RESUMO
BACKGROUND: Escalated combination therapy with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone (escBEACOPP) regimen is superior to cyclophosphamide, vincristine, procarbazine and prednisone alternating with doxorubicin, bleomycin, vinblastine and dacarbazine (COPP-ABVD) for advanced-stage Hodgkin's lymphoma (HL) patients. However, the original schedule of eight cycles of escBEACOPP was associated with significant toxicity. This study was conducted in an attempt to reduce the toxicity of the original schedule, while attempting to preserve improved initial tumor control. PATIENTS AND METHODS: Forty-five newly diagnosed patients with advanced-stage HL and International Prognostic Score > or = 3 received two initial cycles of escBEACOPP and then were evaluated by positron emission tomography (PET)/computed tomography scan. If a good imaging response was obtained, they were treated by four cycles of ABVD. RESULTS: Following the first two cycles of escBEACOPP, the overall response was 100% and at the end of all therapy, 40 (89%) patients were in complete response (disappearance of all clinical evidence of disease and PET negativity), three (7%) in partial response (PET-positive residual lesions and a size reduction of the majority of large masses by >50%), while two (4%) had progressive disease. After a median follow-up of 48 months, progression-free survival (PFS) and overall survival at 4 years were 78% and 95%, respectively. The 4-year PFS for early PET-negative patients (n = 31) and early PET-positive patients (n = 13) were 87% and 53%, respectively (P = 0.01). CONCLUSIONS: These data indicate that combined escBEACOPP-ABVD may improve the outcome in patients with high-risk advanced HL. The potential benefit of early-interim PET activity as a guide to continuing therapy in these patients merits further study in the future.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adolescente , Adulto , Bleomicina/uso terapêutico , Ciclofosfamida/uso terapêutico , Dacarbazina/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Doença de Hodgkin/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Prednisona/uso terapêutico , Procarbazina/uso terapêutico , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Vimblastina/uso terapêutico , Vincristina/uso terapêutico , Adulto JovemRESUMO
Allogeneic SCT is an effective therapy for lymphoma. Reduced-intensity conditioning (RIC) reduces non-relapse mortality (NRM) associated with myeloablative conditioning but relapse rates are high when performed in active disease. This study was designed to explore the safety and outcome of ibritumomab tiuxetan (Zevalin) combined with RIC in patients with advanced lymphoma. The study included 12 patients, median age 54 years (37-62), with a median of four prior treatments (2-6) and active disease documented on PET-CT. Zevalin 0.4 mCi/kg was given on day -14 and fludarabine combined with BU (n=6) or melphalan (n=6) was started on day -6. GVHD prevention was tapered 3 months after SCT to augment the graft-versus-lymphoma effect. All patients engrafted, a median of 14 days after SCT. Eighty-three percent achieved CR/PR. With a median follow-up of 21 months (12-37), 2-year PFS is 33%. Only three patients relapsed; cumulative incidence 25%. NRM was 42%, predominantly due to acute GVHD. Zevalin-RIC is feasible with consistent engraftment, acceptable organ toxicity, but high rates of acute GVHD. The low incidence of relapse suggests augmented anti-lymphoma effect. Zevalin-RIC merits further study. Better results may be achieved in patients earlier in disease course and with longer duration of immune-suppression.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma não Hodgkin/terapia , Agonistas Mieloablativos/uso terapêutico , Condicionamento Pré-Transplante/métodos , Adulto , Intervalo Livre de Doença , Feminino , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Radioimunoterapia/métodos , Indução de Remissão , Transplante Homólogo , ômega-Conotoxina GVIARESUMO
Immune-mediated anti-leukemia effects, often termed graft-versus-leukemia (GvL), operate after bone marrow or blood cell transplants for acute lymphoblastic leukemia, acute myelogenous leukemia and chronic myelogenous leukemia. Sometimes the magnitude of this anti-leukemia effect exceeds that of high-dose anti-leukemia drugs and radiation and can result in leukemia cure. We analyzed leukemia relapse data after transplants for chronic lymphocytic leukemia (CLL) in this context. These data support the notion of a strong GvL effect in CLL. However, as most of these data are from studies of allotransplants, it is uncertain whether GvL operates in settings where the anti-leukemia effector cells and target CLL cells are genetically identical except for leukemia-related mutations. It is also uncertain whether GvL is distinct from GvHD. These potential limitations have important implications on whether immune therapy of CLL will work in non-allotransplant settings.
Assuntos
Transplante de Medula Óssea/imunologia , Doença Enxerto-Hospedeiro/imunologia , Efeito Enxerto vs Leucemia/imunologia , Leucemia Linfocítica Crônica de Células B/terapia , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Transfusão de Linfócitos , Doadores de Tecidos , Transplante Homólogo/imunologia , Transplante Isogênico/imunologia , Gêmeos MonozigóticosRESUMO
During the past years targeted therapies have gained a major role in the treatment of cancer patients, including those with hematological malignancies. Extramedullary involvement is a rare manifestation of acute and chronic leukemias and of multiple myeloma. Nevertheless, with the expanding use of targeted treatments there is an impression that the incidence of extramedullary relapses is increasing. We reviewed the reports on this phenomenon in patients treated with all-trans-retinoic acid and arsenic trioxide for acute promyelocytic leukemia, thalidomide and bortezomib for multiple myeloma and imatinib for chronic myeloid leukemia. The pathogenetic mechanisms suggested are: life prolongation by these treatments allowing for disease progression arising from dormant cells; poor penetration of the drugs to sanctuary sites like the central nervous system; the requirement of some of these drugs, especially thalidomide, for the marrow microenvironment to exert their action; and finally, a possible active role for some of the drugs, like all-trans-retinoic acid. Since the use of these targeted therapies is expanding we should be aware of this association.
Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Promielocítica Aguda/tratamento farmacológico , Infiltração Leucêmica/patologia , Mieloma Múltiplo/tratamento farmacológico , HumanosRESUMO
BACKGROUND: The clinical impact of fused PET/CT data on staging and patient management of Hodgkin disease (HD) and non-Hodgkin lymphoma (NHL) was assessed. PATIENTS AND METHODS: A total of 103 consecutive patients with newly diagnosed NHL (n = 68) and HD (n = 35) were assessed retrospectively. Three comparisons were carried out in an attempt to assess the added value of each modality. RESULTS: For NHL patients, there were significant differences between staging by CT versus PET/CT (P = 0.0001). Disease was upstaged by PET/CT in 31% (mostly in stages I and II) and downstaged in only 1% of patients. In 25% of the patients, the treatment approach was changed according to CT versus PET/CT findings. For HD patients, disease was upstaged by PET/CT in 32% and downstaged by PET/CT in 15% (P = NS). As for NHL, upstaging by PET/CT versus CT was evident mostly for stages I and II. The treatment strategy was altered as determined by CT versus PET/CT in 45% of the patients. CONCLUSIONS: The addition of PET/CT to CT changed the management decisions in approximately a quarter of NHL and a third of HD patients, mostly in early disease stages. Thus, PET/CT performed as the initial staging procedure may well obviate the need for additional diagnostic CT in the majority of patients.
Assuntos
Doença de Hodgkin/patologia , Linfoma não Hodgkin/patologia , Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluordesoxiglucose F18 , Seguimentos , Doença de Hodgkin/diagnóstico por imagem , Humanos , Linfoma não Hodgkin/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
Allogeneic stem-cell transplantation (SCT) with both myeloablative and reduced-intensity conditioning (RIC) is an effective therapy in AML/MDS. However, the relative merits of each may differ in different settings. To define the role of dose intensity, we analyzed SCT outcomes of 112 consecutive patients with AML/MDS. A total of 45 patients met eligibility criteria for standard myeloablative conditioning and were given intravenous-busulfan (12.8 mg/kg) and cyclophosphamide (ivBuCy). A total of 67 noneligible patients were given RIC with fludarabine and intravenous-busulfan (6.4 mg/kg, FB2, n=41) or a modified myeloablative regimen with fludarabine and myeloablative doses of intravenous-busulfan (12.8 mg/kg, FB4, n=26). The overall survival (OS) at 2 years was 50, 49 and 47% after ivBuCy, FB4 and FB2, respectively (P=NS). Nonrelapse mortality was higher after ivBuCy, 22 vs 8% (P=0.05), but relapse rates were lower. Active disease at SCT was the most significant predictor of reduced survival in multivariable analysis (HR 4.5, P=0.0001). Myeloablative and RIC regimens had similar outcomes when leukemia was in remission at SCT; however, patients with active disease could only be salvaged by myeloablative conditioning. Among the latter, OS was 45% after ivBuCy but no FB2 recipient survived (P=0.02). Patients with active disease, ineligible for standard myeloablation, could tolerate modified myeloablation well; however, long-term outcome cannot be determined yet.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide/terapia , Agonistas Mieloablativos/uso terapêutico , Síndromes Mielodisplásicas/terapia , Condicionamento Pré-Transplante/métodos , Doença Aguda , Adolescente , Adulto , Idoso , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Transplante Homólogo , Resultado do TratamentoRESUMO
Allogeneic stem cell transplantation (SCT) is a potentially curative approach for patients with hematological malignancies. Reduced-intensity conditioning regimens allow SCT in elderly patients; however, there are only limited data on the feasibility and outcomes of unrelated donor SCT in these patients. In this study, we analyzed, retrospectively, data of 36 patients with various hematological malignancies and median age 58 years (range, 55-66), who were given unrelated donor SCT after reduced-intensity conditioning. The preparative regimen consisted of fludarabine combined with oral busulfan (8 mg/kg, n=8), intravenous busulfan (6.4 mg/kg, n=11), treosulfan (30 g/m(2), n=5) or melphalan (100-150 mg/m(2), n=12). Patients were also given serotherapy, ATG (n=32), or alemtuzumab (n=4). The probabilities of overall survival, disease-free survival, and nonrelapse mortality at 1 year after SCT were 52, 43, and 39%, respectively. Acute graft-versus-host disease (GVHD) grade II-IV and chronic GVHD occurred in 31 and 45%, respectively. Multivariable analysis determined that survival rates were higher in patients with chemosensitive disease (HR 4.5), and patients conditioned with intravenous busulfan or treosulfan (HR 3.9). Unrelated donor SCT is feasible in elderly patients, with outcomes that are similar to younger patients. Favorable outcome was observed in patients with myeloid malignancies, and those transplanted in remission and early in the course of disease. Age alone should not be considered a contraindication to unrelated donor SCT.
Assuntos
Neoplasias Hematológicas/cirurgia , Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante , Idoso , Alemtuzumab , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Anticorpos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Contraindicações , Doença Enxerto-Hospedeiro , Neoplasias Hematológicas/classificação , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Acute myelogenous leukemia (AML) is considered to be in complete remission when fewer than 5% of the cells in bone marrow are blasts. Nevertheless, approximately two thirds of patients relapse due to persisting leukemic blasts. The persistence of these cells, below the threshold of morphological detection, is termed minimal residual disease (MRD) and various methods are used for its detection. These methods include classical cytogenetics, fluorescence in situ hybridization, qualitative and quantitative RT-PCR and multiparametric flow cytometry. Currently, less than half of the AML patients have a specific marker detectable by RT-PCR techniques. The major specific molecular markers are involvement of the MLL gene with up to 50 different partners and partial tandem duplications, the core binding factor leukemias with AML1/ETO and CBFbeta/MYH11 rearrangements, PML/RARalpha in acute promyelocytic leukemia, internal tandem duplications and mutations of FLT3 and some other rare translocations. In addition, several other genes show abnormal expression levels in AML, including the Wilms tumor gene, the PRAME gene and Ig/TCR rearrangements. Most of these genetic abnormalities can be detected by qualitative but more importantly by quantitative RT-PCR. The kinetics of disappearance of molecular markers in AML differs between the various types of leukemias, although at least a 2 log reduction of transcript after induction chemotherapy is necessary for long-term remission in all types. Conversely, the change of PCR from negativity to positivity is highly predictive of relapse. Whereas in acute lymphoblastic leukemia, multiparametric flow cytometry is an established method for MRD detection, this is less so in AML. The reason is the absence of well-characterized leukemia-specific antigens and the existence of phenotypic changes at relapse. On the other hand, this method is convenient due to its simplicity and universal applicability. In conclusion, several methods can be used for MRD detection in AML patients; each has its pros and cons. Several issues still remain to be settled including the choice of the best method and the timing for MRD monitoring and above all the practical clinical implications of MRD in the various types of AML.
Assuntos
Leucemia Mieloide Aguda/diagnóstico , Citogenética , Humanos , Hibridização in Situ Fluorescente , Leucemia Mieloide Aguda/genética , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/normas , Mutação , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Técnicas de Amplificação de Ácido Nucleico , Translocação GenéticaRESUMO
Chronic myeloid leukemia in blast crisis (BC) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) are associated with extremely poor outcome. Allogeneic transplantation during BC or active leukemia is most often unsuccessful due to high-rates of both treatment-related complications and relapse. Long-term results are significantly better if a second chronic phase or remission can be achieved prior to transplantation. Similarly, DLI given for the treatment of post-transplant relapse is more successful when given during a second remission. In this study we report our results with a previously unreported approach consisting of short-term treatment with imatinib mesylate (formerly, STI571) to induce or maintain remission, followed by allogeneic transplantation or DLI and the impact on transplantation/DLI outcome. Sixteen patients were treated either in preparation for transplantation (n = 12), for DLI (n = 1), or for both (n = 3). Ten had CML in BC; seven myeloid and three lymphoid BC. Six patients had Ph(+) ALL. The donors were matched unrelated (n = 9), matched siblings (n = 5) or haplo-identical (n = 2). Eleven of 15 patients given imatinib pre-transplant were transplanted in complete hematologic response. Engraftment and GVHD rates were not different from expected. Seven patients had grade II-III hepatic toxicity after transplantation. After a median follow-up of 10 months (range, 3-16 months) six remain alive, two after further therapy. The 1-year survival rate was 25%. Four patients were given imatinib prior to DLI, all had complete response. Two remain in remission >6 months from relapse. In conclusion, treatment with imatinib allows transplantation in a more favorable status or maintaining remission with low toxicity until transplantation is feasible. Pre-transplant imatinib seems safe and not associated with excess post-transplant complications. Imatinib may have substantial activity in combination with DLI. Further study of a larger group of patients is required to assess the impact on long-term outcome and the role of post-transplant imatinib in controlling residual disease.
Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Piperazinas/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Pirimidinas/uso terapêutico , Transplante de Células-Tronco , Adulto , Benzamidas , Feminino , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Transplante de Células-Tronco/mortalidade , Taxa de Sobrevida , Fatores de Tempo , Transplante Homólogo , Resultado do TratamentoRESUMO
Macrophages play a major role in almost all stages of the complex process of wound healing. It has been previously shown that the incorporation of a hypo-osmotic shock step, in the process of monocyte-concentrate preparation from a blood unit, induces monocyte/macrophage activation. As the macrophages are produced using a unique, closed and sterile system, they are suitable for local application on ulcers in elderly and paraplegic patients. Enhanced phagocytosis by the activated cells, as well as increased secretion of cytokines such as IL-1, IL-6, were detected in a recent study which are in accord with the very encouraging clinical results. In the present study, we used DNA microarrays to analyse the differential gene expressions of the hypo-osmotic shock-activated monocytes/macrophages and compare them to non-treated cells. Of the genes that exhibited differences of expression in the activated cell population, 94% (68/72) displayed increased activity. The mRNA levels of 43/68 of these genes (63%) were found to be 1.5-fold or higher (1.5-7.98) in the activated macrophages cell population as compared to the non-treated cells. Only four genes were found to have lower mRNA levels in the activated cells, with ratios of expression of 0.62-0.8, which may suggest that the changes are insignificant. A significant number of the genes that showed increased levels of expression is known to be directly involved in macrophage function and wound healing. This may correlate with the increased secretion of different cytokines by the activated macrophages depicted previously. Other groups of genes expressed are known to be involved in important pathways such as neuronal growth and function, developmental defects and cancer. The hypo-osmotic shock induces a gene expression profile of cytokines and receptors in the activated cells. These may evoke potential abilities to produce a variety of protein products needed in the wound healing process and may bring to light possibilities for other therapeutic applications of these cells.
Assuntos
Técnicas de Cultura de Células/métodos , Ativação de Macrófagos , Macrófagos/imunologia , Monócitos/imunologia , Células Cultivadas , Citocinas/biossíntese , Citocinas/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Substâncias de Crescimento/biossíntese , Substâncias de Crescimento/genética , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Pressão Osmótica , RNA Mensageiro/biossíntese , Receptores Imunológicos/biossíntese , Receptores Imunológicos/genética , Úlcera Cutânea/terapiaRESUMO
We report two patients who were treated with thalidomide for resistant multiple myeloma (MM) and developed extramedullary plasmacytomas despite a good response in the bone marrow. The first patient had progressive disease 18 months post autologous peripheral stem cell transplant. Two and a half months after the initiation of thalidomide therapy extensive new plasmacytomas of the skin and nasal mucosa appeared while the medullary response continued. The second patient was treated with thalidomide for resistant MM. Despite a medullary response he developed neurological signs compatible with cranial nerve involvement and an MRI study was suggestive of a plasmacytoma involving the sellar region. We assume that a change in the expression of some adhesion molecules on the myeloma and/or the stromal cells is responsible for this phenomenon. Treating Physicians should be aware of this phenomenon in MM patients receiving thalidomide.
Assuntos
Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Plasmocitoma/patologia , Talidomida/efeitos adversos , Adulto , Medula Óssea/patologia , Neoplasias da Medula Óssea/patologia , Neoplasias Encefálicas/patologia , Progressão da Doença , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/patologia , Neoplasias Nasais/patologia , Neoplasias Cutâneas/patologia , Talidomida/administração & dosagemRESUMO
Phagocytosis and secretion of interleukins and growth factors put the macrophage in the centre of the wound healing process. For the last four years over 400 human ulcers have been treated in elderly and paraplegic patients by local application of monocytes prepared from a blood unit, in a unique, closed, sterile system. The process of preparation includes a step of hypo-osmotic shock, which induces monocyte/macrophage activation. This is different from any other known method of activation. In the present study we evaluated the efficacy of the hypo-osmotic shock. We found enhanced levels of IL-1 (P = 0.004) and IL-6 (P = 0.001) in the incubation medium (100% autologous serum) of the activated cells, as compared with controls, prepared in the same system. The IL-1 reached a plateau after 6 and 12 h incubation at 37 degrees C, in both experimental and control incubation medium. The level of IL-6 was further elevated after 12 and 24 h incubation in experimental and control incubation mediums (P = 0.001). The phagocytosis of fluorescent beads was markedly enhanced after hypo-osmotic shock (P = 0.005). The osmotic shock induced macrophages were compared to those stimulated with LPS, and osmotic shock was proved to be at least as efficient method of stimulation as LPS.
Assuntos
Soluções Hipotônicas/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Meios de Cultivo Condicionados , Humanos , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Microesferas , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Pressão Osmótica , Fagocitose/efeitos dos fármacos , CicatrizaçãoRESUMO
Pyrimidine 5' nucleotidase (P5'N-1) deficiency is an autosomal recessive condition causing hemolytic anemia characterized by marked basophilic stippling and the accumulation of high concentrations of pyrimidine nucleotides within the erythrocyte. It is implicated in the anemia of lead poisoning and is possibly associated with learning difficulties. Recently, a protein with P5'N-1 activity was analyzed and a provisional complementary DNA (cDNA) sequence published. This sequence was used to study 3 families with P5'N-1 deficiency. This approach generated a genomic DNA sequence that was used to search GenBank and identify the gene for P5'N-1. It is found on chromosome 7, consists of 10 exons with alternative splicing of exon 2, and produces proteins 286 and 297 amino acids long. Three homozygous mutations were identified in this gene in 4 subjects with P5'N-1 deficiency: codon 98 GAT-->GTT, Asp-->Val (linked to a silent polymorphism codon 92, TAC-->TAT), codon 177, CAA-->TAA, Gln-->termination, and IVS9-1, G-->T. The latter mutation results in the loss of exon 9 (201 bp) from the cDNA. None of these mutations was found in 100 normal controls. The DNA analysis was complicated by P5'N-1 pseudogenes found on chromosomes 4 and 7. This study is the first description of the structure and location of the P5'N-1 gene, and 3 mutations have been identified in affected patients from separate kindreds. (Blood. 2001;97:3327-3332)
Assuntos
5'-Nucleotidase/deficiência , 5'-Nucleotidase/genética , Anemia Hemolítica/genética , 5'-Nucleotidase/química , Processamento Alternativo , Sequência de Aminoácidos , Anemia Hemolítica/enzimologia , Sequência de Bases , Criança , Pré-Escolar , Cromossomos Humanos Par 7 , DNA Complementar/química , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Eritrócitos/enzimologia , Eritrócitos/metabolismo , Éxons , Feminino , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação , Noruega , Linhagem , Nucleotídeos de Pirimidina/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , África do SulRESUMO
Hypophosphatemia associated with bone marrow transplantation has been infrequently reported. The suggested mechanism is phosphate uptake by the replicating cells. Various cytokines are associated with the development of hypophosphatemia. The present study evaluated the interrelationship between cytokine release, the rise in WBC and the development of hypophosphatemia during the engraftment period. Blood samples were obtained from 60 patients undergoing peripheral blood stem cell transplant, on the day of admission and then daily from the day of transplant until discharge. Hypophosphatemia developed in 62% of the patients. The median day of minimal phosphorus level was +8 and it antedated engraftment by 2 days. There was a significant correlation between the day of minimal phosphorus level and the day of maximal WBC and a significant correlation between the fall in phosphorus level and WBC rise. IL-6 and IL-8 showed similar kinetics. Higher IL-6 and IL-8 levels were directly associated with lower phosphorus levels. In conclusion, hypophosphatemia commonly occurs in the post-transplant period. We assume that both a direct effect of cytokine release and an increased consumption by the dividing WBCs contribute to its appearance. As its occurrence usually antedates engraftment it can be used as a forerunner for WBC recovery.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hipofosfatemia/sangue , Adulto , Idoso , Biomarcadores/sangue , Citocinas/sangue , Citocinas/metabolismo , Feminino , Humanos , Hipofosfatemia/etiologia , Interleucina-6/sangue , Interleucina-8/sangue , Cinética , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Chronic lymphocytic leukemia (CLL) shows evidence of familial aggregation, but the genetic basis is poorly understood. The existence of a linkage between HLA and Hodgkin lymphoma, another B-cell disorder, coupled with the fact that CLL is frequently associated with autoimmune disease, led to the question of whether the major histocompatibility complex (MHC) region is involved in familial cases of CLL. To examine this proposition, 5 microsatellite markers on chromosome 6p21.3 were typed in 28 families with CLL, 4 families with CLL in association with other lymphoproliferative disorders, and 1 family with splenic lymphoma with villous lymphocytes. There was no evidence of linkage in these families to chromosome 6p21.3. The best estimates of the proportions of sibling pairs with CLL that share 0, 1, or 2 MHC haplotypes were not significantly different from the null expectation. This implies that genes within the MHC region are unlikely to be the major determinants of familial CLL. (Blood. 2000;96:3982-3984)
Assuntos
Leucemia Linfocítica Crônica de Células B/genética , Complexo Principal de Histocompatibilidade/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 6 , Saúde da Família , Feminino , Ligação Genética , Genótipo , Antígenos HLA/genética , Humanos , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Estatísticas não ParamétricasRESUMO
High dose chemotherapy and autologous stem cell transplantation are widely used in relapsed and primary refractory Hodgkin's disease. We transplanted 42 patients with Hodgkin's disease between 1990-1998. Median follow-up was 31 months (range 1-102). 29 (69%) were transplanted after relapse and 13 (31%) were refractory to first line therapy. Median age at transplantation was 29 years (range 19-58) and 23 (55%) were males. All were treated with the BEAM protocol (carmustine, etoposide, cytarabine and melphelan). 18 who were in remission received radiotherapy following transplantation. The source of the stem cells was bone marrow in 17% and peripheral blood in 83%. At initial diagnosis: 57% had stage III-IV disease and B symptoms were present in 52%. 75% were treated with MOPP, ABVD or with related versions. Radiotherapy followed in 52%. Prior to transplantation, 45% of the relapsed group were in the advanced stage. 33% and 12% of all patients had lung and bone involvement, respectively. The complete remission rate was 86% for the 2 groups. 2 (5%) died from transplant-related complications and MDS/AML developed in 2 (5%) after transplantation. The 3-year overall survival (OS) and disease-free survival (DFS) were 68% and 60%, respectively. The 3-year OS for the relapsed group was 64% compared with 76% for the refractory group, and the 3-year DFS for the relapsed group was 60% vs. 42% for the refractory group (neither difference significant). Radiotherapy following transplantation did not have a beneficial effect on DFS. No prognostic factors for outcome of transplantation were found, most probably due to the limited number of patients and the high variability of disease characteristics. We conclude that high dose chemotherapy and autologous stem cell transplantation are effective and relatively safe for relapsed or primary refractory Hodgkin's disease. The DFS at 3 years was longer for those transplanted after relapse than those with primary refractory disease, but not significantly. Patients with primary refractory disease can be salvaged with high dose chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/terapia , Adulto , Bleomicina/administração & dosagem , Carmustina/administração & dosagem , Terapia Combinada , Citarabina/administração & dosagem , Dacarbazina/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Doença de Hodgkin/radioterapia , Humanos , Masculino , Mecloretamina/administração & dosagem , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Podofilotoxina/administração & dosagem , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Vimblastina/administração & dosagem , Vincristina/administração & dosagemRESUMO
Acute lymphoblastic leukemia (ALL) is a malignant disease whose incidence is relatively low among adults, unlike in children. Adults with ALL have a lower rate of long-term disease-free survival. During the last 20 years, a German multicenter group has shown that their protocols have achieved good results in adults ALL. We reviewed the medical records of 35 ALL patients, aged 19-63 years, whom we treated with these protocols (1988-1997). The remission rate was 94%. At a median follow-up of 46 months the 2-year overall survival was 54% and the disease-free survival was 94%. Although 2 patients died of bone marrow transplant complications, no death was directly associated with drug toxicity. The main grade 3 or 4 side effects (WHO classification) were neutropenia (91%), thrombocytopenia (71%) and anemia (71%). With there protocols we achieved high overall and disease-free survival rates, especially in comparison with other reports. Despite the high rate of severe treatment toxicity, there were no fatalities directly related to treatment. These results emphasize the need to concentrate treatment of adult ALL patients in large medical centers with expertise in the use of the complicated treatment protocols required.
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Intervalo Livre de Doença , Feminino , Seguimentos , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
All-trans-retinoic acid (ATRA) is considered the recommended induction treatment for acute promyelocytic leukemia. In the pre-ATRA era pulmonary bleeding was a common cause of death in these patients, mostly due to disseminated intravascular coagulation which was further exacerbated by the administration of chemotherapy. Although ATRA syndrome, the most serious adverse effect of ATRA treatment, involves the lungs, pulmonary hemorrhage has only rarely been reported as a manifestation of ATRA syndrome. Here we describe 2 patients who developed diffuse alveolar hemorrhage during treatment with ATRA. The possible mechanisms of pulmonary bleeding in these cases are discussed.
Assuntos
Antineoplásicos/efeitos adversos , Hemorragia/etiologia , Leucemia Promielocítica Aguda/tratamento farmacológico , Pneumopatias/etiologia , Tretinoína/efeitos adversos , Adulto , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Testes de Coagulação Sanguínea , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Dispneia/induzido quimicamente , Evolução Fatal , Febre/induzido quimicamente , Hemorragia/induzido quimicamente , Humanos , Leucemia Promielocítica Aguda/complicações , Pneumopatias/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Alvéolos Pulmonares/efeitos dos fármacos , Indução de Remissão , Síndrome , Tretinoína/administração & dosagem , Tretinoína/uso terapêuticoRESUMO
We have treated 17 refractory or relapsed multiple myeloma patients resistant to chemotherapy with thalidomide at a dose of 200-800 mg/day. Eleven patients responded, five of whom had a very good partial response (> 75% decline in M protein) and another five exhibited a partial response (> 50% decline in M protein). Except for one patient, treatment was well tolerated with only mild side-effects. Thalidomide should be included in the therapeutic options for refractory myeloma.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Talidomida/uso terapêutico , Adulto , Idoso , Relação Dose-Resposta a Droga , Resistência a Múltiplos Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Fluorescence in situ hybridization (FISH), as a new clinical test, is not presently standardized. For practical reasons, each laboratory must build its own criteria. In this work, we present our standardization criteria for clinical practice, which include not only the methods for cell fixation, specimen preparation, and hybridization conditions, but mainly the definition of false-positive range and the scoring criteria of microscopic analysis. These include signal assessment, difference between individual microscopists, evaluation of specimen homogeneity, and the minimum number of scored nuclei required for a clinically reliable result. For this purpose, we analyzed by FISH 24 healthy volunteer donors, 31 patients affected by non-chronic myelogenous leukemia (CML) hematological malignancies, 47 CML patients at diagnosis, and 82 CML patients during treatment for the BCR/ABL fusion. In this article, we present several quality control and assurance methods that can be useful in providing standardization of the FISH technique.