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1.
Ann Hematol ; 102(5): 1159-1169, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36991231

RESUMEN

Primary central nervous system lymphomas (PCNSLs) classically remain confined within the CNS throughout their evolution for unknown reasons. Our objective was to analyse the rare extracerebral relapses of PCNSL in a nationwide population-based study. We retrospectively selected PCNSL patients who experienced extracerebral relapse during their follow-up from the French LOC database. Of the 1968 PCNSL included in the database from 2011, 30 (1.5%, median age 71 years, median KPS 70) presented an extracerebral relapse, either pure (n = 20) or mixed (both extracerebral and in the CNS) (n = 10), with a histological confirmation in 20 cases. The median delay between initial diagnosis and systemic relapse was 15.5 months [2-121 months]. We found visceral (n = 23, 77%), including testis in 5 (28%) men and breast in 3 (27%) women, lymph node (n = 12, 40%), and peripheral nervous system (PNS) (n = 7, 23%) involvement. Twenty-seven patients were treated with chemotherapy, either with only systemic targets (n = 7) or mixed systemic and CNS targets (n = 20), 4 were consolidated by HCT-ASCT. After systemic relapse, the median progression-free survival and overall survival (OS) were 7 and 12 months, respectively. KPS > 70 and pure systemic relapses were significantly associated with higher OS. Extracerebral PCNSL relapses are rare, mainly extranodal, and frequently involve the testis, breast, and PNS. The prognosis was worse in mixed relapses. Early relapses raise the question of misdiagnosed occult extracerebral lymphoma at diagnostic workup that should systematically include a PET-CT. Paired tumour analysis at diagnosis/relapse would provide a better understanding of the underlying molecular mechanisms.


Asunto(s)
Neoplasias del Sistema Nervioso Central , Linfoma , Masculino , Humanos , Femenino , Anciano , Estudios Retrospectivos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Recurrencia Local de Neoplasia/tratamiento farmacológico , Linfoma/diagnóstico , Linfoma/epidemiología , Linfoma/terapia , Pronóstico , Neoplasias del Sistema Nervioso Central/terapia , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica
3.
Eur J Cancer ; 117: 121-130, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31279304

RESUMEN

BACKGROUND: Primary central nervous system lymphomas (PCNSLs) are mainly diffuse large B-cell lymphomas (DLBCLs) of the non-germinal centre B-cell subtype, with unmet medical needs. This study aimed to evaluate the efficacy and toxicity of ibrutinib in DLBCL-PCNSL PATIENTS AND METHODS: This prospective, multicentre, phase II study involved patients with relapse or refractory(R/R) DLBCL-PCNSL or primary vitreoretinal lymphoma. The treatment consisted of ibrutinib (560 mg/day) until disease progression or unacceptable toxicity occurred. The primary outcome was the disease control (DC) rate after two months of treatment (P0 < 10%; P1 > 30%). RESULTS: Fifty-two patients were recruited. Forty-four patients were evaluable for response. After 2 months of treatment, the DC was 70% in evaluable patients and 62% in the intent-to-treat analysis, including 10 complete responses (19%), 17 partial responses (33%) and 5 stable diseases (10%). With a median follow-up of 25.7 months (range, 0.7-30.5), the median progression-free and overall survivals were 4.8 months (95% confidence interval [CI]; 2.8-12.7) and 19.2 months (95% CI; 7.2-NR), respectively. Thirteen patients received ibrutinib for more than 12 months. Two patients experienced pulmonary aspergillosis with a favourable (n = 1) or fatal outcome (n = 1). Ibrutinib was detectable in the cerebrospinal fluid (CSF). The clinical response to ibrutinib seemed independent of the gene mutations in the BCR pathway. CONCLUSION: Ibrutinib showed clinical activity in the brain, the CSF and the intraocular compartment and was tolerated in R/R PCNSL. The addition of ibrutinib to standard methotrexate-base induction chemotherapy will be further evaluated in the first-line treatment. CLINICAL TRIAL NUMBER: NCT02542514.


Asunto(s)
Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Linfoma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Neoplasias de la Retina/tratamiento farmacológico , Terapia Recuperativa , Adenina/análogos & derivados , Anciano , Anciano de 80 o más Años , Neoplasias del Sistema Nervioso Central/patología , Femenino , Estudios de Seguimiento , Humanos , Linfoma/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Piperidinas , Pronóstico , Estudios Prospectivos , Neoplasias de la Retina/patología , Tasa de Supervivencia
4.
Ann Oncol ; 30(4): 621-628, 2019 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-30698644

RESUMEN

BACKGROUND: Primary central nervous system lymphomas (PCNSLs) are mainly diffuse large B-cell lymphomas (DLBCLs) of the non-germinal center B-cell (non-GCB) subtype. This study aimed to determine the efficacy of rituximab plus lenalidomide (R2) in DLBCL-PCNSL. PATIENTS AND METHODS: Patients with refractory/relapsed (R/R) DLBCL-PCNSL or primary vitreoretinal lymphoma (PVRL) were included in this prospective phase II study. The induction treatment consisted of eight 28-day cycles of R2 (rituximab 375/m2 i.v. D1; lenalidomide 20 mg/day, D1-21 for cycle 1; and 25 mg/day, D1-21 for the subsequent cycles); in responding patients, the induction treatment was followed by a maintenance phase comprising 12 28-day cycles of lenalidomide alone (10 mg/day, D1-21). The primary end point was the overall response rate (ORR) at the end of induction (P0 = 10%; P1 = 30%). RESULTS: Fifty patients were included. Forty-five patients (PCNSL, N = 34; PVRL, N = 11) were assessable for response. The ORR at the end of induction was 35.6% (95% CI 21.9-51.2) in assessable patients and 32.0% (95% CI 21.9-51.2) in the intent-to-treat analysis, including 13 complete responses (CR)/unconfirmed CR (uCR; 29%) and 3 partial responses (PR; 7%). The best responses were 18 CR/uCR (40%) and 12 PR (27%) during the induction phase. The maintenance phase was started and completed by 18 and 5 patients, respectively. With a median follow-up of 19.2 months (range 1.5-31), the median progression-free survival (PFS) and overall survival (OS) were 7.8 months (95% CI 3.9-11.3) and 17.7 months (95% CI 12.9 to not reached), respectively. No unexpected toxicity was observed. The peripheral baseline CD4/CD8 ratio impacted PFS [median PFS = 9.5 months (95% CI, 8.1-14.8] for CD4/CD8 ≥ 1.6; median PFS = 2.8 months, [95% CI, 1.1-7.8) for CD4/CD8 < 1.6, P = 0.03). CONCLUSIONS: The R2 regimen showed significant activity in R/R PCNSL and PVRL patients. These results support assessments of the efficacy of R2 combined with methotrexate-based chemotherapy as a first-line treatment of PCNSL. CLINICAL TRIALS NUMBER: NCT01956695.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Linfoma Intraocular/tratamiento farmacológico , Lenalidomida/administración & dosificación , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Rituximab/administración & dosificación , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias del Sistema Nervioso Central/mortalidad , Esquema de Medicación , Femenino , Estudios de Seguimiento , Francia/epidemiología , Humanos , Análisis de Intención de Tratar , Linfoma Intraocular/mortalidad , Lenalidomida/efectos adversos , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Supervivencia sin Progresión , Prueba de Estudio Conceptual , Estudios Prospectivos , Inducción de Remisión/métodos , Rituximab/efectos adversos
5.
Ann Oncol ; 29(3): 715-723, 2018 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-29253087

RESUMEN

Background: Peripheral T-cell lymphoma (PTCL) remains a therapeutic challenge. Due to the rarity and the heterogeneity of PTCL, no consensus has been achieved regarding even the type of first-line treatment. The benefit of autologous stem-cell transplantation (ASCT) is, therefore, still intensely debated. Patients and methods: In the absence of randomized trials addressing the role of ASCT, we performed a large multicentric retrospective study and used both a multivariate proportional hazard model and a propensity score matching approach to correct for sample selection bias between patients allocated or not to ASCT in intention-to-treat (ITT). Results: Among 527 patients screened from 14 centers in France, Belgium and Portugal, a final cohort of 269 patients ≤65 years old with PTCL-not otherwise specified (NOS) (N = 78, 29%), angioimmunoblastic T-cell lymphoma (AITL) (N = 123, 46%) and anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK-ALCL) (N = 68, 25%) with partial (N = 52, 19%) or complete responses (N = 217, 81%) after induction was identified and information about treatment allocation was carefully collected before therapy initiation from medical records. One hundred and thirty-four patients were allocated to ASCT in ITT and 135 were not. Neither the Cox multivariate model (HR = 1.02; 95% CI: 0.69-1.50 for PFS and HR = 1.08; 95% CI: 0.68-1.69 for OS) nor the propensity score analysis after stringent matching for potential confounding factors (logrank P = 0.90 and 0.66 for PFS and OS, respectively) found a survival advantage in favor of ASCT as a consolidation procedure for patients in response after induction. Subgroup analyses did not reveal any further difference for patients according to response status, stage disease or risk category. Conclusions: The present data do not support the use of ASCT for up-front consolidation for all patients with PTCL-NOS, AITL, or ALK-ALCL with partial or complete response after induction.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Linfoma de Células T Periférico/terapia , Adulto , Anciano , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Quimioterapia de Inducción , Linfoma de Células T Periférico/mortalidad , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Trasplante Autólogo , Adulto Joven
6.
Bone Marrow Transplant ; 52(7): 941-949, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28112752

RESUMEN

High-dose chemotherapy preceding autologous hematopoietic stem cell transplantation (auto-HSCT) is one treatment option for patients with Hodgkin (HL) or non-Hodgkin lymphoma (NHL). The most frequently used intensive chemotherapy is a combination of carmustine (BCNU), etoposide, cytarabine and melphalan (BEAM). However, BCNU is consistently in short supply, and there has been a recent dramatic increase in its cost, necessitating the utilization of conditioning alternatives. The busulfan-based conditioning regimen known as the busulfan-cyclophosphamide-etoposide (BuCyE) combination is the second most-studied conditioning regimen worldwide after BEAM, and it exhibits a benefit/risk ratio that is comparable to that of BEAM. In addition to these two combinations, the present manuscript also summarizes data reported for other conditioning combinations. Owing to the lack of prospective and comparative studies, a comparison of the toxicities and medicoeconomical profiles of these treatments is warranted to identify effective replacements for BCNU-based conditioning.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carmustina/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin/terapia , Linfoma no Hodgkin/terapia , Autoinjertos , Citarabina/uso terapéutico , Humanos , Melfalán/uso terapéutico , Podofilotoxina/uso terapéutico
7.
Ann Oncol ; 23(10): 2687-2695, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22767588

RESUMEN

BACKGROUND: This study explored the efficacy and safety of rituximab as treatment of clinical or molecular residual disease after autologous stem-cell transplantation (ASCT) in follicular lymphoma (FL). PATIENTS AND METHODS: Forty patients with CD20+ FL and clinically (group A, n = 14) or clono-specific PCR-detectable (group B, n = 25) residual disease persisting 3 months after ASCT received rituximab 375 mg/m² once weekly for 4 weeks. RESULTS: Response rate at day 50 was 36% [90% confidence interval (CI) 15-61] in group A (World Health Organization criteria) and 52% (90% CI 34-70) in group B (conversion PCR-undetectable status to undetectable status). The best response rate was 71% [nine complete responses (CRs) and one partial response] in group A and 76% in group B. At 36 months, all 10 responses persisted in group A, whereas 46% of patients in group B still had PCR-undetectable disease. Furthermore, 68% of patients in group B were still in clinical CR. Rituximab after ASCT was safe with few grade 3-4 toxic effects (15% patients), mainly acute reactions and infections. CONCLUSION: Rituximab induced a high rate of durable CRs in patients with clinically detectable disease, as well as durable eradication of PCR-detectable disease in patients with FL after ASCT. Continued molecular responses assessed with a highly sensitive and clono-specific PCR technique were correlated with an excellent disease control.


Asunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Antineoplásicos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Linfoma Folicular/tratamiento farmacológico , Neoplasia Residual , Adolescente , Adulto , Anciano , Humanos , Linfoma Folicular/patología , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Estudios Prospectivos , Rituximab , Adulto Joven
8.
Ann Oncol ; 23(9): 2386-2390, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22422944

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.


Asunto(s)
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 Tratamiento
9.
Ann Oncol ; 23(6): 1555-61, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22012966

RESUMEN

BACKGROUND: There is no consensual first-line chemotherapy for elderly patients with mantle cell lymphoma (MCL). The GOELAMS (Groupe Ouest-Est des Leucémies Aiguës et Maladies du Sang) group previously developed the (R)VAD+C regimen (rituximab, vincristine, doxorubicin, dexamethasone and chlorambucil), which appeared as efficient as R-CHOP (rituximab, cyclophosphamide, doxorubicine, vincristine, prednisone) while less toxic. Based on this protocol, we now added bortezomib (RiPAD+C: rituximab, bortezomib, doxorubicin, dexamethasone and chlorambucil) given its efficacy in relapsed/refractory MCL patients. The goal of the current phase II trial was to evaluate the feasibility and efficacy of the RiPAD+C regimen as frontline therapy for elderly patients with MCL. PATIENTS AND METHODS: Patients between 65 and 80 years of age with newly diagnosed MCL received up to six cycles of RiPAD+C. RESULTS: Thirty-nine patients were enrolled. Median age was 72 years (65-80). After four cycles of RiPAD+C, the overall response rate was 79%, including 51% complete responses (CRs). After six cycles, CR rate increased up to 59%. After a 27-month follow-up, median progression-free survival (PFS) is 26 months and median overall survival has not been reached. Four patients (10%) discontinued the treatment because of a severe toxicity and seven patients (18%) experienced grade 3 neurotoxicity. CONCLUSION: The bortezomib-containing RiPAD+C regimen results in high CR rates and prolonged PFS with predictable and manageable toxic effects in elderly patients with MCL.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células del Manto/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ácidos Borónicos/administración & dosificación , Bortezomib , Clorambucilo/administración & dosificación , Dexametasona/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Humanos , Estimación de Kaplan-Meier , Linfoma de Células del Manto/mortalidad , Masculino , Pirazinas/administración & dosificación , Rituximab , Resultado del Tratamiento
10.
Med Mal Infect ; 40(4): 238-40, 2010 Apr.
Artículo en Francés | MEDLINE | ID: mdl-19783113

RESUMEN

After primary infection, some bacteria can remain in a latent state for several years before a new bacteremia, often due to a weakened immune status. This is common for Mycobacterium tuberculosis, less for other pathogens more difficult to have in mind when facing patients with fever. We report the case of an 84-year-old female patient presenting with fever in the months following antilymphoma chemotherapy, due to bacteremic brucellosis (with a hemophagocytic syndrome) probably latent after primary infection as a child.


Asunto(s)
Bacteriemia/fisiopatología , Brucella melitensis , Brucelosis/fisiopatología , Anciano de 80 o más Años , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales de Origen Murino , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bacteriemia/complicaciones , Bacteriemia/tratamiento farmacológico , Bacteriemia/terapia , Brucelosis/complicaciones , Brucelosis/tratamiento farmacológico , Brucelosis/terapia , Terapia Combinada , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Doxiciclina/uso terapéutico , Quimioterapia Combinada , Femenino , Francia , Humanos , Huésped Inmunocomprometido , Inmunoglobulinas Intravenosas/uso terapéutico , Linfoma no Hodgkin/complicaciones , Linfoma no Hodgkin/tratamiento farmacológico , Recurrencia , Rifampin/uso terapéutico , Rituximab , España/etnología , Factores de Tiempo , Vidarabina/administración & dosificación , Vidarabina/efectos adversos , Vidarabina/análogos & derivados
11.
Ann Oncol ; 20(1): 110-6, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18701429

RESUMEN

BACKGROUND: Extranodal natural killer (NK)/T-cell lymphoma, nasal type, and aggressive NK-cell leukemia are highly aggressive diseases with a poor outcome. PATIENTS AND METHODS: We report a multicentric French retrospective study of 15 patients with relapsed, refractory, or disseminated disease, treated with L-asparaginase-containing regimens in seven French centers. Thirteen patients were in relapse and/or refractory and 10 patients were at stage IV. RESULTS: All but two of the patients had an objective response to L-asparaginase-based treatment. Seven patients reached complete remission and only two relapsed. CONCLUSION: These data, although retrospective, confirm the excellent activity of L-asparaginase-containing regimens in refractory extranodal NK/T-cell lymphoma and aggressive NK-cell leukemia. Therefore, L-asparaginase-based regimen should be considered as a salvage treatment, especially for patients with disseminated disease. First-line L-asparaginase combination therapy for extranodal NK/T-cell lymphoma and aggressive NK-cell leukemia should be tested in prospective trials.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Asparaginasa/administración & dosificación , Leucemia/tratamiento farmacológico , Linfoma Extranodal de Células NK-T/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Humanos , Leucemia/patología , Linfoma Extranodal de Células NK-T/patología , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Resultado del Tratamiento , Mundo Occidental
12.
Oncology ; 69(1): 19-26, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16088231

RESUMEN

OBJECTIVE: This multicenter phase III study compared the MEMID regimen (mitoxantrone, VP16, methylglyoxal, ifosfamide and dexamethasone) with CEOP, a CHOP-like regimen (cyclophosphamide, epirubicin, vincristine and prednisone), in elderly patients (> or =65 years) with aggressive non-Hodgkin's lymphoma (NHL). METHODS: One hundred and forty-nine patients were eligible, 72 in the MEMID arm and 77 in the CEOP arm. The primary endpoint was to compare overall survival (OS) between groups, and secondary endpoints were event-free survival (EFS), response rate and toxicity. RESULTS: Neutropenia (p < 10(-5)), anemia (p < 10(-5)) and thrombocytopenia (p = 0.0006) were significantly more frequent in patients who received MEMID. We observed an objective response rate of 55.5% in the MEMID arm and 64.9% in the CEOP arm (p = 0.24). The median OS and EFS were 15.4 and 8.5 months in the MEMID arm, and 20.3 and 10.5 months in the CEOP arm (p = 0.59 and 0.47), respectively. The median EFS was 15.4 months in the MEMID arm and 20.3 months in the CEOP arm (p = 0.59). CONCLUSION: The increased toxicity without survival benefit confirms the superiority of CHOP and CHOP-like regimens for elderly patient with aggressive NHL.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma no Hodgkin/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/administración & dosificación , Dexametasona/administración & dosificación , Supervivencia sin Enfermedad , Epirrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Humanos , Ifosfamida/administración & dosificación , Linfoma no Hodgkin/patología , Masculino , Mitoxantrona/administración & dosificación , Neutropenia/inducido químicamente , Prednisona/administración & dosificación , Estudios Prospectivos , Piruvaldehído/administración & dosificación , Análisis de Supervivencia , Trombocitopenia/inducido químicamente , Resultado del Tratamiento , Vincristina/administración & dosificación
13.
Ann Oncol ; 16(3): 466-72, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15695500

RESUMEN

BACKGROUND: This randomized study compared the efficacy and safety of fludarabine-mitoxantrone (FM) with mini-CHVP (cyclophosphamide, doxorubicin, vindesine, prednisone) in elderly patients with advanced, low-grade non-Hodgkin's lymphoma. PATIENTS AND METHODS: End points were remission rates [overall response (OR) and complete response (CR)], failure-free survival (FFS), survival and toxicity. One hundred and fifty-five patients were randomized, 144 were evaluable for safety and 142 for response. Each treatment arm was given as six monthly cycles, followed by three bimonthly cycles. FM comprised fludarabine (20 mg/m(2) i.v.), days 1-5, plus mitoxantrone (10 mg/m(2) i.v.), day 1. CHVP cycles comprised cyclophosphamide (750 mg/m(2) i.v. infusion), doxorubicin (25 mg/m(2) i.v.) and vindesine (3 mg/m(2) i.v.) on day 1, and prednisone (50 mg/m(2)) on days 1-5. RESULTS: FM therapy resulted in superior remission rates (OR 81% versus 64%, CR 49% versus 17%; P = 0.0004). Median FFS for FM patients was 36 months, compared with 19 months for CHVP patients, and has not yet been reached for early CR patients at 53 months. Treatment arm was the major risk factor influencing survival. Both treatments were well tolerated, with only few infectious complications. CONCLUSION: FM was more effective than CHVP in achieving OR and CR, and favorably affected the outcome.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/inmunología , Vidarabina/análogos & derivados , Factores de Edad , Anciano , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Linfoma no Hodgkin/patología , Masculino , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Prednisona/administración & dosificación , Factores de Riesgo , Vidarabina/administración & dosificación , Vindesina/administración & dosificación
14.
Semin Oncol ; 30(2): 291-6, 2003 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-12720155

RESUMEN

Published data on transplantation in Waldenstrom's macroglobulinemia (WM) are still limited. We present a retrospective multicentric study of 27 WM patients who underwent 19 autologous (median age, 54 years) and 10 allogeneic (median age, 46 years) transplantations. Median time between diagnosis and transplantation was 36 months; 66% of patients had received three or more treatment lines and 72 % had chemosensitive disease. High-dose therapy (HDT) and autologous transplantation induced a 95% response rate (RR), including 10 major responses. With a median follow-up of 18 months, 12 patients are alive at 10 to 81 months and eight are free of disease progression at 10 to 34 months. The toxic mortality rate (TRM) was 6%. Allogeneic transplantation was preceded by HDT in nine patients and by a nonmyeloablative regimen in one patient. The RR was 80%, including seven major responses. With a median follow-up of 20.5 months, six patients are alive and free of progression at 3 to 76 months. Four patients died, all from toxicity, resulting in a TRM of 40%. HDT followed by autologous transplantation is feasible in WM, even in heavily pretreated patients, with some prolonged responses but a high relapse rate. Conversely, allogeneic transplantation is more toxic, but likely induces a graft-versus-WM effect and may, for some patients, result in long-term disease control.


Asunto(s)
Antineoplásicos/uso terapéutico , Trasplante de Células Madre , Macroglobulinemia de Waldenström/terapia , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante Autólogo , Trasplante Homólogo , Resultado del Tratamiento , Macroglobulinemia de Waldenström/inmunología
15.
Rev Mal Respir ; 19(3): 375-7, 2002 Jun.
Artículo en Francés | MEDLINE | ID: mdl-12161706

RESUMEN

The idiopathic hyper-eosinophilic syndrome is defined as a peripheral blood eosinophilia greater than 1.5 x 10(9)/litre present for at least 6 months and associated with visceral involvement. It may only be accepted after carefully excluding the other common or rare causes of hyper-eosinophilia and should remain a diagnosis of exclusion. The associated visceral lesions are multiple and non-specific. Among these neurological, digestive, dermatological and cardiac manifestations are the most frequently described. Whereas pleuro-pulmonary involvement is also common, asthma is rarely reported. We report a case of ideopathic hyper-eosinophilic syndrome presenting as asthma. This was secondary to eosinophilic infiltration of the bronchial mucosa as demonstrated by cytological examination of induced sputum.


Asunto(s)
Asma/etiología , Síndrome Hipereosinofílico/complicaciones , Adulto , Humanos , Masculino
16.
Leukemia ; 15(11): 1785-91, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11681422

RESUMEN

The blastic variant (BV) form of mantle cell lymphoma (MCL) is considered to be a very aggressive subtype of non-Hodgkin's lymphoma (NHL). In order to determine its clinico-biological features and response to therapy we studied 33 patients (17%) out of 187 suffering from MCL who were diagnosed with a BV of MCL. Blastic variant was diagnosed according to histopathological patterns, immunophenotyping, and bcl1 gene rearrangement and/or cyclin D1 overexpression. Three patients initially diagnosed with large cell NHL were classified as BV. Patients received front-line therapy including CHOP-like regimen or CVP (n = 29), or chlorambucil (n = 4) and CHOP or ESAP as second-line therapy. High-dose intensification with stem cell transplantation (SCT) was performed in 11 cases (autoSCT, n = 8; alloSCT, n = 3). All but two patients were in complete remission (CR) at the time of transplant (CR1, n = 5; CR2, n = 4). Clinical and biological characteristics did not differ from those of the common form of MCL. The median age was 62 years (29-80), with a sex ratio (M/F) of 2.6:1. Of the 33 patients, 66% had extranodal site involvement, 85% had an Ann Arbor stage IV, and 82% had peripheral lymphadenopathy. Circulating lymphomatous cells were seen in 48% of cases. Twelve patients (36%) entered a CR1 with a median duration of 11 months. Fifteen patients (46%) failed to respond and rapidly died of progressive disease. Second-line therapy led to a 26% (6/23) CR2 rate. Nine patients relapsed after high-dose therapy. Twenty-two of the 33 patients (66%) died of refractory or progressive disease. Median overall survival (OS) time was 14.5 months for the 33 BV patients as compared to 53 months for the 154 patients with a common form of MCL, P <0.0001. In the univariate analysis, OS was influenced by age, extranodal site involvement, circulating lymphomatous cells, and international prognosis index (IPI). In the multivariate analysis, only IPI affected OS: patients with IPI > or =2 had 8 months median OS as compared to 36 months median OS for patients with IPI <2, P = 0.003. Blastic variant is one of the worst forms of NHL. An improved recognition of BV of MCL is required, particularly in high-grade CD5+ NHL using immunophenotyping and bcl1 molecular study. Standard therapy using anthracycline or even high-dose intensification produce poor results and an alternative treatment should be proposed to such patients.


Asunto(s)
Linfoma de Células del Manto/diagnóstico , Linfoma de Células del Manto/mortalidad , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Reordenamiento Génico , Genes bcl-1 , Humanos , Inmunofenotipificación , Linfoma de Células del Manto/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento
17.
Blood ; 97(10): 3210-7, 2001 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-11342451

RESUMEN

This work aims to demonstrate that CD4(+)CD56(+) malignancies arise from transformed cells of the lymphoid-related plasmacytoid dendritic cell (pDC) subset. The analysis of malignant cells from 7 patients shows that in all cases, like pDCs, leukemic cells are negative for lineage markers CD3, CD19, CD13, CD33, and CD11c but express high levels of interleukin-3 receptor alpha chain (IL-3Ralpha), HLA-DR, and CD45RA. Tumor cells produce interferon-alpha in response to influenza virus, while upon maturation with IL-3 they become a powerful inducer of naive CD4(+) T-cell proliferation and promote their T-helper 2 polarization. As pDCs, leukemic cells also express pre-Talpha and lambda-like 14.1 transcripts, arguing in favor of a lymphoid origin. In addition, malignant cells express significant levels of CD56 and granzyme B. Overall, those observations suggest that CD4(+)CD56(+) leukemic cells could represent the malignant counterpart of pDCs, both of which are closely related to B, T, and NK cells.


Asunto(s)
Células Dendríticas/patología , Leucemia/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD4/análisis , Antígenos CD40/genética , Antígenos CD40/fisiología , Antígeno CD56/análisis , Diferenciación Celular , Niño , Células Dendríticas/inmunología , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Granzimas , Antígenos HLA-DR/análisis , Humanos , Interferón-alfa/biosíntesis , Interleucina-3/farmacología , Leucemia/inmunología , Antígenos Comunes de Leucocito/análisis , Masculino , Persona de Mediana Edad , Receptores de Interleucina-3/análisis , Serina Endopeptidasas/análisis , Linfocitos T/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Transfección , Células Tumorales Cultivadas
18.
Eur J Cancer ; 36(18): 2360-7, 2000 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11094310

RESUMEN

The aim of this study was to assess the effect of cell determinant (CD)34+ cell dose on the cost and consequences of peripheral blood stem cell transplantation for non-Hodgkin's lymphoma (NHL) patients in front-line therapy. Resource utilisation, length of aplasia, overall (OS) and event-free survival (EFS) were assessed for 63 patients. Economic data were calculated taking into account harvest, hospitalisation, blood product requirements and drugs required until discharge. The point of view of the Hospital Institution was chosen. A significantly earlier haematopoietic engraftment was achieved in patients with a count of more than 5 x 10(6) CD34+/kg. There were no differences for OS and EFS. A high CD34+ cell content resulted in a total cost saving of $4210. This was principally related to a significant reduction in the length of hospitalisation (-$3010) and platelet and red blood cell transfusions (-$815), although the latter was not significant. Several sensitivity analyses showed the robustness of our results. A CD34+ cell dose higher than 5 x 10(6)/kg appeared to be optimal for clinical and economic considerations in NHL patients undergoing transplantation in front-line therapy.


Asunto(s)
Antígenos CD34 , Trasplante de Células Madre Hematopoyéticas/métodos , Linfoma no Hodgkin/terapia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Eliminación de Componentes Sanguíneos , Análisis Costo-Beneficio , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Relación Dosis-Respuesta Inmunológica , Doxorrubicina/administración & dosificación , Femenino , Supervivencia de Injerto , Movilización de Célula Madre Hematopoyética/economía , Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre Hematopoyéticas/economía , Humanos , Linfoma no Hodgkin/economía , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Vincristina/administración & dosificación
19.
J Clin Pathol ; 53(7): 549-51, 2000 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10961180

RESUMEN

With lymph node enlargement, the possibility of a malignant process such as metastatic carcinoma or lymphoma needs to be excluded. This report describes a 47 year old woman with inguinal lymph node enlargement initially suspicious for lymphoma. Fine needle aspiration findings favoured reactive hyperplasia, but a malignant process could not be excluded. The final histological diagnosis was a foreign body granulomatous inflammatory response as a result of regionally disseminated silicone particles from an over looked metatarsophalangeal joint prosthesis. Because of the large number of joint prostheses world wide, it should be kept in mind that migration of wear particles can create granulomatous inflammation and node enlargement.


Asunto(s)
Granuloma de Cuerpo Extraño/patología , Prótesis Articulares/efectos adversos , Seudolinfoma/patología , Elastómeros de Silicona/efectos adversos , Diagnóstico Diferencial , Femenino , Migración de Cuerpo Extraño/complicaciones , Granuloma de Cuerpo Extraño/etiología , Humanos , Persona de Mediana Edad , Seudolinfoma/etiología
20.
Rev Med Interne ; 21(3): 290-4, 2000 Mar.
Artículo en Francés | MEDLINE | ID: mdl-10763192

RESUMEN

INTRODUCTION: Immunocompromised patients are at high risk of Epstein-Barr virus (EBV)-related lymphoproliferative disorders. The lymphoproliferation affects B, T, and natural killer (NK) cells. EXEGESIS: We report the case of a woman suffering from systemic lupus erythematous. She developed an opportunistic pneumonia while immunodepressed during long-term corticotherapy aimed at curing her auto-immune disease. Chronic lymphocytosis was also diagnosed at this time. Several months later, non-Hodgkin's lymphoma was diagnosed. Genomic amplification of the Epstein-Barr virus in the patient's blood and positive EBV latent membrane protein 1 on the lymph nodes provided evidence for a strong correlation between EBV reactivation and lymphoma. CONCLUSION: Two distinct lymphoid diseases occurred during the immunosuppressive therapy for the auto-immune disease. PCR monitoring of Epstein-Barr virus allows for early screening of lymphoproliferative disorders in immunocompromised patients, leading to earlier and more efficient treatment.


Asunto(s)
Antiinflamatorios/efectos adversos , Infecciones por Virus de Epstein-Barr/complicaciones , Huésped Inmunocomprometido , Células Asesinas Naturales , Lupus Eritematoso Sistémico/tratamiento farmacológico , Linfocitosis/complicaciones , Linfoma de Células B/etiología , Linfoma de Células B/virología , Anciano , Biopsia , Enfermedad Crónica , Infecciones por Virus de Epstein-Barr/diagnóstico , Femenino , Humanos , Ganglios Linfáticos/patología , Ganglios Linfáticos/virología , Linfocitosis/diagnóstico , Linfoma de Células B/diagnóstico , Factores de Riesgo , Esteroides
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