Allogeneic BMT in patients above 45 years of age: a single center experience.

Increasing age has been reported to be associated with worse outcome and higher occurrence of complication after allogeneic bone marrow transplantation. We analysed a cohort of 39 patients between the ages of 45 and 57 (median 49 years) with different hematologic malignancies who had undergone BMT in our institution over the preceding 4 years. Pretransplant conditioning consisted of Bu/CY2, GVHD prophylaxis of a combination of cyclosporine and "short" methotrexate. At present 54% of patients remain alive (with a median follow-up 44 months), the probability of survival at 5 years is 53% (5-year DFS 78%). The 5-year survival probability in the control group of younger patients is 53% (P = 0.8003). Main causes of death were GVHD (4 patients, 10%), relapse (5 patients, 13%) and infection (6 patients, 15%). The incidence of acute GVHD grade II-IV was 51% (grade III-IV 0% patients), the incidence of chronic GVHD 49% (limited 18% and extensive 31% patients). Our results suggest that allogeneic BMT can be performed in patients above the age of 45 years with acceptable morbidity and mortality, especially if a family HLA matched donor is available.

Autologous CD34+ cells transplantation after FAMP treatment in a patient with CLL and persisting AIHA: complete remission of lymphoma with control of autoimmune complications.

A 48-year-old male with CLL and concomitant AIHA unresponsive to chlorambucil was treated with fludarabine. The remission of CLL and improvement of the AIHA was achieved, but the patient remained steroid dependent. Therefore, high-dose chemotherapy followed by CD34-selected autologous peripheral blood stem cells transplantation was performed and this led to long-term clinical, immunophenotypic and molecular remission with disappearance of AIHA. Twenty-three months later, the CLL recurred with signs of AIHA. In this patient with AIHA, HDC and selected CD34+ cells completely, though temporarily, controlled both CLL and associated immune complications. This case illustrates the potential application of this approach in the management of CLL patients with immune complications.

[Treatment of multiple myeloma with high-dose chemotherapy and transplantation of autologous hematopoietic stem cells and subsequent maintenance therapy with interferon alfa-2b or interferon alfa 2b and dexamethasone. Report of the ongoing study of the "4W" Czech Myeloma Group]. / Lécba mnohocetného myelomu vysokodávkovanou chemoterapií s transplantací autologních kmenových hemopoetických bunek a následující udrzovací lécbou interferonem alfa-2b nebo interferonem alfa-2b a dexametazonem. Zpráva o probíhající studii "4w" Ceské myelomové skupiny.

We report our results with high-dose chemotherapy in previously untreated multiple myeloma patients (4 courses of VAD chemotherapy, collection of PBSC after priming with cyclophosphamide, 5 g/m2, high-dose chemotherapy with melphalan, 200 mg/m2). Second transplantation was indicated only for patients who did not achieve remission after the first high-dose therapy (paraprotein lower than 25% of the pretreatment value). For the second transplantation melphalan (200 mg/m2) with methylprednisolone (1.5 g for 5 days) were used as conditioning regimen. After high-dose therapy all patients were randomized into two arms of maintenance therapy: interferon alpha-2b or sequential maintenance therapy (interferon alpha-2b for 3 months followed after 4 week pause by 40 mg of dexamethasone days 1-4, 10-13 and 20-23. The administration of interferon alpha was resumed four weeks after the last dexamethasone for next three months. The maintenance therapy continued for 48 months or until the progression. Fifty-five patients were enrolled in the study from January 1996 to August 1997. Thirty-five patients have undergone the first transplantation and 57% of them reached complete remission. There were 10% of non-responders after the first high-dose regimen. The mean time to reach white blood cell count above 1 x 10(9)/L after the application of high dose melphalan and platelets more than 50 x 10(9)/L were 12.2 (range 6-16 days) and 12.4 (range 0-25 days), respectively. Grade 4 mucositis according to SWOG classification requiring total parenteral nutrition was presented in 40% of the patients. The mean number of 1 unit of platelets and 2 units of packed red blood cells transfusions were given within the posttransplant period. Early transplant related mortality was 3%. This paper describes the response and tolerance of each particular step of therapy. The follow-up has been too short to evaluate event-free and overall survivals.

Successful autologous transplantation in a patient with severe aplastic anemia (SAA).

We report a patient who underwent peripheral blood hematopoietic progenitor (PBHP) autologous transplantation for his third SAA relapse. Although his repeated relapses were always successfully reversed by immunosuppression, he developed anaphylaxis with horse, rabbit and mouse immunoglobulins as a side-effect of his previous treatment. He was mobilized with G-CSF and underwent three leukaphereses in the period of hematologic recovery after the second relapse. Fourteen months later, he suffered his third relapse, rescued by autologous PBHP transplantation after cyclophosphamide and melphalan conditioning. At present he is 15 months after transplantation without any treatment, transfusion-independent and in good condition. Others have published the observation that sufficient PBHP can be collected at least in some patients with SAA. Our experience shows that in repeatedly relapsing SAA with no other treatment options autologous transplantation with previously collected PBHP can result in successful hematologic reconstitution.

Successful treatment of severe Shulman's syndrome by allogeneic bone marrow transplantation.

We describe a patient with severe Shulman's syndrome (ShS) (eosinophilic fasciitis). This auto-immune disease involved not only the skin and muscles, but the bone marrow as well - thereby fulfilling the criteria of severe aplastic anemia. As the disease was steroid-resistant, the patient underwent allogeneic bone marrow transplantation (BMT). Remission of ShS was achieved. Eight months later chronic GVHD developed and relapse of ShS (probably induced by GVHD) occurred. He was successfully treated with corticosteroids and the disappearance of GVHD was followed by cessation of the symptoms of ShS. At present (34 months following BMT) he is doing well and displays no signs of ShS or GVHD. This case suggests that an aggressive immunoablative preparative regimen with subsequent allogeneic BMT can result in long-lasting clinical remission of a severe auto-immune disease.

Individual criteria could be optimal for starting G-CSF application after autologous stem cell transplantation.

The optimal time for starting G-CSF application after autologous peripheral stem cell transplantation (APSCT) still remains undetermined. All previous studies used 'fixed' days (0 or +1 vs +5 or +7 post-transplant) for this purpose. As many other drugs have individual, patient-dependent criteria (eg antibiotics, blood products, etc), and the discontinuation of G-CSF also has strict patient-dependent criteria (surprisingly absent when starting the drug) we suppose that attempts to find general criteria suitable for every patient may not be successful. In order to also take the patients' individual predispositions into account we designed a randomized clinical trial to compare 'immediate' administration of G-CSF (day +1: group A) vs 'delayed, patient-dependent' (first day when absolute neutrophil count (ANC) was below 0.5 x 10[9]/1: group B) therapy with G-CSF (both groups received 10 microg/kg/day i.v.). A total of 70 patients after APSCT suffering from non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) conditioned with BEAM, or from multiple myeloma (MM) after melphalan (L-PAM: 200 mg/m2) were enrolled in this study (35 in each group). Both groups were comparable with regard to age, sex, disease stage and previous therapy as well as the number of CD34+ cells transplanted. In group B, G-CSF administration began on day +4 post-transplant (+2 - +5). There were no detectable differences seen in the hematopoietic recovery (time to reach ANC more than 0.5 x 10(9)/l: 12 days vs 13 days; time to platelet recovery, more than 50 x 10(9)/l: 24 days in both groups), use of blood products or antibiotics, infections, or days of hospitalization. Delayed G-CSF application led to significant cost saving in terms of APSCT (approximately US$1341 for each patient). We suggest that 'patient-dependent' criteria for starting G-CSF are reasonable especially in patients conditioned with protocols only slowly inducing neutropenia: eg NHL and HD patients after BEAM, MM after L-PAM or patients after busulphan and cyclophosphamide (BUCY2).

[The central registry of bone marrow donors and the program for bone marrow transplantation from unrelated donors--20 months' experience]. / Centrální registr dárcu kostní drene a program nepríbuzenských transplantací kostní drene--dvacetimesícní zkusenosti.

The authors describe their 20 months' experience with the establishment of a bone marrow register in the Czech Republic and its practical association with the programme of bone marrow transplantations from non-related subjects. During the 20 months of activity 5455 voluntary bone marrow donors were examined and at present more than 500 new voluntary donors are examined every month. For 21 patients a HLA identical unrelated donor is sought. For four patients a HLA compatible donor was found. The first bone marrow transplantation from a unrelated donor was performed and another patient is prepared for transplantation within the next few days. The authors discuss professional, organizational, moral and ethical problems associated with the elaboration of this medical programme.

Littoral cell angioma of the spleen. A case report with ultrastructural and immunohistochemical observations.

We describe histological, immunohistochemical and ultrastructural findings in a case of littoral cell angioma of the spleen in a 44 year old man. Beside phagocytosis and heavy haemosiderin deposits in the cytoplasm, a very characteristic and hitherto undescribed feature of the littoral cells was focal accumulations of eosinophilic globules 0.5-2 microns in size, which often entirely filled the cytoplasm of the tumour cells. Ultrastructurally the globules were composed of abundant cytoplasmic deposits of lysosomes and residual bodies. The globules most probably originate from the phagocytized red blood cells, lymphocytes and plasma cells. Immunohistochemically the tumour cells reacted positively with antibodies against factor VIII-related antigen, KiM1P, KP1 and lysozyme and negatively with antibodies against cytokeratins AE1-AE3, EMA and S-100 protein. Ultrastructurally the tumour cells often formed long cytoplasmic processes without external lamina and pinocytic vesicles. Scarce and poorly formed junctions between the tumour cells were seen. Very rarely cytoplasmic rod-shaped microtubulated bodies, often difficult to distinguish from heavy accumulations of lysosomes were observed.

[Development of therapy of acute myeloid leukemia at the First Internal Medicine Clinic in Plzen]. / Vývoj lécby akutních myeloidních leukémií na I. interní klinice v Plzni.

The authors summarize the development of diagnosis and treatment of acute myeloid leukaemias (AML) at the First Medical Clinic in Plzen in a (group) of 102 patients treated during 1966-1990. On their own results they demonstrate the importance of intensive post-remission treatment with large doses of cytosine arabinoside (ara-c) which makes possible long survival or complete recovery of some patients, and at the same time the necessity and pretentious character of comprehensive supportive treatment is emphasized.

[Cardiotoxicity of anthracycline cytostatic agents--a proposal for routine monitoring and supportive therapy]. / Sledování kardiotoxicity antracyklinových cytostatik--návrh rutinního monitorování a podpurné lécby.

The authors investigated a group of 57 patients with acute leukaemia and 30 patients with malignant lymphomas, who were treated by combinations of cytostatics containing the anthracycline antibiotics daunorubicin and adriamycin. Using examination methods which are widely available they tried to find indicators which detect early manifestations of cardiac damage during this treatment. The most valuable indicators of incipient anthracycline cardiomyopathy were the heart rate at rest and the QTc interval on the ECG tracing. The validity of polygraphy and echocardiography could not be assessed in the present work. The authors suggest a procedure of routine monitoring of patients treated with anthracycline cytostatics and methods of supportive therapy to ensure safe treatment.

[Pure red cell aplasia in chronic lymphatic leukemia. Successful treatment using immunosuppression]. / Cistá aplázie erythropoézy u chronické lymfatické leukémie. Uspesná lécba imunosupresí.

The authors describe two cases of chronic lympocytic leukaemia complicated by pure red cell aplasia of autoimmune origin. The first patient achieved complete recovery of erythropoiesis after short-term immunosuppression by means of cyclophosphamide and prednisone. The second patient did not respond to the same combination of immunosuppressive drugs and remission was achieved by administration of antithymocyte globulin. In the discussion the authors deal with contemporary knowledge of the pathogenesis of autoimmune erythroblastopenia and mechanismus of action of antithymocyte globulin.

[Intensive post-remission therapy of acute myeloid leukemia with high doses of cytosine arabinoside]. / Intenzívní postremisní terapie akutních myeloidních leukémií vysokými dávkami cytosin arabinosidu.

The results are estimated of treatment for acute myeloid leukaemia using intensive post-remission therapy with high doses of cytosine arabinoside (HiDAC). Two women and four men aged 18-34 years were treated with HiDAC. None of them had been given maintenance or boost chemotherapy any more at the time. The patients were rated for the duration of granulocytopenia and thrombocytopenia for the incidence of non-haematological complications and for the duration and quality of survival. The preliminary results are promising and in keeping with those reported by similar clinical centres abroad, namely that maintenance therapy should be phased out in the presence of intensive post-remission treatment.

Latent ischaemic heart disease among the male employees of an industrial enterprise.

Among 3758 men aged 40-50 years--employees of an industrial enterprise, 291 cases of suspected myocardial ischaemia (7.7%) were detected by means of resting ECG. Further 311 cases (8.3%) of latent ischaemic heart disease (IHD) were detected using a standard cardiovascular questionnaire, and 47 other men were positive both on resting ECG (ischaemic changes) and on the questionnaire. Latent IHD was equally frequent among blue and white collar workers. Ischaemic ECG findings were positively associated with a positive questionnaire, presence of hypertension, and hypertension or stroke in family history, and inversely with the alcohol consumption. No relation was found between ischaemic ECG and smoking, hypercholesterolaemia, obesity, education, and physical activity at work or during leisure time. Positive questionnaire data correlated with hypercholesterolaemia; unexpectedly this correlation was closer among non-smokers and moderate smokers than among heavy smokers.