Carlos R. Medeiros

Marrow transplantation for Fanconi anaemia: conditioning with reduced doses of cyclophosphamide without radiation.

Nine patients with Fanconi anaemia (FA) were conditioned for HLA‐identical sibling bone marrow transplant (BMT) with reduced dose of cyclophosphamide (Cy) without radiation or antithymocyte globulin (ATG). The total dose of Cy was 140 mg/kg (n=2) or 120 mg/kg (n=7). The median patient age was 8 years (range 4–19). Graft‐versus‐host disease (GVHD) prophylaxis was with methotrexate and cyclosporine (n=8) or cyclosporine alone (n=1). All patients had sustained engraftment and two developed grade ≥II acute GVHD. Cy toxicity included grade ≥2 mucositis seen in all evaluable patients and haemorrhagic cystitis in two patients. The Kaplan‐Meier survival estimate is 89% with a median follow‐up of 285 d (range 56–528).

Central Nervous System Infections Following Bone Marrow Transplantation: An Autopsy Report of 27 Cases

The authors retrospectively assess the autopsy findings of central nervous system (CNS) infections in marrow transplant recipients. From July 1987 to June 1998, 845 patients at our institution were submitted to bone marrow transplantation (BMT). The CNS of 180 patients was studied through autopsy and these patients had their medical records reviewed. Twenty-seven (15%) patients presented brain parenchyma infection. Fungi were isolated in approximately 60% of the cases. Mean survival time was 153 days (0-1,264 days) and the majority of the patients died during the first 3 months after BMT (18 cases; 67%). Aspergillus sp. were the most prevalent fungi (approximately 30%), followed by Candida sp. infection (approximately 18%). There was one case of Fusarium sp. infection and two cases of unidentified fungus. All patients with fungal infections had documented involvement at widespread sites. Toxoplasma gondii encephalitis was demonstrated in 8 patents (approximately 30%). Bacterial abscesses were responsible for approximately 11% of the findings. Eleven (41%) of the 27 patients died secondary to cerebral causes. These results show that infectious compromise of the CNS following BMT is a highly fatal event, caused mainly by fungi and T. gondii. Furthermore, they provide a likely guide to the possible causes of brain abscesses following BMT.

Low-dose cyclophosphamide conditioning for haematopoietic cell transplantation from HLA-matched related donors in patients with Fanconi anaemia

Allogeneic haematopoietic cell transplantation (HCT) is effective therapy for Fanconi anaemia (FA). FA patients do not tolerate conditioning with 200 mg/kg of cyclophosphamide (Cy), typically used in aplastic anaemia. We previously published results of studies in which Cy doses were gradually reduced from 200 to 100 mg/kg. Here we update results of the initial studies and report data on 30 new patients conditioned with Cy either at 80 mg/kg (n = 7) or at 60 mg/kg (n = 23), given over 4 days before HCT from human leucocyte antigen‐matched related donors. Methotrexate and cyclosporine were given for graft‐versus‐host disease (GVHD) prophylaxis. All seven patients given Cy at 80 mg/kg and 21 of 23 given Cy at 60 mg/kg had sustained engraftment, while two patients, both with clonal cytogenetics abnormalities, experienced graft failure. Grades 2–3 acute GVHD rates were 57% and 14% for patients given the higher and lower Cy doses, respectively (P = 0·001). Four patients given Cy at 80 mg/kg and 22 given Cy at 60 mg/kg were alive at a median of 47 (44–58) months and 16 (3–52) months, respectively. Cy at 60 mg/kg has acceptable toxicities, low rates of GVHD, and is sufficient for engraftment of related grafts in most FA patients.

Reversible posterior leucoencephalopathy syndrome associated with bone marrow transplantation

Reversible posterior leucoencephalopathy syndrome (RPLS) has previously been described in patients who have renal insufficiency, eclampsia, hypertensive encephalopathy and patients receiving immunosuppressive therapy. The mechanism by which immunosuppressive agents can cause this syndrome is not clear, but it is probably related with cytotoxic effects of these agents on the vascular endothelium. We report eight patients who received cyclosporine A (CSA) after allogeneic bone marrow transplantation or as treatment for severe aplastic anemia (SSA) who developed posterior leucoencephalopathy. The most common signs and symptoms were seizures and headache. Neurological dysfunction occurred preceded by or concomitant with high blood pressure and some degree of acute renal failure in six patients. Computerized tomography studies showed low-density white matter lesions involving the posterior areas of cerebral hemispheres. Symptoms and neuroimaging abnormalities were reversible and improvement occurred in all patients when given lower doses of CSA or when the drug was withdrawn. RPLS may be considered an expression of CSA neurotoxicity.

O câncer e sua representação simbólica

The purpose of this study is to investigate the symbolic representation of cancer, in order to help health professionals, patients, relatives involved, and others who might have interest on this subject, through questionnaires. The research collected data to show the different reactions of people directly involved with cancer. The results show that, despite of the demographic differences, the answers were extremely taken as personal. The self image interferes on the perception, reactions, and time line organization of the patients and those affected by the symbolic contamination. As the death gets closer to the patients, this research might help to improve the existents methods of treatment. Not so ever, in order to help others, it is necessary to fortify own self image. After all, we, health professionals are the ones to reproduce those images along the centuries, despite of the scientific improvements.

Bone marrow transplantation in patients with storage diseases: a developing country experience

Bone marrow transplantation (BMT) is a therapeutic option for patients with genetic storage diseases. Between 1979 and 2002, eight patients, four females and four males (1 to 13 years old) were submitted to this procedure in our center. Six patients had mucopolysaccharidosis (MPS I in 3; MPS III in one and MPS VI in 2), one had adrenoleukodystrophy (ALD) and one had Gaucher disease. Five patients had related and three unrelated BMT donor. Three patients developed graft versus host disease (two MPS I and one MPS VI) and died between 37 and 151 days after transplantation. Five patients survived 4 to 16 years after transplantation. Three patients improved (one MPS I; one MPS VI and the Gaucher disease patient), one patient had no disease progression (ALD) and in one patient this procedure did not change the natural course of the disease (MPS III).

Neurological complications of hematopoietic stem cell transplantation (HSCT): a retrospective study in a HSCT center in Brazil

We present the neurological complications evaluated in a series of 1000 patients who underwent hematopoietic stem cell transplantation (HSCT). Central nervous system (CNS) neurological complications, particularly brain hemorrhages, were the most common, followed by seizures and CNS infections. An unusual neurological complication was Wernickes encephalopathy. Less frequent neurological complications were metabolic encephalopathy, neuroleptic malignant syndrome, reversible posterior leukoencephalopathy syndrome, brain infarct and movement disorders. The most common neurological complication of the peripheral nervous system was herpes zoster radiculopathy, while peripheral neuropathies, inflammatory myopathy and myotonia were very rarely found.

Cavernous sinus thrombosis caused by zygomycosis after unrelated bone marrow transplantation.

Abstract: Invasive zygomycosis is a devastating fungal infection occurring as an opportunistic infection after bone marrow transplantation (BMT). Sinusitis can lead to fungal infection in immunosuppressed patients, and cavernous sinus thrombosis, an uncommon condition in immunocompetent patients, typically follows an infection involving the medial third of the face, nose, or paranasal sinuses. Patients undergoing unrelated‐donor BMT (UD‐BMT) are prone to develop life‐threatening infections because of poor recovery of cellular immunity. Despite adequate clinical evaluation and treatment, the prognosis of patients with invasive fungal infections is dismal, especially when intracerebral structures are affected. We describe a case of a patient who underwent an UD‐BMT and developed cavernous sinus thrombosis after sinusitis due to zygomycosis. Moreover, he also had disseminated fungal (Zygomycetes and Aspergillus) and viral (cytomegalovirus and adenovirus) infections.

Carcinoma de células escamosas em língua pós-transplante de medula óssea por Anemia de Fanconi

Anemia Fanconi (AF) e uma sindrome autossomica recessiva, caracterizada por pancitopenia progressiva com hipoplasia de MO, em associacao com varias anormalidades constitucionais, tendo como unico recurso terapeutico com possibilidade potencial de cura o transplante de medula ossea, e sendo tais pacientes propensos ao desenvolvimento de malignidades hematologicas e carcinoma de celulas escamosas (CEC) em diversos locais: reto, vagina, cervice, esofago, cavidade bucal, faringe ou pele, mas especialmente em cabeca e pescoco. Relatamos aqui tres casos de pacientes portadores de AF, que apos TMO desenvolveram CEC em lingua. Alem disso, mencionamos fatores de risco relatados para tal evento, como diagnostico de AF, condicionamento pre-transplante (quimioterapicos e irradiacao), terapia com drogas imunossupressoras para tratamento de doenca enxerto contra hospedeiro (DECH) aguda ou cronica, sexo e idade avancada. Alem do que, discorremos sobre a existencia de tres mecanismos postulados que predispoem individuos com AF ao desenvolvimento de neoplasia: (1) defeito na reparacao do DNA; (2) defeito na detoxificacao de radicais de oxigenio; e (3) imunodeficiencia.

Fungal encephalitis following bone marrow transplantation: clinical findings and prognosis.

BACKGROUND Central nervous system fungal infections (FI) are important complications and a cause of mortality in patients who receive hematopoietic stem cell transplantation (HSCT). AIMS To study the clinical aspects of fungal encephalitis (FE). SETTINGS AND DESIGN The study was carried out at the HSCT Center of the Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil. MATERIALS AND METHODS Clinical records and autopsy reports from patients submitted to HSCT with a diagnosis of FE. RESULTS Twelve patients were diagnosed with FE presenting with lowered level of consciousness, hemiparesis and seizures. We were able to identify two subgroups regarding susceptibility to FE: (1) patients with early onset FI and severe leucopenia, and (2) patients with later onset FI with graft-versus-host disease using immunosuppressive drugs. Eleven of the patients died directly due to the neurological complication, all had post-mortem confirmation of the diagnosis of FI. CONCLUSIONS These clinical, paraclinical and temporal patterns may provide the opportunity for earlier diagnosis and interventions.