Celso Massumoto

Primary Pneumocystis carinii Prophylaxis with Aerosolized Pentamidine after Bone Marrow Transplantation

Patients undergoing immunosuppressive therapy have a 21% risk of developing Pneumocystis carinii pneumonia (PCP) if no prophylaxis is used [1]. During the first 6 months after bone marrow transplantation (BMT), the recipients have an estimated 9% risk of developing PCP [2]. Standard prophylaxis with sulfamethoxazole and trimethoprim (SMX/TMP) daily or intermittent doses has been used effectively in transplant and other immunosuppressed patients [2–4]. However, poor compliance and undesirable myelotoxicity are expected with this schedule, especially if other myelotoxic drugs such as ganciclovir have to be administered. Aerosolized pentamidine (AP) has been considered an attractive alternative in AIDS patients who do not tolerate SMX/TMP because only 4% of the patients discontinue AP prophylaxis due to side effects [5].

FN1, GALE, MET, and QPCT overexpression in papillary thyroid carcinoma: Molecular analysis using frozen tissue and routine fine-needle aspiration biopsy samples

Thyroid nodules are a common clinical problem, and fine‐needle aspiration biopsy (FNAB) is widely used for its evaluation. Only 5% are malignant, being papillary carcinoma (PC) the most frequent neoplasia. Approximately 20% are classified as indeterminate or suspicious for malignancy. Gene‐expression pattern may be useful for diagnosing PC in difficult or ambiguous cases. In our prior study, we were able to apply RT‐PCR method in a series of routinely performed FNAB of thyroid nodules using individual, residual samples. In this study, a total of 70 thyroid samples were evaluated for the expression of MPPED2, H/HBA2, MET, FN1, GALE, and QPCT genes, including 24 cases of frozen thyroid tissue, 12 nodular hyperplasia and 12 PC, and the 46 consecutive thyroid FNAB samples, previously analyzed (3 positive, 10 indeterminate and 32 negative for malignancy, and 1 insufficient). FN1, GALE, MET, and QPCT mRNA expression were significantly different in benign and malignant samples, with similar pattern of overexpression in aspirates compared to frozen tissue. H/HBA2 and MPPED2 expression varied. Histological correlation was possible in five indeterminate cases, revealing one PC and four benign lesions. In conclusion, FN1, GALE, MET, and QPCT were significantly overexpressed in thyroid PC. RT‐PCR method could be applied to routine FNAB, showing a similar pattern of overexpression. Despite the small number of cases evaluated, our results suggest that molecular analysis may be of assistance in patients with indeterminate/suspicious cytology, adding elements for preoperative diagnosis and better management of these patients. Diagn. Cytopathol. 2011.

Clinical features and successful recovery from disseminated nocardiosis after BMT.

Nocardiosis has rarely been described after BMT. When the doses of immunosuppressive therapy were tapered, a 46-year-old BMT recipient developed chronic graft-versus-host disease (GVHD) and immunosuppressive drugs were increased. Sixteen days later the patient developed nocardiosis diagnosed by lung biopsy. Trimethoprim/sulfamethoxazole (TMP/SMZ) was initiated but the doses were reduced because of rising creatinine levels. Skin and cerebral dissemination of nocardiosis was observed and TMP/SMZ doses were increased. After 4 months, the brain lesion was unaltered despite resolution of pulmonary lesions. Clinical improvement was observed after drainage of the brain abscess.

Cerebral Air Embolism

A 42-year-old man had acute respiratory failure after receiving all-trans retinoic acid for acute promyelocytic leukemia. CT of the chest revealed multiple nodular lesions, which on biopsy showed invasive aspergillus species.

The use of monoclonal antibody (rituximab) in the treatment of type II mixed cryoglobulinemia.

Anti-CD20 monoclonal antibody has been successfully used to treat several self-immune diseases. The authors report the case of a 71 year-old female patient under the use of pegylated form of interferon á associated with ribavirin for the treatment of hepatitis C, who, after concluding the therapeutic program - negative Polymerase Chain Reaction (PCR) - developed a severe cutaneous vasculitis, receiving the diagnostic of type II mixed cryoglobulinemia. Four sessions of plasmapheresis were prescribed along the period of 11 days, with no result. The choice made was to administer anti-CD 20 monoclonal antibody (rituximab), 375 mg/m(2), per week, during four consecutive weeks. One could observe fast recovery from the purpura, as well as total remission of urticaria.

Criopreservação de medula óssea e células pluripotentes periféricas utilizando um congelador programável: experiência em 86 congelamentos

The cryopreservation of hematopoietic stem cells can be used for rescuing the hematopoiesis after high dose chemotherapy. PURPOSE. The ice cristal formation during the freezing procedure is the key point that can be harmful to the cells. The cryopreservation of hematopoietic stem cells in a controlled-rate freezer could decrease the cell damage. METHODS. Twenty-three patients with a median age of 26 years (range 03-57) had bone marrow and/or peripheral blood stem cells harvested from March 1993 through October 1994, ending up to 86 freezing procedures. The patients diagnoses are as follows: Non-Hodgkins Lymphoma (n=5); Acute Myelogenous Leukemia (n=8); Acute Lymphocytic Leukemia (n=6); Hodgkins disease (n=3); Multiple Myeloma (n=1). The cells were frozen away in a controlled-rate freezer chamber at the folowing rate: -1°C/min from room temperature to -45°C and then, at -10°C/min down to -80°C. After freezing, the cells were kept into mechanical freezers until the marrow infusion. To mobilize PBSC (peripheral blood stem cells), G-CSF (granulocyte colony stimulating factor) was given. RESULTS. A median of 3.16x108 cells/kg (range 0.86-24.22) of PBSC and 2.03x108 cells/kg (0.19-12.21) of bone marrow cells were frozen. The median time to reach granulocytes greater than 500/µL and platelets greater than 20,000/µL was 12 days (range 8-40) and 31 days (range 8-80), respectively. All patients had marrow engraftment after infusion of hematopoietic stem cells. CONCLUSION. The cryopreservation procedure using a controlled-rate freezer can store hematopoietic stem cells and potentially, cause less damage to the cells.

Fine-needle aspiration biopsy of thyroid nodules as a possible source for molecular studies: analysis of RNA obtained from routine cases.

Thyroid nodules are frequent in clinical practice and fine‐needle aspiration biopsy (FNAB) is widely used for its evaluation, but approximately 20% of the cases are diagnosed as indeterminate for malignancy. Aspirates from thyroid nodules can be used for ancillary methods, but molecular techniques are not routinely applied to these specimens. Forty‐six consecutive, routinely performed, FNAB of thyroid nodules were evaluated for the feasibility of applying RT‐PCR method. RNA was extracted from 1 of 3 fresh residual samples and analyzed to determine its pureness, integrity, and concentration. Cellularity was adequate in all 46, except one, specimens analyzed, scored as 0, 1+, 2+, 3+, and 4+ in 1, 10, 14, 9, and 8 cases, respectively. Thirty‐three nodules measured less than 1.5 cm. Cytological diagnosis was positive for malignancy in 3 cases, indeterminate for malignancy in 3, most probably benign follicular lesion in 7, negative for malignancy in 32, and suggestive of benign follicular lesion in 1. Good quality RNA was successfully isolated in 45/46 (97.8%) samples, with an average RNA concentration of 14 ng/μl and detection of B2M mRNA in 97.7% (44/45). There was no significant correlation between RNA concentration and nodule size or specimen cellularity. In conclusion, molecular analysis using individual, residual samples of thyroid nodules aspirates is feasible and could be employed for molecular preoperative studies in the future, adding elements for final cytological diagnosis of indeterminate cases, without altering the routine procedure. Diagn. Cytopathol. 2008.

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.

Complete remission of mantle-cell non-Hodgkin lymphoma with a dendritic cell vaccine

Hematol Oncol Stem Cell Ther 2(1) First Quarter 2009 hemoncstem.edmgr.com 302 Non-Hodgkin lymphomas (NHL) include more than 20 different histologic subtypes. The number of cases has doubled in the last 25 years, particularly in elderly patients. In Brazil, NHL represents the fifth most common cancer form with incidence of 55 000 cases a year and the cause of more than 26 000 deaths.1 A rare and aggressive form of NHL is mantle-cell lymphoma (MCL), which is believed to originate from naive B-cells in the mantle zone of lymph nodes and accounts for about 5% to 10% of adult NHL.2 This type of cancer is frequently associated with a t(11;14) translocation3 resulting in overexpression of the cyclin D1 gene, routinely used as a diagnostic marker. Common chemotherapy approaches include rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by stem cell transplantation or rituximab-HyperCVAD (cyclophosphamide, vincristine, doxorubicin, decadron, cytarabine, and methotrexate) followed by observation.4,5 Recent studies in patients with relapsed MCL have shown substantial antitumor activity with single-agent bortezomib, single-agent temsirolimus, and the combination of thalidomide and rituximab. Unfortunately these approaches are not able to cure patients or even promote long-lasting responses without severe toxicity.6-8 We present a case with MCL disease that obtained complete remission following therapy with dendritic cell tumor cell vaccine without the major adverse reactions common in traditional therapies.

Rehabilitation of exacerbated case of oral mucositis associated with renal failure following bone marrow transplantation.

Inflammation of oral mucosa induced by anti neoplastic drugs is an important, dose limiting and costly side effect of cancer therapy. Here is presented an exacerbated case of oral mucositis associated with renal failure in a patient who underwent bone marrow transplantation. The clinical aspects and an integrated rehabilitation program are discussed below.