Daniel Sturaro

Low mortality rates related to respiratory virus infections after bone marrow transplantation.

Summary:Respiratory viruses (RVs) frequently cause severe respiratory disease in bone marrrow transplant (BMT) recipients. To evaluate the frequency of RV, nasal washes were collected year-round from BMT recipients with symptoms of upper respiratory tract infection (URI). Direct immunofluorescence assay was performed for respiratory syncytial virus (RSV), influenza (Flu) A and B, adenovirus and parainfluenza (Paraflu) virus. Patients with RSV pneumonia or with upper RSV infection, but considered at high risk for developing RSV pneumonia received aerosolized ribavirin. Oseltamivir was given to patients with influenza. A total of 179 patients had 392 episodes of URI. In all, 68 (38%) tested positive: RSV was detected in 18 patients (26.4%), Flu B in 17 (25%), Flu A in 11 (16.2%) and Paraflu in 7 (10.3%). A total of 14 patients (20.6%) had multiple RV infections or coinfection. RSV pneumonia developed in 55.5% of the patients with RSV-URI. One of the 15 patients (6.6%) with RSV pneumonia died. Influenza pneumonia was diagnosed in three patients (7.3%). RSV and influenza infections peaked in fall–winter and winter–spring months, respectively. We observed decreased rates of influenza and parainfluenza pneumonia and low mortality because of RSV pneumonia. The role of antiviral interventions such as aerosolized ribavirin and new neuraminidase inhibitors remains to be defined in randomized trials.

Use of Oseltamivir to control influenza complications after bone marrow transplantation

Summary:Influenza infection can be severe in bone marrow transplant (BMT) recipients. Although yearly epidemics occur worldwide, and a higher risk of complication is expected in these patients, few studies have addressed the impact of the new neuraminidase inhibitors in the prognosis of influenza after BMT. Influenza A or B infections were found in 39 of the 66 patients (59%) showing a positive nasal wash by DFA. Influenza A was diagnosed in 18 patients and influenza B in 23 patients; two patients were infected by influenza A and B with 84- and 90-day intervals between episodes, respectively. Of the 41 episodes (61%) of influenza A or B, 25 infections occurred during the spring and summer months. Oseltamivir was introduced within 48 h of symptoms appearing. Only two patients (5.1%) developed influenza pneumonia, and no patient died of influenza. A total of 22 patients (56.4%) acquired influenza before day +180 when preventive vaccination strategies are precluded owing to poor immunogenicity of the vaccine during this period. Oseltamivir proved to be safe and appears to have played an important role in the outcome of influenza infection in this population. The therapeutic and/or prophylactic benefits of Oseltamivir in BMT recipients remain to be demonstrated in randomized, prospective trials.

Addition of low-dose busulfan to cyclophosphamide in aplastic anemia patients prior to allogeneic bone marrow transplantation to reduce rejection

Summary:Busulfan was added at the dose of 4 mg/kg to 200 mg/kg cyclophosphamide in 81 patients (3–53 years, median 24) with aplastic anemia to reduce graft rejection. Graft-versus-host disease (GVHD) prophylaxis comprised cyclosporine–methotrexate. The number of prior transfusions was 0–276 (median 26), and 48% had received prior immunosuppressive therapy. Two patients experienced primary graft failure, and 10 secondary rejection at 28–1001 days (median 317 days). The cumulative incidence of rejection was 22%; for heavily transfused patients (⩾50 U) it was 43% compared to 16% for the rest (P=0.06). Overall survival rate at 8 years was 56%; patients who received ⩽15 and >15 transfusions was 78 and 50%, respectively (P=0.01), whereas it was 67 and 28% for ⩽50 and >50 transfusions, respectively (P=0.002). In multivariate analysis, higher number of prior transfusions, shorter period of immunosuppression with cyclosporine and GVHD were associated with inferior survival; moreover, a higher risk of graft rejection were associated with a higher number of prior transfusions and a trend was observed for a shorter cyclosporine administration. Low-dose busulfan is feasible and may be helpful in patients exposed to <50 transfusions. However, rejection remains a significant problem, mainly in heavily transfused patients.

Prognostic impact of diffuse large B-cell lymphoma subgroups in patients undergoing autologous SCT

A total of 53 patients aged 18–60 years with high-intermediate or high-risk diffuse large B-cell lymphoma (DLBCL) were evaluated to analyze the impact of the cell of origin. Of 53 patients, 16 underwent autologous SCT (ASCT) in first remission and the rest received conventional chemotherapy. Immunohistochemistry was evaluated in 47 cases 17 were of germinal center (GC) origin and 30 were of non-GC origin. There was no survival difference between the two groups. Overall survival (OS) and disease-free survival (DFS) at 3 years were 93 and 83%, respectively, for the 14 patients who underwent ASCT. Their DFS was significantly better than that of patients who achieved CR but did not undergo ASCT. We conclude that ASCT is safe and improves the DFS of high-intermediate and high-risk DLBCL, regardless of the cell of origin. This observation should be confirmed in a larger study.

Evaluation of early hospital discharge after allogeneic bone marrow transplantation for chronic myeloid leukemia

CONTEXT AND OBJECTIVE The increasing number of patients waiting for bone marrow transplantation in our service led to the implement of an early hospital discharge program with the intention of reducing the interval between diagnosis and transplantation. In this study we analyzed the results from early discharge, with outpatient care for patients with chronic myeloid leukemia who underwent allogeneic bone marrow transplantation. DESIGN AND SETTING Retrospective study at the Bone Marrow Transplantation Unit of Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo. METHODS We compared clinical outcomes within 100 days post-transplantation, for 51 patients with chronic myeloid leukemia (CML) who received partially outpatient-based allogeneic hematopoietic stem cell transplantation, and the results were compared with a historical control group of 49 patients who received inpatient-based hematopoietic stem cell transplantation. RESULTS There were significantly fewer days of hospitalization (p = 0.004), Pseudomonas-positive cultures (p = 0.006) and nausea and vomiting of grade 2-3 (p < 0.001) in the outpatient group. There were no significant differences in mortality between the groups and no deaths occurred within the first 48 days post-transplantation in the outpatient group. CONCLUSIONS This partially outpatient-based hematopoietic stem cell transplantation program allowed an increased number of transplantations in our institution, in cases of CML and other diseases, since it reduced the median length of hospital stay without increasing morbidity and mortality.

O transplante de medula óssea na leucemia mielóide aguda: análise de 80 pacientes transplantados no complexo do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

The patients records of eighty consecutive patients with acute myeloid leukemia (AML) submitted to allogeneic (allo BMT) and autologous (auto BMT) bone marrow transplantation (BMT) between 1989 and 2001 were assessed. Forty percent were alive in the end of the study; 37.9% of allogeneic patients and 45.4% of autologous. Factors such as gender, the French-American-British AML classification, induction treatment, number of infused cells and the conditioning regiment did not have any impact in survival. Patients with AML from M1 to M4, and who were consolidated with high doses of arabinoside had better a survival rate (p=0.0148). Patients in their first complete remission also had better survival both with allogeneic and autologous BMT, with respective survival rates of 52.6% and 69.2%. Acute graft-versus-host disease (GvHD) had an impact when it was compared the absence, grade I/II with III/IV giving a p-value of 0.0285. Infection was the most frequent cause of death in allogeneic BMT. In autologous BMT relapse was the principal cause of death. Toxicity related to the procedure occurred in 38.9% of patients who died in allogeneic BMT and 16.7% in autologous BMT. In univariant Cox analyses for prognostic factors, the disease status and acute GvHD were significant, but this significance was lost in the multiple variant analyses (p-value = 0.069).

The importance of pharmacotherapeutic follow-up in onco-haematological patients

1. Macedo BS, Garrote CFD, Oliveira ND. Projeto de implantacao deatencao farmaceutica a pacientes portadores de diabetes mellitustipo 2 em programa de saude da familia. Revista Eletronica deFarmacia. 2005;2(2):116-8.2. Faus MJ, Martinez F, Fernadez-Llimos F. Programa Dader deimplantacion del Seguimiento del Tratamiento Farmacologico.Granada: GIAF-UGR; 2000.3. Machuca M, Fernadez-Llimos F, Gastelurrutia MA. Guia deSeguimento Farmacoterapeutico: Metodo Dader. Granada:GIAF-UGR;2003. (disponivel em URL: http://www.giaf-ugr.org/docu/docu-giaf.htm)4. Pharmaceutical Care Research Group, University of Granada (Spain).Pharmacotherapy follow up: The Dader method (3rd revision:2005). Pharmacy Practice. 2006;4(1):44-53.5. Grupo de expertos. Consenso sobre Atencion Farmaceutica. Ars Pharm.42(3-4):221-41;2001. (disponivel em http://pharmacia.ugr.es/ars/)6. Ivama AI, Noblat L, Castro MS. Consenso Brasileiro de AtencaoFarmaceutica: Trilhando caminhos. Brasilia: OPAS;2002.

Transplante de células-tronco hematopoéticas em doenças reumáticas. Parte 2: experiência brasileira e perspectivas futuras

In this review, we discuss the results of hematopoietic stem cell transplantation (HSCT) for severe and refractory rheumatic diseases performed in Brazil. We analyze preliminary results obtained in Brazil with autologous HSCT in anecdotal cases (N = 3) and in the cooperative protocol initiated in 2001 (N = 18). In 8 lupus nephritis patients there were 3 sustained remissions, 3 deaths, 1 mobilisation failure and 1 short follow-up; in 7 systemic sclerosis patients there were 3 sustained remissions after transplantation and 2 after mobilisation, 1 death before mobilisation and another after the first dose of the conditioning in an overlapping syndrome of SLE and SSc, and between 2 patients with vasculitis there was 1 sustained remission in Takayasus arteritis and another in Behcets disease. One patient with juvenile idiopathic arthritis was included in the protocol very recently. The follow-up of the patients varied from 0 to 48 months with a median of 29 months. We conclude the study with a discussion of future prospectives in developed countries, where randomized trials comparing transplantation with the best pharmacological therapy available have started recently, and in Brazil, where several adaptations of existing protocols are required and the cost of transplantation is much lower than that of new biological therapies.