Outcomes after intensive chemotherapy for secondary and myeloid-related changes acute myeloid leukemia patients aged 60 to 75 years old: a retrospective analysis from the PETHEMA registry.

Treatment options for patients with secondary acute myeloid leukemia (sAML) and AML with myeloid-related changes (AMLMRC) aged 60 to 75 years are scarce and unsuitable. A pivotal trial showed that CPX-351 improved complete remission with/without incomplete recovery (CR/CRi) and overall survival (OS) as compared with standard "3+7" regimens. We retrospectively analyze outcomes of 765 patients with sAML and AML-MRC aged 60 to 75 years treated with intensive chemotherapy, reported to the PETHEMA registry before CPX-351 became available. The CR/CRi rate was 48%, median OS was 7.6 months (95% confidence interval [CI]: 6.7-8.5) and event-free survival (EFS) 2.7 months (95% CI: 2-3.3), without differences between intensive chemotherapy regimens and AML type. Multivariate analyses identified age ≥70 years, Eastern Cooperative Oncology Group performance status ≥1 as independent adverse prognostic factors for CR/CRi and OS, while favorable/intermediate cytogenetic risk and NPM1 were favorable prognostic factors. Patients receiving allogeneic stem cell transplant (HSCT), autologous HSCT, and those who completed more consolidation cycles showed improved OS. This large study suggests that classical intensive chemotherapy could lead to similar CR/CRi rates with slightly shorter median OS than CPX-351.

Treatment of osteonecrosis of the femoral head with multiple drilling and bone marrow mesenchymal stem cells expanded ex vivo plus biomolecules derived from platelet-rich plasma: a case report.

Osteonecrosis of the femoral head (ONFH) is a debilitating condition that predominantly affects young individuals, resulting in disability and involving significant healthcare costs. Therefore, it is crucial to develop an effective therapeutic strategy to treat this debilitating disease. In this context, autologous bone marrow-derived mesenchymal stem cells (auto-BM-MSCs) have emerged as a promising approach for treating ONFH. In this case report, we applied this therapy to a patient with ONFH and evaluated both its safety and therapeutic benefits. The treatment consisted of the administration of a single dose of 4×107 ex vivo-expanded auto-BM-MSCs combined with biomolecules derived from platelet-rich plasma. These therapeutic agents were injected into the necrotic zone after accessing it through the technique of multiple small drillings. Subsequently, the progression of ONFH was assessed after 18 months of the auto-BM-MSC administration. Radiographic evaluation showed that the initial femoral head flattening persisted, but no further progression or coxofemoral arthritic changes were observed. Nevertheless, magnetic resonance imaging (MRI) demonstrated a significant improvement in the affected femoral head's area, resulting in a Kerboull angle of 80°, without evidence of flattening or a notable collapse compared to the preoperative condition. Furthermore, the patient exhibited a remarkable functional improvement, as evidenced by a modified Harris hip score of 90 points. The absence of any additional surgery reinforces the positive outcomes achieved through this therapeutic intervention. In conclusion, our case study provides evidence for using the ex vivo-expanded auto-BM-MSCs in combination with platelet-rich plasma-derived biomolecules as a viable and safe treatment for ONFH. However, further research and clinical trials are necessary to validate these promising findings.

A novel therapeutic management for diabetes patients with chronic limb-threatening ischemia: comparison of autologous bone marrow mononuclear cells versus allogenic Wharton jelly-derived mesenchymal stem cells.

BACKGROUND: Chronic limb-threatening ischemia (CLTI) represents the final stage of peripheral arterial disease. Approximately one-third of patients with CLTI are not eligible for conventional surgical treatments. Furthermore, patients with advanced stage of CLTI are prone to amputation and death. Thus, an effective therapeutic strategy is urgently needed. In this context, autologous bone marrow mononuclear cell (auto-BM-MNC) and allogeneic mesenchymal stem cells represent a promising therapeutic approach for treating CLTI. In this study, we compared the safety and beneficial therapeutic effect of auto-BM-MNC versus allogeneic Wharton jelly-derived mesenchymal stem cells (allo-WJ-MSCs) in diabetic patients with CLTI. METHODS: We performed a randomized, prospective, double-blind and controlled pilot study. Twenty-four diabetic patients in the advanced stage of CLTI (4 or 5 in Rutherford's classification) and a transcutaneous oxygen pressure (TcPO2) below 30 mmHg were randomized to receive 15 injections of (i) auto-BM-MNC (7.197 × 106 ± 2.984 × 106 cells/mL) (n = 7), (ii) allo-WJ-MSCs (1.333 × 106 cells/mL) (n = 7) or (iii) placebo solution (1 mL) (n = 10), which were administered into the periadventitial layer of the arterial walls under eco-Doppler guidance. The follow-up visits were at months 1, 3, 6, and 12 to evaluate the following parameters: (i) Rutherford's classification, (ii) TcPO2, (iii) percentage of wound closure, (iv) pain, (v) pain-free walking distance, (vi) revascularization and limb-survival proportion, and (vii) life quality (EQ-5D questionnaire). RESULTS: No adverse events were reported. Patients with CLTI who received auto-BM-MNC and allo-WJ-MSCs presented an improvement in Rutherford's classification, a significant increase in TcPO2 values‬, a reduction in the lesion size in a shorter time, a decrease in the pain score and an increase in the pain-free walking distance, in comparison with the placebo group. In addition, the participants treated with auto-BM-MNC and allo-WJ-MSCs kept their limbs during the follow-up period, unlike the placebo group, which had a marked increase in amputation. CONCLUSIONS: Our results showed that patients with CLTI treated with auto-BM-MNC and allo-WJ-MSCs conserved 100% of their limb during 12 months of the follow-up compared to the placebo group, where 60% of participants underwent limb amputation in different times. Furthermore, we observed a faster improvement in the allo-WJ-MSC group, unlike the auto-BM-MNC group. Trial registration This study was retrospectively registered at ClinicalTrials.gov (NCT05631444).

An early post-transplant relapse prediction score in multiple myeloma: a large cohort study from the chronic malignancies working party of EBMT.

Early relapse (ER) following Autologous Hematopoietic Cell Transplantation (AHCT) confers a poor prognosis. We therefore developed a novel scoring system to predict ER. A total of 14,367 AHCT-1 patients were transplanted between 2014 and 2019, and were conditioned with Melphalan 200 mg/m2 (Mel200) (n = 7228; 2014-2017) (training cohort); Mel200 (n = 5616; 2018-2019) or Mel140 (n = 1523; 2018-2019) (validation cohorts). PFS-12 and the Cumulative Incidence of Relapse at 12 months were 84.1% and 14.7% (training Mel200), 87.2% and 11.6% (validation Mel200), and 80.3% and 16.9% (validation Mel140), respectively. The points in the risk score were: 0, 1,2 for ISS stages I, II, and III; Disease status: 0 (CR/VGPR); 1 (PR); 2 (SD/MR); 4 (Relapse/Progression); and 1 for Karnofsky ≤ 70. The distribution of scores: 0 (24%), 1 (33.9%), 2 (29.6 %), 3 (9.5%), and ≥4 (2.7%). The score separated PFS-12, with the lowest risk group (n = 1752) having a PFS-12 of 91.7% and the highest risk group (n = 195) 57.1%. This also applied in cytogenetically high-risk patients. If the pre-score baseline risks are 15% (standard risk) and 25% (high-risk), a score of ≥4 confers calculated risks of 38% and 54%, respectively. This novel EBMT ER score, therefore, allows for the identification of five discrete prognostic groups.

Role of mesenchymal stromal cells derivatives in diabetic foot ulcers: a controlled randomized phase 1/2 clinical trial.

BACKGROUND: Diabetes-related foot complications have been identified as the most common isolated cause of morbidity among patients with diabetes and the leading cause of amputation. Therefore, new strategies to stimulate skin regeneration may provide a novel therapeutic approach to reduce non-healing ulcer disease. Recently, we demonstrated in proof-of-concept in humans that administration of allogeneic bone marrow mesenchymal stromal cellss derivatives (allo-hBM-MSCDs) is effective in a similar way to the use of allogeneic bone marrow mesenchymal stromal cellss (allo-hBM-MSCs) in grade 2 diabetic foot ulcers (DFUs). AIM: To assess the safety and efficacy profile of the allo-hBM-MSCDs relative to the conventional approach (PolyMen® dressing) in 1/2 clinical trial phases in patients with grade 1 and 2 DFUs. METHODS: In the present study, we used 2 doses of allo-hBM-MSCDs (1 mL) or 1 dose of allo-hBM-MSCs (1 × 106 cells) intradermally injected around wounds and assessed their safety and effectiveness, relative to the conventional approach (PolyMem dressing). Allo-hBM-MSCDs and allo-hBM-MSCs were produced in a certified Good Manufacturing Practice-type Laboratory. Patients with grade 1 and 2 DFUs were randomized to receive allo-hBM-MSCDs (n=12), allo-hBM-MSCs (n=6) or conventional treatment (PolyMem dressing) (n=10). The wound-healing process was macroscopically evaluated until the complete closure of the ulcers. RESULTS: No adverse events were reported. Patients with grade 1 and 2 DFUs treated with either allo-hBM-MSCDs or allo-hBM-MSCs, achieved greater percentages of wound closure, enhanced skin regeneration in shorter times and a greater ulcer-free survival relative to the patients who received conventional treatment. Finally, through proteomic analysis, we elucidated the proteins and growth factors that are secreted by allo-hBM-MSCs and relevant to the wound-healing process. In addition, by combining proteomics with Gene Ontology analysis, we comprehensively classified secreted proteins on both biological process and molecular function. CONCLUSIONS: In this phase 1/2 trial, our cumulative results suggest that 2 doses of allo-hBM-MSCDs combined with a wound dressing are a safe and effective treatment for grade 1 and 2 DFUs.

Mesenchymal stem cells for critical limb ischemia: their function, mechanism, and therapeutic potential.

Peripheral arterial disease is atherosclerotic occlusive disease of the lower extremity arteries and afflicts hundreds of millions of individuals worldwide. Its most severe manifestation is chronic limb-threatening ischemia (Petersen et al. (Science 300(5622):1140-2, 2003)), which is associated with severe pain at rest in the limbs, which progresses to necrosis, limb amputation, and/or death of the patient. Consequently, the care of these patients is considered a financial burden for both patients and health systems. Multidisciplinary endeavors are required to address this refractory disease and to find definitive solutions that lead to improved living conditions. Revascularization is the cornerstone of therapy for preventing limb amputation, and both open vascular surgery and endovascular therapy play a key role in the treatment of patients with CLI. Around one-third of these patients are not candidates for conventional surgical treatment, however, leading to higher amputation rates (approaching 20-25% at one year) with high morbidity and lower quality of life. Advances in regenerative medicine have enabled the development of cell-based therapies that promote the formation of new blood vessels. Particularly, mesenchymal stem cells (MSCs) have emerged as an attractive therapeutic agent in various diseases, including CLI, due to their role in tissue regeneration and immunomodulation. This review discusses the characteristics of MSCs, as well as their regenerative properties and their action mechanisms on CLI.

Decellularized Tissues for Wound Healing: Towards Closing the Gap Between Scaffold Design and Effective Extracellular Matrix Remodeling.

The absence or damage of a tissue is the main cause of most acute or chronic diseases and are one of the appealing challenges that novel therapeutic alternatives have, in order to recover lost functions through tissue regeneration. Chronic cutaneous lesions are the most frequent cause of wounds, being a massive area of regenerative medicine and tissue engineering to have efforts to develop new bioactive medical products that not only allow an appropriate and rapid healing, but also avoid severe complications such as bacterial infections. In tissue repair and regeneration processes, there are several overlapping stages that involve the synergy of cells, the extracellular matrix (ECM) and biomolecules, which coordinate processes of ECM remodeling as well as cell proliferation and differentiation. Although these three components play a crucial role in the wound healing process, the ECM has the function of acting as a biological platform to permit the correct interaction between them. In particular, ECM is a mixture of crosslinked proteins that contain bioactive domains that cells recognize in order to promote migration, proliferation and differentiation. Currently, tissue engineering has employed several synthetic polymers to design bioactive scaffolds to mimic the native ECM, by combining biopolymers with growth factors including collagen and fibrinogen. Among these, decellularized tissues have been proposed as an alternative for reconstructing cutaneous lesions since they maintain the complex protein conformation, providing the required functional domains for cell differentiation. In this review, we present an in-depth discussion of different natural matrixes recently employed for designing novel therapeutic alternatives for treating cutaneous injuries, and overview some future perspectives in this area.

Real-World Evidence of Epidemiology and Clinical Outcomes in Multiple Myeloma, Findings from the Registry of Hemato-Oncologic Malignancies in Colombia, Observational Study.

INTRODUCTION/BACKGROUND: Multiple Myeloma (MM) is a plasma cell derived clonal disorder that represents around 1% of all newly diagnosed neoplasms. Limited data regarding MM treatment in Latin America is available, and access to novel agents for a substantial portion of the population is limited by their high costs. MATERIALS (OR PATIENTS) AND METHODS: RENEHOC is a bidirectional (retrospective and prospective) multicenter observational registry of hematological malignancies in Colombia. MM patients included up to July 2020 were analyzed on this report. RESULTS: 890 are reported with a median follow-up of 18 months (IQR: 7-42 months). Patients were classified by age group (≤ or > 65 years). Median age at diagnosis was 67 years (IQR: 59-75 years) and 47.1% of patients were women. 709 patients (79.6%) received Bortezomib-based schemes as part of the first line. Two hundred and fifty-two patients (28.3%) were consolidated with Autologous Stem Cell Transplantation (ASCT) in first-line. ASCT consolidation and age were the main independent factors influencing outcomes; in the non-ASCT cohort, 5-year overall survival was 48.7% (CI 41.8-55.2) compared to 80.7% (CI 73-86.4) in ASCT patients. CONCLUSION: This data depicts the reality of MM in Colombia, which likely reflects other Latin American countries, where access barriers to diagnosis and treatment are echoed in advanced stage diagnosis and a low rate of transplants. These seem to negatively impact survival despite the availability of most novel drugs approved for this disease. Thus, emphasizing the paradox that prevails in most of the region: availability without equitable access.

Effect of biomolecules derived from human platelet-rich plasma on the ex vivo expansion of human adipose-derived mesenchymal stem cells for clinical applications.

Mesenchymal stem cells are a tool in cell therapies but demand a large cell number per treatment, for that, suitable culture media is required which contains fetal bovine serum (FBS). However, for cell-based therapy applications, the use of FBS is problematic. Several alternatives to FBS have been explored, including human derivatives from platelet-rich plasma (hD-PRP). Although various studies have evaluated the impact of hD-PRP on MSC proliferation and differentiation, few of them have assessed their influence on processes, such as metabolism and gene expression. Here, we cultured human adipose-derived MSCs (hAD-MSCs) in media supplemented with either 10% hD-PRP (hD-PRP-SM) or 10% FBS (FBS-SM) in order to characterize them and evaluate the effect of hD-PRP on cell metabolism, gene expression of associated regenerative factors, as well as chromosome stability during cell expansion. We found that hAD-MSCs cultured in hD-PRP-SM have a greater cell elongation but express similar surface markers; in addition, hD-PRP-SM promoted a significant osteogenic differentiation in the absence of differentiation medium and increased the growth rate, maintaining chromosomal stability. In terms of cell metabolic profile, hAD-MSC behavior did not reveal any differences between both culture conditions. Conversely, significant differences in collagen I and angiopoietin 2 expression were observed between both conditions. The present results suggest that hD-PRP may influence hAD-MSC behavior.

Impact of measurable residual disease by decentralized flow cytometry: a PETHEMA real-world study in 1076 patients with acute myeloid leukemia.

The role of decentralized assessment of measurable residual disease (MRD) for risk stratification in acute myeloid leukemia (AML) remains largely unknown, and so it does which methodological aspects are critical to empower the evaluation of MRD with prognostic significance, particularly if using multiparameter flow cytometry (MFC). We analyzed 1076 AML patients in first remission after induction chemotherapy, in whom MRD was evaluated by MFC in local laboratories of 60 Hospitals participating in the PETHEMA registry. We also conducted a survey on technical aspects of MRD testing to determine the impact of methodological heterogeneity in the prognostic value of MFC. Our results confirmed the recommended cutoff of 0.1% to discriminate patients with significantly different cumulative-incidence of relapse (-CIR- HR:0.71, P < 0.001) and overall survival (HR: 0.73, P = 0.001), but uncovered the limited prognostic value of MFC based MRD in multivariate and recursive partitioning models including other clinical, genetic and treatment related factors. Virtually all aspects related with methodological, interpretation, and reporting of MFC based MRD testing impacted in its ability to discriminate patients with different CIR. Thus, this study demonstrated that "real-world" assessment of MRD using MFC is prognostic in patients at first remission, and urges greater standardization for improved risk-stratification toward clinical decisions in AML.

Hydroxychloroquine as Prophylaxis for Coronavirus SARS-CoV-2 Infection: Review of the Ongoing Clinical Trials / Hidroxicloroquina como profilaxis para la infección por coronavirus SARS-CoV-2: revisión de los ensayos clínicos en curso

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Different outcomes for transplant-eligible newly diagnosed multiple myeloma patients in Latin America according to the public versus private management: a GELAMM study.

The aim of this study was to describe clinical and survival characteristics of transplant-eligible multiple myeloma (MM) patients in Latin America (LA), with a special focus on differences between public and private healthcare facilities. We included 1293 patients diagnosed between 2010 and 2018. A great disparity in outcomes and survival between both groups was observed. Late diagnosis and low access to adequate frontline therapy and ASCT in public institutions probably explain these differences. Patients treated with novel drug induction protocols, followed by autologous stem cell transplantation (ASCT) and maintenance, have similar overall survival compared to that published internationally.

Mesenchymal stem cells derivatives as a novel and potential therapeutic approach to treat diabetic foot ulcers.

SUMMARY: Diabetic foot ulcer morbidity and mortality are dramatically increasing worldwide, reinforcing the urgency to propose more effective interventions to treat such a devastating condition. Previously, using a diabetic mouse model, we demonstrated that administration of bone marrow mesenchymal stem cells derivatives is more effective than the use of bone marrow mesenchymal stem cells alone. Here, we used the aforementioned treatments on three patients with grade 2 diabetic foot ulcers and assessed their beneficial effects, relative to the conventional approach. In the present study, two doses of cell derivatives, one dose of mesenchymal stem cells or one dose of vehicle (saline solution with 5% of human albumin), were intradermally injected around wounds. Wound healing process and changes on re-epithelialization were macroscopically evaluated until complete closure of the ulcers. All ulcers were simultaneously treated with conventional treatment (PolyMen® dressing). Patients treated with either cell derivatives or mesenchymal stem cells achieved higher percentages of wound closure in shorter times, relative to the patient treated with the conventional treatment. The cell derivative and mesenchymal stem cells approaches resulted in complete wound closure and enhanced skin regeneration at some point between days 35 and 42, although no differences between these two treatments were observed. Moreover, wounds treated with the conventional treatment healed after 161 days. Intradermal administration of cell derivatives improved wound healing to a similar extent as mesenchymal stem cells. Thus, our results suggest that mesenchymal stem cell derivatives may serve as a novel and potential therapeutic approach to treat diabetic foot ulcers. LEARNING POINTS: In diabetic mouse models, the administration of mesenchymal stem cells derivatives have been demonstrated to be more effective than the use of marrow mesenchymal stem cells alone. Mesenchymal stem cells have been explored as an attractive therapeutic option to treat non-healing ulcers. Mesenchymal stem cells derivatives accelerate the re-epithelialization on diabetic foot ulcers.

Epidemiology of Hematologic Malignancies in Real-World Settings: Findings From the Hemato-Oncology Latin America Observational Registry Study.

PURPOSE: Limited information is available on multiple myeloma (MM), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma (NHL) management in Latin America. The primary objective of the Hemato-Oncology Latin America (HOLA) study was to describe patient characteristics and treatment patterns of Latin American patients with MM, CLL, and NHL. METHODS: This study was a multicenter, retrospective, medical chart review of patients with MM, CLL, and NHL in Latin America identified between January 1, 2006, and December 31, 2015. Included were adults with at least 1 year of follow-up (except in cases of death within 1 year of diagnosis) treated at 30 oncology hospitals (Argentina, 5; Brazil, 9; Chile, 1; Colombia, 5; Mexico, 6; Panama/Guatemala, 4). RESULTS: Of 5,140 patients, 2,967 (57.7%) had NHL, 1,518 (29.5%) MM, and 655 (12.7%) CLL. Median follow-up was 2.2 years for MM, 3.0 years for CLL, and 2.2 years for NHL, and approximately 26% died during the study observation period. Most patients had at least one comorbidity at diagnosis. The most frequent induction regimen was thalidomide-based chemotherapy for MM and chlorambucil with or without prednisone for CLL. Most patients with NHL had diffuse large B-cell lymphoma (DLBCL; 49.1%) or follicular lymphoma (FL; 19.5%). The majority of patients with DLBCL or FL received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. CONCLUSION: The HOLA study generated an unprecedented level of high-quality, real-world evidence on characteristics and treatment patterns of patients with hematologic malignancies. Regional disparities in patient characteristics may reflect differences in ethnoracial identity and level of access to care. These data provide needed real-world evidence to understand the disease landscape in Latin America and may be used to inform clinical and health policy decision making.

Terapia secuencial: una opción en el paciente hemofílico que no responde al manejo con monoterapia con agentes puente, estudio observacional del GrHeCol (Grupo Hemofilia Colombia) / Sequential therapy: an option for hemophiliac patients not responding to monotherapy with bypassing agents. Observational study of the GrHeCol (Grupo Hemofilia Colombia)

RESUMEN Introducción: la hemofilia A y B severa son condiciones que predisponen al sangrado espontáneo. Una de las complicaciones de la terapia con concentrados de factores de coagulación es el desarrollo de anticuerpos o inhibidores contra los factores VIII o IX. El tratamiento en casos de inhibidores de título alto, para el control de la hemorragia, es la administración de agentes puente como el complejo protrombínico activado y Factor VII recombinante activado. La respuesta a cada uno de ellos no es predecible, en algunos casos puede ser necesario el uso de la terapia secuencial cuando esta estrategia falla. Objetivo: reportar cinco casos de hemofilia A severa e inhibidores de título alto con sangrado severo, sin respuesta clínica con monoterapia y que recibieron terapia secuencial. Métodos: estudio multicéntrico, descriptivo, observacional. Las variables cualitativas se presentan con frecuencias absolutas y relativas, y las cuantitativas se resumen con medidas de tendencia central. Resultados: cuatro pacientes evaluados que aportaron cinco eventos, la mediana de edad 20 años; mediana de días de monoterapia 10; 8,6 días de terapia secuencial, tiempo a resolver el sangrado cuatro días. Ausencia de complicaciones trombóticas. Conclusiones: la terapia secuencial es una opción para aquellos pacientes que no responden a la monoterapia y requieren control hemostático. En los cinco casos reportados, la terapia secuencial logró controlar el sangrado sin complicaciones.

SUMMARY Introduction and objectives: Patients diagnosed with severe hemophilia are at risk of developing inhibitors of low or high title, being the treatment of choice for this latter group of patients the immune tolerance therapy (ITI). In cases where the immune tolerance fails or presents bleeding events, we can use activated prothrombin complex (APCC) or Recombinant activated factor VII (rFVIIa); however, patients may fail to these agents as monotherapy. The aim of this paper is to report five cases of severe hemophilia and high titer inhibitors with mayor bleeding, which fail to respond to monotherapy and required sequential therapy. Methods: Case report study, qualitative variables are presented as absolute and relative frequencies and quantitative are summarized with measures of central tendency. Results: Five patients with median age 20 years; monotherapy treatment with median 10 days; 8.6 days of sequential therapy, time to control the bleeding: 4 days. There were no thrombotic complications. Conclusions: Sequential therapy is an option for patients who do not respond to monotherapy and requires hemostatic control. In all the cases of this report, the patients were responsive with bleeding control.

The role of bone marrow mesenchymal stromal cell derivatives in skin wound healing in diabetic mice.

Mesenchymal stromal cells (MSCs) have shown to be a promising tool in cell therapies to treat different conditions. Several pre-clinical and clinical studies have proved that the transplantation of MSCs improves wound healing. Here, we compare the beneficial effects of mouse bone marrow-derived allogeneic MSCs (allo-mBM-MSCs) and their acelullar derivatives (allo-acd-mMSCs) on skin wound healing in Non-Obese Diabetic (NOD) mice. One dose of allo-mBM-MSCs (1×106 cells) or one dose of allo-acd-mMSCs (1X) were intradermally injected around wounds in 8-10 week old female NOD mice. Wound healing was evaluated macroscopically (wound closure) every two days, and microscopically (reepithelialization, dermoepidermal junction, skin appendage regeneration, leukocyte infiltration, vascularization, granulation tissue formation, and density of collagen fibers in the dermis) after 16 days of MSC injection. In addition, we measured growth factors and specific proteins that were present in the allo-acd-mMSCs. Results showed significant differences in the wound healing kinetics of lesions that received allo-acd-mMSCs compared to lesions that received vehicle or allo-mBM-MSCs. In particular, mice treated with allo-acd-mMSCs reached significantly higher percentages of wound closure at day 4, 6 and 8, relative to the allo-mBM-MSCs and vehicle groups (p < 0.05), while wound closure percentages could not be statistically distinguished between the allo-mBM-MSCs and vehicle groups. Also, allo-acd-mMSCs had a greater influence in the skin would healing process. Specifically, they caused a less pronounced inflammatory severe response (p < 0.0001), more granulation tissue formation at an advanced stage (p < 0.0001), and higher density of collagen fibers (p < 0.05) compared to the other groups. Nevertheless, at day 16, both allo-mBM-MSCs and allo-acd-mMSCs revealed a higher effect on the recovery of the quality skin (continuous epidermis; regular dermoepidermal junction and skin appendages) relative to untreated lesions (p < 0.0001), but not between them. On the other hand, ELISA analyses indicated that the allo-acd-mMSCs contained growth factors and proteins relevant to wound healing such as IGF-1, KGF, HGF, VEGF, ANG-2, MMP-1, CoL-1 and PGE2. Compared to allo-acd-mMSCs, the administration of allo-mBM-MSCs is insufficient for wound healing in diabetic mice and delays the therapeutic effect, which maybe explained by the fact that trophic factors secreted by MSCs are critical for skin regeneration, and not the cells per se, suggesting that MSCs may require some time to secrete these factors after their administration.

Descripción de las caracteristicas clínicas de las neoplasias mieloproliferativas crónicas (NMPC). Primer informe del registro colombiano de NMPC / Description of the clinical characteristics of chronic myeloproliferative neoplasms (MPNs). First report of the colombian registry of MPNs

Resumen Introducción y objetivos: las neoplasias mieloproliferativas crónicas (NMPC) son relativamente raras, con incidencias que varían entre 0.47-1.03/100 000 habitantes. Se presenta el primer informe del trabajo del registro colombiano de NMPC, cuyo objetivo es describir las características clínicas de estos pacientes en nuestro país. Material y métodos: estudio descriptivo observacional, multicéntrico, retrospectivo y prospectivo en ocho centros del país, de abril de 2013 a diciembre de 2014. Las variables cualitativas se presentan con frecuencias absolutas y relativas; y las cuantitativas se resumen en medidas de tendencia central y dispersión. Resultados: once centros fueron aprobados, ocho ingresaron pacientes. En los primeros 179 casos reportados, 50% eran hombres, la edad promedio al diagnóstico 58.7 años (rango 19-92). Noventa y tres muestran trombocitemia esencial (TE); 55, policitemia vera (PV); y 31, mielofibrosis (MF). El 41% tenía esplenomegalia al diagnóstico; el 20% tuvo complicaciones trombóticas; y 12.85%, sangrado. Sólo en 57.5% se realizó JAK; de ellos, en 53.5% fue positivo, en especial sólo 60% de las PV. El 8% de los casos no tenía estudio de médula ósea, el 29.3% tiene algún grado de fibrosis. El hallazgo más frecuente fue hiperplasia megacariocítica en 59.78%. Más de 50% de pacientes estaban sintomáticos al diagnóstico. Sólo el 11% no recibió tratamiento farmacológico; los más frecuentes fueron hidroxiurea en 149 casos y ASA en 79. Con promedio de seguimiento de 52.6 meses; el 97.21% de los pacientes están vivos. Conclusiones: los hallazgos sugieren que algunas características de las NMPC podrían ser diferentes a lo reportado en otras series, lo que valida la importancia del esfuerzo de recoger información local.

Abstract Introduction and objectives: chronic MPNs are relatively rare, with incidences varying between 0.47-1.03 / 100 000 inhabitants. The first report of the work of the Colombian registry of chronic MPNs, whose objective is to describe the clinical characteristics of these patients in our country, is presented. Materials and methods: descriptive observational, multicenter, retrospective and prospective study in eight centers of the country, from April 2013 to December 2014. Qualitative variables are presented with absolute and relative frequencies, and the quantitative ones are summarized in measures of central tendency and dispersion. Results: eleven centers were approved; 8 admitted patients. In the first 179 cases reported, 50% were men; the average age at diagnosis was 58.7 years (range 19-92). Ninety-three present essential thrombocythemia (ET); 55, polycythemia vera (PV); and 31, myelofibrosis (MF). 41% had splenomegaly at diagnosis; 20% had thrombotic complications, and 12.85%, bleeding. JAK was performed in only 57.5%. Of them, in 53.5% was positive, especially in only 60% of the PV. 8% of the cases had no bone marrow study; 29.3% had some degree of fibrosis. The most frequent finding was megakaryocytic hyperplasia in 59.78%. More than 50% of patients were symptomatic at diagnosis. Only 11% did not receive pharmacological treatment, being the most frequent hydroxyurea in 149 cases and ASA in 79, with an average follow-up of 52.6 months. 97.21% of patients are alive. Conclusions: the findings suggest that some characteristics of chronic MPNs could be different from those reported in other series, which validates the importance of the effort to collect local information.