Hematol. Rep., Volume 3, Issue 1 (January 2011) – 8 articles

Bone marrow sampling remains essential in the evaluation of hematopoietic and many non-hematopoietic disorders. One common limitation to these procedures is the discomfort experienced by patients. To address whether a Powered biopsy system could reduce discomfort while providing equivalent or better results, we performed a randomized trial in adult volunteers. Twenty-six subjects underwent bilateral biopsies with each device. Core samples were obtained in 66.7% of Manual insertions; 100% of Powered insertions (p = 0.002). Initial mean biopsy core lengths were 11.1 ± 4.5 mm for the Manual device; 17.0 ± 6.8 mm for the Powered device (p < 0.005). Pathology assessment for the Manual device showed a mean length of 6.1 ± 5.6 mm, width of 1.0 ± 0.7 mm, and volume of 11.0 ± 10.8 mm³. Powered device measurements were mean length of 15.3 ± 6.1 mm, width of 2.0 ± 0.3 mm, and volume of 49.1 ± 21.5 mm³ (p < 0.001). The mean time to core ejection was 86 seconds for Manual device; 47 seconds for the Powered device (p < 0.001). The mean second look overall pain score was 33.3 for the Manual device; 20.9 for the Powered (p = 0.039). We conclude that the Powered biopsy device produces superior sized specimens, with less overall pain, in less time. Full article

Fungal endocarditis (FE) is a rare complication in immunocompromised patients which is difficult to diagnose and has been characterized by excessive mortality (>50%) and morbidity, regardless of treatment. The lack of clinical trials due to the small number of cases contributes further to a poor outcome. In our two cases of aspergilllus endocarditis we reviewed the clinical features, echocardiographic findings, microbiologic data, treatment, and outcome of these 2 cases and provide a current characterization of the syndrome. In this paper we have demonstrated the diversity of presentation of a critical fungal infection in immunocompromised but non neutropenic paediatric patients. The prompt diagnosis and initiation of treatment is crucial for a favourable outcome along with the use of double antifungal treatment with liposomal amphotericin and voriconazole initially which could be later switched to oral voriconazole with a good tissue penetration. Histological samples as well as radiological evidence and echocardiograms should be reviewed by experienced clinicians in order to aid diagnosis and promptly initiate treatment for these patients in order to achieve a favourable outcome. Full article

Over the last two decades umbilical cord blood (UCB) transplantation (UCBT) is increasingly used for a variety of malignant and benign hematological and other diseases. The main factor that limits the use of UCB to low weight recipients, mainly children and adolescents, is its low progenitor cell content. Various alternatives have been exploited to overcome this difficulty, including the transplantation of two UCB units (double umbilical cord blood transplantation, dUCBT). Following dUCBT, donor(s) hematopoietic stem cells (HSC) can be detected in the peripheral blood of the recipient as soon as 14 days post-transplantation. Sustained engraftment of HSC from one or both donors can be observed- dominance or mixed chimerism respectively, although single donor unit dominance has been observed in over 85% of patients. The underlying biology, which accounts for the interactions both between the two infused UCB units- cooperative or competitive, and with the recipient’s immune system, has not been elucidated. Full article

In this study, we have examined the role of post-translational modification of the myeloid master regulator C/EBPα by small ubiquitin-related modifier (SUMO). We have used transient transfection analysis, oligonucleotide pulldown assays and chromatin immunoprecititation in all-trans retinoic acid (ATRA)-inducible promyelocytic cell lines MPRO and NB4. We demonstrate that sumoylated wildtype p42-C/EBPαis associated with negative regulation of the myeloid specific lactoferrin (LF) gene in early myeloid cells and that a reduction in p42-C/EBPα sumoylation coincides with expression of the LF gene in maturing myeloid cells. In the acute promyelocytic leukemia cell line NB4 however, sumoylated p42 remains persistently bound to the LF promoter following ATRA-induction. This correlates with lack of lactoferrin expression in these cells. Changes in sumoylation status of C/EBPα thus appear to contribute to a switch that regulates transcriptional activity of this master regulator during normal neutrophil development. We also demonstrate that sumoylation of the AML associated dominant negative p30-C/EBPα isoform does not alter transactivation activity of the LF promoter. This may be because the p30 C/EBPα isoform binds to the LF promoter much less efficiently than its full length counterpart. Our data suggest that the activity of p42-C/EBPα in the developing neutrophil is more sensitive to changes in sumoylation than the p30 isoform. This difference may contribute to the leukemogenic potential of p30-C/EBPα. Full article

The health background management and outcomes of 5 pregnancies in 4 women affected by Cooley Disease, from Paediatric Institute of Catania University, are described, considering the preconceptual guidances and cares for such patients. These patients were selected among a group of 100 thalassemic women divided into three subgroups, according to their first and successive menstruation characteristics: (i) patients with primitive amenorrhoea, (ii) patients with secondary amenorrhoea and (iii) patients with normal menstruation. Only one woman, affected by primitive amenorrhoea, needed the induction of ovulation. A precise and detailed pre-pregnancy assessment was effected before each conception. This was constituted by a series of essays, including checks for diabetes and hypothyroidism, for B and C hepatitis and for blood group antibodies. Moreover were evaluated: cardiac function, rubella immunity and transaminases. Other pregnancy monitoring, and cares during labour and delivery were effected according to usual obstetrics practice. All the women were in labour when she were 38 week pregnant, and the outcome were five healthy babies born at term, weighting between 2600 and 3200 gs. The only complication was the Caesarean section. The improvements of current treatments, especially in the management of iron deposits, the prolongation of survival rate, will result in a continuous increase of pregnancies in thalassemic women. Pregnancy is now a real possibility for women affected by such disease. We are furthermore studying the possibility to collect the fetus' umbilical cord blood, after the delivery, to attempt eterologus transplantation to his mother trying to get a complete marrow reconstitution. Full article

The impact of BCR-ABL mRNA type (b3a2 vs. b2a2) on chronic myeloid leukemia (CML) phenotype is still a subject of controversies. We searched for a correlation between the BCR-ABL transcripts type and CML patients’ characteristics, including MDR1 gene expression. Ninety-eight untreated chronic phase CML patients were studied. The type of BCR-ABL fusion transcripts and MDR1 gene expression were determined by reverse transcriptase polymerase chain reaction. B3a2 and b2a2 transcripts were found in 53 [54%] and 44 [45%] patients, respectively. One patient co-expressed b3a2/b2a2 and was excluded from analysis. The only difference in the clinical characteristics between the two groups was the platelets count, that was higher in b3a2⁽⁺⁾ patients [791.3 ± 441.3 × 10⁹/L vs. 440.4 ± 283.4 × 10⁹/L in b2a2⁽⁺⁾; p = 0.007]. MDR1 over-expression [MDR1⁽⁺⁾] was observed in 48 patients (49.5%), more frequently in older patients >60 years [71% (24/34) vs. 38% (24/63) in younger; p = 0.008], and was associated with a lower white blood cells (WBC) count [105.5 ± 79.8 × 10⁹/L vs. 143.6 ± 96.5 × 10⁹/L in MDR1^(–) cases; p = 0.047]. On performing the analysis only within the MDR1⁽⁺⁾ group, the b3a2⁽⁺⁾ cases were characterized with a significantly higher platelets count [908.7 ± 470.1 × 10⁹/L vs. 472.9 ± 356.1 × 10⁹/L; p = 0.006] and a lower WBC count [85.4 ± 61.2 × 10⁹/L vs. 130 ± 93.9 × 10⁹/L; p = 0.004) compared to b2a2⁽⁺⁾ patients. No similar differences were found between b3a2⁽⁺⁾ and b2a2⁽⁺⁾ groups with normal MDR1 levels. These results indicate that the type of BCR-ABL transcripts correlates with the hematological parameters of CML, however only in the subgroup of patients characterized by MDR1 over-expression. Full article

Isoniazid induced sideroblastic anemia is a rare event. We report case of a 45 year old Caucasian women with development of severe anaemia 4 month after introduction of Isoniazid as part of Tuberculosis treatment. While haemoglobin fell to 47 g/L and erythrocyte count to 1.5 G/L, reticulocytes were very low (reticulocyte production index of 0.48), but bone marrow aspirate showed an accelerated erythropoiesis with ringsideroblasts. Anaemia rapidly resolved after cessation of Isoniazid. We postulate an Isoniazid induced inhibition of the δ-Amino-levulinat-synthase resulting in marked depletion of heam synthesis. Full article

Normocytic anaemia is caused either by hypoproliferation of haemopoietic tissue or increased destruction of red cells. Osteope­trosis is a rare cause of anaemia. Infantile osteopetrosis (also called malignant osteopetrosis) is diagnosed early in life. But it is the adult osteopetrosis (also called benign osteopetrosis) which is diagnosed in late adolescence or adulthood that present as anaemia which is difficult to diagnose and treat. Approximately one half of patients are asymptomatic, and the diagnosis is made incidentally, often in late adolescence because radiologic abnormalities start appearing only in childhood. In other patients, the diagnosis is based on family history. Still other patients might present with osteomyelitis or fractures. We are presenting here an unusual case of osteopetrosis which was referred to us for the evaluation of anaemia. Full article