Gastrointestinal involvement due to graft-versus-host disease / Compromiso gastrointestinal por enfermedad de injerto contra huésped

Abstract Graft-versus-host disease is a common complication after stem cell transplantation. The digestive tract is affected in many patients who suffer from it, with consequences that can be fatal. The proper approach, which includes endoscopic studies, allows ruling out differential diagnoses and managing the disease early.

Resumen La enfermedad de injerto contra huésped es una complicación frecuente después del trasplante de células madre. El tracto digestivo se afecta en una gran proporción de los pacientes que la sufren, con consecuencias que pueden llegar a ser fatales. El abordaje adecuado, que incluye el uso de estudios endoscópicos, permite descartar diagnósticos diferenciales y brindar un manejo temprano de la enfermedad.

Polyclonal CD5+/CD19+ B1a lymphocytes after allogeneic stem cell transplantation: a potential diagnostic pitfall

In adults, B-lymphocytes comprise approximately 10% of circulating lymphocytes. The majority of peripheral B cells are B2 cells ("Mature" B-cells), which function as part of the humoral adaptive immune system. B1 cells ("Innate-like" B cells) are another sub-class of B lymphocytes, considered as innate immune cells with a characteristic phenotype (CD20+, CD27+, CD43+, CD70-, CD11b+, sIgM++, sIgD+) which can be divided into two subtypes; B1a (CD5+): spontaneously produce broadly reactive natural IgM, and B1b (CD5-): can generate T-cell independent, long-lasting IgM. There is very limited data available, indicating a correlation between allogeneic bone marrow transplantation and an increase in B1a cells. Here we present a case of a 17-year-old female with homozygous sickle cell disease (HbSS disease) who underwent hematopoietic stem cell transplant (HSCT). Approximately seven months post-transplant, she was found to have 16% immature mononuclear cells on complete blood count (CBC)-differential report. A follow-up peripheral blood flow cytometry showed that these cells were polyclonal CD5+/CD20+ B-cells, and comprised 66% of lymphocytes. Further workup and follow up failed to reveal any lymphoproliferative disorders. It is important not to misdiagnose these cells as an atypical CD5+ lymphoproliferative disorder. The presence of B1a cells has not been widely reported in non-neoplastic post-stem cell transplanted patients. This case also adds to and expands our knowledge regarding the presence of increased circulating B1a cells after stem cell transplant in a patient with no history of hematological malignancy.

Cárie dentária em pacientes de transplante de células tronco hematopoiéticas, fígado e rim: aspectos clínicos, epidemiológicos e salivares / Dental caries in patients of hematopoietic stem cell, liver and kidney transplants: clinical, epidemiological and salivary aspects

Este estudo objetivou avaliar a experiência de cárie dentária e fatores associados, em indivíduos de transplante de células tronco hematopoiéticas, fígado e rim. Avaliou-se também o impacto da saúde bucal na qualidade de vida desses indivíduos e sua associação com a experiência de cárie e fluxo salivar. Um estudo transversal analítico controlado, com 40 indivíduos de transplante e 40 controles não indicados ao transplante, pareados por idade e sexo, atendidos na Faculdade de Odontologia da UFMG (Brasil) foi conduzido. Dados sociodemográficos e econômicos, medicações em uso e tempo de pós-transplante foram coletados. Avaliou-se a experiência de cárie pelos índices CPOS e COR (superfície). O impacto da saúde bucal na qualidade de vida foi mensurado pelo instrumento Oral Health Impact Profile (OHIP-14). Coletou-se saliva para obtenção do fluxo, pH, composição química e capacidade tampão. Avaliou-se a ingestão de açúcares livres pelo recordatório de 24 horas. A análise de regressão mostrou que o aumento de um indivíduo morador na casa do paciente aumenta as chances de ter alta experiência de cárie (OR = 1,35; IC95% 1,02-1,79). O aumento de um ponto do fluxo salivar diminuiu as chances de alta experiência de cárie dentária (OR = 0,14; IC95% 0,03-0,72). Quanto ao impacto da saúde bucal na qualidade de vida, os indivíduos em condição de transplante de fígado apresentaram valores significativamente maiores de medianas (4,0 [0-7,0]) comparados aos de transplante de rim (0,5 [0-5]) (p=0,043), para o domínio desconforto psicológico. As medianas do número de superfícies perdidas foram significativamente maiores nos indivíduos de transplante de fígado (45,0 [0-81,0]), comparados aos de rim (12,0 [0-65,0]) (p=0,045). Os indivíduos de transplante de rim (32,5 [1,0-58,0]) apresentaram número de superfícies restauradas significativamente maiores, comparados aos de fígado (13,0 [0-32,0]) (p=0,049). A faixa etária entre 56 e 61 anos (13,0 [7,0-25,0]) apresentou maiores valores do OHIP- 14, comparada à faixa de 25 a 40 anos (4,5 [0-29,0]) (p=0,013). Os valores de OHIP-14 apresentaram correlação positiva moderada significativa, com o número de superfícies dentárias perdidas (ρ=0,433; p=0,005). Não houve correlação entre o valor de OHIP-14 e o fluxo salivar. Concluiu-se que o aumento do fluxo salivar diminuiu as chances de o indivíduo apresentar uma alta experiência de cárie. O aumento do número de indivíduos moradores da casa aumentou as chances de ocorrência de alta experiência de cárie. Indivíduos de transplante de fígado apresentaram maior desconforto psicológico e um maior número de superfícies dentárias perdidas, comparados aos de transplante renal. A maior perda dentária foi correlacionada com um pior impacto da saúde bucal na qualidade de vida dos indivíduos de transplante. Indivíduos a partir de 56 anos de idade demonstraram um maior impacto na qualidade de vida relacionada à saúde bucal.

The aim of this study was evaluate the experience of tooth decay and associated factors in hematopoietic stem cell, liver and kidney transplant patients. The impact of oral health on the quality of life of these individuals and its association with the experience of caries and salivary flow were also evaluated. A controlled analytical cross-sectional study with 40 transplant individuals and 40 controls not indicated for transplantation, matched for age and sex, attended at the UFMG School of Dentistry (Brazil) was conducted. Sociodemographic and economic data, medications in use and post-transplant time were collected. The caries experience was evaluated using the CPOS and COR (surface) indexes. The impact of oral health on quality of life was measured using the Oral Health Impact Profile (OHIP-14). Saliva was collected to obtain flow, pH, chemical composition and buffering capacity. The intake of free sugars was evaluated by the 24-hour recall. The regression analysis showed that the increase of an individual living in the patient's home increases the chances of having a high caries experience (OR =1.35; 95% CI 1.02-1.79). The increase of one point in the salivary flow decreased the chances of high experience of dental caries (OR=0.14; 95% CI 0.03-0.72). As for the impact of oral health on quality of life, individuals in conditions of liver transplantation had significantly higher median values (4.0 [0-7.0]) compared to those of kidney transplantation (0.5 [0- 5]) (p = 0.043), for the psychological discomfort domain. The medians of the number of surfaces lost were significantly higher in the liver transplant subjects (45.0 [0-81.0]), compared to the kidney (12.0 [0-65.0]) (p = 0.045). The kidney transplant individuals (32.5 [1.0-58.0]) had significantly higher number of restored surfaces, compared to the liver (13.0 [0-32.0]) (p = 0.049). The age group between 56 and 61 years old (13.0 [7.0-25.0]) presented higher OHIP-14 values, compared to the age group from 25 to 40 years old (4.5 [0-29.0]) (p=0.013). The OHIP-14 values showed a significant moderate positive correlation, with the number of missing dental surfaces (ρ = 0.433; p = 0.005). There was no correlation between the OHIP-14 value and the salivary flow. It was concluded that the increase in salivary flow decreased the chances of the individual having a high experience of caries. The increase in the number of individuals living in the home increased the chances of high caries experience. Individuals with liver transplantation had greater psychological discomfort and a greater number of missing dental surfaces, compared to those of kidney transplantation. The greater tooth loss was correlated with a worse impact of oral health on the quality of life of transplant individuals. Individuals over 56 years of age demonstrated a greater impact on quality of life related to oral health.

Trasplante autólogo de células madre de médula ósea al disco intervertebral / Autologous bone marrow stem cells transplant to intervertebral disc / Autogreffe de cellules souches de la moelle osseuse au disque intervertébral

INTRODUCCIÓN: se realizó el trasplante de células madre en siete pacientes diagnosticados con enfermedad degenerativa de un solo disco intervertebral. OBJETIVO: evaluar la seguridad del proceder y la tolerancia a las células trasplantadas. MÉTODOS: las células fueron extraídas de medula ósea del propio paciente, aisladas por el método de Ficoll-Hypaque e implantadas en los discos seleccionados como grados II y III de la clasificación de Pfirrmann por imágenes de resonancia. Se evaluaron los resultados al año del injerto. RESULTADOS: no se registraron eventos adversos importantes derivados del procedimiento ni del injerto de células. Con la utilización del índice de Oswestry se evaluaron los resultados clínicos como beneficiosos, así como la posible mejoría en las imágenes de resonancia magnética antes y un año después. CONCLUSIÓN: los resultados demuestran que las células madre obtenidas de médula ósea del propio paciente pueden ser trasplantadas de manera segura, con excelente tolerancia y sin complicaciones usando el método descrito.

INTRODUCTION: stem cell transplant was performed in seven patients diagnosed with degenerative one intervertebral disc. OBJECTIVE: evaluate the safety and tolerance of the procedure to transplanted cells. METHODS: cells were extracted from the patient's own bone marrow. They were isolated by the Ficoll-Hypaque method and they were implemented in discs selected as grades II and III according to Pfirrmann classification resonance imaging. Graft outcomes were evaluated one year later. RESULTS: no significant adverse events were recorded from the procedure or graft cells. By using the Oswestry index, clinical outcomes were evaluated as beneficial, as well as the possible improvement in images from magnetic resonance imaging before and a year later. CONCLUSION: these results show that stem cells derived from the patient's own bone marrow can be safely transplanted with excellent tolerance and no complications using the method described.

INTRODUCTION: une greffe de cellules souches a été réalisée chez sept patients diagnostiqués de maladie dégénérative sur un seul disque intervertébral. OBJECTIF: le but de cette étude est d'évaluer cette procédure et la tolérance aux cellules transplantées. MÉTHODES: les cellules proviennent de la moelle osseuse du patient lui-même, isolées par la méthode de Ficoll-Hypaque et implantées au niveau des disques en grade II et III selon classification RM de Pfirrmann. Les résultats ont été évalués un an après la transplantation. RÉSULTATS: il n'y a pas eu de complications importantes au cours de l'opération ni de la greffe de cellules. Au moyen de l'indice d'Oswestry, les résultats cliniques ont été classifiés de bons ; une amélioration potentielle des images par RM a été aussi remarquée avant et après un an. CONCLUSIONS: les résultats montrent que les cellules souches prélevées de la moelle osseuse du propre patient peuvent être transplantées de manière sure, avec une tolérance excellente, et sans complications, en utilisant la méthode décrite.

Incidência de Arritmias Ventriculares após Terapia Celular em Pacientes com Cardiomiopatia Chagásica / Incidence of Ventricular Arrhythmias after Stem Cell Therapy in Patients with Chagas Cardiomyopathy

Fundamento: O tratamento com células-tronco nas diversas cardiomiopatias pode estar relacionado ao aumento nas arritmias. Objetivos: Determinar se a injeção intracoronária de células-tronco em portadores de cardiomiopatia chagásica está associada ao aumento da incidência de arritmias ventriculares, comparado ao Grupo Controle. Métodos: Estudo de coorte retrospectivo, que avaliou o prontuário de 60 pacientes que participaram de estudo transversal anterior. Foram coletados os seguintes dados: idade, sexo, medicamentos utilizados e variáveis do Holter, que demonstraram presença de arritmia complexa. O Holter foi realizado em quatro momentos: randomização, 2, 6 e 12 meses de seguimento. O Grupo Controle recebeu tratamento medicamentoso e injeção intracoronaria de placebo e o Grupo Estudo tratamento medicamentoso e implante autólogo de células-tronco. Resultados: Não houve diferença entre os Grupos Controle e Estudo nos critérios de arritmia analisados. Na análise intragrupo, foi encontrada diferença com significância entre os exames de Holter do Grupo Estudo na variável total de extrassístoles ventriculares comparada à basal, sendo entre de p = 0,014 entre Holter na randomização e Holter aos 2 meses, p = 0,004 entre Holter na randomização e Holter aos 6 meses, e p = 0,014 entre Holter na randomização e Holter aos 12 meses. A variável taquicardia ventricular não sustentada entre Holter na randomização e Holter aos 6 meses apresentou p = 0,036. Conclusão: A injeção intracoronária de células-tronco não aumentou a incidência de arritmia ventricular complexa em pacientes com cardiomiopatia chagásica, comparada ao Grupo Controle. .

Background: Treatment with stem cells in several cardiomyopathies may be related to the increase in arrhythmias. Objectives: To determine whether intracoronary injection of stem cells in patients with Chagas cardiomyopathy is associated with increased incidence of ventricular arrhythmias, compared to the Control Group. Methods: A retrospective cohort study that evaluated the medical records of 60 patients who participated in a previous cross-sectional study. The following data were collected: age, gender, drugs used and Holter variables that demonstrated the presence of arrhythmias. Holter was performed in four stages: randomization, 2, 6 and 12 months segments. The Control Group received medical treatment and intracoronary injection of placebo and the Study Group had drug treatment and autologous stem cell implant. Results: There was no difference between Control Group and Study Group when analyzing the arrhythmia criteria. In the intra-group analysis, significant difference was found between the Holter tests of the Study Group for the variable total ventricular premature beats when compared with baseline, with p = 0.014 between Holter at randomization and Holter at 2 months, p = 0.004 between Holter at randomization and Holter at 6 months, and p = 0.014 between Holter at randomization and Holter at 12 months. The variable non-sustained ventricular tachycardia between Holter at randomization and Holter at 6 months showed p = 0.036. Conclusion: The intracoronary injection of stem cells did not increase the incidence of ventricular arrhythmias in patients with Chagas cardiomyopathy compared to the Control Group. .

Recent advances in treatment of aplastic anemia

Recent advances in the treatment of aplastic anemia (AA) made most of patients to expect to achieve a long-term survival. Allogeneic stem cell transplantation (SCT) from HLA-matched sibling donor (MSD-SCT) is a preferred first-line treatment option for younger patients with severe or very severe AA, whereas immunosuppressive treatment (IST) is an alternative option for others. Horse anti-thymocyte globuline (ATG) with cyclosporin A (CsA) had been a standard IST regimen with acceptable response rate. Recently, horse ATG had been not available and replaced with rabbit ATG in most countries. Subsequently, recent comparative studies showed that the outcomes of patients who received rabbit ATG/CsA were similar or inferior compared to those who received horse ATG/CsA. Therefore, further studies to improve the outcomes of IST, including additional eltrombopag, are necessary. On the other hand, the upper age limit of patients who are able to receive MSD-SCT as first-line treatment is a current issue because of favorable outcomes of MSD-SCT of older patients using fludarabine-based conditioning. In addition, further studies to improve the outcomes of patients who receive allogeneic SCT from alternative donors are needed. In this review, current issues and the newly emerging trends that may improve their outcomes in near futures will be discussed focusing the management of patients with AA.

Feasibility of Non-TBI Conditioning with Busulfan and Fludarabine for Allogeneic Stem Cell Transplantation in Lymphoid Malignancy

BACKGROUND/AIMS: This retrospective study evaluated the transplantation outcomes of patients with adult lymphoid malignancies who received chemotherapy-based conditioning with busulfan and fludarabine (BuFlu) and busulfan and cyclophosphamide (BuCy2). METHODS: Thirty-eight patients (34 with acute lymphoblastic leukemia and 4 with lymphoblastic lymphoma) were included in the current study. The conditioning regimen was BuCy2 for 14 patients and BuFlu for the remaining 24 patients. Eight and 13 patients were high risk disease in the BuCy2 and BuFlu groups, respectively. RESULTS: The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 56.5% and 55.2% and that of extensive chronic GVHD 17.0% and 55.6% (p = 0.018) for the BuFlu and BuCy2 groups, respectively. The 3-year relapse rate was 27.8% and 31.4% and 3-year overall survival 34.3% and 46.8% for the BuFlu and BuCy2 groups, respectively. Treatment-related mortality (TRM) was significantly lower in the BuFlu group (16.9%) than in the BuCy2 group (57.1%, p = 0.010). In multivariate analyses, the BuFlu regimen was identified as an independent favorable risk factor for TRM (hazard ratio [HR], 0.036; p = 0.017) and extensive chronic GVHD (HR, 0.168; p = 0.034). CONCLUSIONS: Our BuFlu regimen would appear to be an acceptable conditioning option for lymphoid malignancies, including high-risk diseases. It was safely administered with a lower TRM rate than BuCy2 conditioning.

Injeção intracoronariana de células tronco após infarto do miocárdio: subestudo da microcirculação / Intracoronary stem-cell injection after myocardial infarction: microcirculation sub-study

FUNDAMENTO: A injeção de células-tronco no contexto do infarto agudo do miocárdio (IAM) tem sido testada quase exclusivamente pela via anterógrada intra-arterial coronariana (IAC). A via retrógrada intravenosa coronariana (IVC) pode ser uma via adicional. OBJETIVO: Comparar o padrão de distribuição e retenção celular nas vias anterógrada e retrógrada. Investigar o papel da obstrução microvascular pela ressonância magnética na retenção de células pelo tecido cardíaco após a injeção de células mononucleares da medula óssea (CMMO) no IAM. MÉTODOS: Estudo prospectivo, aberto, randomizado. Foram incluídos pacientes com IAM que apresentassem: (1) reperfusão mecânica ou química com sucesso em até 24 horas do início dos sintomas e (2) infarto acometendo mais de 10 por cento da área do ventrículo esquerdo (VE) pela cintilografia miocárdica. Cem milhões de CMMO foram injetadas na artéria relacionada ao infarto pela via IAC ou veia, pela via IVC. Um por cento das células injetadas foi marcado com Tc99m-hexametil-propileno-amina-oxima(99mTc-HMPAO). A distribuição das células foi avaliada 4 e 24 horas após a injeção da cintilografia miocárdica. Ressonância magnética cardíaca foi realizada antes da injeção de células. RESULTADOS: Trinta pacientes foram distribuídos aleatoriamente em três grupos. Não houve eventos adversos graves relacionados ao procedimento. A retenção precoce e tardia das células marcadas foi maior no grupo IAC do que no grupo IVC, independentemente da presença de obstrução da microcirculação. CONCLUSÃO: A injeção pela abordagem retrógrada mostrou-se viável e segura. A retenção de células pelo tecido cardíaco foi maior pela via anterógrada. Mais estudos são necessários para confirmar esses achados.

BACKGROUND: The injection of stem cells in the context of acute myocardial infarction (AMI) has been tested almost exclusively by anterograde intra-arterial coronary (IAC) delivery. The retrograde intravenous coronary (IVC) delivery may be an additional route. OBJECTIVE: To compare the cell distribution and retention pattern in the anterograde and retrograde routes. To investigate the role of microvascular obstruction by magnetic resonance imaging in cell retention by cardiac tissue after the injection of bone marrow mononuclear cells (BMMC) in AMI. METHODS: This was a prospective, open label, randomized study. Patients with AMI who presented: (1) successful chemical or mechanical reperfusion within 24 hours of symptom onset and (2) infarction involving more than 10 percent of the left ventricle (LV) at the myocardial scintigraphy were included in the study. One hundred million BMMC were injected into the infarction-related artery through IAC route, or vein through the IVC route. One percent of the injected cells were labeled with 99mTc-hexamethyl-propylene-amine-oxime (99mTc-HMPAO). Cell distribution was evaluated at 4 and 24 hours after the myocardial scintigraphy injection. Cardiac magnetic resonance imaging was performed before cell injection. RESULTS: Thirty patients were randomized into three groups. There were no serious adverse events related to the procedure. The early and late retention of labeled cells was higher in the IAC group than in IVC group, regardless of the presence of microcirculation obstruction. CONCLUSION: The injection using the retrograde approach was feasible and safe. Cell retention by cardiac tissue was higher using the anterograde approach. More studies are needed to confirm these findings.

Efeitos de terapias de estimulação mecânica e elétrica no fluxo salivar, na mucosite oral induzida por quimioterapia e no nível de citocinas na saliva de pacientes submetidos a TCTH / Effect of mechanical and electrical therapies on salivary flow in oral mucositis induced by chemotherapy and cytokine levels in saliva of patients undergoing HSCT

Objetivo. Avaliar os efeitos das terapias de estimulação salivar no fluxo salivar, da mucosite oral e nos níveis de citocinas salivares em pacientes que receberam transplante alogênico de células-tronco hematopoiéticas. modelo de estudo. Trinta e cinco pacientes foram randomizados em três grupos, classificados pelo tipo de terapia de estimulação salivar submetidos: O grupo do Hiperbolóide, da estimulação elétrica nervosa trancutânea (TENS), o da combinação desseas duas terapias; e do grupo controle. Saliva em repouso e estimulada foram coletadas de 7 dias antes, a 14 dias após transplante. Citocinas salivares foram avaliados pelo método ELISA...

Terapia celular no tratamento do infarto agudo do miocárdio / Cell therapy in the treatment of acute myocardial infarction

Neste artigo, os autores abordam os conceitos e evidências atualmente disponíveis sobre a terapia celular no tratamento de pacientes pós-infarto agudo do miocárdio. Os tipos celulares potencialmente candidatos ao uso clínico são enfatizados, considerando-se as vias de administração e as perspectivas futuras.

In this article, the authors discuss the concepts and available current evidence about cell therapy in the treatment of patients with acute myocardial infarction. The cell types that are potential candidates for clinical use are detailed as are the administration routes and future perspectives.

Graft versus host disease in allogeneic stem cell transplantation - 3 1/2 years experience

To evaluate the frequency and outcome of graft versus host disease after allogeneic stem cell transplant in haematological disorders at Armed Forces Bone Marrow Transplant Centre, Rawalpindi from July 2001 to December 2004. Eighty-six patients with various haematological disorders namely aplastic anaemia [n=32], b-Thalassaemia [n=25], CML [n=22], ALL [n=3], AML [n=1] Fanconi's anaemia [n=2], and Gaucher's disease [n=1], underwent allogeneic stem cell transplantation. All patients received cyclosoprin, prednisolone and short course of methotrexate as GvHD prophylaxis. The patients who developed acute GvHD > grade-II or chronic extensive GvHD received steroids at a starting dose of 2 mg/kg body weight along with gradual increase in cyclosporine dosage [max dose 12.5 mg/kg]. The overall incidence of acute GvHD grade-II to IV was 44.2% [n=38/86] where as the incidence of chronic extensive GvHD was 14% [n=12/86]. Acute GvHD was 68% [n=17/25] in

Allogeneic stem cell transplantation in chronic myeloid leukaemia 2 1/2 year experience

To evaluate out come of allogeneic Stem Cell Transplantation [SCT] in chronic myeloid leukaemia [CMC] at Armed Forces Bone Marrow Transplant Centre, Rawalpindi from April 2002 to October 2004. Twenty-two patients with CML underwent allogeneic SCT from HLA matched siblings. Patients were divided into standard [n=14] and high-risk [n=8] groups. Patients were subjected to conditioning regimens consisting of Busulphan and Cyclophosphamide. Cyclosporin, Prednisolone and Methotrexate were given for GvHD prophylaxis. All donors were subjected to PBSC harvest after G-CSF therapy for five days. All received G-CSF from Day+5 until ANC >0.5 x 109/l. The median age of the patients was 29 years [range 7-53 years] with a male to female ratio of 6.3:1. Engraftment was achieved in all patients. Median time to achieve neutrophil [ANC 0.5x109/l] and platelet [20x109/l] recovery was 13 days and 12 days respectively. Median stay in hospital was 18 days. Acute GvHD [Grade-II-IV] was observed in eleven patients [50%] while chronic GvHD was seen in four patients [18%]. One patient relapsed 8 months post transplant. Two patients [9%] developed Veno-occlusive disease [VOD] liver. One patient had haemorrhagic cystitis. Four patients [18%] had post transplant infectious complications, which included pseudomonas septicemia, aspergillosis, tuberculous pleural effusion and herpes zoster. Overall mortality was 22.7% [n=5]. The major causes of mortality were VOD liver, GvHD grade IV, Pseudomonas septicaemia and aspergillosis. Overall survival was 77.2% [n=17] and disease free survival was [n=16] 72.7%. Follow up ranges were from 23 to 828 days [median 212 days]. The preliminary results of SCT in this small series of patients with CML are very encouraging. To improve the long-term survival it is imperative that patients are transplanted early after diagnosis and conditioning regimens are selected carefully

Early presentation of squamous cell carcinoma after bone marrow transplantation in a boy with Fanconi anemia

The authors report a case of an 11-year-old boy with Fanconi anemia presenting with squamous cell carcinoma of the tongue 763 days after bone marrow transplantation. Few cases have been reported in the literature, usually involving mucosal membranes in adult patients. The factors related to the development of malignancies after bone marrow transplantation are discussed and the early presentation is highlighted, once a high index of suspicion is required for the early identification of this kind of lesion in children.

Os autores relatam o caso de um menino de 11 anos de idade com anemia de Fanconi que foi submetido a transplante de medula óssea. Com 763 dias de evolução, foi detectada uma lesão ulcerada na língua, compatível com carcinoma de células escamosas. Poucos casos semelhantes foram reportados na literatura, geralmente envolvendo as membranas mucosas em pacientes adultos. Os fatores relacionados ao desenvolvimento de neoplasias secundárias em transplante de medula óssea são discutidos e a idade precoce de apresentação do paciente enfatiza a necessidade de um alto índice de suspeição, mesmo em pacientes muito jovens, para que se faça o diagnóstico da lesão em fase inicial.

Hemorrhagic Cystitis Following Allogeneic Hematopoietic Cell Transplantation

We conducted a retrospective study to investigate the incidence, risk factors, and clinical features of hemorrhagic cystitis (HC) following allogeneic hematopoietic cell transplantation (allo-HCT). Adult patients who developed HC after allo-HCT were identified from the HCT database of the Asan Medical Center and their medical records were reviewed. From December 1993 to August 2001, a total of 210 adult patients underwent allo-HCT. Fifty-one patients developed HC with a cumulative incidence of 25.7%. The median onset of HC was post-transplant day 24 (range, -2 to 474), and the median duration was 31 days (range, 8 to 369). Significant risk factors for HC by univariate analysis included diagnosis of chronic myelogenous leukemia (p=0.028), unrelated HCT (p=0.029), grade III-IV acute graft-versus-host disease (GVHD) (p<0.001), extensive chronic GVHD (p=0.001), and positive cytomegalovirus antigenemia between post transplant days 31 and 60 (p=0.031). Multivariate analysis showed that grade III-IV acute GVHD was the most important risk factor for the occurrence of HC after allo-HCT (odds ratio, 3.38; 95% CI, 1.36-8.39). Late-onset HC, which occurred beyond 3 weeks after allo-HCT, was more frequently associated with GVHD than earlyonset HC (p=0.007). Our data suggest that a portion of late-onset HC might be a manifestation of GVHD.

Membranous Glomerulopathy as a Manifestation of Chronic Graft-versus-Host-Disease After Non-myeloablative Stem Cell Transplantation in a Patient with Paroxysmal Nocturnal Hemoglobinuria

Allogeneic stem cell transplantation (allo-SCT) using related or unrelated donor could eradicate paroxysmal nocturnal hemoglobinuria (PNH) clones and may cure the disease. Chronic graft-versus host disease (GVHD) is a major complication of patients who have undergone allo-SCT. Nephrotic syndrome has been described as one of the rare manifestations of chronic GVHD following the usual myeloablative allo-SCT. We report a case of nephrotic syndrome that developed 25 months after non-myeloablative allo-SCT for PNH. The patient had grade II acute GVHD and extensive chronic GVHD after non-myeloablative allo-SCT. Typically the patient presented with preserved renal function and full nephrotic syndrome including generalized edema, proteinuria, hypoalbuminemia, and hypercholesterolemia. Renal biopsy revealed findings of membranous glomerulopathy (MG). The patient is alive with a stable engraftment and full donor chimerism under the administration of tacrolimus for control of chronic GVHD and MG without refractory hemolysis and cytopenia.