RESUMEN
Failure of cisplatin-based chemotherapy in advanced germ cell tumour (GCT) is associated with a poor outcome. High-dose chemotherapy and auto-SCT is one therapeutic option, although the long-term outcome after this procedure is unclear. We conducted a multicentre cohort study of consecutive patients undergoing a single auto-SCT for GCT between January 1986 and December 2004. Of 71 subjects, median follow-up is 10.1 years. OS at 5 years is 44.7% (95% confidence interval (CI) 32.9-56.5%) and EFS is 43.5% (95% CI 31.4-55.1%). There were seven (10%) treatment-related deaths within 100 days of auto-SCT. Three (4.2%) patients developed secondary malignancies. Of 33 relapses, 31 occurred within 2 years of auto-SCT. Two very late relapses were noted 13 and 11 years after auto-SCT. In multivariate analysis, favourable outcome was associated with IGCCC (International Germ Cell Consensus Classification) good prognosis disease at diagnosis, primary gonadal disease and response to salvage chemotherapy. We conclude that auto-SCT results in successful outcome for a relatively large subgroup of patients with high-risk GCT. Late relapses may occur, a finding not previously reported.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Neoplasias de Células Germinales y Embrionarias/terapia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/uso terapéutico , Estudios de Cohortes , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Neoplasias de Células Germinales y Embrionarias/mortalidad , Neoplasias Primarias Secundarias , Pronóstico , Recurrencia , Estudios Retrospectivos , Análisis de Supervivencia , Trasplante Autólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
We analyzed the late outcomes of 429 long-term survivors post allogeneic hematopoietic SCT (allo-HSCT) who received transplant in our center between 1981 and 2002, and were free of their primary disease for > or =2 years after allo-HSCT. Late recurrent primary malignancy was found in 58 (13.5%) patients and was the primary cause of late death. A total of 37 (8.6%) patients died of non-relapse causes at a median of 5.5 years (range, 2-15.6 years) post allo-HSCT. The major non-relapse causes of death were chronic GVHD (cGVHD), secondary malignancy and infection. The probabilities of OS and EFS were 85% (95% cumulative incidence (CI) (81-89%)) and 79% (95% CI (74-83%)) at 10 years, respectively. Long-term allo-HSCT survivors were evaluated for late complications (median follow-up, 8.6 years (range, 2.3-22.8 years)). cGVHD was diagnosed in 196 (53.1%) survivors. The endocrine and metabolic complications were hypogonadism in 134 (36.3%) patients, osteopenia/osteoporosis in 90 (24.4%), dyslipidemia in 33 (8.9%), hypothyroidism in 28 (7.6%) and diabetes in 28 (7.6%). Hypertension was diagnosed in 79 (21.4%), renal impairment in 70 (19.0%), depression in 40 (10.8%) and sexual dysfunction in 33 (8.9%) survivors. We conclude that in patients who receive allo-HSCT as treatment for hematological malignancy and who are free of their original disease 2 years post transplant, mortality is low and the probability of durable remission is high. Lifelong surveillance is recommended.
Asunto(s)
Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/mortalidad , Neoplasias Hematológicas/mortalidad , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Infecciones/etiología , Masculino , Persona de Mediana Edad , Neoplasias Primarias Secundarias/mortalidad , Pronóstico , Recurrencia , Sobrevivientes , Acondicionamiento Pretrasplante , Trasplante Autólogo , Trasplante Homólogo/efectos adversos , Resultado del TratamientoRESUMEN
Outcome is poor with conventional therapy for relapsed transformed non-Hodgkin's lymphoma (NHL). Autologous SCT has been successfully employed; however the impact of allogeneic SCT has not been well defined. We therefore studied 40 consecutive patients who received allogeneic SCT for relapsed composite and transformed NHL (25 transformed, 8 composite (same site) and 7 discordant (different sites)) with related (n=25) and unrelated donors (n=15) to evaluate long-term outcome. Conditioning was myeloablative in the majority (39 of 40). Of 40 patients, 11 survive with median follow-up of 25 months. Death occurred in similar proportions due to relapsed NHL (n=14) or treatment-related complications (transplant-related mortality, TRM; n=15). The cumulative incidence of TRM was 36% at 3 years and disease relapse was 42% at 5 years. Probability of 2- and 5-year event-free survival is 36 and 23% with overall survival 39 and 23%. Performance of SCT within 1 year of NHL diagnosis predicted improved outcome. Relapse and TRM remain significant problems in this setting, indicating the need for strategies whereby patients at high risk of transformation should be selected for early SCT, ideally before their actual transformation.
Asunto(s)
Donadores Vivos , Linfoma no Hodgkin/terapia , Trasplante de Células Madre/métodos , Adulto , Femenino , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Linfoma no Hodgkin/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Tasa de Supervivencia , Acondicionamiento Pretrasplante/métodos , Resultado del TratamientoRESUMEN
Administration of alkylating agents (Alk), topoisomerase II inhibitors (Topo II) and radiotherapy (RT) can result in therapy-related myelodysplastic syndrome or acute myelogenous leukaemia (t-MDS/t-AML), the optimal treatment for which is allo-SCT. A retrospective review was performed of 24 patients who underwent related- or unrelated-donor SCT for t-MDS/t-AML at our institution. Eight patients remain alive and in continuous remission (median follow-up 54 months (range, 12-161)) with estimated 5-year EFS being 30% (95% confidence intervals 16-58%). Corresponding actuarial risks of relapse and non-relapse mortality (NRM) are 39% (19-60%) and 30% (13-50%), respectively. EFS was 40% in Alk/RT-related t-MDS/t-AML and 11% in Topo II-related t-MDS/t-AML (P=0.05), with an increased risk of relapse in the latter (56 vs 29%, respectively (P=0.05)). In multivariate analysis, development of acute GVHD (P=0.009) and Topo II-related t-MDS/t-AML (P=0.018) were associated with inferior EFS. Patients with acute GVHD had an increased risk of NRM (P=0.03) whereas risk of relapse was higher for patients of advanced age (P=0.046) and for patients who underwent bone marrow (vs blood) SCT (P=0.032). Allo-SCT can result in long-term survival for individuals with t-MDS/t-AML although outcome in Topo II-related t-MDS/t-AML patients remains suboptimal.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/terapia , Agonistas Mieloablativos/efectos adversos , Síndromes Mielodisplásicos/terapia , Neoplasias Primarias Secundarias/terapia , Adulto , Alquilantes/efectos adversos , Inhibidores Enzimáticos/efectos adversos , Femenino , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Leucemia Mieloide Aguda/etiología , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/etiología , Síndromes Mielodisplásicos/mortalidad , Pronóstico , Radioterapia/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Inhibidores de Topoisomerasa II , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Curative intent chemotherapy for acute myelogenous leukemia (AML) leads to prolonged severe neutropenia, during which patients are highly susceptible to infection. Traditionally these high-risk patients were treated as inpatients. Our center recently implemented a selective ambulatory management policy for AML patients undergoing chemotherapy. MATERIALS AND METHODS: A retrospective analysis was conducted to assess the occurrence of septicemia in AML patients treated over a 5 years period with curative intent chemotherapy. This review encompasses a change in policy from primarily inpatient care to selective outpatient management coupled with prophylactic antibiotic therapy. RESULTS: A total of 294 patients, receiving 623 cycles of chemotherapy were identified. A significant decrease in septicemia was observed from the inpatient to outpatient cohort (22% to 13% P < 0.05), which correlated with the shift towards outpatient treatment of consolidation cycles. A shift from Gram-negative to Gram-positive organisms as the cause of septicemia was also detected in the outpatient cohort, likely due to the introduction of ciprofloxacin prophylaxis. No significant emerging resistance and no septicemia-related mortality were noted in the outpatient cohort. CONCLUSION: The observed decrease in the incidence of septicemia in the ambulatory cohort adds supportive evidence to the feasibility of selective outpatient management of AML patients with respect to infectious complications.
Asunto(s)
Atención Ambulatoria , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Leucemia Mieloide Aguda/tratamiento farmacológico , Sepsis/epidemiología , Adolescente , Adulto , Anciano , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neutropenia/complicaciones , Neutropenia/etiología , Estudios Retrospectivos , Sepsis/etiología , Sepsis/microbiologíaRESUMEN
BACKGROUND: Controversy exists regarding the role of high-dose therapy followed by stem-cell transplant (SCT) in the treatment of T-cell lymphoblastic lymphoma (T-LBL). We conducted an intention-to-treat analysis of the strategy of SCT as definitive treatment of T-LBL. PATIENTS AND METHODS: From July 1987 to March 2005, 34 adults with T-LBL were diagnosed and treated in British Columbia. Treatment, before planned SCT, consisted of a non-Hodgkin's lymphoma (NHL)/acute lymphoblastic leukemia hybrid chemotherapy protocol (28 patients) or a standard NHL chemotherapy regimen (six patients). RESULTS: Median follow-up of the 23 surviving patients is 51 months (range 13-142 months). Twenty-nine proceeded to SCT (four allogeneic, 25 autologous). For all 34 patients, 4-year overall survival (OS) and event-free survival (EFS) are 72% and 68%, respectively. For patients proceeding to SCT, the 4-year OS and EFS are 79% and 73%, respectively. All patients who received allografts are alive without disease at 38-141 months since diagnosis. For patients who received autografts, the 4-year EFS is 69%. Bone marrow involvement was a significant prognostic factor predicting for a worse survival (P = 0.02). CONCLUSION: A treatment strategy for adults with chemosensitive T-LBL that includes planned consolidation with SCT in first response produces favorable long-term outcome.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirugía , Adulto , Colombia Británica , Quimioterapia Adyuvante , Bases de Datos como Asunto , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Guías de Práctica Clínica como Asunto , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Pronóstico , Recurrencia , Estudios Retrospectivos , Factores de Tiempo , Trasplante Autólogo , Trasplante Homólogo , Resultado del TratamientoRESUMEN
Acute myeloid leukemia (AML) presenting with a high leukocyte count has been associated with an increase in induction mortality and poor results in a number of other survival measures. However, the level at which an elevated leukocyte count has prognostic significance in AML remains unclear. In this report on a series of 375 adult (non-M3) AML patients undergoing induction chemotherapy at a single institution, leukocyte count analyzed as a continuous variable is shown to be a better predictor of induction death (ID) and overall survival (OS) than a leukocyte count of > or = 100 x 10(9)/L, a value characteristically associated with "hyperleukocytosis" (HL). In this patient cohort, a presenting leukocyte count of > or = 30 x 10(9)/L had high sensitivity and specificity for predicting ID, and both performance status (PS) and leukocyte count more accurately predicted for ID than age. Considering these parameters in newly-diagnosed AML patients may facilitate the development of strategies for reducing induction mortality.
Asunto(s)
Antineoplásicos/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/mortalidad , Recuento de Leucocitos , Leucocitos/citología , Inducción de Remisión , Adolescente , Adulto , Anciano , Médula Ósea/metabolismo , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Curva ROC , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: We assessed the feasibility of outpatient chemotherapy and supportive care in patients with acute myeloid leukemia (AML). PATIENTS AND METHODS: All patients receiving curative intent chemotherapy between 09/01 and 10/02 and meeting our criteria received supportive care post induction chemotherapy as well as their entire consolidation chemotherapy cycles as outpatients. Patients received antimicrobial prophylaxis; those developing episodes of fever and not meeting the criteria for admission were treated with outpatient intravenous antibiotics. RESULTS: Seventy-one cycles of induction chemotherapy were administered for newly diagnosed or relapsed AML. In 25 cycles the patient was discharged post chemotherapy prior to count recovery. Of these, 14 patients developed one or more febrile episodes as an outpatient and nine (36%) required readmission to hospital. Sixty-seven consolidation cycles were given on an outpatient basis. In 39 cycles there was one or more febrile episodes and in 14 (21%) admission was required. Infections were documented in four cases during induction and in 27 during consolidation. There were no treatment-related deaths. CONCLUSIONS: Outpatient management of AML is safe and feasible using the strategies outlined in this report.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Promielocítica Aguda/tratamiento farmacológico , Pacientes Ambulatorios , Adulto , Anciano , Carboplatino/administración & dosificación , Ciclofosfamida/administración & dosificación , Citarabina/administración & dosificación , Daunorrubicina/administración & dosificación , Etopósido/administración & dosificación , Estudios de Factibilidad , Femenino , Humanos , Pacientes Internos , Leucemia Promielocítica Aguda/mortalidad , Masculino , Persona de Mediana Edad , Alta del Paciente , Readmisión del Paciente/estadística & datos numéricos , Estudios Prospectivos , Inducción de Remisión , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
In all, 30 patients with CLL proceeded to myeloablative allogeneic BMT using related (n=20, 67%) or unrelated (n=10) donors, at the Princess Margaret Hospital (Toronto) (n=20) or the Leukemia/BMT Program of BC (Vancouver) (n=10), from 1989 to 2001. Median (range) interval from diagnosis to BMT was 4.8 (0.3-13) years, median number of prior therapies was three and median age 48 years. The preparative regimen included total body irradiation in 15 (50%). In all, 14 of 30 patients (47%) are alive, with median (range) follow up of 4.3 (2.4-10.5) years. All are in complete remission, two following therapy for post-BMT progression. Actuarial overall (OS) and event-free survival (EFS) at 5 years is 39% (OS 48% for related donor and 20% for unrelated donor BMT); cumulative incidence of nonrelapse mortality (NRM) and relapse is 47 and 19%, respectively. Both acute (RR=0.008, P=0.01) and chronic (RR=0.006, P=0.02) Graft-versus-host disease (GVHD) were associated with markedly decreased risk of relapse. Patients receiving grafts from unrelated donors had increased NRM (RR=3.6, P=0.02) and decreased OS (RR of death=3.4, P=0.002). Allogeneic BMT has resulted in long-term EFS in approximately 40% of patients with CLL. There is evidence for a strong graft-versus-leukemia effect associated with acute and chronic GVHD, resulting in near complete protection from relapse.
Asunto(s)
Trasplante de Médula Ósea , Enfermedad Injerto contra Huésped/mortalidad , Efecto Injerto vs Leucemia , Leucemia Linfocítica Crónica de Células B/mortalidad , Donantes de Tejidos , Adulto , Trasplante de Médula Ósea/métodos , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped/etiología , Efecto Injerto vs Leucemia/efectos de la radiación , Prueba de Histocompatibilidad/métodos , Humanos , Leucemia Linfocítica Crónica de Células B/complicaciones , Leucemia Linfocítica Crónica de Células B/terapia , Masculino , Persona de Mediana Edad , Recurrencia , Inducción de Remisión/métodos , Estudios Retrospectivos , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo , Irradiación Corporal Total/métodosRESUMEN
Endocarditis is an uncommon complication of hematopoietic stem cell transplantation (HSCT). A retrospective review of 1547 patients who underwent HSCT in Vancouver between January 1986 and December 2001 was performed. In all, 20 cases of endocarditis were identified (1.3% of all patients) with nine patients having received cryopreserved autologous stem cells, six stem cells from a histocompatible sibling and five patients stem cells from an unrelated donor. Five patients had endocarditis diagnosed while alive, a median of 6 months post-HSCT, by transthoracic (four patients) or transesophageal (one patient) echocardiography. The remaining 15 cases of endocarditis were only identified post mortem. The mitral valve was the most frequently involved (10 patients) followed by the aortic valve (six patients); multivalvular disease was noted in five patients. Of the 11 affected allogeneic HSCT patients, 10 had previously developed acute graft-versus-host disease (GVHD). Causative organisms were identified in 11 patients, while nine additional cases were felt to be thrombotic in origin. Of the 20 patients, 19 died with the sole survivor alive 10 years following an aortic valve replacement. Endocarditis is an uncommon complication of HSCT usually involving the cardiac valves on the left side of the heart and is associated with a high mortality rate.
Asunto(s)
Endocarditis/etiología , Endocarditis/mortalidad , Trasplante de Células Madre Hematopoyéticas , Adulto , Anciano , Estudios de Cohortes , Bases de Datos Factuales , Endocarditis/diagnóstico , Endocarditis/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de RiesgoRESUMEN
To establish incidence and risk factors for development of second malignant neoplasms after high-dose chemo/radiotherapy (HDT) and autologous hematopoietic stem cell transplantation (AHSCT), the case files of 800 consecutive patients who underwent AHSCT at our institution between June 1982 and December 2000 were reviewed. In all, 26 patients developed 29 second malignancies (nine myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML), 16 solid tumors and four lymphoproliferative disorders (LPDs)) for a 15-year cumulative incidence of 11% (95% confidence interval (CI), 5-18%). These second tumors occurred at a median of 68 (range 1.5-177) months following AHSCT. The relative risk (RR) compared to the general population of developing a second malignancy following AHSCT was 3.3 (CI 2.2-4.7) P<0.001. The RR of developing MDS/AML, LPD and a solid tumor was 47.2 (CI 21.5-89.5) P<0.001, 8.1 (2.2-20.7) P=0.002 and 1.98 (1.1-3.2) P=0.009, respectively. In multivariate analysis, age >or=35 years at the time of AHSCT (P=0.001) and an interval from diagnosis to AHSCT >or=36 months (P=0.03) were associated with a greater risk of developing a second malignancy. Patients who have undergone HDT and AHSCT are at significant risk for developing a second malignancy and should receive indefinite follow-up.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Neoplasias Primarias Secundarias/etiología , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/etiología , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/etiología , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/etiología , Neoplasias Primarias Secundarias/clasificación , Probabilidad , Estudios Retrospectivos , Factores de Riesgo , Trasplante AutólogoRESUMEN
We describe the course of 25 patients with myelofibrosis (MF) due to agnogenic myeloid metaplasia (n=19) or essential thrombocytosis (n=6) who underwent allogeneic stem cell transplantation (SCT) at one of two Canadian centers. The median age at transplantation was 48.7 (IQR 45.9-50.4) years and transplantation was carried out at a median of 10.7 (IQR 5.67-26.5) months after diagnosis. Granulocyte engraftment (absolute neutrophil count >0.5 x 109/l) occurred at a median of 20 days after transplantation for splenectomized patients, compared with 27.5 days for nonsplenectomized individuals (P=0.03). Increased risk of grade II-IV acute graft-versus-host disease (P=0.04) was noted in patients transplanted after splenectomy. Patients with MF received 0.264+/-0.189 U of packed red blood cells per day over the first 180 days after transplantation, and remained dependent on red blood cell transfusions for a median of 123 (IQR 48-205) days. Complete remission of MF was documented in 33% of evaluable patients. The 1 year cumulative nonrelapse mortality was 48.3%. Median survival for this group of patients was 393 (IQR 109-1014+) days, with a projected 2-year overall survival of 41%. We conclude that allogeneic SCT offers a reasonable chance for prolonged survival in patients with advanced MF, but this occurs at the cost of considerable toxicity and nonrelapse mortality.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Mielofibrosis Primaria/terapia , Transfusión de Eritrocitos , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Enfermedad Veno-Oclusiva Hepática/etiología , Humanos , Masculino , Persona de Mediana Edad , Mielofibrosis Primaria/complicaciones , Mielofibrosis Primaria/etiología , Mielofibrosis Primaria/mortalidad , Esplenectomía , Análisis de Supervivencia , Trombocitosis/complicaciones , Trasplante HomólogoRESUMEN
Tumour lysis syndrome (TLS) is caused by rapid breakdown of malignant cells resulting in electrolyte disturbances and acute renal failure. TLS has rarely been described in patients with acute myelogenous leukaemia (AML). Between November 1997 and July 2001, 114 consecutive adult AML patients aged <60 yr received induction chemotherapy consisting of cytosine arabinoside 1.5 g m(-2) q 12 h x 12 doses and daunorubicin 45 mg m(-2) d(-1) x 3 doses. During induction chemotherapy (CT), seven patients (6.1%, 95% CI 2.5-12.2) developed fulminant TLS, resulting in acute renal failure; five of these seven patients had inversion of chromosome 16 [inv(16)(p13;q22)], and one patient had a biological equivalent [t(16,16)(p13;q22)]. Four of the TLS patients underwent leukapheresis for a presenting white blood cell (WBC) count > 100 x 10(9) L(-1) prior to commencing chemotherapy, and six patients subsequently required haemodialysis for a median of 2 (range 1-8) wk. One TLS patient died of intracerebral hemorrhage on day 10 and another patient of multiorgan failure on day 17. Of the other five patients, all entered a complete remission (CR) and recovered normal renal function. Four patients remain in continuous CR [median follow-up 20 (range 12-25) months]. One patient relapsed at 12 months and again developed TLS on re-induction. In univariate analysis, TLS patients were more likely to have an elevated presentation and pre-chemotherapy WBC counts, elevated serum creatinine, and uric acid levels at presentation, as well as an inv(16). In multivariate analysis, only serum creatinine and inv(16) remained statistically significant (P < 0.001 for each). Patients with an inv(16) are a unique AML subgroup at high risk for fulminant TLS.
Asunto(s)
Antineoplásicos/efectos adversos , Inversión Cromosómica , Cromosomas Humanos Par 16 , Leucemia Mieloide Aguda/tratamiento farmacológico , Síndrome de Lisis Tumoral/etiología , Adolescente , Adulto , Antineoplásicos/administración & dosificación , Citarabina/administración & dosificación , Citarabina/efectos adversos , Daunorrubicina/administración & dosificación , Daunorrubicina/efectos adversos , Femenino , Predisposición Genética a la Enfermedad , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Síndrome de Lisis Tumoral/mortalidad , Síndrome de Lisis Tumoral/fisiopatologíaRESUMEN
OBJECTIVES: After hematopoietic cell transplantation, a variety of complications can occur, including chronic graft-versus-host disease (GVHD), with 25% to 70% of these involving the oral cavity. Those lesions, as well as oral involvement of autoimmune mucocutaneous diseases, might present as painful, erythematous, and ulcerative oral lesions. Management includes topical and systemic immunosuppressive agents, including systemic azathioprine (AZA). The purpose of this study was to evaluate the efficacy of topical AZA in chronic oral GVHD and in oral autoimmune diseases in a series of patients. METHODS: Four men and 2 women with GVHD and 2 men with autoimmune vesiculo-ulcerative oral lesions were treated with topical AZA. A rinse of 5 mL of 5 mg/mL AZA in methylcellulose were rinsed 3 to 4 times daily for over 1 minute and expectorated, or a gel in the same concentration in 3% methylcellulose was topically applied. The outcome was evaluated separately for total ulcer size, assessment of the erythema, and severity of pain by using a visual analogue scale. Global estimated improvements represented a proportional combined improvement of ulcers, erythema, and pain. RESULTS AND CONCLUSIONS: The mean estimated global improvement for 6 patients with GVHD who used AZA rinse was 60% in a mean of 16.67 weeks. Ulcers improved by 58%, erythema by 55%, and pain was reduced by 63%. Two patients with oral lesions of vesiculo-ulcerative diseases (1 AZA rinse and 1 topical gel) improved by 95% and 96%, respectively, in 3 months. One patient with GVHD applied topical AZA gel in addition to mouthrinses, and a 29% estimated global improvement was achieved in addition to 50% of improvement achieved with AZA mouthrinses. The observed effect of topical AZA suggests that it can be used for management of oral immune-mediated inflammatory conditions, and for patients who are provided with systemic immunosuppressives it can allow control of oral findings with lower systemic dosing. The therapeutic potential of topical AZA as mouthrinse versus topical applications and the most effective concentration should be further investigated.
Asunto(s)
Azatioprina/uso terapéutico , Inmunosupresores/uso terapéutico , Úlceras Bucales/tratamiento farmacológico , Estomatitis/tratamiento farmacológico , Estomatitis/inmunología , Adulto , Enfermedades Autoinmunes/complicaciones , Azatioprina/administración & dosificación , Enfermedad Crónica , Eritema/tratamiento farmacológico , Eritema/etiología , Femenino , Geles , Enfermedad Injerto contra Huésped/complicaciones , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Inmunosupresores/administración & dosificación , Masculino , Persona de Mediana Edad , Antisépticos Bucales , Úlceras Bucales/etiología , Úlceras Bucales/inmunología , Penfigoide Benigno de la Membrana Mucosa/complicaciones , Penfigoide Benigno de la Membrana Mucosa/tratamiento farmacológico , Pénfigo/complicaciones , Pénfigo/tratamiento farmacológico , Estomatitis/etiologíaRESUMEN
Despite numerous strategies, the cure of multiple myeloma remains a difficult challenge. Recent approaches have involved dose-intensive therapy followed by stem cell transplantation, most often with autologous stem cells (ASCT). Although ASCT is of benefit, it is not considered curative. Between 1988 and 1995, we utilized an aggressive three-drug conditioning regimen followed by ABMT using marrow purged with either 4-hydroperoxycyclophosphamide (4-HC) or mafosphamide (MAF). Twenty-nine of 42 patients who had first received VAD (14 patients) or VAD followed by cyclophosphamide (7 g/m2 i.v.) + dexamethasone (40 mg/day p.o. x4) + GM-CSF (15 patients) met the eligibility criteria needed to undergo bone marrow harvest and ABMT, ie < or =10% marrow plasma cells and > or =50% decrease in paraprotein level. Alpha-interferon maintenance therapy was given post ABMT. Median follow-up is 7.5 years (range 5.0-11.25). Six early and two late non-relapse deaths occurred; 15 patients have relapsed. Seven patients remain in continuous CR (five) or PR (two), including three with stage IIIB disease at diagnosis. One patient developed a soft tissue sarcoma 8 years post ASCT. Although this protocol produced excessive toxicity compared with current approaches, the results demonstrate that dose-intensive therapy and ASCT can produce durable remission in this disease. Further development of dose-intensive strategies is warranted.
Asunto(s)
Purgación de la Médula Ósea/métodos , Trasplante de Médula Ósea , Ciclofosfamida , Ciclofosfamida/análogos & derivados , Mieloma Múltiple/terapia , Adulto , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Ciclofosfamida/administración & dosificación , Dexametasona/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Humanos , Interferón-alfa/uso terapéutico , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Resultado del Tratamiento , Vincristina/administración & dosificaciónRESUMEN
A 47-year-old male patient developed sepsis and monoarticular arthritis following autologous stem cell transplantation for recurrent Hodgkin's disease. Blood cultures were positive for Agrobacterium yellow group. The knee pain and swelling responded promptly to the institution of empirical broad-spectrum antibiotics. Recurrent bacteremia developed necessitating Hickman line removal for eventual resolution of the infection. Transplant physicians should be aware of this unusual pathogen and the potential for both persistent line-related sepsis and possible septic arthritis.
Asunto(s)
Artritis Infecciosa/etiología , Bacteriemia/etiología , Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin/terapia , Rhizobium , Antibacterianos/uso terapéutico , Artritis Infecciosa/tratamiento farmacológico , Bacteriemia/tratamiento farmacológico , Cateterismo Venoso Central/efectos adversos , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Recurrencia , Rhizobium/efectos de los fármacos , Trasplante AutólogoRESUMEN
Acute graft-versus-host disease (A-GVHD) is a life-threatening complication of allogeneic stem cell transplantation (SCT), and primary therapy consists of high-dose corticosteroids. Patients who fail to respond adequately to corticosteroids require salvage treatment, with anti-T cell antibodies being the most commonly utilized group of agents. We report our institution's experience treating steroid-resistant GVHD in 36 adult patients (median age 39 years, range 24-55) with a rabbit antithymocyte globulin product (thymoglobulin). Eleven patients had undergone sibling SCT (10 histocompatible, 1 one-antigen mismatched) and 25 patients had received unrelated donor bone marrow (17 matched, 8 one-antigen mismatched); 32 patients (89%) had grade III or IV A-GVHD. Thymoglobulin was administered in two different regimens; group 1 patients (n = 13) received 2.5 mg/kg/day x 4-6 consecutive days with maintenance of all other immunosuppressives. Group 2 patients (n = 21) were given the same dose of thymoglobulin on days 1, 3, 5, and 7 with discontinuation of cyclosporine for 14 days, during which the corticosteroid dose was held at 2-3 mg/kg/day. Two patients had severe adverse reactions to thymoglobulin (hypoxemia and hypotension) and could not complete treatment, however, in the other patients, aside from transient leukopenia (25%) and and hepatic dysfunction (25%), the antibody preparation was well tolerated. Of the 34 evaluable patients, 13 patients had a complete response (38%) and 7 patients (21%) had a partial response, for an overall response rate of 59%. Response rate was higher in group 1 patients (77%) compared to group 2 patients (48%), (p = 0.15); skin GVHD was more responsive (96% of patients) than gut GVHD (46% of patients) or hepatic GHVD (36% of patients). Opportunistic infections were a significant complication, with 11 patients developing systemic fungal infections and 9 patients serious viral infections; there were seven episodes of bacteremia following thymoglobulin treatment and one fatal protozoal infection. There were 9 patients (25%) who developed post-SCT lymphoproliferative disorder (PTLD) and 4 patients who had a relapse of underlying primary malignancy; none of these patients survived. Of the 36 patients entered on the study, only 2 patients (6%) survive, at 15+ and 34+ months post-unrelated donor SCT. Although thymoglobulin is associated with an impressive response rate when administered for advanced steroid-resistant GVHD, long-term survival is uncommon, even in responders, primarily due to the high risk of developing either an opportunistic infection or a PTLD.
Asunto(s)
Corticoesteroides , Suero Antilinfocítico/uso terapéutico , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Linfocitos T/inmunología , Enfermedad Aguda , Adulto , Animales , Suero Antilinfocítico/toxicidad , Resistencia a Medicamentos , Femenino , Fiebre/etiología , Enfermedad Injerto contra Huésped/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Infecciones/etiología , Trastornos Linfoproliferativos/etiología , Masculino , Persona de Mediana Edad , Conejos , Inducción de Remisión , Terapia Recuperativa , Tasa de Supervivencia , Trasplante Homólogo/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Allogeneic bone marrow transplantation (BMT) has been used in patients with low-grade lymphoma (LGL) and chronic lymphocytic leukemia (CLL) with the goal of achieving long-term disease-free survival. PATIENTS AND METHODS: Twenty-nine patients with these diagnoses (LGL = 19, CLL = 10) received allogeneic BMT between September 1995 and January 1999. Median age was 42 (range 20-52) years. Twenty-three of twenty-nine patients (79%) were Ann Arbor or Rai stage IV at the time of transplant; twenty-four (83%) had never achieved complete remission (CR). Donor source was HLA-matched sibling (20), unrelated (8) and syngeneic (1). RESULTS: Seventeen patients are currently alive, a median of 29 months (range 1-85) post-BMT with a median KPS of 90%. Twenty-three of twenty-seven evaluable patients (85%) achieved CR post-BMT. Six patients had refractory/recurrent disease. Death occurred related to transplant complications in eight patients and underlying disease in four. Overall and event-free survival for the whole group is 51% and 44%, respectively. CONCLUSIONS: Allogeneic BMT for young patients with advanced stage LGL or CLL is a feasible strategy that can result in achievement of long-term disease-free survival.