RESUMEN
BACKGROUND: High-dose chemotherapy (HDC) with hematopoietic progenitor cell transplantation is a standard option for relapsed/refractory testicular germ-cell tumor (GCT), but only few data have been reported in female patients with GCT. We conducted a retrospective analysis of female patients with GCT treated with HDC and registered with the European Society for Blood and Marrow Transplantation. PATIENTS AND METHODS: Between 1985 and 2013, 60 registered female patients with GCT, median age 27 years (range 15-48), were treated with salvage HDC. Forty patients (67%) had primary ovarian GCT, 8 (13%) mediastinal, 7 (12%) retroperitoneal and 5 (8%) other primary sites/unknown. Twenty-two patients (37%) received HDC as second-line therapy, 29 (48%) as third-line, and 9 (15%) as fourth- to sixth-line. Nine of 60 patients (15%) received HDC as late-intensification with no evidence of metastasis before HDC. The conditioning HDC regimens comprised carboplatin in 51 of 60 cases (85%), and consisted of a single HDC cycle in 31 cases (52%), a multi-cycle HDC regimen in 29 (48%). RESULTS: Nine cases who underwent late intensification HDC were not evaluable for response. Of the other 51 assessable patients, 17 (33%) achieved a complete response (CR), 8 (16%) a marker-negative partial remission (PRm-), 5 (10%) a marker-positive partial remission, 5 (10%) stable disease, and 13 (25%) progressive disease. There were 3 toxic deaths (6%). With an overall median follow-up of 14 months (range 1-219), 7 of 9 (78%) patients with late intensification and 18 of the 25 patients (72%) achieving a CR/PRm- following HDC were free of relapse/progression. In total, 25 of 60 patients (42%) were progression-free following HDC at a median follow-up of 87 months (range 3-219 months). CONCLUSIONS: Salvage HDC based on carboplatin represents a therapeutic option for female patients with relapsed/refractory GCT.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Terapia Recuperativa , Adolescente , Adulto , Antineoplásicos/administración & dosificación , Trasplante de Médula Ósea , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Persona de Mediana Edad , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias de Células Germinales y Embrionarias/terapia , Recurrencia , Estudios Retrospectivos , Análisis de Supervivencia , Acondicionamiento Pretrasplante , Adulto JovenRESUMEN
WHAT IS KNOWN AND OBJECTIVE: Ibrutinib is a recently approved oral anticancer agent with pharmacokinetics that is very sensitive to metabolic inhibition. We report a serious side effect of ibrutinib potentially attributable to interaction with the moderate CYP3A4 inhibitor verapamil. CASE DESCRIPTION: A patient with mantle cell lymphoma was admitted to our emergency department with severe diarrhoea. During a prescription review, the clinical pharmacist identified a potential drug interaction between ibrutinib and verapamil present in a branded combination product also containing trandolapril. Ibrutinib was discontinued for 5 days, and verapamil was stopped. Lercanidipine 10 mg daily was prescribed as an alternative antihypertensive drug. The patient was discharged after 3 days with symptomatic treatment for his diarrhoea. Three months later, the patient maintained control with ibrutinib and olmesartan, but without verapamil. WHAT IS NEW AND CONCLUSION: This is the first description of a serious side effect of ibrutinib likely due to an interaction with the CYP3A4 inhibitor verapamil. Prescriptions of ibrutinib must be carefully checked to identify possible interactions with CYP3A4 inhibitors and patients monitored accordingly.
Asunto(s)
Antineoplásicos/efectos adversos , Inhibidores del Citocromo P-450 CYP3A/efectos adversos , Pirazoles/efectos adversos , Pirimidinas/efectos adversos , Verapamilo/efectos adversos , Adenina/análogos & derivados , Anciano , Antihipertensivos/administración & dosificación , Antihipertensivos/efectos adversos , Antihipertensivos/uso terapéutico , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Inhibidores del Citocromo P-450 CYP3A/administración & dosificación , Inhibidores del Citocromo P-450 CYP3A/farmacología , Diarrea/inducido químicamente , Dihidropiridinas/administración & dosificación , Interacciones Farmacológicas , Humanos , Linfoma de Células del Manto/tratamiento farmacológico , Masculino , Piperidinas , Pirazoles/administración & dosificación , Pirazoles/farmacocinética , Pirimidinas/administración & dosificación , Pirimidinas/farmacocinética , Verapamilo/administración & dosificación , Verapamilo/farmacologíaRESUMEN
BACKGROUND: Muir-Torre syndrome (MTS), a cutaneous variant of Lynch syndrome, consists of hereditary predisposition to cutaneous tumours and gastrointestinal and gynaecological neoplasms, with autosomal dominant transmission. It is associated with mutations in genes coding for proteins in the DNA mismatch repair system. PATIENTS AND METHODS: Herein, we report a case of a male patient presenting Waldenstrom's macroglobulinemia since the age of 50 and which, after the age of 65 years, developed into sebaceous tumours (5 sebaceous adenomas, 1 sebaceoma, 1 sebaceous carcinoma) and colonic lesions (4 adenomas). The clinical phenotype was consistent with MTS. Somatic analysis carried out on one sebaceous tumour showed instability of the microsatellites with loss of expression of MSH2 and MSH6 although constitutional genetic analysis showed no germline mutations known to be harmful. DISCUSSION: This noteworthy case raises a number of questions, including the possibility of association between STM and Waldenstrom's macroglobulinemia, which is discussed herein.
Asunto(s)
Síndrome de Muir-Torre/complicaciones , Macroglobulinemia de Waldenström/complicaciones , Adenoma/genética , Anciano , Carcinoma/genética , Neoplasias del Colon/genética , Humanos , Masculino , Inestabilidad de Microsatélites , Síndrome de Muir-Torre/genética , Neoplasias de las Glándulas Sebáceas/genéticaRESUMEN
Hematopoietic stem cell transplantation (HSCT) for severe ADs was developed over the past 25years and is now validated by national and international medical societies for severe early systemic sclerosis (SSc) and relapsing-remitting multiple sclerosis (MS) and available as part of routine care in accredited center. HSCT is also recommended, with varying levels of evidence, as an alternative treatment for several ADs, when refractory to conventional therapy, including specific cases of connective tissue diseases or vasculitis, inflammatory neurological diseases, and more rarely severe refractory Crohn's disease. The aim of this document was to provide guidelines for the current indications, procedures and follow-up of HSCT in ADs. Patient safety considerations are central to guidance on patient selection and conditioning, always validated at the national MATHEC multidisciplinary team meeting (MDTM) based on recent (less than 3months) thorough patient evaluation. HSCT procedural aspects and follow-up are then carried out within appropriately experienced and Joint Accreditation Committee of International Society for Cellular Therapy and SFGM-TC accredited centres in close collaboration with the ADs specialist. These French recommendations were performed according to HAS/FAI2R standard operating procedures and coordinated by the Île-de-France MATHEC Reference Centre for Rare Systemic Autoimmune Diseases (CRMR MATHEC) within the Filière FAI2R and in association with the Filière MaRIH. The task force consisted of 3 patients and 64 clinical experts from various specialties and French centres. These data-derived and consensus-derived recommendations will help clinicians to propose HSCT for their severe ADs patients in an evidence-based way. These recommendations also give directions for future clinical research in this area. These recommendations will be updated according to newly emerging data. Of note, other cell therapies that have not yet been approved for clinical practice or are the subject of ongoing clinical research will not be addressed in this document.
Asunto(s)
Enfermedades Autoinmunes , Trasplante de Células Madre Hematopoyéticas , Esclerodermia Sistémica , Humanos , Acondicionamiento Pretrasplante/métodos , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/terapia , Trasplante Autólogo , Esclerodermia Sistémica/diagnóstico , Esclerodermia Sistémica/terapiaRESUMEN
Limited therapeutic options are available after relapse of acute leukaemia following first reduced intensity conditioning haematopoietic stem cell transplantation (RIC1). A retrospective study on European Society for Blood and Marrow Transplantation (EBMT) registry data was performed on 234 adult patients with acute leukaemia who received a second RIC transplantation (RIC2) from 2000 to 2012 as a salvage treatment for relapse following RIC1. At the time of RIC2, 167 patients (71.4%) had relapsed or refractory disease, 49 (20.9%) were in second CR and 18 (7.7%) in third or higher CR. With a median follow-up of 21 (1.5-79) months after RIC2, 51 patients are still alive. At 2 years, the cumulative incidence of non-relapse mortality (NRM), relapse incidence (RI), leukaemia-free survival (LFS) and overall survival (OS) were 22.4% (95% confidence interval (CI): 17-28.4), 63.9% (56.7-70.1), 14.6% (8.8-18.5) and 20.5% (14.9-26.1), respectively. In patients with acute myelogenous, biphenotypic and undifferentiated leukaemia (representing 89.8% of all patients), duration of remission following RIC1 >225 days, presence of CR at RIC2, patient's Karnofsky performance status >80 at RIC2 and non-myeloablative conditioning were found to be the strongest predictors of patients' favourable outcome.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia , Acondicionamiento Pretrasplante/métodos , Enfermedad Aguda , Adulto , Anciano , Aloinjertos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Leucemia/mortalidad , Leucemia/prevención & control , Masculino , Persona de Mediana Edad , Recurrencia , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
Historically, invasive aspergillosis (IA) has been a major barrier for allogeneic hematopoietic stem cell transplantation (allo-HSCT). The influence of invasive IA on long-term survival and on transplant-related complications has not been investigated in a larger patient cohort under current conditions. Our aim was to analyze the long-term outcome of patients undergoing allo-HSCT with a history of prior IA. We used European Society for Blood and Marrow Transplantation database data of first allo-HSCTs performed between 2005 and 2010 in patients with acute leukemia. One thousand one hundred and fifty patients with data on IA before allo-HSCT were included in the analysis. The median follow-up time was 52.1 months. We found no significant impact of IA on major transplant outcome variables such as overall survival, relapse-free survival, non-relapse mortality, cumulative incidence of acute GvHD grade II-IV, chronic GvHD, pulmonary complications and leukemia relapse. However, we found a trend toward lower overall survival (P=0.078, hazard ratio (HR) (95% confidence interval (CI)): 1.16 (0.98, 1.36)) and higher non-relapse mortality (P=0.150, HR (95% CI): 1.19 (0.94, 1.50)) in allo-HSCT recipients with pre-existing IA. Our data suggest that a history of IA should not generally be a contraindication when considering the performance of allo-HSCT in patients with acute leukemia.
Asunto(s)
Aspergilosis , Trasplante de Células Madre Hematopoyéticas , Leucemia , Enfermedad Aguda , Adolescente , Adulto , Anciano , Aloinjertos , Aspergilosis/complicaciones , Aspergilosis/mortalidad , Aspergilosis/terapia , Niño , Preescolar , Enfermedad Crónica , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Lactante , Leucemia/mortalidad , Leucemia/terapia , Masculino , Persona de Mediana Edad , Tasa de SupervivenciaRESUMEN
The outcome of adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL) relapsing after pediatric-inspired front-line therapy is ill known. Here 229 relapsing Ph- ALL younger adults (18-63 years) treated within the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003/-2005 trials were considered. Salvage regimens consisted of potentially curative therapies in 194 cases, low-intensity therapies in 21, allogeneic stem cell transplant (allo-SCT) in 6 and best supportive care in 8. Overall, 77 patients received allo-SCT after relapse. The median follow-up was 3.1 years. A second complete remission (CR2) was achieved in 121 patients (53%). In multivariate analysis, only younger age <45 years (P=0.008) and CR1 duration ⩾18 months (P=0.009) predicted CR2. Overall survival (OS) at 2 and 5 years was 19.3% (14-24%) and 13.3% (8-18%), respectively. In CR2 patients, disease-free survival (DFS) at 2 and 5 years was 29.0% (21-38%) and 25% (17-33%). In multivariate analysis, CR1 duration ⩾18 months and allo-SCT after relapse were associated with longer DFS (P<0.009 and P=0.004, respectively) and longer OS (P=0.004 and P<0.0001, respectively). In conclusion, although younger adults relapsing after pediatric-inspired ALL therapies retain a poor outcome, some of them may be cured if CR1 duration ⩾18 months and if allo-SCT can be performed in CR2. New therapies are definitely needed for these patients.
Asunto(s)
Mesilato de Imatinib/administración & dosificación , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Rituximab/administración & dosificación , Adolescente , Adulto , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/patología , Masculino , Persona de Mediana Edad , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Inducción de Remisión , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: Ten years after the first clinical studies, the clinical impact of myeloid growth factors in acute myeloid leukemia is still unclear. One of the objectives of the Groupe Ouest-Est Leucémies Aigues Myeloblastiques (GOELAM) 2 trial was to evaluate the benefit of granulocyte colony-stimulating factor (GCSF) given only after the two courses of intensive consolidation chemotherapy (ICC) used to maintain complete remission (CR). PATIENTS AND METHODS: One hundred ninety-four patients who were in CR after induction treatment were randomly assigned to receive G-CSF (100 patients) or no G-CSF (94 patients) after two courses of ICC (ICC 1, high-dose cytarabine plus mitoxantrone; ICC 2, amsacrine plus etoposide). G-CSF (filgrastim) was administered from the day after chemotherapy until granulocyte recovery at a daily dose of 5 microg/kg. RESULTS: In the G-CSF group, the median duration of neutropenia (< 0.5 x 10(9)/L) was dramatically reduced, both after ICC 1 (12 v 19 days, P <.001) and after ICC 2 (20 v 28 days, P <.001). The median duration of hospitalization was also significantly shorter in the G-CSF group (24 v 27 days after ICC 1, P <.001; 29 v 34 days after ICC 2, P <. 001). The median duration of intravenous antibiotics was significantly reduced after ICC 1 and ICC 2, and the median duration of antifungal therapy was significantly reduced after ICC 1. However, the incidence of microbiologically documented infections, the toxic death rate, the 2-year disease-free survival, and the 2-year overall survival were not affected by G-CSF administration. Moreover, the median interval between ICC1 and ICC2 was reduced by only 2 days, and the number of patients undergoing ICC2 was not increased in the G-CSF arm. CONCLUSION: G-CSF should be administered routinely after ICC to reduce the duration of neutropenia and hospitalization. However, G-CSF did not seem to significantly increase the feasibility of this two-course program or modify overall outcome.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Leucemia Mieloide/tratamiento farmacológico , Enfermedad Aguda , Adolescente , Adulto , Amsacrina/administración & dosificación , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Antimetabolitos Antineoplásicos/administración & dosificación , Antineoplásicos/administración & dosificación , Antineoplásicos Fitogénicos/administración & dosificación , Citarabina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Filgrastim , Hospitalización , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Neutropenia/prevención & control , Proteínas Recombinantes , Inducción de Remisión , Resultado del TratamientoRESUMEN
The orphan homeobox gene HOX11L2 was previously found to be transcriptionally activated as a result of the t(5;14)(q35;q32) translocation in three T-ALL cases. We now tested by RT-PCR Hox11L2 expression in 23 consecutive cases of T-ALL (15 children aged 0.8-14 years, eight adults aged 17-55 years) and as control 13 B-ALL patients from a single institution. Hox11L2 expression was undetectable in all patients with B-ALL, nor in adults with T-ALL. Nine children (60% of the cases), all boys, expressed Hox11L2. Blast cells from most of the latter patients carried surface CD1a, CD10 and not CD34 antigens, in contrast to the other children. FISH, M-FISH and IPM-FISH analysis failed to detect a t(5;14)(q35;q32) in one of them, which suggests a possible distinct genetic mechanism in Hox11L2 expression induction. Hence, Hox11L2 expression seems to be the most frequent abnormality in childhood T-ALL to date, comparable to the t(12;21) in child B-ALL.
Asunto(s)
Proteínas de Homeodominio/genética , Leucemia-Linfoma de Células T del Adulto/genética , Proteínas Oncogénicas/genética , Adolescente , Adulto , Factores de Edad , Anciano , Antígenos CD/análisis , Estudios de Casos y Controles , Niño , Preescolar , Cromosomas Humanos Par 14 , Cromosomas Humanos Par 5 , Femenino , Regulación de la Expresión Génica , Humanos , Inmunofenotipificación , Incidencia , Lactante , Leucemia-Linfoma de Células T del Adulto/mortalidad , Masculino , Proteínas Proto-Oncogénicas , Estudios Retrospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Supervivencia , Tasa de Supervivencia , Translocación GenéticaRESUMEN
Allogeneic hematopoietic transplantation is increasingly used in patients aged 55 years or more with AML. The question of whether outcomes can be improved with an allele-level 8/8 HLA-matched unrelated donor (MUD) rather than an older HLA-matched sibling (MSD, more than 55 years) is still unanswered. We thus analyzed outcomes in 714 patients aged 55 years and older with AML in first CR (CR1) who received PBSCs after a reduced-intensity conditioning hematopoietic cell transplant from a MUD (n=310) or a MSD (n=404) in a recent period (2005-2010). The 3-year cumulative incidences (CIs) of non-relapse mortality were 17% and 23% with MSD and MUD, respectively (P=0.17). The 3-year CIs of relapse were 37% and 30%, respectively (P=0.12), resulting in a 3-year CI of leukemia-free survival of 46% and 47%, respectively (P=0.51). The 3-year overall survival was 49% with both MSD and MUD. In conclusion, HLA-identical sibling donors aged 55 years or more should not be excluded because of age for patients aged 55 years and older with AML in CR1.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/terapia , Donadores Vivos , Obtención de Tejidos y Órganos , Factores de Edad , Anciano , Aloinjertos , Supervivencia sin Enfermedad , Femenino , Filgrastim , Estudios de Seguimiento , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/prevención & control , Histocompatibilidad , Humanos , Inmunosupresores/uso terapéutico , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Hermanos , Acondicionamiento Pretrasplante , Resultado del TratamientoRESUMEN
Serial determination of soluble CD8 (sCD8), soluble IL-2 receptors (sIL-2R), and tumor necrosis factor-alpha serum levels were performed in bone marrow transplant patients upon initiation, day 0 (D0) and at D10 of an anti-IL-2 receptor (alpha chain) monoclonal antibody (B-B10) in vivo treatment for steroid-resistant grade greater than or equal to 2 acute graft-versus-host disease (aGVHD). D0 and D10 sCD8 serum levels correlated strongly with response to B-B10 treatment (p = .003 and .001, respectively); 76% of the patients with D0 sCD8 levels less than 500 U/ml responded favorably to B-B10 treatment, versus only a 30% response if the sCD8 levels were greater than 500 U/ml (p = .02). Likewise, D0 tumor necrosis factor-alpha levels significantly correlated with subsequent response to B-B10 treatment (p = .03). D0 sIL-2R levels were not significantly different in B-B10-responsive and nonresponsive aGVHD patients. These results suggest that the serial determination of sCD8 and TNF serum levels could provide valuable predictive information as to steroid-resistant aGVHD responsiveness to anti-IL-2R treatment.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antígenos CD/análisis , Antígenos de Diferenciación de Linfocitos T/análisis , Trasplante de Médula Ósea/efectos adversos , Enfermedad Injerto contra Huésped/inmunología , Receptores de Interleucina-2/sangre , Factor de Necrosis Tumoral alfa/análisis , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Antígenos CD8 , Niño , Preescolar , Resistencia a Medicamentos , Femenino , Enfermedad Injerto contra Huésped/terapia , Humanos , Masculino , Receptores de Interleucina-2/inmunologíaRESUMEN
A double-blind, placebo-controlled trial of BT563, including 13 European centers, was initiated in October 1989 to compare the efficacy of the combination of in vivo anti-CD25 mAb (BT 563), cyclosporine, and steroids versus placebo and CSA-steroids in the treatment of grade II and III acute graft-versus-host disease (GVHD). Sixty-nine patients participated in the study, which excluded non-genotypically identical allogeneic bone marrow transplant recipients. No statistically significant differences were observed, clinically or biologically, between the 2 groups before the onset of the treatment. Treatment responses were scored during and after the 3-week treatment period (mAb or placebo). Efficacy was evaluated on days 4, 10, 20, 30, and 60 or on any day the patient's condition was found to be deteriorating. Preceding and systemically untreated GVHD of grade I was observed in 59% of the cases. No statistically clinically significant differences between the 2 groups were observed during or upon completion of treatment in GVHD grade. Nine patients in the placebo group and 6 in the active group were withdrawn of the study. Thirteen of these 15 patients were withdrawn because of failure of GVHD therapy (9 in the placebo group and 4 in the BT563 group). At day 20 after onset of the treatment, the response rate was 63% and 70% for the placebo and BT563 groups, respectively (NS). Probability of survival at 1 year was 59% and 66% (NS) for the placebo and active groups, respectively. In conclusion, despite preliminary promising results in the treatment of steroid-resistant acute GVHD, the role of first-line treatment with an in vivo anti-interleukin-2 receptor mAb remains to be determined.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Trasplante de Médula Ósea/inmunología , Ciclosporina/uso terapéutico , Enfermedad Injerto contra Huésped/terapia , Inmunosupresores/uso terapéutico , Metilprednisolona/uso terapéutico , Enfermedad Aguda , Adolescente , Adulto , Niño , Preescolar , Método Doble Ciego , Femenino , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/fisiopatología , Humanos , Terapia de Inmunosupresión/métodos , Masculino , Persona de Mediana Edad , Placebos , Trasplante HomólogoRESUMEN
In the present work, we describe a new DR14 allele. Sequencing of its second DRB1 exon showed it to be DRB1*1404 from codon numbers 9 to 56 and 61 to 86, and DRB1*11 from codons 57 to 60 inclusive.
Asunto(s)
Alelos , Genes MHC Clase II , Antígenos HLA-DR/genética , Haplotipos/genética , Antígenos de Histocompatibilidad Clase II/genética , Adulto , Secuencia de Aminoácidos , Secuencia de Bases , Niño , Femenino , Genotipo , Subtipos Serológicos HLA-DR , Cadenas HLA-DRB1 , Prueba de Histocompatibilidad , Humanos , Masculino , Datos de Secuencia Molecular , Alineación de Secuencia , Homología de SecuenciaRESUMEN
Autologous stem cell transplantation has become an important therapy in lymphoma, multiple myeloma and solid tumors. The rationale for the selection of CD34+ cells from peripheral blood or bone marrow progenitor cell collections is based on the observation that contaminating tumor cells can be depleted approximately 3 to 6 logs. This procedure may be limited because of lack of sufficient numbers of progenitor cells in the leukapheresis concentrates. The use of frozen/thawed peripheral blood mononuclear cell (PBMC) samples makes it possible to pool two or even more stem cell harvests collected at different time points to increase the total number of CD34+ progenitor cells. We report in this work the feasibility of frozen/thawed peripheral blood CD34+ positive cell selection, using the large-scale (Ceprate SC) and the lab-scale avidin-biotin immunoadsorption system (Ceprate LC). This procedure consists of a washing step and a positive selection step. Our results show that frozen/thawed CD34+ cells were obtained with a purity of 86.68 +/- 3.62%, a viability of 97.94 +/- 0.97% and a recovery of 91.85 +/- 10.84% (range 80 to 112%). The CFU-GM assays were performed in a methylcellulose based medium; 89.13 +/- 19.63 colonies were obtained for 10(3) cells plated. Two patients were grafted with peripheral blood CD34+ cells selected after freezing. Our clinical data show that these cells are capable of rapidly reconstituting hematopoiesis after high-dose chemotherapy.
Asunto(s)
Antígenos CD34/análisis , Conservación de la Sangre/métodos , Separación Celular/métodos , Criopreservación , Trasplante de Células Madre Hematopoyéticas/métodos , Células Madre Hematopoyéticas , Técnicas de Inmunoadsorción , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ensayo de Unidades Formadoras de Colonias , Terapia Combinada , Resultado Fatal , Estudios de Factibilidad , Células Madre Hematopoyéticas/química , Humanos , Leucaféresis , Linfoma no Hodgkin/sangre , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/terapia , Mieloma Múltiple/sangreRESUMEN
Extragonadal germ cell tumors are classified according to the staging system of the International Germ Cell Cancer Collaborative Group (IGCCCG). The 5-year overall and disease-free survival rates for poor prognosis patients are 41 and 48%, respectively after standard-dose chemotherapy. We report the experience of the EBMT Solid Tumours Working Party (STWP) with first-line HDCT with hematopoietic progenitor cell support (HPCS) in patients with poor prognosis extragonadal nonseminomatous germ cell tumor (NSGCT). Between 1990 and 2001, 22 extragonadal NSGCT patients (21 M, 1 F), median age 30 years (range 17-52) were treated with first-line HDCT with HPCS. Primary site was mediastinum in 11 patients, retroperitoneum in 10, and unknown in one. The Carbopec regimen, consisting of high doses of carboplatin, etoposide, and cyclophosphamide, was used in most cases (12 patients). No treatment-related deaths occurred. No patient developed myelodysplasia or a secondary leukemia. In total, 17 of 22 patients (77%) achieved complete remission. At a median follow-up of 50 months (range 26-132), 15 patients (68%) are alive disease-free. The survival rates of patients with poor prognosis extragonadal NSGCT treated with first-line HDCT in the EBMT STWP experience appear higher than that expected according to the IGCCCG classification.
Asunto(s)
Antineoplásicos/administración & dosificación , Germinoma/tratamiento farmacológico , Adolescente , Adulto , Antineoplásicos/toxicidad , Femenino , Germinoma/complicaciones , Germinoma/mortalidad , Trasplante de Células Madre Hematopoyéticas , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Sistema de Registros , Inducción de Remisión , Estudios Retrospectivos , Ajuste de Riesgo , Análisis de SupervivenciaRESUMEN
We previously demonstrated the potential of anti-IL-2R and anti-TNF alpha moAbs in the treatment of acute graft-versus-host disease (GVHD). However, one major problem was the recurrence of acute GVHD on treatment discontinuation. To target the two main effectors of acute GVHD lesions, T and NK cells on the one hand and TNF alpha on the other, we combined anti-CD2 and anti-TNF alpha moAbs. Then to prevent acute GVHD recurrence, we administered anti-IL-2R moAbs known for their inhibitory effect on activated cells. We included 15 patients with steroid-resistant acute GVHD. Seven were grafted from a genotypically-identical sibling, 5 from HLA-matched unrelated donors and 3 from partially-matched related donor. Prophylaxis of acute GVHD consisted of cyclosporin A +/- methotrexate or corticosteroids. Before treatment 6 patients had grade II, 2 patients grade III and 7 patients grade IV acute GVHD. Anti-TNF alpha (B-C7) moAbs (10 mg/day/4 days) were combined with anti-CD2 (B-E2) moAbs (10 mg/day/10 days) on the fifth day (day 5), anti-IL-2 receptor (B-B10) moAbs were given at 10 mg/day/10 days followed by 5 mg every other day for another 50 days. On day 15, 5 patients achieved a complete remission, 4 a very good partial response (62% a good response), 2 had a partial response and 4 did not respond. GVHD recurred in 4 of the 9 responders, although anti-IL-2R moAb treatment was maintained. Three patients are long-term survivors without chronic GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Trasplante de Médula Ósea , Antígenos CD2/inmunología , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Interleucina-2/inmunología , Factor de Necrosis Tumoral alfa/inmunología , Enfermedad Aguda , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Trasplante de Médula Ósea/inmunología , Niño , Citocinas/sangre , Resistencia a Medicamentos , Quimioterapia Combinada , Femenino , Enfermedad Injerto contra Huésped/inmunología , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Proteínas Recombinantes/inmunologíaRESUMEN
The efficacy of gastrointestinal decontamination in reducing the incidence of severe bacterial or fungal infections and of moderate to severe acute graft-versus-host disease (GVHD) has been suggested. We report here a retrospective study of 71 patients grafted consecutively in our institution with bone marrow from HLA genotypically identical siblings. Complete decontamination (plastic isolator or laminar airflow room, sterile nursing and oral antimicrobial drugs) was carried out in all patients. Sixty eight patients were evaluable. Only six patients had aerobic Gram negative rods or anaerobic bacteria in their faeces and 44 of 68 (65%) had yeasts in their faeces. Most patients had oropharyngeal and/or nasal colonisation with bacteria (Gram positive cocci: 39 patients (57%); Gram negative rods: 13 patients (19%)) or yeasts (29 patients (43%)). Thirty nine patients (57%) experienced severe grade > or = II acute GVHD (grade II-IV). A significant relation was found between bacterial oropharyngeal or nasal colonisation and GVHD (P < 0.01) but not between gastrointestinal microflora and GVHD, whatever microorganisms were considered (bacteria, yeasts).
Asunto(s)
Infecciones Bacterianas/etiología , Trasplante de Médula Ósea , Enfermedad Injerto contra Huésped/microbiología , Micosis/etiología , Nasofaringe/microbiología , Enfermedad Aguda , Adolescente , Adulto , Infecciones Bacterianas/prevención & control , Niño , Preescolar , Heces/microbiología , Femenino , Enfermedad Injerto contra Huésped/terapia , Antígenos HLA , Humanos , Masculino , Persona de Mediana Edad , Micosis/prevención & control , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Attempts to improve the efficacy of pretransplant conditioning regimens have been published, the potential of a better antileukemic effect being impaired by more frequent and severe toxicities. The efficacy of an intensified regimen, TAM (TBI, high-dose cytosine arabinoside and melphalan), is evaluated by analyzing long-term follow-up of a homogenous group of 42 high-risk ALL patients allografted in first CR. Age at time of BMT was 25.9 +/- 10.4 years (3-41). Twenty-two patients had more than three adverse prognostic factors. Ten patients had a Ph chromosome. Probability of overall survival was 45 +/- 9%, and for all surviving patients median follow-up time was 66 months. Event-free survival was 40 +/- 8% at 7 years after transplantation and the expected relapse rate reached 31%. Twenty-two deaths occurred, six after a relapse but 16 appeared to be directly due to the BMT procedure. None of the pretransplant characteristics significantly affected outcome after BMT. TAM appeared to be an efficient antileukemic therapy for conditioning high-risk ALL patients before allogeneic transplantation, but was still very toxic. The use of TAM in adult ALL patients in first CR is not recommended and the real role of intensified conditioning regimens remains to be demonstrated.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea , Linfoma de Burkitt/terapia , Leucemia-Linfoma de Células T del Adulto/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Linfoma de Burkitt/radioterapia , Niño , Preescolar , Terapia Combinada , Citarabina/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Leucemia-Linfoma de Células T del Adulto/radioterapia , Masculino , Melfalán/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Irradiación Corporal TotalRESUMEN
This retrospective study was undertaken to evaluate cure rates, toxicity and late effects of early intensive therapy followed by autologous stem cell transplantation (ASCT) in patients with advanced Hodgkin's disease (HD). One hundred and fifty-eight cases of ASCT registered in the French database (SFGM) were retrospectively analyzed. Disease status at the time of ASCT was first partial response (PR) in 85, first complete remission (CR1) in 45 or primary refractory in 28 cases. The median time interval between diagnosis and ASCT was 7 months (range 4-13). At the time of analysis in December 1995, 121/158 patients (76.6%) were alive, including 111 (70.2%) in continuous CR with a median follow-up for surviving patients of 46 months (range 8-123). Peri-ASCT toxic death rate was 3%, and the actuarial risk of new malignancies was 4.9% at 5 years. The cumulative probability of 5-year overall survival (OS) was 75.2% for the entire group of patients, 80.6% for the chemosensitive ones, and 33.9% for the primary refractory (chemosensitive vs refractory, P < 0.0001). The cumulative probability of 5-year event-free survival (EFS) was 66.1% for the entire group of patients, 73.7% for the chemosensitive ones, and 26.1% for the primary refractory (chemosensitive vs refractory, P < 0.0001). The only significant prognostic factor for both OS and EFS was disease status at the time of ASCT. Early ASCT in advanced HD is feasible, with a low risk of toxicity and without a higher rate of late effects compared with conventional treatment. Results achieved in chemosensitive patients at the time of transplantation lay the basis of future prospective randomized trials comparing ACST as front-line treatment to conventional treatment in high-risk cases.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin/terapia , Adolescente , Adulto , Femenino , Enfermedad de Hodgkin/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Primarias Secundarias/etiología , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Trasplante AutólogoRESUMEN
To assess the place of allogeneic hematopoietic stem cell transplantation (HSCT) in the advanced stage of acute myeloid leukemia (AML), we retrospectively analyzed 379 consecutive patients who underwent allogeneic HSCT for advanced AML. The median follow-up of the entire cohort was 7.5 years. Sixty-nine patients (18%) were transplanted with primary resistant disease. Three hundred and ten (82%) were relapsed patients, 94 (30%) of whom were in untreated relapse, 67 (22%) in refractory relapse and 149 (48%) in 2nd or 3rd complete remission at time of transplantation. The 5-year probabilities of overall survival (OS), disease-free survival (DFS), and transplant-related mortality (TRM) were 22 +/- 4%, 20 +/- 4%, 45 +/- 6%, respectively. In multivariate analysis, we demonstrated the favorable impact on OS, DFS and TRM of two factors over which we have no control (age <15 years, complete remission achievement) and three factors over which we have some control (female donor, acute and chronic graft-versus-host disease). The results of this study suggest that the graft-versus-leukemia effect is important in advanced AML and that new HSCT modalities are needed for some patients with this indication.