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)

Salvaged single-unit cord blood transplantation for 26 patients with hematologic malignancies not in remission

Treatments for patients with hematologic malignancies not in remission are limited, but a few clinical studies have investigated the effects of salvaged unrelated cord blood transplantation (CBT). We retrospectively studied 19 patients with acute leukemia, 5 with myelodysplastic syndrome (MDS with refractory anemia with excess blasts [RAEB]), and 2 with non-Hodgkin's lymphoma who received 1 CBT unit ≤2 loci human leukocyte antigen (HLA)-mismatched after undergoing myeloablative conditioning regimens between July 2005 and July 2014. All of them were in non-remission before transplantation. The infused total nucleated cell (TNC) dose was 4.07 (range 2.76-6.02)×107/kg and that of CD34+ stem cells was 2.08 (range 0.99-8.65)×105/kg. All patients were engrafted with neutrophils that exceeded 0.5×109/L on median day +17 (range 14-37 days) and had platelet counts of >20×109/L on median day +35 (range 17-70 days). Sixteen patients (61.5%) experienced pre-engraftment syndrome (PES), and six (23.1%) patients progressed to acute graft-versus-host disease (GVHD). The cumulative incidence rates of II-IV acute GVHD and chronic GVHD were 50% and 26.9%, respectively. After a median follow-up of 27 months (range 5-74), 14 patients survived and 3 relapsed. The estimated 2-year overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) rates were 50.5%, 40.3%, and 35.2%, respectively. Salvaged CBT might be a promising modality for treating hematologic malignancies, even in patients with a high leukemia burden.

Relationship between complaints presented by emergency patients and the final outcome / Relação entre queixas apresentadas por pacientes na urgência e o desfecho final / Relación entre las quejas presentadas por pacientes en la urgencia y el desenlace final

AbstractObjective: to relate complaints presented by emergency room patients, classified using the Manchester Triage System, with the final outcome (discharge/death/transfer).Methods: prospective cohort study, involving 509 patients who were admitted to the emergency room and remained there for more than 24 hours after admission, being monitored to the final outcome. Data were analyzed with a statistical program using descriptive and analytical statistics.Results: the mean age of the patients was 59.1 years and 59.3% were male. The main complaints were unwell adult (130 - 22.5%), shortness of breath in adults (81 - 14.0%), abdominal pain in adults (58 - 10.0%) and behaving strangely (34 - 5.9%), with 87% of the patients being discharged. More deaths were found in the patients classified in the severe colors, with 42.8% classified as red, 17.0% as orange and 8.9% as yellow. Among the patients classified as green, 9.6% died.Conclusion: in the various colors of the Manchester Triage System, death prevailed in patients that presented the complaints of unwell adult, shortness of breath, head injury, major trauma, diarrhea and vomiting. The higher the clinical priority the greater the prevalence of death.

ResumoObjetivo:relacionar queixas apresentadas pelos pacientes classificados pelo Sistema de Triagem de Manchester em um pronto-socorro com o desfecho final (alta/óbito/transferência).Métodos:estudo de coorte prospectivo, realizado com 509 pacientes que deram entrada no pronto-socorro e que nele permaneceram por mais de 24 horas após a admissão, sendo acompanhados até o desfecho final. Os dados foram digitados e analisados com estatística descritiva e analítica em um pacote estatístico.Resultados:entre os pacientes, 59,3% eram do sexo masculino, com idade média de 59,1 anos. As queixas principais eram de mal-estar no adulto (130-22,5%), dispneia em adulto (81-14,0%), dor abdominal em adulto (58-10,0%), alterações de comportamento (34-5,9%), sendo que, desses, 87% recebeu alta. Foram encontrados mais óbitos nos pacientes classificados nas cores mais graves, sendo 42,8% classificados como vermelho, 17,0% laranja e 8,9% como amarelo. Entre os pacientes classificados como verde, 9,6% evoluiu para óbito.Conclusão:nas diversas cores do Sistema de Triagem Manchester, o óbito prevaleceu nos pacientes que apresentaram a queixa de mal-estar no adulto, dispneia, sofreram trauma craniano, trauma maior, diarreia e vômito. Quanto maior a prioridade clínica maior a prevalência de óbito.

ResumenObjetivo:relacionar las quejas presentadas por los pacientes clasificados por el Sistema de Clasificación de Manchester, en un servicio de urgencia, con el desenlace final (alta/muerte/ transferencia).Métodos:estudio de cohorte prospectiva, realizado con 509 pacientes que dieron entrada en el servicio de urgencia y que en él permanecieron por más de 24 horas después de la admisión, siendo seguidos hasta el desenlace final. Los datos fueron introducidos y analizados con estadística descriptiva y analítica, en un programa estadístico.Resultados:entre los pacientes, 59,3% eran del sexo masculino, con edad promedio de 59,1 años. Las quejas principales eran de malestar en adulto (130-22,5%), disnea en adulto (81-14,0%), dolor abdominal en adulto (58- 10,0%), alteraciones de comportamiento (34-5,9%), siendo que, de estos, 87% recibió alta. Fueron encontradas más muertes entre los pacientes clasificados con los colores más graves, siendo 42,8% clasificados como rojo, 17,0% naranja y 8,9% como amarillo. Entre los pacientes clasificados como verde, 9,6% evolucionó para la muerte.Conclusión:en los diversos colores del Sistema de Clasificación Manchester, la muerte prevaleció en los pacientes que presentaron la queja de malestar en adulto, disnea, sufrieron trauma craniano, trauma mayor, diarrea y vómito. Cuanto mayor es la prioridad clínica mayor es la prevalencia de la muerte.

Allogeneic hematopoietic stem cell transplantation in the elderly: Predicting the risk for non relapse mortality

We have retrospectively reviewed 137 medical records of patients older than 50 years receiving an allogeneic hematopoietic stem cell transplantation (HSCT) between January 1997 and July 2013. Median follow up was 1.3 years. Sex, age, diagnosis, disease stage, comorbidities (according to HCT-CI score), type of donor, histocompatibility, conditioning regimen and graft-versus-host disease (GVHD) prophylaxis were evaluated. The incidence and severity of acute and chronic GVHD, overall survival (OS), disease free survival (DFS), non-relapse mortality (NRM) and relapse were investigated according those variables. Acute GVHD incidence was 41% (7.3% GIII-IV). Patients with acute myeloid leukemia had lesser aGVH GII-IV (14% vs. 35%, p < 0.01) comparing to the entire population. Extensive cGVHD incidence was 9.4%. Global OS 1-3 years was 44-20%, DFS 33-20%, relapse 35-41% and NRM 36-43% respectively. The presence of comorbidities showed a significant increase in NRM (CT-CI 0 vs. 1 vs ≥ 2: 1-3 years 17-24% vs. 40-46% vs. 45-67%, p = 0.001, MA HR 2.03, CI 95% 1.02-5.29), as well as cyclosporine vs. tacrolimus (1-3 years 47-53% vs. 25-36%, p = 0.01). Tacrolimus patients had higher 1-3 years OS (49-25% vs. 31-13%, p = 0.01) and DFS (41-26% vs. 20-11%, p < 0.01). Age, type of donor and myeloablative conditioning showed no significant differences in any outcome. Allogeneic HSCT is a valid therapeutic option for older patients in Argentina. The main risk factor for a significantly increased NRM and a trend to inferior OS was the number of comorbidities. Age was not a factor for a worse result. The other factor having a significant effect in better outcome was tacrolimus administration.

Se efectuó un análisis retrospectivo de 137 historias clínicas de pacientes mayores de 50 años que recibieron un trasplante alogénico de precursores hematopoyéticos (TAPH). Se evaluaron las siguientes características: sexo, edad, enfermedad, estadio, comorbilidades (según el HCT-CI), donante, acondicionamiento e inmunosupresión. Se analizó la incidencia de enfermedad injerto vs. huésped aguda (aEICH) y crónica (cEICH), supervivencia global (SG), supervivencia libre de enfermedad (SLE), recaída y mortalidad libre de enfermedad (MLE). Los trasplantes fueron realizados entre 1997-2013, mediana de seguimiento 1.3 años. La incidencia de aEICH fue de 41% (7.3% GIII-IV). Los pacientes con leucemia mieloide aguda presentaron menor incidencia de EICHa GII-IV (14% vs. 34%, p < 0.01). La incidencia de EICHc extenso fue de 9.4%. La SG a 1-3 años fue 44-20%, SLE 33-20%, recaída 35-41% y la MLE 36-43%. Los pacientes con comorbilidades tuvieron un aumento significativo de la MLE (HCT-CI 0 vs. 1 vs. ≥2: 1-3 años 17-24% vs. 40-46% vs. 45-67%, p = 0.001, AMV HR 2.03, IC 95% 1.02-5.29), al igual que el uso de ciclosporina vs. tacrolimus (1-3 años 47-53% vs. 25-36%, p = 0.01). Los pacientes que recibieron tacrolimus tuvieron una mayor SG (1-3 años 49-25% vs. 31-13%, p = 0.01) y SLE (1-3 años 41-26% vs. 20-11%, p < 0.01). La edad, tipo de donante y acondicionamiento no resultaron significativos para ningún evento. El TAPH es una herramienta terapéutica válida en pacientes mayores. Los factores pronósticos que inciden mayormente en el trasplante son las comorbilidades y no la edad. El otro factor que demostró un efecto significativo fue el uso de tacrolimus.

Thoracic Air-leak Syndromes In Hematopoietic Stem Cell Transplant Recipients with Graft-versus-Host Disease: A Possible Sign for Poor Response to Treatment and Poor Prognosis

Bronchiolitis obliterans (BO) or bronchiolitis obliterans organizing pneumonia (BOOP) is one of manifestations of graft-versus-host disease (GVHD), a complication of hematopoietic stem cell transplantation (HSCT). Recently there are reports about thoracic air-leakage syndrome (TALS), but real incidence, clinical course, and implications of TALS remain unclear. Retrospective review of 18 TALS patients among 2,177 patients who received allogeneic HSCT between January 2000 to July 2007 was done. Clinical manifestations, treatments, and outcomes of TALS were reviewed. The incidence of TALS was 0.83% (18/2,177). The onset of TALS was mean 425.9+/-417.8 days (60-1,825 days) after HSCT, and the duration was mean 16.3+/-21 days (2-90 days). The most common types of TALS were spontaneous pneumothroax (n=14), followed by subcutaneous emphysema (n=6), pneumomediastinum (n=5), interstitial emphysema (n=2), and pneumopericardium (n=1). TALS persisted in six patients, who died during the same hospitalization. The 12 patients recovered from TALS, but only 2 survived, while others died due to aggravation of GVHD. TALS may complicate BO/BOOP and be an initial manifestation of BO/BOOP. TALS is hard to be resolved, and even after the recovery, patients die because of aggravation of GVHD. We suggest specifically in HSCT patients, when once developed, TALS seems hard to be cured, and as a result, be related to high fatality.

O transplante de células tronco hematopoéticas alogênico e autogênico na leucemia mielóide aguda em primeira remissão completa: análise de 62 pacientes / The allogeneic and autologous hematopoietic stem cell transplantation in acute myeloid leukemia in first complete remission: analyses of 62 patients

O transplante de células tronco hematopoéticas alogênico e autogênico na leucemia mielóide aguda em primeira remissão completa: analise de 62 pacientes. Os pacientes foram submetidos a transplante de células tronco hematopoéticas alogênico e autogênico. Ao final do estudo estavam vivos no alogênico 43,3% e no autogênico 62,5%. Consolidação intensiva teve melhor sobrevida no alogênico. Os pacientes com DECH aguda grau II tiveram melhor sobrevida. Dois pacientes com DECH crônica extensa morreram. Óbito por infecção ocorreu com maior freqüência no alogênico seguido de recidiva. No autogênico a recidiva foi a principal causa de óbito. Morte por toxicidade ocorreu em 47% dos pacientes que foram a óbito no alogênico e em 8,3% no autogênico. Na analise múltipla de Cox a consolidação intensiva e DECH crônica, tiveram significância...

The allogeneic and autologous hematopoietic stem cell transplantation in acute myeloid leukemia in first complete remission: analyses of 62 patients. The patients were submitted to allogeneic and autologous hematopoietic stem cell transplantation. The end of the study were kept alive in allogeneic 43,3% and in autologous 65,2%. Patient in allogeneic who were consolidated had better survival. Patients with acute GVHD grade II had better survival. Two patients with chronic GVHD in intense, died. Infection was the most frequent dead cause in allogeneic following relapse. In autologous the relapse was the principal cause of death. Toxicity occurred in 47% of patients who died in allogeneic and 8,3% in autologous. In cox multiple analyses intensive consolidation and chronic GVHD had significance...

Disfunción hepática en el trasplante de celulas progenitoras hematopoyéticas: Impacto sobre la mortalidad / Liver dysfunction in recipients of hematopoietic stem cells: Impact on mortality

El compromiso hepático en receptores de transplante alogénico de células progenitoras hemotopoyéticas (TCPH) es una complicación muy frecuente y es responsable de la morbimortalidad precoz. La toxicidad por fármacos la enfermedad injerto versus huésped ( EICH) , la enfermedad venooclusiva (EVO) y las infecciones fúngicas, bacterianas y virales constituyen las principales etiologias. El objetivo de este estúdio retrospectivo fue estabelecer la prevalencia y etiología de la afectación hepática, evaluar el impacto en la mortalidad y analizar el valor predictivo de las transaminasas pré TCPH en la ocurrencia de EICH agudo, crônico y mortalidad. De un total de 236 pacientes transplantados, se evaluaron 82 sometidos a TCPH alogénico. El 88% de los pacientes tuvo afectación hepática: EICH agudo 40.2%, EICH crônico 15.9%, de causa indeterminada 9.8% sepsis 7.3%, toxicidad por fármacos 6.1%, EVO 3.7%, hepatitis aguda y recidiva de enfermedad 2.4%. La mortalidad evaluada al año fue 36.6%. La insuficiência hepática aguda (IHA) represento el 10% de las muertes. Las causas de IHA fueron: progresón de EICH agudo, recidiva de la enfermedad hematológica en el hígado, hepatitis herpética y EVO. El valor predictivo positivo de las transaminasas pré TCPH para EICH agudo, crônico y mortalidad fue 0.27, 0.14 y 0.43 respectivamente. No se hallaron diferencias significativas entre pacientes con pruebas bioquímicas hepáticas pré TCPH alteradas o normales en la ocurrencia de EICH agudo, crónico o mortalidad.

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

Bone marrow transplantation for hematological disorders--Shiraz experience.

OBJECTIVE: In the past 8 years, 120 cases of hematological disorders were transplanted from the HLA identical donors. METHOD: Using chemotherapy based conditioning regimen with cyclophosphamide 200 mg/kg and busulfan 15-16 mg/kg, 80 cases of beta-thalassemia major and 35 cases of leukemia and five patients with aplastic anemia had received bone marrow transplantation. RESULT: The five-year-survival in thalassemic group was 72%, for leukemic group (acute and chronic) was 58%, and also for aplastic anemia 65%. Transplantation related mortality was the cause of death in 29 cases. The two major causes of death were acute graft versus host disease and poor medical condition of patients before marrow transplantation. CONCLUSION: At the present time, allogenic marrow transplantation is curative mode of treatment for many hematological diseases.