Cyclosporine as prophylaxis for graft-versus-host disease: a randomized study in patients undergoing marrow transplantation for acute nonlymphoblastic leukemia

Seventy-five patients, 13 to 49 years of age, with acute nonlymphoblastic leukemia in first remission were treated with cyclophosphamide, fractionated total body irradiation, and marrow transplantation from an HLA-identical sibling and randomized to receive either cyclosporine (CSP) (n = 36) or methotrexate (MTX) (n = 39) as prophylaxis for graft-v-host disease (GVHD). All patients engrafted, and 22 who were given CSP and 21 who were given MTX, are alive at 20 to 47 (median, 35) months (P = .5). Engraftment as assessed by granulocyte recovery (P less than .0005) and platelet transfusion requirement (P = .01) was faster in patients on CSP. Twelve patients (33%) on CSP and 22 (56%) on MTX developed acute GVHD of grades II through IV (P = .07) and 15 of 30 on CSP and 14 of 32 on MTX that were at risk developed chronic GVHD. The most frequent causes of death were interstitial pneumonitis and marrow relapse of leukemia, which occurred with similar frequency in both groups. Beneficial effects observed in patients on CSP included less severe mucositis and shorter duration of hospitalization; adverse effects included renal function impairment and hypertension. These data confirm that CSP is a useful immunosuppressant in patients undergoing marrow transplantation but fail to show a significant improvement in survival as compared with the standard regimen of MTX.     

Marrow transplantation with or without donor buffy coat cells for 65 transfused aplastic anemia patients

Sixty-five multiply transfused patients with severe aplastic anemia were given cyclophosphamide followed by grafts anemia were given cyclophosphamide followed by grafts from HLA-identical siblings. The effect of the administration of viable donor buffy coat cells following the marrow inoculum was evaluated with regard to graft rejection and survival. Results in 43 patients so treated are presented along with those in 22 concurrent patients given marrow alone. Most patients given buffy coat had positive in vitro tests of sensitization indicating a high risk for graft rejection, while all but one of the patients given marrow alone had negative tests. Thirty of the 43 (70%) patients given marrow and buffy coat are alive between 10 and 61 mo (median 36) after grafting; 4 died after graft rejection and 6 with acute or chronic graft-versus-host disease (GVHD). Eleven of the 22 (50%) patients given marrow alone are alive between 29 and 65 mo (median 52); 7 died after graft rejection and 3 with GVHD. The addition of buffy coat cell infusions to the marrow inoculum reduced the risk of rejection and increased survival in the currently reported transfused patients when compared to patients grafted before 1976. However, there was an increased risk of chronic GVHD. Recipients of marrow from female donors survived slightly better (73%) than recipients of male marrow (58%).     

Sustained, retransplantable, multilineage engraftment of highly purified adult human bone marrow stem cells in vivo

Data from many laboratory and clinical investigations indicate that CD34+ cells comprise approximately 1% of human bone marrow (BM) mononuclear cells, including the progenitor cells of all the lymphohematopoietic lineages and lymphohematopoietic stem cells (stem cells). Because stem cells are an important but rare cell type in the CD34+ cell population, investigators have subdivided the CD34+ cell population to further enrich stem cells. The CD34+/CD38- cell subset comprises less than 10% of human CD34+ adult BM cells (equivalent to < 0.1% of marrow mononuclear cells), lacks lineage (lin) antigens, contains cells with in vitro replating capacity, and is predicted to be highly enriched for stem cells. The present investigation tested whether the CD34+/CD38- subset of adult human marrow generates human hematopoiesis after transfer to preimmune fetal sheep. CD34+/ CD38- cells purified from marrow using immunomagnetic microspheres or fluorescence-activated cell sorting generated easily detectable, long- term, multilineage human hematopoiesis in the human-fetal sheep in vivo model. In contrast, transfer of CD34+/CD38+ cells to preimmune fetal sheep generated only short-term human hematopoiesis, possibly suggesting that the CD34+/CD38+ cell population contains relatively early multipotent hematopoletic progenitor cells, but not stem cells. This work extends the prior in vitro evidence that the earliest cells in fetal and adult human marrow lack CD38 expression. In summary, the CD34+/ CD38- cell population has a high capacity for long-term multilineage hematopoietic engraftment, suggesting the presence of stem cells in this minor adult human marrow cell subset.     

Texture analysis of ultrasound images is a sensitive method to follow‐up muscle damage induced by eccentric exercise

The grey level of co‐occurrence matrix (GLCM) is a texture analysis approach accounting for spatial distribution of the pixels from an image and can be a promising method for exercise‐induced muscle damage (EIMD) studies. We followed up the time changes of two GLCM texture parameters and echo intensity (EI) on ultrasound images after eccentric contractions. Thirteen untrained women performed two sets of ten elbow flexions eccentric contractions. Ultrasound images were acquired at baseline and 24 h, 48 h, 72 h and 96 h after exercise. Two GLCM texture parameters were calculated for the brachialis muscle: contrast (CON) and correlation (COR). Peak torque, EI, muscle thickness (MT) and soreness were measured. The peak torque and soreness decreased immediately after the intervention in comparison with all the measures. MT increased immediately after the intervention remaining for 72 h (P<0·05). Significant increases (P<0·05) were observed for COR (48, 72 and 96 h) and EI only at 72 and 96 h. The increasing COR represents high similarity between grey levels, which could be observed on US images after few days on eccentric training for elbow flexors.     

α‐Thalassemia 2, 3.7 kb deletion and hemoglobin AC heterozygosity in pregnancy: a molecular and hematological analysis

α‐Thalassemia is a synthesis hemoglobinopathy with a worldwide distribution. α‐thalassemia‐2^3.7kb (α‐Thal2^3.7kb) was investigated by PCR and standard hematologic analysis techniques in 106 pregnant women – 53 heterozygous for hemoglobin (Hb) A and C (AC) and 53 homozygous for the normal Hb A (AA) with similar ages and race ancestry. Eleven (21%) of AC women were α‐Thal2^3.7kb heterozygous and 1 (2%) was homozygous, while 12 AA women (23%) were heterozygous. In the AA group, the MCV differed among those with normal α genes and those with α‐Thal2^3.7kb (P = 0.031). Statistical analysis of AC group patients with normal α genes and α‐Thal2^3.7kb carriers showed differences in MCV (P = 0.001); MCH (P = 0.003) and Hb C concentrations (P = 0.011). Analysis of AA and AC group patients with normal α genes showed differences in RBC (P = 0.033), Hb concentration (P = 0.003) and MCHC (P < 0.0001). There were no statistically significant differences for any hematologic parameters between AC and AA group patients with the α‐Thal2^3.7kb genotype. The AC α‐Thal2^3.7kb homozygous women had low hematologic parameters. Serum ferritin levels were normal among the groups studied. These results emphasize the importance of diagnosis and follow‐up of patients with hemoglobinopathy carriers during pregnancy in order to administer adequate therapy and avoid further complications for mothers and newborns.     

Further evidence reveals that okra mottle virus arose from a double recombination event

As a result of surveys of okra begomoviruses (genus Begomovirus, family Geminiviridae) conducted over the last five years in Central Brazil, we report the complete genome sequence of an isolate of okra mottle virus (OMoV). The DNA-A and DNA-B components were 2660 and 2653 nucleotides (nt) long, respectively, and they were most closely related to the DNA-A (~99 % nt identity) and DNA-B (~98 % nt identity) components of an OMoV isolate from a soybean plant. A phylogenetic tree was generated based on these sequences, and it was shown that both of the OMoV DNA components were grouped in a branch with Brazilian begomoviruses known to infect weeds. By recombination analysis, strong evidence was observed that the OMoV genome may have been the product of a double inter-species recombination event.