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.

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.

Efficacy and Safety of Allogeneic Hematopoietic Stem Cell Transplantation with Decitabine-containing Regimen in Myelodysplastic Syndromes and Myelodysplastic Syndromes Transformed Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with decitabine (Dec)-conditioning regimen in the treatment of myelodysplastic syndrome (MDS) and MDS transformed acute myeloid leukemia (MDS-AML).@*METHODS@#The characteristics and efficacy data of 93 patients with MDS and MDS-AML who received allo-HSCT in our center from April 2013 to November 2021 were retrospectively analyzed. All patients were administered by myeloablative conditioning regimen containing Dec (25 mg/m2 /d×3 d).@*RESULTS@#Among the 93 patients, 63 males and 30 females, were diagnosed as MDS（n ＝77）, MDS-AML（n ＝16）. The incidence of I/II grade regimen-related toxicity (RRT) was 39.8%, and III grade RRT was only found in 1 patient (1%). Neutrophil engraftment was successful in 91 (97.8%) patients after a median neutrophil engraftment time of 14 (9-27) days; Successful platelet engraftment was achieved in 87 (93.5%) patients, with a median engraftment time of 18 (9-290) days. The incidence of acute graft versus host disease（aGVHD） and grade III-IV aGVHD was 44.2% and 16.2%, respectively. The incidence of chronic graft versus host disease（cGVHD） and moderate-to-severe cGVHD was 59.5% and 37.1%, respectively. Of the 93 patients, 54 (58%) developed posttransplant infections, among which lung infection (32.3%) and bloodstream infection (12.9%) were the most common. The median follow-up after transplantation was 45 (0.1-108) months. The 5-year overall survival (OS) rate, disease-free survival (DFS) rate, treatment-related mortality, and cumulative incidence of relapse were 72.7%, 68.4%, 25.1%, and 6.5%, respectively. And the 1-year graft-versus-host disease/relapse-free survival rate was 49.3%. The patients in different group of relative high-risk prognostic scoring or low-risk prognostic scoring, with or without poor-risk mutation(s), with mutations number ≥3 or <3 had similar 5-year OS rate (more than 70%). Multivariate analysis showed that the incidence of grade III-IV aGVHD was the independent risk factor affecting OS（P =0.008）and DFS (P =0.019).@*CONCLUSION@#Allo-HSCT with Dec-conditioning regimen is feasible and effective in the treatment of patients with MDS and MDS-AML, especially those in high prognostic risk and with poor-risk mutations.

Utilidad de la tomografía computada de cavidades paranasales como evaluación otorrinolaringológica pretrasplante renal / Usefulness of computed tomography of the paranasal sinus as a kidney pre-transplant otorhinolaryngological evaluation

Resumen Introducción: El trasplante renal corresponde al tratamiento de elección para la enfermedad renal crónica. No existe un protocolo universalmente aceptado para la evaluación otorrinolaringológica del receptor del riñón a implantar, existiendo una gran heterogeneidad en su práctica. La tomografía computada de cavidades paranasales es uno de los estudios más habitualmente utilizados para descartar patologías otorrinolaringológicas que contraindiquen la intervención. Objetivo: Describir los hallazgos imagenológicos de las tomografías computadas solicitadas como evaluación pretrasplante renal. Determinar si estos hallazgos condicionaron una contraindicación para trasplante o algún cambio en el manejo del paciente. Material y Método: Estudio descriptivo de corte transversal mediante la revisión de fichas clínicas de pacientes derivados a estudio pretrasplante renal durante el año 2018 en el Hospital Carlos Van Buren. Resultados: Se obtuvo información de 40 pacientes derivados para evaluación otorrinolaringológica. El promedio de edad fue de 49 ± 11,4 años; 55% fueron mujeres. La causa más frecuente de enfermedad renal fue idiopática (70%). A 34 de 40 pacientes se les solicitó evaluación tomográfica. A cinco pacientes se les indicó corticoides intranasales y se derivó un paciente a evaluación dental. No se generó ninguna contraindicación para el trasplante renal. Discusión: Existe poca literatura sobre la utilidad de la tomografía de cavidades paranasales como estudio pretrasplante renal. En el presente estudio no se encontró ningún hallazgo que contraindicara la intervención. Conclusión: Se necesitan más estudios para poder asegurar si la evaluación otorrinolaringológica y el uso de tomografía tiene alguna implicancia en la evolución de los pacientes sometidos a trasplante renal.

Abstract Introduction: Kidney transplantation is the treatment of choice for chronic kidney disease. There is no universally accepted protocol for the otorhinolaryngological evaluation of the recipient, and there is heterogeneity in clinical practice. Computed tomography of the paranasal cavities is one of the most commonly used studies to rule out otorhinolaryngological pathologies that contraindicate the intervention. Aim: To describe the imaging findings of the computed tomographies requested as a pre-transplant evaluation. To determine if these findings determined a contraindication for transplantation or any change in the patient's management. Material and Method: Descriptive cross-sectional study by reviewing the clinical records of patients referred to a pre-kidney transplant study during 2018 at the Hospital Carlos Van Buren. Results: Information was obtained from 40 patients referred for otorhinolaryngological evaluation. The average age was 49 ± 11.4 years; 55% were women. The most common cause of kidney disease was idiopathic (70%). 34 of 40 patients had a computed tomography. Five patients received intranasal corticosteroids and one patient was referred for dental evaluation. There were no contraindications for renal transplantation. Conclusion: There is little literature on the usefulness of paranasal cavity tomography as a pre-kidney transplant study. In the present study, no finding was found that would contraindicate the intervention. More studies are needed to be able to ascertain whether the otorhinolaryngological evaluation and the use of tomography have any implications in the evolution of patients undergoing kidney transplantation.

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)

Oral health as a predictive factor for oral mucositis

OBJECTIVES: Oral mucositis is a complication frequently associated with hematopoietic stem cell transplantation, decreasing a patient's quality of life and increasing the occurrence of opportunistic infections. The purpose of this study was to determine the incidence and severity of oral mucositis and to assess the correlation of this disease with the oral health of an individual at the time of hematopoietic stem cell transplantation. METHODS: Before transplantation, patients' oral health and inflammatory conditions were determined using the gingival index and the plaque index, which are based on gingival bleeding and the presence of dental plaque, respectively. Additionally, the dental health status was determined using the decayed, missing, and filled teeth index. The monitoring of oral mucositis was based on the World Health Organization grading system and was performed for five periods: from Day 0 to D+5, from D+6 to D+10, from D+11 to D+15, from D+16 to D+20, and from D+21 to D+30. RESULTS: A total of 97 patients (56% male and 44% female) who underwent hematopoietic stem cell transplantation at the Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo between January 2008 and July 2009 were prospectively examined. The incidence of ulcerative mucositis was highest from days +6 to +10 and from days +11 to +15 in the patients who underwent autologous and allogeneic hematopoietic stem cell transplantation, respectively. CONCLUSION: The data, including the dental plaque and periodontal status data, showed that these oral health factors were predictive of the incidence and severity of oral mucositis in a cohort of patients with similar conditioning regimens before hematopoietic stem cell transplantation. .

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.

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

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

Use of therapeutic laser for prevention and treatment of oral mucositis

Oral mucositis (OM) affects patients who are submitted to hematopoietic stem cell transplantation (HSCT) due to high doses of chemotherapy and/or radiotherapy. The purpose of this investigation was to perform a comparative study of the frequency and evolution of OM among patients subjected to therapeutic laser and to the conventional therapy (use of mouthwash called "Mucositis Formula"). The patients were subjected to a myeloablative conditioning regimen before the allogeneic HSCT. Twenty-two patients were selected and divided into 2 groups: group I was irradiated with InGaAlP laser (660 nm) and GaAlAs laser (780 nm), 25 mW potency, 6.3J/cm² dose, in 10-s irradiation time, followed to conventional treatment; group II was subjected only to the conventional treatment. Both World Health Organization (WHO) scale and the Oral Mucositis Assessment Scale (OMAS) were used to evaluate the results. Data were analyzed by the non-parametric Wilcoxon test, with p<0.05 considered as statistically significant. Group I presented a lower frequency of OM (p=0.02) and lower mean scores, according to WHO and OMAS scales (p<0.01 and p=0.01, respectively). In conclusion, laser reduced the frequency and severity of OM, suggesting that therapeutic laser can be used both as a new form of prevention and treatment of OM.

A mucosite oral (MO) afeta pacientes que são submetidos ao transplante de células-tronco hematopoéticas (TCTH) devido as altas doses de quimioterapia e/ou radioterapia. A proposta desta investigação foi realizar um estudo comparativo da freqüência e a evolução da MO entre os pacientes submetidos ao laser terapêutico e da terapia convencional (uso de solução de bochecho chamada "Fórmula para Mucosite").Os pacientes foram submetidos ao regime de condicionamento mieloablativo antes da realização do TCTH alogênico.Vinte e dois pacientes foram selecionados e divididos em 2 grupos: grupo I foi irradiado com laser AlGaInP (660 nm) e laser GaAlAs (780 nm), potência de 25 mW, dose de 6,3J/cm², tempo 10 s, seguido do tratamento convencional; grupo II submetido apenas ao tratamento convencional. Ambas as escalas da World Health Organization (WHO) e Oral Mucositis Assessment Scales (OMAS) foram utilizadas para avaliar os resultados. Os dados foram analizados pelo teste não-paramétrico de Wilcoxon, com p<0,05 considerado estatisticamente significante. O grupo I apresentou menor frequência de MO (p=0,02) e menor média de acordo com as escalas WHO e OMAS (p<0,01 e p=0,01, respectivamente). Em conclusão, o laser reduziu a frequência e gravidade da MO, sugerindo que o laser terapêutico pode ser usado para ambos como uma nova forma de prevenção e tratamento da MO.

Endocrine Complications after Hematopoietic Stem Cell Transplantation during Childhood and Adolescence

Long-term survivors of hematopoietic stem cell transplantation (HSCT) during childhood and adolescence are at risk of developing endocrine complications. The purpose of this study was to evaluate the long-term endocrine complications and their associated risk factors among such patients. We reviewed the data from 111 patients (59 males and 52 females) who underwent HSCT at the mean age of 8.3+/-4.1 yr. Thirty patients (27.0%) had growth impairment, and seven (21.2%) out of 33 patients who attained final height reached final height below 2 standard deviation (SD). The final height SD score of the patients conditioned with total body irradiation (TBI) was significantly lower than that of the patients conditioned without TBI (-1.18+/-1.14 vs. -0.19+/-0.78, P=0.011). Thirteen patients (11.7%) developed hypothyroidism (11 subclinical, 2 central) 3.8+/-1.8 (range 1.6-6.2) yr after HSCT. Nineteen (65.5%) out of 29 females had evidence of gonadal dysfunction, and 18 (64.3%) out of 28 males had evidence of gonadal dysfunction. The risk for gonadal dysfunction was significantly higher in females conditioned with busulfan/cyclophosphamide (P=0.003). These results suggest that the majority of patients treated with HSCT during childhood and adolescence have one or more endocrine complications. Therefore, multiple endocrine functions should be monitored periodically after HSCT until they reach adult age.