摘要:

Abstract:Partial splenic embolization is an alternative procedure to total splenectomy in patients with hypersplenism, and was performed in 10 patients with beta‐thalassaemia major who were then followed for 5 to 7 years. The results were compared with those of a 7‐yr follow‐up of 6 splenectomized thalassaemics. The blood consumption decreased and the leucocyte counts increased in both groups of patients. However, after partial splenic embolization, severe thrombocytosis — which is typical of splenectomized patients — did not develop and there were no severe complications from the operation, such as infections or reappearance of hypersplenism. In addition, the minor surgical injury and avoidance of abdominal scars were further advantages of partial splenic embolization over total sp

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb00029.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:Forty‐six consecutive patients with acute lymphoblastic leukaemia (ALL), having a median age of 23 years (range 14 to 64), underwent induction and consolidation chemotherapy with weekly parenteral vincristine, adriamycin, 1‐asparaginase and daily oral prednisone (VAAP), followed by standard central nervous system (CNS) prophylaxis. Maintenance therapy was given for 3 years and consisted of daily 6‐mercaptopurine, weekly methotrexate, and monthly intrathecal chemotherapy, with drug intensification comprising either vincristine, adriamycin and 1‐asparaginase (VAA) or cyclophosphamide, vincristine, cytosine arabinoside and prednisone (COAP). Complete remission (CR) was achieved in 36 patients (78%) and only the FAB L1 morphology was a significant predictive factor (Chi‐squared = 3.91: p<0.05). Eight of the 10 non‐responders had significant drug resistance and 3 deaths were associated with marrow hypoplasia. Median follow‐up is 52 months. Median duration of CR is 28 months, median survival of all patients is 16 months, and for those who achieved CR is 44 months. There was no difference between the two maintenance arms. Significant prognostic factors for survival are French‐American‐British (FAB) subtype, in which the L1 is better than L2 (p = 0.05), and age (p = 0.035). Nineteen patients have experienced medullary relapse and 7 (37%) achieved subsequent CR; this is durable in a single patient who underwent allogeneic bone marrow transplantation. Eight patients (17%) had CNS disease at diagnosis; 5 achieved CR and 1 is alive and disease‐free at 65 + months. There has been 1 CNS relapse. These results demonstrate that prolonged remissions and survival can be achieved with this protocol and many patients possibly cured. The level of toxicity is acceptable and the pattern of induction failure indicates that a margin exists for intensifying chemotherapy and thereby possibly furthe

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb00030.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:Immunoreactive erythropoietin levels were measured in 42 patients with lymphoid malignancies with anaemia and bone marrow involvement. Results were compared to a control group of 16 patients suffering from anaemia due to other causes. Significant inverse correlations between serum erythropoietin level and haemoglobin concentration were shown for the patients with lymphoid malignancies and also for the control subjects. Overall, the erythropoietin levels of patients with lymphoid malignancies with bone marrow infiltration and with normal renal function did not differ significantly from erythropoietin levels of the anaemic controls. We conclude that anaemia in patients with lymphoproliferative disorders with bone marrow infiltration and normal renal function is caused primarily by a diminished/inadequate response to erythropoietin at the level of the target cell.

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb00031.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:The incidence of thrombotic complications chronologically related to L‐asparaginase administration is retrospectively analyzed in 238 adult ALL patients treated according to the GIMEMA protocol ALL 0288. The patients (126 males and 112 females, aged 12–68 years, median 29) received E. coli L‐asparaginase (L‐ase) in the induction phase at a dosage of 6000 U/m2/day × 7 d starting on d 15, as well as vincristine, prednisone, daunorubicin and cyclophosphamide, the last‐named by random 1:1. Ten patients (4.2%) developed thrombotic complications 5–15 d (median lid) after the start of L‐ase treatment. The thrombotic events, which were lethal in 5 patients, involved the cerebral sinus (5 cases), the cerebral arteria (2 cases), the portal vein (1 case), the pulmonary district (1 case), and a deep vein in the lower extremity (1 case). The occurrence of these complications was not related to the general thrombotic risk factors, nor to the main clinical and laboratory data registered at diagnosis and immediately before the start of L‐asparaginase treatment. The present study documents for the first time in a sufficiently large series of adult ALL patients that the incidence and the severity of thrombotic events related to L‐ase administration are relevant and need fur

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb00032.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:Eleven previously untreated patients with chronic‐phase Philadelphia‐chromosome‐positive chronic myelogenous leukemia were treated with cytotoxic chemotherapy followed by interferon‐alfa‐2b (IFN‐α) maintenance. Initial chemotherapy consisted of three cycles of mitoxantrone 10 mg/m2on day 1 and 2, and cytarabine 100 mg/m2daily for 5 d. Complete hematological response was obtained in 9 (82%) patients with moderately associated toxicity. However, cytogenetic responses after three cycles were poor and transient (1 partial suppression and 2 minor suppression of Ph chromosome). Maintenance therapy with IFN‐α was started in 10 patients at 5 × 106U/m2daily with dose reduction if hematologic toxicity or severe side‐effects occurred. Of 9 evaluable patients treated for more than 3 months, 6 patients maintained a complete hematological response, whereas 1 patient remained in partial remission and 2 patients showed progressive disease. Cytogenetic evaluation showed partial suppression of Ph chromosome in 1 patient, whereas 1 patient had a minor response and 5 patients had no change or evolution of new chromosome abnormalities. As the results are not superior to IFN‐α treatment alone, it is concluded that initial cytoreduction by mitoxantrone and cytarabine has no impact on the outc

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb00033.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:The most promising nucleoside analogs that are currently undergoing preclinical and clinical testing for anti‐HIV activity belong to the dideoxynucleoside group. We have studied the toxicity of 3′‐azido,3′‐deoxythymidine (AZT), 2′,3′‐dideoxycytidine (DDC), and 2′,3′‐dideoxyinosine (DDI) in canine bone marrow progenitor cells in culture. AZT potently inhibited both canine CFU‐GM and CFU‐E with IC50values of 2 and 8 μmol/l respectively, while DDC was relatively non‐toxic to either progenitor with IC50of>200μmol/l and 80μmol/l respectively. DDI was mildly toxic to the bone marrow progenitors, with IC50values of 62 μmol/l for CFU‐GM and 70 μmol/l for CFU‐E. Dipyridamole, a nucleoside transport inhibitor, did not influence the toxicity of these dideoxynucleosides in either progenitor at concentrations up to 10 μmol/l. Using uridine as the prototype endogenous nucleoside, we have demonstrated that there is a saturable “zero‐trans” nucleoside transport system in canine bone marrow mononuclear cells, which is completely inhibited by 1 μmol/l dipyridamole (Ki = 0.02 μmol/l). None of the dideoxynucleosides appeared to be a substrate for this transport system, and dipyridamole did not alter their influx. Permeation of radiolabeled AZT into bone marrow mononuclear cells was slow and non‐saturable, while the permeation of DDI was even slower. DDC did not permeate bone marrow cells well, with very little cell accumulation even after 2 hours of equilibration. Our toxicity data from canine bone marrow progenitor cells paralleled the clinical hematotoxicity profiles of these dideoxynucleosides in AIDS patients and suggest that the myelotoxicity of a nucleoside analog is related to its ability to permeate the progenitor cells in question. Canine bone marrow progenitor cultures may serve well as

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb00034.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:Patients undergoing allogeneic bone marrow transplantation (BMT) were randomized into two groups. One group (n = 21) received single donor platelet concentrates (PC) that were as fresh as possible, the other group (n = 18) received single donor PC stored for 2 to 5 days. Actual mean storage times for PC were 1.12 ± 1.25 (mean ± SD) and 2.67 ± 1.30 d, respectively (p<0.001). The total need for platelets during 60 d after BMT in patients receiving fresh PC was 22.1 ± 17.8 × 109platelets/liter blood volume/d, and for stored PC 29.2 ± 19.2 × 109platelets/liter blood volume/d (n.s.). A multiple regression analysis of the data showed no correlation between PC storage time and the PC requirement (p = 0.85). Posttransfusion corrected count increment (CCI) at 1 hour was 10.4 ± 5.1 for PC stored 0–1 d, 10.3 ± 7.0 for PC stored 2–3 d, and 11.4 ± 9.2 for PC stored 4–5 d. The corresponding CCI, at 18 h were 6.5 ± 4.4, 5.4 ± 3.3 and 6.8 ± 4.6. We conclude that there is no major difference between fresh and stor

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb00035.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:The defective enzymes of 54 patients with pyruvate kinase (PK) deficiency were characterized according to the recommendations of the International Committee for Standardization in Haematology (ICSH). The erythrocyte PK activity in whole blood was calculated considering the 16‐fold higher activity of the reticulocyte enzyme (AR) compared to the erythrocyte enzyme (AE). The following parameters turned out to give a good correlation to the degree of haemolytic anaemia and can therefore serve as a prognostic tool: All patients with a severe course of the disease had residual erythrocyte PK activities less than 33% of the normal enzymes (percentage activity), and patients with mild haemolytic anaemia exhibited residual activity values below and above this threshold value. Studies of enzyme cooperativity showed that positive cooperative or mixed cooperative phosphoenolpyruvate (PEP) binding with a predominant positive cooperative part appeared in all cases with a mild clinical course, and about one‐third of the severe ones. Negative cooperativity or mixed cooperativity with predominant negative cooperative part was observed only with severe haemolytic anaemia. Furthermore, the determination of glucose‐6‐phosphate (G‐6‐P) turned out to be a good prognostic criterion, i.e. all patients with mild clinical course exhibited G‐6‐P‐concentrations lower than 0.11 μmol/l red blood cells. In the case of patients with severe haemolytic anaemia, about 80% showed values higher th

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb00036.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:Interferon‐α‐2b has been demonstrated to prolong remission duration and survival in responding multiple myeloma patients. The aim of this study was to evaluate intensification of this maintenance therapy through the addition of glucocorticoids. Eighteen myeloma patients at diagnosis received six‐12 courses of conventional chemotherapy and then interferon + glucocorticoids. This treatment included 3 megaunits of interferon three times a week, plus 4 days of pulsed high‐dose dexamethasone (40 mg/d for 4 d every 28 d for 6 months/year) in patients50%) was achieved during interferon + glucocorticoids treatment in 7/13. 4/18 patients relapsed with a median follow‐up of 22 months (range 13–40). These findings indicate that interferon + glucocorticoids, after inductional chemotherapy, further reduces tumor burden and may prolo

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb00037.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:Proteolysis of coagulation factors and inhibitors resulting in haemorrhage can be mediated by elastase. Indirect signs of this are elevated levels of elastase complexed to its inhibitor in plasma, α1‐antitrypsin (Eα1‐AT). We have measured intracellular elastase activity in leukaemic cells from 60 patients with acute leukaemia. Elastase activity was detected in 92% of the patients with acute nonlymphoblastic leukaemia (ANL), no activity was found in the patients with acute lymphoblastic leukaemia (ALL). High levels were found in cells from patients with promyelocytic leukaemia. Moderate to high total circulating blast elastase activity was measured in 70 % of the ANL patients with haemorrhage compared with 36% of the patients without bleeding complications (p<0.05). The available intracellular elastase activity was correlated to the level of Eα1‐AT (rs= 0.42, p<0.01) but not to the elastase specific split product of fibrinogen, Bβ 30–43. In complete remission the levels of Eα1AT were normalized. Intracellular elastase activity might be a useful supplement to differentiate

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb00038.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY