Risk factors for adverse outcomes following haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide: a two-center analysis.

Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative therapy for several malignant hematologic diseases and alternative donors, including haploidentical, play a significant role in HCT. Despite the increasing use of haplo-HCT with PTCy, some questions remain open. The objective of the present study was to investigate risk factors for adverse outcomes after haplo-HCT with PTCy. This is a retrospective study conducted at two Brazilian centers. A total of 103 patients with hematologic malignancies who underwent first allogeneic, haploidentical HCT with PTCy were included. Risk factors for death were age at transplant (HR = 1.03 for each year; p = 0.002) and high/very high disease risk index (DRI; HR = 2.77; p = 0.0007) and mother as the donor compared with other donors (HR = 3.53; p = 0.005). In multivariate analysis, PFS was significantly poorer for older patients (HR = 1.02; p = 0.006), high/very high DRI (HR = 2.39; p = 0.003), and mother as the donor compared with other donors (HR = 3.18; p = 0.006). Relapse rate was higher for high/very high DRI (HR = 4.01; p = 0.002) and mother as the donor compared with other donors (HR = 2.52; p = 0.05). NRM was higher for older patients (HR = 1.03 for each year; p = 0.03). Tacrolimus was a protective factor for grades II-IV aGVHD (HR = 0.46; p = 0.04) compared with cyclosporine. Peripheral blood (PBSC) was a risk factor for cGVHD (HR = 3.48; p = 0.006), while tacrolimus was protective (HR = 0.30; p = 0.009). Mother as the donor compared with other donors was also a risk factor for poorer OS, PFS, and relapse, suggesting that this combination should be avoided. Tacrolimus was protective for both grades II-IV aGVHD and cGVHD, suggesting that tacrolimus may be more effective than cyclosporine in preventing GVHD. PBSC was a risk factor for cGVHD without any impact on relapse. Prospective studies comparing tacrolimus with cyclosporine are awaited.

Impact of Anti-CMV IgG Titers and CD34 Count Prior to Hematopoietic Stem Cell Transplantation from Alternative Donors on CMV reactivation.

Cytomegalovirus (CMV) reactivation remains one of the main infectious complications following hematopoietic stem cell transplantation (HSCT). In this study, we explored the role of anti-CMV antibody titers in HSCT from alternative donors and to compare the risk of CMV reactivation between posttransplant cyclophosphamide-based haploidentical HSCT and antithymocyte globulin-based unrelated donor (URD) HSCT. We included 98 CMV-positive patients, 30 undergoing haploidentical HSCT and 68 undergoing URD HSCT. The majority of patients had a malignant disease (84%), received a myeloablative conditioning regimen (78%), and received a bone marrow graft (90%). The median pretransplantation anti-CMV IgG level was 109 U/mL. With median follow-up of 2.2 years, a total of 72 CMV reactivations occurred in 50 patients. There was no difference in CMV reactivation pattern between haploidentical HSCT recipients and URD HSCT recipients. In multivariable analysis until the first event, the incidence of CMV reactivation was higher in patients with anti-CMV IgG levels >100 U/mL (hazard ratio [HR], 2.38; P = .005) and in patients diagnosed with grade II-IV acute graft-versus-host disease (GVHD) (HR, 10.8; P = .003) after day +50 and lower in patients who received higher doses of CD34 cells (HR, .44; P = .006). In multivariable analysis for recurring events, the incidence of CMV reactivation was higher in patients receiving reduced-intensity conditioning (HR, 1.69: P = .04) and in patients with acute GVHD (HR, 1.88; P = .02), and lower in those who received higher doses of CD34 cells (HR, .55; P = .01). In summary, we have shown that pretransplantation anti-CMV IgG titers are correlated with CMV reactivation risk. More studies are needed to assess how this information can be incorporated in HSCT. The use of high-dose cellular grafts, a modifiable risk factor, also protects against CMV reactivation.

Serum ferritin as risk factor for sinusoidal obstruction syndrome of the liver in patients undergoing hematopoietic stem cell transplantation.

Hepatic sinusoidal obstruction syndrome (SOS) is a serious complication in hematopoietic stem cell transplant (HSCT) recipients. To determine the impact of pretransplantation hyperferritinemia on the risk of SOS after HSC transplantation, we retrospectively studied 427 HSCT recipients (179 autologous and 248 allogeneic). Serum ferritin levels were measured before transplantation. Patients with and without a diagnosis of SOS were compared regarding demographics; underlying disease; transplant characteristics; receipt of imatinib, busulfan, total body irradiation, gemtuzumab, vancomycin, acyclovir, or methotrexate; and baseline serum ferritin. Univariate and multivariate (stepwise logistic regression) analyses were performed. SOS was diagnosed in 88 patients (21%) at a median of 10 days (range, 2-29 days) after transplantation. By multivariate analysis, allogeneic HSC transplantation (odds ratio [OR] = 8.25; 95% confidence interval [95% CI], 3.31-20.57), receipt of imatinib (OR = 2.60; 95% CI, 1.16-5.84), receipt of busulfan (OR = 2.18; 95% CI, 1.25-3.80), and ferritin serum level higher than 1000 ng/dL (OR = 1.78; 95% CI, 1.02-3.08) were risk factors for SOS. A ferritin serum level higher than 1000 ng/dL in the pretransplantation period is an independent risk factor for SOS. The results suggest the need for prospective studies addressing the use of iron chelation in the pretransplantation period.

Streptococcal bacteraemia in patients submitted to hematopoietic stem cell transplantation: the role of tooth brushing and use of chlorhexidine.

A retrospective evaluation of 73 consecutive recipients of hematopoietic stem cell transplantation (HSCT) was conducted to investigated the role of oral care and incidence of streptococcal bacteremia in patients submitted to hematopoietic stem cell transplantation. Patients were retrospectively evaluated and divided into group A (GA=38) and group B (GB=35). During hospitalization patients from GA performed oral hygiene daily with extra soft toothbrush and toothpaste besides performing mouth cleaning with an ethanol-free 0.12% chlorhexidine solution tree times a day. In contrast GB patients performed mouth cleaning with extra soft toothbrush and toothpaste, but no chlorhexidine was used. Using the Chi square test it was observed that all patients from GA presented negative blood culture for alpha-hemolytic Streptococcus viridans and Candida albicans and only 1 patient without oral mucositis from GB presented positive blood cultures for Streptococcus intermedius (p=0.48). The results indicate that methodology used for oral care before the HSCT and the practice of tooth brushing during the period were effective in preventing streptococcal bacteremia. Moreover, our data suggest that the mouth cleaning with chlorhexidine during HSCT may be not mandatory.

Parvovirus B19 in the Context of Hematopoietic Stem Cell Transplantation: Evaluating Cell Donors and Recipients.

BACKGROUND: Parvovirus B19 (B19V) is a common human pathogen, member of the family Parvoviridae. Typically, B19V has been found to infect erythroid progenitors and cause hematological disorders, such as anemia and aplastic crisis. However, the persistence of genomic deoxyribonucleic acid (DNA) has been demonstrated in tonsils, liver, skin, brain, synovial, and testicular tissues as well as bone marrow, for both symptomatic and asymptomatic subjects. Although the molecular and cellular mechanisms of persistence remain undefined, it raises questions about potential virus transmissibility and its effects in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. METHODS: With this aim, we retrospectively screened allogeneic stem cell donors from 173 patients admitted for allo-HSCT from January 2008 to May 2013 using a seminested polymerase chain reaction approach. RESULTS: We found 8 positive donor samples, yielding a 4.6% of parvovirus prevalence (95% confidence interval, 2.36-8.85). Pre- and post-HSCT samples (n = 51) from the 8 recipients of the positive donors were also investigated, and 1 case exhibited B19V DNA in the post-HSCT follow-up (D + 60). Direct DNA sequencing was performed to determine the genotype of isolates and classification, performed by phylogenetic reconstruction, showed a predominance of genotype 1a, whereas the rare genotype 3b was detected in 2 additional patients. By molecular cloning, different B19V 1a substrains polymorphisms were evidenced in the single case in which donor and its recipient were B19V+. CONCLUSIONS: Our results suggest that HSCT allografts are not a main source for B19V transmission, pointing to potential events of reinfection or endogenous viral reactivation.

Anatomía e histoquímica de Tarenaya hassleriana (cleomaceae), especie de interés medicinal / Anatomy and histochemistry of Tarenaya hassleriana (cleomaceae), an interesting medicinal species

La decocción de la planta de Tarenaya hassleriana es utilizada en la región del Río de La Plata por sus propiedades como rubefaciente, digestiva, y antiescorbútica. El objetivo del estudio fue investigar caracteres de la hoja y tallo para identificar esta especie a partir de muestras enteras o fragmentadas. Se emplearon técnicas habituales de microscopia óptica y análisis histoquímico para identificar almidón, sustancias lipofílicas, fenólicas y mirosina. Los caracteres diagnósticos fueron: en la hoja, folíolos con venación eucamptódroma, con estomas anomocíticos presentes en ambas caras; tricomas glandulares uniseriados y pluriseriados, con cabezas unicelulares y pluricelulares conteniendo sustancias lipofílicas; mesofilo dorsiventral; en el tallo, la corteza primaria formada por varias capas de colénquima tangencial seguido de parénquima; el cilindro vascular secundario rodea la médula sólida, en cuyo parénquima se halló almidón, cristales poliédricos y esferocristales. Se detectaron idioblastos de mirosina en la epidermis y parénquimas de la hoja y el tallo. Los parámetros micrográficos descriptos garantizan una correcta identificación de T. hassleriana.

Plant decoction of Tarenaya hassleriana is used as a traditional medicine in the Río de La Plata area. It has rubefacient, digestive, and antiscorbutic properties. The aim of this study was to investigate leaf and stem microcharacters to identify this species from whole or fragmented samples. The usual techniques of optical microscopy were employed. Histochemical tests for starch, lipophilic substances, phenolic substances, and mirosina were used. The main differential traits were: leaflets with eucamptodromous venation, amphistomatic with anomocytic stomata type; uniseriate and pluriseriate glandular trichomes, with unicellular and pluricellular heads containing lipophilic substances; dorsiventral mesophyll; stem with a primary cortex formed by tangential collenchyma followed by parenchyma; the secondary vascular cylinder surrounding the pith with starch, polyhedral microcrystals and spherocrystals. Idioblast of myrosin were detected in the epidermis and parenchyma of leaves and stems. The micrographic parameters described ensure a correct identification of T. hassleriana.

Anatomía comparada de raíces medicinales de hierbas terrestres rioplatenses (Buenos Aires, República Argentina) / Comparative anatomy of medicinal roots of rioplatenses terrestrial herbs (Buenos Aires, Argentine Republic)

Se estudió la anatomía de la raíz de 22 hierbas terrestres pertenecientes a 10 familias que se utilizan en medicina vernácula en la región rioplatense. Para disponer de un patrón que defina la autenticidad botánica se planteó el objetivo de generar una clave diacrítica basada en la micrografía de las raíces. Se utilizó material fresco y de herbario que fue fijado en formalina-aceto-alcohólica, y en el caso de ejemplares de herbario fueron rehidratados previo a su fijación. Para las preparaciones se realizaron cortes a mano alzada y con micrótomo de rotación, para luego efectuar la tinción y el montaje de acuerdo con técnicas convencionales. Se realizaron análisis histoquímicos para la identificación de almidón, sustancias lipídicas y fenólicas. Algunos de los principales caracteres micrográficos de identificación de las raíces fueron: presencia de estructura secundaria anómala en Alternanthera philoxeroides y A. pungens, Dysphania ambrosioides y Mirabilis jalapa; presencia de corteza aerenquimática en Hyptis mutabilis y Pluchea sagittalis; tipo y distribución de estructuras secretoras: esquizógenas en Bidens pilosa, Conyza bonariensis, Solidago chilensis y Xanthium spinosum, lisígenas en M. jalapa y tubos laticíferos en Cichorium intybus y Taraxacum officinale; presencia de drusas en A. philoxeroides y A. pungens , rafidios en Cyclopogon elatus y M. jalapa o arena cristalina en D. ambrosioides y Salpichroa origanifolia; presencia de xilema secundario con poros solitarios dispuestos al azar en Marrubium vulgare, múltiples radiales en Raphanus sativus, solitarios y múltiples radiales en Lepidium auriculatum y L. bonariense. Como resultado de los estudios histoquímicos se hallaron sustancias lipídicas en las paredes celulares de la endodermis, en el súber, y en forma de gotas oleosas en las estructuras secretoras esquizógenas de las Asteraceae; se observó inulina en el parénquima de las raíces de especies de la familia Asteraceae y amiloplastos en las raíces de Lepidium, Mirabilis, Raphanus y Salpichroa. (AU)

Relevamiento etnofarmacobotánico de plantas medicinales usadas en tres zonas diferentes del cantón Quevedo, Provincia de Los Ríos (Ecuador) / Ethnopharmacobotanical survey of medicinal plants used in three different areas of the canton Quevedo, Los Rios Province (Ecuador)

La información sobre nombres vulgares,parte usada, indicaciones, forma de preparación y administración de las plantas utilizadas en medicina tradicional en Quevedo (Ecuador) fue recolectada mediante entrevistas, a tres "sanadores" considerados referentes de los hábitos medicinales de sus respectivas comunidades. Las especies citadas fueron organizadas en forma de tabla donde se describen sus usos terapéuticos y formas de empleo. Los datos botánicos de las plantas citadas fueron recopilados de la bibliografía. Las familias más utilizadas fueron: Asteraceae, Rubiaceae, Fabaceae, Myrtaceae, Solanaceae, Rutaceae, Apiaceae, Orchidaceae. Las plantas medicinales son el principal recurso terapéutico para un amplio sector de la población. Las afecciones más comúnmente tratadas con plantas medicinales son: infecciones de riñón y estómago, dolor de cabeza, nervios, insomnio y gripe. Aunque no es frecuente encontrar plantas de la familia Orchidaceae en la medicina tradicional, Catasetum macroglossum fue la única orquídea citada de uso en la medicina popular ecuatoriana. El conocimiento etnobotánico se transmite de una generación a otra, principalmente a través de las mujeres. La investigación cientifica puede contribuir eficazmente a preservar el patrimonio cultural.

Information about common names, part used indications, preparation and administration of the plants used in traditional medicine of Quevedo, Los Ríos province (Ecuador) was gathered from interviews to three "healers" considered leaders about the medicinal habits of their respective communities. Species cited were organized in a tabular form that describes their therapeutic uses and forms of employment. Botanical data of the mentioned plants were collected from the literature. The main families used were: Asteraceae, Rubiaceae, Fabaceae, Myrtaceae, Solanaceae, Rutaceae, Apiaceae and Orchidaceae. Conclusions: medicinal plants are the main therapeutic resource for a large segment of the population. The illnesses most commonly treated with medicinal plants are kidney and stomachal infections, headache, nervousness, insomnia, and flu. Although the use of Orchidaceae is unfrequent in traditional medicine, Catasetum macroglossum was the only orchid from Ecuatorian folk medicine. Mainly women transmit ethnobotanical knowledge from one generation to another. Scientific research can contribute effectively to preserve the cultural heritage.

Anatomía foliar de arbustos y árboles medicinales de la región chaqueña semiárida de la Argentina / Foliar anatomy of medicinal trees and shrubs of the semi-arid Chaco region of Argentina

Se estudió la anatomía foliar de 32 arbustos y árboles medicinales de los Distritos Chaqueños Occidental y Serrano (Argentina). El objetivo de este trabajo fue proveer una clave para el reconocimiento de estos taxones a partir de hojas fragmentadas, desmenuzadas o pulverizadas. Para el estudio las muestras de herbario fueron reconstituidas y fijadas en FAA; y, en cuanto a las preparaciones, se utilizaron técnicas histológicas convencionales. Algunos de los principales caracteres de identificación fueron: los tricomas estrellados en Capparicordis tweediana y Ruprechtia triflora, cistolíticos en Celtis spp.; escamoso-peltados en Zanthoxylum coco; epidermis papilosa (e.g., Schinopsis lorentzii); los estomas ciclocíticos en Bulnesia sarmientoi, Maytenus vitis-idaea, Moya spinosa y Schinopsis spp.; idioblastos cristalíferos epidérmicos en Scutia buxifolia; la epidermis cristalífera en Maytenus vitis-idaea; la epidermis pluristrata en Jodina rhombifolia; la presencia de hipodermis en Castela coccinea, Maytenus vitis-idaea, Prosopis ruscifolia y Ziziphus mistol; los haces bicolaterales en Lycium cestroides; la presencia de arena cristalina en Calycophyllum multiflorum y Lycium cestroides; la ausencia total de cristales en la familia Capparaceae. Para la identificación de las especies estudiadas se presenta una clave dicotómica e ilustraciones originales.

Transplante de células-tronco hematopoéticas para tumores sólidos: recomendações do Consenso Brasileiro de Transplante de Medula Óssea / Autologous hematopoietic stem cell transplantation in solid tumors: the Brazilian Consensus on Stem Cell Transplantation

O transplante de células-tronco hematopoéticas autólogo permite o escalonamento de dose de drogas quimioterápicas e é uma estratégia atraente para tratamento de tumores sólidos, principalmente em doenças recaídas. Não há, no entanto, estudos randomizados fase III que demonstrem benefício deste procedimento em tumor sólido. Em tumor germinativo de testículo, há estudos fase II com excelentes resultados, proporcionando cura para doentes refratários a platina ou que estão em terceira linha de quimioterapia. Com base nisto, o transplante de células-tronco hematopoéticas autólogo é considerado tratamento padrão para tumor germinativo recaído. Para câncer de mama, o papel desta modalidade de tratamento permanece controverso apesar dos vinte anos de experiência. Ainda é utilizado em ensaios clínicos e talvez exista algum subgrupo que se beneficie. O procedimento não oferece benefício para câncer de ovário, pulmão ou tumor cerebral. O transplante alogeneico de células-tronco hematopoéticas para tumores sólidos se baseia no efeito enxerto-contra-tumor, que é observado para algumas doenças: câncer mamário, colorretal, ovariano, pancreático e, finalmente, renal, em que há a maior experiência. Porém, o tratamento ainda é considerado experimental.

Autologous hematopoietic stem cell transplantation, which allows chemotherapy dose-escalonation, is an attractive strategy for solid tumors treatment, specially relapsed diseases. However, there are no phase III trials showing benefits. There are phase II trials showing excellent results for germ cell tumors, including cure for platinrefractory and heavily pretreated patients. Because of this, autologous stem cell transplantation is considered standard of care for relapsed germ cell tumor. The role of this treatment remains controversial for breast cancer despite twenty years of experience. It's still done in clinical trials and it may benefit a subgroup of patients. The procedure offers no benefit for ovary, lung or cerebral cancer. Allogeneic stem cell transplantation for solid tumors relies on graft versus tumor effect, which is observed for some diseases: breast, colorectal, ovarian, pancreatic and, at last, kidney cancer, for which there is most experience. This treatment, however, is still experimental.

Streptococcal bacteremia in patients submitted to hematopoietic stem celltransplantation: The role of tooth brushing and use of chlorhexidine

A retrospective evaluation of 73 consecutive recipients of hematopoietic stem cell transplantation (HSCT) wasconducted to investigated the role of oral care and incidence of streptococcal bacteremia in patients submittedto hematopoietic stem cell transplantation. Patients were retrospectively evaluated and divided into group A(GA=38) and group B (GB=35). During hospitalization patients from GA performed oral hygiene daily with extrasoft toothbrush and toothpaste besides performing mouth cleaning with an ethanol-free 0.12% chlorhexidine solutiontree times a day. In contrast GB patients performed mouth cleaning with extra soft toothbrush and toothpaste,but no chlorhexidine was used. Using the Chi square test it was observed that all patients from GA presentednegative blood culture for alpha-hemolytic Streptococcus viridans and Candida albicans and only 1 patient withoutoral mucositis from GB presented positive blood cultures for Streptococcus intermedius (p=0.48). The resultsindicate that methodology used for oral care before the HSCT and the practice of tooth brushing during the periodwere effective in preventing streptococcal bacteremia. Moreover, our data suggest that the mouth cleaning withchlorhexidine during HSCT may be not mandatory (AU)