RESUMEN
In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here the SFGM-TC addressed the issue of post-transplant CMV and EBV reactivation, and EBV-related Lymphoproliferative Disorders.
Asunto(s)
Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/terapia , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/terapia , Activación Viral , Citomegalovirus/fisiología , Infecciones por Citomegalovirus/etiología , Selección de Donante/normas , Infecciones por Virus de Epstein-Barr/etiología , Trasplante de Células Madre Hematopoyéticas/normas , Herpesvirus Humano 4/fisiología , Humanos , Terapia de Inmunosupresión/normas , Terapia de Inmunosupresión/estadística & datos numéricos , Trastornos Linfoproliferativos/etiología , Monitoreo Fisiológico/normas , Prevención Primaria/normas , Trasplante HomólogoRESUMEN
In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the management of short and long-term endocrine dysfunction following allogeneic stem cell transplantation. The key aim of this workshop was to give an overview on secondary adrenal insufficiency and osteoporosis post-transplant.
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Insuficiencia Suprarrenal/terapia , Enfermedades del Sistema Endocrino/etiología , Enfermedades del Sistema Endocrino/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Osteoporosis/terapia , Insuficiencia Suprarrenal/etiología , Adulto , Densidad Ósea , Niño , Suplementos Dietéticos , Difosfonatos/uso terapéutico , Glucocorticoides/efectos adversos , Humanos , Inmunosupresores/efectos adversos , Osteoporosis/etiología , Trasplante Homólogo , Vitaminas/uso terapéuticoRESUMEN
In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the management of short and long-term endocrine dysfunction following allogeneic stem cell transplantation. The key aim of this workshop was to give an overview on dyslipidemia and thyroid disorders post-transplant.
Asunto(s)
Dislipidemias/terapia , Enfermedades del Sistema Endocrino/etiología , Enfermedades del Sistema Endocrino/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedades de la Tiroides/terapia , Conducta de Elección , Consenso , Dieta , Dislipidemias/etiología , Ácidos Fíbricos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/normas , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Monitoreo Fisiológico/métodos , Monitoreo Fisiológico/normas , Enfermedades de la Tiroides/etiología , Trasplante HomólogoRESUMEN
In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the management of short and long-term endocrine dysfunction following allogeneic stem cell transplantation. The key aim of this workshop was to give an overview gonadal failure, fertility preservation and post-transplant.
Asunto(s)
Enfermedades del Sistema Endocrino/terapia , Preservación de la Fertilidad/normas , Trastornos Gonadales/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/normas , Infertilidad/prevención & control , Amenorrea/inducido químicamente , Consenso , Enfermedades del Sistema Endocrino/diagnóstico , Enfermedades del Sistema Endocrino/etiología , Femenino , Fertilidad/fisiología , Preservación de la Fertilidad/métodos , Trastornos Gonadales/diagnóstico , Trastornos Gonadales/etiología , Humanos , Infertilidad/diagnóstico , Infertilidad/etiología , Masculino , Embarazo , Índice de Embarazo , Trasplante HomólogoRESUMEN
INTRODUCTION: We present the results of the COVID-19 rule-out protocol at Ghent University Hospital, a step-wise testing approach which included repeat NFS SARS-CoV-2 rRT-PCR, respiratory multiplex RT-PCR, low-dose chest CT and bronchoscopy with BAL to confirm or rule-out SARS-CoV-2 infection in patients admitted with symptoms suggestive of COVID-19. RESULTS: Between 19 March 2020 and 30 April 2020, 455 non-critically ill patients with symptoms suspect for COVID-19 were admitted. The initial NFS for SARS-CoV-2 rRT-PCR yielded 66.9%, the second NFS 25.4% and bronchoscopy with BAL 5.9% of total COVID-19 diagnoses. In the BAL fluid, other respiratory pathogens were detected in 65% (13/20) of the COVID-19 negative patients and only in 1/7 COVID-19 positive patients. Retrospective antibody testing at the time around BAL sampling showed a positive IgA or IgG in 42.9 % of the COVID-19 positive and 10.5% of the COVID-19 negative group. Follow-up serology showed 100% COVID-19 positivity in the COVID-19 positive group and 100% IgG negativity in the COVID-19 negative group. CONCLUSION: In our experience, bronchoscopy with BAL can have an added value to rule-in or rule-out COVID-19 in patients with clinical and radiographical high-likelihood of COVID-19 and repeated negative NFS testing. Furthermore, culture and respiratory multiplex PCR on BAL fluid can aid to identify alternative microbial etiological agents in this group. Retrospective analysis of antibody development in this selected group of patients suggests that the implementation of serological assays in the routine testing protocol will decrease the need for invasive procedures like bronchoscopy.
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COVID-19 , Broncoscopía , COVID-19/diagnóstico , Humanos , Estudios Retrospectivos , SARS-CoV-2 , Tomografía Computarizada por Rayos XRESUMEN
We analyzed the outcome of 25 consecutive patients with chronic hematological malignancy who underwent allogeneic stem-cell transplantation conditioned with fludarabine (30 mg/m2/day, thrice) and total body irradiation (2 Gy). All patients received peripheral blood stem cells from an HLA-identical sibling donor. With a median follow-up of 769 days (range, 244 - 1231), the estimated 2-year overall survival (OS), event-free survival (EFS), transplantation-related mortality and relapse rates were 53%, 45%, 27%, and 39%, respectively. All patients had initial engraftment. Acute Grade II - IV graft-versus-host disease (GVHD) was recorded in 14 patients (56%), including 7 (28%) with Grade III - IV GVHD. Sixteen of the 23 patients (70%) who survived more than 100 days developed chronic GVHD. OS and EFS were adversely influenced by acute Grade III - IV GVHD (p < 0.001 and p = 0.033, respectively), but chronic GVHD seemed to favorably influence these two parameters (p = 0.03 and p < 0.001, respectively). Patients with full-donor chimerism at day 30 had lower relapse rates, as did those who received high-dose allogeneic CD8+ lymphocytes with their graft (p = 0.026). Collectively, these results provide a framework for refining nonmyeloablative conditioning, to improve outcome with an acceptable risk of GVHD.
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Antineoplásicos/uso terapéutico , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Acondicionamiento Pretrasplante , Vidarabina/análogos & derivados , Irradiación Corporal Total , Adulto , Terapia Combinada , ADN (Citosina-5-)-Metiltransferasas/antagonistas & inhibidores , Femenino , Enfermedad Injerto contra Huésped/terapia , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Quimera por Trasplante , Trasplante Homólogo , Vidarabina/uso terapéuticoRESUMEN
CC-chemokine receptor 7 (CCR7), a chemokine receptor required for transmigration into lymphoid organs, is only expressed by naive and central memory T cells. T cells with a capacity of homing into lymphoid organs can initiate acute graft-versus-host disease (GVHD) in mice and respond vigorously in vitro to alloantigens in humans, but their impact on clinical outcomes is unknown. We evaluated prospectively the distribution of naive, central memory and CCR7neg memory T-cell subsets in 39 bone marrow and 23 granulocyte colony-stimulating factor-mobilized peripheral blood stem cell allografts and investigated their impact on patient outcomes. Ranges of the relative proportions of CCR7+ cells within CD4+ and CD8+ T-cell populations were broad, but did not differ between the two sources of allografts. By multivariate analysis, high percentage of donor-derived CD4+CCR7+ T cells (>73.5%) significantly correlated with incidence, earliness of onset and severity of acute GVHD, conferring the highest adjusted hazard ratio (HR=3.9; 95% confidence interval 1.4-10.8; P=0.008) without interfering in other clinical events, especially chronic GVHD and relapse. Determination of the percentage of CD4+CCR7+ T cells in the graft provides a predictive indicator of acute GVHD. Partial depletion of this subset may reduce the risk of acute GVHD while preserving immunotherapeutic effects.
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Linfocitos T CD4-Positivos/inmunología , Enfermedad Injerto contra Huésped , Neoplasias Hematológicas/cirugía , Receptores de Quimiocina/inmunología , Trasplante de Células Madre , Adolescente , Adulto , Anciano , Niño , Preescolar , Citometría de Flujo , Enfermedad Injerto contra Huésped/inmunología , Neoplasias Hematológicas/inmunología , Humanos , Incidencia , Persona de Mediana Edad , Receptores CCR7 , Recurrencia , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Trasplante HomólogoRESUMEN
Despite the favorable prognosis of patients with acute myeloid leukemia (AML) with t(8;21)(q22;q22) translocation, relapses still occur in about 30% of the cases but no initial factors can strongly predict the risk of relapse. Several recent studies suggest that monitoring minimal residual disease (MRD) may identify patients at risk of relapse. We prospectively monitored AML1-ETO rearrangement by real-time quantitative PCR (RQ-PCR) in 21 patients uniformly treated in our center. Blood (PB) and bone marrow (BM) samples were collected during and after therapy. At diagnosis, levels of AML1-ETO transcript showed large variations and there was a trend for a higher relapse rate in patients with high pretreatment expression levels (P=0.065). After induction therapy, absolute transcript levels (below 10(-3), compared to Kasumi cell line), or a greater than 3 log decrease by comparison to diagnosis levels, were significant predictors of the absence of relapse (P=0.02 and P=0.02, respectively). MRD levels after consolidation therapy were also significant indicators of relapse (P=10(-5)). Comparison of BM and PB samples showed similar sensitivity for detecting AML1-ETO transcript. In conclusion, RQ-PCR appears to be an early predictive factor of the relapse risk in AML with t(8;21). PB samples can be used adequately to evaluate the level of MRD by this technique.
Asunto(s)
Cromosomas Humanos Par 21/genética , Cromosomas Humanos Par 8/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Adolescente , Adulto , Antineoplásicos/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Reordenamiento Génico , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Análisis de Regresión , Sensibilidad y Especificidad , Tasa de Supervivencia , Translocación Genética/genéticaRESUMEN
We have examined p53 alleles in 151 DNAs from patients with myelodysplastic syndrome using single-strand conformation polymorphism analysis of polymerase chain reaction products. We focused our study on the four highly conserved regions of the p53 gene and detected five patients with aberrantly migrating fragments. We confirmed the putative mutation in each case by direct sequencing analysis. Of these five patients, three had chromosome 17 monosomy associated with p53 mutation, one patient showed one mutated p53 allele and one wild-type allele, and the last patient demonstrated only the mutant allele, suggesting a homozygous state. Unlike many other types of human cancers, point mutations in the p53 tumor-suppressor gene appear to be a rare event in myelodysplastic syndromes.
Asunto(s)
Cromosomas Humanos Par 17 , Genes p53 , Mutación , Síndromes Mielodisplásicos/genética , Alelos , Secuencia de Bases , Médula Ósea/patología , Aberraciones Cromosómicas , Trastornos de los Cromosomas , Codón , ADN/genética , ADN/aislamiento & purificación , Exones , Variación Genética , Humanos , Intrones , Cariotipificación , Datos de Secuencia Molecular , Síndromes Mielodisplásicos/patología , Oligodesoxirribonucleótidos , Reacción en Cadena de la PolimerasaRESUMEN
We recently isolated the RhoH/TTF gene by its fusion to the LAZ3/BCL6 gene, in a non-Hodgkin's lymphoma (NHL) cell line, which bore a t(3;4)(q27;p11-13) translocation. This gene encodes a novel Rho GTP-binding protein and is specifically expressed in hematopoietic tissues. We made its precise mapping at band 4p13, and described its partial genomic structure. Using fluorescence in situ hybridization and molecular analyses, we report here on the rearrangement of the RhoH/TTF gene, at band 4p13, in four cases of NHL with t(3;4)(q27;p13) translocation and its fusion to the LAZ3/BCL6 gene at band 3q27, in three of these cases. RT-PCR analysis of two cases allowed the detection of variable fusion transcripts emerging from the rearranged alleles, and in one case, a deregulated expression of both RhoH/TTF and LAZ3/BCL6 genes, by promoter substitution, was observed. We also show here another rearrangement of the RhoH/TTF gene in a patient with multiple myeloma and t(4;14)(p13;q32) translocation, with breakage within the IGH gene. It is the first report which describes the recurrent chromosomal alteration of a GTP-binding protein encoding gene, in patients with hematopoietic malignancies.
Asunto(s)
Cromosomas Humanos Par 4 , Proteínas de Unión al GTP/genética , Reordenamiento Génico , Linfoma no Hodgkin/genética , Mieloma Múltiple/genética , Secuencia de Bases , Northern Blotting , Cromosomas Humanos Par 3 , Proteínas de Unión al ADN/genética , Femenino , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Hibridación Fluorescente in Situ , Persona de Mediana Edad , Datos de Secuencia Molecular , Proteínas Proto-Oncogénicas c-bcl-6 , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Translocación GenéticaRESUMEN
Adult chronic myelomonocytic leukemia (CMML), as defined by the French-American-British (FAB) group, is associated with a variable survival, ranging from a few weeks to several years. From 1971 to 1986, we made the diagnosis of CMML in 107 cases, according to FAB criteria (except for patients with 20% to 30% bone marrow [BM] blasts who were also included). Median survival was 30 months (range 1 to 81 months) and life expectancy did not seem to be influenced by treatment modalities other than supportive care. Eighteen patients (17%) progressed to acute nonlymphoblastic leukemia (ANLL). In a Cox regression model, main factors associated with short survival were: an excess of marrow blasts (P = 10(-6], anemia (P = .17 x 10(-5], high peripheral blood (PB) monocytosis (P = .26 x 10(-5], presence of PB blasts (P = .49 x 10(-4], and to a lesser extent hyperleukocytosis (P = .001), presence of PB immature granulocytes, thrombopenia, and splenomegaly. Survival (less than 1 year v greater than 1 year) could be predicted at diagnosis in a multivariate stepwise discriminant analysis using two parameters only (percentage of BM blasts and hemoglobin level), with 82% accuracy. Among patients surviving greater than 1 year, initial PB leukocyte count was higher in patients with intermediate survival (12 to 42 months) than in long survivors (greater than 42 months) and was the only discriminating factor between these two subgroups in multivariate analysis. Abnormal cytogenetic findings and increased lysozymuria were also poor prognostic factors, but could not be analyzed in the multivariate models, as they were determined in a minority of patients. Parameters associated with subsequent progression to ANLL included younger age at diagnosis, thrombopenia, increased BM blasts, and splenomegaly. Our study allows for the identification of subgroups with different prognoses in CMML, on the basis of a small number of hematologic parameters, particularly initial percentage of BM blasts, hemoglobin level, and leukocytosis. These subgroups probably require different therapeutic approaches.
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Leucemia Mieloide/mortalidad , Anciano , Enfermedad Crónica , Femenino , Humanos , Leucemia Mieloide/sangre , Leucemia Mieloide/terapia , Masculino , Pronóstico , Análisis de Regresión , Factores de TiempoRESUMEN
PURPOSE: A single-center retrospective analysis was conducted in 167 patients with Waldenström's macroglobulinemia (WM) to delineate prognostic factors. PATIENTS AND METHODS: One hundred sixty-seven patients diagnosed between January 1969 and December 1988, fulfilling diagnostic criteria of WM, were entered onto this study. One hundred twenty-eight patients were treated with chlorambucil (0.1 mg/kg/d): 117 at diagnosis and 11 during the disease course. Seventeen variables were analyzed in all patients and in treated patients for their prognostic value on survival using the Kaplan-Meier method and a Cox multivariate regression analysis. RESULTS: Median survival duration for all patients was 60 months. Pretreatment factors associated with shorter survival in the entire population were age > or = 60 years (P = .006), male sex (P = .0001), general symptoms (P = .01), hemoglobin less than 10 g/dL (P = .008), leukocytes less than 4 X 10(9)/L (P = .02), neutrophils less than 1.7 X 10(9)/L (P = .02), and platelets less than 150 X 10(9)/L (P = .0006). Organomegaly, signs of hyperviscosity, renal failure, monoclonal immunoglobulin M (M IgM) level, blood lymphocytosis, and percentage of marrow lymphoid cells were not significantly correlated with survival. In a Cox multivariate regression analysis, the combination of factors that gave the best prognostic value was the association of sex (P = .0002), neutrophils (P = .002), age (P = .008), and hemoglobin (P = .02). CONCLUSION: Our findings suggest that some pretreatment parameters, including older age, male sex, general symptoms, and cytopenias, carry a poor prognosis in WM. By contrast, high initial tumor burden (indicated by organomegaly, high IgM level, and high percentage of marrow lymphoid cells) does not seem to be significantly associated with short survival. Our results help define a high-risk population that could perhaps benefit from newer therapeutic approaches.
Asunto(s)
Macroglobulinemia de Waldenström/mortalidad , Anciano , Causas de Muerte , Clorambucilo/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Análisis de Regresión , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Macroglobulinemia de Waldenström/tratamiento farmacológico , Macroglobulinemia de Waldenström/fisiopatologíaRESUMEN
PURPOSE: To analyze the type of prior tumor and treatment in therapy-related acute promyelocytic leukemia (tAPL) that occurs after chemotherapy and/or radiotherapy (RT), and the hematologic characteristics and outcome of tAPL. PATIENTS AND METHODS: Sixteen patients with tAPL who were gathered during a 10-year period (1982 to 1991) in seven hematologic centers were analyzed retrospectively. RESULTS: There were 13 women and three men. The median age was 46 years (range, 12 to 82). Prior tumor was breast carcinoma in 10 cases, another solid tumor in three cases, and lymphoma in three cases. Two patients had received RT alone, and 14 had received chemotherapy (with RT in 11 cases). Prior chemotherapeutic agents generally included a combination of cyclophosphamide (used for limited periods), fluorouracil (5-FU), vinca alkaloids, and doxorubicin, mitoxantrone, or etoposide (VP16). By contrast, alkylating agents other than cyclophosphamide had been used in only two patients. Median interval between onset of treatment for the prior tumor and diagnosis of APL was 25 months. No patient had a known preleukemic phase. Hematologic and cytogenetic characteristics of the cases of tAPL were identical to those of the usual de novo APL, which included the presence of t(15; 17) in nine of the 10 patients tested. Two patients had early death. Seven patients were treated with intensive chemotherapy, and six achieved complete remission (CR). Three of them subsequently relapsed. Seven patients were treated with all-trans-retinoic acid (ATRA), and four achieved CR through the differentiation of blasts into mature granulocytes. None has relapsed so far. CONCLUSIONS: Our findings suggest that tAPL is not exceptional, and usually has several features in common with other types of therapy-related AML with specific karyotype (ie, t(8;21),t(9;11), inv(16)): solid tumor rather than hematologic malignancy as primary tumor, short interval of development, absence of known preleukemic phase, prior chemotherapy with a combination of several drugs that often included an agent that targets topoisomerase II (doxorubicin or mitoxantrone, but less often VP16). Hematologic characteristics and response to therapy (intensive chemotherapy or ATRA) in tAPL do not seem to differ from those of de novo APL.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Leucemia Promielocítica Aguda/etiología , Leucemia Inducida por Radiación/etiología , Radioterapia/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Humanos , Cariotipificación , Leucemia Promielocítica Aguda/inducido químicamente , Leucemia Promielocítica Aguda/tratamiento farmacológico , Leucemia Inducida por Radiación/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/radioterapia , Estudios Retrospectivos , Factores de RiesgoRESUMEN
PURPOSE: We analyzed prognostic factors in 80 adult patients with lymphoblastic lymphoma (LBL). PATIENTS AND METHODS: Twenty-one patients received six monthly courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and maintenance chemotherapy for 12 months. The LNH-84 protocol (30 patients) consisted of four courses of high-dose CHOP followed by consolidation for 4 months. Both FRALLE (22 patients) and LALA (seven patients) protocols were two intensive chemotherapy regimens for acute lymphoblastic leukemia (ALL) that included an induction with daunorubicin, vincristine, cyclophosphamide, prednisolone (and asparaginase for the FRALLE regimen), consolidation, and maintenance chemotherapy that lasted for 2 years. RESULTS: Sixty-six patients (82%) achieved a complete remission (CR). The CR duration rate and overall survival rate at 30 months were estimated to be 46% and 51%, respectively, with a median follow-up of 55 months. Only two of 37 relapses occurred after 26 months. Chemotherapy protocol did not influence CR rate, CR duration, and survival. A higher CR rate was associated with an age of less than 40 years, lactic dehydrogenase (LDH) level of less than two times the upper limits of normal, and no or one extranodal site of disease. Short survival was associated with a failure to achieve CR, age older than 40 years, B symptoms, LDH level more than two times the upper limits of normal, and hemoglobin level of less than 100 g/L. Bone marrow involvement had no prognostic value. We could not evaluate precisely the prognostic value of Ann Arbor stage because inclusion criteria differed among treatment groups. CONCLUSION: Our findings suggest that age and LDH are two important pretreatment prognostic factors for adult LBL, and that the optimal prognostic staging system remains a controversial issue.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Adulto , Factores de Edad , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Trasplante de Médula Ósea , Terapia Combinada , Esquema de Medicación , Femenino , Humanos , L-Lactato Deshidrogenasa/sangre , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimología , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirugía , Pronóstico , Análisis de RegresiónRESUMEN
PURPOSE: To analyze retrospectively survival and prognostic factors of patients with non-Hodgkin's lymphoma (NHL) autografted from 1979 to 1995 in a single institution. PATIENTS AND METHODS: A total of 120 patients, 64 with aggressive and 56 with low-grade NHL, were autografted. The carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM) regimen was used in 104. The autograft was marrow in 101 patients. Marrow was purged in vitro by mafosfamide for 63 patients (adjusted dose [AD] in 32; unique dose [UD] in 31); 27 patients received a CD34+-selected graft. Following intensification, 45 patients received additional radiotherapy on previous sites of involvement. RESULTS: Outcome at 5 years for patients transplanted with low-grade NHL in first complete remission (CR1), in first partial remission (PR1), and in second complete remission (CR2) or beyond showed an event-free survival (EFS) of 75% +/- 12%, 46% +/- 18%, and 57% +/- 24%, a relapse incidence (RI) of 21% +/- 12%, 49% +/- 19%, and 43% +/- 25%, and a transplant-related mortality (TRM) of 5% +/- 5%, 10% +/- 7%, and 0%, respectively. For patients with aggressive NHL transplanted in CR1, in PR1, in CR2 or beyond, and in resistant relapse or in primary refractory disease, the EFS was of 73% +/- 9%, 58% +/- 19%, 29% +/- 16%, and 10% +/- 9%, the RI 22% +/- 9%, 14% +/- 9%, 77% +/- 18%, and 66% +/- 20%, and the TRM 6% +/- 6%, 32% +/- 21%, 11% +/- 10%, and 71% +/- 22%, respectively. In patients autografted upfront in first remission, additional radiotherapy was associated with a higher EFS, in univariate (P = .03) and multivariate analysis (P = .02, relative risk [RR] = .021). The role of graft purging with mafosfamide on the outcome reflected by the dose of colony-forming unit-granulocyte-macrophage (CFU-GM) per kilogram infused postpurging was assessed by univariate analysis: patients in first remission who received lower doses of CFU-GM had a lower RI and a higher EFS. CONCLUSION: This retrospective analysis suggests that marrow purging and posttransplant radiotherapy improve the outcome of patients with NHL autografted in first remission.
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Purgación de la Médula Ósea , Trasplante de Células Madre Hematopoyéticas , Linfoma no Hodgkin/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carmustina/administración & dosificación , Terapia Combinada , Ciclofosfamida/análogos & derivados , Citarabina/administración & dosificación , Supervivencia sin Enfermedad , Etopósido/administración & dosificación , Femenino , Humanos , Linfoma no Hodgkin/patología , Linfoma no Hodgkin/radioterapia , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Pronóstico , Recurrencia , Inducción de Remisión , Estudios RetrospectivosRESUMEN
Thrombocytopenia is generally of central origin in MDS, but can be due to peripheral platelet destruction in some cases. We studied platelet lifespan in 61 MDS cases with platelets < 70,000/mm3 and marrow blasts < 10%. Nine of them (15%) had a major platelet lifespan reduction (< 3.5 days), and were considered for splenectomy. Three of them were not splenectomized due to rapid death, patient refusal and older age plus liver predominance of platelet sequestration, respectively. The remaining six patients (two females and four males, median age 50 years, range 32 to 65) were splenectomized 3 to 21 months after diagnosis. Before splenectomy, five of them had RA and one had CMML. Platelets counts ranged from 5000 to 30,000/mm3 and did not durably respond to other treatments. Three of the patients has a relapse of platelet counts, concomitantly required platelet transfusion due to recurrent blending, whereas three had anemia (two required erythrocyte transfusion) and four had neutropenia. Three months after surgery, platelet counts ranged from 55,000 to 160,000/mm3 (> 100,000/mm3 in four cases), no patient required platelet or erythrocyte transfusion, but there was no effect on neutrophil counts. Three patients had a relapse of platelet counts, concomitant with progression to AML in two of them, whereas the third relapsing case achieved normal platelet counts with further danazol. One patient died with normal platelet counts 12 months after splenectomy (from sepsis, probably related to neutropenia rather than splenectomy). Two patients remained with normal platelet counts 10 and 52 months after surgery. Our findings suggest that the mechanism of thrombocytopenia should be studied more often in 'low risk' MDS (i.e. with low bone marrow blast counts) with thrombocytopenia, as about 15% of them appear to have peripheral platelet destruction. Some of those patients may benefit from splenectomy.
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Síndromes Mielodisplásicos/cirugía , Esplenectomía , Trombocitopenia/etiología , Enfermedad Aguda , Corticoesteroides/uso terapéutico , Adulto , Anciano , Anemia Refractaria/sangre , Anemia Refractaria/tratamiento farmacológico , Anemia Refractaria/cirugía , Anemia Refractaria con Exceso de Blastos/sangre , Anemia Refractaria con Exceso de Blastos/tratamiento farmacológico , Anemia Refractaria con Exceso de Blastos/cirugía , Enfermedades Autoinmunes/etiología , Plaquetas/patología , Senescencia Celular , Hemorragia Cerebral/etiología , Hemorragia Cerebral/mortalidad , Terapia Combinada , Danazol/uso terapéutico , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Interleucina-3/uso terapéutico , Leucemia Mieloide/mortalidad , Leucemia Mielomonocítica Crónica/sangre , Leucemia Mielomonocítica Crónica/tratamiento farmacológico , Leucemia Mielomonocítica Crónica/cirugía , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/sangre , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/mortalidad , Neutropenia/etiología , Recuento de Plaquetas , Recurrencia , Estudios Retrospectivos , Síndrome de Sjögren/etiología , Esplenectomía/efectos adversos , Resultado del Tratamiento , Negativa del Paciente al Tratamiento , Vasculitis/etiologíaRESUMEN
We treated 28 cases of myelodysplastic syndrome (MDS) with neutropenia by very low-dose GM-CSF (0.25 or 0.5 micrograms/kg/day). Median age was 69 years. Nine patients had RA, 18 had RAEB, and one had RARS. Eighteen patients had absolute neutrophil counts (ANC) < or = 0.5 x 10(9)/l, and ten had ANC between 0.5 and 1.0 x 10(9)/l. Ten patients had experienced > or = WHO grade II infection(s) during the preceding 3 months. Eighteen patients (64%) had a response (i.e. ANC at least doubled and > or = 1 x 10(9)/l after 1 month), including 4/8 patients treated at 0.25 mu/kg/day, and 14/20 treated at 0.5 microgram/kg/day (difference not significant). Two of the non-responders obtained a response after dose escalation to 0.5 and 1 microgram/kg/day, respectively. The only prognostic factor of response was FAB subtype (10/11 responses in patients with RA or RARS, vs. 8/17 in RAEB, p = 0.04). Patients with ANC < or = 0.5 x 10(9)/l had a 55% (10/18) response rate, which was not significantly lower than the 80% (8/10) response rate observed in patients with ANC > 0.5 x 10(9)/l. Side-effects were generally moderate, except in three patients where the drug had to be discontinued, including the only patient who progressed to AML. In responders, GM-CSF was continued during 2 to 14 months (median 6), and the response persisted in all but one case, who relapsed after 60 days of treatment. During follow-up, only one responder had > or = WHO grade II infections, as compared to five of the non-responders (of whom two had fatal infectious episodes). In conclusion, very low-dose GM-CSF can durably increase ANC in about two thirds of MDS with neutropenia. Although it remains to be shown in randomized trials that it can reduce the incidence of infections and improve survival in MDS, very low-dose GM-CSF may be an interesting approach in MDS, associated to reasonable cost.
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Factor Estimulante de Colonias de Granulocitos y Macrófagos/administración & dosificación , Síndromes Mielodisplásicos/complicaciones , Neutropenia/terapia , Anciano , Anciano de 80 o más Años , Eritema/etiología , Femenino , Estudios de Seguimiento , Factor Estimulante de Colonias de Granulocitos y Macrófagos/efectos adversos , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Neutropenia/etiología , Neutrófilos , PronósticoRESUMEN
We analyzed P glycoprotein (PGP) expression and its correlation with hematological parameters and outcome in 50 cases of newly diagnosed adult acute lymphoblastic leukemia (ALL). PGP expression was evaluated by flow cytometry using MRK16 monoclonal antibody (MoAb) and/or immunocytochemistry on marrow slides, using JSB1 MoAb. Thirty-two of the 50 patients (64%) were PGP positive by at least one of the two methods, which gave concordant results in 15 of the 18 cases in which they were both used. No correlation between PGP expression and clinical and hematological parameters including WBC counts, immunophenotype and karyotype was seen, although there was a trend for more frequent CD34 expression in PGP-positive cases. All patients were treated with intensive chemotherapy. We found no difference in complete remission (CR) rate, actuarial disease-free survival and survival in PGP-positive and PGP-negative cases. Our findings suggest that the clinical significance of PGP expression is less clear in ALL than in AML. Wider use of functional techniques of evaluation of mdr1 gene expression, which assess the 'pumping' activity of PGP, and their correlation with quantitative analysis of mdr1 mRNA and protein, would probably improve knowledge of the role of PGP in ALL. Analysis of other mechanisms of drug resistance, especially multidrug resistance-associated protein (MRP) expression, would also be useful.
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Adulto , Biomarcadores , Femenino , Citometría de Flujo , Humanos , Técnicas para Inmunoenzimas , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Pronóstico , Análisis de SupervivenciaRESUMEN
Conventional cytogenetic (CC) studies performed in multiple myeloma (MM) are difficult because of the low proliferation rate of plasma cells (PC). The purpose of this study was to compare results obtained by CC and by FISH for the detection of numeric chromosomal changes in patients with MM. PC DNA content, CC and interphase FISH analysis were performed on 29 consecutive patients with MM. Fifteen patients (control group) had known Cytogenetic abnormalities identified by CC. The other 14 patients (study group) had a normal karyotype but an abnormal DNA content. Bone marrow material prepared for CC or cytospin slides were probed with classical satellite III or alpha satellite DNA sequences for chromosomes 3, 7, 8, 9, 11 and 15 (chromosomes 3, 7, 9, 11, 15 probes for hyperdiploid patients and the chromosome 8 probe for hypodiploid patients). In the control group, an unexplained discrepancy between CC and FISH occurred for only one chromosome in one patient. Also in this group, four patients had only one abnormal cell by CC and the numeric changes in these patients were always confirmed by FISH analysis. In the study group, FISH analysis showed an abnormal result in all but one patient. From these data, we conclude that FISH improves the detection of cytogenetic abnormalities in multiple myeloma. Using commercially available DNA probes for the most frequent numeric changes and slides for CC or cytospin slides, we demonstrated abnormal cytogenetics by FISH in 28/29 patients. In further studies, use of FISH could permit a more accurate description of numeric changes and their prognostic value in MM as well as an approach to clonal evolution. It would also be of interest in the study of monoclonal gammopathies of undetermined significance.
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Aneuploidia , Mieloma Múltiple/genética , Adulto , Anciano , Femenino , Humanos , Hibridación Fluorescente in Situ , Interfase/genética , Masculino , Persona de Mediana EdadRESUMEN
Two main types of therapy-related acute myeloid leukemias (tAML) and myelodysplastic syndromes (tMDS) have been described. The first classical type typically occurs late after use of alkylating agents and presents as MDS with -7/del 7q and/or -5/del5q. The second form occurs early after the use of agents targeted at topoisomerase II, and presents as AML with 11q23 or other rearrangements of de novo AML. Recently, we and others reported, in AML and MDS, a strong correlation between cytogenetic rearrangements leading to 17p deletion, a specific type of dysgranulopoiesis and p53 mutation; several of those cases of 17p- syndrome were therapy-related. Over the last 15 years, we observed 25 cases of tAML and tMDS with 17p deletion, which represented 36% of the AML and MDS with 17p deletion diagnosed during that period. Median age was 59 years. Twenty-one patients had tMDS and four tAML. Typical dysgranulopoiesis and p53 mutation and/or overexpression were seen in 22 of 24 and 16 of 19 evaluable patients, respectively. 17p deletion resulted from unbalanced translocations involving 17p (18 cases), monosomy 17 (five cases), i(17q) (one case) or del 17p (one case). Twenty-one patients also had -5/del 5q, and/or -7/del 7q. Median interval from treatment of the first tumor of tAML and tMDS was 94 months (range 19-252). Median survival was only 7 months. Based on primary tumor and antineoplastic agents used, patients could be relatively well divided into two groups: a first group of 11 cases, occurring mainly after a lymphoid neoplasm (eight cases) treated by chemotherapy with an alkylating agent (10 cases), and a second group of 14 cases occurring after essential thrombocythemia (ET) or polycythemia vera (PV) treated mainly by hydroxyurea (10 cases), pipobroman (eight cases), 32P (six cases) but rarely by alkylating agents (two cases). -7/del 7q was found in 10 of the 11 patients in the first group, as compared to three of the 14 patients of the second group (P = 0.0001). Therefore, therapy-related cases represent a high proportion of AML and MDS with the 17p- syndrome. They have many features in common with classical tMDS and tAML, including long interval from the first tumor, a usual preleukemic phase, and frequent occurrence of -5/del 5q. About one half of them, in addition, occur after alkylating agents and generally carry -7/del 7q. The other half, however, occur mainly after ET or PV treated by hydroxyurea or other non-alkylating agents, and usually have no -7/del 7q. These findings bring further support to a possible relationship between prior drugs used and cytogenetic rearrangements in tAML and tMDS.