RESUMEN
INTRODUCTION: Steroid-refractory graft-versus-host disease (GVHD) remains a challenging therapeutic problem after allogeneic hematopoietic stem cell transplantation (HSCT). The aim of this study was to evaluate the clinical effect of extracorporeal photopheresis (ECP), and its impact on intensivity of immunosuppresive therapy in allogeneic HSCT patients. PATIENTS AND METHODS: In this study 443 Therakos ECP procedures were performed in 21 patients after allogeneic HSCT with acute (aGVHD, 8 patients) or chronic (cGVHD, 13 patients) therapy-refractory GVHD. The median age at ECP onset was 20.5 years (range, 10-55). Venous access was provided by a nontunelized central venous catheter (12 patients) or 9.6-French portacath (9 patients). RESULTS: In the cGVHD group 9/13 patients were improved with a 4-year overall survival rate of 67.7%. ECP led to steroid discontinuation in 6 and substantial dose reduction in 5 patients. The prednisone dose equivalent per kilogram body weight decreased from 0.32 mg to 0.07 mg after therapy. Therapy of aGVHD led to complete or partial symptom remission in 3/9 subjects. The change in steroid dose in the aGVHD group was not significant, there were no long-term survivors. Portacath access was well tolerated and provided adequate blood flow rates. CONCLUSIONS: The ECP therapy significantly reduced the rates of remissions with steroid discontinuation among cGVHD but not aGVHD patients. Rare ECP-related complications were either catheter related or anticoagulation induced during ECP procedures. Photopheresis was a safe, effective method to treat steroid-resistant cGVHD.
Asunto(s)
Enfermedad Injerto contra Huésped/fisiopatología , Trasplante de Células Madre Hematopoyéticas , Fotoféresis , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trasplante HomólogoRESUMEN
Following on from the recently published articles reported side effects occurring due to donation of stem cells, we describe a case of a donor with transient, biopsy-proved acute focal segmental proliferative glomerulonephritis (GN) due to peripheral blood stem cells (PBSC) mobilization with granulocyte colony-stimulating factor (G-CSF). A 44-year-old woman with no relevant past medical history suffering from obesity and hypertension well controlled with metoprolol without hypertensive retinopathy was admitted to our hospital as a donor of PBSC. She received G-CSF subcutaneously-filgrastim (Amgen)-at a dose of 5 microg/kg twice a day for 6 days. The macroscopic hematuria and proteinuria occurred on 5th day of G-CSF administration. Due to mobilization and collection of stem cells, proteinuria was becoming more intense and reached the nephrotic range. The immunological, infectious, urological and gynecological causes of such complication were excluded. The final histological recognition was early stage of focal segmental proliferative GN. To our knowledge this a first report of GN in a donor due to mobilization of PBSC confirmed with renal biopsy. These findings suggest that filgrastim may induce transient urinary excretion of protein and hematuria in PBSC donors as the symptoms of acute GN without adversely affecting renal function.
Asunto(s)
Glomeruloesclerosis Focal y Segmentaria/etiología , Glomeruloesclerosis Focal y Segmentaria/patología , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Movilización de Célula Madre Hematopoyética , Donantes de Tejidos , Enfermedad Aguda , Adulto , Femenino , Glomeruloesclerosis Focal y Segmentaria/inmunología , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Factor Estimulante de Colonias de Granulocitos/farmacología , Movilización de Célula Madre Hematopoyética/efectos adversos , Células Madre Hematopoyéticas/efectos de los fármacos , HumanosRESUMEN
Reticulated platelets (RP) are the youngest forms of platelets in blood and reflect the rate of bone marrow platelet production. In the present study, we used flow cytometric analysis to determine the percentage of RPs in patients undergoing allogeneic stem cell transplantation. We investigated 10 patients after transplantation from HLA identical siblings: five with acute myeloid leukemia (AML), four with chronic myeloid leukemia (CML), and one patient with myelodysplastic syndrome (MDS). Of the patients examined, four patients underwent allogeneic bone marrow transplantation and six patients underwent peripheral blood stem cell transplantation. It was observed that the initially reduced percentage of RPs (2.9 +/- 1.7%; mean +/- SD) was significantly higher (P = 0.0109) in all patients (13.6 +/- 6.4%) in the following 10-26 days. The RP percentage peak preceded the recovery of peripheral platelet count up to 45.6 x 10(9)/l on average by 3 days. We found no difference in RP% between the AML and CML patients but we did observe that in CML patients the RP percentage increased on average 7 days earlier than in AML patients. The elevated RP percentage reflects increased bone marrow regeneration and can be considered an additional marker of thrombopoietic recovery in the patients undergoing allogeneic stem cell transplantation.
Asunto(s)
Plaquetas/fisiología , Médula Ósea/fisiología , Trasplante de Células Madre Hematopoyéticas , Leucemia Mielógena Crónica BCR-ABL Positiva/cirugía , Leucemia Mieloide Aguda/cirugía , Síndromes Mielodisplásicos/cirugía , Regeneración , Adulto , Biomarcadores , Trasplante de Médula Ósea , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recuento de PlaquetasRESUMEN
In this multicenter study, we assessed the use of palifermin (recombinant human-keratinocyte growth factor 1) in the prevention of oral mucositis (OM) and acute GvHD (aGvHD) induced by a hematopoietic stem cell transplant (HSCT). Fifty-three patients with hematological diseases received three doses of palifermin (60 mug/kg once daily i.v.) pre- and post-conditioning regimens (total six doses). A retrospective control group of 53 transplant patients received no palifermin. There was a significant reduction in the incidence of OM of WHO (World Health Organization) grades 1-4 (58 vs 94%, P<0.001), 3-4 (13 vs 43%, P<0.001) and the median duration of OM (4 vs 9 days, P<0.001) in the palifermin group compared to the control group. The incidence of analgesics (32 vs 75.5%, P<0.001), opioid analgesics (24 vs 64%, P<0.001) and total parenteral nutrition (11 vs 45%, P<0.001) was also significantly reduced. The analysis of distribution of affected organs revealed that aGvHD was less prevalent in the palifermin group (P=0.036). There was no significant difference in the onset of any OM after HSCT, time to engraftment and length of hospitalization between groups. The drug was generally well tolerated and safe. Our results suggest that the use of palifermin reduces OM and probably aGvHD after HSCT, but a randomized trial is needed.
Asunto(s)
Factor 7 de Crecimiento de Fibroblastos/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Enfermedades Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Estomatitis/prevención & control , Adolescente , Adulto , Femenino , Factor 7 de Crecimiento de Fibroblastos/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: The previous study by the Polish Adult Leukemia Group has demonstrated that addition of cladribine to standard DNR+AraC induction potentiates the antileukemic activity. The goal of this study was to compare the efficacy of bone marrow or peripheral blood hematopoietic cell collection in patients who obtained remission after daunorubicine plus cytarabine induction with cladribine (DAC-7) or without addition of cladribine (DA-7) in preparation for autotransplantation. PATIENTS AND METHODS: Sixty-six patients aged 41 years (range, 17-58 years) were included in this study: 33 cases in the DAC-7 and 33 in the DA-7 arm. Hematopoietic cells were collected from the bone marrow (ABMT, n = 29) or from the peripheral blood (ABCT, n = 37) using cytopheresis after administration of AraC (2 x 2 g/m2) on days 1, 3, 5 and subsequent G-CSF (10 microg/kg) from day 7 as mobilization therapy. RESULTS: The numbers of harvested CD34+ cells were similar in the DAC-7 and DA-7 pretreated patients both after harvesting from peripheral blood (2.55 x 10(6)/kg vs 2.5 x 10(6)/kg) and from bone marrow (1.62 x 10(6)/kg vs 1.55 x 10(6)/kg), respectively. The proportion of patients with sufficient material for autologous bone marrow transplantation was higher in the DAC-7 compared with the DA-7 arm. All patients engrafted; hematopoietic recovery was similar in both subgroups. CONCLUSION: Addition of cladribine to a standard DA induction does not impair the harvesting of hematopoietic cells and their engraftment after autotransplantation.
Asunto(s)
Trasplante de Médula Ósea , Cladribina/uso terapéutico , Movilización de Célula Madre Hematopoyética , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Antígenos CD34/sangre , Quimioterapia Combinada , Humanos , Inmunosupresores/uso terapéutico , Persona de Mediana Edad , Recolección de Tejidos y Órganos/métodos , Acondicionamiento Pretrasplante , Trasplante AutólogoRESUMEN
To assess the efficacy of an original DAC-7 regimen: daunorubicine (DNR) 60 mg/m2/day, days 1-3; cytarabine (AraC) 200 mg/m2/day, days 1-7; cladribine (2-CdA) 5 mg/m2/day, days 1-5, 400 untreated adult acute myeloid leukemia patients (including 63 with preceding myelodysplastic syndrome), aged 45 (16-60) years were randomized to either DAC-7 (n=200) or DA-7 (without 2-CdA, n=200). The overall CR rate equaled 72% for DAC-7 and 69% for DA-7 arm (P=NS). After a single course of DAC-7 induction, the CR rate equaled 64% and was significantly higher compared to 47% in the DA-7 arm (P=0.0009). Median hospitalization time during the induction was 7 days shorter for DAC-7 compared to the DA-7 group (33 vs 40 days, P=0.002). Toxicity was comparable in both groups. The probability of 3-year leukemia-free survival (LFS) for DAC-7 and DA-7 group equaled 43 and 34%, respectively (P=NS). There was a trend toward higher LFS rate for patients aged >40 years receiving DAC-7 compared with DA-7 regimen (44 vs 28%, P=0.05). This study proves that addition of 2-CdA increases antileukemic potency of DNR+AraC regimen, thus resulting in a higher CR rate after one induction cycle when compared to DA-7, without additional toxicity. It shortens hospitalization time and may improve long-term survival in patients aged >40 years.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Adolescente , Adulto , Cladribina/administración & dosificación , Citarabina/administración & dosificación , Daunorrubicina/administración & dosificación , Femenino , Humanos , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
The rate of apoptosis as well as expression of Bcl-2 and Bax was evaluated before and after induction therapy in leukocytes of 70 patients with acute myeloblastic leukemia (AML), retrospectively divided into group A (with longer survival) and group B (with shorter survival). We found, that leukocytes of untreated AML patients showed susceptibility to apoptosis similar to control cells. Marked increase in percentage of apoptotic leukocytes was observed after induction therapy exclusively in patients with longer survival, which was accompanied by better normalization of routine hematological parameters. In this group, the Bcl-2/Bax ratio was similar to the control and remained unchanged after treatment. In AML patients with shorter survival, a twofold increase in this ratio was observed both before and after the completion of induction therapy. In both groups of untreated patients, western blot analysis revealed the presence of prominent additional bands reacting with anti-Bcl-2 or anti-Bax antibody, which were undetectable in control leukocytes. After the therapy, these bands disappeared, especially in patients from group A. In conclusion, the lack of therapy-induced enhancement in leukocyte apoptosis, an increased ratio of Bcl-2/Bax as well as persistent presence of abnormal Bcl-2 and Bax protein bands after induction therapy in AML patients may be considered as factors associated with unfavorable clinical outcome.
Asunto(s)
Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Leucocitos/patología , Proteínas Proto-Oncogénicas c-bcl-2/sangre , Proteínas Proto-Oncogénicas/sangre , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis , Crisis Blástica , Humanos , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/tratamiento farmacológico , Recuento de Leucocitos , Leucocitos/fisiología , Persona de Mediana Edad , Resultado del Tratamiento , Proteína X Asociada a bcl-2RESUMEN
The common dilemma in the treatment of elderly patients with acute myeloid leukemia (AML) is whether to use intensive myelosuppresive therapy with higher risk of treatment related mortality (TRM), but a chance for complete remission (CR), or to treat less intensively in order to prolong survival time with a better quality of life. The aim of this prospective, phase II study was to assess the efficacy and toxicity of low dose combination induction treatment consisted of cytarabine at a dose of 10 mg/m2 every 12 h s.c. for 7 days, VP-16 at a dose of 100 mg/day p.o. for 7 days and mitoxantrone at a dose of 6 mg/m2 i.v daily on days 1-3. Two induction courses were planned. In the group of 44 patients 12 (27%) achieved CR, 4 (9%) patients were in PR and there were 9 (20%) early deaths (ED). Age, performance status, preceding myelodysplastic syndrome, karyotype, WBC and % of blasts in bone marrow were not significant prognostic factors for CR probability. The following initial factors appeared to be related to a shorter duration of survival time from the start of treatment: age >70 (p<0.03), poor performance status (p<0.03), and % of BM blasts 50 (p<0.05). We conclude that, despite promising results in the pilot study the efficacy of this induction treatment is not better than the efficacy of other regimens. The hematological toxicity of this treatment seems to be comparable with "3+7" regimen.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Mieloide/tratamiento farmacológico , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Citarabina/administración & dosificación , Esquema de Medicación , Etopósido/administración & dosificación , Femenino , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Polonia , Pronóstico , Estudios Prospectivos , Inducción de Remisión , Tasa de SupervivenciaRESUMEN
Authors' analysis refers to reasons for which some women did not meet criteria for the programme of collection of cord blood by The Cord Blood Bank in Warsaw. The main reasons were: 1) reactivation of infection with CMV virus, 2) complications of delivery and 3) technical problems. We present also preliminary results of blood tests aimed at identification of some viral (hepatitis B and C, HIV, CMV), bacterial (Treponema pallidum) and protozoal infections (Toxoplasma) in the selected group of pregnant women.
Asunto(s)
Donantes de Sangre , Sangre Fetal , Adulto , Infecciones por Citomegalovirus/sangre , Femenino , Seropositividad para VIH/sangre , Hepatitis B/sangre , Hepatitis C/sangre , Humanos , Embarazo , Sífilis/sangre , Toxoplasmosis/sangreRESUMEN
36 patients with relapsed (29) or refractory (7) acute lymphoblastic or nonlymphoblastic leukaemia received regimens employing 1-3 courses of mitoxantrone (or idarubicin), intermediate doses of cytarabine and etoposide. Complete remission (CR) was achieved in 30% of patients (5/15 ALL, 6/21 AML, 5 cases of refractory and 6 of relapsed leukaemia). Duration of CR was 3-6+ months (3 patients are still alive). Toxicity of the treatment was acceptable, however 5 patients with severe granulocytopenia died from sepsis.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adulto , Agranulocitosis/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Citarabina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Humanos , Idarrubicina/administración & dosificación , Masculino , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Recurrencia , Inducción de RemisiónAsunto(s)
Leucemia Mieloide Aguda/patología , Leucemia Mieloide/epidemiología , Neoplasias Primarias Secundarias/epidemiología , Adulto , Anciano , Médula Ósea/patología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Leucemia Mieloide/mortalidad , Leucemia Mieloide/patología , Leucemia Mieloide/terapia , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Neoplasias Primarias Secundarias/mortalidad , Neoplasias Primarias Secundarias/patología , Neoplasias Primarias Secundarias/terapia , Factores de TiempoRESUMEN
We present a case of a 17-year old patient with extreme hepatosplenomegaly, hyperthrombocytosis, hyperleucocytosis and the presence of myelo- and megakaryoblasts in the peripheral blood film. Numerous complications that occurred in the course of the disease made cytostatic treatment difficult. Since Ph chromosome and hybrid gene bcr/abl were absent, the diagnosis of unclassified chronic myeloproliferative syndrome in the phase of blast crisis was established. Immunophenotyping confirmed a mixed myelo- megakaryoblastic character of the crisis. In the differential diagnosis other myeloproliferative syndromes were taken into account including i(17q) syndrome. The patient died after a 13-month observation due to neoplasm progression and sepsis.
Asunto(s)
Aberraciones Cromosómicas/diagnóstico , Cromosomas Humanos Par 17 , Trastornos Mieloproliferativos/diagnóstico , Cromosoma Filadelfia , Adolescente , Crisis Blástica , Trastornos de los Cromosomas , Enfermedad Crónica , Resultado Fatal , Humanos , Inmunofenotipificación , Masculino , Trastornos Mieloproliferativos/genética , SíndromeRESUMEN
AGLT and osmotic fragility test (method according to Dacie) were performed in patients with hereditary spherocytosis, their relatives and in patients with other hematological diseases. Abnormal results of both tests were observed not only in all cases of hereditary spherocytosis but also in other patients with spherocytes present in the peripheral blood film. In our opinion, AGLT is a good screening test for hereditary spherocytosis and can replace the more time consuming Dacie's method.
Asunto(s)
Enfermedades Hematológicas/diagnóstico , Tamizaje Masivo/métodos , Esferocitosis Hereditaria/diagnóstico , Humanos , Fragilidad OsmóticaRESUMEN
In 23 patients with myelodysplasia syndromes cytomorphological examinations of peripheral red blood cells and bone marrow cells were carried out. Apart from anisocytosis and poikilocytosis observed in all patients, the most frequent changes were macrocytosis and megalocytosis or erythrocytes and their precursors, presence of erythroblasts in peripheral blood and disturbances of megakaryopoiesis. None of these changes was characteristic in a given type of these syndromes.
Asunto(s)
Anemia Refractaria/sangre , Anemia Sideroblástica/sangre , Médula Ósea/patología , Eritrocitos/patología , Adulto , Anciano , Anemia Refractaria/patología , Anemia Sideroblástica/patología , Recuento de Células , Eritroblastos/patología , Recuento de Eritrocitos , Células Precursoras Eritroides/patología , Femenino , Humanos , Masculino , Megacariocitos/patología , Persona de Mediana EdadRESUMEN
The activity of alkaline phosphatase and peroxidase was measured in polymorphonuclears in 20 cases of myelodysplasia syndromes, 10 cases of chronic myeloid leukaemia. Reduced phosphatase activity was found in 5 cases and peroxidase activity in 3 cases of myelodysplasia syndromes. No evident correlation was noted between the activity of these enzymes and prognosis. Increased proportion of peroxidase-negative granulocytes was observed, moreover, in most cases of chronic myeloid leukaemia. The observations will be continued in larger material.
Asunto(s)
Fosfatasa Alcalina/sangre , Granulocitos/enzimología , Leucemia Mielógena Crónica BCR-ABL Positiva/sangre , Leucemia Mieloide Aguda/sangre , Síndromes Mielodisplásicos/sangre , Peroxidasas/sangre , Policitemia Vera/sangre , Mielofibrosis Primaria/sangre , HumanosRESUMEN
Mitoxantrone is a new anthracenodione derivative with a high antineoplastic activity in proliferative diseases of the haemopoietic system. In the Institute of Haematology in Warsaw and in the Department of Haematology, Silesian Medical Academy in Katowice this agent was used in combination with cytarabine in 49 cases of acute leukaemia (35 with acute myeloid leukaemia and 14 with acute lymphoblastic leukaemia). The preparations used were Mitoxantrone (POLFA Works in Jelenia Góra) and Novantrone (Lederle). These agents were given intravenously in doses of 10-20 mg/m2 for 3 days in combination with cytarabine in three doses: 100 mg/m2 on days 1 through 7, and 1 g/m2 or 3 g/m2 every 12 hours on days 1 through 4 of the treatment. Complete remission was obtained in 17 cases (35%), including 13 with acute myeloid leukaemia (37%) and 4 with acute lymphoblastic leukaemia (29). The most frequent side effects were: long-lasting pancytopenia (in 100% of cases), hair loss (39%) and gastrointestinal toxicity (33%). No significant differences were noted in the effectiveness and toxicity between these two preparations. In the light of the presented results it may be accepted that the combination of mitoxantrone with cytarabine is an important advance in the treatment of acute leukaemias.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Citarabina/administración & dosificación , Leucemia Mieloide Aguda/tratamiento farmacológico , Mitoxantrona/administración & dosificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Adulto , Anciano , Esquema de Medicación , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Inducción de RemisiónRESUMEN
In 91 patients with acute non-lymphoblastic leukaemia the peroxidase index was determined in blast cells or promyelocytes in bone marrow. Complete remission was obtained exclusively in patients with the value of the index 0-9% or over 69%. The duration of the remission and the survival time were significantly longer in patients with a high peroxidase index. This index may be useful for prediction of the course of acute non-lymphoblastic leukaemia in adults and its high value is associated with better prognosis.