RESUMEN
In a previous survey of newly diagnosed haematological malignancies (HMs) in Sardinia from 1974 to 1993, we observed a marked increase in the incidence of many HMs that we chiefly attributed to improvements in case ascertainment. To better define the nature of this increase, we extended the survey by an additional decade (1994-2003), applying the same previously used methods. The incidence of HMs further increased from 1994 to 2003. The incidence rate of total HMs (THMs), standardised to the world population, was 30.15 × 10(5) person-years vs. 21.58 from 1984 to 1993 and 15.26 from 1974 to 1983. The temporal variations in the incidence differed in different HMs and were correlated with the diseases clinical characteristics and the increased availability of diagnostic tools and skills in Sardinia. These observations support the hypothesis that the temporal differences in the incidence rates observed for many HMs in Sardinia over the 30-year survey period were caused by temporal differences in diagnostic efficiency rather than by disease occurrence. An important exception was the increase in non-Hodgkin's lymphoma, which represents a true increase in occurrence, similarly to most Western countries. The incidence rates of HMs already having or reaching stable values in the decade 1994-2003 were similar to those of most Western countries. No significant evidence emerged to suggest that Sardinian particularities influenced the occurrence of HMs. This study demonstrates the extent to which diagnostic efficiency can influence incidence evaluations and emphasises the importance of prolonged observation to determine the validity of incidence rates for both temporal and geographic comparisons.
Asunto(s)
Neoplasias Hematológicas/epidemiología , Adulto , Distribución por Edad , Anciano , Femenino , Neoplasias Hematológicas/diagnóstico , Humanos , Incidencia , Italia/epidemiología , Masculino , Persona de Mediana Edad , Morbilidad/tendencias , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/epidemiología , Trastornos Mieloproliferativos/diagnóstico , Trastornos Mieloproliferativos/epidemiología , Distribución por Sexo , Factores de TiempoRESUMEN
We have collected, by an active retrospective survey, all the cases of hematologic malignancies (HM) newly diagnosed during the time period 1974-1993 in the resident population of Sardinia. Diagnosis was deemed valid, after consultation of clinical records, in more than 90% of the 7264 collected cases. The number of newly diagnosed cases by year more than doubled during the 20-year period investigated. This striking increase can be only partially accounted for by ageing of population. Indeed, age-specific and age-adjusted rates of most of HM increased during this period, although Hodgkin Disease (HD), Chronic Myeloid Leukemia (CML) and Acute Lymphoblastic Leukemia (ALL) were notable exceptions. The observed increase in rates is likely, in a large part, to be fictitious, due to easier access to a health care system, which in the meantime, improved its diagnostic efficiency. This was particularly evident for Chronic Lymphocytic Leukemia (CLL), Multiple Myeloma (MM) and some others myelo- and lympho-proliferative disorders, but its relevance declined after 1984-1989. A likely true increase in occurrence was evidenced for Non-Hodgkin Lymphomas (NHL) and similarly, although to a lesser extent and more doubtful, for Myelodysplasias (MDS) and Acute Myeloid Leukemia (AML). At the end of the studied period each type of HM presented age and sex distributions and age-adjusted rates that show only minor differences from those reported for other western countries. No argument emerged to suggest that any genetic peculiarities of the Sardinian population might have affected the occurrence of HM. The confounding effects of improved diagnostic efficiency have prevented a reliable assessment of influence on incidences of environmental and socio-economic changes that, in relatively recent times, have occurred in Sardinia.
Asunto(s)
Neoplasias Hematológicas/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , Niño , Preescolar , Femenino , Neoplasias Hematológicas/clasificación , Neoplasias Hematológicas/diagnóstico , Humanos , Incidencia , Lactante , Recién Nacido , Italia/epidemiología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Distribución por Sexo , Factores de TiempoRESUMEN
In all, 134 elderly patients (median age 66 years, range 60-75 years) with newly diagnosed acute promyelocytic leukemia (APL) were enrolled in two successive protocols of the Italian multicenter group GIMEMA. All patients received an identical induction with all-trans retinoic acid and idarubicin; 116 (86%) entered complete remission (CR), two (2%) were resistant and 16 (12%) died during induction. After CR, 106 patients received further therapy whereas 10 did not, because of refusal (n=5) or toxicity (n=5). Consolidation consisted of three chemotherapy courses in the AIDA protocol (AIDA, 67 patients) or, since 1997, of an amended protocol including only the first cycle (amended AIDA, aAIDA, 39 patients). In the AIDA group, 43 patients (64%) completed consolidation, while seven (11%) and 17 (25%) patients were withdrawn after first and second courses, respectively; nine patients (13%) died in CR and 12 (18%) relapsed. In the aAIDA group, all patients received the assigned treatment; two patients (5%) died in CR and six (15%) relapsed. In the AIDA and aAIDA series, the 3-year overall and discase-free survival rates were 81 and 83% (P=NS), 73 and 72% (P=NS), respectively. We highlight here the frequency and severity of complications linked to intensive chemotherapy in this clinical setting and suggest that, in APL of the elderly, less intensive postremission therapy allows significant reduction of severe treatment-related toxicity and may be equally effective.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Idarrubicina/uso terapéutico , Leucemia Promielocítica Aguda/tratamiento farmacológico , Tretinoina/uso terapéutico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Femenino , Humanos , Idarrubicina/efectos adversos , Leucemia Promielocítica Aguda/genética , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , ARN Mensajero/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Inducción de Remisión , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de Supervivencia , Resultado del Tratamiento , Tretinoina/efectos adversosRESUMEN
The objective of the study was to evaluate the incidence, characteristics, treatment and outcome of acute megakaryoblastic leukemia (AMeL) in patients enrolled in GIMEMA trials. Between 1982 and 1999, 3603 new consecutive cases of AML aged over 15 years were admitted to GIMEMA trials. Of them, 24 were AMeL. The incidence of AMeL among AML patients enrolled in GIMEMA trials was 0.6% (24/3603). Diagnosis was based on morphological criteria. Out of 11 cytogenetic studies performed two presented chromosome 3 abnormalities. Twelve patients (50%) reached a CR, five (21%) died in induction and seven (27%) were unresponsive. The median duration of CR was 35 weeks (range 10-441). Seven patients underwent transplantation procedures (1 BMT, 4 aBMT, 2 aPBSCT). Four patients died in CR due to chemotherapy-related complications. Comparing the CR rate between AMeL and the other cases of AML enrolled in GIMEMA trials, no differences were observed. These results were mirrored for different age groups. The median survival was 40 weeks. At present, after a follow-up of a minimum of 2 years, only two patients are alive in CR, all the others having died. A 5-year Kaplan-Meier curve shows a disease-free survival of 17% and an actuarial overall survival of 10%. AMeL is a rare form of AML. The CR duration and the overall survival in this group of patients are very poor, even if similar to those observed in other AML. Furthermore, a high number of deaths in CR were observed. On the basis of these data, a specific therapeutic approach, possibly with innovative treatments, should be evaluated.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea , Leucemia Megacarioblástica Aguda/terapia , Adolescente , Adulto , Anciano , Niño , Terapia Combinada , Análisis Citogenético , Femenino , Humanos , Inmunofenotipificación , Leucemia Megacarioblástica Aguda/mortalidad , Leucemia Megacarioblástica Aguda/patología , Persona de Mediana Edad , Inducción de Remisión , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVES: Fludarabine (FAMP) is the most active single agent in relapsed and refractory patients with B-cell chronic lymphocytic leukemia (B-CLL). However, it is not clear whether it should be used immediatly after failure of chlorambucil (CLB). We addressed such an issue retrospectively analyzing a series of patients in whom FAMP was used as third-line therapy after a sequential use of CLB and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or CHOP-like regimen, respectively. DESIGN AND METHODS: On a retrospective basis, 57 B-CLL patients fulfilling the above mentioned criteria and followed-up in seven different hematologic institutions, were evaluated. RESULTS: Of 57 patients who were evaluated for response, 3 (5.2%) achieved a complete response (CR), 30 (52.6%) had a partial response (PR) and the remaining 24 (42.1%) failed to respond to FAMP. Overall median survival from the start of FAMP therapy was 30 months. Survival by tumor response did not show any difference between responders and non-responders (p = 0.536). The survival was significantly shorter in the group of patients with progressive disease than in all other patients included in our study (p = 0.05). Using each patient as his own control (McNemar test) we attempted to evaluate the value of FAMP in inducing a therapeutic response after failure of previous therapies. Among the 37 patients resistant to CLB the response rate was 40.3% with FAMP (p = 0.037) and only 17.5% with CHOP (p = 1.0). Among 35 patients resistant to a CHOP-like regimen, the response rate was 29.8% (p = 0.066) after FAMP therapy. INTERPRETATION AND CONCLUSIONS: From our results, it seems that FAMP works better than a CHOP-like regimen in patients resistant to CLB although results do not translate into a survival advantage for responders.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Clorambucilo/administración & dosificación , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Prednisona/administración & dosificación , Vidarabina/administración & dosificación , Vincristina/administración & dosificación , Adulto , Anciano , Resistencia a Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Vidarabina/análogos & derivadosRESUMEN
INTRODUCTION: Although definite risk classes are well known, risk-adapted modulation of first-line therapy is seldom attempted in adult ALL. So, a prospective validation of the therapeutic efficacy of a protocol (or a component thereof) in specific risk groups is uncommon. MATERIALS AND METHODS: From 1996-1999 a risk-oriented program (08/96) was evaluated in 102/121 unselected patients (median age 35 years, blast count 0-450 x 10(9)/l, 100 B(lin) (lineage), 21 T(lin)) responsive to induction therapy. The standard risk (SR) class was B(lin) CD10+ Ph- with blasts < 10 x 10(9)/l (prior studies: disease-free survival (DFS) rate 52% at five years with dose-intensive anthracycline-containing programs). The SR protocol was therefore anthracycline-rich (early consolidation cycles with total idarubicin 96 mg/m2), and comprised long-term maintenance. High-risk (HR) patients were eligible to the following three options: allogeneic hematopoietic stem cell transplantation (HSCT) from related family donor; short sequence with high-dose cyclophosphamide-cytarabine-methotrexate followed by melphalan/total body irradiation with autologous HSCT; or T(lin) ALL chemotherapy regimen inclusive of high-dose cytarabine and methotrexate. RESULTS: Treatment realization and three-year DFS rates according to risk class, HR subset and postremission treatment intensity were the following. SR group (n = 28): realization rate 93%, DFS 68.5%. HR group (n = 74): realization rate 80%, DFS 39% (P = 0.052 vs SR category). In HR group, three-year DFS rates by disease subtype were the following. B(lin) Ph- (n = 35) 43%; Ph+ (n = 19) 13% at 2.7 years (P = 0.006 vs other HR subtypes); T(lin) (n = 18) 59.5%. And DFS rates by treatment intensity were: allograft (n = 21) 40%; autograft (n = 28) 27%; shift to SR protocol (n = 13) 52% (P = ns vs allograft/autograft); T(lin) program (n = 10) 57%. Matched analyses of treatment protocols and disease subtypes suggested a possible therapeutic role of the autograft regimen in B(lin) Ph- ALL with a blast count < 25 x 10(9)/l, and of T(lin) protocol for T(lin) ALL. Comparisons with retrospective control cohorts were confirmatory of anthracycline activity in SR subclass. CONCLUSION: The intended strategy was applicable to the majority of study patients, confirming the value of anthracyclines in SR class and, preliminarily, the usefulness a T(lin)-specific treatment. Apart from the case of Ph+ ALL, the indications for high-dose procedures with HSCT remains largely undetermined in this study.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Anciano , Antineoplásicos/administración & dosificación , Ciclofosfamida/administración & dosificación , Citarabina/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Humanos , Idarrubicina/administración & dosificación , Masculino , Melfalán/administración & dosificación , Metotrexato/administración & dosificación , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Factores de Riesgo , Trasplante Homólogo , Irradiación Corporal TotalRESUMEN
BACKGROUND AND OBJECTIVES: The reasons for the worldwide increase in non-Hodgkin's lymphoma (NHL) are not clearly understood. We investigated whether an increasing trend over time has also occurred in the Italian region of Sardinia, the population of which exhibits peculiar genetic features, due to millenary isolation and pressure from 2,500 years of malarial endemism. We also investigated the geographic variation in NHL risk within the region. DESIGN AND METHODS: We designed a descriptive epidemiology study of NHL among the Sardinian population by following up the incidence of this disease in the period 1974-1993. We calculated the standardized incidence rate (SIR) of NHL by year for the total population and by gender. The time trend of Hodgkin's disease (HD) was also evaluated as a comparison term and for validation purposes. We also mapped NHL risk in the 361 administrative units (communes) of the region. RESULTS: NHL incidence in the Sardinian population over the whole study period was 7.5 x 10(-5) year(-1) (men: 8.2; women: 6.7), and increased from 4.1 in 1974 to 9.1 in 1993. The increasing trend was consistent by gender, and mostly affected subjects aged 55 years or older. Nodal and extra-nodal forms of NHL shared the same pattern of increasing incidence. Excluding the few NHL cases related to AIDS did not change the results. No such pattern was observed for HD incidence. The NHL incidence rate (age > or = 25 years) ranged from 0.0-60.0 x 10(-5) year-1 across communes. Areas at risk were located mainly in the northern part of the region, but risk among men was also elevated in the major urban area in southern Sardinia. INTERPRETATION AND CONCLUSIONS: Our study shows that NHL incidence increased 2.2-fold in Sardinia from 1974 to 1993, a finding which is consistent with other world-wide report. The risk has risen in a few areas, mainly in central and northern Sardinia and in the major urban areas. Analytic studies are under way to investigate a broad range of risk factors, including viral, occupational, and environmental factors, that might account for our results.
Asunto(s)
Enfermedad de Hodgkin/epidemiología , Linfoma no Hodgkin/epidemiología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Italia , Masculino , Persona de Mediana Edad , Factores Sexuales , Topografía MédicaRESUMEN
One hundred consecutive patients with severe aplastic anemia (SAA) received horse antilymphocyte globulin (ALG), cyclosporin A (CyA), 6-methylprednisolone (6Mpred), and granulocyte colony-stimulating factor (G-CSF) as first-line therapy. The median age was 16 years (range, 1-72 years) and median neutrophil count was 0.2 x 10(9)/L (range, 0-0.5 x 10(9)/L). Trilineage hematologic recovery (at a median interval of 96 days from treatment) was seen in 77 patients (48 complete, 29 partial) after 1 (n = 50) or more courses of ALG (n = 27). Of the 23 nonresponders, 11 patients died at a median interval of 83 days (range, 16-1132 days), 6 were considered treatment failures and underwent transplantation, and 6 were pancytopenic. Cytogenetic abnormalities were seen in 11% of patients, clonal hematologic disease in 8%, and relapse of marrow aplasia in 9%. The actuarial survival at 5 years was 87% (median follow-up 1424 days): 76% versus 98% for patients with neutrophil counts less than versus greater than 0.2 x 10(9)/L (P =.001) and 88% versus 87% for patients aged less than versus more than 16 years (P =.8). The actuarial probability of discontinuing CyA was 38%. Patients who did not achieve a white blood cell (WBC) count of 5 x 10(9)/L during G-CSF treatment have a low probability of responding (37%) and a high mortality rate (42%). This update confirms a high probability for SAA patients of becoming transfusion independent and of surviving after treatment with ALG, CyA, 6Mpred, and G-CSF, with a significant effect of neutrophil counts on outcome. Problems still remain, such as absent or incomplete responses, clonal evolution, relapse of the original disease, and cyclosporine dependence. Early transplantation, also from alternative donors, may be warranted in patients with poor WBC response to G-CSF. (Blood. 2000;95:1931-1934)
Asunto(s)
Anemia Aplásica/tratamiento farmacológico , Suero Antilinfocítico/administración & dosificación , Ciclosporina/administración & dosificación , Glucocorticoides/administración & dosificación , Factor Estimulante de Colonias de Granulocitos y Macrófagos/administración & dosificación , Inmunosupresores/administración & dosificación , Prednisolona/administración & dosificación , Adolescente , Adulto , Anciano , Anemia Aplásica/mortalidad , Niño , Preescolar , Quimioterapia Combinada , Femenino , Glicosilfosfatidilinositoles/metabolismo , Humanos , Lactante , Masculino , Persona de Mediana Edad , Recurrencia , Factores de TiempoRESUMEN
In the present study we examined gene expression and glucose-6-phosphate dehydrogenase (G6PD) activity in leukemic cells isolated from G6PD normal and deficient subjects. The results have shown that G6PD activity strongly increases in G6PD normal leukemic cells as well as in G6PD deficient leukemic cells when compared to peripheral blood mononuclear cells (PBMC). Higher levels of G6PD gene expression were observed in leukemic cells from G6PD deficient patients compared to G6PD normal. A similar pattern of gene expression was also observed for 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase. These results support the hypothesis that G6PD deficient cell, in order to sustain their growth, must respond to the low activity of their mutant enzyme with an increase in quantity through an induction of gene expression.
Asunto(s)
Expresión Génica , Deficiencia de Glucosafosfato Deshidrogenasa/enzimología , Glucosafosfato Deshidrogenasa/metabolismo , Leucemia/enzimología , Adulto , Células Cultivadas , Humanos , Hidroximetilglutaril-CoA Reductasas/metabolismo , Leucemia/metabolismo , Leucocitos Mononucleares/enzimología , Leucocitos Mononucleares/metabolismo , Masculino , Reacción en Cadena de la Polimerasa , ARN Mensajero/metabolismo , Receptores de LDL/metabolismoRESUMEN
Two hundred fifty-three patients with newly diagnosed acute promyelocytic leukemia (APL) were eligible to enter the multicentric GIMEMA-AIEOP "AIDA" trial during the period July 1993 to February 1996. As a mandatory prerequisite for eligibility, all patients had genetic evidence of the specific t(15;17) lesion in their leukemic cells confirmed by karyotyping or by reverse transcription-polymerase chain reaction (RT-PCR) of the PML/RAR alpha fusion gene (the latter available in 247 cases). Median age was 37.8 years (range, 2.2 to 73.9). Induction treatment consisted of oral all-trans retinoic acid (ATRA), 45 mg/m2/d until complete remission (CR), given with intravenous Idarubicin, 12 mg/m2/d on days 2, 4, 6, and 8. Three polychemotherapy cycles were given as consolidation. Hematologic and molecular response by RT-PCR was assessed after induction and after consolidation. At the time of analysis, 240 of the 253 eligible patients were evaluable for induction. Of these, 11 (5%) died of early complications and 229 (95%) achieved hematologic remission. No cases of resistant leukemia were observed. Of 139 cases studied by RT-PCR after induction, 84 (60.5%) were PCR-negative and 55 (39.5%) PCR-positive. One hundred sixty-two patients were evaluable by RT-PCR at the end of consolidation. Of these, 159 (98%) tested PCR-negative and 3 (2%), PCR-positive. After a median follow up of 12 months (range, 0 to 33), the estimated actuarial event-free survival for the whole series of 253 eligible patients was 83% +/- 2.6% and 79% +/- 3.2% at 1 and 2 years, respectively. This study indicates that the AIDA protocol is a well-tolerated regimen that induces molecular remission in almost all patients with PML/RAR alpha-positive APL. Preliminary survival data suggest that a remarkable cure rate can be obtained with this treatment.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Médula Ósea/química , Leucemia Promielocítica Aguda/tratamiento farmacológico , Proteínas de Neoplasias/análisis , Proteínas de Fusión Oncogénica/análisis , Adolescente , Adulto , Anciano , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Médula Ósea/patología , Niño , Preescolar , Cromosomas Humanos Par 15/genética , Cromosomas Humanos Par 15/ultraestructura , Cromosomas Humanos Par 17/genética , Cromosomas Humanos Par 17/ultraestructura , Supervivencia sin Enfermedad , Femenino , Humanos , Idarrubicina/administración & dosificación , Idarrubicina/efectos adversos , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/mortalidad , Leucemia Promielocítica Aguda/patología , Leucocitosis/inducido químicamente , Masculino , Persona de Mediana Edad , Neoplasia Residual , Reacción en Cadena de la Polimerasa , Estudios Prospectivos , Inducción de Remisión , Síndrome , Translocación Genética , Resultado del Tratamiento , Tretinoina/administración & dosificación , Tretinoina/efectos adversosRESUMEN
The outcome of a cohort of 218 consecutive patients who failed to respond to a single course of standard daunorubicin plus ARAC (three + seven) induction regimen has been retrospectively evaluated to assess the characteristics of this group of AML patients and the effectiveness of second-line induction programs. Seventy-four of the 218 patients (33.9%) attained complete remission with salvage chemotherapies. The multivariate analysis of pretherapy characteristics of the patients showed that peroxidase positivity and age were the most important factors in determining whether or not the patient would have a favorable response to second-line induction regimen. In addition, comparison of marrow characteristics at diagnosis with those of marrow after the first-line therapy (marrow leukemic index, MLI) provided the greatest differences between second-line CR and resistant patients. Finally, peroxidase positivity and MLI predicted for remission duration and overall survival. Allogeneic BMT, however, appeared the most important factor for survival and event-free survival of remitting patients. These results are of importance when considering that better defined prognostic factors provide an objective rationale for selecting appropriate strategies for the treatment of patients who do not respond to a single course of induction regimen.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea , Leucemia Mieloide/tratamiento farmacológico , Leucemia Mieloide/cirugía , Enfermedad Aguda , Terapia Combinada , Citarabina/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Inducción de Remisión , Estudios Retrospectivos , Terapia Recuperativa , Resultado del TratamientoRESUMEN
The Leukemia Cooperative Groups of the EORTC and the GIMEMA conducted a prospective randomized phase III trial, in order to assess the value of autologous BMT (ABMT) vs a second intensive consolidation course (IC2), following a common intensive consolidation course (IC1) for patients with AML. Patients with an HLA-identical sibling donor were not randomized, but were included in an allogeneic BMT (alloBMT) program. This is an analysis of prognostic factors which influence the outcome of treatment after alloBMT in first complete remission (CR). The study included 730 patients < 46 years of age in CR, 270 having a histocompatible sibling donor. In 169 of these patients alloBMT was performed in first CR. Early remitters (122 patients achieving CR with one course of treatment) had a DFS at 3 years of 67%, significantly longer than that of 44% for late remitters (47 patients achieving CR after more than one course of treatment) (P = 0.006). The relapse risk for early vs late remitters was 16 and 40% at 3 years (P = 0.001) and the treatment-related mortality (TRM) at 2 years was 21 vs 27%. Age appeared to be a prognostic factor for TRM, WBC for DFS, whereas the FAB classification was not of prognostic importance. Patients with poor risk cytogenetic abnormalities showed a trend towards a higher relapse risk. Patients transplanted shortly after achieving CR appeared to have a worse prognosis than those transplanted further into remission. Overall, the number of courses of induction therapy needed to achieve CR was the most important prognostic factor for outcome after allogeneic BMT.
Asunto(s)
Trasplante de Médula Ósea , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Aberraciones Cromosómicas , Femenino , Humanos , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/genética , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Acondicionamiento Pretrasplante , Trasplante HomólogoRESUMEN
Patients with severe aplastic anemia (SAA) and a neutrophil (PMN) count of less than 0.5 x 10(9)/L are exposed to a high risk of early mortality when treated with antilymphocyte globulin (ALG) and steroids, with the major problem being infectious complications. The addition of human recombinant granulocyte colony-stimulating factor (rhG-CSF) to ALG may reduce early mortality by improving neutrophil counts in the short term. To test the feasibility of this approach, the SAA Working Party of the European Group for Blood and Marrow Transplantation (EBMT) designed a pilot study that included rhG-CSF (5 micrograms/kg/d, days 1 through 90), horse ALG (HALG; 15 mg/kg/d, days 1 through 5), methylprednisolone (2 mg/kg/d, days 1 through 5, then tapering the dose), and cyclosporin A (CyA; 5 mg/kg/d orally, days 1 through 180). Patients with newly diagnosed acquired SAA (untreated) and with neutrophil counts of < or = 0.5 x 10(9)/L were eligible. Forty consecutive patients entered this study and are evaluable with a minimum follow up of 120 days: the median age was 16 years (range, 2 to 72 years), the interval from diagnosis to treatment was 24 days, and the median PMN count was 0.19 x 10(9)/L. Twenty-one patients had hemorrhages, and 19 were infected at the time of treatment. Overall, treatment was well tolerated: the median maximum PMN count during rhG-CSF administration was 12 x 10(9)/L (range, 0.4 x 10(9)/L to 44 x 10(9)/L). There were three early deaths (8%) due to infection. Four patients (10%) showed no recovery, whereas 33 patients (82%) had trilineage hematologic reconstitution and became transfusion-independent at a median interval of 115 days from treatment. Median follow up for surviving patients is 428 days (range, 122 to 1,005). Actuarial survival is 92%: 86% and 100% for patients with PMN counts less than 0.2 x 10(9)/L or between 0.2 x 10(9)/L and 0.5 x 10(9)/L, respectively. This study suggests that the addition of rhG-CSF to ALG and CyA is well tolerated, is associated with a low risk of mortality, and offers a good chance of hematologic response. This protocol would appear to be an interesting alternative treatment for SAA patients with a low PMN count who lack an HLA-identical sibling.
Asunto(s)
Anemia Aplásica/terapia , Suero Antilinfocítico/uso terapéutico , Ciclosporina/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Análisis Actuarial , Adolescente , Adulto , Anciano , Anemia Aplásica/mortalidad , Transfusión Sanguínea , Niño , Preescolar , Terapia Combinada , Estudios de Factibilidad , Femenino , Humanos , Leucaféresis , Masculino , Persona de Mediana Edad , Neutropenia/prevención & control , Neutrófilos/efectos de los fármacos , Proyectos Piloto , Prednisolona/uso terapéutico , Proteínas Recombinantes/uso terapéutico , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
We report the case of a young female patient, a Jehovah's witness, affected by peroxidase-positive acute leukemia. The patient, completely aware of the risks both of the disease and of the usual treatment for acute myeloid leukemia, refused any transfusional support. An atypical treatment plan with low hematological toxicity but also with reduced probability of positive results was therefore proposed and accepted. Initial treatment with vincristine and prednisone induced remission; therapy was then continued for 32 months with monthly cycles of aracytin and 6-thioguanine, at accurately tailored dosages to avoid excessive hematological toxicity. The patient never needed blood support and never suffered infectious or hemorrhagic events. She is still in remission, 11 years off-therapy. The ethical and legal aspects of treatment decisions in such situations are discussed. In the author's opinion, neither withholding all treatment nor insisting on standard measures is correct: on the contrary, as always, treatment in such cases must be tailored on the patient's needs, which include not only his physical condition but his religious beliefs as well.
Asunto(s)
Cristianismo , Leucemia Mieloide Aguda/terapia , Adulto , Transfusión Sanguínea , Femenino , Humanos , Inducción de Remisión/métodos , Factores de TiempoRESUMEN
In this study serum cholesterol was measured in different types of human hematologic malignancies characterized by a wide range of cell proliferation. In all tumoral types a significant decrease of HDL cholesterol was observed, whereas total serum cholesterol generally remained unchanged. Another interesting observation of our study was the apparent inverse correlation between the extent of cell proliferation in these neoplastic disorders and the level of HDL cholesterol. Since a decrease of HDL cholesterol was previously observed, in our laboratory, in different experimental models of normal and neoplastic cell proliferation, we suggest that the decrease of HDL cholesterol may be a generalized phenomenon related to massive cellular growth in normal and malignant processes.
Asunto(s)
HDL-Colesterol/sangre , Colesterol/sangre , Enfermedades Hematológicas/sangre , Neoplasias/sangre , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana EdadRESUMEN
In the present study, lipoprotein metabolism was investigated during compensatory hyperplasia of bone marrow after haemolysis induced by phenylhydrazine (20 mg/kg b.w.) administration in rats. The rats were sacrificed at different time intervals (0, 1, 2 and 5 days) after phenylhydrazine treatment. Analysis of the different fractions of lipoproteins has shown that during bone marrow hyperplasia there is an alteration of lipoprotein profiles, mainly due to a decrease of HDL2 and HDL3 subfractions.
Asunto(s)
Médula Ósea/patología , HDL-Colesterol/sangre , Animales , Hemólisis/efectos de los fármacos , Hiperplasia/sangre , Masculino , Fenilhidrazinas , Ratas , Ratas EndogámicasAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Adolescente , Adulto , Citarabina/administración & dosificación , Daunorrubicina/administración & dosificación , Etopósido/administración & dosificación , Humanos , Italia/epidemiología , Leucemia Mieloide Aguda/mortalidad , Tablas de Vida , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Inducción de Remisión , Tasa de Supervivencia , Tioguanina/administración & dosificaciónRESUMEN
Philadelphia (Ph) chromosome-positive chronic myelogenous leukaemia (CML) was studied in a subject heterozygous for the X chromosome-linked alloenzyme system of glucose-6-phosphate dehydrogenase (G6PD). Determination of G6PD mosaicism showed homogeneous expression in granulocytes, erythrocytes and platelets. Cytogenetic studies showed the typical Ph translocation in all metaphases from bone marrow and peripheral blood myeloid cells, bcr rearrangement was detected in bone marrow and in granulocytes. B cells were stimulated with Epstein-Barr virus (EBV) in order to evaluate involvement of lymphocytes, EBV-transformed lymphoblastoid cells expressed a single G6PD phenotype and therefore probably derived from the leukaemic stem cell. However they had a normal karyotype and a constitutional bcr restriction pattern. Molecular analysis in this case of CML clarifies the differentiative potential of cells belonging to the leukaemic clone, by demonstrating that clonal Ph-negative B cells maintain normal differentiative capacity and have a bcr gene sequence which is not rearranged.