Trasplante de médula ósea haploidéntico en un paciente pediátrico con síndrome de Wiskott-Aldrich. A propósito de un caso / Haploidentical bone marrow transplantation in a pediatric patient with Wiskott-Aldrich syndrome. A case report

El síndrome de Wiskott-Aldrich es un error innato de la inmunidad de herencia ligada al cromosoma X, producido por variantes en el gen que codifica la proteína del síndrome de Wiskott-Aldrich (WASp). Reportamos el caso clínico de un paciente de 18 meses con diagnóstico de Wiskott-Aldrich que no presentaba donante antígeno leucocitario humano (HLA) idéntico y recibió un trasplante de células progenitoras hematopoyéticas (TCPH) con donante familiar haploidéntico. La profilaxis para enfermedad de injerto contra huésped incluyó ciclofosfamida (PT-Cy). El quimerismo del día +30 fue 100 % del donante y la evaluación postrasplante de la expresión de la proteína WAS fue normal. Actualmente, a 32 meses del trasplante, presenta reconstitución hematológica e inmunológica y quimerismo completo sin evidencia de enfermedad injerto contra huésped. El TCPH haploidéntico con PT-Cy se mostró factible y seguro en este caso de síndrome de WiskottAldrich en el que no se disponía de un donante HLA idéntico.

Wiskott-Aldrich syndrome (WAS) is an X-linked genetic disorder caused by mutations in the gene that encodes the Wiskott-Aldrich syndrome protein (WASp). Here, we report the clinical case of an 18-month-old boy diagnosed with Wiskott-Aldrich syndrome, who did not have an HLA-matched related or unrelated donor and was treated successfully with a hematopoietic stem cell transplant (HSCT) from a haploidentical family donor. Graft-versus-host disease (GvHD) prophylaxis included post-transplant cyclophosphamide (PT-Cy). At day +30, the peripheral blood-nucleated cell chimerism was 100% and the WAS protein had a normal expression. Currently, at month 32 post-transplant, the patient has hematological and immune reconstitution and complete donor chimerism without evidence of GvHD. HSCT with PT-Cy was a feasible and safe option for this patient with WAS, in which an HLA matched donor was not available.

Effect and safety of 10-day decitabine-containing conditioning regimen for allogeneic hematopoietic stem cell transplantation in 31 patients with acute myeloid leukemia/myelodysplastic syndrome / 中华血液学杂志

Objective: To investigate the early effect and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a 10-day decitabine-containing conditioning regimen in the treatment of acute myeloid leukemia (AML) /myelodysplastic syndrome (MDS) . Methods: From April 2021 to May 2022, 31 AML/MDS patients who received allo-HSCT with a 10-day decitabine-containing conditioning regimen were analyzed. Results: AML (n=10), MDS-AML (n=6), CMML-AML (n=1), and MDS (n=14) were identified in 31 patients, 16 males, and 15 females, with a median age of 41 (20-55) yr. Neutrophils and platelets were successfully implanted in 31 patients (100%), with a median implantation duration of 12 (9-30) and 14 (9-42) days, respectively. During the preconditioning period, 16 patients (51.6%) developed oral mucositis, with 15 cases of Ⅰ/Ⅱ grade (48.4%) and one case of Ⅲ grade (3.2%). After transplantation, 13 patients (41.9%) developed CMV viremia, six patients (19.4%) developed hemorrhagic cystitis, and four patients (12.9%) developed a local infection. The median time of acute graft versus host disease (aGVHD) following transplantation was 33 (12-111) days. The cumulative incidence of aGVHD and Ⅲ/Ⅳ grade aGVHD was 41.9% (95% CI 26.9%-61.0%) and 22.9% (95% CI 13.5%-47.5%), respectively. There was no severe cGVHD, and mild and moderate chronic GVHD (cGVHD) incidence was 23.5% (95% CI 12.1%-43.6%). As of November 30, 2022, only one of the 31 patients had relapsed, with a 1-yr cumulative relapse rate (CIR) of 3.2% (95% CI 0.5%-20.7%). There was only one relapse patient death and no non-relapse deaths. The 1-yr overall survival (OS) and disease-free survival (DFS) rates were 92.9% (95% CI 80.3%-100%) and 96.8% (95% CI 90.8%-100%), respectively. Conclusions: A 10-day decitabine-containing conditioning regimen for allo-HSCT reduced relapse and was safe and feasible in treating AML/MDS.

Efficacy and safety of secondary allogeneic hematopoietic stem cell transplantation in 70 patients with recurrent hematologic malignancies after transplantation / 中华血液学杂志

Objectives: To investigate the role of donor change in the second hematopoietic stem cell transplantation (HSCT2) for hematological relapse of malignant hematology after the first transplantation (HSCT1) . Methods: We retrospectively analyzed patients with relapsed hematological malignancies who received HSCT2 at our single center between Mar 1998 and Dec 2020. A total of 70 patients were enrolled[49 males and 21 females; median age, 31.5 (3-61) yr]. Results: Forty-nine male and 21 female patients were enrolled in the trial. At the time of HSCT2, the median age was 31.5 (3-61) years old. Thirty-one patients were diagnosed with acute myeloid leukemia, 23 patients with ALL, and 16 patients with MDS or other malignant hematology disease. Thirty patients had HSCT2 with donor change, and 40 patients underwent HSCT2 without donor change. The median relapse time after HSCT1 was 245.5 (26-2 905) days. After HSCT2, 70 patients had neutrophil engraftment, and 62 (88.6%) had platelet engraftment. The cumulative incidence of platelet engraftment was (93.1±4.7) % in patients with donor change and (86.0±5.7) % in patients without donor change (P=0.636). The cumulative incidence of CMV infection in patients with and without donor change was (64.0±10.3) % and (37.0±7.8) % (P=0.053), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute graft versus host disease was (19.4±7.9) % vs (31.3±7.5) %, respectively (P=0.227). The cumulative incidence of TRM 100-day post HSCT2 was (9.2±5.1) % vs (6.7±4.6) % (P=0.648), and the cumulative incidence of chronic graft versus host disease at 1-yr post-HSCT2 was (36.7±11.4) % versus (65.6±9.1) % (P=0.031). With a median follow-up of 767 (271-4 936) days, 38 patients had complete remission (CR), and three patients had persistent disease. The CR rate was 92.7%. The cumulative incidences of overall survival (OS) and disease-free survival (DFS) 2 yr after HSCT2 were 25.8% and 23.7%, respectively. The cumulative incidence of relapse, OS, and DFS was (52.6±11.6) % vs (62.4±11.3) % (P=0.423), (28.3±8.6) % vs (23.8±7.5) % (P=0.643), and (28.3±8.6) % vs (22.3±7.7) % (P=0.787), respectively, in patients with changed donor compared with patients with the original donor. Relapses within 6 months post-HSCT1 and with persistent disease before HSCT2 were risk factors for OS, DFS, and CIR. Disease status before HSCT2 and early relapse (within 6 months post-HSCT1) was an independent risk factor for OS, DFS, and CIR post-HSCT2. Conclusion: Our findings indicate that changing donors did not affect the clinical outcome of HSCT2.

Clinical study of 19 cases of steroid-refractory gastrointestinal acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation with fecal microbiota transplantation / 中华血液学杂志

Objective: To investigate the clinical efficacy of fecal microbiota transplantation (FMT) for treating steroid-refractory gastrointestinal acute graft-versus-host disease (GI-aGVHD) . Methods: This analysis included 29 patients with hematology who developed steroid-refractory GI-aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Huaian Hospital Affiliated to Xuzhou Medical University from March 2017 to March 2022. Among them, 19 patients underwent FMT treatment (the FMT group) and 10 patients did not (the control group). The efficacy and safety of FMT were assessed, as well as the changes in intestinal microbiota abundance, lymphocyte subpopulation ratio, peripheral blood inflammatory cytokines, and GVHD biomarkers before and after FMT treatment. Results: ① Complete remission of clinical symptoms after FMT was achieved by 13 (68.4%) patients and 2 (20.0%) controls, with a statistically significant difference (P<0.05). Intestinal microbiota diversity increased and gradually recovered to normal levels after FMT and FMT-related infections did not occur. ②The proportion of CD3(+) and CD8(+) cells in the FMT group after treatment decreased compared with the control group, and the ratio of CD4(+), regulatory T cells (Treg), and CD4(+)/CD8(+) cells increased (all P< 0.05). The interleukin (IL) -6 concentration in the FMT group was lower than that in the control group [4.15 (1.91-5.71) ng/L vs 6.82 (2.40-8.91) ng/L, P=0.040], and the IL-10 concentration in the FMT group was higher than that in the control group [12.11 (5.69-20.36) ng/L vs 7.51 (4.10-9.58) ng/L, P=0.024]. Islet-derived protein 3α (REG3α) was significantly increased in patients with GI-aGVHD, and the REG3α level in the FMT group was lower than that in the control group after treatment [30.70 (10.50-105.00) μg/L vs 74.35 (33.50-139.50) μg/L, P=0.021]. Conclusion: FMT is a safe and effective method for the treatment of steroid-refractory GI-aGVHD by restoring intestinal microbiota diversity, regulating inflammatory cytokines, and upregulating Treg cells.

Diagnosis and treatment of 26 cases of adenovirus infection after allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To analyze the clinical characteristics and prognosis of adenovirus infection after allogeneic hematopoietic stem cell transplantation. Methods: A total of 26 patients with adenovirus infection admitted to the posttransplant ward of the First Affiliated Hospital of Soochow University from 2018 to 2022 were enrolled. Their data on baseline and clinical characteristics, treatment, and follow-up were analyzed. Results: The median patient age was 30 (22, 44) years. Twenty-two patients received related haploid stem cell transplantation, three received unrelated stem cell transplantation, and one received umbilical cord stem cell transplantation. Antithymocyte globulin was included in the conditioning regimen in 25 patients. The median time of adenovirus infection was +95 (+44, +152) days. The median peripheral blood lymphocyte count was 0.30 (0.11, 0.69) × 10(9)/L. Twelve patients had acute graft-versus-host disease. Twenty-four patients received antirejection therapies at diagnosis. Sixteen cases had combined infection with other pathogens with adenovirus infection. Eight cases were diagnosed as asymptomatic infection, and 18 were diagnosed as adenovirus disease, including pneumonia (38.89% ) , gastrointestinal disease (38.89% ) , encephalitis (33.33% ) , hepatitis (5.56% ) , and urinary tract inflammation (5.56% ) . The age of >30 years was a risk factor for adenovirus disease (P=0.03) . Eighteen patients received tapering of immunosuppression, and all 26 patients received at least one antiviral drug. Other treatments included high-dose gamma globulin and donor lymphocyte infusion. Adenovirus infection improved in 10 cases and progressed in 16 cases. The median follow-up time was 30 (7, 237) days. Twenty-two patients died. The all-cause mortality rate was (88.5±7.1) % , and the attributable mortality rate was 45.5% . There was no significant difference in the 100 d survival rate between asymptomatic infected patients and patients diagnosed with adenovirus disease (37.5% vs 22.2% , HR=1.83, 95% CI 0.66-5.04, P=0.24) . Conclusion: The age of >30 years was a risk factor for adenovirus disease. Mortality was high in patients with adenovirus infection after allogeneic hematopoietic stem cell transplantation.

Incidence and clinical characteristics of engraftment syndrome after syngeneic hematopoietic stem cell transplantation in patients with hematological diseases / 中华血液学杂志

Objective: To explore the incidence and clinical characteristics of engraftment syndrome (ES) after syngeneic hematopoietic stem cell transplantation (syn-HSCT) in patients with hematological diseases. Methods: The clinical data of 21 patients who received syn-HSCT at People's Hospital of Peking University from January 1994 to May 2018 were retrospectively analyzed. Results: Seven (33.3% ) of 21 patients developed ES. The onset of ES symptoms occurred at a median of 8 (range: 5-13) days after HSCT, and the diagnosis of ES occurred at a median of 10 (range: 7-14) days after HSCT. Steroids were administered immediately after the diagnosis of ES, the median time of symptom continuance was 2 (range: 1-5) days, and all patients showed complete resolution of ES symptoms. In the multivariate analysis, patients with acute myeloid leukemia and faster neutrophil reconstitution were the risk factors for ES (HR=15.298, 95% CI 1.486-157.501, P=0.022, and HR=17.459, 95% CI 1.776-171.687, P=0.014) . Meanwhile, there was no significant difference in the overall survival and disease-free survival between patients with ES and those without ES. Conclusion: A high incidence of ES was observed in syn-HSCT recipients. Moreover, the prognosis of ES was excellent.

Long-term outcome of hematopoietic stem cell transplantation in two children with Mucopolysaccharidosis / 中华医学遗传学杂志

OBJECTIVE@#To explore the long-term efficacy of allogeneic hematopoietic stem cell transplantation (alloHSCT) in patients with Mucopolysaccharidosis (MPS), which has rarely been reported in China.@*METHODS@#A 18-month-old boy and a 23-month-old girl undergoing alloHSCT for MPS VI and MPS IH Shanghai Children's Medical Center on March 30, 2006 and September 6, 2006 were selected as the study subjects. A busulfan-based myeloablative regimen was used as the conditioning regimen. Peripheral stem cells were respectively collected from a human leucocyte antigen (HLA) matched sibling carrier donor and a HLA 9/10 matched unrelated donor. Both patients were followed up for more than 15 years. The functions of internal organs before and after the transplantation were compared, and child 1 was also compared with his untreated brother and healthy brother.@*RESULTS@#Both children have achieved full donor chimerism after the transplantation, and their enzymatic activities have remained stable. The enzymatic activity of the child 1 was slightly lower than normal but similar to that of his carrier donor, whilst that of the child 2 was normal. Both children have attended schools with good academic performance. Compared with his untreated brother, the respiratory function and hearing of child 1 have significantly improved. However, his orthopedic and cardiac disorders have still remained and required medical intervention. For child 2, her obstructive pulmonary disease was resolved and cognitive development was well preserved after the HSCT. Her heart disease has become stabilized and even improved with time, though her corneal clouding and skeletal malformation still required surgery.@*CONCLUSION@#MPS patients can sustain long-term and stable enzymatic activities after successful alloHSCT. Compared with untreated patients, their health can be significantly improved, along with considerably prolonged survival, though the long-term efficacy of HSCT for different organs may vary to a certain extent.

Efficacy and safety of allogeneic hematopoietic stem cell transplantation in the treatment of 28 patients with hepatitis-related aplastic anemia / 中华血液学杂志

Objective: To evaluate the efficacy and safety of HLA-haploidentical hematopoietic stem cell transplantation (allo-HSCT) for hepatitis-related aplastic anemia (HRAA) patients. Methods: Retrospective analysis was performed on hepatitis-associated aplastic anemia patients who received haplo-HSCT at our center between January 2012 and June 2022. October 30, 2022 was the final date of follow-up. Results: This study included 28 HRAA patients receiving allo-HSCT, including 18 males (64.3% ) and 10 females (35.7% ), with a median age of 25.5 (9-44) years. About 17 cases of severe aplastic anemia (SAA), 10 cases of very severe aplastic anemia (VSAA), and 1 case of transfusion-dependent aplastic anemia (TD-NSAA) were identified. Among 28 patients, 15 patients received haplo-HSCT, and 13 received MSD-HSCT. The 2-year overall survival (OS) rate, the 2-year failure-free survival (FFS) rate, the 2-year transplant-related mortality (TRM) rate, the 100-day grade Ⅱ-Ⅳ acute graft-versus-host disease (aGVHD) cumulative incidence rate, and the 2-year chronic graft-versus-host disease (cGVHD) cumulative incidence rate were 81.4%, 81.4% (95% CI 10.5% -20.6% ), 14.6% (95% CI 5.7% -34.3% ), 25.0% (95% CI 12.8% -45.4% ), and 4.2% (95% CI 0.6% -25.4% ), respectively. After transplantation, all patients had no significant liver function damage. Compared with the MSD-HSCT group, only the incidence of cytomegaloviremia was significantly higher in the haplo-HSCT group [60.0% (95% CI 35.2% -84.8% ) vs 7.7% (95% CI 0-22.2% ), P=0.004]. No statistically significant difference in the Epstein-Barr virus was found in the 2-year OS, 2-year FFS, 2-year TRM, and 100-day grade Ⅱ-Ⅳ aGVHD cumulative incidence rates and 2-year cGVHD cumulative incidence rate. Conclusion: Allo-HSCT is safe and effective for HRAA, and haplo-HSCT can be used as a safe and effective alternative for newly diagnosed HRAA patients who cannot obtain HLA-matched sibling donors.

Hematoma duodenal posvideoendoscopia digestiva alta para diagnóstico de enfermedad de injerto contra huésped en pediatría: a propósito de dos casos / Duodenal hematoma after upper gastrointestinal endoscopy in pediatric graft vs host disease: Report of two cases

La enfermedad de injerto contra huésped es una complicación grave que se presenta después del trasplante de médula ósea, con morbilidad y mortalidad elevadas. El patrón de oro para evaluar su compromiso gastrointestinal es la endoscopia digestiva alta y baja con toma de biopsia. El desarrollo de hematoma duodenal intramural es una complicación poco frecuente asociada con este procedimiento .Se presentan dos casos de hematoma duodenal intramural posendoscopia en pacientes con trasplante y sospecha de enfermedad injerto contra huésped que presentaron un cuadro agudo de dolor abdominal y sangrado intestinal. El diagnóstico se realizó por tomografía y recibieron tratamiento conservador, con un resultado favorable. En ambos casos, el diagnóstico de enfermedad injerto contra huésped gastrointestinal se hizo a través de las biopsias colónicas con histología duodenal normal, lo que sugiere evitar la toma de muestras duodenales para prevenir esta grave complicación en pacientes de alto riesgo y, de este modo, disminuir la morbilidad.

Graft versus host disease is a serious complication that occurs following bone marrow transplant with significant morbidity and mortality. The gold standard to diagnose gastrointestinal graft versus host disease is upper and lower gastrointestinal endoscopy with histological validation. The development of intramural duodenal hematoma is a rare complication associated with this procedure. We present two cases of intramural duodenal haematoma after duodenal biopsies in bone marrow transplant patients that presented clinically with severe abdominal pain and intestinal bleeding. In both cases, CT scans confirmed the diagnosis and they were treated conservatively with favorable outcomes.Final diagnosis of gastrointestinal graft versus host disease was based on the colonic samples with normal duodenal histoarchitecture, which could lead to avoiding duodenal samples in future patients in order to prevent this serious complication and thus diminish morbidity.

Risk factors and survival analysis for central nervous system complications after allogeneic hematopoietic stem cell transplantation / 中南大学学报(医学版)

OBJECTIVES@#To investigate the risk factors as well as their impact on patients' survival of central nervous system (CNS) complications following allogeneic hematopoietic stem cell transplantation (HSCT).@*METHODS@#All relevant clinical data from a total of 323 patients, who underwent allogeneic HSCT in Xiangya Hospital of Central South University from September 2016 to September 2019, were retrospectively reviewed in this study. The complications' occurrence time, common symptoms and some other clinical data of the patients who developed CNS complications were analyzed descriptively. The risk factors for CNS complications following allogeneic HSCT were analyzed through univariate and multivariate analysis. And the survival analysis was conducted as well.@*RESULTS@#Among the 323 patients who underwent allogeneic HSCT, 32 patients developed CNS complications. These complications occurred in these patients at a median of 32 (range from -1 to 584) d after transplantation. Common symptoms were disturbance of consciousness (78.1%), convulsion (59.4%), and headache (12.5%). Univariate analysis showed that there were significant differences in neutrophil engraftment, platelet (PLT) engraftment, serum cytomegalovirus (CMV) DNA positive, combined with acute graft-versus-host disease (aGVHD), donor selection (@*CONCLUSIONS@#The delay or the failure of PLT engraftment and combined with aGVHD are the risk factors for CNS complications. The facts indicate that we should prevent CNS complications when patients who underwent allogeneic HSCT with the delay or the failure of PLT engraftment or aGVHD. Compared with non-CNS complication group, patients who developed CNS complications usually have poor prognosis.

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.

Doença do Enxerto-versus-hospedeiro ocular: Revisão / Graft-versus-Host Disease: Review

Resumo Doença do Enxerto-versus-hospedeiro (do inglês Graft-versus-Host Disease - GVHD) é uma complicação importante e com altas taxas de morbidade e mortalidade nos pacientes submetidos ao transplante alogênico de células-tronco hematopoiéticas. O acometimento ocular, denominado GVHD ocular, pode acometer todas as estruturas dos olhos, porém a unidade lacrimal (glândulas lacrimais e superfície ocular) é o principal alvo da resposta inflamatória mediada por células T doadas. O desenvolvimento de doença do olho seco grave é a principal manifestação clínica ocular, e a associação de diversas opções terapêuticas se faz necessário. O objetivo desta revisão é descrever as manifestações clínicas, os critérios diagnósticos, o impacto na qualidade de vida, o tratamento atual e as perspectivas desta doença, que precisa de um acompanhamento multidisciplinar.

Abstract Graft-versus-host Disease (GVHD) is a major complication with high morbidity and mortality rates on patients undergoing hematopoietic stem cell transplantation. The ocular involvement, named ocular GVHD, may affect all structures of the eyes, but the lacrimal unit (lacrimal glands and ocular surface) is the main target of the inflammatory response mediated by the donor T cells. The development of dry eye disease is the main clinical ocular manifestation, and the association of a variety of therapeutics options is necessary. The aim of the review is to describe the clinical manifestations, diagnostic criteria, impact in quality of life, the current treatment and future perspectives of this disease that demands a multidisciplinary follow-up.

Desafíos terapéuticos en la enfermedad injerto contra huésped / Therapeutic challenges in graft versus host disease

La enfermedad injerto contra huésped es una entidad en la cual las células inmunológicas competentes de un tejido injertado reconocen y dañan antígenos presentes en el receptor del trasplante, que es incapaz de defenderse de ellas. Es una complicación frecuente del trasplante alogénico de médula ósea, y con menor frecuencia se produce luego de trasplantes de órganos sólidos o transfusiones de hemoderivados no irradiados. Se comunica el caso de una paciente de sexo femenino de 23 años, con leucemia linfoblástica aguda.y trasplante alogénico de médula ósea, que presentó una enfermedad injerto contra huésped con compromiso cutáneo y gastrointestinal dependiente de corticoides, con mejoría de los signos y síntomas cutáneos luego del tratamiento con infliximab y fotoféresis extracorpórea. (AU)

Graft versus host disease is an entity in which competent grafted immune cells recognize and damage tissue antigens present in the transplant recipient, who is unable to defend from them. It is one of the most serious complications in patients undergoing allogeneic bone marrow transplantation, although less frequently it may be associated with solid organ transplants or transfusions of not irradiated blood products. We report the case of a 23 year-old patient with acute lymphoblastic leukemia and allogeneic bone marrow transplantation, that presented graft versus host disease with skin and gastrointestinal involvement, dependent on corticosteroids, that showed improvement in signs and skin symptoms after treatment with infliximab and extracorporeal photopheresis. (AU)

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.

Cutaneous graft-versus-host disease after hematopoietic stem cell transplant - a review

Abstract Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplants (allo-HSCT) associated with significant morbidity and mortality. The earliest and most common manifestation is cutaneous graft-versus-host disease. This review focuses on the pathophysiology, clinical features, prevention and treatment of cutaneous graft-versus-host disease. We discuss various insights into the disease's mechanisms and the different treatments for acute and chronic skin graft-versus-host disease.

Bone Marrow Chimerism Detection Using Next Generation Sequencing Based on Single Nucleotide Polymorphisms Following Liver Transplantation: Comparison With Short Tandem Repeat-PCR

No abstract available.

Risk Factor and Clinical Outcome of Bronchiolitis Obliterans Syndrome after Allogeneic Hematopoietic Stem Cell Transplantation

PURPOSE: The development of bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (HSCT) deteriorates patients' quality of life. This study aimed to analyze the prevalence, clinical features, risk factors and prognostic factors of BOS. MATERIALS AND METHODS: This retrospective study included patients who underwent allogeneic HSCT from January 2002 to December 2008 and survived for > or =100 days after transplantation. RESULTS: Of 860 patients who survived for > or =100 days, 36 (4.2%) met the diagnostic criteria. The duration of BOS development after transplantation was 466.00 (284.00-642.75) [median (interquartile range)] days. The risk factor for the development of BOS was peripheral blood as the stem cell source with a hazard ratio (HR) of 2.550 [95% confidence interval (CI): 1.274-5.104, p=0.008]. In multivariate analysis, pretransplant FEV1/FVC (HR: 0.956, 95% CI: 0.921-0.993, p=0.020) and time from HSCT to diagnosis of BOS (HR: 0.997, 95% CI: 0.994-0.999, p=0.009) were independent prognostic factors associated with mortality. CONCLUSION: Peripheral blood as a stem cell source is a risk factor for the development of BOS. A decreased pretransplant FEV1/FVC and shorter duration of time from transplantation to diagnosis of BOS are poor prognostic factors for BOS.

Colonic complications following human bone marrow transplantation / Complicações do cólon após transplante de medula óssea humana

BACKGROUND: Human bone marrow transplantation (BMT) becomes an accepted treatment of leukemia, aplastic anemia, immunodeficiency syndromes, and hematologic malignancies. Colorectal surgeons must know how to determine and manage the main colonic complications. OBJECTIVE: To review the clinical features, clinical and pathological staging of graft vs host disease (GVHD), and treatment of patients suffering with colonic complications of human bone marrow transplantation. PATIENTS AND METHODS: We have reviewed the records of all patients that received an allogeneic bone marrow transplant and were evaluated at our Colon and Rectal Surgery department due to gastrointestinal symptoms, between January 2007 and January 2012. The study was carried out in patients who developed colonic complications, all of them with clinical, histopathological or laboratory diagnosis. RESULTS: The study group was constituted by 77 patients, 43 male and 34 female patients. We identified colonic complications in 30 patients (38.9%); five patients developed intestinal toxicity due to pretransplant chemotherapy (6.4%); graft vs. host disease was present in 16 patients (20%); 13 patients (16.8%) developed acute colonic GVHD, and 3 (3.8%) chronic GVHD. Infection was identified in 9 patients (11.6%). CONCLUSIONS: The three principal colonic complications are the chemotherapy toxicity, GVHD, and superinfection; the onset of symptoms could help to suspect the type of complication (0-20 day chemotherapy toxicity, 20 and more GVHD), and infection could appear in any time of transplantation. (AU)

EXPERIÊNCIA: O transplante de medula óssea humana (MOH) passou a ser um tratamento adotado para leucemia, anemia aplástica, síndromes de imunodeficiência e neoplasias hematológicas. Cirurgiões colorretais devem saber como determinar e tratar as principais complicações do cólon. OBJETIVO: Revisar as características clínicas, estadiamentos clínico e patológico da doença do enxerto versus hospedeiro (DEVH) e o tratamento de pacientes padecendo com as complicações colônicas do transplante de medula óssea humana. PACIENTES E MÉTODOS: Revisamos os registros de todos os pacientes que receberam um transplante de medula óssea alogênica e foram avaliados em nosso Departamento de Cirurgia do Cólon e Reto em função de sintomas gastrointestinais, entre janeiro de 2007 e janeiro de 2012. O estudo teve por base os pacientes que desenvolveram complicações do cólon, todos com diagnóstico clínico, histopatológico ou laboratorial. RESULTADOS: O grupo de estudo foi constituído por 77 pacientes, sendo 43 homens e 34 mulheres. Identificamos complicações do cólon em 30 pacientes (38,9%); cinco pacientes exibiam toxicidade intestinal por quimioterapia antes do transplante (6,4%); DEVH estava presente em 16 pacientes (20%), 13 pacientes (16,8%) foram acometidos por DEVH colônica aguda três pacientes (3,8%) DEVH crônica. Infecção foi detectada em 9 pacientes (11,6%). CONCLUSÕES: As três principais complicações do cólon são: toxicidade por quimioterapia, DEVH e superinfecção. O surgimento dos sintomas poderia ajudar a levantar suspeitas sobre o tipo de complicação (0-20 dias, toxicidade por quimioterapia; 20 ou mais dias, DEVH). Infecções podem ocorrer em qualquer momento do transplante. (AU)

The Impact of HLA and KIR Ligand Mismatching on Unrelated Allogeneic Hematopoietic Stem Cell Transplantation in Korean Adult Patients

BACKGROUND: The impact of HLA and KIR ligand mismatching on the outcome of hematopoietic stem cell transplantation (HSCT) remains unclear. Previous reports have identified considerable ethnic differences in the impact of HLA and KIR ligand mismatches, as well as KIR ligand status, on HSCT; however, to date, no data has been acquired in Korean adult patients. METHODS: We investigated the association of high-resolution HLA matching on five loci (HLA-A, -B, -C, -DRB1, and -DQB1), KIR ligand mismatching, and KIR ligand status on the outcome of allogeneic HSCT from unrelated donors in 154 Korean adult patients treated at Seoul National University Hospital. RESULTS: In a multivariate analysis, less than 9/10 allelic matches in five HLA loci was an independent risk factor for acute graft-versus-host disease (GVHD) (grade II to IV) (P=0.019, odds ratio [OR]=2.7). In addition, HLA-A allele mismatching was increasingly prevalent in patients with acute GVHD compared to patients without (61.9% vs. 34.5%, P=0.06). For KIR ligand status, the patient and donor combination of both C1/C1 ligands showed better event-free and overall survival than combinations with C2 ligand patients or donors (P=0.048, P=0.034, respectively) by log-rank test. CONCLUSIONS: Korean adult transplant patients with less than 9 of 10 HLA allele matches in the HLA-A, -B, -C, -DRB1, and DQB1 loci have a higher likelihood of developing acute GVHD (grade II to IV). Impact of KIR ligand status on clinical outcome should be further studied in a larger patient population.

Etanercept for steroid-refractory acute graft versus host disease following allogeneic hematopoietic stem cell transplantation

BACKGROUND/AIMS: The treatment for steroid-refractory acute graft versus host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT) needs to be standardized. We report our clinical experience with etanercept for steroid-refractory acute GVHD. METHODS: Eighteen patients who underwent allo-SCT and presented with steroid-refractory acute GVHD at Ajou University Hospital were studied retrospectively. They were given 25 mg of etanercept subcutaneously twice weekly for 4 weeks. The clinical responses were evaluated with regard to the severity of acute GVHD. RESULTS: The median patient age was 43.5 years. Using nonparametric tests, etanercept had a down-grading effect on acute GVHD (p = 0.005), although no patient experienced complete remission. Partial responses were seen in 80%, 17%, and 57% of grade II to IV patients, respectively. Skin and gut GVHD were well controlled with etanercept, whereas hepatic GVHD was not. Four patients died of fatal infections. No factors affecting the clinical outcome of etanercept were identified. CONCLUSIONS: Etanercept has a modest effect on steroid-refractory acute GVHD after allo-SCT, with tolerable side effects.