RESUMEN
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
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
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.
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Microbiología del Aire , Aspergilosis/microbiología , Infecciones Comunitarias Adquiridas/microbiología , Infección Hospitalaria/microbiología , Aspergilosis/transmisión , Recuento de Colonia Microbiana , Infecciones Comunitarias Adquiridas/transmisión , Infección Hospitalaria/transmisión , Humanos , Incidencia , Estudios Prospectivos , Esporas FúngicasRESUMEN
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.
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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
Since 1992, we have established a protocol of food management (restrictive diet, food distribution protocol and fungal surveillance) for allogeneic stem-cell transplant (SCT) recipients hospitalised in protected ward. This study analyses the results of 10-year surveillance of fungal contamination of this diet. Among the 456 types of foods tested filamentous fungi were isolated in 37 of them (8.1%). Aspergillus fumigatus was isolated in one type of food only, while the majority of the food was contaminated to a lower extent.
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Microbiología de Alimentos , Unidades Hospitalarias , Evaluación de Programas y Proyectos de Salud , Aspergillus/aislamiento & purificación , Servicio de Alimentación en Hospital , Alemania , Humanos , Micosis/prevención & control , Estudios RetrospectivosRESUMEN
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.
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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
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.
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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 TratamientoAsunto(s)
Presentación de Antígeno , Antígenos de Histocompatibilidad Clase II/inmunología , Linfoma de Células B/inmunología , Linfocitos B/inmunología , Linfocitos B/patología , Antígenos de Histocompatibilidad Clase II/análisis , Antígenos de Histocompatibilidad Clase II/biosíntesis , Humanos , Linfoma de Células B/diagnósticoRESUMEN
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
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.
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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
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.
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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 HomólogoAsunto(s)
Esplenomegalia/diagnóstico , Esplenomegalia/etiología , Algoritmos , Biopsia , Electroforesis de las Proteínas Sanguíneas , Examen de la Médula Ósea , Causalidad , Árboles de Decisión , Diagnóstico Diferencial , Humanos , Inmunofenotipificación , Esplenectomía , Esplenomegalia/epidemiología , Esplenomegalia/metabolismo , Esplenomegalia/terapiaRESUMEN
In this retrospective multicentre study, we analysed the results of 82 consecutive second early allogeneic transplants for primary (n = 28) or secondary ([n = 54) graft failures performed between 1985 and 1997 in patients with acute leukaemia (n = 33), aplastic anaemia (n = 29) or chronic myeloid leukaemia (n = 20). HLA-matched siblings were used in 64 cases. The same donors were used for both transplants in 56 cases and the first transplant was T-cell depleted in 30 cases. The median age at transplant was 25 years and the median intertransplant time interval was 2 months. Estimates of the 3-year overall survival and day 100 transplant-related mortality were 30% and 53% respectively. A recipient age < 34 years at transplant, an intertransplant time interval > or = 80 d and a positive recipient cytomegalovirus serology were predictors of a better outcome. The use of cyclosporin A (CsA) after second transplant had a dramatic impact on outcome, the best results being observed with CsA alone. The day 40 probability of neutrophil recovery was 73%. The use of peripheral blood progenitor cells (PBPCs) was associated with a higher and faster neutrophil recovery. Other factors associated with neutrophil recovery were an intertransplant time interval > or = 80 d and a positive recipient cytomegalovirus serology. Therefore, second early allogeneic transplantation for graft failure is an effective treatment, especially if patients can receive CsA for graft-versus-host disease prevention and are retransplanted more than 80 d from first transplant.
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Rechazo de Injerto/cirugía , Trasplante de Células Madre Hematopoyéticas , Leucemia/cirugía , Adolescente , Adulto , Anemia Aplásica/cirugía , Distribución de Chi-Cuadrado , Niño , Preescolar , Ciclosporina/uso terapéutico , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/diagnóstico , Humanos , Inmunosupresores/uso terapéutico , Lactante , Leucemia Mielógena Crónica BCR-ABL Positiva/cirugía , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Reoperación , Estudios Retrospectivos , Estadísticas no Paramétricas , Trasplante Homólogo , Resultado del TratamientoRESUMEN
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.
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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
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
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.