RESUMO
The incidence of cytomegalovirus (CMV) reactivations in patients with multiple myeloma (MM) receiving autologous stem cell transplantation (ASCT) is relatively low. However, the recent increased use of novel agents, such as bortezomib and/or immunomodulators, before transplant, has led to an increasing incidence of Herpesviridae family virus infections. The aim of the study was to establish the incidence of post-engraftment symptomatic CMV reactivations in MM patients receiving ASCT, and to compare this incidence with that of patients treated with novel agents or with conventional chemotherapy before transplant. The study was a survey of 80 consecutive patients who underwent ASCT after treatment with novel agents (Group A). These patients were compared with a cohort of 89 patients treated with VAD regimen (vincristine, doxorubicin, and dexamethasone) before ASCT (Group B). Overall, 7 patients (4.1%) received an antiviral treatment for a symptomatic CMV reactivation and 1 died. The incidence of CMV reactivations was significantly higher in Group A than in Group B (7.5% vs. 1.1%; P = 0.048). When compared with Group B, the CMV reactivations observed in Group A were significantly more frequent in patients who received bortezomib, whether or not associated with immunomodulators (9.4% vs. 1.1%; P = 0.019), but not in those treated with immunomodulators only (3.7% vs. 1.1%; P = 0.396). These results suggest that MM patients treated with bortezomib-based regimens are at higher risk of developing a symptomatic CMV reactivation after ASCT.
Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ácidos Borônicos/uso terapêutico , Infecções por Citomegalovirus/epidemiologia , Hospedeiro Imunocomprometido , Mieloma Múltiplo/terapia , Pirazinas/uso terapêutico , Transplante de Células-Tronco , Adulto , Idoso , Bortezomib , Estudos de Casos e Controles , Estudos de Coortes , Infecções por Citomegalovirus/imunologia , Dexametasona/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Incidência , Quimioterapia de Indução , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Transplante Autólogo , Vincristina/uso terapêuticoRESUMO
BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, a common mutation of the gene encoding the enzyme that catalyzes reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a carbon donor in the metabolism of folate, determines a striking reduction in the enzyme activity in carriers of mutation at homozygous status. PATIENTS AND METHODS: We retrospectively analyzed the incidence of MTHFR C677T and the influence of genotype on methotrexate (MTX) toxicity in patients with acute leukemia undergoing maintenance chemotherapy. Seventy-eight patients were analyzed and 61 were evaluable for toxicity. MTX toxicity was assessed on bone marrow, liver and mucosae. RESULTS: The incidence of the C677T mutation was as expected in the general Italian population with 23.08% of patients being TT, 38.46% of patients CT and 38.46% of patients CC. The TT genotype was significantly associated with an increase of toxicity during MTX administration. No specific pattern of toxicity was detected, although in TT patients myelosuppression and liver toxicity were more pronounced. CONCLUSIONS: TT genotype may indicate a need to reduce the dose of MTX during prolonged administration. Considering the high prevalence of homozygous individuals in the Italian population, pretreatment screening may be worthwhile.
Assuntos
Leucemia/tratamento farmacológico , Leucemia/genética , Dose Máxima Tolerável , Metotrexato/efeitos adversos , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Polimorfismo Genético , Adolescente , Adulto , Idoso , Criança , Relação Dose-Resposta a Droga , Feminino , Testes Genéticos , Homozigoto , Humanos , Masculino , Metotrexato/administração & dosagem , Metilenotetra-Hidrofolato Redutase (NADPH2) , Pessoa de Meia-Idade , Farmacogenética , Valor Preditivo dos Testes , Probabilidade , Estudos Retrospectivos , Medição de Risco , Sensibilidade e EspecificidadeRESUMO
Within 285 adult acute lymphoblastic leukemias (ALL) included in the multicenter GIMEMA 0496 trial and prospectively studied by conventional cytogenetics, 18 cases (6%) with long arm deletion of chromosome 6 (6q) were identified. These cases were divided into: (i) del(6q) only (n = 6); (ii) del(6q) plus other numerical and/or structural abnormalities (n = 8); (iii) del(6q) and other 'specific' translocations (n = 4). The biologic and clinical features of the patients carrying this anomaly, as well as their outcome, were compared with those of 267 patients without del(6q). A T cell phenotype was more frequently associated with del(6q) cases in general (P = 0.001) and particularly with cases presenting del(6q) as the isolated abnormality (P = 0.0027). No significant difference with respect to multidrug resistance (MDR)/P glycoprotein expression was observed between the two groups of patients (21% vs 28% of MDR-positive cases, respectively). A BCR-ABL fusion transcript was less frequently detected in cases with del(6q) (11%) compared with those without the anomaly (29%). p15 and p16 deletions were identified by Southern blot analysis in 21% of cases with del(6q) and in 26% of cases without del(6q). In this latter group, a T cell phenotype was less frequently associated with p15 and/or p16 deletion than in the group carrying del(6q) (36% vs 100% of cases, P = 0.011). Overall, patients with ALL and del(6q) had a high complete remission (CR) rate (83%); however, they had a lower 18 month event-free survival (31% vs 41%) and a higher relapse rate (70% vs 37%, P = 0.02) compared with patients without del(6q). To date, this is the largest series of adult ALL cases reported with del(6q) homogeneously treated, which have also been prospectively studied for MDR expression and for the detection of known fusion genes. This anomaly, as an isolated change, identifies a subset of cases with hyperleukocytosis (median WBC count 52 x 10(9)/l) and a strict correlation with a T cell phenotype. Overall, del(6q) seems to be associated with an unfavorable clinical outcome, although this finding will need to be confirmed by extended FISH analysis.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 6 , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Adulto , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Humanos , Cariotipagem , Fenótipo , Reação em Cadeia da Polimerase , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologia , PrognósticoRESUMO
Thrombotic thrombocytopenic purpura (TTP) is a severe disorder affecting the microcirculation of multiple organ systems. Plasma therapy has significantly reduced the mortality rate. Infections, pregnancy, cancers, drugs, and surgery were frequently associated with the initial episodes and relapses. Women who are either pregnant or in the postpartum period make up 10-25% of TTP patients, suggesting the interrelationship between TTP and pregnancy. The introduction of aggressive treatment with plasma transfusion or plasmapheresis improved maternal and fetal survival rates. We describe a case of a first successful pregnancy concomitant to a late relapse of TTP, in which the identification of important risk factors for both TTP and pregnancy allowed us easier hematological and obstetrical management. Proposed guidelines for pregnancy-related TTP management and a brief review of current treatment options for this rare condition are also included.
Assuntos
Complicações Hematológicas na Gravidez/prevenção & controle , Púrpura Trombocitopênica Trombótica/prevenção & controle , Adulto , Aspirina/administração & dosagem , Gerenciamento Clínico , Feminino , Heparina/administração & dosagem , Humanos , Guias de Prática Clínica como Assunto , Gravidez , Complicações Hematológicas na Gravidez/diagnóstico , Complicações Hematológicas na Gravidez/tratamento farmacológico , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Recidiva , Fatores de RiscoRESUMO
BACKGROUND AND OBJECTIVES: Recently, a chimeric monoclonal antibody (MoAb) directed against the CD20 antigen (rituximab) has been successfully introduced in the treatment of several CD20-positive B-cell neoplasias and particularly of follicular lymphomas. Based on these premises we evaluated the efficacy and the toxicity of chimeric anti-CD20 monoclonal antibody (MoAb) in relapsed/progressed hairy cell leukemia (HCL). DESIGN AND METHODS: Ten patients with relapsed/progressed HCL entered the study. Eight patients were males and two females with a median age of 55 years (range 41-78) and all of them had been previously treated with 2-chlorodeoxyadenosine and/or deoxycoformycin and a-interferon. Two out of 10 patients were anemic (Hb < 10 g/dL), 4 thrombocytopenic (Plt < 100 x 10(9)/L), 3 had fewer than 1.0 x 10(9)/L neutrophils and 3 had circulating hairy cells (HC). All patients received 375 mg/m2 i.v. of anti-CD20 MoAb once a week for 4 doses. RESULTS: All patients were evaluable for response, one patient showing a complete remission and 4 a partial response. Adverse reactions, such as fever, chills, bone pain, hypotension and thrombocytopenia, were transient and mild (grade 1-2) and occurred only during the first course of treatment. One month after the last infusion, patients who had had anemia, neutropenia or thrombocytopenia, recovered normal peripheral blood values. Circulating HC also disappeared within one month. Immunostained bone marrow biopsies were checked 1, 3 and 6 months after the end of therapy and in 5 out of 10 patients a >50% reduction of bone marrow HC infiltration was recorded. INTERPRETATION AND CONCLUSIONS: On the basis of these preliminary results observed in 10 patients with progressed HCL, it appears that treatment with anti-CD20 MoAb is safe and effective in at least 50% of patients, particularly in those with a less evident bone marrow infiltration (50%) and in those previously splenectomized.
Assuntos
Anticorpos Monoclonais/farmacocinética , Anticorpos Monoclonais/uso terapêutico , Antígenos CD20/imunologia , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Leucemia de Células Pilosas/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Murinos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Rituximab , Equivalência Terapêutica , Resultado do TratamentoRESUMO
INTRODUCTION: One hundred-and-six adult cases of acute lymphoblastic leukemia were prospectively investigated using a highly sensitive interphase fluorescence in situ hybridization assay which utilizes DNA probes that detect a double BCR/ABL fusion signal (D-FISH) in cells carrying the t(9;22) to evaluate the reliability and specificity of this method for the detection of the Ph translocation. The results were compared with those obtained in the same cases by conventional cytogenetics and by reverse-transcription polymerase chain reaction. MATERIALS AND METHODS: The study was performed using DNA probes that span the common breakpoints of the t(9;22) translocation and that detect a double BCR/ABL fusion in cells carrying this karyotypic anomaly, one on the abnormal chromosome 9 and one on the Ph chromosome. RESULTS: Interphase D-FISH detected a high number of rearranged cases (22/106) compared to conventional cytogenetics (15/106) and RT-PCR (21/106). CONCLUSION: Interphase D-FISH emerges as a reliable, fast and relatively inexpensive tool for the detection of BCR/ABL rearrangements in adult ALL patients at diagnosis. It has a sensitivity clearly higher than conventional karyotyping and it may prove also superior to that of RT-PCR in cases with unusual BCR/ABL breakpoints. Our results suggest that D-FISH might be considered as the initial test for the diagnosis of Ph+ adult ALL.
Assuntos
Proteínas de Fusão bcr-abl/genética , Hibridização in Situ Fluorescente/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Translocação Genética/genética , Adolescente , Adulto , Análise Citogenética , Feminino , Proteínas de Fusão bcr-abl/análise , Rearranjo Gênico/genética , Humanos , Hibridização in Situ Fluorescente/normas , Interfase , Masculino , Pessoa de Meia-Idade , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Estudos Prospectivos , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e EspecificidadeAssuntos
Proteínas de Fusão bcr-abl/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Transcrição Gênica , Adulto , Terapia Combinada , Intervalo Livre de Doença , Proteínas de Fusão bcr-abl/análise , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodosRESUMO
Twenty-five patients (22 adults and 3 infants) with ALL1/AF4-positive acute lymphoblastic leukemia (ALL) were prospectively monitored by reverse transcriptase-polymerase chain reaction (RT-PCR) between January 1992 and July 1999. After high-dose induction and consolidation chemotherapy without bone marrow transplantation, all patients had a complete hematologic remission. Using nested RT-PCR (sensitivity 10(-4)), we observed conversion to PCR negativity in 11 (44%) of the patients. Thirteen of the 14 patients who did not have a molecular remission had a relapse at a median time of 4 months (range, 1 - 20 months). Of the 11 patients who had a conversion to PCR negativity, 5 reconverted to PCR positivity within 1 to 14 months. These 5 patients all progressed to hematologic relapse after 2, 3, 4, 4, and 7 months, respectively. Of the remaining 6 patients, 4 are in persistent hematologic and molecular remission at 12, 14, 88, and 96 months, whereas 2 are early in their follow-up. Actuarial probabilities of relapse and overall survival were 100% and 0% at 14 and 24 months and 67% and 43% at 96 and 100 months, respectively, in patients who had persistent RT-PCR positivity and in those who had a molecular remission. For both relapse and survival, the differences observed between the two groups were significant (P =.003 and P <.005, respectively). This study, which represents the first prospective analysis of residual-disease monitoring carried out in a substantial series of patients with t(4;11)-positive ALL, emphasizes the clinical relevance of RT-PCR-based methods to monitor minimal residual disease in this leukemia subset. (Blood. 2000;95:96-101)
Assuntos
Cromossomos Humanos Par 11 , Cromossomos Humanos Par 4 , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Translocação Genética , Adulto , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Lactente , Cariotipagem , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Estudos Prospectivos , Recidiva , Indução de Remissão , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de TempoRESUMO
Between July 1992 and June 1996, 901 new cases of adult acute lymphoblastic leukaemia were recorded in the GIMEMA Archive of Adult Acute Leukaemia; 21 of them (2.3%) had a previous primary malignancy (PM). We found that secondary acute lymphoblastic leukaemia cases (sALL) presented with older age, a high incidence of pre-pre-B immunophenotype and a significantly higher prevalence of cancer among relatives compared to de novo ALL. The leukaemogenic activity of the cytotoxic drugs employed for the treatment of PM may have played a potential role in only a proportion of patients, opening the possibility that some sALL patients may have developed two or more malignancies due to individual predisposing factors.
Assuntos
Segunda Neoplasia Primária/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: To provide cladribine (CdA) to physicians for the treatment of patients with previously treated or untreated hairy cell leukemia (HCL), and to determine the response rate, response duration, survival, and toxicity with this agent. PATIENTS AND METHODS: This Group C phase II study was open to all eligible patients whose primary physician obtained written permission from the National Cancer Institute (NCI) to register patients onto this protocol. Of 979 patients registered, 861 were assessable for response and 895 for toxicity. RESULTS: The complete remission (CR) rate was 50% and the partial remission (PR) rate was 37%. At a median follow-up of 52 months, 12% of patients were reported to have progressed and 62 (7%) have died of disease. CONCLUSION: This large experience confirms the excellent response rates and remission duration of CdA in patients with HCL. Nevertheless, the response rates in this setting, which approximates general clinical practice, were lower than in other series. In general, CdA was well tolerated, but the potential increased risk for secondary malignancies requires additional follow-up evaluation. CdA can now be considered as one of the best agents for the treatment of HCL.
Assuntos
Antineoplásicos/uso terapêutico , Cladribina/uso terapêutico , Leucemia de Células Pilosas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Cladribina/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/diagnóstico , Análise de SobrevidaRESUMO
Between 1983 and 1994 the incidence of secondary haematological neoplasms (SHM) was evaluated in 1170 new cases of ALL enrolled in the GIMEMA trials. Of the 942 patients who achieved complete remission (CR); seven developed a SHM: four AMLs and three NHLs. The median latency from onset of ALL and of secondary haematological neoplasm was 69 months for AML and 61 months for NHL. Three out of four patients with secondary AML were unresponsive to the new chemotherapy and died, whereas the fourth patient achieved a new CR. Among the three NHL cases, two patients are presently alive in CR, whereas the third patient was refractory to chemotherapy and died. The relative risk of haematological malignancy among the GIMEMA trials population, as compared to that of the Italian Cancer Registries, was 15.25-fold higher, and the actuarial estimated cumulative proportion of ALL patients with a secondary haematological neoplasm at 5 and 10 years were 0.59% and 3.63% respectively. The incidence of adult ALL who developed a SHM, although apparently lower than in the paediatric ALL series, was higher when compared to the normal population. The difference between paediatric and adult ALL is probably due to the lack of craniospinal radiotherapy and to the lower doses of epipodoxiphyllotoxins used in adult trials. The higher percentage of childhood ALL with a prolonged event-free survival could result in an increase of secondary neoplasms in these cases, which suggests that secondary haematological neoplasms in adult ALL patients are real, although rare, events.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Hematológicas/etiologia , Segunda Neoplasia Primária/induzido quimicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Idoso , Criança , Ensaios Clínicos como Assunto , Humanos , Pessoa de Meia-Idade , Indução de Remissão , Falha de TratamentoRESUMO
Fifty-seven patients aged < 55 years with acute lymphoblastic leukemia (ALL) in second or third bone marrow (BM) relapse or refractory to first-line therapy were enrolled in an Italian cooperative study. The ALL R-87 protocol included idarubicin (IDA) plus intermediate dose cytarabine (IDARA-C) and Prednisone (PDN) as induction, followed by a consolidation phase and BMT. Complete remission (CR) was achieved in 41/57 patients (72%). The CR rate was significantly higher in patients aged < 15 years at diagnosis and at time of treatment compared to those aged > or = 15 (84% vs 50%, p=0.01 and 85% vs 54%, p = 0.02, respectively). Nineteen of 41 responders (46.3%) underwent bone marrow transplant (BMT) (10 autologous and 9 allogeneic). The estimated probabilities of event free survival (EFS +/- SE) and survival +/- SE at 6 years were 0.13 +/- 0.05 and 0.20 +/- 0.06, respectively, for all enrolled patients. Univariate analysis showed that children had a better EFS rate compared to adults (0.16 +/- 0.07 vs 0.08 +/- 0.07, p = 0.014). The estimated probability of disease free survival (DFS +/- SE) at 6 years was 0.18 +/- 0.07 for all responders. No differences in DFS were observed between patients submitted to allogeneic or autologous BMT (0.33 +/- 0.16 vs 0.25 +/- 0.15). Among patients treated in second or third relapse, a first CR length > or = 48 months favorably influenced both DFS (p = 0.014) and EFS (p = 0.018). Our results show the efficacy of the intermediate dose ARA-C plus IDA schedule for high risk adult and childhood ALL patients. No differences in disease outcome were observed between allogeneic and autologous BMT.
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Criança , Pré-Escolar , Citarabina/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Idarubicina/administração & dosagem , Lactente , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prednisona/administração & dosagem , Recidiva , Indução de Remissão , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVE: The anthracycline analogue idarubicin, either alone or in combination with other antineoplastic drugs, has shown antileukemic activity in relapsed and refractory acute lymphoblastic leukemia (ALL). In an attempt to minimize the non-hematologic toxicity and obtain a potent antileukemic effect, MSKCC activated a pilot study in previously treated adult ALL, using HD-ARA-C combined with idarubicin administered as a single high-dose infusion. We herein report our experience with a series of pediatric and adult high risk ALL and NHL patients treated with the protocol above, which confirms its feasibility, response rate and individual compliance. METHODS: In a clinical phase II study the combination of a single high dose (HD) idarubicin and HD cytosine-arabinoside (ARA-C), as designed at the Memorial Sloan Kettering Cancer Center, was applied to 70 adults and children with refractory or early relapse acute lymphoblastic leukemia (ALL) and T-cell lymphoblastic non-Hodgkin's lymphoma (NHL). Therapy consisted of HD-ARA-C 3 g/m2/d on days 1-5, idarubicin 40 mg/m2 on day 3, prophylactic intrathecal methotrexate on days 1 and 4, and G-CSF 5 mg/kg/d s.c. from day 7 to hematopoietic reconstitution (PMN > 0.5 x 10(9)/L). RESULTS: Fifty-five of the 70 patients (78%) achieved complete remission (CR), four died in aplasia due to infection and 11 were non-responders. Recovery of blood counts occurred at a median of 21 days from the start of treatment. Non-hematologic side effects were extremely limited and consisted predominantly of infections. INTERPRETATION AND CONCLUSIONS: In view of the highly unfavorable series of patients selected, this study confirms the feasibility and antileukemic activity of the HD-idarubicin + HD- ARA-C combination in patients with refractory and early relapse ALL and NHL. The excellent tolerance to this regimen does not preclude bone marrow transplantation as post-remission treatment.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Citarabina/uso terapêutico , Idarubicina/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Humanos , Lactente , Masculino , Cidade de Roma , UniversidadesRESUMO
Sixty-one adults aged <55 years with acute lymphoblastic leukaemia (ALL) in first bone marrow relapse were enrolled in an Italian cooperative study (ALL R-87 protocol) from 12 GIMEMA Institutions. The treatment programme consisted of: (1) an induction phase with intermediate-dose cytarabine (IDARA-C 1 g/m2, 6 h daily infusion x 6 d) plus idarubicin (IDA; 5 mg/m2/d x 6 d) and prednisone (40 mg/m2/d x 21 d), (2) a consolidation phase followed by (3) bone marrow transplant (BMT). Median first complete remission (CR) duration was 8.5 months (range 1-54 months). 34/61 patients achieved CR (56%); 24 (39%) failed to respond and three (5%) died during induction. Most responders (24 patients) could not enter the BMT programme; 15 relapsed early (median time to relapse 2 months); nine were withdrawn due to toxicity and one died in CR of infection. Nine of the 34 CRs underwent BMT (five autologous and four allogeneic). Three of the four allotransplanted patients are alive in continuous CR at 22, 43 and 63 months; only one of the five who underwent an autologous BMT is alive in CR at 46 months. The estimated disease-free survival (DFS +/- SE) at 36 months was 0.16 +/- 0.08 for all responders. Univariate analysis showed that previous therapy was the only prognostic factor influencing DFS. The estimated probabilities of event-free survival (EFS +/- SE) and survival +/- SE at 37 months were 0.09 +/- 0.04 and 0.10 +/- 0.04, respectively. The EFS was significantly better in patients with a preceding CR > or = 24 months, compared to those with a shorter first remission. Our results confirm the tolerance and efficacy of IDARA-C plus IDA in inducing CR in poor-risk adult ALL. Even though the number of transplanted patients was small, allogeneic BMT seems to give a real opportunity of cure in this category of patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transplante de Medula Óssea/mortalidade , Terapia Combinada/mortalidade , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Feminino , Humanos , Idarubicina/administração & dosagem , Idarubicina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Estudos Prospectivos , Recidiva , Análise de Sobrevida , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVE: The anthracycline analogue idarubicin, either alone or in combination with other antineoplastic drugs, has shown antileukemic activity in relapsed and refractory acute lymphoblastic leukemia (ALL). In an attempt to minimize the non-hematologic toxicity and obtain a potent antileukemic effect, MSKCC activated a pilot study in previously treated adult ALL, using HD-ARA-C combined with idarubicin administered as a single high-dose infusion. We herein report our experience with a series of pediatric and adult high risk ALL and NHL patients treated with the protocol above, which confirms its feasibility, response rate and individual compliance. METHODS: In a clinical phase II study, the combination of a single high dose (HD) of idarubicin and HD cytosine-arabinoside (ARA-C), as designed at the Memorial Sloan Kettering Cancer Center, was applied to 70 adults and children with refractory or early relapse acute lymphoblastic leukemia (ALL) and T-cell lymphoblastic non-Hodgkin's lymphoma (NHL). Therapy consisted of HD-ARA-C 3 g/m2/d on days 1-5, idarubicin 40 mg/m2 on day 3, prophylactic intrathecal methotrexate on days 1 and 4, and G-CSF 5 mg/kg/d s.c. from day 7 to hematopoietic reconstitution (PMN > 0.5 x 10(9)/L). RESULTS: Fifty-five of the 70 patients (78%) achieved complete remission (CR), four died in aplasia due to infection and 11 were non-responders. Recovery of blood counts occurred at a median of 21 days from the start of treatment. Non-hematologic side effects were extremely limited and consisted predominantly of infections. INTERPRETATION AND CONCLUSIONS: In view of the highly unfavorable series of patients selected, this study confirms the feasibility and antileukemic activity of the HD-idarubicin + HD-ARA-C combination in patients with refractory and early relapse ALL and NHL. The excellent tolerance to this regimen does not preclude bone marrow transplantation as post-remission treatment.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Criança , Pré-Escolar , Citarabina/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Hospitais Universitários , Humanos , Idarubicina/administração & dosagem , Lactente , Masculino , Cidade de RomaRESUMO
In this study we used reverse transcriptase-polymerase chain reaction (RT-PCR) for the longitudinal monitoring of minimal residual disease in 12 patients with All-1/AF-4 positive ALL. Of these, seven also showed at presentation a typical t(4;11) cytogenetic translocation. Seven patients were infants <18 months of age and five were adults. Eleven patients were treated with high-dose intensive induction and consolidation chemotherapy without bone marrow transplantation and one received conservative treatment due to poor performance status. Three had resistant disease, four relapsed within 12 months after achieving complete remission, and five are in continuous complete remission (CCR) at 32, 39, 52, 53 and 61 months from diagnosis, respectively. The sequential analysis of the ALL-1/AF-4 hybrid transcript showed a persistently negative RT-PCR in the five CCR long-term survivors. The PCR analysis resulted persistently positive in the remaining seven cases, including the four cases who relapsed after the achievement of clinical CR. These data emphasize the clinical relevance of PCR monitoring analysis in t(4;11) ALL patients and should be considered in order to better determine variable post-remission treatment according to risk prediction.
Assuntos
Proteínas de Ligação a DNA/análise , Proteínas Nucleares/análise , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proto-Oncogenes , Fatores de Transcrição , Adulto , Antineoplásicos/uso terapêutico , Sequência de Bases , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 4 , Feminino , Histona-Lisina N-Metiltransferase , Humanos , Lactente , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Proteína de Leucina Linfoide-Mieloide , Neoplasia Residual , Reação em Cadeia da Polimerase , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prognóstico , DNA Polimerase Dirigida por RNA , Proteínas Recombinantes de Fusão/análise , Estudos Retrospectivos , Fatores de Elongação da Transcrição , Translocação GenéticaRESUMO
We report the 10-year follow-up of the GIMEMA ALL 0183 trial. From 1983 to 1987, 358 adults with acute lymphoblastic leukaemia (ALL) were entered into this trial, which included a mild induction, an early intensive consolidation, a post-consolidation phase randomized in conventional maintenance (arm A) and in more intensive regimen (arm B). CNS prophylaxis did not include CNS irradiation. The overall complete remission (CR) rate was 79.3% (284/358); 212 patient were randomized (110 in arm A and 102 in arm B). The median overall CR duration was 20 months and the median overall survival (OS) 21 months; both curves reach a plateau after 6 years; at 10 years 25% of patients were projected to be in long-term remission and survivors. The median disease-free survival (DFS) was 17 months, at 10 years 27% and 28% of patients were DFSs in arm A and in arm B respectively. In multivariate analysis age, WBC count and L2 FAB subtype were found to significantly influence OS and DFS. With regard to our previous report OS appears to linearly correlate with initial WBC count and age (P = 0.0002 and P = 0.042 respectively). 195 (68.7%) patients relapsed (only 25 had isolated CNS). The overall second CR rate was 56.5%; 23 patients underwent transplantation (12 BMT and 11 ABMT). Post-relapse survival was found to be influenced by the duration of first CR.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Citarabina/administração & dosagem , Feminino , Seguimentos , Humanos , Idarubicina/administração & dosagem , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Análise Multivariada , Recidiva , Análise de Sobrevida , Taxa de SobrevidaRESUMO
This paper reported on a series of 49 elderly patients over 60 years of age affected by acute lymphoblastic leukemia (ALL), observed at our institution from 1969 to 1993. The biological characteristics considered, median WBC count, FAB classification, immunophenotype at onset of disease, were no different from those of our adult ALL series. Overall complete remission (CR) rate of these patients was 59%, 18% had resistant disease and 23% died during induction. Overall median survival was 9 months and overall median duration of CR was 7 months. All patients were divided according to treatment into two groups: group A (13 patients) received an intensive treatment including vincristine (VCR), prednisone (PDN), daunorubicin (DNR) and L-asparaginase (L-Asp), while in group B (36 patients) were included patients who received mild conventional induction with VCR and PDN. In group A, 77% of patients achieved CR and 23% died during induction. All patients were hospitalized during induction treatment. During follow-up, among 10 CRs, five (50%) died in CR because of hemorrhage (two), infections (two) and myocardial infarction (one); five (50%) relapsed. Median survival was 4 months and median duration of CR was 3.5 months. In group B, 53% of patients obtained CR, 25% had resistant disease and 22% died during induction. During induction, 44% of patients were hospitalized. During follow-up, among 19 CRs, 14 (74%) relapsed and three (15%) died in CR because of infection (two) and cardiorespiratory failure (one). Three patients (15%) are still alive: two in first CR and one in second CR. No statistical differences between the two groups in terms of CR rate or survival were noted. Standardized therapeutic trials are needed better to evaluate results in these patients, considering also the introduction of new therapeutic agents or supportive treatments, such as growth factors.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Asparaginase/administração & dosagem , Daunorrubicina/administração & dosagem , Feminino , Humanos , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
AIMS--(1) To assess the diagnostic relevance of peripheral blood immunocytochemistry in hairy cell leukaemia (HCL); (2) to compare the immunostaining of bone marrow biopsy specimens with bone marrow and peripheral blood cytospins; (3) to evaluate the sensitivity of the different markers used; (4) to identify the ultrastructural localisation of DBA.44 in HCL variant. METHODS--Immunoenzymatic staining procedures, immunoperoxidase and immunoalkaline phosphatase, were used with a panel of monoclonal antibodies directed to HCL associated antigens. Ultrastructural immunostaining was performed using colloidal gold conjugated antibodies. RESULTS--HCL showed strong cytoplasmic reactivity for CD22, CD25, CD103, DBA.44, kappa, or lambda light chains. Peripheral blood diagnostic hairy cells were found in all the cases with absolute counts ranging from 0.11 x 10(9)/l up to 6.4 x 10(9)/l and values increasing with the size of the spleen. A median of 36.5% of leukaemic cells was found in bone marrow aspirates and 70% in bone marrow trephine specimens. The monoclonal antibodies CD22 and DBA.44 showed the highest and the lowest percentage of positive hairy cells, respectively; this difference was statistically significant (p = 0.0025). Ultrastructural immunolabelling with DBA.44 showed a cytoplasmic membrane localisation of the antigen in one case of HCL variant. CONCLUSIONS--(1) Immunocytochemistry is a useful technique which enhances the accuracy of diagnosis in HCL; (2) peripheral blood immunocytochemistry is recommended because it highlights hairy cells in all cases; (3) CD22 appears to be the most sensitive of the markers tested; (4) ultrastructural analysis is a useful tool in selected cases of HCL variant.
Assuntos
Antígenos CD/análise , Antígenos de Neoplasias/análise , Biomarcadores Tumorais/análise , Leucemia de Células Pilosas/imunologia , Adulto , Idoso , Anticorpos Monoclonais , Antígenos de Neoplasias/sangue , Doenças da Medula Óssea/imunologia , Doenças da Medula Óssea/patologia , Feminino , Humanos , Leucemia de Células Pilosas/diagnóstico , Leucemia de Células Pilosas/patologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
Adhesion molecule expression on acute and chronic lymphoid leukemia cells of B lineage (B-ALL and B-CLL) may subserve several functions. Adhesion of leukemic cells to endothelial cells and to extracellular matrix components is relevant to homing, trafficking and spread of the malignant cells, and thus to clinical presentation, course and disease prognosis. Adhesive interactions between malignant cells and accessory cells, particularly stromal cells in the bone marrow environment, may support growth of the malignant cells via cytokine-delivered messages. They may also deliver signals that prevent or trigger programmed cell death of tumor cells. Here we review data on the adhesive phenotype of leukemic blasts from pro-B (CALLA +) ALL and of cells from B-CLL cases. We show that expression of certain adhesion molecules may help define disease subsets with distinctive clinical and prognostic features. One adhesion molecule, the lymphocyte homing receptor CD44, allows definition of two groups of B-CLL patients with significantly different survival.