect on survival has been suggested. Objective: The objective of the determine was to study the frequency and clinical effects of incompatibility at the HLA-DPB1 locus in the haplo-R-HSCT setting. Methods: Clinical records and electronic files of 91 patients with a hematological disease who underwent haplo-HSCT from January 2009 to October 2017 in a university medical center were scrutinized. Overall survival (OS) was estimated by the Kaplan-Meier method; the cumulative incidence of transplant-related mortality (TRM) and relapse rates was determined. Acute graft-versus-host disease was assessed by binary logistic regression. Cox regression model with a 95% confidence interval was used to examine the association between the different variables and their effect on OS. Results: Of the 91 donor-recipient pairs, 24 (26.37%) shared complete DPB1 identity, 60 (65.93%) had a mismatch at one allele, and 7 (7.70%) were mismatched at two alleles. Twenty-four different HLA-DPB1 alleles were found; the most frequent were DPB1*04:01 (34.1%) and DPB1*04:02 (27.5%). Two-year OS, the cumulative incidence of TRM and relapse was 51.3 ± 6.8%, 28 ± 6% and 60 ± 7.8% for all haplo-related transplants, respectively, with no statistical difference between HLA-DPB1 matched and partially matched patients. In Cox regression analysis, no risk factors associated with OS, TRM, or relapses were identified. Conclusion: HLA-DPB1 mismatching in the haplo-R-HSCT setting did not influence transplant outcomes and was clinically tolerable. A high degree of homozygosity was found.

Mobilization kinetics of CD34+ hematopoietic stem cells stimulated by G-CSF and cyclophosphamide in patients with multiple sclerosis who receive an autotransplant.

BACKGROUND AIMS: Autologous hematopoietic stem cell transplantation (AHSCT) is an alternative for multiple sclerosis (MS) patients who do not respond to conventional treatment. Mobilization kinetics of CD34+ cells in MS patients has not been studied. METHODS: Patients with MS mobilized with granulocyte colony-stimulating factor (G-CSF) and cyclophosphamide (Cy) were prospectively studied. Three counts of CD34+ cells were done in peripheral blood: at baseline before mobilization, at the start, and immediately at the end of apheresis. Complete blood counts were performed at the times of CD34+ cell counting. Standard statistical descriptive analysis of MS patients' salient features was performed, and after log 10 transformation of the data, Pearson test was performed to assess correlation between variables and CD34+ cell count. In addition, multiple linear regression of relevant data was carried out for multivariate analysis. RESULTS: Data of 51 consecutive MS patients with median age of 48 (31-64) years were analyzed. The CD34+ cell count increased 26-fold after mobilization. During large volume leukapheresis (LVL), the number of CD34+ cells in peripheral blood increased from 51.29 CD34+/µL at the start to 62.3 CD34+/µL at the end. A negative correlation between CD34+ cell count after leukapheresis and age (r = -0.32, P = 0.02) was observed. Neither the CD34+ baseline count nor sex correlated with the CD34+ count in peripheral blood immediately at the end of apheresis. CONCLUSIONS: Mobilization with G-CSF and Cy in MS patients resulted in effective CD34+ hematoprogenitors release from the bone marrow and in intra-apheresis recruitment.

Sexual Dimorphism in Children and Adolescents With Acute Lymphoblastic Leukemia: Influence on Incidence and Survival.

Acute lymphoblastic leukemia (ALL) incidence and poor prognosis are higher in male individuals. There is a lack of studies assessing the influence of sex in ALL. We documented this influence in a homogenous cohort. Three hundred three ALL Hispanic patients 1 to 20 years of age diagnosed over 10 years at a university hospital were evaluated. Patients were divided by sex and stratified by age. Survival rates were assessed by the Kaplan-Meier method, and the Cox model was used for univariate and multivariate analysis. The median age for female individuals was 6 years versus 9 years for male individuals (P=0.002). In the whole cohort, there was a male preponderance (P=0.025), with a 1.3 male-to-female ratio. For male individuals, the 5-year relapse-free survival was 46%; for female individuals, it reached 58.7%, (P=0.009). Male individuals 1-9 years of age had a lower 5-year relapse-free survival than female individuals, 51.5% versus 66.7% (95% confidence interval, 65.35-68.01; P=0.020); this was not the case for overall survival (P=0.660). The male-to-female ratio in the 10 to 15 years' group was 1.59, and 2.35 in the 16 to 20 years' group. Incidence and relapse of ALL were higher in male individuals. A skewed distribution in the 10 to 20 years' age group disproportionately affected male individuals, suggesting a hormonal influence.

Association of CYP2C19*2 polymorphism with clopidogrel resistance among patients with high cardiovascular risk in Northeastern Mexico.

Objective: Oral antiplatelet drugs are a key to modern pharmacotherapy in cardiovascular atherothrombotic diseases. Clopidogrel (CLO) constitutes the main preventive treatment of atherothrombosis. However, a considerable inter-individual variation in CLO response has been documented, resulting in suboptimal therapy and an increased risk of recurrent adverse effects in some patients. The enzyme CYP2C19 has been reported to be the CYP isoform that activates CLO to its active metabolite. Several single nucleotide polymorphisms in the CYP2C19 gene have been identified as strong predictors of CLO-impaired pharmacological response. At least 16 variants have been associated with changes in CYP2C19 activity. Materials and Methods: The following research was composed of a total of 102 subjects with high cardiovascular risk in the northeast of Mexico, with a maintenance dose of 75 mg of CLO per day. The platelet reactivity was measured with VerifyNow P2Y12 assay, while the presence of CYP2C19*2 was identified by real-time polymerase chain reaction. Results: Patients were categorized by CYP2C19 metabolizer status based on *2 genotypes using the common consensus star allele nomenclature as normal metabolizer (G/G), intermediate metabolizer (G/A), and poor metabolizer (A/A), respectively. The phenotype frequency for CYP2C19*2 was 74.5% (G/G), 21.6% (G/A), and 3.9% (A/A). The subjects with the A allele presented ≥235 P2Y12 reaction unit levels, classifying them how poor metabolizer. The prevalence of reduced CLO effectiveness was associated with the presence of CYP2C19*2 polymorphism among Mexican patients. Conclusion: The presence of the CYP2C19*2 allele is related to resistance to the antiplatelet effect of CLO (p = 0.003).

Objetivo: Los antiplaquetarios orales son clave en la farmacoterapia moderna de las enfermedades aterotrombóticas cardiovasculares. Clopidogrel (CLO) constituye el principal tratamiento preventivo de aterotrombosis (AT). Sin embargo, se ha documentado una considerable variación interindividual en la respuesta a CLO, lo que da como resultado una terapia subóptima y mayor riesgo de efectos adversos en algunos pacientes. La enzima CYP2C19 es la isoforma CYP que activa CLO a su metabolito activo. Se han identificado varios polimorfismos de un solo nucleótido en el gen CYP2C19 como fuertes predictores de respuesta farmacológica alterada a CLO. Al menos 16 variantes se han asociado con cambios en la actividad de CYP2C19. Método: Se reclutaron un total de 102 sujetos con alto riesgo cardiovascular del noreste de México, con dosis de mantenimiento de 75 mg de CLO/día. La reactividad plaquetaria se midió con el ensayo Verify Now P2Y12, la presencia de CYP2C19*2 se identificó mediante polymerase chain reaction en tiempo real. Resultado: Los pacientes fueron clasificados por el estado metabolizador CYP2C19*2 utilizando nomenclatura consenso, como metabolizador normal (G/G), metabolizador intermedio (G/A) y metabolizador pobre (A/A), respectivamente. La frecuencia del fenotipo para CYP2C19*2 fue 74.5% (G/G), 21.6% (G/A) y 3.9% (A/A). Los sujetos con alelo A presentaron ≥235 niveles P2Y12 reaction unit, clasificándolos como metabolizadores deficientes. La prevalencia de eficacia reducida a CLO se asoció con la presencia del polimorfismo CYP2C19*2 en pacientes mexicanos. Conclusiones: La presencia del alelo CYP2C19*2 se relaciona con resistencia al efecto antiagregante plaquetario del CLO (p = 0.003).