Maria Elvira Pizzigatti Correa

A randomised, prospective comparison of allogeneic bone marrow and peripheral blood progenitor cell transplantation in the treatment of haematological malignancies

We present the results of a prospective, randomised study comparing PBPC and BM focusing on engraftment, acute and chronic GVHD and survival. Forty patients with haematological malignancies received HLA-identical sibling BM (group A) or PBPC (group B). Evaluable patients were 19 (A) and 18 (B). Median age was 35 (17–56) in A and 29.5 (9–51) in B. Conditioning was mainly Bu-Cy2; GVHD prophylaxis was CSA-MTX. PBPC were harvested after 5 days of G-CSF 10 μg/kg/day. Median days for an ANC >0.5  × 109/l was 18 (13–30) in A and 16 (11–25) in B (P = 0.10). Platelets >20 × 109/l occurred at +17 (10–40) in A and +12 (9–36) in B (P = 0.01). The probability of ⩾2 grade a-GVHD was 19% (A) and 27% (B) (P = 0.53). The probability of all grade c-GVHD was 70% with BM. In spite of the small number of patients in group B (PBPC), our data suggest the great majority of them will have c-GVHD (P = 0.08); extensive disease was present in 50 and 100%, respectively (P = 0.05). The estimates of overall survival for A and B at 1000 days are 51 and 47%, respectively (P = 0.67); DFS at 1000 days are 52 and 58%, respectively (P = 0.50). PBPC resulted in faster platelet engraftment. The incidence of acute and chronic GVHD was similar in both groups, but the severity of c-GVHD was higher with PBPC. No differences in survival and DFS have been observed to date.

The role of basic oral care and good clinical practice principles in the management of oral mucositis

BackgroundThe Basic Oral Care Group is one of eight subcommittees functioning within the Mucositis Study Group Guidelines Panel of the Multinational Association of Supportive Care in Cancer and International Society for Oral Oncology (MASCC/ISOO). The Basic Oral Care Group, comprised of the four authors of this paper, represented the disciplines of nursing (DBM, JJ), dentistry (MEPC), and pediatric dentistry (PW). This group reviewed research and clinical literature to update the original 2004 Mucositis Management Guidelines in the areas of basic oral care, bland rinses, protocols and education, and good clinical practices such as pain management, oral assessment, oral care, and dental care.Materials and methodsOver 100 articles published between 2000 and 2005 were identified, and 32 of these were useful for the analysis. Each article was rated by at least two authors using a structured rating form and systematic determination of levels of evidence, based on the American Society of Clinical Oncology criteria. Discussion at the 2005 MASCC/ISOO Geneva preconference meeting of the Guidelines Panel resulted in the development of consensus on the interpretation of the literature.ResultsBased on the literature and on Panel discussions, a revision of the original guidelines for protocols and education was produced by the group, and they developed a set of recommendations related to good clinical practices.ConclusionsAlthough research remains scanty for components of basic oral care, bland rinses, protocols, and education, the original 2004 guidelines with the help of newer literature from 2000 to 2005 and expert consensus among the Guidelines Panel enabled the development of useful clinical practice guidelines for managing oral mucositis in patients receiving cancer treatment with radiation and/or chemotherapy.

Clinical and histomorphometric evaluation of extraction sockets treated with an autologous bone marrow graft.

PURPOSE The aim of this study was to evaluate the potential of an autologous bone marrow graft in preserving the alveolar ridges following tooth extraction. MATERIALS Thirteen patients requiring extractions of 30 upper anterior teeth were enrolled in this study. They were randomized into two groups: seven patients with 15 teeth to be extracted in the test group and six patients with 15 teeth to be extracted in the control group. Hematologists collected 5 ml of bone marrow from the iliac crest of the patients in the test group immediately before the extractions. Following tooth extraction and elevation of a buccal full-thickness flap, titanium screws were positioned throughout the buccal to the lingual plate and were used as reference points for measurement purposes. The sockets were grafted with an autologous bone marrow in the test sites and nothing was grafted in the control sites. After 6 months, the sites were re-opened and bone loss measurements for thickness and height were taken. Additionally, before implant placement, bone cores were harvested and prepared for histologic and histomorphometric evaluation. RESULTS The test group showed better results (P<0.05) in preserving alveolar ridges for thickness, with 1.14+/-0.87 mm (median 1) of bone loss, compared with the control group, which had 2.46+/-0.4 mm (median 2.5) of bone loss. The height of bone loss on the buccal plate was also greater in the control group than in the test group (P<0.05), 1.17+/-0.26 mm (median 1) and 0.62+0.51 (median 0.5), respectively. In five locations in the control group, expansion or bone grafting complementary procedures were required to install implants while these procedures were not required for any of the locations in the test group. The histomorphometric analysis showed similar amounts of mineralized bone in both the control and the test groups, 42.87+/-11.33% (median 43.75%) and 45.47+/-7.21% (median 45%), respectively. CONCLUSION These findings suggest that the autologous bone marrow graft can contribute to alveolar bone repair after tooth extraction.

Skin and oral lesions associated to imatinib mesylate therapy.

IntroductionImatinib mesylate is a tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML) throughout all the phases of the disease. In most cases, this drug is well tolerated; however, some cases experience side effects.Results and discussionSkin rashes and oral lesions are uncommon and appear to be dose-dependent. The authors report two cases of CML Ph+ in chronic phase patients who presented skin and oral lesions probably induced by imatinib therapy.

Taste disorders and oral evaluation in patients undergoing allogeneic hematopoietic SCT

The aim of this study was to evaluate taste perception, salivary flow rate and oral pathologies in three different groups of patients undergoing hematopoietic SCT (HSCT) classified according to time post transplant. Group I (n=20) up to 150 days after HSCT, group II (n=20) between 151 and 1095 days and group III (n=21) more than 1095 days. Taste acuity was measured by four basic tastes of four solutions, in three concentrations (M): NaCl, sucrose, citric acid and caffeine. Patients classified flavors as sweet, sour, salty, bitter and without flavor. The intensity was considered high, medium and low. Unstimulated saliva was collected and salivary flow rates (ml/min) were determined. Of 61 patients, 31 had chronic GVHD. For the sweet solution, the high and low concentrations represented a challenge for those patients. No patients were sensitive to the low concentration of caffeine solution (P=0.05). Saliva flow rate was diminished in 10 of 61 (16%) patients and hyposalivation was more intense in groups II/III (P=0.007). There was no correlation between taste dysfunction and oral chronic GVHD. The results indicated taste alterations only for the sweet and salty tastes even in patients up to 3 years after HSCT and may not correlate with oral chronic GVHD and with hyposalivation.

Perforin and granzyme B involvement in oral lesions of lichen planus and chronic GVHD

BACKGROUND Oral lesions of lichen planus and chronic graft-vs.-host disease (cGVHD) have similar clinical and histological features, but distinct etiology. Apoptosis induced by cytotoxic T lymphocyte has been proposed as a mechanism of keratinocytes death. Cytotoxicity can be mediated by granules containing granzyme B and perforin. Since common features can reflect similarities in immunological mechanisms, we studied the role of those molecules in both diseases. METHODS We analyzed 29 cases of oral lichen planus and 27 of oral cGVHD. The sections were studied on H&E, perforin and granzyme B staining. RESULTS The total means (epithelium plus connective tissue number) of the granzyme B- and perforin-positive cells were significantly higher in cGVHD than in oral lichen planus lesions (P<0.05). Also, it was found that the higher the number of perforin+ cells, the higher the number of granzyme-B+ cells in the epithelium and in the connective tissue for both groups (P < 0.05). In oral lichen planus, the number of single apoptotic bodies had a positive correlation with connective tissue granzyme immunostaining and a negative correlation with perforin (P<0.01). On the contrary, in oral cGVHD, the number of apoptotic body clusters presented a positive correlation with connective tissue perforin (P<0.01). CONCLUSIONS Our findings indicate that apoptosis in oral lichen planus seems to be correlated with granzyme B release, while in oral cGVHD, perforin seems to be more important. Although these diseases present clinical and histological similarities, subtle differences seem to exist in their pathogenetic mechanisms.

Early and late oral features of chronic graft-versus-host disease

Background Chronic graft-versus-host disease is a serious complication of allogeneic hematopoietic cell transplantation, and the mouth is one of the affected sites. Objective The aim of this study was to evaluate the oral features of this disease after hematopoietic cell transplantation. Methods This was a cross-sectional multicenter study that enrolled patients submitted to transplantation. Oral evaluations used the National Institutes of Health criteria, salivary flow rates, and the range of mouth opening. Pain and xerostomia were evaluated through a visual analogue scale. Patients were divided into two groups based on the transplantation time (up to one year and more than one year). Results Of the 57 evaluated recipients, 44 had chronic graft-versus-host disease: ten (22.72%) in the group with less than one year after transplantation, and 34 (77.27%) in the group with more than one year after transplantation. Lichenoid/hyperkeratotic plaques, erythematous lesions, xerostomia, and hyposalivation were the most commonly reported oral features. Lichenoid/hyperkeratotic plaques were significantly more common in patients within the first year after the transplant. The labial mucosa was affected more in the first year. No significant changes occurred in the frequency of xerostomia, hyposalivation, and reduced mouth opening regarding time after transplantation. Conclusion Oral chronic graft-versus-host disease lesions were identified early in the course of the disease. The changes observed in salivary gland function and in the range of mouth opening were not correlated with the time after transplantation.

A multicenter feasibility study of chronic graft-versus-host disease according to the National Institute of Health criteria: efforts to establish a Brazil-Seattle consortium as a platform for future collaboration in clinical trials.

Background New criteria for the diagnosis and classification of chronic graft-versus-host disease were developed in 2005 for the purpose of clinical trials with a consensus sponsored by the National Institute of Health. Objectives The aim of this study is to present the results of a multicenter pilot study performed by the Brazil-Seattle chronic graft-versus-host disease consortium to determine the feasibility of using these criteria in five Brazilian centers. Methods The study was performed after translation of the consensus criteria into Portuguese and training. A total of 34 patients with National Institute of Health chronic graft-versus-host disease were enrolled in the pilot study between June 2006 and May 2009. Results Of the 34 patients, 26 (76%) met the criteria of overlap syndrome and eight (24%) the classic subcategory. The overall severity of disease was moderate in 21 (62%) and severe in 13 (38%) patients. The median time from transplant to onset of chronic graft-versus-host disease was 5.9 months (Range: 3 - 16 months); the median time for the overlap syndrome subcategory was 5.9 months (Range: 3 - 10 months) and for the classic subcategory, it was 7.3 months (Range: 3 - 16 months). At a median follow up of 16.5 months (Range: 4 - 39 months), overall survival was 75%. Conclusions It was feasible to use the National Institute of Health consensus criteria for the diagnosis and scoring of chronic graft-versus-host disease in a Brazilian prospective multicenter study. More importantly, a collaborative hematopoietic cell transplantation network was established in Brazil offering new opportunities for future clinical trials in chronic graft-versus-host disease and in other areas of research involving hematopoietic stem cell transplantation.

Diretrizes para o diagnóstico, classificação, profilaxia e tratamento da doença enxerto contra hospedeiro crônica

A falta de criterios diagnosticos padronizados, amplamente utilizados, pode comprometer tanto a avaliacao real da incidencia da doenca contra hospedeiro cronica bem como a correlacao de sua gravidade com a taxa de mortalidade pos-transplante. Na I Reuniao de Diretrizes da Sociedade Brasileira de Transplante de Medula Ossea, realizada em junho de 2009, o Grupo de Estudos de DECH Brasil - Seattle (GEDECH), baseado na realidade dos Centros brasileiros, apresentou as recomendacoes para diagnostico, classificacao, profilaxia e tratamento da doenca enxerto contra hospedeiro cronica propostas pelo National Institutes of Health. Estas propostas incluiram padronizacao das caracteristicas utilizadas no diagnostico e ferramentas para a pontuacao dos orgaos envolvidos e avaliacao global da gravidade a serem utilizados em estudos clinicos da doenca enxerto contra hospedeiro cronica. Estes criterios sao uteis para uma melhor analise da incidencia desta doenca, alem de poder avaliar a gravidade do comprometimento de um orgao ou sitio envolvido e a influencia na mortalidade tardia do transplante. A profilaxia e os tratamentos propostos para esta importante complicacao dos transplantes de celulas-tronco hematopoeticas foram discutidos e graduados de acordo com niveis de evidencia estabelecidos pelo National Institutes of Health.

Candida in saliva of Brazilian hemophilic patients

Hemophilia is a common hereditary hemorrhagic disorder, however little is known about the oral microflora of hemophilic patients. The aim of this study was to quantify the Candida and identify its species in non-stimulated saliva of hemophilic patients, and consider its relationship with clinical factors influencing Candida carriage. This study comprised evaluation of 86 hemophilic patients of the Hematology Center/UNICAMP and 43 healthy subjects as controls. All patients were submitted to anamnesis, intraoral examination and unstimulated saliva collection. Candida counts and species identification were performed in salivary samples. Candida was present in 64% of the hemophilic patients and in 44% of the healthy controls. C. albicans represented 65% and 68% of the isolated species, in hemophiliacs and control group respectively, and C. tropicalis was the second most common species in both groups. These results indicate that hemophilic patients carry Candida more frequently and in higher counts than healthy controls, independently of oral clinical parameter considered, as viral infections, complete dentures, transfusions of hemoderivatives, and salivary flow.