Alemtuzumab as graft-versus-host disease (GVHD) prophylaxis strategy in a developing country: lower rate of acute GVHD, increased risk of cytomegalovirus reactivation

Acute graft-versus-host disease (aGVHD) and cytomegalovirus reactivation are important complications after allogeneic stem cell transplantation (alloHSCT). Here, we evaluated the impact of treatment with alemtuzumab on the occurrence of aGVHD, cytomegalovirus reactivation and survival after alloHSCT. This was a prospective cohort study conducted at the allo-HSCT unit of Hospital das Clínicas, Universidade Federal de Minas Gerais, Brazil, from January 2009 to December 2011. Fifty-seven patients who underwent alloHSCT were included. Forty-five (79%) patients had a malignant disease. Alemtuzumab was administered before the conditioning regimen at a dose of 1 mg/kg in children and 30 mg/day for 2 days in adults or children weighing more than 40 kg (a total dose of 60 mg) with a non-malignant disease or patients with a malignant disease and high-risk for GVHD mortality. Alemtuzumab was used in 23 (40%) patients, of whom 17 received a reduced-intensity conditioning. Eleven patients presented aGVHD (grade 2–4) and only 1 of them received alemtuzumab. Cumulative incidence of aGVHD (grade 2–4) at day 100 after transplantation (D+100) was 4 for patients receiving alemtuzumab and 29% for patients not receiving alemtuzumab. Cumulative incidence of cytomegalovirus reactivation for patients receiving or not alemtuzumab was 62 and 38%, respectively. Sixteen patients died in the first 100 days after alloHSCT, most of them due to bacterial sepsis. Only 2 patients died of aGVHD until D+100. Overall survival was 50% without any impact of alemtuzumab. Alemtuzumab effectively controlled aGVHD but increased the risk of cytomegalovirus reactivation without improving survival.

Resposta reprodutiva de vacas de corte associada a marcadores moleculares relacionados à fertilidade / Reproductive performance of beef cattle cows associated with molecular markers related to the fertility

O objetivo deste estudo foi buscar associação entre a taxa de prenhez após inseminação e natalidade com marcadores moleculares ligados aos genes do receptor para IGF-1, LHβ, Leptina e receptores do FSH e LH. Utilizaram-se 249 vacas adultas Aberdeen Angus, das quais 199 foram submetidas a protocolos distintos para a IATF, seguida pelo repasse com touros, e 50 vacas formaram o grupo controle representado pelo acasalamento com touros. Foram avaliados o escore de condição corporal (ECC) e o escore de condição ovariana (ECO) ao início da estação reprodutiva. O ECC influenciou a taxa de natalidade, respectivamente de 55,6%, 75,8% e 82,4% (P<0,05) para os animais com ECC menor que 2,5, entre 2,5 a 2,9, e maior ou igual a 3,0, por ocasião da estação reprodutiva. Os marcadores relacionados ao gene do receptor para o IGF-1 (AFZ-1 e HEL5) mostraram associação com a taxa de natalidade. Vacas homozigóticas para o marcador AFZ-1 apresentaram 84,4% de natalidade em comparação às heterozigóticas, com 71,5% (P<0,05). A presença do alelo*161 para o marcador HEL5 foi negativa sobre a natalidade, respectivamente de 33,3% e 76,5% para vacas com e sem esse alelo (P<0,05). Esses resultados demonstram uma importante associação entre os marcadores envolvidos com o receptor para o IGF-1 e desempenho reprodutivo de vacas Angus.

The association between the reproductive performance, expressed by pregnancy rate at fixed timed artificial insemination and birth rate in the subsequent season in beef cows, and molecular markers linked to genes for IGF-1 receptor, LHβ, leptin, and FSH and LH receptors were evaluated. Data from 249 Aberdeen Angus adult cows were used in this study. One hundred and ninety-nine cows were subjected to four different protocols for FTAI, followed by clean-up bulls and 50 cows formed the control group, matted only with bulls for 90 days during the mating season. Body condition score (BCS) and ovarian condition score (OCE) were evaluated at the beginning of the breeding season. The birth rate in the following year was 75.5%, with no treatments influence. The BCS has influenced the birth rate, respectively 55.6%, 75.8% and 82.4% (P<0.05) for animals with BCS less than 2.5; 2.5 to 2.9; and greater than or equal to 3.0, at the beginning of the breeding season. The markers related to IGF-1 receptor gene (AFZ-1 and HEL5) were associated with the birth rate in beef cows. Cows homozygous for AFZ-1 marker showed 84.4% of birth rate, while heterozygous cows showed 71.5% (P <0.05). The presence of allele *161 to the HEL5 marker was negative on birth rate. Cows with this allele had only 33.3% of birth rate, while cows without this allele had 76.5% of birth rate (P <0.05). These results demonstrate a significant association between the markers involved with the IGF-1 receptor and reproductive performance of Aberdeen Angus beef cows.

Use of inflammatory molecules to predict the occurrence of fever in onco-hematological patients with neutropenia

Febrile neutropenia remains a frequent complication in onco-hematological patients, and changes in the circulating level of inflammatory molecules (IM) may precede the occurrence of fever. The present observational prospective study was carried out to evaluate the behavior of plasma tumor necrosis factor alpha (TNF-α), soluble TNF-α I and II receptors (sTNFRI and sTNFRII), monocyte chemoattractant protein-1 [MCP-1 or chemokine (c-c motif) ligand 2 (CCL2)], macrophage inflammatory protein-1α (MIP-1α or CCL3), eotaxin (CCL11), interleukin-8 (IL-8 or CXCL8), and interferon-inducible protein-10 (IP-10 or CXCL10) in 32 episodes of neutropenia in 26 onco-hematological patients. IM were tested on enrollment and 24-48 h before the onset of fever and within 24 h of the first occurrence of fever. Eight of 32 episodes of neutropenia did not present fever (control group) and the patients underwent IM tests on three different occasions. sTNFRI levels, measured a median of 11 h (1-15) before the onset of fever, were significantly higher in patients presenting fever during follow-up compared to controls (P = 0.02). Similar results were observed for sTNFRI and CCL2 levels (P = 0.04 for both) in non-transplanted patients. A cut-off of 1514 pg/mL for sTNFRI was able to discriminate between neutropenic patients with or without fever during follow-up, with 65% sensitivity, 87% specificity, and 93% positive predictive value. Measurement of the levels of plasma sTNFRI can be used to predict the occurrence of fever in neutropenic patients.

Retardo da realização da IATF sobre o desempenho reprodutivo na estação de acasalamento de vacas de corte lactantes / Delay of beginning to FTAI on reproductive performance during to mating season of beef lactating cows

Compararam-se efeitos de diferentes protocolos para a IATF com o acasalamento natural (Controle) sobre o desempenho reprodutivo de 249 vacas Aberdeen Angus, distribuídas em cinco grupos: Controle (n=50); Crestar 2º uso (n=64); OvSynch (n=65); Primer 1ºuso (n=35) e Primer 2º uso (n=35). A IATF dos animais dos grupos Crestar 2º uso, OvSynch, e Primer 1º uso foi realizada 27 dias após o início da estação do grupo controle e a IATF do grupo Primer 2º uso ocorreu 38 dias após o início da estação do grupo-controle. A partir de sete dias após a IATF, os animais foram submetidos ao repasse por touros até o término da estação de acasalamento, que foi de 91 dias para o grupo-controle, 64 dias para os grupos Crestar 2º uso, OvSynch e Primer 1º uso e de 53 dias para o grupo Primer 2º uso. A taxa de gestação ao final da estação de acasalamento não se diferenciou entre os grupos (P>0,05), sendo de 85,9%; 83,1%; 82,9%; 88,6% e 80,0%, respectivamente, para Crestar 2º uso; OvSynch; Primer 1º uso; Primer 2º uso e Controle. A taxa de parição resultante da IATF foi de 23,4%; 29,2%; 48,6% e 62,9% para os grupos Crestar 2º uso, OvSynch, Primer 1º uso, Primer 2º uso, respectivamente, com diferença significativa (P<0,05) entre Crestar e Primer 1º e 2º uso. OvSynch não se diferenciou de Crestar e Primer 1º uso. Primer 1º uso não se diferenciou de Primer 2º uso. A perda gestacional, do diagnóstico de gestação ao nascimento, foi de 10,5%. O intervalo de partos estimado (IEP) não apresentou diferenças, com média de 478 dias. O escore de condição corporal (ECC) de fêmeas gestantes ao final da estação reprodutiva foi diferente do de fêmeas não gestantes (controle), mas não dos demais grupos, possivelmente pela influência do tratamento em induzir a ciclicidade dos animais com ECC inferior. O atraso da realização da IATF após 27 ou 38 dias do início da estação de acasalamento não afetou a taxa de gestação final e o IEP dos animais, quando comparado ao acasalamento por touros.

The effects of different FTAI protocols were compared to the natural mating of bulls on the reproductive performance of 249 Aberdeen Angus cows. Five groups were formed: Control (n=50); Crestar 2nd use (n=64); OvSynch (n=65); Primer 1st use (n=35) and Primer 2nd use (n=35). The FTAI of the animals in the Crestar 2nd use, OvSynch and Primer 1st use groups was accomplished 27 days after the beginning of the mating season for the control group and the FTAI in the Primer 2nd use group happened 38 days after the beginning of the mating season of the control group. From seven days after the FTAI cows were exposed to bulls until the end of the mating season. The mating season was of 91 days for the control group, 64 days for the Crestar 2nd use, OvSynch and Primer 1st use groups and 53 days for the Primer 2nd use group. The pregnancy rate at the end of the mating season didn't differ among the groups (P>0.05), being 85.9; 83.1; 82.9; 88.6 and 80.0% respectively, for Crestar 2nd use, OvSynch, Primer 1st use, Primer 2nd use and Control. The birth rate resulting from FTAI was 23.4; 29.2; 48.6 and 62.9% for the Crestar 2nd use, OvSynch, Primer 1st use, Primer 2nd use groups, with significant difference (P<0.05) among Crestar and Primer 1st and 2nd use. OvSynch didn't differ in Crestar and Primer 1st use. Primer 1st use didn't differ from Primer 2nd use. The average reproductive losses between the gestation diagnosis and the birth were10.5%. The estimated calving interval (CI) didn't present differences among the animal groups, with an average of 478 days. The body condition score (BCS) of pregnant cows at the end of the reproductive station differed from BCS of empty cows in the control group, but it didn't differ in the other groups, possibly due to the hormonal treatment influence in inducing the oestrus and ovulation in animals with lower BCS. The delay of the accomplishment of FTAI after 27 or 38 days of the beginning of the mating season didn't affect the final pregnancy rate and CI of the cows, when compared to natural mating.

Perdas reprodutivas e reconcepção em bovinos de corte segundo a idade ao acasalamento / Reproductive disorders and reconception of beef cows according to of mating age

Avaliou-se o desempenho reprodutivo de novilhas de corte acasaladas aos 14 meses (14M), aos 24 meses (24 M) e de vacas multíparas (V), totalizando 4.012 animais. As perdas reprodutivas (PR) foram de 19,3 por cento, 11,6 por cento e 7,6 por cento para 14M, 24M e V, respectivamente, sendo que 14M diferiu de V (P<0,01). A ocorrência de distocia foi de 20,7 por cento, 5,1 por cento e 0,8 por cento para as categorias 14M, 24M e V, respectivamente, sendo que 14M diferiu de V (P<0,01). Ocorreu maior mortalidade causada por distocia entre os animais do grupo 14M que entre os do grupo V (P<0,01), 7,4 por cento e 0,4 por cento, respectivamente. A reconcepção foi maior nos animais de 14M (85,3 por cento) e V (81,1 por cento), comparada à dos de 24M (70,7 por cento) (P<0,01). A categoria que teve maior concentração de parição no primeiro período, 52,3 por cento (até 19/09), foi a de 24M (P<0,01). Animais acasalados mais jovens tendem a apresentar maiores perdas reprodutivas e ocorrências de distocia.

Reproductive performances of beef heifers mated at 14 months of age (14M), at 24 months of age (24M) and pluriparous cows (C), based on data from 4.012 animals were evaluated. The reproductive disorders were 19.3 percent, 11.6 percent and 7.6 percent, respectively, at 14M, 24M and for C; 14M was different from C (P<0.01). The occurrence of dystocia was 20.7 percent, 5.1 percent and 0.8 percent for the 14M, 24M and C, respectively. The 14M group was different from C (P<0.01). The mortality caused by dystocia was higher for 14M group 7.4 percent than for the C group 0.4 percent (P<0.01), respectively. The reconception rate was higher for the 14M (85.3 percent) and V (81.1 percent) than for the 24M group (70.7 percent) (P<0.01). The category which concentrated the parturition in the first period (until 09/19) (52.3 percent) was the 24M. Animals mated earlier tended to show high reproductive disorders and incidence of dystocia.