RESUMO
Failure of second-generation tyrosine kinase inhibitors (2GTKI) is a challenging situation in patients with chronic myeloid leukemia (CML). Asciminib, recently approved by the US Federal Drug Administration, has demonstrated in clinical trials a good efficacy and safety profile after failure of 2GTKI. However, no study has specifically addressed response rates to asciminib in ponatinib pretreated patients (PPT). Here, we present data on responses to asciminib from 52 patients in clinical practice, 20 of them (38%) with prior ponatinib exposure. We analyzed retrospectively responses and toxicities under asciminib and compared results between PPT and non-PPT patients.After a median follow-up of 30 months, 34 patients (65%) switched to asciminib due to intolerance and 18 (35%) due to resistance to prior TKIs. Forty-six patients (88%) had received at least 3 prior TKIs. Regarding responses, complete cytogenetic response was achieved or maintained in 74% and 53% for non-PPT and PPT patients, respectively. Deeper responses such as major molecular response and molecular response 4.5 were achieved in 65% and 19% in non-PPT versus 32% and 11% in PPT, respectively. Two patients (4%) harbored the T315I mutation, both PPT.In terms of toxicities, non-PPT displayed 22% grade 3-4 TEAE versus 20% in PPT. Four patients (20% of PPT) suffered from cross-intolerance with asciminib as they did under ponatinib.Our data supports asciminib as a promising alternative in resistant and intolerant non-PPT patients, as well as in intolerant PPT patients; the resistant PPT subset remains as a challenging group in need of further therapeutic options.
Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Piridazinas , Antineoplásicos/efeitos adversos , Resistencia a Medicamentos Antineoplásicos , Proteínas de Fusão bcr-abl/genética , Humanos , Imidazóis , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Niacinamida/análogos & derivados , Inibidores de Proteínas Quinases/efeitos adversos , Pirazóis , Piridazinas/efeitos adversos , Estudos RetrospectivosRESUMO
The therapeutic landscape of chronic myeloid leukemia (CML) has profoundly changed over the past 7 years. Most patients with chronic phase (CP) now have a normal life expectancy. Another goal is achieving a stable deep molecular response (DMR) and discontinuing medication for treatment-free remission (TFR). The European LeukemiaNet convened an expert panel to critically evaluate and update the evidence to achieve these goals since its previous recommendations. First-line treatment is a tyrosine kinase inhibitor (TKI; imatinib brand or generic, dasatinib, nilotinib, and bosutinib are available first-line). Generic imatinib is the cost-effective initial treatment in CP. Various contraindications and side-effects of all TKIs should be considered. Patient risk status at diagnosis should be assessed with the new EUTOS long-term survival (ELTS)-score. Monitoring of response should be done by quantitative polymerase chain reaction whenever possible. A change of treatment is recommended when intolerance cannot be ameliorated or when molecular milestones are not reached. Greater than 10% BCR-ABL1 at 3 months indicates treatment failure when confirmed. Allogeneic transplantation continues to be a therapeutic option particularly for advanced phase CML. TKI treatment should be withheld during pregnancy. Treatment discontinuation may be considered in patients with durable DMR with the goal of achieving TFR.
Assuntos
Antineoplásicos/uso terapêutico , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Compostos de Anilina/uso terapêutico , Tomada de Decisão Clínica , Conferências de Consenso como Assunto , Dasatinibe/uso terapêutico , Gerenciamento Clínico , Proteínas de Fusão bcr-abl/genética , Proteínas de Fusão bcr-abl/metabolismo , Expressão Gênica , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Expectativa de Vida/tendências , Monitorização Fisiológica , Nitrilas/uso terapêutico , Pirimidinas/uso terapêutico , Qualidade de Vida , Quinolinas/uso terapêutico , Análise de SobrevidaAssuntos
Antineoplásicos/efeitos adversos , Benzamidas/efeitos adversos , Histiocitoma Fibroso Benigno/induzido quimicamente , Histiocitoma Fibroso Benigno/diagnóstico , Piperazinas/efeitos adversos , Pirimidinas/efeitos adversos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Benzamidas/farmacologia , Benzamidas/uso terapêutico , Biópsia , Feminino , Histiocitoma Fibroso Benigno/patologia , Humanos , Mesilato de Imatinib , Terapia de Imunossupressão , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Piperazinas/farmacologia , Piperazinas/uso terapêutico , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Pele/efeitos dos fármacos , Pele/patologia , Resultado do TratamentoAssuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Antineoplásicos/uso terapêutico , Gerenciamento Clínico , Resistencia a Medicamentos Antineoplásicos , Genes abl , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Terapia de Alvo Molecular , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Risco , Resultado do TratamentoRESUMO
Central nervous system (CNS) involvement by Hodgkin Lymphoma (HL) is rarely reported. Retrospective and prospective cohort studies suggest an incidence of 0.2-0.5%, mostly in relapsed disease. In spite of a 3 to 18-fold increased risk of HL in patients with human immunodeficiency virus (HIV), only two cases have been reported so far. In this paper, we now report a third case of HIV patient with HL who progressed with isolated CNS infiltration after a standard chemotherapy induced clinical remission. In 1991, when the first case of intracerebral involvement in HIV+ HL was reported an increase of this type of cases would have been expected, but only one more case has been reported since then.
Assuntos
Neoplasias Encefálicas/patologia , Infecções por HIV/patologia , HIV , Doença de Hodgkin/patologia , Adulto , Neoplasias Encefálicas/complicações , Infecções por HIV/complicações , Doença de Hodgkin/complicações , Humanos , MasculinoRESUMO
The use of the tyrosine kinase inhibitor imatinib, which blocks the enzymatic action of the BCR-ABL fusion protein, has represented a critical advance in chronic myeloid leukemia (CML) treatment. However, a subset of patients initially fails to respond to this treatment. Use of complementary DNA (cDNA) microarray expression profiling allows the identification of genes whose expression is associated with imatinib resistance. Thirty-two CML bone marrow samples, collected before imatinib treatment, were hybridized to a cDNA microarray containing 6500 cancer genes, and analyzed using bootstrap statistics. Patients refractory to interferon-alpha treatment were evaluated for cytogenetic and molecular responses for a minimum of 12 months. A set of 46 genes was differentially expressed in imatinib responders and non-responders. This set includes genes involved in cell adhesion (TNC and SCAM-1), drug metabolism (cyclooxygenase 1), protein tyrosine kinases and phosphatases (BTK and PTPN22). A six-gene prediction model was constructed, which was capable of distinguishing cytogenetic response with an accuracy of 80%. This study identifies a set of genes that may be involved in primary resistance to imatinib, suggesting BCR-ABL-independent mechanisms.
Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Perfilação da Expressão Gênica , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Adolescente , Adulto , Idoso , Benzamidas , Análise Citogenética , Feminino , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Proteínas de Fusão bcr-abl/genética , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/enzimologia , Masculino , Pessoa de Meia-Idade , Mutação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Medição de RiscoRESUMO
BACKGROUND: Interferon alfa is a conservative and widely used alternative to bone marrow transplantation in treatment of patients with early chronic myeloid leukemia (CML). A meta-analysis was conducted to develop a reliable prognostic scoring system for estimation of survival of patients with CML treated with interferon alfa. METHODS: Patients treated in prospective studies, including major randomized trials, were separated into learning and validation samples. Cox regression analysis and the minimum P-value approach were used to identify prognostic factors for patient survival and to discover groups in the learning sample with the greatest differences in survival. These findings were then validated by applying the new scoring system to patients in the validation sample. RESULTS: We collected data on 1573 patients who were participants in 14 studies involving 12 institutions; 1303 patients (learning sample, n = 981; validation sample, n = 322) were eligible for inclusion in this analysis, and their median survival time was 69 months (range, 1-117 months). Because two previously described prognostic scoring systems failed to discriminate risk groups satisfactorily, we developed a new scoring system that utilizes the following covariates: age, spleen size, blast count, platelet count, eosinophil count, and basophil count. Among 908 patients with complete data in the learning sample, three distinct risk groups were identified (median survival times of 98 months [n = 369; 40.6%], 65 months [n = 406; 44.7%], or 42 months [n = 133;14.6%]; two-sided logrank test, P< or =.0001). The ability of the new scoring system to discriminate these risk groups was confirmed by analysis of 285 patients with complete data in the validation sample (two-sided logrank test, P = .0002). CONCLUSIONS: A new prognostic scoring system for estimating survival of patients with CML treated with interferon alfa has been developed and validated through use of a large dataset.
Assuntos
Antineoplásicos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Interferon-alfa/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Índice de Gravidade de Doença , Adulto , Idoso , Contagem de Células Sanguíneas , Europa (Continente)/epidemiologia , Feminino , Humanos , Japão/epidemiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Análise de Sobrevida , Taxa de Sobrevida , Estados Unidos/epidemiologiaRESUMO
OBJECTIVES: To provide more reliable data on the epidemiology of chronic myeloid leukaemia (CML) in Spain than are currently available. MATERIAL AND METHODS: The EUTOS population-based project of European LeukemiaNet is a population registry of new CML cases in patients 18 years of age or older from 22 European areas. The Spanish section included the autonomous communities of Madrid, Castilla-La Mancha and Aragon, from 1-2-2010 to 31-12-2012. RESULTS: A total of 250 cases were recorded in 35 months. The overall incidence was 1.08 cases/10(5) inhabitants-year, with a predominance of men (58%) and clear differences among the communities. The incidence standardised by age was similar (overall, 1.04; men, 1.31; women, 0.81). The median age was 54 years. The incidence increased with age, reaching a peak at>65 years, although 31.7% of cases appeared between the ages of 20 and 44 years. Four percent of cases were diagnosed in advanced stages (2.4% in accelerated phase, 1.6% in blast crisis), 56% were asymptomatic, 38% had splenomegaly, and the Sokal score was high in 11% (lower than what was previously reflected in the literature). CONCLUSIONS: The current incidence of CML in Spain is higher than previously reported and similar to that of the European studies. Unlike the classical descriptions, CML presented mostly in asymptomatic form, with no splenomegaly, less leucocytosis and in stages with better prognosis.
RESUMO
Most reports on chronic myeloid leukaemia (CML) treatment with tyrosine kinase inhibitors (TKIs) focus on efficacy, particularly on molecular response and outcome. In contrast, adverse events (AEs) are often reported as infrequent, minor, tolerable and manageable, but they are increasingly important as therapy is potentially lifelong and multiple TKIs are available. For this reason, the European LeukemiaNet panel for CML management recommendations presents an exhaustive and critical summary of AEs emerging during CML treatment, to assist their understanding, management and prevention. There are five major conclusions. First, the main purpose of CML treatment is the antileukemic effect. Suboptimal management of AEs must not compromise this first objective. Second, most patients will have AEs, usually early, mostly mild to moderate, and which will resolve spontaneously or are easily controlled by simple means. Third, reduction or interruption of treatment must only be done if optimal management of the AE cannot be accomplished in other ways, and frequent monitoring is needed to detect resolution of the AE as early as possible. Fourth, attention must be given to comorbidities and drug interactions, and to new events unrelated to TKIs that are inevitable during such a prolonged treatment. Fifth, some TKI-related AEs have emerged which were not predicted or detected in earlier studies, maybe because of suboptimal attention to or absence from the preclinical data. Overall, imatinib has demonstrated a good long-term safety profile, though recent findings suggest underestimation of symptom severity by physicians. Second and third generation TKIs have shown higher response rates, but have been associated with unexpected problems, some of which could be irreversible. We hope these recommendations will help to minimise adverse events, and we believe that an optimal management of them will be rewarded by better TKI compliance and thus better CML outcomes, together with better quality of life.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Inibidores de Proteínas Quinases/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidoresRESUMO
The Evaluating Nilotinib Efficacy and Safety in Clinical Trials as First-Line Treatment (ENEST1st) study included 1089 patients with newly diagnosed chronic myeloid leukemia in chronic phase. The rate of deep molecular response (MR(4) (BCR-ABL1⩽0.01% on the International Scale or undetectable BCR-ABL1 with ⩾10,000 ABL1 transcripts)) at 18 months was evaluated as the primary end point, with molecular responses monitored by the European Treatment and Outcome Study network of standardized laboratories. This analysis was conducted after all patients had completed 24 months of study treatment (80.9% of patients) or discontinued early. In patients with typical BCR-ABL1 transcripts and ⩽3 months of prior imatinib therapy, 38.4% (404/1052) achieved MR(4) at 18 months. Six patients (0.6%) developed accelerated or blastic phase, and 13 (1.2%) died. The safety profile of nilotinib was consistent with that of previous studies, although the frequencies of some nilotinib-associated adverse events were lower (for example, rash, 21.4%). Ischemic cardiovascular events occurred in 6.0% of patients. Routine monitoring of lipid and glucose levels was not mandated in the protocol. These results support the use of frontline nilotinib, particularly when achievement of a deep molecular response (a prerequisite for attempting treatment-free remission in clinical trials) is a treatment goal.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirimidinas/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Proteínas de Fusão bcr-abl/genética , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Pessoa de Meia-Idade , Pirimidinas/efeitos adversosRESUMO
This population-based registry was designed to provide robust and updated information on the characteristics and the epidemiology of chronic myeloid leukemia (CML). All cases of newly diagnosed Philadelphia positive, BCR-ABL1+ CML that occurred in a sample of 92.5 million adults living in 20 European countries, were registered over a median period of 39 months. 94.3% of the 2904 CML patients were diagnosed in chronic phase (CP). Median age was 56 years. 55.5% of patients had comorbidities, mainly cardiovascular (41.9%). High-risk patients were 24.7% by Sokal, 10.8% by EURO, and 11.8% by EUTOS risk scores. The raw incidence increased with age from 0.39/100,000/year in people 20-29 years old to 1.52 in those >70 years old, and showed a maximum of 1.39 in Italy and a minimum of 0.69 in Poland (all countries together: 0.99). The proportion of Sokal and Euro score high-risk patients seen in many countries indicates that trial patients were not a positive selection. Thus from a clinical point of view the results of most trials can be generalized to most countries. The incidences observed among European countries did not differ substantially. The estimated number of new CML cases per year in Europe is about 6370.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/epidemiologia , Sistema de Registros/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto JovemRESUMO
Reliable knowledge about an individual's prognosis is needed to select the appropriate treatment for patients with chronic myeloid leukemia (CML). The New CML score using age, spleen size, blast cell count, eosinophil count, basophil count, and platelet count shows good discrimination for survival (96, 65, or 42 months, P =.0001) and has been thoroughly validated. Careful analyses indicate that the New CML score is considerably more precise in identifying high-risk patients than the Sokal score. Achievement of complete hematologic response (CHR) up to 9 months shows a distinct impact on survival, which, however, depends on the baseline prognosis. Ten-year survival probabilities for low- and intermediate-risk patients with a CHR were 0.51 (95% confidence interval [CI], 0.42 to 0.60) and 0.23 (95% CI, 0.15 to 0.31) and without a CHR were 0.26 (95% CI, 0.16 to 0.37) and 0.12 (95% CI, 0.04 to 0.20). In high-risk patients CHR had no impact on prognosis. Therapeutic options were widened by the approval of imatinib for the treatment of CML. However, it will still take 2 or more years to know whether the high rates of CHR and cytogenetic complete remission (CCR) achieved with imatinib translate into a clinically relevant survival advantage for all patients.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Índice de Gravidade de Doença , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Prognóstico , Indução de Remissão , Fatores de Risco , Análise de SobrevidaRESUMO
Thirteen patients (mean age 60.7 years; female:male ratio 10:3) with essential thrombocythaemia were treated with 3 million units (MU)/day interferon alfa-2b subcutaneously (s.c.) for 12 weeks, with all patients requiring a dose reduction after 4 weeks. The mean pretreatment platelet count was 1,400 x 10(9)/L and megakaryocytes were increased in all cases. Splenomegaly was present in six patients and haemorrhagic phenomena were observed in two. Nine patients (69.2%) had objective responses, including two (15.4%) complete responses (platelets less than 450 x 10(9)/L) which were then maintained with 5 MU interferon twice a week. Acute toxicity consisted of flu-like symptoms in 12 patients. Chronic toxicity (mainly leucopenia) was observed in nine patients. In conclusion, initial therapy and then requiring maintenance therapy at a reduced dose. However, the frequent side effects observed make it advisable to use a low dose of interferon alfa-2b, and to treat only those patients with significant symptoms and signs of thrombocytosis.
Assuntos
Interferon-alfa/uso terapêutico , Trombocitemia Essencial/terapia , Adulto , Idoso , Feminino , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Proteínas Recombinantes , Fatores de TempoRESUMO
Twenty-eight allogeneic BMT patients (16 with acute leukemia, 12 with chronic myeloid leukemia) were included in a single center, prospective, randomized, controlled trial to assess the value of recombinant human erythropoietin (rh-Epo) in this setting. rh-Epo was administered through a central venous catheter as a single bolus injection (days 0-7: 100 U/kg/d; days 7-30: 150 U/kg/d). No secondary effects to rh-Epo treatment were detected. An earlier appearance of reticulocytes and a diminished need of red blood cells (RBCs) transfusions were observed in patients who were treated with rh-Epo (4 units vs 12 units; p < 0.05). The time to unsupported platelets above 25 x 10(9)/l was less in patients treated with rh-Epo than in control patients (19 days vs 31; p < 0.05), and they received significantly fewer platelet transfusions (36 units vs 138.5; p < 0.05). Our results show that rh-Epo treatment is capable of accelerating the erythroid reconstitution and decreasing the need for RBC transfusions. A beneficial effect on platelet reconstitution is also suggested, but further studies are necessary to confirm this point.
Assuntos
Transplante de Medula Óssea , Eritropoese/efeitos dos fármacos , Eritropoetina/uso terapêutico , Adolescente , Adulto , Transplante de Medula Óssea/patologia , Ensaio de Unidades Formadoras de Colônias , Terapia Combinada , Eritropoetina/efeitos adversos , Feminino , Humanos , Leucemia/tratamento farmacológico , Leucemia/cirurgia , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Leucemia Mieloide de Fase Crônica/cirurgia , Masculino , Estudos ProspectivosRESUMO
We present our experience with bone marrow transplantation (BMT) in 30 consecutive patients with high risk acute lymphoblastic leukemia. With a median follow-up of 4 years the disease-free survival (DFS) was 44% for the whole group, with a significant difference between patients in first or second complete remission (CR 1 and 2, as one group), compared with patients with more advanced disease (greater than CR2), 69.5% versus 15.4% (p less than 0.01). The main cause of BMT failure was leukemic relapse, with a relapse rate of 15% for patients in CR 1 and 2 and of 77% for patients with greater than CR2 (p less than 0.01). Among patients with active disease at BMT those who had 15% blast cells or less in the marrow fared better than those with more advanced disease or extramedullary relapse. Transplant-related death was 17%. Graft-versus-host disease (GVHD) was associated with an antileukemic effect; the DFS for patients with acute and/or chronic GVHD was better than for patients with no GVHD at all.
Assuntos
Transplante de Medula Óssea , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Adolescente , Adulto , Criança , Doença Enxerto-Hospedeiro/etiologia , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Recidiva , Indução de Remissão , Taxa de Sobrevida , Transplante HomólogoRESUMO
Fractionated total body irradiation (FTBI) and methotrexate-cyclosporin A(MTX-CSA) have been found useful in reducing interstitial pneumonia (IP) and acute graft-versus-host-disease (GVHD) in bone marrow transplantation patients, but an increase in relapse rate has been observed by some authors when these strategies are used. To evaluate this relapse risk, we performed a retrospective analysis in 24 consecutive first chronic phase chronic myeloid leukemia patients who received an HLA-identical non-T cell-depleted graft in a single institution. All were conditioned with cyclophosphamide plus FTBI (12 Gy in six fractions delivered twice daily for 3 days) (CY-FTBI) and received MTX-CSA as GVHD prophylaxis. Serial hematologic and cytogenetic bone marrow analysis were performed at least three times (days +30, +100, +360) and at variable intervals thereafter in long-term survivors. Actuarial probabilities of developing IP and acute GVHD greater than or equal to II were respectively 5.9% and 44.2%, with a GVHD-associated mortality of 33%. Four-year actuarial relapse and disease-free survival rates were 7.7% and 48.2% respectively. No exclusively cytogenetic relapses were observed. Our results suggest that CY-FTBI and MTX-CSA are not associated with an increase in relapse rate in 1CP-CML patients.
Assuntos
Transplante de Medula Óssea/métodos , Ciclosporina/administração & dosagem , Leucemia Mieloide de Fase Crônica/cirurgia , Metotrexato/administração & dosagem , Irradiação Corporal Total/métodos , Adolescente , Adulto , Transplante de Medula Óssea/efeitos adversos , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/radioterapia , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Leucemia Mieloide de Fase Crônica/radioterapia , Masculino , Fibrose Pulmonar/prevenção & controle , Recidiva , Irradiação Corporal Total/efeitos adversosRESUMO
We describe here a patient with Philadelphia-positive chronic myeloid leukemia who had a hematologic and cytogenetic relapse after bone marrow transplantation. A diagnosis of accelerated phase was made when an additional malignant clone was detected. This clone was probably derived from the primitive Philadelphia clone, with duplication and rearrangement of the Philadelphia chromosome. The patient was treated with interferon alpha 2a and experienced a complete cytogenetic and molecular remission, with full reconstitution of the donor marrow.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Interferon Tipo I/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mieloide de Fase Acelerada/tratamento farmacológico , Feminino , Rejeição de Enxerto , Humanos , Cariotipagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Leucemia Mieloide de Fase Acelerada/cirurgia , Pessoa de Meia-IdadeRESUMO
The non-Candida, non-Aspergillus fungal infections are being reported with increasing frequency in BMT patients. One of these agents is Penicillium which has rarely been implicated as a pathogen in these patients. Only a few cases of isolated fungemias have been reported to date. We present the first documented case of invasive lung infection due to Penicillium brevicompactum in an allogeneic BMT recipient. As this case shows, the diagnosis of non-Candida, non-Aspergillus fungal infections may be incorrect if only histologic findings are available, mainly because misdiagnosis with other more common fungus can occur. A positive culture is required in order to make an accurate diagnosis.
Assuntos
Transplante de Medula Óssea , Pneumopatias Fúngicas/microbiologia , Infecções Oportunistas/microbiologia , Penicillium/isolamento & purificação , Adulto , Antifúngicos/uso terapêutico , Aspergilose/complicações , Aspergilose/diagnóstico , Diagnóstico Diferencial , Encefalite/complicações , Evolução Fatal , Feminino , Humanos , Hospedeiro Imunocomprometido , Pneumopatias Fúngicas/diagnóstico , Pneumopatias Fúngicas/tratamento farmacológico , Pneumopatias Fúngicas/etiologia , Pneumopatias Fúngicas/patologia , Necrose , Neutropenia/complicações , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/tratamento farmacológico , Infecções Oportunistas/etiologia , Infecções Oportunistas/patologia , Penicillium/patogenicidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recidiva , Transplante HomólogoRESUMO
Fifty patients with aplastic anemia (AA) were treated with BMT or immunosuppressive therapy (IST). Twenty-one patients underwent BMT using cyclophosphamide (CY) and 7 Gy total lymphoid irradiation (TLI) and cyclosporin A (CsA) plus methotrexate (MTX). Actuarial survival is 71% at 5.3 years with an incidence of graft failure of 0% and of acute GVHD of 38.9%. Univariate analysis of variables influencing survival showed a trend for a poorer outcome in patients who received > 30 transfusions prior to BMT and in male recipients from female donors. Twenty-nine patients > 40 years of age or without matched siblings received antithymocyte/antilymphocyte globulin (ATG/ALG). Response rate to the first course of treatment was 46.4%. Subsequent courses of IST rescued 33% of patients who relapsed or had not responded. Actuarial survival is 62% at 8.6 years. In our experience both treatment strategies have given encouraging results although overall morbidity is higher in the IST group because 25% of patients are therapy or transfusion-dependent. The role of irradiation in the conditioning regimen of BMT patients, recently challenged, is discussed.
Assuntos
Anemia Aplástica/terapia , Transplante de Medula Óssea , Imunossupressores/uso terapêutico , Irradiação Linfática , Análise Atuarial , Adolescente , Adulto , Idoso , Anemia Aplástica/tratamento farmacológico , Anemia Aplástica/mortalidade , Transfusão de Sangue/estatística & dados numéricos , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/mortalidade , Criança , Ciclofosfamida/efeitos adversos , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Humanos , Imunossupressores/efeitos adversos , Incidência , Irradiação Linfática/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
Chimerism studies employing PCR and Southern techniques targeting VNTR loci were performed in 17 severe acquired aplastic anemia patients who were long-term survivors after BMT. They were studied a median of 4 years after BMT (1-12). All patients had normal blood counts. All patients conditioned with radiation-based schemes showed a full donor pattern of hemopoiesis. Conversely, out of five patients who received only cyclophosphamide as conditioning therapy, two of them had a late graft failure (2.4 and 3 years after BMT). One of these relapsing patients had a durable mixed chimerism, which was first detected 1 month after BMT. Our results seem to suggest that durable mixed chimerism can antecede graft failure in some patients conditioned only with cyclophosphamide, and that a more stringent monitoring can be clinically rewarding in this group of patients.