RESUMEN
Allogeneic stem cell transplantation (SCT) is best performed with an HLA-identical sibling donor (matched related donor, MRD) to reduce the risk of early complications such as acute graft-vs.-host disease (aGvHD). However, as only about 30% of recipients have an MRD for this potentially curative approach, the use of family donors with one or two mismatches in the HLA-antigens (mismatch related donor, MMRD) or fully matched unrelated donors (MUD) (''alternative donors'') has been introduced in the allogeneic SCT setting in recent years. To evaluate the feasibility of allogeneic SCT from alternative donors by using peripheral blood stem cells (PBSC) we initiated a prospective, phase II study in 1996. From April 1996 to July 1998, 18 patients with various hematological malignancies underwent allogeneic SCT from alternative donors (two patients with MUD and 16 patients with MMRD). All patients received stable engraftment and none of the patients had graft rejection. The rate of aGvHD (grades II-IV) and the relapse rate at last follow-up (seven to nine yr after SCT) were with 40% and 24%, respectively, comparable with those found in patients receiving allogeneic SCT from MRD. However, five yr after allogeneic SCT only 17% were alive, which was mainly due to the treatment-related mortality (TRM) rate of 59%. We conclude that allogeneic PBSC transplantation by using alternative donors is associated with an unsatisfying long-term TRM rate. The significance of TRM and particular late deaths has to be evaluated further in this transplantation setting.
Asunto(s)
Leucemia/terapia , Trasplante de Células Madre , Donantes de Tejidos , Antígenos CD/sangre , Familia , Femenino , Filgrastim , Estudios de Seguimiento , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Prueba de Histocompatibilidad , Humanos , Leucemia/mortalidad , Masculino , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/terapia , Proteínas Recombinantes , Análisis de Supervivencia , Factores de Tiempo , Trasplante HomólogoRESUMEN
BACKGROUND: Severe acute graft-versus-host disease (aGVHD) of the gut is a serious and frequent posttransplantation event associated with a high mortality rate. We report on our experience with factor XIII replacement in patients with severe aGVHD of the bowel after allogeneic hematopoietic stem cell transplantation. METHODS: Twenty-seven patients after allogeneic stem cell transplantation and severe aGVHD of the gut were enrolled. All patients suffered from bloody diarrhea that required packed red blood cell infusions. All patients received high-dose immunosuppression in combination with coagulation factor XIII (5,000 units initially, followed by 20 IU/kg body weight three times a day) for up to 3 weeks. RESULTS: After 8 days of factor XIII replacement and unchanged high-dose immunosuppression, we observed a significant reduction in the red blood cell requirement of 21 patients. CONCLUSION: We conclude that factor XIII replacement might be a useful supplementation in the treatment of aGVHD of the bowel.
Asunto(s)
Factor XIII/uso terapéutico , Enfermedad Injerto contra Huésped/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedades Intestinales/terapia , Enfermedad Aguda , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trasplante HomólogoAsunto(s)
Trasplante de Médula Ósea/inmunología , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas , Inmunosupresores/uso terapéutico , Leucemia/terapia , Ácido Micofenólico/uso terapéutico , Enfermedad Aguda , Adulto , Enfermedad Crónica , Ciclosporina/uso terapéutico , Femenino , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Prueba de Histocompatibilidad , Humanos , Terapia de Inmunosupresión/métodos , Inmunosupresores/efectos adversos , Leucemia/mortalidad , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Ácido Micofenólico/efectos adversos , Ácido Micofenólico/análogos & derivados , Núcleo Familiar , Recurrencia , Estudios Retrospectivos , Tasa de Supervivencia , Irradiación Corporal TotalAsunto(s)
Anticuerpos Monoclonales/uso terapéutico , Trasplante de Médula Ósea/inmunología , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas , Inmunoglobulina G/uso terapéutico , Inmunosupresores/uso terapéutico , Ácido Micofenólico/uso terapéutico , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Citomegalovirus/fisiología , Infecciones por Citomegalovirus/fisiopatología , Daclizumab , Quimioterapia Combinada , Humanos , Inmunoglobulina G/efectos adversos , Inmunosupresores/efectos adversos , Ácido Micofenólico/análogos & derivados , Activación ViralRESUMEN
Hematopoietic stem cell transplantation (HSCT) is a treatment option for autoimmune diseases but can also cause clinical features similar to those of autoimmune diseases. In some of these cases the autoimmune-like condition is associated with autoimmune cytopenia, a complication that can be unresponsive to established treatment strategies and which may be fatal. The majority of cases reported on immune hemolytic anemia have been of alloimmune origin due to ABO red blood cell antigen incompatibilities between donor and recipient. We now report a patient with a lupus-like syndrome, presenting with severe thrombocytopenia and hemolytic anemia 9 months after HLA-mismatch, ABO compatible-related PBSCT who experienced no response to high-dose steroids, but who had a sustained response to repeated IvIG therapy.
Asunto(s)
Anemia Hemolítica/tratamiento farmacológico , Enfermedad Injerto contra Huésped/diagnóstico , Trombocitopenia/tratamiento farmacológico , Trasplante Homólogo/efectos adversos , Adulto , Anemia Hemolítica/diagnóstico , Anemia Hemolítica/etiología , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/etiología , Diagnóstico Diferencial , Supervivencia sin Enfermedad , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Prueba de Histocompatibilidad/efectos adversos , Humanos , Inmunoglobulinas Intravenosas/administración & dosificación , Lupus Vulgar/diagnóstico , Masculino , Recuento de Plaquetas , Trombocitopenia/diagnóstico , Trombocitopenia/etiologíaRESUMEN
Toxoplasmosis is a rare but often fatal complication that occurs after patients undergo allogeneic hematopoietic stem cell transplant. At our institution, toxoplasmosis was diagnosed in 8 of 301 patients who received stem cell transplants. Disseminated toxoplasmosis with a rapid fatal course was observed in 2 patients. Six patients had cerebral toxoplasmosis diagnosed on the basis of neurological signs and observation of the patients' mental confusion, seizures, and typical lesions (which were assessed by computed tomography, magnetic resonance imaging, or both). Seroconversion of antitoxoplasma immunoglobulin and a discovery of toxoplasma deoxyribonucleic acid in the cerebrospinal fluid (confirmed by use of polymerase chain reaction) were documented in all patients. Treatment consisted of clindamycin therapy (for 2 patients) and of pyrimethamine-clindamycin therapy, sulfadiazine therapy, or both (for 5 patients). Patients showed improvement after therapy, as assessed by clinical and radiological means. Three of 8 patients survive-1 without any residual neurological symptoms and 2 with minimal neurological symptoms.
Asunto(s)
Clindamicina/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Pirimetamina/uso terapéutico , Sulfadiazina/uso terapéutico , Toxoplasmosis Cerebral/tratamiento farmacológico , Toxoplasmosis Cerebral/etiología , Adulto , Animales , Anticuerpos Antiprotozoarios/inmunología , Quimioterapia Combinada , Femenino , Humanos , Inmunoglobulina M/inmunología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Toxoplasma/aislamiento & purificación , Toxoplasmosis Cerebral/diagnóstico , Trasplante HomólogoRESUMEN
Mycophenolate mofetil (MMF), a new immunosuppressive drug successfully used in renal and heart transplant recipients, was used in combination with cyclosporin A (CsA), methotrexate (MTX) and prednisolone for the prophylaxis of acute graft-versus-host disease (aGVHD) after bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) from human leukocyte antigen (HLA)-mismatched, unrelated (n = 9) and related donors (n = 4) in an open single-centre phase II study. Thirteen patients, transplanted from HLA-mismatched donors of 18-57 yr of age, received 1 g MMF daily, starting at day 10, in addition to CsA and prednisolone for aGVHD prophylaxis. All patients were engrafted between days 13 and 15. Four of the 13 patients experienced aGVHD grade I/II (n = 2) and grade III (n = 2). All patients except 3 were alive on day 100 post-transplantation. No severe adverse effects of MMF were recorded. In our pilot study, we demonstrated that MMF can be used safely for the prophylaxis of aGVHD.
Asunto(s)
Trasplante de Médula Ósea , Enfermedad Injerto contra Huésped/prevención & control , Antígenos HLA/análisis , Histocompatibilidad/inmunología , Inmunosupresores/uso terapéutico , Ácido Micofenólico/análogos & derivados , Enfermedad Aguda , Adolescente , Adulto , Anciano , Trasplante de Médula Ósea/inmunología , Ciclosporina/administración & dosificación , Ciclosporina/uso terapéutico , Combinación de Medicamentos , Femenino , Glucocorticoides/administración & dosificación , Glucocorticoides/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Masculino , Metotrexato/administración & dosificación , Metotrexato/uso terapéutico , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/efectos adversos , Ácido Micofenólico/uso terapéutico , Proyectos Piloto , Prednisolona/administración & dosificación , Prednisolona/uso terapéutico , Seguridad , Tasa de Supervivencia , Donantes de TejidosRESUMEN
Mobilization of peripheral blood cell progenitor cells was investigated in 36 healthy sibling donors using three different split doses of glycosylated rhG-CSF (lenograstim). The donors were randomized into three groups: group 1 was given lenograstim at 8, group 2 at 11 and group 3 at 15 micrograms/kg/day in two split doses, subcutaneously for 4 and 5 days, respectively. Leukapheresis was performed on day 4 or 5 depending on the WBC and CD34+ cell count. We were able to demonstrate that there was a significant correlation between circulating CD34+ cells on the day of harvest and CD34+ cells in the apheresis products in all three groups. The number of CD34+ cells pre-apheresis was inversely correlated with age in group 1 and group 2. However, in group 3, the number of CD34+ cells pre-apheresis did not correlate with age. There was also a difference between the number of progenitor cells mobilized in the three dose groups regarding the time of harvest. Apheresis was performed in groups 1 and 2 on day 5 of mobilization in order to obtain a sufficient number of stem cells for allogeneic transplantation. In contrast, with the split dose of 15 micrograms/kg/day, harvest could be routinely performed on day 4 of stimulation. We conclude that lenograstim given twice a day at doses of 8, 11 and 15 micrograms/kg/day provided different CD34+ cell yields in normal donors, in particular, with regard to the time of harvest. The number of CD34+ cells pre-apheresis was not correlated with age in the group of donors mobilized with a split dose of 15 micrograms/kg/day, indicating that this dosage might also be suitable for older donors.
Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Movilización de Célula Madre Hematopoyética , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Antígenos CD34 , Donantes de Sangre , Femenino , Humanos , Lenograstim , Masculino , Proteínas Recombinantes/administración & dosificación , Trasplante HomólogoRESUMEN
We report 27 patients with relapsed acute or chronic leukemia who underwent a second hematopoietic stem cell transplant (HSCT) from a related or unrelated donor. Seventeen patients were diagnosed with acute myelogenous leukemia (AML), six with acute lymphocytic leukemia (ALL) and four with chronic myeloid leukemia (CML). Ages ranged from 22 to 49 years (median 37); 13 patients were female and 14 male. Relapse was diagnosed between 1 and 45 months after the first HSCT. Sixteen patients who relapsed had received an autologous transplant initially and 11 an allogeneic transplant. Ten patients relapsed within 6 months and 17 patients later than 6 months. Chemotherapy was used as reinduction for relapse after HSCT in 16 patients who had received an autologous transplant and in three who had received an allogeneic transplant, since the latter did not respond to reduction of immunosuppression to induce a graft-versus-leukemia (GVL) reaction. Five of these 19 patients (26%) achieved complete remission (CR), seven patients did not respond to chemotherapy and seven achieved a partial remission (PR). The stem cell source for the second HSCT included bone marrow (n = 12) and PBSC (n = 4) from genotypically identical unrelated donors, PBSC (n = 7) and bone marrow (n = 3) from related donors. Currently eight of the 27 patients are alive and disease-free after the second HSCT. One patient is alive and disease-free after two allogeneic transplants (day +1538), eight patients, who relapsed after an autologous transplant followed by an allogeneic transplant (days +248 to +1140), acute myeloid leukaemia (n = 6) and chronic myeloid leukemia (n = 2) are alive and disease-free. The overall disease-free survival is 30% (8/27). The overall disease-free survival of autologous transplant patients subsequently undergoing an allogeneic transplant is 43% (P = 0.049). It is suggested that a second HSCT is possible for patients with leukemia relapse following the first autologous transplant. A second transplant might also be offered to patients relapsing after the first allogeneic HSCT. Bone Marrow Transplantation (2000) 25, 41-45.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia/patología , Leucemia/terapia , Enfermedad Aguda , Adulto , Enfermedad Crónica , Femenino , Humanos , Leucemia/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia , Análisis de Supervivencia , Trasplante HomólogoAsunto(s)
Trasplante de Médula Ósea/inmunología , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas , Inmunosupresores/uso terapéutico , Leucemia/terapia , Ácido Micofenólico/análogos & derivados , Enfermedad Aguda , Enfermedad Crónica , Ciclosporina/uso terapéutico , Quimioterapia Combinada , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Inmunosupresores/efectos adversos , Donadores Vivos , Ácido Micofenólico/efectos adversos , Ácido Micofenólico/uso terapéutico , Núcleo Familiar , Prednisolona/uso terapéuticoRESUMEN
The efficacy and safety of mycophenolate mofetil (MMF) in combination with CsA and prednisolone for the treatment of acute and chronic GVHD (aGVHD and cGVHD, respectively) after BMT and PBSCT from HLA-mismatched and -matched donors was evaluated in an open single center trial. Twenty-four patients, 17-48 years of age, with acute (n = 17) and chronic GVHD (n = 7) were treated with 2 g MMF daily in addition to CsA and prednisolone. Overall grade improvement of aGVHD was found in 11 of 17 (65%) patients treated with MMF. MMF therapy in the treatment of cGVHD led to moderate improvement in three of six patients with limited cGVHD. The most common adverse hematologic events of MMF were leukopenia (n = 6), anemia (n = 4) and thrombocytopenia (n = 3). Hematological adverse events were not severe and did not require the discontinuation of MMF. In this preliminary study, we have shown that MMF can be used safely for the treatment of aGVHD. In addition, the MMF therapy resulted in significant dose reduction of prednisolone for the treatment of GVHD.