Rosaura Saboya

CMV pneumonia in allogeneic BMT recipients undergoing early treatment or pre-emptive ganciclovir therapy.

The incidence, treatment and outcome of CMV interstitial pneumonia (CMV-IP) were reviewed in 139 consecutive allogeneic BMT patients undergoing extended CMV antigenemia surveillance and two different ganciclovir (GCV) strategies to control CMV infection. Nineteen cases of CMV-IP were reviewed, 16 of 63 patients (25.4%) who received early GCV treatment (ET) and three of 76 patients (3.9%) who received pre-emptive (PE) GCV therapy. In the ET group, the median time for occurrence of CMV-IP was 55 (range 36 to 311) days. Two patients had three episodes of CMV-IP recurrences after day +100. CMV-IP-related death occurred in two patients (15.4%). In the PE group, 41 patients received pre-emptive GCV therapy prompted by the appearance of positive antigenemia ⩾2 cells. The median time for the occurrence of CMV-IP was 92 (range 48 to 197) days. Response to therapy was observed when GCV was introduced within 6 days of antigenemia positivity. The use of IVIg in association with GCV did not play a major role in response to therapy. The median time for occurrence of CMV-IP was delayed during PE strategy and the cost-effectiveness of CMV surveillance after day +100 should be investigated in this population. Bone Marrow Transplantation (2000) 26, 413–417.

Factors affecting hematopoietic progenitor cell mobilization: an analysis of 307 patients.

We reviewed the data of 307 patients treated with autologous bone marrow transplantation with the aim to identify factors associated with poor hematopoietic stem cell (HSC) mobilization after administration of cyclophosphamide and granulocyte-colony stimulating factor. Success in mobilization was defined when > or = 2.0 x 10(6) CD34+ cells/kg weight could be collected with < or = 3 leukapheresis procedures. Success was observed in 260 patients (84.7%) and nonsuccess in 47 patients (15.3%). According to the stepwise regression model: diagnosis, chemotherapy load, treatment with mitoxantrone and platelet count before mobilization were found to be independent predictive factors for HSC mobilization. These results could help in the previous recognition of patients at risk for non response to mobilization and allow to plan an alternative protocol for this group of patients.

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.

Strongyloides stercoralis hyperinfection after allogeneic stem cell transplantation

Strongyloides hyperinfection is a potentially fatal syndrome associated with deficient cell-mediated immunity. However, despite the severe deficiency of cell-mediated immunity seen after hematopoietic stem cell transplantation (HSCT), this syndrome has rarely been reported, even in endemic areas such as South America. A 35-year-old man underwent a peripheral blood cell allograft from his HLA-identical sibling in October 2007 for ALL in third refractory relapse. The conditioning comprised oral busulfan (16mg/kg) and i.v. melphalan (140mg/m). GVHD prophylaxis comprised cyclosporine (3mg/kg/day). The CD34þ cell dose was 6.58 10 per kg. Prophylaxis consisted of fluconazole, acyclovir and cefepime. Engraftment was prompt, and the early post transplant course was uneventful. He was admitted 54 days after transplantation with abdominal pain, macroscopic hematuria with clots, dry cough and fever. He was on a low dose of prednisone. The chest X-ray revealed bilateral crackles. Hemoglobin was 10.6 g/100ml, the WBC count was 3.2 10/l (83% neutrophils, 12% lymphocytes, 5% monocytes and 0% eosinophils) and the platelet count was 25 10/l. Kidney function was normal. CMV antigenemia was detected. History showed that he had always lived in the Amazonian basin in Brazil, had consumed untreated or unfiltered water, had suffered insect bites and did not use protective footwear. The patient was treated with continuous bladder irrigation and broad-spectrum antibiotics, including ganciclovir. In the presence of computed tomography findings of probable invasive aspergillosis and diffuse bilateral infiltrates on the chest X-ray, liposomal amphotericin was started at the dose of 3mg/kg daily. Hemorrhagic cystitis was resolved with supportive treatment. The patient developed diarrhea, nausea, abdominal discomfort and anorexia, with cough and hemoptysis. Stool examinations showed Strongyloides stercoralis larvae on direct microscopy. He was treated with thiabendazole 25mg/kg for 7 days and sputum samples for detection of S. stercoralis were collected. Combination therapy with ivermectin (200mcg/kg/day) and thiabendazole (25mg/kg/day) for 7 days was initiated after the stool examinations continued to be persistently positive. The gram stain indicated the presence of multiple filariform larvae of S. stercoralis in the sputum. All subsequent stool examinations were negative, and the signs and symptoms disappeared after 3 days of treatment. The patient was discharged from hospital on day 75 after PBSC transplantation to continue the treatment in the outpatient clinic. The plan was to repeat antiparasitic treatment after 21 days. The low rates of strongyloidiasis after HSCT can be explained by routine screening for this parasite and the use of prophylactic treatment before transplantation. Examination of three or more stool samples has a sensitivity of 60–70% to detect S. stercoralis. In our hospital, three stool samples are examined before HSCT in all patients. Serology by ELISA can also be used to diagnose S. stercoralis. In a study of sera from 164 hematological patients tested for the presence of Ab to S. stercoralis, the Ab was detected in serum using ELISA. The sensitivity, specificity, and positive and negative predictive values were 68, 89, 48 and 95%, respectively. In endemic areas, the use of serology is controversial, and only a negative test is useful. A retrospective analysis showed that the overall rate of S. stercoralis infection was 1.0 per 10 000 new cancer cases in the United States. Most of the patients (88%) were US residents. Evidence of hyperinfection syndrome was observed in two HSCT recipients who developed fatal S. stercoralis hemorrhagic alveolitis despite receiving highdose thiabendazole and ivermectin therapy. One case of alveolar hemorrhage, post-HSCT, due to strongyloides hyperinfection was recently described. Therapy with parenteral ivermectin and thiabendazole was initiated, but the patient’s condition deteriorated and he died of respiratory failure and septic shock. There are two other reported cases of strongyloidiasis in autologous HSCT patients, one developing fatal hyperinfection after corticosteroids. They were both treated with albendazole and ivermectin. Our patient was not neutropenic, was on low doses of corticosteroids and had received cyclosporine, which has anti-helminth activity. Although there are no described cases of strongyloidosis hyperinfection while on cyclosporine, a recent report showed that three consecutive cadaveric kidney transplant recipients who were on tacrolimus died within 2 months from strongyloides hyperinfection. Two of the recipients had received their kidneys from a single cadaveric donor, wheras the third received it from a different donor. Both the donors came from areas endemic for strongyloidiasis. The best way to treat strongyloidiasis is unclear. Relapse is more frequent in immunocompromised patients, particularly with the use of corticosteroids. Combination therapy is frequently used to treat strongyloides hyperinfection Bone Marrow Transplantation (2009) 43, 741–742 & 2009 Macmillan Publishers Limited All rights reserved 0268-3369/09

Phialemonium curvatum infection after bone marrow transplantation

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Transplante de células-tronco hematopoéticas e leucemia mieloide aguda: diretrizes brasileiras

We report a case of cutaneous infection caused by Phialemonium curvatum GAMS et COOKE, 1983, after bone marrow transplantation. The genus Phialemonium was created by GAMS & MCGINNIS in 1983 including three new species: Ph. obovatum, Ph. curvatum and Ph. dimorphosporum, and represents an intermediate genus between Acremonium and Phialophora. Nowadays, the genus Phialemonium is considered to be a pheoid fungus which may cause the eventual lesions observed in pheo- and hyalohyphomycosis. Species of this genus have been described as opportunistic agents in humans and animals, mainly as a result of immunosuppression. In the present case, the patient had multiple myeloma and received an allogenic bone marrow transplant from his HLA-compatible brother. Two months after transplantation, he developed purplish and painful nodular lesions on the right ankle. Some of these lesions drained spontaneously and apparently hyaline mycelial filaments were observed, whose culture was initially identified as Acremonium sp. Subsequent studies showed that the fungus was Phialemonium curvatum. The infection was treated with amphotericin B, followed by ketoconazole. The patient was submitted to surgical debridement followed by two skin grafts to repair the bloody area. The duration of the treatment was 4 months and secondary prophylaxis with ketoconazole alone was maintained for one additional month. No recurrence was observed after discontinuation of treatment. The authors comment on the pathogenicity of the genus Phialemonium.

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

O objetivo deste trabalho foi definir diretrizes para a indicacao do transplante de celulas-tronco hematopoeticas (TCTH) no tratamento da leucemia mieloide aguda (LMA) no Brasil. O papel do TCTH no tratamento da LMA foi discutido pelosautores e apresentado para a Sociedade Brasileira de Transplante de Medula Ossea na reuniao sobre Diretrizes Brasileiras para o TCTH, que o ratificou. Este consenso foi baseado na revisao da literatura internacional e na experiencia brasileira em TCTH para o tratamento da LMA. O tratamento ideal para leucemia mieloide aguda em primeira remissao completa (1RC) ainda nao esta definido. Ha consenso na indicacao do TCTH alogenico, com condicionamento mieloablativo, para pacientes que apresentem alteracoes citogeneticas consideradas de alto risco. O TCTH alogenico nao esta indicado na 1RC para pacientes de baixo risco citogenetico e, aparentemente, o TCTH alogenico, autologo ou a quimioterapia de consolidacao sao equivalentes para os pacientes de risco intermediario.

Bone marrow transplantation and acute myeloid leukemia : Brazilian guidelines

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.

Busulfan and melphalan as conditioning regimen for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia in first complete remission

This report aims to define guidelines for the indication of hematopoietic stem cell transplantation in the treatment of acute myeloid leukemia in Brazil. This report on the role of hematopoietic stem cell transplantation in the treatment of acute myeloid leukemia was presented to and ratified by the Brazilian Bone Marrow Transplantation Society at the meeting on the Brazilian Guidelines for hematopoietic stem cell transplantation. This consensus is based on a review of the international literature and on the Brazilian experience in hematopoietic stem cell transplantation. The optimal treatment for acute myeloid leukemia in first complete remission is not yet defined. There is a consensus on the indication of allogeneic transplantation with myeloablative conditioning for patients presenting cytogenetic changes considered high risk. Allogeneic transplantation is not indicated in first complete remission for patients with low cytogenetic risk, and it appears that allogeneic transplantation, autologous transplantation, and consolidation chemotherapy are equivalent for patients with intermediate risk. In advanced disease and secondary leukemia, allogeneic transplant is the main therapeutic tool. New medications and therapeutic regimens have enabled the adoption of transplant in older individuals.

Transplante de medula óssea com doador familiar parcialmente compatível

Background Allogeneic hematopoietic stem cell transplantation with HLA-identical donors has been established for the treatment of acute myeloid leukemia patients for over 30 years with a cure rate of 50% to 60%. Objectives To analyze the overall survival of patients and identify factors that influence the outcomes of this type of transplant in patients in 1st complete remission who received a busulfan and melphalan combination as conditioning regimen. Methods Twenty-five consecutive patients with acute myeloid leukemia were enrolled between 2003 and 2008. The median age was 34 years old (Range: 16 - 57 years). All patients received cyclosporine and methotrexate for prophylaxis against graft-versus-host disease. Median neutrophil engraftment time was 16 days (Range: 7 - 22 days) and 17 days (Range: 7 - 46 days) for platelets. Sinusoidal obstructive syndrome was observed in three patients, seven had grade II acute graft-versus-host disease and one extensive chronic graft-versus-host disease. Results The overall survival by the Kaplan-Meier method was 48% after 36 months with a plateau at 36 months after transplantation. Intensive consolidation with high-dose arabinoside resulted in an improved survival (p-value = 0.0001), as did grade II acute graft-versus-host disease (p-value = 0.0377) and mild chronic graft-versus-host disease (p-value < 0.0001). Thirteen patients died, five due to infection within 100 days of transplant, two due to hemorrhages, one to infection and graftversus-host disease and three relapses followed by renal failure (one) and infection (two). The cause of death could not be determined for two patients. Conclusion The busulfan and melphalan conditioning regimen is as good as other conditioning regimens providing an excellent survival rate.