Allogeneic bone marrow transplantation versus chemotherapy in high-risk childhood acute lymphoblastic leukaemia in first remission

We compared the outcome of children with high-risk acute lymphoblastic leukaemia (HR-ALL) in first complete remission (first CR) treated with chemotherapy (CHEMO) or with allogeneic bone marrow transplantation (BMT) in a multicentre study.   All children treated by the Italian Paediatric Haematology Oncology Association for HR-ALL in first CR between 1986 and 1994 were eligible for the study. 30 children were given BMT at a median of 4 months from first CR, with preparative regimens including total-body irradiation ( n  =25/30). 130 matched controls for BMT patients were identified among 397 HR-ALL CHEMO patients. Matching on main prognostic factors and duration of first CR was adopted to control the selection and time-to-transplant biases. The comparative analysis was based on the results of a stratified Cox model. The estimated hazard ratios of BMT versus CHEMO at 6 months, 1 year and 2 years after CR were 1.38 (CI 0.59–3.24), 0.69 (CI 0.27–1.77) and 0.35 (CI 0.06–1{\raise 5mu ..91), with an overall non-significant difference between the two groups ( P  = 0.34). With a median follow-up of 4 years, the disease-free survival was 58.5% (SE 9.3) in the BMT group and 47.7% (SE 4.8) in the CHEMO group, at 4 years from CR. Non-leukaemic death occurred in 4% of CHEMO and 10% of BMT patients. In the BMT group the estimated cumulative incidence of relapse at 1.5 years from CR was 31.5% (SE 8.8) and did not change thereafter, whereas in the CHEMO group the corresponding figure was 29.2% (SE 4.1) and the incidence continued to increase thereafter (48.2% (SE 4.8) at 4 years from CR).   The results of this study suggest that, with respect to the CHEMO group, the higher risk of early failure in the BMT group is outweighed by the lower risk of relapse after 1 year. Results prompt the need for a prospective study, in order to demonstrate the likely advantage of BMT in HR childhood ALL in first CR.     

Histological changes in murine haemophilic synovitis: a quantitative grading system to assess blood-induced synovitis

Haemophilia is a congenital disorder that results in frequent bleeding into joints, in which a chronic and debilitating arthritis develops. The presence of blood evokes an inflammatory and proliferative synovial reaction. Although the molecular mechanisms and biochemical pathways which underlie this disorder are not known, significant advances have been made by studying a murine model of human haemophilic synovitis. In order to better understand and correlate the pathological, molecular and biochemical changes, it has become necessary to grade the histological changes observed. Despite a search of the literature and review of relevant publications, none of the currently utilized schemes were appropriate, and therefore a novel grading scheme was developed. After review of over 1000 histological sections, six characteristic changes were identified: (i) synovial hyperplasia; (ii) vascularity; (iii) discolouration by haemosiderin; (iv) the presence of blood (erythrocytes); (v) villus formation; and (vi) cartilage erosion. Synovial hyperplasia and vascularity were present in variable amounts and were quantitatively scored (0-3), while the other changes were qualitatively scored as absent or present (0 or 1). Application of the grading scheme was tested and a high interobserver correlation (greater than 80%) was found. The scheme was easy to learn even by novices, with no prior experience. The availability of the histological grading scheme for murine synovitis will allow for precise evaluation of the pathological changes following joint bleeding, and facilitate correlations with molecular and biochemical changes that lead to these changes.     

Modified β-Cyclodextrin (SBE7-β-CyD) with Viscous Vehicle Improves the Ocular Delivery and Tolerability of Pilocarpine Prodrug in Rabbits

The complexation of pilocarpine prodrug, O,O'-dipropionyl-(1,4-xylylene) bispilocarpate, with various β-cyclodextrin (β-CyD) derivatives was studied by the phase solubility method. The effects of coadministered sulphobutyl ether β-CyD (SBE7-β-CyD) with and without poly(vinyl alcohol) (PVA) on the miotic response and eye irritation of the prodrug were investigated in pigmented rabbits. The pilocarpine prodrug formed 1:1 inclusion complexes with variably substituted sulphobutyl ether derivatives of β-CyD (SBE4-β-CyD and SBE7-β-CyD), and 1:1 and 1:2 complexes with hydroxypropyl-β-CyD (HP-β-CyD) at pH 7:4. Coadministered SBE7-β-CyD eliminated the eye irritation due to the pilocarpine prodrug, but also decreased the miotic response. Ocular absorption of the prodrug was improved by increasing the viscosity of prodrug/SBE7-β-CyD solution with PVA without inducing any eye irritation. Eye irritation due to viscous prodrug/SBE7-β-CyD solutions was comparable with isotonic NaCl solution. We conclude that administration of pilocarpine prodrug in viscous SBE7-β-CyD solution decreases substantially eye irritation while ocular absorption is not affected.     

Surgical excision of a giant pelvic pseudotumour in a patient with haemophilia A

The development of pseudotumors represents one of the most challenging complications facing physicians who care for patients with hemophilia. The successful removal of the giant pseudotumor described in this case report was achieved by a multidisciplinary team and demonstrates that this approach, albeit associated with significant risk, may be curative.     

A simple new technique to prevent bleeding in transplant nephrectomy

Renal transplantectomy is still a frequent procedure for a transplant surgeon. Nevertheless, it is constantly marred by complications, first of all bleeding. In fact, the local circumstances after the operation and the general health state of the uremic patients lead to a high incidence of this complication. To avoid this, we adopt a particular technique for renal extracapsular transplantectomy, performing three running sutures between the two faces of the renal capsule. This prevents the formation of the hematoma which is the basis of the continuous bleeding and following infection. We collected a series of nine patients who underwent transplantectomy in which we used this technique. No complications were noted.     

Time to First Shock in Implantable Cardioverter Defibrillator (ICD) Patients with Chagas Cardiomyopathy

The time to first ICD shock has been extensively studied in patients with coronary artery disease (CAD). However, there are no published data on ICD shocks in patients with Chagas cardiomyopathy (ChC). The occurrence of the first appropriate ICD shock during the first 6 months of follow-up in 20 patients with ChC (group 1) and 35 CAD patients (group 2) was analyzed retrospectively. All patients had received a third-generation pectoral ICD for ventricular tachycardia or fibrillation (VT/VF). Indications for ICD implantation were refractoriness to drug therapy or noninducibility of VT/VF at EPS in cardiac arrest survivors. Results: The mean age, left ventricular ejection fraction (LVEF), and sex in groups I and II were 57.4 ± 7 years versus 64 ± 9 (P < 0.01), 30.9%± 10% versus 32.9%± 10% (P = NS), and 10 men versus 31 women (P < 0.005), respectively. Six months after ICD implantation, 85% (17/20) group I patients received appropriate ICD shocks versus 51 % (18/35) in group 2, a statistically significant difference (P < 0.02, RR: 1.65, OR: 5.35). Conclusions: The incidence of appropriate ICD shocks within the first 6 months postimplantation was significantly higher in ChC patients than in CAD patients. ChC patients were younger and more often women than CAD patients.     

Postauthorization safety surveillance of ADVATE [antihaemophilic factor (recombinant), plasma/albumin‐free method] demonstrates efficacy,safety and low‐risk for immunogenicity in routine clinical practice

Summary. Postauthorization safety surveillance of factor VIII (FVIII) concentrates is essential for assessing rare adverse event incidence. We determined safety and efficacy of ADVATE [antihaemophilic factor (recombinant), plasma/albumin‐free method, (rAHF‐PFM)] during routine clinical practice. Subjects with differing haemophilia A severities and medical histories were monitored during 12 months of prophylactic and/or on‐demand therapy. Among 408 evaluable subjects, 386 (95%) received excellent/good efficacy ratings for all on‐demand assessments; the corresponding number for subjects with previous FVIII inhibitors was 36/41 (88%). Among 276 evaluable subjects receiving prophylaxis continuously in the study, 255 (92%) had excellent/good ratings for all prophylactic assessments; the corresponding number for subjects with previous FVIII inhibitors was 41/46 (89%). Efficacy of surgical prophylaxis was excellent/good in 16/16 evaluable procedures. Among previously treated patients (PTPs) with >50 exposure days (EDs) and FVIII ≤2%, three (0.75%) developed low‐titre inhibitors. Two of these subjects had a positive inhibitor history; thus, the incidence of de novo inhibitor formation in PTPs with FVIII ≤2% and no inhibitor history was 1/348 (0.29%; 95% CI, 0.01–1.59%). A PTP with moderate haemophilia developed a low‐titre inhibitor. High‐titre inhibitors were reported in a PTP with mild disease (following surgery), a previously untreated patient (PUP) with moderate disease (following surgery) and a PUP with severe disease. The favourable benefit/risk profile of rAHF‐PFM previously documented in prospective clinical trials has been extended to include a broader range of haemophilia patients, many of whom would have been ineligible for registration studies.     

Arthroscopic synovectomy in haemophilia: indications, technique and results

Summary.  Recurrent spontaneous haemarthrosis are commonly seen in patients affected by haemophilia. The knee and the elbow are most commonly affected and both are amenable to arthroscopic treatment. Arthroscopic synovectomy is indicated after failure of appropriate medical management with recurrent bleeding. Many patients also demonstrate motion loss and functional deterioration. The benefits of arthroscopic synovectomy include the ability to perform adequate synovial debridement, but also concomitant lysis of adhesion and capsular release to regain range of motion. Results of arthroscopic synovectomy demonstrate a significant decrease in episodes of haemarthrosis, and significant improvement in pain, range of motion and function. The primary predictor of outcome is degree of pre-existing degenerative changes within the joint. In more severe cases, the results of arthroscopic synovectomy are unpredictable and serious consideration should be given to primary arthroplasty.