Search

Background High-dose cytosine arabinoside (HDAC) is being used increasingly to treat haematological malignancies. The therapy is associated with various non-haematological negative side-effects, frequently involving the skin. Objective Our aim was to evaluate the actual occurrence of adverse skin reactions to HDAC over the 10-year period from 1989 to 1999. Methods One hundred and seventy-two subjects, 118 with acute myelogenous leukaemia and 54 with acute lymphoblastic leukaemia, between 16 and 71 years of age were treated with 226 post-remission consolidation regimens with HDAC (54 subjects underwent two cycles of treatment). Treatment was combined with standard doses of other cytotoxic drugs. A prospective study of the skin changes was then performed. Results The overall incidence of cutaneous reactions was almost 53%, with rashes occurring in 72.7% and 40.6% of subjects who received total doses of 30 and 24 g/m2, respectively. In the group of subjects who received a second cycle of treatment not all of those who experienced exanthema after the first cycle (44.4%) experienced this reaction after the second cycle (only 33.3%). The most commonly observed reactions were morbilliform eruptions on the trunk and extremities and acral erythema, although severe reactions with swelling and generalized urticaria developed in some cases. Conclusions HDAC-induced cutaneous reactions in 53% of subjects. The skin changes were found to be dose related and most cleared spontaneously without requiring treatment. A clinical grading of cutaneous toxicity has been proposed to allow better comparison of cutaneous adverse effects in different reports.

Dear Editor,The development of destructive haemophilic cysts(pseudotumours) occurs in approximately 1% ofpatients with severe haemophilia [1]. The recurrentbleeding can cause an encapsulated haematoma,most commonly in the pelvic bones, femur, tibia,small bones of the hand and soft tissues. Destruc-tive haemophilic cysts are typically slow growingand asymptomatic; however, in some cases, surgicalintervention is necessary to prevent progressiveenlargement and potential complications. For exam-ple, bone fractures, massive haemorrhage, infectionand compression, and eroding of adjacent struc-tures [2].Surgeryinpatientswithhaemophiliaischallenging,and for those who develop inhibitors to replacementfactors,successful surgical interventionis even harderto achieve. The development of bypassing agents,such as recombinant activated factor VII (rFVIIa) hasgreatly improved the treatment options available toinhibitor patients; for example, allowing patients toundergo elective orthopaedic surgery despite the risksof bleeding or thromboembolic events [3]. Since1998, the Institute of Hematology and Blood Trans-fusion has gained wide experience with rFVIIa in thetreatment of on-demand bleeding and minor surgeryin patients with haemophilia and inhibitors.We report here the removal of an abdominal bloodcyst in a patient with severe haemophilia A andinhibitors. Haemostatic control was effectively main-tained both before and during surgery with rFVIIa.A 51-year-old haemophilia A patient was diag-nosed with haemophilia A at 3 months of age (FVIIIlevels below 1%, nonsense mutation in exon 24)when massive bleeding occurred following herniec-tomy. After this initial bleeding episode, the patientwas repeatedly hospitalized for bleeding into hisjoints (knees and elbows), haematuria, and forbleeding into the tonsils during tonsillitis. Duringthis period, the patient was treated with cryoproteinfollowed by plasma-derived FVIII concentrates,including the period prior to detection of FVIIIinhibitors.Inhibitors to FVIII were first detected in 1983when the patient was aged 28 years. Despite immu-nosuppressive therapy with corticosteroids andcyclophosphamide the inhibitors remained, withtitres oscillating between 1 and 54 BU mL

Summary Haemostatic parameters were studied in 28 adult patients (pts) treated for acute myeloid leukaemia (AML) using an intermediate dose of AraC (1000 mg/m2 – 6 days) and mitoxantrone (6 mg/m2 – 6 days) as the second regimen after the ‘3 and 7’ regimen (18 pts were in complete remission — CR and 10 had AML resistant to ‘3 and 7’). Increased levels of plasminogen activator inhibitor (PAI) activity (p

Paroxysmal nocturnal hemoglobinuria is an acquired clonal disease characterized by proliferation of stem cells, deficient of proteins linked to the membrane via glycophosphatidylinositol (GPI) anchors. PNH cell characterization by flow cytometry was introduced in 1986, since 1996 is considered as method of choice for PNH diagnosis. Flow cytometry PNH analysis is nowadays crucial for disease monitoring in terms of progression, regression, remission or response to therapy and screening for small PNH clones (1.0%) in patients with aplastic anemia or myelodysplastic syndrome. Flow cytometry is unfortunately still poorly standardized, there is a variety of different methodological approaches for PNH evaluation and results from external quality assurances schemes reveal heterogeneous results. The aim of this work is to review the applicability of flow cytometry for the diagnosis and monitoring of PNH with respect to our experience and in the context of the recent trends and guidelines for PNH evaluation by flow cytometry.

We present two years' experience in the treatment of adult acute lymphoblastic leukemia (ALL) according to the German GMALL 07/2003 study protocol at CELL (Czech leukemia study group--for life) hematological centers in the Czech Republic.A total number of 37 patients were included in this analysis. We evaluated complete remission and molecular remission rate, incidence of relapse, patients' status at the end of the follow-up period, incidence of chemotherapy-related adverse events and causes of death. A statistical analysis of risk factors affecting survival was carried out.Complete remission was achieved in 36 (97%) patients and molecular remission in 16 (62%) of 26 evaluable patients. Disease relapse occurred in 5 (14%) patients. At the end of the follow-up period with a median of 261 days, 28 (76%) patients were alive in complete remission, one (3%) with relapsed disease and 8 (22%) dead. Treatment toxicity resulted in death in 5 cases, relapse or progression of ALL in 3 patients. Adverse events most often followed consolidation I, induction phase I, consolidation II and induction phase II. Infectious complications in the context of febrile neutropenia, GIT mucositis and side effects of PEG-asparaginase were the most common adverse events observed. The toxicity of allogeneic transplantation was not unexpected, four (25%) patients died after transplantation. Two-year progression-free and overall survival were 66% and 70%, respectively. High risk ALL, age over 35 years, CNS infiltration, disease relapse and permanent minimal residual disease were identified as the major adverse prognostic risk factors. Practical experiences and possible pitfalls of the protocol are described in the discussion.Our initial impression is promising. The treatment is feasible, the results very good and the toxicity acceptable. Patients at high risk should be headed to allogeneic transplantation, since the results ofconsolidation chemotherapy alone are very poor in this group. We believe that this study protocol could become a standard adult acute lymphoblastic leukemia treatment in the Czech Republic.

We have retrospectively evaluated a cohort of 144 patients (including 17 pediatric ones) with de novo acute promyelocytic leukemia registered in databases of institutions cooperating within the CELL group (The Czech Leukemia Study Group for Life). The patients were diagnosed according to WHO criteria from 1989 until 2006. The aim was to check how well fared the patients, the majority of whom was not included into clinical trials, in real life. Of 140 evaluable patients, 97 (69.3%) attained complete remission (CR). The projected overall survival (OS) 4 years after diagnosis was 58.9%, and 55.3% at 6 years. In 8 patients (6.0%), no antileukemic therapy at all was given (either they died shortly after admission to the ward or therapy was not feasible due to their clinical status). Of 125 patients with documented commencement of some kind of therapy, 96 (76.8%) achieved CR. Of 102 patients with induction treatment with a combination of anthracycline and tretinoin (ATRA), 84 individuals (82.4%) attained CR (typically, this cohort might have been subjected to clinical trials). This result was better than that of patients treated by chemotherapy only (n = 15; CR 46.7%; P = 0.003) or by ATRA monotherapy (n = 13; CR 62.5%; P = 0.17). Another parameter with a significant impact on attaining CR was the leukocyte (WBC) count at diagnosis: its median values in patients achieving and not achieving CR were 2.1 and 24.0 x 10(9)/l, respectively (P0.0001). The WBC counts affected OS as well (P = 0.0001). However, when only patients after attaining CR were evaluated, the initial WBC counts no longer affected OS (P = 0.18). Achieving CR was also influenced by the performance status (PS) 0-1 (P = 0.005), which was in turn closely correlated to WBC counts (P = 0.0006). Additional factors (most likely connected with leukocytosis) influenced attaining CR with borderline statistical significance: e.g. FAB M3v morphology, LDH serum level, fibrinogen level, presence of internal tandem duplication (ITD) of the FLT3 gene (which was strongly associated with leukocytosis and also with the short PML/RARalpha transcript resulting from the bcr3 break in the PML gene). It may be speculated that FLT3-ITD is just one of the possible factors that lead to leukocytosis. The platelet counts at diagnosis had no impact on entering CR. Thus, we have not validated the current PETHEMA risk stratification in distinguishing intertermediate and low risk patients. Our study points to a significant difference of the results obtained in real life and of the results that could be achieved in patients who were fit to enter clinical trials. Among the prognostic factors, the most important one was the WBC count, the PS (which is highly affected by the WBC count), and feasibility of administration of the most potent induction therapy with anthracyclines and ATRA.

Analyses of hematopoietic stem cell transplantation (SCT) results are of high importance for decision-making on treatment strategy for patients with SCT as a possible therapeutic alternative. In this paper the Czech National Registry of SCT and Transplantation Centre in Pilsen present their joint retrospective analysis of the results of allogeneic SCT in patients with chronic myeloid leukemia (CML) performed in the Czech Republic from 1988 to spring 2005. 295 patients (179 men and 116 women) ranging in age from 6.9 to 59.5 years (median 37.3) underwent transplants. In most cases the donor was an HLA-identical sibling (164; 55.6%) or a voluntary unrelated donor from the register (110; 37.3%), in a minority of cases another relative of the patient (21; 7.1%). Myeloablative conditioning was used in 90% of patients. The source of hematopoietic stem cells was bone marrow in 57%, peripheral blood in 41% and combination of both in 2% of cases. 83.4% of patients underwent transplant in the chronic phase of the illness while 7.8% in the acceleration phase and 6.1% in the blastic phase respectively. The median interval from the diagnosis to SCT was 316 days. Median follow-up after SCT was 2 years. SCT was complicated by acute graft versus host disease of grade II-IV in 33.7% of patients and by chronic graft versus host disease in 36.3% of patients. Median survival was not reached, 18 (6.1%) of patients died due to the relapse of CML and the cause of 101 (34.2%) deaths was transplant-related. Significant trends were observed during the study period: SCT were performed more frequently in older patients, less than one year from the diagnosis, reduced-intensity conditioning was used more often and the source of hematopoietic stem cells was peripheral blood in the majority of patients (p = 0.188 -0.0001). Also, transplantation activity changed - the annual rate of SCT increased steadily until 1999, while there was no such an increase between 2000 and 2005. The use of peripheral stem cells was associated with chronic graft versus host disease (p = 0.007). In Cox multivariate analysis the EBMT risk score and the interval from the diagnosis to SCT were identified as independent factors in patient survival. An "ideal" patient, aged under 30, undergoing transplant in the chronic phase of CML within one year since the diagnosis after 2000 had a survival probability of 88% for three years after SCT. It can be concluded that results of allogeneic SCT in CML in the Czech Republic reflect current global trends, are comparable with results achieved in other countries and show significant improvements.

To assess the prognostic relevance of activating mutations of FLT3 gene on outcome of allogeneic transplantations in AML patients, we performed an analysis of all patients with FLT3 mutations registered in the Czech Acute Leukemia Clinical Register (ALERT) from 2003 till the end of 2005. Within the mentioned period 170 patients with AML of median age 56 years (23-77) were investigated for FLT3 mutation, within them 36 cases (21%) with FLT3 mutations (32 FLT3 ITD and 4 FLT3 D835) were found. Out of FLT3 ITD positive patients 13 had allogeneic transplantation, 20 patients with mutations of FLT3 were treated with chemotherapy without transplantation. Results of the treatment of these patients were compared with the results of the group of patients without FLT3 mutation, which was according to other characteristics identical with the group of patients with FLT3 mutations (n=134). Median overall survival (OS) was significantly shorter for patients with FLT3 ITD (34.8 weeks) than for those without FLT3 mutations (67.7 weeks; P=0.028). Median OS of patients with FLT3 ITD who had allogeneic transplantation was 42.5 weeks; median OS of patients with FLT3 ITD treated only with chemotherapy was 29.6 weeks (P=0.362). After allogeneic transplantation, median OS of FLT3 mutations negative patients was similar to FLT3 ITD positive patients (46.7 versus 42.5 weeks; P=0.443). Our results suggest that at present there is no strong evidence that FLT3 status alone should influence the decision to proceed to allogeneic transplantation in AML patients. Decision to proceed to alogeneic transplantation should not be based on the FLT3 status only, but it should also consider other prognostic factors.

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.

In view of the increasing interest in the immunotherapy of CML it seems highly desirable to broaden the present knowledge on the immune reactivity of CML patients. A group of 24 patients and 24 healthy controls were studied for the total of 15 immunological parameters, including the prevalence of antibodies against human herpesviruses and papillomaviruses. To clearly discriminate between changes associated with the disease and those induced by the therapy, all patients were enrolled prior to the start of any anti-leukaemic therapy. Statistically significant differences between patients and controls were found in the levels of IgA, C4 component of complement, CRP and IL-6, the production of Th1 cytokines in stimulated CD3 cells and the E. coli stimulatory index. The analysis of the interrelationship between the results obtained in the individual patients presented some unexpected findings, such as the lack of correlation between the CRP and IL-6 levels. It will be the purpose of a follow-up to determine whether and how the immune status of the patients prior to the treatment correlates with their response to therapy and how the individual immunological profiles change in the course of the disease. These observations will be utilized in the future immunotherapeutic studies to constitute the vaccine- and placebo-treated groups.

Morphological examination is the routine first step in the diagnosis of hematological malignancies, including chronic lymphocytic leukemia (CLL). Atypical cell morphology according to the FAB criteria is known to herald disease progression. Several years ago, it was proposed that FAB morphology at diagnosis had a considerable prognostic impact. However, this proposal has not been widely adopted in practice. Thus we questioned the prognostic value of the morphological examination, which was performed retrospectively in 88 patients out of our 110 institutional registry patients (70 males and 40 females, median age 57 yrs) with CLL at diagnosis. We related the results to the more modern prognostic markers. Atypical FAB morphology was shown to correlate with IgVH gene mutation status, trisomy of chromosome 12 and deletion of 17p detected either by conventional G-banding or by fluorescence in situ hybridization (FISH) analysis. The correlation of FAB morphology with CD38 antigen expression or with the histopathological pattern of bone marrow infiltration was not significant. Overall survival (OS) data were available for 84 morphologically examined patients. The patients with atypical morphology (64 patients) had a significantly shorter OS (103 months) than the 20 patients presenting with typical CLL morphology (237 months; p=0.03). Only the mutation status of IgVH genes correlated more closely with OS (p=0.002). Of note, there was no leukemia-related death within "unmutated" cases who had typical FAB morphology (p=0.14), and vice versa, the mutation status had a significant prognostic impact within the morphologically atypical cases (p=0.01). Thus FAB morphology and the mutation status may yield complementary prognostic information. OS was affected both by the presence of cytogenetic aberrations (p=0.03) - most adversely by deletions of 17p and 11q, and by CD38 expression (p=0.003). We conclude that careful examination of peripheral blood smears according to FAB is a simple, cheap and valuable tool in the first-line assessment of prognosis of CLL patients and should not be overlooked even in 3rd millennium when more sophisticated prognostic markers are at hand. This ought to be confirmed in larger prospective studies with multivariate analysis of data.

The HLA-DPB1 gene is probably one of HLA class II genes affecting the haematopoietic stem cell transplantation. The aim of the study was to analyse the HLA-DPB1 gene and its match/mismatch in patients transplanted from unrelated HSC donors. The PCR-SSP method was used for the typing of the HLA system.The cohort consisted of 201 pairs of patient/unrelated HSC donor. Match in HLA-A, -B, -Cw, -DRBI and -DQBI (e.g. 10/10 match) was found in 81 pairs. The HLA-DPBI was tested in them. 18 different HLA-DPBI alleles were identified in this cohort. Complete match (e.g.12/12) was detected in 3% of the 201 analysed pairs only.The probability of finding 12/12 matching unrelated HSC donor is limited due to the high percentage of mismatches and inaccessibility of previous HLA-DPB1 results.

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).

Thrombocytopenic patients refractory to platelet concentrates (PC) could be treated during bleeding episodes with the recombinant activated FVII (rFVIIa). However, monitoring of administration of the rFVIIa or a response to platelet substitution therapy in thrombocytopenia patients is not well documented so far. Using of whole blood ROTEG analysis we monitored the changes in haemostatic parameters following in vivo platelet concentrate administration compared to ex vivo rFVIIa administration in patients with a severe to mild thrombocytopenia secondary to haemato-oncological disease. We use non-activated thrombelastography (NATEG) and a mild intrinsic activation thrombelastography (INTEG). NATEG analysis was sufficiently sensitive to monitor changes following PC and rFVIIa administration. Both, platelet infusion and rFVIIa treatment induced significant shortening of clotting time (CT) and clot formation time (CFT) parameters (p0.05). When we compared the effect of platelet vs. rFVIIa treated whole blood by NATEG analysis we did not found any significant difference. Analysis with INTEG system was less sensitive and changes in CT and CFT were not significant. The monitoring with thrombelastography could enable efficient application of platelet concentrate and furthermore the using of rFVIIa as an alternative treatment of patients refractory to platelet infusion or with allergic reactions.

In order to assess the incidence and analyze reasons which cause prolongation of hospital stay in patients engrafted after peripheral blood stem cell transplantation (PBSCT), we performed this retrospective analysis. One hundred patients (receiving 123 conditioning regimens) were included in the analysis. Criteria for discharge were presence of myeloid engraftment and absence of severe concomitant problems. Ninety subjects (73%) were discharged just after engraftment was reached on day +12 (10-14). Discharge was delayed in 33 patients (27%) and the mean prolongation was 3 days (1-11). In 31 patients (25%) delayed discharge was due to complications: in 14 patients (11.4%) because of GIT problems, in 16 patients (13%) because of infectious complications and in one patient because of cardiotoxicity. A significantly higher number of infectious complications was found in patients conditioned with BEAM (19.7% vs 4.2%, P < 0.05) while GIT toxicity was the most common reason for discharge delays in patients conditioned with melfalan 200 mg/m2 (8.2% vs 14.7%, NS). No risk factors of hospital stay prolongation were determined. We conclude that in spite of rapid engraftment, non-hematological toxicities and infections remain important limitations for further reduction of the length of patient hospitalization in a significant number of patients after PBSCT.

Cytomegalovirus infections and their sequelae are the most serious complications in patients after allogenic bone marrow transplantations. Therefore in recent years quite rightly attention is paid to new diagnostic methods which make earlier and more sensitive detection of incipient CMV infection possible. The method of the two-stage polymerase chain reaction (PCR) was used for early detection of CMV infection and its possible further monitoring in 38 recipients of allogenic bone marrow. A positive result was recorded in 15 (39%) patients whereby in 10 (13%) repeated positivity was involved. In three in this group of patients (8%) CMV disease developed, always preceded by PCR positivity. Sensitivity, specificity, positive and negative predictive CMV PCR values were 100, 66, 20 and 100%. Concomitant comparison with serological examination (antibody titre class IgM/seroconversion) revealed the small contribution of serology (corresponding values are 67, 54, 11 and 95%) in patients after bone marrow transplantations. The presented results provide evidence of the contribution of PCR in the diagnosis of CMV in those patients where due to their high sensitivity and excellent predictive value it is possible to avoid the toxicity of unnecessary antiviral treatment.

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.

Haemostatic parameters were studied in 12 adult patients with acute myeloid leukaemia and acute lymphoblastic leukaemia in complete remission using high-dose cytosine arabinoside regiments together with with other drugs. Increased tissue plasminogen activator (t-PA:Ag) antigen 4 hours after AraC application (p0.05) as well as increased levels of plasminogen activator inhibitor activity (PAI) (p0.05) and fibrinopeptide A (FPA) antigen (p0.05) were observed on day 2. All patients during bone marrow aplasia suffered from infectious complications (7 from sepsis and 5 from fever of undetermined origin). During that period of infection the increased levels of FPA on day 21 (p0.05), PAI on days 15 and 21 (p0.05) and fibrinogen on day 21 (p0.05) as well as decreased values of antithrombin III (p0.05) on day 21 and protein C on day 15 (p0.05) were measured. t-PA:Ag, plasminogen, alpha 2 antiplasmin and fibrin(ogen) degradation products were within normal throughout infectious complications. None of the patients experienced clinically manifest thrombotic complication. Though the results demonstrate that changes found were not clinically important (even if they were statistically significant), and that haemostasis was compensated as well as that thrombosis was not serious problem, authors recommend routine haemostasis monitoring in acute leukaemia patients, especially at diagnosis, in association with chemotherapy and during infectious complications.

The authors investigated the incidence of the plasminogen activator inhibitor-2 (PAI-2) in 88 patients with haematological tumours. In four patients (4.5%) an elevated PAI-2 level was found: in patient (no. 1) with non-differentiated leukaemia which developed as a result of transformation of myelodysplastic syndrome, in a female patient (no. 2) with non-differentiated blastic crisis of chronic myeloid leukaemia, in a female patient (no. 3) with acute monocytic leukaemia (M5) and in a pregnant female (patient no. 4) with a malignant lymphogranuloma. In none of the other patients with another type of acute myeloid leukaemia or other haematological tumours PAI-2 was detected. High PAI-2 levels after successful cytostatic treatment and attainment of complete remission reached normal levels, during a relapse high PAI-2 levels were recorded again. The authors assume that the presence of PAI-2 may suggest a monocytic origin of the cells which produce it. They conclude also that its value may reflect the activity of the disease with high levels during presentation or relapse of the disease and a drop or disappearance of PAI-2 after successful treatment and achieved remission.

An accelerrated-phase CML patient with e19a2 junction of BCR/ABL gene - the first case of transplanted CML with micro bcr

Project ALERT (Acute LEukemia clinical RegisTry) was initiated 11 years ago. The database is representative for the Czech population, at least in the category of curatively treated AML patients. Presented cohort consists of 1890 AML patients registered from January 1996 to February 2007.

Combined chemotherapy, protocol MACOP-B, was administered to 21 patients with non-Hodgkin lymphoma (NHL) with a medium or high grade of malignity, clinical stage II-IV. Complete remission was achieved in 17 patients (81%), in one instance partial remission was induced. One patient died from a cardiovascular and one from a thromboembolic complication during treatment. In one patient the results were not evaluated. Three patients developed severe granulocytopenia which called for reduction or delay of treatment and a septic condition developed. In addition to myelosuppression the main complications were stomatitis and mycosis. No death caused by infectious or haemorrhagic complications was recorded. The described chemotherapy is recommended in particular in immunoblastic lymphomas, diffuse lymphomas from cleaved and non-cleaved cells and diffuse lymphomas with mixed cellularity.

In 35 cases of acute leukaemia in addition to the basic morphological and cytochemical examination immunophenotyping with locally produced monoclonal antibodies from the Institute of Molecular Genetics, Czechoslovak Academy of Sciences, Prague, was made. In 33 instances it proved possible to differentiate the leukaemic cells, two leukaemias were described as non-differentiated. Local antibodies MEM 78, MEM 75, MEM 57, MEM 32, MEM 31, MEM 18 and HL-40 can be considered basic monoclonal antibodies for the diagnosis of acute leukaemia.

The authors describe the indirect immunoperoxidase method which makes possible immunophenotyping of cells on dried smears of peripheral and bone marrow. They used only local currently available monoclonal antibodies with a diagnostic value in lymphoproliferative conditions. The above procedure makes it possible to examine stored non-fixed smears, to evaluate the morphology of positive and negative cells and to evaluate findings retrospectively.