Cyclosporine A alleviates severe anaemia associated with refractory large granular lymphocytic leukaemia and chronic natural killer cell lymphocytosis

Large granular lymphocytic (LGL) leukaemia and chronic natural killer cell lymphocytosis (CNKL) are chronic indolent disorders often associated with neutropenia and constitutional symptoms. Severe anaemia occurs in about 20% of patients and is currently treated with corticosteroids followed by oral cyclophosphamide in non-responders. 30% of patients fail initial measures, and salvage therapy is inadequate. We describe three transfusion-dependent patients (two with T-LGL leukaemia, one with CNKL) refractory to corticosteroids, cyclophosphamide, and in one case fludarabine. Cyclosporine A (CSA) initiation resulted in prompt transfusion-independence and was well tolerated in all patients, making it an attractive alternative therapy for this disorder.     

Transduction of umbilical cord blood CD34+ NOD/SCID-repopulating cells by simian foamy virus type 1 (SFV-1) vector

Foamy viruses are nonpathogenic retroviruses that offer unique opportunities for gene transfer into various cell types including hematopoietic stem cells. We used a simian foamy virus type 1 vector (SFV-1) containing a LacZ reporter gene with a titer of 1-5 x 10(6) viral particles/ml that was free of replication-competent retrovirus to transduce human umbilical cord blood CD34+ cells. Transduced CD34+ cord blood cells were transplanted into NOD/SCID mice and plated in serum-free methylcellulose culture to determine the transduction efficiency of human hematopoietic progenitor cells. A transduction efficiency of about 20% was obtained. At 6-10 weeks posttransplantation, human hematopoietic cell engraftment and marking were determined. Marrow from transplanted mice demonstrated human cell engraftment by the presence of human (CD45+) cells containing both CD19+ lymphoid and CD33+ myeloid cells. Serial sampling of NOD/SCID bone marrow revealed the presence of 6.7-14.0% CD45+ cells at 6 weeks posttransplant as compared to 3.6-27.2% CD45+ cells at 9-10 weeks posttransplant. Human progenitors examined from NOD/SCID bone marrow cells 9 weeks posttransplant revealed from 7.4 to 25.9% of the colonies exhibiting X-gal staining. Our study demonstrates the ability of a simian foamy virus vector to transduce the SCID-repopulating cell and offers a promising new gene delivery system for use in hematopoietic stem cell gene therapy.     

Early lymphocyte recovery predicts superior survival after autologous hematopoietic stem cell transplantation for patients with primary systemic amyloidosis.

PURPOSE: Absolute lymphocyte count recovery at day 15 (ALC-15) post-autologous stem cell transplantation (ASCT) is a powerful prognostic indicator for survival for multiple hematologic malignancies and metastatic breast cancer. The relationship of ALC-15 with clinical outcomes in primary systemic amyloidosis is unknown. EXPERIMENTAL DESIGN: We evaluated 145 consecutive patients with primary systemic amyloidosis who underwent ASCT at the Mayo Clinic from 1996 to 2003. The ALC-15 threshold was set at 500 cells/microL based on our previous observations. RESULTS: The median patient follow-up was 22 months (range, 3-87 months). Higher hematologic complete response was observed in patients with an ALC-15 > or = 500 cells/microL compared with patients with an ALC-15 < 500 cells/microL (41% versus 21%, P < 0.0008, respectively). The median overall survival and progression-free survival times were significantly better for the 59 patients that achieved an ALC-15 > or = 500 cells/microL compared with 86 patients with ALC-15 < 500 cells/microL (not reached versus 53 months, P < 0.0003 and not reached versus 27 months, P < 0.0001, respectively). Multivariate analysis showed ALC-15 to be an independent prognostic factor for overall survival and progression-free survival. CONCLUSIONS: ALC-15 > or = 500 cells/microL is associated with significantly improved clinical outcomes following ASCT in patients with primary systemic amyloidosis.     

Prediction of early (4-week) mortality in acute myeloid leukemia with intensive chemotherapy

The progress with intensive chemotherapy and supportive care measures has improved survival in patients with newly diagnosed acute myeloid leukemia (AML). Given the recent development of effective low intensity therapies, an optimal decision on the therapy intensity may improve survival through the avoidance of early mortality. We reviewed the outcome of 3728 patients with newly diagnosed AML who received intensive chemotherapy between August 1980 and May 2020. Intensive chemotherapy was defined as a cumulative cytarabine dose ≥ 700 mg/m² during induction therapy. We divided the whole cohort into a training and validation group at a 3:1 ratio. The population was divided into a training (2790 patients) and a validation cohort (938 patients). The median age was 55 years (range, 15-99). Among them, 442 patients (12%) had core-binding factor AML. Binary logistic regression identified older age, worse performance status, hyperbilirubinemia, elevated creatinine, hyperuricemia, cytogenetic abnormalities other than CBF and -Y, and pneumonia as adverse prognostic factors for an early 4-week mortality. This risk classification for early mortality was verified in the validation cohort of patients. In the validation cohort of more recently treated patients from 2000 to 2017, the 4-week mortality rates with intensive chemotherapy were 2%, 14%, and 50% in the low-, high-, and very high-risk group, respectively. The mortality rates with low intensity therapies were 3%, 9%, and 20%, respectively. The risk classification guides treatment intensity by the assessment of age, frailty, organ dysfunction, cytogenetic abnormality, and infection to avoid early mortality.     

Ixodid ticks infesting cattle in three agroecological zones in central Oromia: species composition,seasonal variation,and control practices

A cross-sectional study was conducted to determine the species, prevalence, and seasonal variation of ticks on cattle in central Oromia. In addition, questionnaire survey was used to assess the control practices of ticks in central Oromia. During the study period from August 2008 through April 2009, a total of 10,440 adult ixodid ticks were collected from a total of 918 cattle (153 cattle during dry and wet seasons from each of three agroecologies) in three agroecological zones during wet and dry seasons. A total of seven species of ixodid ticks belonging to four genera were identified during the wet period, whereas similar numbers of genera but six species of ixodid ticks were recorded during the dry season. Amblyomma, Boophilus, Rhipicephalus, and Hyalomma tick genera were identified during the two seasons. Five different species of ticks were identified from the highland altitude. Significantly (p?<?0.05) higher proportion of Boophilus decoloratus (88.2 %) was identified during the wet season, Hyalomma truncatum (1.5 %) was with the least proportion. Rhipicephalus evertsi evertsi (50.8 %) was the most abundant during the dry period, whereas Hyalomma marginatum rufipes (5 %) was with smallest proportion. In the midland, a total of six species of ticks were identified. Significantly (p?<?0.05) higher proportion of Amblyomma variegatum (76.6 %) than the other species was recorded during the wet season in the midland. But Rhipicephalus pulchellus (0.05 %) was collected with the lowest proportion. R. e. evertsi (46.3 %) was the most abundant tick species during the dry season, whereas R. pulchellus (0 %) was with lowest proportion. In the lowland, a total of seven species of ticks during the wet and six during the dry season were identified. A significantly (p?<?0.05) higher proportion of A. variegatum (30.3 %) was recorded during the wet season, whereas R. pulchellus (1.4 %) was identified with the lowest proportion in the lowland. R. e. evertsi (24.8 %) was the most abundant tick species during the dry season in the lowland, but R. pulchellus (0 %) was with the lowest proportion during the same season in the lowland. Results of the study revealed that the highest mean total tick burden was recorded during the early rainy season than the dry season from the end of March to April. And the lowest mean tick count was recorded during the early dry and the late dry season during December and February, respectively. The overall tick count across seasons showed significant variation (F?=?114 and p?=?0.000). The questionnaire survey on the tick control practices has revealed that (90 %) diazinon and (57.3 %) cypermethrin were the commonly used acaricides with a frequency of one to three times per year during the peak of tick infestation. In conclusion, this study demonstrated that ixodid ticks occur with high prevalence and burden and still play major roles in reducing productivity of cattle and cause health problems of cattle in central Oromia. Further studies on the role of ticks in the transmission of pathogens to cattle, other animals, and zoonotic pathogens to man in Oromia are urgently needed.     

The effects of anagrelide on human megakaryocytopoiesis

Anagrelide, an inhibitor of platelet aggregation, decreases the number of platelets in normal subjects and in patients with myeloproliferative disorders. We describe studies aimed at discovering the general mechanism(s) by which anagrelide acts. We examined three hypotheses: (1) anagrelide shortens platelet survival, (2) anagrelide inhibits the proliferation of megakaryocytic-committed progenitor cells (CFU-M), and (3) anagrelide inhibits maturation of megakaryocytes. We observed that anagrelide did not shorten platelet survival. Proliferation of CFU-M in vivo was not affected by anagrelide, although high concentrations of anagrelide inhibited CFU-M in vitro . In-vivo and in-vitro anagrelide altered the maturation of megakaryocytes, causing a decrease in their size and changing other morphometric features. We conclude that anagrelide decreases the number of platelets primarily by interfering with the maturation of megakaryocytes.     

Inter-Rater Agreement between Trachoma Graders: Comparison of Grades Given in Field Conditions versus Grades from Photographic Review

ABSTRACT

Purpose: Trachoma surveillance is most commonly performed by direct observation, usually by non-ophthalmologists using the World Health Organization (WHO) simplified grading system. However, conjunctival photographs may offer several benefits over direct clinical observation, including the potential for greater inter-rater agreement. This study assesses whether inter-rater agreement of trachoma grading differs when trained graders review conjunctival photographs compared to when they perform conjunctival examinations in the field.

Methods: Three trained trachoma graders each performed an independent examination of the everted right tarsal conjunctiva of 269 children aged 0–9 years, and then reviewed photographs of these same conjunctivae in a random order. For each eye, the grader documented the presence or absence of follicular trachoma (TF) and intense trachomatous inflammation (TI) according to the WHO simplified grading system.

Results: Inter-rater agreement for the grade of TF was significantly higher in the field (kappa coefficient, κ, 0.73, 95% confidence interval, CI 0.67–0.80) than by photographic review (κ?=?0.55, 95% CI 0.49–0.63; difference in κ between field grading and photo grading 0.18, 95% CI 0.09–0.26). When field and photographic grades were each assessed as the consensus grade from the three graders, agreement between in-field and photographic graders was high for TF (κ?=?0.75, 95% CI 0.68–0.84).

Conclusions: In an area with hyperendemic trachoma, inter-rater agreement was lower for photographic assessment of trachoma than for in-field assessment. However, the trachoma grade reached by a consensus of photographic graders agreed well with the grade given by a consensus of in-field graders.