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- Ensayo clínico NCT03320928
Skin Disease and Pulmonary Mortality After Transplantation
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
The study encompassed 79 patients who were retrospectively identified. Eligible patients were those who had developed acute-GVHD of the skin and had been treated by photochemotherapy at the dermatology department at Huddinge University Hospital before the end of 2005. The follow-up of survival and relapse was a minimum ten year follow up. Patients with elevated bilirubin or excessive diarrhoea fulfilling the criteria of acute-GVHD of liver or gastrointestinal acute-GVHD were excluded, this to prevent confounding of the primary outcome measure by secondary ARDS elicited from the viscera and to limit the confounding of generalized toxicity or infections. The patients were diagnosed in accordance with the Glucksberg criteria, i.e. the extent of skin rash was stratified into skin disease stage 1 for an erytomatoeus rash covering <25% of the TBSA, skin disease stage 2 for a rash affecting 25 - 50% of the BSA and skin disease stage 3 for a rash affecting more than 50% of the TBSA.(Glucksberg H., 1974, Ringden O., 1996). The acute-GVHD diagnosis was supported with biopsy- and post-mortem histopathology. The patients who received methotrexate i.v. as an immunosuppressive treatment combined with photochemotherapy were compared with the patients who only received photochemotherapy. Photochemotherapy was administered at the department of dermatology where treatment data, including number of treatments and dose, treatment effect and adverse effects of photochemotherapy were recorded. Methotrexate was administered at the transplant unit. Non-negotiable variables and outcomes where primarily chosen to limit the bias. Toxicity was estimated by photo toxicity, renal impairment, liver damage and myelosuppression. The effect on acute-GVHD, creatinine, ALAT, leukocyte counts was determined from the prospective data records at the transplantation unit. All data including cause of death was cross checked with the centre for allogeneic stem-cell transplantation, (CAST) quality register and the records from CAST, the intensive care unit and the department of haematology including the death certificate. The study was undertaken in accordance with the Helsinki declaration and approved by the regional ethics committee, number 2012/969-31/3 with addendum 2014/1569-32 and number 425/97.
Treatment of acute-GVHD The acute-GVHD was treated with Corticosteroids in a dose of 2mg/kg prednisolone i.v. with additional bolus doses of methylprednisolone at the hands of the attending doctor. The variable corticosteroid treatment at the start of photochemotherapy was divided into: no corticosteroids, corticosteroid treatment but not corticosteroid resistant acute-GVHD, and finally corticosteroid resistant acute-GVHD (Remberger M., 2001). Oral 8-methoxypsoralene (8-MOP), (0.4-0.8 mg/kg), was ingested 1.5-2 h before the BSA was radiated by Long-wave UVA (320-400 nm) from a Waldmann UV1000 supine unit (Waldmann, Villingen-Schwenningen, Germany) with 26 Waldmann F85 100-W fluorescent photochemotherapy lamps or a Waldmann UV3003K half-body unit with 15 Waldmann F85 100-W photochemotherapy lamps (Parrish J.A., 1974, Henseler T., 1981). During UVA the genital area of male patients was protected. Eyes were shielded for 24 h thereafter during therapy. The dose of photochemotherapy was divided into the binary variable; low dose i.e. (0 - 9) treatments versus 10 treatments or more. Methotrexate was administered i.v. in 7,5 mg/m2 body surface area (1-3) times not more often than three times a week (Nassar A 2014). Concomitant injection of methotrexate during the period of photochemotherapy was registered as the binary variable; present or not present.
Outcome The Primary outcome; Crude pulmonary mortality was defined as lethal outcome of pulmonary disease and comprised IPS including interstitial pneumonitis with or without pulmonary infection, but also pneumonia and undefined respiratory insufficiency or interstitial fibrosis. As secondary outcome pulmonary mortality was divided into a binary variable; where those causes primarily associated with severe immunosuppression e.g. pulmonary mortality secondary to opportunistic infections; i.e. CMV-pneumonitis, fungal pneumonia or with a diagnosis of CMV-infection or fungal infections at the time of pulmonary mortality, was separated from the group of patients who died from pulmonary mortality without concomitant opportunistic disease (Yanik G., 2005, Watkins T.R., 2005, Forslow U., 2006, Bjorklund A., 2007) Chronic graft-versus-host disease was both included as a secondary outcome of acute-GVHD treatment and included as a predictor in the multivariate analysis for non-opportunistic pulmonary mortality.
The study size
The Study Size was all the patients in the closed photochemotherapy cohort who had cutaneous acute-GVHD without concomitant visceral disease at the start of photochemotherapy.
Statistical methods Shapiro-wilk was used to define if the variables were parametric or non-parametric. Parametric data was described with mean and +- SD, while non-parametric data was described with median and max-min. Kaplan and Meier curves was used to depict cumulative incidence of survival and Cox proportional hazards ratio was used to evaluate the risk for death in respiratory disease not explained by infectious agents. Log-rank test was used to variables that did not fit into the cox-model.
Tipo de estudio
Inscripción (Actual)
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Niño
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Método de muestreo
Población de estudio
Descripción
Inclusion Criteria:
- Treatment with photochemotherapy for aGVHD of the skin at the Dermatology Department at Huddinge Hospital before the end of 2005.
Exclusion Criteria:
- Retransplantation or DLI before photochemotherapy
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Crude Pulmonary Mortality
Periodo de tiempo: 10 years
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The Primary outcome; Crude pulmonary mortality was defined as lethal outcome of pulmonary disease and comprised IPS including interstitial pneumonitis with or without pulmonary infection, but also pneumonia and undefined respiratory insufficiency or interstitial fibrosis.
As secondary outcome pulmonary mortality was divided into a binary variable; where those causes primarily associated with severe immunosuppression e.g.
pulmonary mortality secondary to opportunistic infections; i.e.
CMV-pneumonitis, fungal pneumonia or with a diagnosis of CMV-infection or fungal infections at the time of pulmonary mortality, was separated from the group of patients who died from pulmonary mortality without concomitant opportunistic disease.
The cause of Death was derived from the Death certificate.
|
10 years
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Relapse
Periodo de tiempo: 10 years
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Relapse Incidence
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10 years
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Survival
Periodo de tiempo: 10 years
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Survival
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10 years
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Complete response in acute-GVHD
Periodo de tiempo: Two weeks after the end of treatment
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Complete response in acute-GVHD after photochemotherapy
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Two weeks after the end of treatment
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Colaboradores e Investigadores
Patrocinador
Publicaciones y enlaces útiles
Publicaciones Generales
- Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA, Lerner KG, Thomas ED. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974 Oct;18(4):295-304. doi: 10.1097/00007890-197410000-00001. No abstract available.
- Parrish JA, Fitzpatrick TB, Tanenbaum L, Pathak MA. Photochemotherapy of psoriasis with oral methoxsalen and longwave ultraviolet light. N Engl J Med. 1974 Dec 5;291(23):1207-11. doi: 10.1056/NEJM197412052912301. No abstract available.
- Ringdén O, Deeg HJ. Clinical spectrum of graft-versus-host disease. In: Ferrara JL, Deeg HJ, Burakoff S (eds). Graft vs Host Disease, Second Edition. Marcel Dekker: New York, NY, US, 1996, pp 525 - 595.
- Remberger M, Aschan J, Barkholt L, Tollemar J, Ringden O. Treatment of severe acute graft-versus-host disease with anti-thymocyte globulin. Clin Transplant. 2001 Jun;15(3):147-53. doi: 10.1034/j.1399-0012.2001.150301.x.
- Henseler T, Wolff K, Honigsmann H, Christophers E. Oral 8-methoxypsoralen photochemotherapy of psoriasis. The European PUVA study: a cooperative study among 18 European centres. Lancet. 1981 Apr 18;1(8225):853-7. doi: 10.1016/s0140-6736(81)92137-1.
- Yanik G, Cooke KR. The lung as a target organ of graft-versus-host disease. Semin Hematol. 2006 Jan;43(1):42-52. doi: 10.1053/j.seminhematol.2005.09.004.
- Watkins TR, Chien JW, Crawford SW. Graft versus host-associated pulmonary disease and other idiopathic pulmonary complications after hematopoietic stem cell transplant. Semin Respir Crit Care Med. 2005 Oct;26(5):482-9. doi: 10.1055/s-2005-922031.
- Forslow U, Mattsson J, Ringden O, Klominek J, Remberger M. Decreasing mortality rate in early pneumonia following hematopoietic stem cell transplantation. Scand J Infect Dis. 2006;38(11-12):970-6. doi: 10.1080/00365540600786481.
- Bjorklund A, Aschan J, Labopin M, Remberger M, Ringden O, Winiarski J, Ljungman P. Risk factors for fatal infectious complications developing late after allogeneic stem cell transplantation. Bone Marrow Transplant. 2007 Dec;40(11):1055-62. doi: 10.1038/sj.bmt.1705856. Epub 2007 Sep 24.
- Nassar A, Elgohary G, Elhassan T, Nurgat Z, Mohamed SY, Aljurf M. Methotrexate for the Treatment of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation. J Transplant. 2014;2014:980301. doi: 10.1155/2014/980301. Epub 2014 Oct 27.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Enfermedades de la piel
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Inhibidores de la síntesis de ácidos nucleicos
- Inhibidores de enzimas
- Agentes antirreumáticos
- Antimetabolitos, Antineoplásicos
- Antimetabolitos
- Agentes antineoplásicos
- Agentes inmunosupresores
- Factores inmunológicos
- Agentes dermatológicos
- Agentes de control reproductivo
- Agentes abortivos, no esteroideos
- Agentes abortivos
- Antagonistas del ácido fólico
- Metotrexato
Otros números de identificación del estudio
- TIM Photochem 3
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
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