Chronic graft-versus-host-disease treatment in Brazil: analyses of failure-free survival.

Failure-free survival (FFS), defined as the absence of new systemic treatment, recurrence of original malignancy and mortality not associated with recurrence after allogeneic hematopoietic stem cell transplantation (HCT), is a robust clinical measure to interpret results of initial systemic treatment of chronic graft-versus-host disease (cGVHD). We evaluate FFS after initial treatment of cGVHD in a mixed-race cohort from a resource-constrained country. This retrospective study included 354 consecutive patients after their first HCT between January 2014 and August 2020, who received initial systemic treatment for moderate or severe cGVHD at 13 Brazilian centers. Cox regression models were used to identify risk factors for treatment failure. The overall median follow-up among survivors was 28 months (range 1-71) after initial treatment. FFS was 89% at 6 months, 71% at 1 year and 52% at 2 years. New systemic treatment was the major cause of failure. In multivariable models, prior grades II-IV acute GVHD, a National Institutes of Health severity score of 3 in liver, gastrointestinal tract or lung involvement, and onset of initial treatment of cGVHD within 12 months after transplantation were all associated with an increased risk of treatment failure. Our results could serve as a benchmark for the design of future clinical trials evaluating initial treatment of cGVHD in resource-constrained locations.

Treatment of oral chronic graft-versus-host disease: a retrospective cohort study.

OBJECTIVE: The aim of this study was to evaluate patients with complete response of oral chronic graft-versus-host disease to immunosuppressive treatment. METHODS: A total of 29 patients submitted to allogeneic hematopoietic stem cell transplantation, with oral chronic graft-versus-host disease, were enrolled in this retrospective study, from September 2012 to February 2018. Patients were treated with combined topical dexamethasone solution and topical tacrolimus ointment, combined topical dexamethasone and topical tacrolimus, systemic immunosuppressive medication, and topical dexamethasone only. RESULTS: The mean time of complete response of lichenoid lesions, erythema, and ulcers using dexamethasone and systemic immunosuppressive medication was of 105, 42 and 42 days, respectively (p=0.013).When we associated dexamethasone, tacrolimus and systemic immunosuppressive medication, the mean time of complete response of lichenoid lesions, erythema and ulcers was of 91,84 and 77 days (p=0.011). When dexamethasone was used alone, the mean time of complete response of lichenoid lesions, erythema and ulcers was 182, 140, 21 days, respectively (p=0.042). CONCLUSION: Our study shows that lichenoid lesions require more time to heal. Notably, lichenoid lesions tend to respond better to dexamethasone combined with tacrolimus and systemic immunosuppressive medication, whereas erythema and ulcers respond better to dexamethasone combined with systemic immunosuppressive medication and dexamethasone only, respectively.

Treatment of oral chronic graft-versus-host disease: a retrospective cohort study / Tratamento da doença do enxerto contra hospedeiro crônica oral: um estudo de coorte retrospectivo

ABSTRACT Objective The aim of this study was to evaluate patients with complete response of oral chronic graft-versus-host disease to immunosuppressive treatment. Methods A total of 29 patients submitted to allogeneic hematopoietic stem cell transplantation, with oral chronic graft-versus-host disease, were enrolled in this retrospective study, from September 2012 to February 2018. Patients were treated with combined topical dexamethasone solution and topical tacrolimus ointment, combined topical dexamethasone and topical tacrolimus, systemic immunosuppressive medication, and topical dexamethasone only. Results The mean time of complete response of lichenoid lesions, erythema, and ulcers using dexamethasone and systemic immunosuppressive medication was of 105, 42 and 42 days, respectively (p=0.013).When we associated dexamethasone, tacrolimus and systemic immunosuppressive medication, the mean time of complete response of lichenoid lesions, erythema and ulcers was of 91,84 and 77 days (p=0.011). When dexamethasone was used alone, the mean time of complete response of lichenoid lesions, erythema and ulcers was 182, 140, 21 days, respectively (p=0.042). Conclusion Our study shows that lichenoid lesions require more time to heal. Notably, lichenoid lesions tend to respond better to dexamethasone combined with tacrolimus and systemic immunosuppressive medication, whereas erythema and ulcers respond better to dexamethasone combined with systemic immunosuppressive medication and dexamethasone only, respectively.

RESUMO Objetivo Avaliar os pacientes com resposta completa da doença do enxerto contra hospedeiro crônica oral ao tratamento com imunossupressor. Métodos Vinte e nove pacientes submetidos ao transplante alogênico de células tronco hematopoiéticas, com doença do enxerto contra hospedeiro crônica oral, foram incluídos neste estudo retrospectivo, de setembro de 2012 a fevereiro de 2018. Os pacientes foram tratados com dexametasona para bochecho associada ao tacrolimo pomada, dexametasona para bochecho associada ao tacrolimo tópico, tratamento imunossupressor sistêmico, e dexametasona tópica apenas. Resultados O tempo médio para resposta completa das lesões liquenoides, eritema e ulcerações usando dexametasona e imunossupressor sistêmico foi de 105, 42 e 42 dias, respectivamente (p=0,013). Quando a dexametasona estava associada ao tacrolimo e a medicação imunossupressora sistêmica, o tempo médio para resposta completa das lesões liquenóides, eritema e ulcerações foi de 91, 84 e 77 dias (p=0,011). Quando foi utilizada apenas dexametasona, o tempo médio para resposta completa das lesões liquenoides, eritema e ulcerações foi de 182, 140 e 21 dias, respectivamente (p=0,042). Conclusão Nosso estudo mostra que as lesões liquenoides requerem mais tempo para cicatrização completa. É notável que as lesões liquenoides tendem a responder melhor ao tratamento da dexametasona combinada com o tacrolimo e o imunossupressor sistêmico. Já o eritema e as ulcerações respondem melhor à dexametasona combinada com medicação imunossupressora sistêmica, e dexametasona apenas, respectivamente.

Photobiomodulation Therapy and Dexamethasone in the Management of Oral Acute Graft-Versus-Host Disease: Case Report.

Background: Acute graft-versus-host disease (GVHD) in the oral cavity is a rare complication of hematopoietic stem cell transplantation (HSCT) and treatment has a varying length of time for wound healing. Objective: This case report present a 63-year-old female patient with a diagnosis of acute lymphoid leukemia, submitted a related allogeneic HSCT, which after 6 months evolved with oral acute GVHD, presenting odynophagia, dysphagia, and difficulty of hygiene. Methods: We started the mouthwash dexamethasone and nystatin oral suspension and five sessions of photobiomodulation therapy (PBMT) (660 nm, 100 mW, 0.028 cm2, 2 J, 70 J/cm2, 20 sec/point) has been used with daily applications in the oral cavity (at the lesion sites and in healthy areas). Results: Complete healing of the oral lesions was observed in 5 days although the patient had acute skin and gastrointestinal GVHD. Conclusions: The treatment of oral acute GVHD with PBMT is still rare in the literature, but due to a good result in wound healing with PBMT, we have used this therapeutic option in combination with dexamethasone and have been successful in healing and reducing pain.

Impact of Anti-CMV IgG Titers and CD34 Count Prior to Hematopoietic Stem Cell Transplantation from Alternative Donors on CMV reactivation.

Cytomegalovirus (CMV) reactivation remains one of the main infectious complications following hematopoietic stem cell transplantation (HSCT). In this study, we explored the role of anti-CMV antibody titers in HSCT from alternative donors and to compare the risk of CMV reactivation between posttransplant cyclophosphamide-based haploidentical HSCT and antithymocyte globulin-based unrelated donor (URD) HSCT. We included 98 CMV-positive patients, 30 undergoing haploidentical HSCT and 68 undergoing URD HSCT. The majority of patients had a malignant disease (84%), received a myeloablative conditioning regimen (78%), and received a bone marrow graft (90%). The median pretransplantation anti-CMV IgG level was 109 U/mL. With median follow-up of 2.2 years, a total of 72 CMV reactivations occurred in 50 patients. There was no difference in CMV reactivation pattern between haploidentical HSCT recipients and URD HSCT recipients. In multivariable analysis until the first event, the incidence of CMV reactivation was higher in patients with anti-CMV IgG levels >100 U/mL (hazard ratio [HR], 2.38; P = .005) and in patients diagnosed with grade II-IV acute graft-versus-host disease (GVHD) (HR, 10.8; P = .003) after day +50 and lower in patients who received higher doses of CD34 cells (HR, .44; P = .006). In multivariable analysis for recurring events, the incidence of CMV reactivation was higher in patients receiving reduced-intensity conditioning (HR, 1.69: P = .04) and in patients with acute GVHD (HR, 1.88; P = .02), and lower in those who received higher doses of CD34 cells (HR, .55; P = .01). In summary, we have shown that pretransplantation anti-CMV IgG titers are correlated with CMV reactivation risk. More studies are needed to assess how this information can be incorporated in HSCT. The use of high-dose cellular grafts, a modifiable risk factor, also protects against CMV reactivation.

Impact of Treatment Prior to Allogeneic Transplantation of Hematopoietic Stem Cells in Patients with Myelodysplastic Syndrome: Results of the Latin American Bone Marrow Transplant Registry.

It has been suggested that bridging therapy with intensive chemotherapy and/or hypomethylating agents followed by hematopoietic stem cell transplantation (HSCT) can be valuable in the treatment of patients with myelodysplastic syndromes (MDS). However, the influence of this approach on HSCT outcomes remains poorly defined. Therefore, our objective was to investigate the influence of treatment before HSCT in patients with MDS. We retrospectively analyzed data from the Latin American registry of 258 patients from 17 Latin American centers who underwent HSCT from 1988 to 2019. Our data showed that there was pre-HSCT. We detected no significant difference regarding the impact on overall survival of treated and untreated patients before HSCT. Despite these data, the type of previous treatment among treated patients showed a significant difference in overall survival. Treatment with hypomethylating agents together with pre-HSCT chemotherapy seems to result in better survival of the studied population. These data correspond to the first results obtained through cooperative work between various centers in Latin America comparing the different approaches to patients and reflecting their reality and challenges. Therefore, the selection of pretransplant bridge therapy should be analyzed and focus given primarily to those approaches that result in better survival of patients with MDS.

Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: Graft- versus -host disease.

The Brazilian Consensus on Nutrition in Hematopoietic Stem Cell Transplantation: Graft- versus -host disease was approved by Sociedade Brasileira de Transplante de Medula Óssea , with the participation of 26 Brazilian hematopoietic stem cell transplantation centers. It describes the main nutritional protocols in cases of Graft- versus -host disease, the main complication of hematopoietic stem cell transplantation.

Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: Graft- versus -host disease / Consenso Brasileiro de Nutrição no Transplante de Células Tronco Hematopoiéticas: doença do enxerto contra o hospedeiro

ABSTRACT The Brazilian Consensus on Nutrition in Hematopoietic Stem Cell Transplantation: Graft- versus -host disease was approved by Sociedade Brasileira de Transplante de Medula Óssea , with the participation of 26 Brazilian hematopoietic stem cell transplantation centers. It describes the main nutritional protocols in cases of Graft- versus -host disease, the main complication of hematopoietic stem cell transplantation.

RESUMO O Consenso Brasileiro de Nutrição no Transplante de Células Tronco Hematopoiéticas: doença do enxerto contra o hospedeiro foi aprovado pela Sociedade Brasileira de Transplante de Medula Óssea, com a participação de 26 centros brasileiros de transplante de células-tronco hematopoiéticas. O Consenso descreve as principais condutas nutricionais em casos de doença do enxerto contra o hospedeiro, a principal complicação do transplante de células-tronco hematopoiéticas.

Acute and chronic Graft-versus-host disease after hematopoietic stem cell transplantation.

graft-versus-host disease (GVHD) is one of the main complications of hematopoietic stem cell transplantation, affecting about 50% to 80% of the patients. Acute GVHD and its clinical manifestations are discussed in this article, as well as the new NIH criteria for the diagnosis and classification of chronic GVHD. Therapy for both chronic and acute GVHD is an important field of discussion, as there is no proven superiority for the majority of therapies used after primary treatment has failed. Hence, this review is meant to be a useful consultation tool for hematologists dealing with this complex transplantation procedure complication.

Acute and chronic Graft-versus-host disease after hematopoietic stem cell transplantation / Doença do enxerto contra o hospedeiro aguda e crônica após transplante de células-tronco hematopoiéticas

ABSTRACT graft-versus-host disease (GVHD) is one of the main complications of hematopoietic stem cell transplantation, affecting about 50% to 80% of the patients. Acute GVHD and its clinical manifestations are discussed in this article, as well as the new NIH criteria for the diagnosis and classification of chronic GVHD. Therapy for both chronic and acute GVHD is an important field of discussion, as there is no proven superiority for the majority of therapies used after primary treatment has failed. Hence, this review is meant to be a useful consultation tool for hematologists dealing with this complex transplantation procedure complication.

RESUMO A doença do enxerto contra hospedeiro (DECH) é uma das principais complicações do transplante de células-tronco Hematopoéticas, acometendo cerca de 50% a 80% dos pacientes. A DECH aguda e suas manifestações clínicas são discutidas neste artigo, bem como a classificação revisada do NIH para diagnóstico e classificação da DECH crônica. A terapêutica para DECH aguda e crônica é um importante campo de discussão uma vez que não há superioridade comprovada para a maioria das terapêuticas utilizadas após o tratamento primário. Assim, esta revisão pretende ser instrumento de consulta para hematologistas transplantadores que lidam com esta complexa complicação do procedimento.

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.

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.

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 percent) met the criteria of overlap syndrome and eight (24 percent) the classic subcategory. The overall severity of disease was moderate in 21 (62 percent) and severe in 13 (38 percent) 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 percent. 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.