RESUMO
BACKGROUND: Patients with ileostomies regularly suffer from short bowel syndrome or high volume output associated with loss of absorptive surface and subsequent impairment of absorption for drugs and different nutrients resulting in electrolyte and fluid balance disorders as well as renal insufficiency. Adaptation of these fundamental functions of the gut with adequate fluid uptake, absorption of sufficient different nutrients and vitamins represents a major challenge to rehabilitate these patients shortly after surgery. Patients with ileostomy often develop metabolic acidosis with normal anion gap. In our retrospective study we would like to draw attention to these metabolic disorders in patients with ileostomy in comparison to patients with colostomy and patients undergoing gastrectomy for gastric cancer. METHODS: In the period from 2005 to 2012 we examined 164 patients with ileostomy in our rehabilitation clinic, 109 patients with colostomy and 193 patients after surgery for gastric cancer of the possible presence of metabolic acidosis by using capillary blood gas analysis (metabolic acidosis was anticipated, if base excess was ≤- 3,0 mmol/l). Patients are treated as inpatients both in early stage and for follow-up rehabilitation. The length of time in our rehabilitation clinic lies in between 24-28 days. On the basis of random samples we tested blood samples in 19 patients with ileostomy in succession for ferritin, folic acid, zinc, selenium and vitamin B12. Statistical analysis comprised the classical intervals (mean and standard deviation, range and T-test for dependent and independent samples). RESULTS: In total we tested 164 inpatients with ileostomy in our rehabilitation clinic (median age 67.4 years, range 19-79 years). Surgery for ileostomy took place about 1.4 months on average ago (range »-56 months). 60 (36.5%) inpatients suffered from metabolic acidosis often combined with renal insufficiency. Supportive therapy intravenously administered in 10 patients and sodium bicarbonate given by mouth in 40 patients significantly improved metabolic acid (base excess improved on average from -7.2 to -3.2 mmol/l, p<0.00138) and renal function calculated on the basis of serum creatinine (serum creatinine decreased from 1.49 on average to 1.34 mg/dl, p<0.04039). Body weight remained constant over the whole period on average with 74 kg. Diuretics did not show any influence on the base excess. In 19 patients with ileostomy who did not take any kind of supplements, among the parameters tested were a high percentage of zinc (9 of 19 patients, 47%) and selenium deficiency (13 of 19 patients, 68%). 50 patients with ileostomy were younger than 65 years of age and thus in the working age population. In the group of patients after gastrectomy because of gastric cancer (n=193, median age 69.1 years, range 36-82 years), surgery for gastrectomy took place about 1.8 months on average ago and in this group only 14 patients (7%) showed metabolic acidosis. In the group of patients with colostomy (n=109, median age 69.5 years, range 39-82 years), surgery for colostomy took place about 2.1 months on average ago and in this group only 6 patients (5.5%) suffered from metabolic acidosis. CONCLUSION: Medical rehabilitation is indicated for patients with enterostoma. Acceptance of the enterostoma by the patient himself, psychological stabilization, achievement of self-sufficiency in stoma care, improvement of physical abilities and finally being fit for full or limited employment are the most important objectives in rehabilitation medicine. Metabolic acidosis was often found in patients with ileostomy and was an important clinical appearance. Blood gas analysis is recommended to verify metabolic acidosis and if confirmed sodium bicarbonate and in cases of high volume output salt-depleting ileostomy additionally intravenous fluid support should be offered controlling body weight in the follow-up. As could be shown by our analysis patients with ileostomy should also be tested for zinc and selenium deficiency.
Assuntos
Ileostomia/efeitos adversos , Ileostomia/reabilitação , Síndrome do Intestino Curto/etiologia , Síndrome do Intestino Curto/reabilitação , Desequilíbrio Ácido-Base/etiologia , Desequilíbrio Ácido-Base/reabilitação , Adulto , Idoso , Idoso de 80 Anos ou mais , Colostomia/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/complicações , Neoplasias Gástricas/reabilitação , Neoplasias Gástricas/cirurgia , Resultado do TratamentoRESUMO
Autologous stem cell transplantation has augmented treatment successes. However, high-dose chemotherapy is still accompanied by dose-limiting toxicities, for example, severe mucositis. Mucosal lesions serve as portals of entry for infections. In order to reduce the oral microbial burden, we prospectively evaluated the microbiological impact of a complex regimen of mouth rinses consisting of concomitantly applied polyene antifungals, povidone-iodine, chlorhexidine, sage tea, and prophylactic ciprofloxacin and fluconazole. A total of 15 patients were enrolled into this longitudinal evaluation. Colony-forming units (CFU) were quantitated from saliva, buccal and palatinal swabs during high-dose chemotherapy and autologous stem cell transplantation. The number of CFU did not show any significant changes after initiation of the mouth rinses and the prophylactic antibiotics. The median CFU count was 268 x 10(6)/ml saliva before chemotherapy and decreased after initiation of intravenous antibiotics only. Neither prophylactic nor therapeutic antifungals significantly reduced the number of cultures positive for yeasts. Since 90% of our patients had febrile neutropenia at some time point during the observation period, the approach evaluated cannot be recommended as prophylaxis of febrile neutropenia as such.
Assuntos
Anti-Infecciosos/farmacologia , Antibioticoprofilaxia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Mucosa Bucal/microbiologia , Antissépticos Bucais/farmacologia , Adulto , Feminino , Fungos/isolamento & purificação , Bactérias Gram-Negativas/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Estudos Prospectivos , Transplante AutólogoRESUMO
Following conventional chemotherapy, eight myeloma patients presenting with advanced tumor stages were treated with an intensified high-dose regimen and autologous peripheral blood stem cell transplantation. High-dose chemotherapy consisted of idarubicin 20 mg/m2 on days -13, -12 and -11, melphalan 100 mg/m2 on days -5 and -4 and cyclophosphamide 60 mg/kg (plus mesna 60 mg/kg) on days -3 and -2 (IMC). Seven patients achieved a complete remission or a very good partial remission (reduction of M-component > or =90%). There were no toxic deaths. Severe mucositis and fever of unknown origin were seen in all patients. Reversible supraventricular tachycardias without clinical signs of cardiac failure occurred in five patients. One patient developed a persistent deterioration of cardiac function. We surmise that high-dose chemotherapy with IMC is very effective and well tolerated in myeloma patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Idarubicina/administração & dosagem , Idarubicina/efeitos adversos , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/patologia , Estadiamento de Neoplasias , Taquicardia Supraventricular/induzido quimicamenteRESUMO
BACKGROUND: The pathogenesis of Sneddon's syndrome is unclear. This study addresses the question whether cerebral thromboembolism may be involved in the pathogenesis of the neurologic complications of the disorder. The study consisted of 13 patients with Sneddon's syndrome defined by both generalized livedo reticularis and a history of one or more cerebrovascular ischemic events; none had clinical or Doppler ultrasonographic evidence of atherosclerosis. METHODS: Transcranial Doppler microembolic monitoring of the middle cerebral artery; blood screening for antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies). RESULTS: Five patients (38%) showed clinically silent microembolism at transcranial Doppler monitoring, with individual microembolic event rates of the middle cerebral artery between 2 per hour and 33 per hour. In this group, the time since the last ischemic symptom was significantly shorter than in the eight patients without microemboli. Antiphospholipid antibodies were detected in three patients (23%), all of whom belonged to the microemboli-positive group. CONCLUSIONS: These data suggest that the detectability of both clinically silent cerebral microembolism and antiphospholipid antibodies may provide paraclinical evidence of active disease in patients with Sneddon's syndrome. The results support the notion that an immune-mediated prothrombotic state facilitating the formation of arterial thrombi with subsequent cerebral embolization, and/or triggering in situ thrombosis of cerebral vessels, plays a pathogenetic role in the neurologic manifestations of this disorder.
Assuntos
Transtornos Cerebrovasculares/etiologia , Embolia e Trombose Intracraniana/complicações , Adulto , Anticorpos Antifosfolipídeos/análise , Feminino , Humanos , Hipertensão/etiologia , Embolia e Trombose Intracraniana/diagnóstico por imagem , Embolia e Trombose Intracraniana/imunologia , Masculino , Pessoa de Meia-Idade , Radiografia , Dermatopatias Vasculares/etiologia , SíndromeRESUMO
Striking numerical and structural chromosome abnormalities (-Y, +8, i(7q), del (10)(q24), and del (11)(q21)) were detected by cytogenetic analysis in a patient's bone marrow with morphological features of both acute lymphoblastic leukemia and myelodysplastic disorder. Surface marker analysis characterized blast cells to be CD2+ CD7+ CD3+ CD4- CD8- expressing gamma/delta-T-cell receptor antigen and coexpressing CD11b and CD16. Exhibiting an identical phenotype as the leukemic cells, a prominent gamma/delta-TCR+ lymphocyte population was found in the bone marrow as well as in the peripheral blood. Cells of the latter compartment coexpressed CD56 and HLA-DR antigens and exhibited nonspecific cytotoxic activity. In the bone marrow cells NSCA could be induced after stimulation with interleukin 2 in vitro. Morphological, immunological, and cytogenetic findings suggest that gamma/delta-T-ALL emerged from a myelodysplastic disorder after sequential steps of malignant transformation. Leukemic cells with "mixed lineage" character may provide evidence for a common progenitor cell in the bone marrow. Assuming that the leukemic cells represent the malignant counterpart of normal CD3+ gamma/delta-TCR+ cells the results may contribute to our understanding of the origin and differentiation as well as the possible steps of malignant transformation of a gamma/delta-TCR+ lymphocyte population.
Assuntos
Anemia Sideroblástica/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Medula Óssea/patologia , Antígeno CD56 , Transformação Celular Neoplásica/patologia , Aberrações Cromossômicas , Humanos , Imunofenotipagem , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologiaRESUMO
Allogeneic bone marrow transplantation (BMT) was performed in a 34-year-old man for non-Hodgkin's lymphoma. Two years before bone marrow harvest, pulmonary sarcoidosis was diagnosed in the donor. After steroid therapy, disease of the donor was in clinical remission with only minor radiological signs at the time of BMT. On day 90 after BMT, active sarcoidosis was diagnosed in the recipient. Besides radiologic signs and increased angiotensin converting enzyme levels, diagnosis was proved by characteristic histologic changes in lung and liver biopsies. Immunosuppressive therapy was changed from high dose cyclosporine to high dose methylprednisolone and symptoms promptly resolved within 10 weeks. This case indicates the possibility of transmission of sarcoidosis by marrow transplantation.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Sarcoidose/etiologia , Adulto , Ciclosporina/uso terapêutico , Humanos , Hepatopatias/tratamento farmacológico , Hepatopatias/etiologia , Hepatopatias/patologia , Pneumopatias/diagnóstico , Pneumopatias/tratamento farmacológico , Pneumopatias/etiologia , Linfoma não Hodgkin/terapia , Masculino , Metilprednisolona/uso terapêutico , Sarcoidose/diagnóstico , Sarcoidose/tratamento farmacológico , Transplante HomólogoRESUMO
Ex vivo production of interleukin 10 (IL-10) and interferon-gamma (IFN-gamma) was investigated in patients with (n = 5) or without (n = 5) chronic graft-versus-host disease (cGVHD) after allogeneic BMT. Patients were matched for time after transplantation and type of transplant. Anti-CD3-induced IL-10 production in MNCs isolated from patients with cGVHD (range/median: 26-650 pg/10(6) MNC; 400 pg/10(6) MNC) was significantly reduced compared to patients without cGVHD (646-2662 pg/10(6) MNC; 1314 pg/10(6) MNC; P < 0.05) or healthy controls (679-6361 pg/10(6) MNC; 3054 pg/10(6) MNC, P < 0.01). In vitro inhibition of IL-10 by an anti-IL-10 monoclonal antibody enhanced the release of IFN-gamma by anti-CD3-stimulated MNCs from 354 +/- 34 pg/10(6) MNCs to 899 +/- 61 pg/10(6) MNCs. Thus, low IL-10 production may cause high IFN-gamma release. In anti-CD3-activated MNCs obtained from patients with cGVHD IFN-gamma production was significantly increased (324-3331 pg/10(6) MNC; 1849 pg/10(6) MNC) compared to healthy donors (127-900 pg/10(6) MNC; 305 pg/10(6) MNC P < 0.01). In addition, median IFN-gamma release by anti-CD3-activated MNCs obtained from patients without cGVHD (464 pg/10(6) MNC) was about five-fold lower than in patients with cGVHD. In contrast to cytokine production, the differential leukocyte count (percentages of monocytes, T cells and CD4/CD8 ratio) was essentially the same both in patients with or without cGVHD. Thus, a different activation of Th-1 and Th-2 cells by anti-CD3 may be responsible for the deviant cytokine productions in patients with cGVHD. In conclusion, we observed significantly decreased IL-10 production in patinets with cGVHD and an increased median IFN-gamma secretion, which may contribute to the altered cytokine production after allogeneic BMT leading to cGVHD. Thus, supplementing IL-10 may become a new strategy for preventing cGVHD.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Doença Enxerto-Hospedeiro/sangue , Neoplasias Hematológicas/terapia , Interferon gama/sangue , Interleucina-10/sangue , Adolescente , Adulto , Criança , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Transplante HomólogoRESUMO
Ex vivo IgG production was determined in 17 children and adolescents and in 14 adult patients between 10 months and 6 years after BMT. Twenty-four patients received allogeneic transplants. Seven patients were transplanted with autografts. Seven patients received immunosuppressive therapy. B cells were purified by positive selection with a CD20 antibody. After IL-2 or IL-10 stimulation, IgG production of SAC-preactivated B cells in patients with immunosuppression (median/range: 11/4-15 ng/ml or 14210-29 ng/ml) was significantly reduced compared with patients receiving allogenic (30/3-860 ng/ml or 33/2-3431 ng/ml; P < 0.01) or autologous transplants (75/7-1431 ng/ml or 269-/7-13600 ng/ml, P < 0.01). In 14/31 patients ex vivo IgG production was defective. Investigations of B cell function in patients with defective IgG production was performed significantly earlier after BMT compared with patients with normal IgG production ex vivo (2 +/- 1 years vs 3.3 +/- 1.5 years; P < 0.05). In addition, only patients with a B cell deficiency received immunosuppression. However, patients ex vivo IgG produced by B cells was decreased, but IgG production/sIgG+ B cells was within range of healthy volunteers. The number of IgG-committed B cells in these patients was significantly reduced compared to patients without deficiency (23/19-45/microliter vs 100/14-336/microliter; P < 0.05), indicating an in vivo switching defect. Although IL-10 is known to induce IgG-isotype switching in vitro, production of IL-10 by anti-CD3 activated MNCs obtained from patients with a switching defect did not differ from patients without B cell defects (1699/400-2662 pg/ml vs 724-112-1826 pg/ml). In nine patients IgG production and IgG production/sIgG+ B cells were impaired. The number of sIgG+ B cells was not decreased compared with patients without B cell deficiency (115/18-288/microliter), indicating a defective terminal differentiation of IgG-committed B cells to plasma cells. Although autocrine IL-6 is essential for plasma cell formation of isotype-determined B cells, it was comparable in patients with a terminal deficiency and without deficiency (3838/583-5967 pg/ml vs 2423/1643-6184 pg/ml). However, IL-10 production by anti-CD3 activated MNCs in patients with a terminal B cell defect (426/54-2262 pg/ml, P < 0.05) was significantly lower than in patients without deficiency, indicating a deviant cytokine production by T cells which might in part account for the B cell defect. Defective isotype switching as well as impaired terminal differentiation of B cells were found. Further analysis of factors regulating isotype-switching in vivo as well as cytokine receptor expression or signalling processes of differentiation factors in activated B cells might help to characterize the nature of these B cell deficiencies after BMT.
Assuntos
Linfócitos B/imunologia , Transplante de Medula Óssea/imunologia , Deficiência de IgG/etiologia , Switching de Imunoglobulina , Adolescente , Adulto , Formação de Anticorpos , Linfócitos B/efeitos dos fármacos , Linfócitos B/patologia , Diferenciação Celular , Células Cultivadas , Criança , Pré-Escolar , Feminino , Doenças Hematológicas/terapia , Neoplasias Hematológicas/terapia , Humanos , Imunoglobulina G/biossíntese , Terapia de Imunossupressão/efeitos adversos , Interleucina-10/sangue , Interleucina-2/farmacologia , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Plasmócitos/imunologia , Plasmócitos/patologia , Transplante Autólogo/imunologia , Transplante Homólogo/imunologiaRESUMO
For autologous stem cell transplantation, it is common practice to infuse at least 2 x 10(6)/kg CD34+ cells to ensure rapid engraftment. However it was recently claimed that increasing the threshold to 5 x 10(6)/kg leads to a faster platelet engraftment. To evaluate these threshold values in our patient population we undertook a retrospective analysis of 127 autologous transplants performed at our institution between 1992 and 1998. Diagnoses included Hodgkin's and non-Hodgkin's lymphoma, myeloma, acute leukaemias and solid tumours. The transplant was peripheral blood stem cells in 107 cases and CD34-selected peripheral blood stem cells in 20 cases. The median number of transplanted CD34+ cells was 3.2 x 10(6)/kg (range 0.64-25.9 x 10(6)/kg). Haematopoietic recovery to a neutrophil count >0.5 x 10(9)/l took a median of 10 (range 5-16) days from transplant. When comparing patients receiving at least 5 x 10(6)/kg and 2-5 x 10(6)/kg CD34+ cells we found a significant reduction in the median number of days with fever (1 vs 3.5 days, P = 0.0025), incidence of fever (78.8 vs 92.1%, P = 0.032) as well as duration of antibiotic treatment (7 vs 10 days, P = 0.038). This was paralleled by a faster neutrophil recovery to 0.5 x 10(9)/l (9 vs 10 days, P = 0.047). There was no significant difference in the number of platelet or red cell transfusions between the two groups. We conclude that transplantation with a stem cell dose of at least 5 x 10(6)/kg CD34+ cells reduces infectious complications and should thereby increase the safety of this type of therapy while reducing duration (and cost) of antibiotic therapy. The transplantation threshold should thus not remain at 2 x 10(6)/kg particularly in patients with a good stem cell mobilisation capacity.
Assuntos
Antibacterianos/uso terapêutico , Antígenos CD34/análise , Febre/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adolescente , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante AutólogoRESUMO
High-dose chemotherapy (HDCT) followed by autologous blood stem cell transplantation is considered the treatment of choice for patients with relapsed or resistant aggressive non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). However, several authors report failure of standard mobilization regimens in 29% to 56% of these patients making the completion of HDCT impossible and as a result, negatively influencing long-term outcome. Thus, effective new regimens for patients failing initial mobilization are needed. Here we report the results of using etoposide as a mobilizing agent in 16 patients with primary resistant or relapsed malignant lymphoma who had failed prior mobilization of peripheral blood stem cells (PBSC) with cyclophosphamide (4 g/m2) followed by G-CSF. The use of etoposide 500 mg/m2 (days 1-4) + G-CSF resulted in the successful collection of adequate numbers of PBSC with a median harvest of 3.6 x 10(6)/kg (range 2.2-12.6) CD34+ cells in all 16 patients. In 7/16 (44%) patients, the target yield of at least 2.0 x 10(6) CD34+ cells was harvested by a single apheresis and the maximum number of separations for all patients was two. No excessive toxicities appeared, allowing all patients to proceed to myeloablative chemotherapy. In addition, median peak values of circulating CD34+ cells were significantly higher after etoposide as compared to cyclophosphamide (49.2/microl vs 4.7/microl; P = 0.0004). These results indicate that etoposide + G-CSF is a highly effective mobilization regimen in patients who have failed cyclophosphamide mobilization.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Ciclofosfamida/uso terapêutico , Etoposídeo/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas , Linfoma/terapia , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RecidivaRESUMO
Experimental evidence suggests a stimulatory effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on both platelets and coagulation. RhG-CSF is increasingly used to stimulate healthy volunteer donors for blood stem cell mobilization. We therefore assessed 25 healthy donors receiving rhG-CSF for changes in in vitro bleeding test (IVBT), coagulation parameters and cerebral microembolism by transcranial Doppler (TCD) ultrasound. A significant shortening of IVBT was found on day 4 of rhG-CSF administration together with increased levels of fibrinogen and factor VIII and reduced activities of protein C and protein S. Although these changes are quite small it is possible that they may lead to a hypercoagulable state especially in donors with other risk factors for thromboembolism. However, TCD examination failed to detect any signs of microembolism. We therefore conclude that rhG-CSF leads to significant changes in coagulation parameters, but has no effect on TCD detectable microembolism as a stroke risk factor. However donors receiving rhG-CSF should be examined carefully to detect pre-existing changes in the coagulation system and we would like to suggest a routine thrombophilia screen.
Assuntos
Plaquetas/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Mobilização de Células-Tronco Hematopoéticas/efeitos adversos , Adolescente , Adulto , Tempo de Sangramento , Coagulação Sanguínea/efeitos dos fármacos , Testes de Coagulação Sanguínea , Feminino , Filgrastim , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Ultrassonografia Doppler TranscranianaRESUMO
We present a 46-year-old patient with Ph-chromosome negative, bcr-negative chronic myeloid leukaemia (CML) in accelerated phase with a clonal trisomy 21 in the leukaemic blast cells. A rapid progress of disease with appearance of monocytosis is described, showing similar features to chronic myelomonocytic leukaemia (CMML). Heterogeneous characteristics and possible distinction of these two entities are discussed.
Assuntos
Cromossomos Humanos Par 21 , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Trissomia , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/fisiopatologia , Masculino , Pessoa de Meia-IdadeRESUMO
We performed a phase II study to determine the efficacy of maximal cytoreductive therapy with up to five cycles of Dexa-BEAM (dexamethasone, carmustine [BCNU], etoposide, cytarabine, and melphalan) followed by high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) for patients with advanced relapsed or refractory indolent lymphoma. Thirty-two patients with primary refractory or relapsed indolent lymphoma were treated with the Dexa-BEAM regimen. Thirteen patients had primary refractory disease, 4 patients partial remission, and 15 patients first or subsequent relapse. Patients achieving PR or CR received HDCT with ASCT. The conditioning regimen used was BEAM (carmustine [BCNU], etoposide, cytarabine, and melphalan). Twenty-two patients responded to Dexa-BEAM resulting in a response rate of 78%. Maximum response was observed after 3.2 (range 2-5) courses. One patient with progressive disease died in septic shock during neutropenia. Nineteen patients with partial or complete remission after Dexa-BEAM received HDCT. Hematopoietic stem cells (HSC) were collected after two cycles of Dexa-BEAM. The median number of CD34+ HSC reinfused was 3.1 x 10(6)/kg (range 1.6-8.2 x 10(6)/kg). There was no transplantation-related death. All patients receiving HDCT achieved complete remission. Overall survival (OS) and freedom from treatment failure (FFTF) for all patients are estimated to be 68% and 65% at two years, respectively. With a mean follow-up of 20 months (range 8-42 months), 16/19 patients receiving HDCT are in continuous complete remission. The Dexa-BEAM regimen is effective in overcoming drug resistance in patients with indolent lymphoma who failed to respond to conventional treatment or who relapsed. The CR rate of 100% of those patients receiving HDCT and ASCT after maximal cytoreductive treatment with Dexa-BEAM suggests the use of HDCT at the time of maximal response.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Linfoma/tratamento farmacológico , Terapia de Salvação , Adulto , Carmustina/administração & dosagem , Citarabina/administração & dosagem , Dexametasona/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Indução de Remissão , Análise de Sobrevida , Condicionamento Pré-Transplante , Transplante AutólogoRESUMO
Mantle-cell lymphoma (MCL) is not a curable disease using conventional chemotherapy. Patients with MCL have the shortest median time to progression and the shortest median survival of all lymphoma subtypes after first-line treatment. In the present study we determined the efficacy of maximal cytoreductive therapy with up to four cycles of Dexa-BEAM (dexamethasone, carmustine [BCNU], etoposide, cytarabine, and melphalan) followed by high-dose chemotherapy (HDCT) and autologous hematopoietic stem cell support (ASCT) for patients with advanced relapsed or refractory MCL. Nine consecutive patients with relapsed or refractory MCL were included. Three patients had partial remission (PR), three patients progressive disease (PD) upon first line tretment, and three patients first or subsequent relapse. After 2 to four cycles of Dexa-BEAM eight patients achieved complete remission (CR), resulting in a response rate of 88%. Six of 8 patients responding to Dexa-BEAM received high-dose chemotherapy HDCT (BEAM) and autologous hematopoietic stem cell transplantation (ASCT). With a median follow up of 24 months six patients are alive. Five of those six patients are still in contiuous CR (range 13-54 months).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Linfoma de Célula do Manto/terapia , Terapia de Salvação , Adulto , Carmustina/administração & dosagem , Citarabina/administração & dosagem , Dexametasona/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Indução de Remissão , Análise de Sobrevida , Transplante AutólogoRESUMO
We investigated platelet function of 21 healthy blood donors before, 4 hrs and 1 to 7 days after a single oral dose of 0.02 (n = 3), 0.05 (n = 3), 0.1 (n = 3), 0.5 (n = 2) and 1.0 g (n = 10) aspirin. Three additional donors received 0.02 g aspirin/day for 5 days. A new and simple in vitro bleeding test (Thrombostat) using whole blood was far more sensitive than all other tests for platelet function (subaquatic bleeding time, thrombelastrogram, resonance-thrombogram, platelet adherence, spreading and aggregation). With this method using 2mM CaCl2 as additional agent all donors showed significantly increased in vitro bleeding volumes, for at least 2 days after ingestion of 0.1 to 1 g aspirin. In the majority of cases the aspirin effect could be detected even after 5-6 days. In 2 of 3 donors even 0.05 g aspirin was detectable. There was already a definite effect seen after 2 days in all 3 cases when 0.02 g was ingested daily. The new in vitro bleeding test should be suitable for the control of low dose aspirin prophylaxis of arterial thromboembolic disorders.
Assuntos
Aspirina/farmacologia , Plaquetas/efeitos dos fármacos , Testes de Função Plaquetária/métodos , Cloreto de Cálcio/farmacologia , Humanos , Técnicas In Vitro , Adesividade Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária , Ristocetina/farmacologiaRESUMO
Allogeneic BMT was performed in a 33-year-old man because of CML. Donor was his HLA-identical brother. GVHD prophylaxis consisted of short-term MTX and i.v. CsA. On day 17 cutaneous GVHD grade-III developed and high-dose methyl-prednisone was added. Initial daily dose of CsA was 4 mg/kg i.v. CsA dosage was adapted to maintain blood trough levels between 200 and 350 ng/ml. On day 27 the patient developed severe musculoskeletal pain of knees, legs, feet, hands, shoulders and ellbows. Only high-dose opioids and dextropropoxyphen were effective for analgesia. Additional medication besides CsA consisted of parenteral nutrition, steroids and antibiotics for total intestinal decontamination. Clinical and radiological examinantion revealed no causes for musculoskeletal pain. Serum levels for lactate-dehydrogenase, aldolase, alkaline-phosphatase, creatinphosphokinase with isoenzymes, electrolytes including magnesium were within normal ranges. Pain decreased within 4 days after switching, from intravenous to oral application. This case indicates that CsA in high dosage given intravenously combined with steroids can cause severe musculoskeletal pain as side effect in allogeneic BMT.
RESUMO
Acalculous cholecystitis (AAC) is a well known complication in critically ill patients. Risk factors include mechanical ventilation, total parenteral nutrition and multiple blood transfusions. AAC has very rarely been described in patients undergoing allogeneic BMT. We report a case of AAC in a 25-year old female occuring after successful allografting for acute myeloid leukemia. The patient presented with leukocytosis, acute abdominal pain, right upper quadrant guarding and laboratory signs of liver dysfunction coincidentally with oral recontamination 38 days after BMT. AAC was diagnosed during explorative laparatomy and cholecystectomy was performed. Following surgery the patient developed acute graft versus host disease but recovered completely.
RESUMO
Several reports have showed an increased risk of secondary malignancies after bone marrow transplantation (BMT), especially after total body irradiation (TBI). We report on a 39-year-old female who underwent BMT with a matched unrelated donor because of acute myeloid leukemia in second complete remission. Previously, the patient received chemotherapy for induction, consolidation, maintenance and reinduction after diagnosis of relapse. Conditioning regimen consisted of cyclophosphamide and TBI. MTX and CSA was administered for GvHD prophylaxis. Engraftment was confirmed on day 28. Within 6 months following BMT, no complication occurred. Continuous complete remission was demonstrated by repeated bone marrow smears. On day 300 the patient complained of chest pain and dyspnea. X-ray and CT-scan showed thickening of the pleura and pleural effusion. A pleuracarcinosis was diagnosed by cytologic examination of a pleural aspirate. By an open thoracotomy a disseminated inoperable disease became apparent. Diagnosis of an adenocarcinoma was confirmed by histologic examination. The patient died 2 months later due to disseminated tumour in complete remission of AML. Solid tumours are rare as secondary malignancies after BMT. Usually the neoplasmas are late events occurring more than 10 years after BMT. In this case predisposing factors such as genetic disposition, long-term smoking, intensive pretransplant chemotherapy, TBI and immunosuppression may have lead to the early secondary malignancy.
Assuntos
Adenocarcinoma/etiologia , Transplante de Medula Óssea/efeitos adversos , Leucemia Mieloide Aguda/terapia , Adulto , Feminino , Humanos , Leucemia Mieloide Aguda/complicações , Complicações Pós-Operatórias , Transplante HomólogoRESUMO
Transfusion of allogeneic blood products carry a small but not negligible risk for the transmission of infections and may have immunosuppressive or immunogenic effects. The discovery, licensing, and clinical use of hematopoietic cytokines such as erythropoietin or thrombopoietin may reduce the requirements for allogeneic blood transfusions. However, the effectiveness has so far only been demonstrated in limited clinical situations. Further progress in avoiding allogeneic transfusions can be expected from the development of artificial blood cell substitutes. The potential and limits of these new techniques and substances to manage pancytopenia in cancer patients are reviewed briefly. Copyright 2000 S. Karger GmbH, Freiburg
RESUMO
BACKGROUND: Thrombotic thrombocytopenic purpura (TTP), in 1924 first described by Moschcowitz, is a clinically heterogeneous syndrome associated with thrombocytopenia, Coombs-negative hemolytic anemia, neurologic changes, renal impairment, and fever. TTP is found after various bacterial or viral infectious diseases, autoimmune diseases and also in association with different drugs. PATHOGENESIS: After initial endothelial cell injury unusually large von Willebrand factors (vWF) are found in plasma of patients with thrombotic thrombocytopenic purpura. Because of impaired proteolysis these large forms lead to thrombosis of the small vessels. The microangiopathy is followed by mechanical destruction of red cells. In peripheral blood smears these fragmentocytes are important for diagnosis and clinical course. THERAPY: The therapy of choice is plasma exchange against fresh frozen plasma, whereupon the mortality could be dramatically reduced in the past decades. In case of treatment resistance to plasma exchange there exists no common treatment schedule. One therapy option is immunosuppressive treatment with corticosteroids and vincristine. In case of chronic relapsing TTP splenectomy should be discussed. In spite of severe thrombocytopenia substitution of thrombocytes is contraindicated.