RESUMO
Several prognostic factors have been recognized in patients with multiple myeloma (MM). Among the most important are: the serum levels of beta2-microglobulin, albumin, and LDH; the labeling index; and an abnormal karyotype. Patients with amyloidosis (AL) have poor prognosis; however, little is known concerning the prognostic significance of AL associated to MM. In 201 consecutive patients with de novo MM, we performed a fat-pad biopsy needle aspiration (FPBNA) that was stained with Congo red. Sixty eight (34%) patients had AL and a poorer prognosis disease: lower performance status, presence of B symptoms, higher LDH and calcium values, and worse response to chemotherapy. Cox regression model for overall survival detected three variables having independent prognostic significance: the presence of AL (RR = 3.4, P < 0.004), serum albumin levels <3.5 g/dl (RR 3.2, p < 0.005), and patients not achieving complete remission or very good partial remission (RR 2.9, p < 0.02). In 28% of patients with de novo MM, FPBNA was useful to detect incidental amyloidosis. During follow-up, 69% of these patients had symptoms of AL. Excluding 16 patients with obvious symptoms of AL at diagnosis, overall survival was worse in patients who developed later symptoms of AL. MM-associated AL represents a poorer prognosis disease even in the absence of symptoms at diagnosis, and this specific association may be considered as an independent high-risk prognostic factor. The routine study of periumbilical fat-pad tissue should be mandatory in all patients with MM.
Assuntos
Amiloidose/diagnóstico , Amiloidose/patologia , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/patologia , Tecido Adiposo/patologia , Adulto , Idoso , Amiloidose/sangue , Amiloidose/tratamento farmacológico , Antineoplásicos/uso terapêutico , Biópsia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/tratamento farmacológico , Prognóstico , Modelos de Riscos Proporcionais , Análise de Regressão , Indução de Remissão , Fatores de RiscoRESUMO
Autologous peripheral blood stem cell transplantation is the therapy of choice for the treatment of multiple myeloma (MM) patients younger than 70 years old. Between August 1993 and November 2004, 54 patients with MM were autografted after conditioning with high-dose oral melphalan 140 mg/m(2) in combination with etoposide and carmustine (28 patients) or with high-dose melphalan 200 mg/m(2) I.V. (26 patients). The oral and IV melphalan groups were comparable. There were no significant differences in disease-free survival (DFS) and overall survival (OS) between the groups; however, in patients transplanted in remission, OS and DFS were better in the I.V. melphalan group. Four good-prognostic factors were identified: interval between diagnosis and transplant <18 months, number of prior chemotherapy lines < or =2, remission status (complete or partial), and the use of I.V. melphalan. In conclusion, I.V. melphalan is the therapy of choice for conditioning patients with MM who are in remission.
Assuntos
Melfalan/uso terapêutico , Mieloma Múltiplo/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Administração Oral , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Carmustina/administração & dosagem , Carmustina/uso terapêutico , Terapia Combinada , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Etoposídeo/administração & dosagem , Etoposídeo/uso terapêutico , Feminino , Humanos , Infusões Intravenosas , Masculino , Melfalan/administração & dosagem , México , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Indução de Remissão , Transplante Autólogo , Resultado do TratamentoRESUMO
We studied 298 patients with severe aplastic anaemia (SAA) allografted in four Latin American countries. The source of cells was bone marrow (BM) in 94 patients and PBSCs in 204 patients. Engraftment failed in 8.1% of recipients with no difference between BM and PBSCs (P=0.08). Incidence of acute GvHD (aGvHD) for BM and PBSCs was 30% vs 32% (P=0.18), and for grades III-IV was 2.6% vs 11.6% (P=0.01). Chronic GvHD (cGvHD) between BM and PBSCs was 37% vs 59% (P=0.002) and extensive 5% vs 23.6% (P=0.01). OS was 74% vs 76% for BM vs PBSCs (P=0.95). Event-free survival was superior in patients conditioned with anti-thymocyte globulin (ATG)-based regimens compared with other regimens (79% vs 61%, P=0.001) as excessive secondary graft failure was seen with other regimens (10% vs 26%, P=0.005) respectively. In multivariate analysis, aGvHD II-IV (hazard ratio (HR) 2.50, confidence interval (CI) 1.1-5.6, P=0.02) and aGvHD III-IV (HR 8.3 CI 3.4-20.2, P<0.001) proved to be independent negative predictors of survival. In conclusion, BM as a source of cells and ATG-based regimens should be standard because of higher GvHD incidence with PBSCs, although the latter combining with ATG in the conditioning regimen could be an option in selected high-risk patients.
Assuntos
Anemia Aplástica/terapia , Soro Antilinfocitário/administração & dosagem , Antígenos HLA , Irmãos , Transplante de Células-Tronco , Doença Aguda , Adolescente , Adulto , Idoso , Aloenxertos , Anemia Aplástica/mortalidade , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , América Latina , Masculino , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
We prospectively conducted a quantitative and phenotypic analysis of T, B, natural killer (NK), NKT, type 1 and 2 dendritic cells (DC), and regulatory T cells, before and after mobilization with intermediate doses of granulocyte colony-stimulating factor (G-CSF) (16 microg/kg per day). Between November, 2003, and December, 2004, we collected stem cells from 25 HLA identical sibling donors for allogeneic hematopoietic stem cell transplantation. Before mobilization and 3 h after the fourth and fifth doses of G-CSF, blood samples were taken for blood counts and flow cytometry. The median number of regulatory T cells before and after G-CSF was statistically different (69 +/- 41 x 10(6)/L versus 161 +/- 159 x 10(6)/L, p < 0.01). We observed a 1.7-fold increase in NK and NKT cells (p < 0.009 and p < 0.02, respectively). DC were mobilized with a 11.5-fold increase in type 2 (p < 0.004) and a 8.5-fold increase in type 1 DC (p < 0.003). The patients received a mean of: 2.2 x 10(7)/kg +/- 1.4 x 10(7)/kg of NK cells, 0.95 x 10(7)/kg +/- 0.81 x 107/kg of NKT cells, 0.43 x 107/kg +/- 0.53 x 10(7)/kg of type 1 DC, 0.3 v 10(7)/kg +/- 0.45 x 10(7)/kg of type 2 DC and 1.4 x 10(7)/kg +/- 1.2 x 10(7)/kg of regulatory T cells. Using intermediate doses of G-CSF, we have demonstrated the mobilization of different lymphocyte subsets, in particular regulatory T cells and DC, which can be expanded later and used in the treatment of cancer and autoimmune diseases.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Transplante de Células/métodos , Células Dendríticas/imunologia , Fator Estimulador de Colônias de Granulócitos/farmacologia , Ativação Linfocitária , Linfócitos/imunologia , Receptores de Interleucina-2/análise , Células-Tronco/citologia , Adulto , Antígenos CD/análise , Remoção de Componentes Sanguíneos/métodos , Feminino , Mobilização de Células-Tronco Hematopoéticas/métodos , Humanos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , IrmãosRESUMO
Using a reduced-intensity stem cell transplantation (RIST) schedule, 24 patients with Philadelphia (Ph1) (+) chronic myelogenous leukemia (CML) in first chronic phase (CP) were prospectively allografted in four Latin American countries: México, Brazil, Colombia and Venezuela, using HLA-identical siblings as donors. The median age of the patients was 41 years (range 10-71 years); there were eight females. Patients received a median of 4.4 x 10(6)/kg CD34 cells. The median time to achieve above 0.5 x 10(9)/l granulocytes was 12 days, range 0-41 days, and the median time to achieve above 20 x 10(9)/l platelets was also 12 days, range 0-45 days. In all, 22 patients are alive 81-830 (median 497) days after RIST. The 830-day probability of survival is 92%, and the median survival has not been reached, being beyond 830 days. A total of 11 patients (46%) developed acute graft-versus-host disease (GVHD), and seven of 23 (30%) developed chronic GVHD. Two patients died 43 and 210 days after RIST, one as a result of sepsis and the other of chronic GVHD. The 100-day mortality was 4.4%, and transplant-related mortality was 8%. RIST for patients with CML in CP appears to be an adequate therapeutic option.
Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Transplante de Células-Tronco/métodos , Adolescente , Adulto , Idoso , Antígenos CD34/biossíntese , Benzamidas , Remoção de Componentes Sanguíneos , Criança , Feminino , Doença Enxerto-Hospedeiro/terapia , Humanos , Mesilato de Imatinib , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Condicionamento Pré-Transplante , Resultado do TratamentoRESUMO
Waldenström's macroglobulinemia is a rare malignant disorder of B lymphocytes. There are no studies on the use of interferon-alpha (IFN-alpha) as frontline therapy in this disease. Between April 1991 and September 2000, we treated 21 newly diagnosed patients using 8 mg/m(2) chlorambucil and 40 mg/m(2) prednisone p.o. daily for 10 days and 3 megaU/m(2) IFN-alpha three times a week. Patients who responded after induction continued receiving IFN until relapse or death. We found a high frequency of peripheral neuropathy (43%) and grade 3 diffuse marrow fibrosis (43%). Objective response was achieved in 12 (57%) patients, including 4 (19%) complete responders. Median time from treatment to response was 8 months (range 3-18). Median progression-free survival was 70 months (95% CI 47-93), and overall survival was 91 months (95% CI 50-132). Patients who achieved objective response lived longer (91 vs. 33 months, p < 0.03), as did patients who had lactic dehydrogenase (LDH) < 180 U/L (89 vs. 54 months, p < 0.01). Grade 3 hematologic toxicity was observed during induction in 5 patients. IFN-alpha is an effective agent for the induction and maintenance treatment of Waldenström's macroglobulinemia patients. LDH > 180 U/L and failure to respond are adverse prognostic factors.
Assuntos
Interferon-alfa/uso terapêutico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Idoso , Clorambucila/administração & dosagem , Clorambucila/uso terapêutico , Intervalo Livre de Doença , Esquema de Medicação , Quimioterapia Combinada , Feminino , Fibrose , Humanos , Interferon-alfa/administração & dosagem , L-Lactato Desidrogenase/análise , Masculino , Doenças do Sistema Nervoso Periférico/fisiopatologia , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Indução de Remissão , Fatores de Tempo , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/fisiopatologiaRESUMO
Reduced intensity conditioning (RIC) have allowed the application of transplantation to older patients and to patients with underlying medical problems. Between October, 1999, and June, 2003, 61 patients with acute leukemia or chronic myeloid leukemia received allogeneic peripheral blood hematopoietic stem cell transplantation (HSCT) from HLA-identical siblings. Thirty-four were conditioned with myeloablative protocols and twenty-seven with RIC regimens. The patients in the myeloablative group were younger (29 vs. 37 years; p < 0.0003), most of them were transplanted in complete remission (74% vs. 59%; p < 0.03), had a shorter interval between diagnosis and HSCT (12 vs. 21 months; p < 0.02) and a greater proportion belonged to standard-risk prognosis (68% vs. 48%; p < 0.1). The median times to neutrophil, platelet and red blood cell engraftment for the myeloablative and RIC groups were 14 versus 11 days (p < 0.009), 17 versus 9 days (p < 0.0001), and 19 versus 12 days (p < 0.007), respectively. Transfusion requirements were lower in the RIC group. Severe mucositis was present in 32% and 7%, respectively (p < 0.01). The proportion of patients having acute graft versus-disease (GVHD), chronic GVHD, and infections was the same, as well as early and late mortality, disease-free survival, and overall survival. Analyzing all the patients together, three factors significantly influenced overall survival: standard risk patients, complete remission at transplant, and the absence of severe acute GVHD. In conclusion, our data suggest that even in high-risk patients, RIC transplantation seems to be as useful as ablative HSCT.
Assuntos
Transfusão de Sangue/métodos , Leucemia/terapia , Transplante de Células-Tronco/métodos , Transplante Homólogo , Adolescente , Adulto , Transplante de Células , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/patologia , Humanos , Imunossupressores/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Mucosa/metabolismo , Mucosa/patologia , Prognóstico , Recidiva , Indução de Remissão , Risco , Fatores de Tempo , Condicionamento Pré-Transplante , Resultado do TratamentoRESUMO
In the present study, we assessed the clinical effect of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in the treatment of refractory, grade III-IV hemorrhagic cystitis (HC) in six patients who underwent bone marrow transplantation (BMT). These were four males and two females, aged 24-40 years (median age 30.5 years). All received allogeneic BMT from HLA-identical siblings after preparation with busulfan-cyclophosphamide. HC was evident 24. 5 days (range 15-33 days) after BMT. Median duration of HC before treatment was 5 days (range 4-9 days). Treatment consisted of intravesical instillation of rhGM-CSF (400 microg) for 3 consecutive days. A complete response was observed in three patients, the other three showed a partial response. Median time to achieve response was 36 h (range 0.2-72 h). Hematuria was controlled after the first (two patients), second (two patients) or third (two patients) dose of intravesical rhGM-CSF. Patients were discharged from the hospital 10. 5 days (range 3-41 days) after treatment. All patients have been followed for up to 10 months and none have required further treatment. No systemic or bladder side-effects have been observed. Although our results indicate that intravesical instillation of rhGM-CSF is effective in the treatment of HC, a phase II clinical trial, including a larger series of patients, is needed.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Cistite/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Adulto , Cistite/etiologia , Intervalo Livre de Doença , Transfusão de Eritrócitos , Feminino , Hematúria/complicações , Hemorragia , Humanos , Leucemia/complicações , Masculino , Proteínas Recombinantes/administração & dosagem , Transplante Homólogo , Resultado do Tratamento , Doenças da Bexiga Urinária/complicaçõesRESUMO
A 24-year-old woman with CML underwent allogeneic BMT in August 1995 from a one-antigen HLA mismatched brother. Conditioning included BuCy2 and CsA and MTX were used to prevent GVHD. In July 1997 she developed right leg pain, lytic bone lesions of distal femur and a solid mass of soft tissue. Histological diagnosis of malignant fibrous histiocytoma was made. Despite treatment with surgery and chemotherapy (doxorubicin and ifosfamide), the patient died 1 year later with local recurrence of the tumor and liver, lung and brain metastases. The CML was in CR.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Histiocitoma Fibroso Benigno/etiologia , Leucemia Mieloide de Fase Crônica/terapia , Segunda Neoplasia Primária/etiologia , Adulto , Feminino , Neoplasias Femorais/diagnóstico , Neoplasias Femorais/etiologia , Histiocitoma Fibroso Benigno/diagnóstico , Humanos , Masculino , Segunda Neoplasia Primária/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/etiologia , Transplante HomólogoRESUMO
Between August 1994 and June 1999, 56 patients were prospectively randomized to receive ifosfamide 10 g/m2 + GM-CSF 5 microg/kg/day (IFO+GM-CSF n = 28) and cyclophosphamide 4 g/m2 + GM-CSF 5 microg/kg/day (CY+GM-CSF n = 28). Both groups were comparable for age, gender, diagnosis, disease stage and previous chemotherapy. The IFO+GM-CSF group demonstrated a shorter median interval between therapy and apheresis (10 days (8-14) vs 13 days (8-25) P = 0.002), median number of doses of GM-CSF (9 (7-13) vs 15 (9-31) P = 0.001), median of days with aplasia (0.5 (0-10) vs 6 (0-21) P = 0.001), median days with fever (0 (0-6) vs 3 (0-9) P = 0.006) and median of days using i.v. antibiotics (0 (0-11) vs 7.5 (0-19) P = 0.002). The median MNC yield was similar in both groups. The CD34+ cell yield was better in the CY+GM-CSF group (3.14 (0.9-11.8) vs 5.33 (0. 08-32)) but not at significant levels (P = 0.1). White blood cell hematopoietic recovery was more rapid in the CY+GM-CSF group (16 (10-22) vs 13 (10-24) P = 0.02). Platelet engraftment was similar in both groups. Costs of mobilization and transplantation were almost the same: $28 570 ($18 527-$47 028) and $30 020 ($17 281-$67 591), respectively (P = 0.9). There were no differences in disease-free survival and overall survival between both groups. Mild and transient non-hematological toxicity (hemorrhagic cystitis, decrease in serum creatinine clearance and CNS dysfunction) was seen most frequently in the IFO+GM-CSF group.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/terapia , Ifosfamida/uso terapêutico , Linfoma não Hodgkin/terapia , Mieloma Múltiplo/terapia , Adolescente , Adulto , Carmustina/administração & dosagem , Criopreservação , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Mobilização de Células-Tronco Hematopoéticas/efeitos adversos , Células-Tronco Hematopoéticas/patologia , Doença de Hodgkin/mortalidade , Humanos , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Estudos Prospectivos , Proteínas Recombinantes , Análise de Regressão , Taxa de Sobrevida , Transplante AutólogoRESUMO
BACKGROUND: The use of conventional cyclosporine (Sandimmune) requires great care, as this drug exhibits a narrow therapeutic index and wide interindividual variability in its pharmacokinetics. Recently, a new microemulsion formulation (Neoral) was developed. With this formulation, cyclosporine is absorbed at the small intestine without the presence of bile. Therefore, the objective of this study was to compare the bioavailability of cyclosporine after the administration of conventional and microemulsion formulations in healthy Mexican volunteers in order to approach the optimal dosage regimen of microemulsion in the Mexican population. METHODS: The trial was conducted using 23 healthy volunteers according to a randomized crossover design. Volunteers received one 7.5-mg/kg dose as each formulation, with a 1-week washout period between treatments. Blood samples of 0.5 mL were obtained according to the following schedule: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 h after medication. RESULTS: These indicated that Cmax and AUC0-24 values were higher with the microemulsion than with the conventional formulation. CONCLUSIONS: The microemulsion had a better absorption profile than the conventional formulation, because plasma levels with the conventional formulation demonstrated oscillations rather than reflecting an erratic absorption. Lower doses of the microemulsion are required to obtain Cmax values similar to those obtained with conventional cyclosporine.
Assuntos
Ciclosporina/farmacocinética , Administração Oral , Disponibilidade Biológica , Estudos Cross-Over , Ciclosporina/administração & dosagem , Composição de Medicamentos , Avaliação de Medicamentos , Feminino , Nível de Saúde , Humanos , Masculino , México , VoluntáriosRESUMO
BACKGROUND: Bone marrow transplantation (BMT) is the therapy of choice for patients with chronic myeloid leukemia (CML) who have a human leukocyte antigen (HLA)-identical donor and are under 50 years of age. METHODS: Here, 45 patients with CML were treated with busulfan (Bu) 16 mg/kg and cyclophosphamide (Cy) 120 mg/kg before allogeneic BMT from an HLA-identical sibling 27 (60%) or a 1-antigen mismatch donor 18 (40%). Eighteen patients (40%) were in the early chronic phase (CP) and 27 (60%) in late CP. We used cyclosporin-A (CsA) in 20 patients and cyclosporin-A-methotrexate (CsA-MTX) in 25 for graft-vs.-host disease (GVHD) prophylaxis. RESULTS: We observed a high incidence of acute and chronic GVHD (69% and 67%, respectively). A multivariate analysis identified differences in the sex of the donor and the recipient (p = 0.03) and grade III-IV acute GVHD (p = 0.0001) as significant adverse influences on disease-free survival. Age, sex, chronic GVHD, disease phase, one antigen-mismatch and use of CsA or CsA-MTX had no statistical significance. The 3-year probabilities of relapse, disease-free survival, and overall survival were 11%, 55%, and 60%, respectively. Transplant-related mortality occurred in 31% of the cases. The high frequency of GVHD is explained by HLA determination by serological typing, differences in sex between the donor and recipient, and a high proportion (40%) of 1 antigen-mismatch donors. CONCLUSIONS: BMT is a procedure feasible for patients with CML in early and late chronic phase and even in those with an HLA non-identical donor. Strategies directed to decrease acute GVHD could improve the outcome of these patients.
Assuntos
Transplante de Medula Óssea , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Transplante Homólogo , Adolescente , Adulto , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/estatística & dados numéricos , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Histocompatibilidade , Humanos , Infecções/etiologia , Infecções/mortalidade , Inflamação/etiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Tábuas de Vida , Masculino , México , Pessoa de Meia-Idade , Cromossomo Filadélfia , Pré-Medicação , Modelos de Riscos Proporcionais , Recidiva , Análise de Sobrevida , Doadores de Tecidos , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo/efeitos adversos , Transplante Homólogo/estatística & dados numéricos , Resultado do TratamentoRESUMO
There are limited data on hematopoietic cell transplantation (HCT) in primary plasma cell leukemia (pPCL), an aggressive plasma cell disorder. We report outcomes of 147 patients with pPCL receiving autologous (n=97) or allogeneic (n=50) HCT within 18 months after diagnosis between 1995 and 2006. Median age was 56 years and 48 years for autologous HCT and allogeneic HCT, respectively. Progression-free survival (PFS) at 3 years was 34% (95% confidence interval (CI), 23-46%) in the autologous group and 20% (95% CI, 10-34%) in the allogeneic group. Cumulative incidence of relapse at 3 years was 61% (95% CI, 48-72%) in the autologous group and 38% (95% CI, 25-53%) in the allogeneic group. Overall survival (OS) at 3 years was 64% (95% CI, 52-75%) in the autologous group and 39% (95% CI, 26-54%) in the allogeneic group. Non-relapse mortality (NRM) at 3 years was 5% (95% CI, 1-11%) in the autologous group and 41% (95% CI, 28-56%) in the allogeneic group. The encouraging OS after autologous HCT, establishes the safety and feasibility of this consolidative treatment option after initial induction therapy for pPCL. Allogeneic HCT, although associated with a significantly lower relapse rate, carries a much higher risk of NRM and no OS benefit.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Plasmocitária/cirurgia , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The international staging system (ISS) for multiple myeloma (MM) is a validated alternative to the Durie-Salmon staging system (DSS) for predicting survival at diagnosis. We compared these staging systems for predicting outcomes after upfront autologous stem cell transplantation by analyzing the outcomes of 729 patients between 1995 and 2002. With a median follow-up of 56 months, the univariate probabilities (95% CI) of non-relapse mortality (NRM), relapse, progression-free survival (PFS) and overall survival (OS) at 5 years were 7, 68, 25 and 52%, respectively. The median OS for stages I, II, III by DSS and ISS were 82, 68, 50 and 64, 68, 45 months, respectively. The concordance between the two staging systems was only 36%. Staging systems were formally compared using Cox models fit with DSS and ISS stages. The relative risks of PFS and OS were significantly different for stages I vs II and II vs III for DSS, but only for stages II vs III for ISS. Although both systems were predictive of PFS and OS, the DSS was superior in formal statistical comparison using Brier score. However, neither system was strongly predictive of outcomes, indicating the need for newer schemes incorporating other prognostic markers.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/patologia , Estadiamento de Neoplasias/métodos , Adulto , Idoso , Progressão da Doença , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/cirurgia , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Condicionamento Pré-Transplante , Transplante Autólogo , Resultado do TratamentoRESUMO
To analyze the relationship between the cellular composition of peripheral blood allografts and clinical outcome, we performed a prospective study in 45 adult patients who underwent allogeneic peripheral blood hematopoietic stem cell transplantation (HSCT) from a histocompatibility leukocyte antigen identical sibling donor for different hematological malignancies. The dose of CD34+, CD3+, CD4+, CD8+, and CD19+ lymphocytes, natural killer (NK) cells, natural killer T (NKT) cells, type 1 and type 2 dendritic cells (DC1 and DC2), as well as regulatory T (Treg) lymphocytes was analyzed. All patients were conditioned with busulphan and cyclophosphamide (BuCy2) +/- VP-16 and received a short course of methotrexate and cyclosporin-A as graft-versus-host disease (GVHD) prophylaxis. Acute GVHD (aGVHD) was present in 9 of 43 (21%) patients, and chronic GVHD (cGVHD) developed in 18 of 39 (46%) patients. There was a significantly higher incidence of aGVHD in patients receiving more than 6x10(6)/kg CD34+ cells. In univariate analysis, variables associated with better survival were as follows: a dose of less than 1.5x10(7)/kg NKT cells and less than 1.7x10(6)/kg DC2 for disease-free survival (DFS), and a dose of less than 3x10(7)/kg NK cells, less than 1.5x10(7)/kg NKT cells, less than 3x10(6)/kg DC1, and less than 1.7x10(6)/kg DC2 for overall survival (OS). In the Cox regression analysis, the dose of NKT cells was the only variable associated with better DFS, while the doses of NK, NKT, and CD34+ cells (less than 8x10(6)/kg) were associated with better OS. In conclusion, different circulating cell populations, other than CD34+ cells, are also of relevance in predicting the clinical outcome after allogeneic peripheral blood HSCT.
Assuntos
Células Dendríticas/metabolismo , Fator Estimulador de Colônias de Granulócitos/metabolismo , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Células Matadoras Naturais/citologia , Adolescente , Adulto , Antígenos CD19/biossíntese , Antígenos CD34/biossíntese , Complexo CD3/biossíntese , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Criança , Feminino , Doença Enxerto-Hospedeiro/terapia , Humanos , Células Matadoras Naturais/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Linfócitos T Reguladores/metabolismo , Condicionamento Pré-Transplante/métodos , Transplante HomólogoRESUMO
Between June 2003 and November 2004, we collected mobilized peripheral blood units from 29 patients with non-Hodgkin's lymphoma and multiple myeloma for autologous peripheral blood stem cell transplantation. They received granulocyte colony-stimulating factor (G-CSF) (16 micro g/kg/day) for a total of 5 days. Immediately before and 3 h after the fourth and fifth dose of G-CSF, we performed flow cytometry analysis to quantify: T cells (CD3+CD4+, CD3+CD8+), B cells (CD19+), NK cells (CD3-CD16+CD56+), NKT cells (CD3+CD16+CD56+), type 1 dendritic cells (DC1) (lin-HLA-DR+CD11c+), type 2 dendritic cells (DC2) (lin-HLA-DR+CD123+), regulatory T cells (Tregs) (CD4+CD25+), and activated T cells (CD3+HLA-DR+). All cell subsets were mobilized after G-CSF treatment with the exception of B, NK, and NKT lymphocytes. The median number of Treg cells before and after G-CSF was statistically different (29+/-14.9x10(6)/l vs 70.1+/-46.1x10(6)/l, P<0.02). DCs were mobilized significantly with a 5.9-fold increase in DC2 (15.1+/-30.3x10(6)/l vs 89.8+/-81.0x10(6)/l, P<0.02) and a 2.6-fold increase for DC1 (41+/-42.5x10(6)/l vs 109.5+/-58.0x10(6)/l, P<0.04). Patients received a mean of 3.1+/-1.2x10(7)/kg NK cells, 1.3+/-0.9x10(7)/kg NKT cells, 0.41+/-0.29x10(7)/kg DC1, 0.2+/-0.22x10(7)/kg DC2, and 1.8+/-1.9x10(7)/kg Tregs. In conclusion, intermediate doses of G-CSF induce mobilization of different lymphocyte subsets, with the exception of B, NK, and NKT cells. The mobilization of certain suppressive populations (DC2 and Treg) could be in theory deleterious, at least in patients with cancer.
Assuntos
Células Dendríticas , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas , Linfócitos , Linfoma não Hodgkin , Mieloma Múltiplo , Adulto , Idoso , Antígenos de Diferenciação/metabolismo , Fracionamento Celular/métodos , Células Dendríticas/patologia , Feminino , Filgrastim , Humanos , Linfócitos/patologia , Linfoma não Hodgkin/metabolismo , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Proteínas Recombinantes , Transplante AutólogoRESUMO
The purpose of this study was to compare the long-term effectiveness among danazol, corticosteroids, cytotoxics, and dapsone in the treatment of hematological manifestations of systemic lupus erythematosus (SLE). Medical charts of all patients seen at the Rheumatic Disease Unit from January to December of 1998 were reviewed. Patient characteristics, disease and treatment information were collected. The main outcome measures were the cause of and time to discontinuation of drugs used to treat hematological manifestations of SLE resulting from all causes, mainly toxicity and inefficacy or both. Bivariate analysis including one-way ANOVA and chi2 tests were used to compare differences between means and proportions, respectively. Survival curves among the different drugs were evaluated using the Kaplan-Meier method. Multivariate analysis (Cox-regression) was used to adjust for potential confounders. After all medical records were reviewed 41 cases were eligible. Two cases had hemolytic anemia, 34 had thrombocytopenia, and five had both. These cases had received a total of 121 cycles of treatment at different times and they represent the study population (corticosteroids n = 37, danazol n = 51, citotoxic drugs n = 29, and dapsone n = 4). Crude rates of discontinuations due to any cause, toxicity and inefficacy werenot statistically significant among the drugs. However, the Kaplan-Meier curves showed statistically significant difference for discontinuations due to all causes as well as inefficacy. Prednisone and cytotoxic drugs had the lowest probability of continuation. In contrast, there were not statistically significant differences among the drugs with respect to first relapse. This is the first study examining the long-term termination rates of several drugs used to treat hematological manifestations of SLE. Using rates of discontinuation adjusted for time there were statistically significant differences among the drugs. Danazol had the highest probability of continuation.
Assuntos
Anti-Inflamatórios/administração & dosagem , Danazol/administração & dosagem , Antagonistas de Estrogênios/administração & dosagem , Lúpus Eritematoso Sistêmico/complicações , Prednisolona/administração & dosagem , Trombocitopenia/tratamento farmacológico , Adulto , Anemia Hemolítica/tratamento farmacológico , Anemia Hemolítica/etiologia , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Azatioprina/administração & dosagem , Azatioprina/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Dapsona/administração & dosagem , Dapsona/efeitos adversos , Antagonistas de Estrogênios/efeitos adversos , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Masculino , Prednisolona/efeitos adversos , Recidiva , Trombocitopenia/etiologiaRESUMO
Between December 1993 and November 2001, 30 patients with chronic myeloid leukemia who relapsed after stem cell transplantation were studied. Seventeen patients were not treated before donor lymphocyte infusion (DLI), eight patients received interferon-alpha (IFN-alpha), and five underwent chemotherapy. The method of DLI was the bulk dose regimen. The median time between DLIs was 6 weeks. The median number of infusions was three; the median time from transplant to relapse was 17 months and from relapse to DLI 2 months. Eleven patients (37%) were in molecular/cytogenetic relapse, 14 (47%) in chronic phase, and five (16%) in accelerated or blastic phase. Seventeen patients (57%) developed acute graft-versus-host disease (GVHD). Chronic GVHD was observed in 15 of 24 (62%) patients. Four (13%) patients developed cytopenia after a median of 30 days. Nineteen (63%) patients achieved response, 15 of them developed GVHD. The response rate according to the disease phase was molecular or cytogenetic relapse: 91%, chronic phase: 57%, and accelerated or blastic phase: 20%. The median time to response was 6 months. Patients treated with IFN-alpha or no treatment as well as those who were in molecular/cytogenetic relapse and those who received a CD3(+) cell dose <1 x 10(8)/kg and CD4(+) <8 x 10(7)/kg had better survival. We conclude that patients who receive lower doses of lymphocytes have better survival. In some patients IFN-alpha seems to be a good choice to potentiate the graft-versus-leukemia (GVL) effect.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Transfusão de Linfócitos , Recidiva Local de Neoplasia/terapia , Transplante de Células-Tronco , Doadores de Tecidos , Adolescente , Adulto , Antineoplásicos/uso terapêutico , Complexo CD3/análise , Antígenos CD4/análise , Terapia Combinada , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Humanos , Incidência , Interferon-alfa/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Transfusão de Linfócitos/efeitos adversos , Linfócitos/imunologia , Masculino , Análise Multivariada , Prognóstico , Análise de Sobrevida , Transplante Homólogo , Resultado do TratamentoRESUMO
Primary plasma cell leukemia (PPCL) is a rare form of disease accounting for 1-2 percent of myelomas. Between September 1990 and November 2000, among 540 patients with myeloma studied, 24 fulfilled the criteria of PPCL (4.4 percent). We found high frequencies of female patients (62 percent), Bence Jones proteinuria (79 percent), anemia (88 percent), bleeding (54 percent), confusional syndrome (42 percent), weight loss (71 percent), hepatomegaly (25 percent), splenomegaly (21 percent), leukocytosis (62 percent), and thrombocytopenia (71 percent). High serum levels of creatinine, calcium, lactate dehydrogenase (LDH), and beta(2)-microglobulin were detected in 50 percent, 37 percent, 58 percent, and 71 percent, respectively. Four patients were treated with vincristine, melphalan, cyclophosphamide, prednisone, and adriamycin (VMCPA), 12 with vincristine, adriamycin, and dexamethasone (VAD), and 8 with M-80 (oral melphalan 80 mg/m(2) plus dexamethasone 40 mg/m(2)). There was a trend toward lower values of Karnofsky score (P=0.07) and higher values of LDH (P=0.2) in the VAD group. Other clinical characteristics were comparable among the three groups. Complete plus partial responses were achieved in one and six patients treated with VMCPA and M-80, respectively. All patients treated with VAD failed to respond to treatment. Patients receiving the M-80 regimen experienced higher platelet toxicity (P=0.05), vomiting (P<0.0003), and mucositis. Also, the need for red blood cell transfusions was higher in the M-80 group. Median overall survival was 60 days. Overall survival was better in patients achieving complete or partial response. In conclusion, our study illustrates that intermediate doses of melphalan plus dexamethasone are an effective chemotherapy regimen for this aggressive disease. Response to treatment is the only prognostic factor for survival in these patients.