Infection-related mortality after HLA-identical and haploidentical hematopoietic cell transplantation using reduced-intensity conditioning in an outpatient setting.

BACKGROUND: Despite the improvements in supportive care for allogeneic-hematopoietic cell transplantation (allo-HCT) recipients, infectious complications and infection-related mortality (IRM) continue to be a major issue for transplantation centers. METHODS: We herein report the infectious complications and IRM of 107 and 89 patients that underwent haploidentical (haplo-HCT) or HLA-identical HCT at a tertiary referral center during 2013-2020. Patients in the haplo-HCT group received post-transplant cyclophosphamide (PT-Cy), and all received reduced-intensity conditioning regimens. RESULTS: More haplo-HCT recipients presented severe infections in the pre-engraftment period (22.4% vs. 6.7%, p = 0.003). Viral (14.9% vs. 4.5%, p = 0.016) and fungal (12.1% vs. 1.1%, p = 0.003) etiologies were more common in this period in this group. The 100-day and 2-year cumulative incidence of IRM was 15% and 21% for the haplo-HCT and 5.6% and 17% for the HLA-identical group; no significant differences were observed between the groups. Fungal pathogens mainly contributed to IRM (33.3%). Infections were the most common cause of mortality (40/81, 49.4%). There were significant differences in donor/recipient CMV serostatus between transplant groups (0.002). CONCLUSIONS: No differences in IRM were observed based on allo-HCT type, with more haplo-HCT patients suffering from severe infections in the pre-engraftment period. Studies to assess future prevention, diagnostic, and treatment strategies to reduce IRM are warranted.

Monthly variation in diagnosis of acute lymphoblastic leukemia and survival outcome in children and adults: 15-year trends at a single center

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.

Direct Oral Anticoagulants for the Treatment of Cancer-Associated Venous Thromboembolism: A Latin American Perspective.

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in patients with cancer. On the basis of results from randomized controlled trials, direct oral anticoagulants (DOACs) are now recommended for the treatment of cancer-associated VTE. The decision to use a DOAC requires consideration of bleeding risk, particularly in patients with gastrointestinal (GI) malignancies, the cost-benefit and convenience of oral therapy, and patient preference. While efficacy with apixaban, edoxaban, and rivaroxaban versus dalteparin has been consistent in the treatment of cancer-associated VTE, heterogeneity is evident with respect to major GI bleeding, with an increased risk with edoxaban and rivaroxaban but not apixaban. Although cost and accessibility vary in different countries of Latin America, DOACs should be considered for the long-term treatment of cancer-associated VTE in all patients who are likely to benefit. Apixaban may be the preferred DOAC in patients with GI malignancies and LMWH may be preferred for patients with upper or unresected lower GI tumors. Vitamin K antagonists should only be used for anticoagulation when DOACs and low molecular weight heparin are inaccessible or unsuitable.

Monthly variation in diagnosis of acute lymphoblastic leukemia and survival outcome in children and adults: 15-year trends at a single center.

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.

A high transfusion burden following an ambulatory-allogeneic hematopoietic cell transplantation using reduced-intensity conditioning is associated with adverse outcomes.

OBJECTIVES: Ambulatory allogeneic hematopoietic cell transplantation (allo-HCT) after reduced-intensity conditioning (RIC) is a cost-effective option for hematology patients. Data on the impact of transfusion burden in this setting are scarce; we analyzed this retrospectively. METHODS: A study of 177 HLA-identical and haploidentical allo-HCT recipients on an outpatient basis was conducted between 2013 and 2019. Packed red blood cell (PRBC) and platelet transfusions were documented from days 0-100 after HCT. RESULTS: A total of 121 patients (68.4%) required transfusion while 56 (31.6%) did not. In the multivariate analysis, a lower disease-free (DFS) and overall survival (OS) were documented for patients that received ≥9 total blood products (p = 0.018) (p = 0.014), those who required hospitalization (p = 0.001) (p < 0.001), had acute graft-versus-host disease (p = 0.016) (p = 0.004), and a high/very high Disease-Risk-Index (p = 0.002; p = 0.004), respectively. Transfusion of ≥5 PRBC units was associated with a lower OS (p = 0.027). The cumulative incidence of transplant-related mortality at two years for an HLA-identical transplant was 9.5% and for haploidentical, it was 27.1% (p = 0.027); this last group had significantly more transfusion demands than HLA-identical recipients (p = 0.029). CONCLUSION: Increased blood product utilization is an independent predictor of decreased survival in ambulatory RIC allo-HCT recipients. Further evidence leading to individualized guidelines to transfuse in this complex scenario is needed.

First Comparative Study of the Effectiveness of the Use of Tranexamic Acid against ε-Aminocapróic Acid via the Oral Route for the Reduction of Postoperative Bleeding in TKA: A Clinical Trial.

Total primary knee replacement results in significant postoperative bleeding. There are reports that 20 to 50% of the patients require a blood transfusion, which has been related to many complications, resulting in the search for strategies to reduce bleeding. The use of oral antifibrinolytics is becoming a low cost and safe way of achieving this goal. The hypothesis of this study was that the use of oral aminocaproic acid could provide similar results to the use of oral tranexamic acid (TXA). The purpose was to compare the effects of oral aminocaproic acid as a hemostatic agent versus the use of oral TXA administered in multiple doses pre and postsurgery in patients undergoing total primary knee replacement. We enrolled 92 patients that were randomly divided into two groups: received three doses of aminocaproic acid (2,000 mg per dose) or three doses of oral TXA (1,300 mg per dose). The drugs were administered according to the following schedule: 2 hours before surgery and 6 and 12 hours after surgery. The variables that were analyzed to compare the effectiveness of the hemostatic agents were total blood loss; hidden blood loss; external blood loss; transfusion rate; intraoperative blood loss; decreases in hemoglobin and hematocrit values; surgical drainage output; visual analogue scale; and surgical complications. There were no significant differences between any of the study variables for the group receiving oral aminocaproic acid and the group receiving oral TXA (p > 0.05), with the exception of patients who received TXA, who presented with more adverse events (p = 0.04). Our study showed that the use of oral aminocaproic acid was similar to its counterpart TXA regarding the evaluated parameters. Although patients who received TXA presented an average of 140 mL less blood loss than patients in the ε-ACA group, the difference did not appear to be clinically important, the transfusion rate was very low, and there were no between-group differences in postoperative complications.

Revisiting the complete blood count and clinical findings at diagnosis of childhood acute lymphoblastic leukemia: 10-year experience at a single center

Abstract Background Heterogeneity regarding clinical and laboratory findings at diagnosis of acute lymphoblastic leukemia exists. The frequency of complete blood count abnormalities and its combinations, symptoms and physical findings were investigated in Hispanic children from an open population at the diagnosis of acute lymphoblastic leukemia. Methods The patient charts and electronic records of under 16-year-old children diagnosed with acute lymphoblastic leukemia over 10 years at a regional hematology center of a university hospital were analyzed to retrieve data concerning the complete blood count at first evaluation. Type and distribution of abnormal data, frequency of symptoms and physical findings at presentation were documented. Results The records of 203 children aged 0-15 years diagnosed with acute lymphoblastic leukemia from 2006 to 2016 were revisited. The results of the blood workup showed a median white blood cell count of 7120 × 109/L (range: 450-600,000 × 109/L), and a median hemoglobin concentration of 7.5 g/dL (range: 2.4-15.3 g/dL), whereas the median platelet count was 47,400 × 109/L (range: 4000-544,000 × 109/L). Leukocytosis and leukopenia were present in 36.6% and 36.1% of cases, respectively; anemia was diagnosed in 82.9% children. The order of frequency for major clinical symptoms was fatigue 62%, fever 60%, bone and joint pain 39%, hyporexia 33% and weight loss 21%, while main physical findings were hepatomegaly 78%, splenomegaly 63%, lymphadenopathy 57%, pallor 48%, and purpura 30%. Conclusion Data differing from those classically expected at diagnosis of acute lymphoblastic leukemia in children were documented in a cohort of Hispanic children over one decade with a wide spectrum of complete blood count abnormalities, forms of presentation and frequency of physical findings.

Revisiting the complete blood count and clinical findings at diagnosis of childhood acute lymphoblastic leukemia: 10-year experience at a single center.

BACKGROUND: Heterogeneity regarding clinical and laboratory findings at diagnosis of acute lymphoblastic leukemia exists. The frequency of complete blood count abnormalities and its combinations, symptoms and physical findings were investigated in Hispanic children from an open population at the diagnosis of acute lymphoblastic leukemia. METHODS: The patient charts and electronic records of under 16-year-old children diagnosed with acute lymphoblastic leukemia over 10 years at a regional hematology center of a university hospital were analyzed to retrieve data concerning the complete blood count at first evaluation. Type and distribution of abnormal data, frequency of symptoms and physical findings at presentation were documented. RESULTS: The records of 203 children aged 0-15 years diagnosed with acute lymphoblastic leukemia from 2006 to 2016 were revisited. The results of the blood workup showed a median white blood cell count of 7120 × 109/L (range: 450-600,000 × 109/L), and a median hemoglobin concentration of 7.5 g/dL (range: 2.4-15.3 g/dL), whereas the median platelet count was 47,400 × 109/L (range: 4000-544,000 × 109/L). Leukocytosis and leukopenia were present in 36.6% and 36.1% of cases, respectively; anemia was diagnosed in 82.9% children. The order of frequency for major clinical symptoms was fatigue 62%, fever 60%, bone and joint pain 39%, hyporexia 33% and weight loss 21%, while main physical findings were hepatomegaly 78%, splenomegaly 63%, lymphadenopathy 57%, pallor 48%, and purpura 30%. CONCLUSION: Data differing from those classically expected at diagnosis of acute lymphoblastic leukemia in children were documented in a cohort of Hispanic children over one decade with a wide spectrum of complete blood count abnormalities, forms of presentation and frequency of physical findings.

A tick beat in the electrocardiogram: Persistent third degree block as only manifestation of Lyme disease.

Lyme disease is the most common tick-borne illness in North America. A 23-year-old female presented to our emergency department with a chief complaint of sudden dyspnea and chest pain. An electrocardiogram revealed a third degree heart block. She was a resident of the Northeast region of Mexico and referred a recent travel to an endemic area for Borrelia burgdorferi in the center of Mexico in the past weeks. Lyme carditis was diagnosed after enzyme linked immunosorbent assay for IgM antibodies against B. burgdorferi was reported positive and corroborated by a confirmatory immunoblot analysis. Persistent AV block was the only manifestation in our patient, a presentation scarcely reported in literature.

Contributions of a regional approach to document hematologic disease in Mexico: a 10-year experience in an open population.

OBJECTIVES: To demonstrate the importance of regional efforts to register features and report frequency of hematology diseases in the context of incomplete national registries. METHODS: Frequencies and salient characteristics of hematologic diseases in Northeast Mexico were documented in a reference center at a tertiary care university hospital during the decade 2005-2015. Disease categories were grouped by age, sex and diagnosis. Age group distribution followed WHO guidelines in years as children (0-17), adults (18-64) and elders (+65). RESULTS: 2406 patients were included: 1239 (51.5%) were females and 1167 (48.5%) males; F:M ratio was 1.06:1; median age was 35 years (0-95). The frequency by age group included adults, 1370 cases (56.9%), children, 695 cases (28.9%), and elderly, 341 (14.2%). Most frequent diagnoses were acute lymphoblastic leukemia (ALL) 18.2% (n = 438), anemia 15.9% (n = 383), non-Hodgkin's lymphoma (NHL) 15.7% (n = 378), immune thrombocytopenic purpura (ITP) 9.8% (n = 235) and Hodgkin's lymphoma (HL) 6.5% (n = 156). Median age for the whole cohort was 35 years; for children, was 6 years, for adults 40 and for the elderly 73. Results for ALL, anemia and ITP were comparable to high-income countries; NHL, HL and chronic myeloid leukemia presented a decade earlier. DISCUSSION: Complete, opportune reliable information on the number of cases, age and sex distribution with the potential to influence strategies for timely diagnosis and treatment options for important hematologic diseases can be accrued by regional centers. CONCLUSION: Information on hematology diseases derived of regional registries in low-middle income countries is a reasonable alternative to complement and update national registries.

Survival Rates of Adults With Acute Lymphoblastic Leukemia in a Low-Income Population: A Decade of Experience at a Single Institution in Mexico.

BACKGROUND: The therapeutic progress for adults with acute lymphoblastic leukemia (ALL) has been slow, with a 5-year survival of 30% to 45% in developed countries. Scarce information is available regarding the treatment and survival rates from nonindustrialized populations. In the present study, the characteristics of adults with ALL at a single institution were documented. PATIENTS AND METHODS: The clinical files of patients aged ≥ 18 years who had been diagnosed with ALL from 2005 to 2015 at a reference center in Mexico were scrutinized. Overall survival (OS) and event-free survival (EFS) were determined using the Kaplan-Meier method. The hazard ratios for death and relapse were estimated using Cox regression analysis. RESULTS: A total of 94 adults were included. Their median age was 33 years; 69 (73.4%) had high-risk and 25 (26.6%) had standard-risk ALL. Of the 94 patients, 67 (71.3%) achieved complete remission (CR), 20 (21.3%) experienced disease resistance, and 7 (7.4%) died early during induction to remission, mainly of sepsis. The 5-year EFS and OS was 23.4% and 31.1% for the whole group and 24.9% and 38.9% for patients who achieved CR, respectively. Of the 94 patients, 50 (43.9%) died of sepsis or disease progression. Relapse developed in 43 patients (45.7%). The median survival after relapse was 6.93 months. Bone marrow was the most frequent site of relapse (21 patients [48.8%]) and conferred a significantly lower 5-year OS of 16.4%. CONCLUSION: Adults with ALL in Mexico had high-risk characteristics and an increased relapse rate; however, the OS after CR was similar to the greatest achieved in developed countries, suggesting that a threshold for curing adult ALL with current therapeutic strategies has been reached.

Non-Hodgkin lymphomas: impact of rituximab on overall survival of patients with diffuse large B-cell and follicular lymphoma.

BACKGROUND AND AIMS: Information comparing treatment outcome for diffuse large B cell (DLBCL) and follicular (FL) non-Hodgkin lymphoma (NHL) patients treated with schemes with and without rituximab from low- and middle-income countries is scarce. Clinical characteristics, response to therapy and long-term outcome of DLBCL and FL patients were studied. METHODS: Patients with DLBCL and FL diagnosed over 8 years at a reference center in northeast Mexico were included. Kaplan-Meier method was used to determine overall survival (OS) and progression-free survival (PFS). Cox regression model was used to evaluate the association between risk factors, rituximab therapy and clinical outcome. RESULTS: One hundred-sixteen patients with DLBCL and 65 with FL in advanced stages were included. Median age was 57.8 and 56 years, respectively. Clinical characteristics between groups receiving or not receiving rituximab were comparable. Stages III and IV were found in 63.8% of DLBCL and 84.6% in FL patients, respectively. OS and PFS at 60 months were 63.8 and 51.2% in DLBCL and 70.6 and 33.8% in FL. No difference in OS was found in DLBCL and FL when rituximab-based regimens vs. non rituximab-based regimens were compared, but a statistically significant difference was documented in PFS in FL patients. CONCLUSION: Addition of rituximab to CHOP-like regimens did not improve OS in DLBCL and FL NHL subtypes. In comparison to developed countries, diagnosis of NHL was made a decade earlier and in advanced clinical stages. Cost-efficiency of adding rituximab to therapy for these patients should be assessed.

Use of complementary and alternative medicine by patients with hematological diseases experience at a university hospital in northeast Mexico.

BACKGROUND: Complementary and alternative medicine includes a diverse group of medical and healthcare systems, practices and products not considered part of conventional medicine. Although there is information on unconventional practices in oncological diseases, specific data regarding the use of complementary and alternative medicine by hematology patients is scarce. OBJECTIVE: The aim of this study is to document the prevalence of this modality of unconventional therapy in patients with malignant and benign hematological diseases, particularly children with acute lymphoblastic leukemia. METHODS: An observational study of adult patients and guardians of children with malignant or benign hematological diseases was carried out by applying a structured questionnaire detailing the use and results of the most prevalent complementary and alternative medicine practices. RESULTS: One hundred and twenty patients were included; 104 had malignant and 16 had benign hematological diseases. The use of complementary and alternative medicine was greater in benign diseases but the difference was not statistically significant (64.7% versus 41.7%; p-value = 0.08). Patients and guardians with high school or college educations used these alternative practices more than patients with less schooling (60.7% versus 54.7%; p-value = 0.032). The use of folk remedies was most prevalent followed by herbal preparations and spiritual healing. Sixty-four percent of patients that used these unconventional practices reported improvement in their symptoms and increased capacity to perform daily activities. CONCLUSION: No significant difference was documented between patients with malignant or benign hematological diseases using these alternative practices. The majority of complementary and alternative medicine users reported improvement of the disease or chemotherapy-related symptoms.

Use of complementary and alternative medicine by patients with hematological diseases: experience at a university hospital in northeast Mexico

BACKGROUND: Complementary and alternative medicine includes a diverse group of medical and healthcare systems, practices and products not considered part of conventional medicine. Although there is information on unconventional practices in oncological diseases, specific data regarding the use of complementary and alternative medicine by hematology patients is scarce. OBJECTIVE: The aim of this study is to document the prevalence of this modality of unconventional therapy in patients with malignant and benign hematological diseases, particularly children with acute lymphoblastic leukemia. METHODS: An observational study of adult patients and guardians of children with malignant or benign hematological diseases was carried out by applying a structured questionnaire detailing the use and results of the most prevalent complementary and alternative medicine practices. RESULTS: One hundred and twenty patients were included; 104 had malignant and 16 had benign hematological diseases. The use of complementary and alternative medicine was greater in benign diseases but the difference was not statistically significant (64.7% versus 41.7%; p-value = 0.08). Patients and guardians with high school or college educations used these alternative practices more than patients with less schooling (60.7% versus 54.7%; p-value = 0.032). The use of folk remedies was most prevalent followed by herbal preparations and spiritual healing. Sixty-four percent of patients that used these unconventional practices reported improvement in their symptoms and increased capacity to perform daily activities. CONCLUSION: No significant difference was documented between patients with malignant or benign hematological diseases using these alternative practices. The majority of complementary and alternative medicine users reported improvement of the disease or chemotherapy-related symptoms.

Anticuerpos monoclonales en el diagnóstico de la tromboastenia de Glanzmann / Monoclonal antibodies in the diagnosis of Glanzmann's thrombasthenia

La tromboastenia de Glanzmann (TG) es una trombocitopatía causada pro el déficit en la cantidad de glucoproteínas IIb y IIIa (GP IIb/IIIa) de la membrana plaquetaria. Son descritos tres pacientes con TG; todos presentaban un tiempo de sangrado prolongado con recuento plaquetario normal y porcentajes mínimos de agregación plaquetaria cuando se usaron adenosin difosfato, colágena y epinefrina como inductores. Dos de los pacientes eran hermanos y tenían el antecedente de consanguinidad. Dos de los pacientes tenían historia de hemorragia principalmente de mucosas y el otro era asintomático. En los tres se realizaron estudios de inmunocitoquímica con la técnica de la imunoperoxidasa tipo indirecto usando un anticuerpo monoclonal (HPI-1D cortesía del Dr. W.L. Nichols Clínica Mayo, Rochester, Minnesota EUA) específico contra las GP IIb/IIIa. En los pacietnes sintomáticos la captación del anticuerpo fue totalmente negativa y en el que no presentó síntomas el anticuerpo fue parcialmente captado. Esta técnica en nuestra experiencia es más rápida y económica que la agregometría plaquetaria permitiendo realizar el diagnóstico con seguridad. La TG es una entidad aparentemente muy rara en nuestro país; sin embargo, es probable que su diagnóstico no establezca en muchos casos por carecer de la tecnología adecuada

Tombosis venosa profunda en un paciente con brucelosis y un probable inhibidor lupico: informe de un caso / Deep venous thrombosis in a patient with brucellosis and a probable lufoid inhibitor: report of a case

Se presenta el caso de una paciente de 18 años de edad que ingresó al hospital por un padecimiento de 15 días de evolución caracterizada por dolor y edema de los miembros inferiores. En su estudio intra-hospitalario se demostró brucelosis aguda por un título sérico de 1:800 y cultivos positivos para brucella sp.; trombosis venosa profunda iliofemoral en asociación con un tiempo de protrombina normal y de tromboplastina parcial prolongado. Haciendo una mezcla del plasma de la enferma con un volumen igual d eun plasma normal, se demostró un anticoagulante ciruclante y mediante el tiempo de coagulación con caolina, se identificó un inhibidor tipo lúpico. La paciente recibió tratamiento con tetraciclinas orales y anticoagulación sistémica y cuatro meses después de su egreso del hospital se encontraba asintomática y no recibía tratamiento alguno. Sus estudios de control, tanto para la brucellosis como de coagulación estaban normales. Se hacen algunas consideraciones acerca de una posible asociación entre la brucelosis y el anticoagulante circulante