RESUMEN
The purpose of this paper is to describe the outcome of patients who underwent double allogeneic hematopoietic stem cell transplantation (AHSCT) with reduced-intensity conditioning regimens (RIC). Forty-five patients who received double RIC-AHSCT between 1997 and 2006 were retrospectively studied. The predominant diagnosis was acute myeloid leukemia (AML) (n = 17). Other diagnoses were aplasic anemia (AA) (n = 5), myelodysplasic disorder (n = 5), acute lymphoblastic leukemia (ALL) (n = 4), chronic myelomonocytic leukemia (CML) (n = 3), myeloma (n = 3), non-Hodgkin lymphoma (NHL) (n = 3), chronic lymphocytic leukemia (CLL) (n = 2), Hodgkin's disease (HD) (n = 2), and chronic myelomonocytic leukemia (n = 1). Main indications for RIC-AHSCT 2 were relapse (n = 25, 56%) and early (n = 8, 18%) or late (n = 12, 26%) graft failure. Median delays to reach a neutrophil count of 0.5 × 10(9)/L and platelet counts of 50 × 10(9)/L were significantly smaller after the second AHSCT. Among 25 patients who relapsed after RIC-AHSCT 1, 14 patients (56%) presented a response improvement after RIC-AHSCT 2. In this group, 9 patients sustained a complete response and 5 patients a partial response. Moreover, among the 20 patients who had early or late graft failure following RIC-AHSCT 1, 9 (45%) finally reached an engraftment. Disease-free survival (DFS) was significantly improved after RIC-AHSCT 2. Thirteen patients (28%) died of transplant-related mortality (TRM) at a median delay of 69 days (range: 0-451) after RIC-AHSCT 2. Double RIC-AHSCT is a feasible procedure that allows a response or engraftment not observed after RIC-AHSCT 1. The main indication is relapse. However, TRM remains high.
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Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Rechazo de Injerto/sangre , Rechazo de Injerto/mortalidad , Supervivencia de Injerto , Neoplasias Hematológicas/sangre , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Trasplante HomólogoRESUMEN
BACKGROUND: To evaluate the efficacy of extracorporeal photopheresis (ECP) in noncutaneous T-cell lymphoma and large granular lymphocytes leukemia (LGL). PATIENTS AND METHODS: We have treated 12 refractory/relapsed patients. Six peripheral T-cell lymphoma (PTCL), one T-lymphoblastic lymphoma and five LGL with blood involvement received six biweekly leukapheresis as induction phase, followed by one course a week for 4 weeks as consolidation and one course of maintenance per month for responders until progression/relapse or disappearance of the peripheral clone. RESULTS: Six patients responded to phototherapy. Two PTCL and two LGL achieved a complete response (CR) and two other PTCL a partial response. The median duration of CR was 117 months (45-150 months) for these four patients. The peripheral clone followed by flow cytometry decreased in all six responders. Two patients with a complete disappearance of the peripheral clone have not relapsed. CONCLUSIONS: As for cutaneous T-cell lymphoma, ECP therefore to be efficient for PTCL and LGL. Early decrease and disappearance of the peripheral clone were the indicators of clinical response and nonrelapse, respectively.
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Leucemia Linfocítica Granular Grande/tratamiento farmacológico , Linfoma de Células T/tratamiento farmacológico , Fotoféresis , Adulto , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
One hundred de novo multiple myeloma patients with t(4;14) treated with double intensive therapy according to IFM99 protocols were retrospectively analyzed. The median overall survival (OS) and event-free survival (EFS) were 41.4 and 21 months, respectively, as compared to 65 and 37 for patients included in the IFM99 trials without t(4;14) (P<10(-7)). We identified a subgroup of patients presenting at diagnosis with both low beta(2)-microglobulin <4 mg/l and high hemoglobin (Hb) >/=10 g/l (46% of the cases) with a median OS of 54.6 months and a median EFS of 26 months, respectively, which benefits from high-dose therapy (HDT); conversely patients with one or both adverse prognostic factor (high beta(2)-microglobulin and/or low Hb) had a poor outcome. The achievement of either complete response or very good partial response after HDT was also a powerful independent prognostic factor for both OS and EFS.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Heterogeneidad Genética , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Translocación Genética , Adulto , Anciano , Cromosomas Humanos Par 14 , Cromosomas Humanos Par 4 , Citarabina/administración & dosificación , Dexametasona/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Hemoglobinas , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Análisis Multivariante , Pronóstico , Estudios Retrospectivos , Vincristina/administración & dosificación , Microglobulina beta-2/sangreRESUMEN
Acute lymphoblastic leukemia (ALL) in the elderly is characterized by its ominous prognosis. On the other hand, imatinib has demonstrated remarkable, although transient, activity in relapsed and refractory Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL), which prompted us to assess the use of imatinib in previously untreated elderly patients. ALL patients aged 55 years or older were given steroids during 1 week. Ph+ve cases were then offered a chemotherapy-based induction followed by a consolidation phase with imatinib and steroids during 2 months. Patients in complete response (CR) after consolidation were given 10 maintenance blocks of alternating chemotherapy, including two additional 2-month blocks of imatinib. Thirty patients were included in this study and are compared with 21 historical controls. Out of 29 assessable patients, 21 (72%, confidence interval (CI): 53-87%) were in CR after induction chemotherapy vs 6/21 (29%, CI: 11-52%) in controls (P=0.003). Five additional CRs were obtained after salvage with imatinib and four after salvage with additional chemotherapy in the control group. Overall survival (OS) is 66% at 1 year vs 43% in the control group (P=0.005). The 1-year relapse-free survival is 58 vs 11% (P=0.0003). The use of imatinib in elderly patients with Ph+ ALL is very likely to improve outcome, including OS.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Metilprednisolona/uso terapéutico , Cromosoma Filadelfia , Piperazinas/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirugía , Pirimidinas/uso terapéutico , Resultado del Tratamiento , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Benzamidas , Supervivencia sin Enfermedad , Humanos , Mesilato de Imatinib , Metilprednisolona/administración & dosificación , Piperazinas/administración & dosificación , Pirimidinas/administración & dosificación , Trasplante de Células MadreRESUMEN
A multidisciplinary working group devoted to epidemiological surveillance of invasive aspergillosis (IA) was created in January 2000 in Grenoble University Hospital. This article presents the results of a three-year IA surveillance. The multidisciplinary working group surveyed all hospitalized patients, and the mycology laboratory detected most suspected IA cases. Cases were reviewed monthly by the Aspergillosis Committee, and were classified according to international consensus criteria. Possible nosocomial acquisition was determined. Among the 490 alerts, 74 IA cases were observed: six proven cases (8%), 36 (49%) probable cases and 32 (43%) possible cases. The incidence was 4.4 (95% CI 3.4-5.4) IA/100 000 patient-days. Among the proven and probable IA cases, we observed 10 nosocomial cases and six cases of undetermined origin. No cases were noted in the protected rooms in the haematology unit. Only one cluster of cases (three nosocomial cases) was detected in the haematology unit. Forty-three percent of cases (N=32) were hospitalized in the haematology unit, and all other cases were hospitalized elsewhere. This three-year survey found a high rate of non-nosocomial IA cases and a high frequency of IA cases hospitalized in units other than haematology. Thus, this study shows the importance of IA surveillance in haematology units and all high-risk units.
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Aspergilosis/epidemiología , Aspergillus/aislamiento & purificación , Infección Hospitalaria/epidemiología , Hospitales de Enseñanza , Vigilancia de la Población/métodos , Aspergilosis/microbiología , Aspergillus/clasificación , Infección Hospitalaria/microbiología , Femenino , Francia/epidemiología , Enfermedades Hematológicas , Unidades Hospitalarias , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estaciones del AñoRESUMEN
PURPOSE: To analyze the impact of pre- and posttransplantation factors on the outcome of allogeneic transplantation after nonmyeloablative conditioning regimens. PATIENTS AND METHODS: Ninety-two allogeneic transplantations after nonmyeloablative preparative regimens were reported to the Société Française de Greffe de Moelle Registry registry. Initial diagnoses were lymphoid diseases (n = 22), myeloma (n = 14), acute leukemia and myelodysplasia (n = 41), chronic myelogenous leukemia (n = 12), and solid tumors (n = 3). Forty-six patients had previously received a transplant, and 49 had progressive disease before transplantation. Three types of conditioning regimens were used with fludarabine or antithymocyte globulins. Eighty-nine patients underwent transplantation, 60 from peripheral-blood progenitor cells. Eighty-six patients received graft-versus-host disease (GHVD) prophylaxis for a median duration of 53 days. RESULTS: Seventy-nine patients engrafted, with 40 complete and 21 mixed chimerisms. The acute GHVD rate at 3 months was 50% +/- 11%. Fifty-two patients achieved complete remission and 12, partial remission. At 18 months after transplantation, the overall survival (OS) and the transplant-related mortality (TRM) were 32% +/- 12% and 38% +/- 14%, respectively. Initial diagnosis and disease status before transplantation significantly influenced survival. Age and GHVD prophylaxis type significantly influenced TRM. We also showed an impact of GHVD prophylaxis duration on OS and TRM. In multivariate analysis, three factors remained of prognostic value on OS: initial diagnosis, disease status at transplantation, and GHVD prophylaxis duration. CONCLUSION: This series shows encouraging results from nonmyeloablative conditioning regimens before allotransplantation and demonstrates the impact of some pre- and posttransplantation factors on outcome after transplantation.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Acondicionamiento Pretrasplante , Adolescente , Adulto , Niño , Femenino , Enfermedad Injerto contra Huésped , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neoplasias/terapia , Inducción de Remisión , Estudios Retrospectivos , Análisis de Supervivencia , Trasplante Homólogo , Resultado del TratamientoRESUMEN
Thalidomide is effective in multiple myeloma (MM), even in patients who have relapsed after high-dose therapy. A potent graft-versus-myeloma (GVM) effect can be induced against MM after allogeneic stem cell transplantation (allo-SCT). In all, 31 MM patients received thalidomide as a salvage therapy after progression following allo-SCT. The median maximum daily dose of thalidomide was 200 mg (range, 50-600). Thalidomide had to be discontinued in six patients (19%) because of toxicity. In all, nine patients (29%; 95% CI, 13-45) achieved an objective response with thalidomide therapy (six partial and three very good partial responses, VGPR). Five patients developed graft-versus-host disease (GVHD) after thalidomide therapy, including the three patients achieving a VGPR. These data demonstrate that thalidomide is potentially effective in MM patients failing allo-SCT.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Mieloma Múltiple/terapia , Terapia Recuperativa/métodos , Talidomida/uso terapéutico , Adulto , Femenino , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Inducción de Remisión , Estudios Retrospectivos , Análisis de Supervivencia , Talidomida/administración & dosificación , Talidomida/toxicidad , Trasplante Homólogo , Resultado del TratamientoRESUMEN
Non-myeloablative allogeneic stem cell transplantation has been reported to induce sustained complete remission even in advanced diseases (acute leukemia, lymphomas). The tolerance of this procedure allows treatment of poor candidates to conventional allogeneic transplantation with persisting or relapsing myeloma patients. Twelve patients previously treated with at least VAD regimen and autologous transplantation were included. All patients had a serum beta2 microglobuline >3 mg/l at diagnosis. The conditioning regimen consisted of fludarabine 25 mg/m/day x 5, antithymoglobulin 2.5 mg/kg/day x 5, busulphan 2 mg/kg/day x 2; the transplant was peripheral stem cells (except one) from an HLA-matched sibling and was followed by cyclosporin for 45 to 90 days. This treatment results in a well-tolerated procedure (no mucositis, duration of aplasia <7 days). A dramatic graft anti-myeloma effect is documented even in progressive disease (11/12 PR + CR, 4/12 CR). However, five patients underwent CMV disease, one died of CMV encephalitis (UPN 3) and delayed severe GVHD occurred in four patients. Our data suggest that a better survival could be achieved when patients are transplanted with a controlled disease. In high risk patients, we now propose a non-myeloablative transplantation in addition to the conventional and intensive chemotherapy as first-line of treatment.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple/terapia , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Persona de Mediana Edad , Mieloma Múltiple/sangre , Proyectos Piloto , Terapia Recuperativa , Acondicionamiento Pretrasplante , Trasplante Autólogo , Trasplante HomólogoRESUMEN
The recent clinical trial in lymphoma using tumor antigen-loaded DCs (Hsu et al, Nature Med 1996; 2: 52) demonstrates the efficiency of the use of professional antigen presenting cells (APCs) for taking up, processing and presenting tumor protein in a vaccine strategy in cancer. However, the production of large quantities of clinical grade APCs remains to be resolved. Here, we describe that both dendritic cells (DCs) and macrophages (MOs) can be efficiently differentiated in large numbers from lymphoma patients in spite of their disease and previous therapy. These cells were produced using the VAC and MAK cell processors according to standard operating procedures. DCs and MOs were differentiated from circulating monocytes in gas permeable hydrophobic bags, with 2% autologous serum and in the presence of GM-CSF and IL-13 or GM-CSF alone, respectively. DCs and MOs were then purified by counter flow centrifugation. Phenotypic, morphological and functional analysis showed that cells differentiated from patients with lymphoma present quite similar features to DCs and MOs produced from monocytes of healthy donors. Moreover, we show that MOs, when combined with CD20 antibody (Rituximab), can efficiently engulf tumor cells and propose that a such combination could be used for initiating a clinical trial in lymphoma. Thus, the possibility of producing functional DC and MOs in large amounts in conditions compatible with therapeutic application will allow the development of new immune strategies to eradicate lymphoma.
Asunto(s)
Células Presentadoras de Antígenos , Diferenciación Celular , Células Dendríticas , Linfoma no Hodgkin/terapia , Macrófagos , Adulto , Presentación de Antígeno/fisiología , Femenino , Humanos , Leucocitos Mononucleares/patología , Activación de Linfocitos/fisiología , Linfoma no Hodgkin/patología , Masculino , Persona de Mediana Edad , Fagocitosis , Fenotipo , Receptores Fc/fisiología , Linfocitos T/fisiologíaRESUMEN
As small cell lung carcinoma (SCLC) is frequently a widespread disease at diagnosis, highly radiosensitive and often only partially responsive to chemotherapy, radioimmunotherapy (RIT) would appear to be a promising technique for treatment. We report the preliminary results of a Phase I/II trial of RIT in SCLC using a two-step method and a myeloablative protocol with circulating stem cells transplantation. Fourteen patients with proved SCLC relapse after chemotherapy were treated with RIT. They were first injected i.v. with a bispecific (anti-carcinoembryonic antigen/anti-diethylenetriaminepentaacetic acid) monoclonal antibody (20-80 mg in 100 ml of saline solution) and then 4 days later with di-(In-diethylenetriaminepentaacetic acid)-tyrosyl-lysine hapten labeled with 1.48-6.66 GBq (40-180 mCi) of I-131 and diluted in 100 ml of saline solution. In patients receiving 150 mCi or more, circulating stem cells were harvested before treatment and reinfused 10-15 days later. Treatment response was evaluated by CT and biochemical data during the month before and 1, 3, 6, and 12 months after treatment. All patients received the scheduled dose without immediate adverse reactions to bispecific antibody or 1-131 hapten. Toxicity was mainly hematological, with two cases of grade 2 leukopenia and three cases of grade 3 or 4 thrombopenia. Body scanning 8 days after injection of the radiolabeled hapten generally showed good uptake at the tumor sites. Estimated tumor dose was 2.6-32.2 cGy/mCi. Among the 12 patients evaluated to date, we have observed 9 progressions, 2 partial responses (one almost complete for 3 months), and 1 stabilization of more than 24 months. Efficiency and toxicity were dose-related. The maximal tolerable dose without hematological rescue was 150 mCi. These preliminary results are encouraging, and dose escalation is currently continuing to reach 300 mCi. RIT should prove to be an interesting therapeutic method for SCLC, although repeated injections and hematological rescue will probably be required, as well as combination with other treatment modalities.
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Anticuerpos Biespecíficos/uso terapéutico , Antígeno Carcinoembrionario/inmunología , Carcinoma de Células Pequeñas/radioterapia , Haptenos/uso terapéutico , Radioisótopos de Yodo/uso terapéutico , Neoplasias Pulmonares/radioterapia , Ácido Pentético/inmunología , Radioinmunoterapia , Anciano , Animales , Anticuerpos Antiidiotipos/sangre , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Dosificación RadioterapéuticaRESUMEN
The class II human leucocyte antigens (HLA class II) are principally peptide presentation molecules. Signal transduction by these molecules has also been shown to transmit activation signals in both B and T lymphocytes by a pathway including protein tyrosine kinase activation, an intracellular calcium flux, and both the activation and transcriptional regulation of protein kinase C (PKC) isoforms. Apoptosis can also result from human leukocyte antigen class II stimulation. Inhibitors of gene transcription were used to inhibit activation and, therefore, to distinguish the signal transduction pathways important for apoptosis. This approach provided evidence that cellular activation and apoptosis undertook separate signaling pathways, and that PKC and intracellular calcium were shared between the two pathways, while tyrosine kinase activity was essential for cell activation. Further studies using cord blood B cells showed that these cells were incapable of generating a calcium flux after HLA class II ligation and were not subject to cell death. The importance of sustained levels of calcium for programmed cell death (PCD) was underlined since the restoration of a calcium flux enabled PCD of cord blood B cells via HLA class II. These results demonstrate that HLA class II stimulation initiates two distinct signal transduction pathways.
Asunto(s)
Apoptosis/fisiología , Antígenos de Histocompatibilidad Clase II/fisiología , Adulto , Anticuerpos Monoclonales/farmacología , Apoptosis/efectos de los fármacos , Linfocitos B/citología , Calcio/farmacología , Canales de Calcio/fisiología , Trasplante de Células/fisiología , Cesárea , Dactinomicina/farmacología , Femenino , Sangre Fetal/citología , Feto/citología , Antígenos de Histocompatibilidad Clase II/inmunología , Humanos , Activación de Linfocitos/efectos de los fármacos , Embarazo , Proteína Quinasa C/farmacología , Sistemas de Mensajero Secundario , Bazo/citologíaRESUMEN
Cord blood is increasingly used for hematopoietic stem cell transplantation since less severe graft-versus-host disease has been reported leading to the notion that cord blood is "naive." Human leucocyte antigen (HLA) class II molecules are expressed throughout B lymphocyte ontogeny (except the plasmocytes), are responsible for antigen presentation, and can also transmit signals. Cord blood B stimulate an allogeneic response, and this property is believed to indicate the presence of a class II-associated peptide. In this study we examined the capacity of cord blood B to transmit signals via HLA-DR. Activation and relocalization of protein kinase C (PKC) isoenzymes alpha and betaII was detected along with tyrosine kinase activation and proliferation. However, in contrast to resting adult B, generation of an intracellular calcium ([Ca++]i) flux and rapid aggregation were not detected. To address the question of whether or not HLA-DR signals throughout B lymphocyte ontogeny, we extended this study to include malignant adult B (B chronic lymphocytic leukemia [B-CLL], B mantle cell lymphoma, and B large cell leukemia). Tyrosine kinase activation and proliferation were observed in all these cell populations, albeit in the absence of [Ca++]i flux or an increase in PKC. HLA-DR therefore transmits signals throughout B lymphocyte ontogeny, although different signaling pathways are initiated in adult vs. fetal vs. malignant B. The lack of intracellular [Ca++]i flux in both cord blood and malignant B lymphocytes may represent a feature of HLA class II signaling at a particular stage of differentiation, although the downregulation of PKC clearly distinguishes between cord blood B and B-CLL.
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Presentación de Antígeno/fisiología , Linfocitos B/inmunología , Sangre Fetal/inmunología , Antígenos HLA-DR/inmunología , Células Madre Neoplásicas/inmunología , Transducción de Señal , Adulto , Factores de Edad , Agregación Celular , Diferenciación Celular , División Celular , Activación Enzimática , Sangre Fetal/citología , Humanos , Recién Nacido , Isoenzimas/metabolismo , Leucemia Linfocítica Crónica de Células B/inmunología , Leucemia Linfocítica Crónica de Células B/patología , Activación de Linfocitos , Linfoma de Células B/inmunología , Linfoma de Células B/patología , Linfoma de Células B Grandes Difuso/inmunología , Linfoma de Células B Grandes Difuso/patología , Fosforilación , Fosfotirosina/análisis , Proteína Quinasa C/metabolismo , Proteína Quinasa C beta , Proteína Quinasa C-alfa , Procesamiento Proteico-PostraduccionalRESUMEN
INTRODUCTION: Non-myeloablative peripheral stem cell transplantation has been shown to induce tumour rejection in patients with acute leukaemia. However, the immunological mechanisms involved and the immune reconstitution achieved have not been investigated. MATERIALS AND METHODS: We describe the cases of two patients for whom we have studied the lymphocyte reconstitution achieved, using both phenotypic and genetic analyses of the T-cell repertoire, after peripheral stem cell transplantation. RESULTS: : In both cases we observed immune reconstitution with T-cell repertoire evolution and presence of activated CD8(+) T cells. In one of the patients an activated clone expressing Vbeta8 represents 46% of the CD8(+) cells. Expansion of this clone occurred in the absence of graft vs host disease symptoms. In the second case a skin lesion typical of graft vs host disease appeared after complete remission had been achieved. The T-cell repertoire in a biopsy of the lesion was distinct from that observed in the blood. CONCLUSION: Our study indicates that peripheral donor cells can effectively reconstitute a grafted patient while inducing an immune response against antigens expressed by the leukaemic/myeloma cells. Our data provide arguments for different populations of T cells associated with graft vs leukaemia/lymphoma and GVH effects.
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Sangre/inmunología , Trasplante de Células Madre Hematopoyéticas , Inmunoterapia/métodos , Piel/citología , Enfermedad Aguda , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Células Sanguíneas/inmunología , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/inmunología , Carmustina/administración & dosificación , Células Clonales/inmunología , Ciclofosfamida/administración & dosificación , Citarabina/administración & dosificación , Daunorrubicina/administración & dosificación , Dexametasona/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Supervivencia de Injerto , Reacción Injerto-Huésped/inmunología , Efecto Injerto vs Leucemia/inmunología , Humanos , Inmunofenotipificación , Leucemia Mieloide/tratamiento farmacológico , Leucemia Mieloide/terapia , Masculino , Persona de Mediana Edad , Repeticiones de Minisatélite , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/terapia , Prednisona/administración & dosificación , Receptores de Antígenos de Linfocitos T alfa-beta/análisis , Piel/inmunología , Subgrupos de Linfocitos T/citología , Acondicionamiento Pretrasplante , Trasplante Homólogo/inmunología , Vincristina/administración & dosificación , Irradiación Corporal TotalRESUMEN
Fluorescence in situ hybridization (FISH) on interphase nuclei has been shown to be an efficient method for detecting aneuploidy in multiple myeloma (MM). The aim of this study was to test the feasibility of FISH techniques for detecting malignant cells in the harvests of MM patients submitted to autologous transplantation. As trisomy 9 (T9) is a frequent event in MM, we used it as a genetic marker of malignant plasma cells. T9 was detected in 45 out of 55 MM bone marrow samples (81.8%) using a chromosome 9 centromeric (C9C) probe. Twenty-four of the 55 MM patients were subjected to high-dose therapy followed by autologous unselected progenitor cell transplantation. Trisomy 9 was detected in 20 patients and was used as a marker of malignant cells. Upon karyotypic analysis, three of the four remaining patients without T9 showed an unbalanced translocation leading to a complete trisomy of the long arm of chromosome 1 (T1q). We thus used a 1q juxtacentromeric probe, pUC1.77, as another genetic marker of malignant plasma cells in these three further patients. FISH with C9C or pUC1.77 probes was performed on the harvests of these 23 patients and detected clonal cells in 11 transplants. The disease-free survival from graft was significantly longer for the patients who had no malignant cells in their transplant (P=0.009). The median disease-free survival was 23 months in these patients, as compared to 12 months in the patients whose transplant was contaminated. As almost all MM are cytogenetically abnormal, FISH with adequate probes represents a simple, quantitative tool for rapid detection of malignant cells in the harvests. Our results also suggest that the presence of MM cells in the transplant may be predictive of poor outcome.
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Hibridación Fluorescente in Situ , Adulto , Anciano , Femenino , Estudios de Seguimiento , Reordenamiento Génico , Trasplante de Células Madre Hematopoyéticas , Humanos , Interfase , Cariotipificación , Masculino , Persona de Mediana Edad , Mieloma Múltiple/patología , Trasplante Autólogo/patología , Resultado del TratamientoRESUMEN
To determine the results of allogeneic hematopoietic stem cell (HSC) transplantation for chronic myelogenous leukemia (CML) at various stages of the disease in children, a retrospective analysis was carried out on the outcome of transplants performed on 76 children and teenagers with CML between 1982 and 1998. In all, 60 patients were transplanted from a matched sibling donor (MSD) and 16 from a matched unrelated donor (MUD). There was a higher incidence of acute graft-versus-host disease after MUD transplantation (P<10(-3)). The main cause of death was transplant-related toxicity in both groups. In MSD recipients, the probability of relapse at 5 years for patients transplanted in the first chronic phase was lower than in patients transplanted in the advanced phase (relative risk (rr)=5.90; 95% confidence interval (CI), 1.85-18.82, P<0.01). The estimated 5-year event-free survival (EFS) rate was higher after MSD vs MUD transplantation (61% (95% CI, 48-73%) vs 27% (95% CI, 4-49%), rr=0.25, P<10(-3)). In children transplanted from MSD, the 5-year EFS was higher when transplantation was performed in the first chronic phase vs the advanced phases (73% (95% CI, 59-87%) vs 32% (95% CI, 10-54%), P<10(-3)). Disease status at transplantation was the unique factor influencing survival in patients undergoing transplantation from MSD with a better outcome for those transplanted in the first chronic phase. Allogeneic HSC offers a possibility of curing childhood CML with a significant advantage for patients transplanted in chronic phase using a human leukocyte antigen-identical sibling donor.
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Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Adolescente , Trasplante de Médula Ósea/mortalidad , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Enfermedad Injerto contra Huésped/etiología , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Masculino , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Donantes de Tejidos , Trasplante Homólogo , Resultado del TratamientoRESUMEN
The daily number of outdoor spores was counted and the cases of community-acquired invasive aspergillosis (IA) were observed over a period of 31 months. The outdoor fungal load preceding IA occurrences was significantly higher than that measured during IA-free periods, underlining the importance of preventive measures to protect high-risk patients, even at home.