ABSTRACT Introduction: Pre-apheresis peripheral blood CD34+ cell count (PBCD34+) is the most important predictor of good cell mobilization before hematopoietic stem cell transplantation, albeit flow cytometry is not always immediately available. Identification of surrogate markers can be useful. The CD34+ cells proliferate after mobilization, resulting in elevated lactate dehydrogenase (LDH) activity and correlating with the PBCD34+ count. Objective: To determine the LDH cut-off value at which adequate CD34+ cell mobilization is achieved and its diagnostic yield. Materials and methods: A total of 103 patients who received an autologous stem cell transplantation (ASCT) between January 2015 and January 2020 were included. Demographic and laboratory characteristics were obtained, including complete blood count, pre-apheresis PBCD34+ and LDH levels. Receiver operating characteristic (ROC) curves were performed to identify the optimal serum LDH activity cut-off points for ≥ 2 and ≥ 4 × 106 cells/kg post-mobilization CD34+ count and their diagnostic yield. Results: A post-mobilization serum LDH cut-off value of 462 U/L yielded a sensitivity (Se) = 86.8% (positive predictive value [PPV] = 72.7%), a pre- and post-mobilization serum LDH difference cut-off value of 387 U/L, an Se = 45.7% (PPV = 97%) and an LDH ratio of 2.46, with an Se = 47.1% (PPV = 97%) for an optimal mobilization count (CD34+ ≥ 4 × 106). Conclusion: The LDH measurement represents a fast and affordable way to predict PBCD34+ mobilization in cases where flow cytometry is not immediately available. According to the LDH diagnostic yield, it could be used as a surrogate marker in transplant centers, supporting the CD34+ count, which remains the gold standard.

ABSTRACT Introduction: Acute myeloid leukemia (AML) is most commonly presented in older adults; however, it appears 10 years earlier in Latin American countries. Clinical evolution in older adults from this populations has not been characterized. We analyzed outcomes and survival predictors. Methods: Patients ≥ 55 years old diagnosed with AML at a hematology referral center from 2005 to 2020 receiving intensive chemotherapy (IC), low-dose cytarabine (LDAC) and best supportive care (BSC) were included. Survival analysis included the Kaplan-Meier and Cox models and the cumulative incidence of relapse (CIR). Results: Seventy-five adults were included and the overall survival (OS) was 4.87, 1.67 and 1.16 months, using IC, LDAC and BSC, respectively. The IC led to a higher OS (p < 0.001) and was a protective factor for early death, at a cost of more days spent hospitalized and more non-fatal treatment complications; non-significant differences were found between the LDAC and BSC. Eight (10.7%) patients underwent hematopoietic cell transplantation, with a higher OS (p = 0.013). Twenty (26.7%) patients achieved complete remission; 12 (60%) relapsed with a 6-month CIR of 57.9% in those < 70 years old vs. 86.5% in those ≥ 70 years old, p = 0.034. Multivariate analysis showed the white blood cell count (WBC) and IC had a significant impact on the patient survival, whereas chronological age and the Charlson comorbidity index (CCI) did not. Conclusion: AML in low-middle income countries demands a different approach; the IC improves survival, even with a high incidence of relapse, and should be offered as first-line treatment. Eligibility criteria should include WBC and a multidimensional evaluation. The age per se and the CCI should not be exclusion criteria to consider IC.

ABSTRACT Background: The date of acute lymphoblastic leukemia (ALL) diagnosis has been studied regarding potential etiologic roles with contrasting results and the issue remains controversial. The principal aim of this study was to analyze monthly variation of ALL diagnosis in a large homogenous Hispanic Latin American cohort over 15 years; its association with survival rates was also assessed. Methods: Clinical files and electronic records of 501 consecutive patients of all ages with ALL in northeastern Mexico over the years of 2004–2018 were scrutinized. Patients were divided into children <18 and adults >18 years. The Chi-square heterogeneity analysis was used to test for non-uniform variation. The Poisson regression analysis was used to fit sinusoidal (harmonic) models to the data, using the month of diagnosis as a covariate in a separate model. Results: During the study period 363 children (72.5%) and 138 adults (27.5%) (p < 0.001) were diagnosed with ALL. Heterogeneity across the months of diagnosis was confirmed (p = 0.019) and the Poisson regression analysis confirmed a significant monthly variation (p < 0.001) (95% CI, 3.024–3.745), a higher annual peak being observed in the month of March (p = 0.002), followed by a second peak in October (p = 0.026). The five-year OS for children was 68.2% (95% CI, 67.64–68.74) and for adults, 43.7% (95% CI, 42.67–44.71) (p < 0.001). No significant association between the month of diagnosis and OS was found (p = 0.789). Conclusion: The monthly variation of ALL diagnosis was documented; these results confirm the heterogeneous behavior of the disease and appear to be consistent with an interplay of environmental and biologic factors. Further studies are needed to examine putative candidate agents.

Abstract Introduction Hemorrhagic cystitis (HC) is a common complication of haploidentical hematopoietic stem cell transplantation (haplo-HSCT), characterized by irritative symptoms of the urinary tract and a higher morbidity and mortality rate. The worldwide incidence is reported between 10% and 70%. The use of alkylating agents and BK viral infection are the most frequent etiologies. The aim of this study was to report the HC incidence in an outpatient haplo-HCST program with a reduced intensity-conditioning (RIC) regimen, cataloguing risk factors, complications and final outcomes. Methods The medical database of patients who received a haplo-HSCT between January 2012 and November 2017 was retrospectively analyzed. Demographic variables, general characteristics and HC incidence were included. Results One hundred and eleven patients were included, 30 (27%) of whom developed HC, most of them (70%) being grade II, with a 30-day (7-149) median time of post-transplant HC onset. The BK virus was detected in 71% of the urine samples analyzed. All HC patients responded to treatment, except two (6.6%), who died due to HC complications. Conclusions There was no difference in the HC incidence or severity, compared to that reported when performing haplo-HSCT in hospitalized patients, although the donor-recipient sex mismatch did relate to a higher HC incidence.

In this article, the perspectives on both the diagnosis and treatment of acute leukemias, chronic leukemias, multiple myeloma, anemia, platelet, and coagulation disorders are briefly discussed. We emphasize the limitations facing the practice of hematology in low- and middle-income countries.

Abstract Acute leukemia is the leading cause of death in children worldwide, particularly in developing countries where the growing number of cases with unfavorable prognosis and high risk of early relapse have positioned pediatric cancer as a priority. The late and imprecise diagnosis, malnutrition and unfavorable environmental conditions, and toxicity-associated therapy are some of the factors that compromise the success of the treatment and affect survival rates in vulnerable regions. An early and exhaustive classification of malignant neoplasms at the clinical debut and the proper follow-up of treatment’s response constitute one of the most powerful prognostic factors. Remarkably, the ultrasensitive detection of residual and relapse clones that determine the minimal/measurable residual disease (MRD) has been a milestone in the comprehensive management of hematologic malignancies that favorably improve the complete remission cases. In this review, we discuss the scientific and technological advances applied to laboratory diagnosis in MRD determination: from the multiparametric immunophenotyping to next-generation sequencing and cytomics. As a result of multidisciplinary research in the main concentration oncology centers and laboratories, residual leukemia detection strategies that combine molecular analysis and cellular markers are recommended as the most valuable tools, making them the paradigm for stratification campaigns in vulnerable regions.

Resumen La leucemia aguda es la principal causa de muerte por enfermedad en la población infantil mundial, en particular en los países con economías en desarrollo, donde el creciente número de casos con pronóstico desfavorable y riesgo de recaídas tempranas ha posicionado a esta enfermedad como una prioridad de salud. El diagnóstico tardío y de baja precisión, la ausencia de condiciones favorables de alimentación y entorno ambiental, así como la toxicidad asociada a la terapia, son algunos de los factores que condicionan el éxito del tratamiento y afectan las tasas de supervivencia en las regiones más vulnerables. La clasificación temprana y exhaustiva del tumor maligno en la presentación clínica y durante el seguimiento de respuesta al tratamiento es uno de los más poderosos factores pronósticos. En especial, la detección ultrasensible de clonas residuales y reemergentes que determinan la enfermedad residual mínima medible ha sido un hito en el manejo integral de las neoplasias hematológicas y ha impactado favorablemente en las cifras de remisión completa. En esta revisión se comentan los avances científicos y tecnológicos aplicados al diagnóstico de laboratorio y a la determinación de la enfermedad residual mínima: desde la inmunofenotipificación multiparamétrica hasta la secuenciación y la citómica de última generación. Como resultado de las investigaciones multidisciplinarias en los principales centros oncológicos de concentración y los laboratorios de clase mundial, las estrategias de detección de la leucemia residual que combinan análisis moleculares y marcadores celulares han sido recomendadas como las de mayor utilidad, por lo que son el paradigma para las campañas de estratificación en las regiones vulnerables.

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)

Abstract The pandemic of coronavirus infectious disease-2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a threat to global health. This has become an obstacle for the practice of hematology, mostly in low-middle income countries. For those hematologist and oncologists who perform hematopoietic stem cell transplantation HSCT the usual challenges of this kind of medical procedures have increased because of the COVID-19 pandemic. The importance of find the best route for performing HSCT avoiding excessive COVID-19 risk is of great importance. By doing so, we have been able to conduct 170 hematopoieic stem cell transplants during the COVID-19 pandemia.

Resumen La pandemia de COVID-19 ha causado daños graves a la práctica de la medicina y se ha convertido en un obstáculo para la práctica de algunas especialidades. Los trasplantes de células hematopoyéticas han sufrido las consecuencias de la pandemia y muchos centros de trasplante hematopoyético en todo el mundo suspendieron sus labores. Gracias a la implementación de medidas de escrutinio y aislamiento de los pacientes sometidos a trasplante hematopoyético, hemos podido trasplantar a 170 pacientes en la época del COVID-19.

Abstract Medical practice in general has changed due to coronavirus disease 2019 (COVID-19) pandemic. Some hematologic diseases require immunosuppresive therapy placing patients at high risk of infection, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Aplastic anemia (AA) especially the very severe type in which the count of absolute neutrophils is less than 200/ml is a life-threatening condition. Although bone marrow transplant is a potential curative treatment, it should be delayed temporally in order to prevent a contagion. Hospitalization may expose patients to infection, thus an ambulatory immunosuppression with oral cyclosporine and thrombopoietin agonist should be an adequate option. This work reviews international and national treatment recommendations and follow-up of patients with AA based on experiences from countries that have already faced this health emergency.

Resumen La pandemia de enfermedad por coronavirus 2019 (COVID-19) ha cambiado la perspectiva médica para el tratamiento de no solo de enfermedades hematológicas, sino en general de la medicina. Respecto a la anemia aplásica (AA), principalmente la muy severa, en la que el paciente se presenta con menos de 200 neutrófilos absolutos, el riesgo de infección potencialmente mortal es alta y el inicio de terapia inmunosupresora también representa un riesgo, al menos temporal, para COVID-19. Se ha recomendado incluso aplazar el trasplante de células progenitoras hematopoyéticas en muchos pacientes para evitar un contagio. Una inmunosupresión moderada preferentemente ambulatoria que incluya agentes trombomiméticos es la opción terapéutica en tiempos de la pandemia actual. En esta revisión se enlistan las recomendaciones internacionales y nacionales respecto al tratamiento y seguimiento de pacientes con AA con base en experiencias de países que ya han pasado por esta emergencia sanitaria.

ABSTRACT Background and objective T-cell acute lymphoblastic leukemia (T-ALL) in children represents a high-risk disease. There is a lack of studies assessing the outcome of T-ALL in Hispanic populations, in which it is a rare malignancy. We report the characteristics and results of treatment for childhood T-cell ALL in children over 14 years at a Latin American reference center. Material and methods From January 2005 to December 2018, there occurred the analysis of twenty patients ≤ 16 years of age from a low-income open population diagnosed at a university hospital in Northeast Mexico. Clinical and laboratory characteristics, treatment regimens and outcomes were assessed by scrutinizing clinical records and electronic databases. Diagnosis was confirmed by flow cytometry, including positivity for CD-2, 5, 7 and surface/cytoplasmic CD3. Survival rates were assessed by the Kaplan-Meier method. Results There was a male preponderance (70 %), with a 2.3 male-to-female ratio (p= .074), the median age being 9.5 years. Leucocytes at diagnosis were ≥ 50 × 109/L in 13 (65 %) children, with CNS infiltration in 6 (30 %) and organomegaly in 10 (50 %). The five-year overall survival (OS) was 44.3 % (95 % CI 41.96–46.62), significantly lower in girls, at 20.8 % (95 % CI 17.32–24.51) vs. 53.1 % (95 % CI 50.30–55.82), (p= .035) in boys; there was no sex difference in the event-free survival (EFS) (p= .215). The survival was significantly higher after 2010 (p= .034). Conclusion The T-cell ALL was more frequent in boys, had a higher mortality in girls and the survival has increased over the last decade with improved chemotherapy and supportive care.

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.

RESUMEN Objetivo El dengue es una enfermedad viral generalmente autolimitada, que en México se considera un problema de salud pública. Puede acompañarse de alteraciones de laboratorio como neutropenia, linfopenia y trombocitopenia. El objetivo del estudio fue evaluar la incidencia de alteraciones hematológicas en pacientes con dengue. Métodos Se incluyeron retrospectivamente 64 pacientes, 14 embarazadas, con diagnóstico de dengue en los Hospitales Universitario de Monterrey y Civil Nuevo de Guadalajara, de enero de 2014 a diciembre de 2017. Resultados El dato clínico más común en el grupo general fue cefalea y dolor retroocular en 53 pacientes (83%), seguido de la fiebre, que se presentó en 12 pacientes embarazadas (86%). La mediana de cuenta plaquetaria en el grupo general fue de 51.4x103/pl, además, se encontró trombocitopenia en el 88% de los pacientes, mientras que en las pacientes embarazadas fue de 141.1 x103/pl, con trombocitopenia en 57% de ellas (p=0.002). La recuperación plaquetaria ocurrió en 7 días en el grupo general y 4.5 días en las pacientes embarazadas. Conclusiones Contrario a lo reportado en la literatura, las pacientes embarazadas presentaron una menor incidencia de trombocitopenia y una mayor cuenta plaquetaria, al momento del diagnóstico sin impacto en mortalidad materna ni en el curso del embarazo.

ABSTRACT Objective Dengue is a generally self-limited viral disease, considered a public health problem in Mexico. It can be accompanied by laboratory alterations such as neutropenia, lymphopenia and thrombocytopenia. The objective of the study was to evaluate the incidence of hematological alterations in patients with dengue. Methods We retrospectively included 64 patients, including 14 pregnant women, with a diagnosis of dengue at the Hospital Universitario de Monterrey and Civil Nuevo de Guadalajara from January 2014 to December 2017. Results The most common clinical symptom in the general group was headache and retro-ocular pain in 53 patients (83%), while in pregnant patients it was fever in 12 patients (86%). The median platelet count in the general group was 51.4x103/ μ!, with thrombocytopenia in 88% of patients, while in pregnant patients it was 141.1 x103/ with thrombocytopenia in 57% of patients (p=0.002). Platelet recovery was achieved in 7 days in the general group and 4.5 days in pregnant patients. Conclusions Contrary to that reported in the literature, pregnant patients had a lower incidence of thrombocytopenia and a higher platelet count at time of diagnosis without impact on maternal mortality or in the course of pregnancy.

RESUMEN Objetivo El dengue es una enfermedad viral generalmente autolimitada, que en México se considera un problema de salud pública. Puede acompañarse de alteraciones de laboratorio como neutropenia, linfopenia y trombocitopenia. El objetivo del estudio fue evaluar la incidencia de alteraciones hematológicas en pacientes con dengue. Métodos Se incluyeron retrospectivamente 64 pacientes, 14 embarazadas, con diagnóstico de dengue en los Hospitales Universitario de Monterrey y Civil Nuevo de Guadalajara, de enero de 2014 a diciembre de 2017. Resultados El dato clínico más común en el grupo general fue cefalea y dolor retroocular en 53 pacientes (83%), seguido de la fiebre, que se presentó en 12 pacientes embarazadas (86%). La mediana de cuenta plaquetaria en el grupo general fue de 51.4x103/pl, además, se encontró trombocitopenia en el 88% de los pacientes, mientras que en las pacientes embarazadas fue de 141.1 x103/pl, con trombocitopenia en 57% de ellas (p=0.002). La recuperación plaquetaria ocurrió en 7 días en el grupo general y 4.5 días en las pacientes embarazadas. Conclusiones Contrario a lo reportado en la literatura, las pacientes embarazadas presentaron una menor incidencia de trombocitopenia y una mayor cuenta plaquetaria, al momento del diagnóstico sin impacto en mortalidad materna ni en el curso del embarazo.

ABSTRACT Objective Dengue is a generally self-limited viral disease, considered a public health problem in Mexico. It can be accompanied by laboratory alterations such as neutropenia, lymphopenia and thrombocytopenia. The objective of the study was to evaluate the incidence of hematological alterations in patients with dengue. Methods We retrospectively included 64 patients, including 14 pregnant women, with a diagnosis of dengue at the Hospital Universitario de Monterrey and Civil Nuevo de Guadalajara from January 2014 to December 2017. Results The most common clinical symptom in the general group was headache and retro-ocular pain in 53 patients (83%), while in pregnant patients it was fever in 12 patients (86%). The median platelet count in the general group was 51.4x103/ μ!, with thrombocytopenia in 88% of patients, while in pregnant patients it was 141.1 x103/ with thrombocytopenia in 57% of patients (p=0.002). Platelet recovery was achieved in 7 days in the general group and 4.5 days in pregnant patients. Conclusions Contrary to that reported in the literature, pregnant patients had a lower incidence of thrombocytopenia and a higher platelet count at time of diagnosis without impact on maternal mortality or in the course of pregnancy.