Alberto Zubizarreta

Scedosporium inflatum infection in immunocompromised haematological patients

We report four cases of Scedosporium inflatum (S. inflatum) infection in severely immunocompromised haematological patients. Six well‐documented cases of S. inflatum disseminated infection in haematological patients have been reported: four in Australia and two in Spain. Their clinical and pathological characteristics are heterogenous, particularly in the Australian cases. However, the clinical and pathological profile emerging from our and other Spanish cases is homogenous and very similar to the clinico‐pathological spectrum of other disseminated mycoses, including Aspergillus and S. apiospermum. The optimal treatment of S. inflatum infection is unknown and the outcome in haematological patients is very poor. Eight patients died despite systemic antifungal treatment.

Allogeneic bone marrow transplantation versus intensification chemotherapy for acute myelogenous leukaemia in first remission: a prospective controlled trial.

In 1982 we began a prospective controlled trial to assess the effectiveness of allogeneic bone marrow transplantation and intensive post‐remission chemotherapy for patients with acute myelogenous leukaemia in first complete remission. Fourteen patients, 3–45 years of age, who had an HLA‐identical sibling donor, received bone marrow transplantation. Twenty‐five patients who either lacked an HLA‐identical sibling or were over 45 years of age received intensive consolidation chemotherapy including high‐dose cytosine arabinoside with or without adriamycin.

Pneumococcal pericarditis with cardiac tamponade in a patient with chronic graft-versus-host disease

We report a case of pneumococcal pericarditis in a 13-year-old boy following allogeneic BMT from an HLA-identical unrelated donor. The post-transplant course was complicated by chronic GVHD which led to reinstitution of immunosuppressive therapy. Eight months after BMT the patient developed pericarditis with cardiac tamponade, and Streptococcus pneumoniae was isolated in the pericardiocentesis fluid. This is the first reported case of pneumococcal pericarditis after BMT. Although pericardial effusions after allogeneic BMT are often sterile and related to conditioning therapy or associated with chronic GVHD, rapid microbiological investigation and empirical treatment with antibiotics are necessary. Prophylaxis for pneumococcal infection in patients with chronic GVHD is recommended.

THE USEFULNESS OF 1,25‐DIHYDROXY‐VITAMIN D3 (1,25(OH)2 vit D3) IN THE TREATMENT OF IDIOPATHIC MYELOFIBROSIS

In a recent annotation published in this journal, McCarthy (1 98.5) reviewed the causes and underlying mechanism of the deposition of collagen in bone marrow and discussed the possibility of using 1,25(OH)2 vit D3 to control such deposition and its ability to reverse myelofibrosis. He had published this suggested form of treatment previously (McCarthy ef al , 1984). The theory is that the active metabolite of vitamin D3 is able to inhibit the proliferation of megakaryocytes which usually promote collagen synthesis by releasing PDGF: in addition. that it can facilitate the reabsorption and increase the catabolism of collagen by being able to promote differentiation of CFIJ-GM in macrophages and monocytes which producc collagenase. Following the original suggestion (McCarthy et al, 1984), other authors (Arlet et al, 1984) published the results of treating three patients. One of these had myelofibrosis associated with chronic myelomonocytic leukaemia (CMML), one had myelofibrosis associated with posthypoparathyroid thrombocythacmia and one had ‘acute myelofibrosis’; there was apparent improvement in all the patients, and particularly in thc third, after treatment with 1 .2.5(OH)2 vit D 3 was started. We treated four patients in whom a diagnosis of idiopathic myelofibrosis had been made previously with 1,25(OH), vit D3 at a dose of 2.5 pg/d for 6 months. These patients had becri followed up for 1-7 years before treatment. None of these patients were transfusion dependent. Haematological data before and after treatment is given in Table 1. In addition, the collagen content of a bone marrow biopsy was assessed by two separate observers. In order to prevent the onset of secondary hypercalcaemia a calcium-deficient diet was given and fluid intake was increased; serum calcium, phosphorus and creatinine and urinary calcium and

A prospective controlled study of a computer-assisted acenocoumarol dosage program

The increase in oral anticoagulant (OA) treatment has led to development of new strategies for its control. We tested the efficacy of the GAO software (Dade Behring) in providing adequate acenocoumarol dosages for patients whose international normalised ratios (INRs) were no more than 0.5 points out of range. From December 1998 to August 1999, all outpatients in this setting were randomly assigned to receive computer-generated or traditionally fixed OA doses. Patients in their first 4 weeks of treatment were excluded. Overall, 8,352 dosages were calculated by the computer and 7,586 by the medical staff. The main endpoint of the study was the time spent in target INR range. The computer matched the traditional dosing, achieving a small but statistically significant greater efficacy in maintaining patients within the INR target range. The percentage of INR determinations over 5.5 was very low in both groups. Our results validate the computerised acenocoumarol dosing in our centre, achieving at least similar levels of effectiveness and safety compared with traditional dosage by medical staff.

Unusual ultrastructural findings in neuroblastoma

A morphologic study was made of the cell population which had infiltrated the bone marrow of a five‐year‐old boy. These cells showed a tendency to form rosette‐like structures. These structures as well as the presence (at ultrastructural level) of neurosecretory granules, cell processes, and microtubules in the neoplastic cells led to a diagnosis of neuroblastoma. Certain characteristics, not previously reported in neuroblastoma, were identified, such as gap junction type intercellular contacts, paracrystalline arrays in mitochondrial atypical cristae and nucleolus‐like bodies (nematosomes). Gap junctions are involved in the intercellular transfer of ions and low molecular weight metabolites and may explain the tendency to form cellular cluster in “rosettes” which are characteristic of this neoplasm. The presence of nematosomes in the tumor cell cytoplasm is one more piece of evidence which substantiates the nervous origin of these cells.

Simultaneous occurrence of follicular lymphoma in two monozygotic twins

Numerous cases of familial aggregation of Hodgkins disease (HD) or non-Hodgkins lymphoma (NHL) have been reported. An increased risk of HD in monozygotic twins of HD patients, compared to dizygotic twins has been demonstrated (Mack et al, 1995), providing strong evidence of a genetic susceptibility underlying HD. Among close relatives of patients with NHL, some authors have found that NHL was more frequent than expected by chance (Pottern et al, 1991), whereas others failed to prove this (Haim et al, 1982). NHL in monozygotic twins is a very rare ®nding which is associated to T phenotype (Schneider et al, 1995). In June 1995 a 48-year-old male was diagnosed with follicular lymphoma (small cleaved cell), stage IIA, having British Journal of Haematology, 1999, 107, 461±465

Treatment of acute leukemia in children: recent advances and future challenges.

Recently advances have been made in the treatment of acute leukemia in children, it is now possible to cure more than 70% of children with acute lymphoblastic leukemia. With the introduction of more intensive chemotherapy regimens in patients at higher risk of relapse and the identification of cases that could be less intensely treated to diminish long-term toxicity, it could be possible to improve these excellent results. In contrast, pediatric acute myeloid leukaemia seems to be a more heterogeneous disease and its response to conventional chemotherapy is not as uniform. Introduction of new and more efficacious therapies is necessary to improve the poor outcome, especially among patients with high-risk features.

Translocation (10;11)(p13;p15) in an infant acute myeloid leukemia with MLL gene rearrangement

Molecular rearrangements of the MLL gene at the 11q23 region have been identified in most cases of infant leukemia, regardless of the phenotype. We present a case of acute myeloid leukemia which coexpressed myeloid and lymphoid markers in a 12-month-old girl. Karyotype analysis revealed the presence of a thus far unreported translocation t(10;11)(p13;p15). Although no 11q23 abnormalities were cytogenetically detectable, an MLL gene molecular rearrangement was found.