[Initial 111In-platelet kinetics: indicator of platelet sequestration/destruction site or quality control of platelet labelling?].

Taking into consideration the existing disagreement in the literature, the aim of this paper was to estimate the value of the initial kinetics of autologous platelets labelled with 111In-oxinate, performed during the first 20 minutes after their intravenous injection. Two hypothesis were tested: 1. Initial 111In-platelet kinetics indicates the platelet sequestration site (in patients with normal mean platelet life span)/destruction site (in patients with shortened mean platelet life span), 2. Initial 111In-platelet kinetics indicates the quality of platelet separation and labelling procedure. We performed initial labelled platelet kinetics in thrombocytopenic patients (in order to test the first hypothesis) as well as in control (healthy) subjects (in order to test the second hypothesis). Thirty-nine persons were investigated: 33 with thrombocytopenia: 25 with shortened mean platelet life span, caused by chronic im mune thrombocytopenic purpura (ITP), eight with normal platelet life span and thrombocytopenia caused by myelodysplastic syndrome (MDS), six healthy, control subjects (C). In all 39 persons platelet blood count on the day of platelet labelling was determined, autologous platelet labelling with 111In-oxinate was performed, general and differential yields of platelet labelling (GYL and DYL), as well as mean labelled platelets life span were determined. Besides that, initial labelled platelets kinetics was performed with initial 111In-platelets accumulation in the liver (IPAL) calculation, as well as the late platelet kinetics for platelet sequestration index and platelet sequestration/destruction site determination. We obtained two types of initial labelled platelets kinetics (not only in the patients with shortened platelet life span, but also in the subjects with normal labelled platelets life span), which differed in the IPAL value and in the ratio of the liver and the heart radioactivity: IPAL < 20% and IPAL>20%. We found statistically significant difference in GYL and DYL between the two groups: IPAL<20% and IPAL > 20%. Both yields were higher in IPAL<20% group. There was no significant difference between the two IPAL groups in the platelet blood count, labelled platelet life span, sequestration index and sequestration site. No correlation could be found between IPAL on one side and platelet blood count, sequestration index, and sequestration site on another. We concluded that initial labelled platelet kinetics could not indicate the platelet sequestration/destructon site (which is accomplished by the late labelled platelets kinetics), but nevertheless, it is very sensitive and useful method of platelet separation and labelling quality control. While in vitro quality control parameters (GYL and DYL) indicate the quality of only one part of this procedure, initial labelled platelet kinetics reflects discrete platelet function disturbance that might happen from the moment of blood sample collection till the labelled platelets intravenous injection.

[Prediction of the splenectomy efficacy in chronic immune thrombocytopenic purpura].

The aim of this investigation was to estimate the possibility of predicting the splenectomy response in patients with chronic immune thrombocytopenic purpura (ITP). The patients' age, sex, megakaryocytes abundance, platelet blood count, production, life span, sequestration/destruction site were considered as possible predictive factors. Thirty-four ITP patients (23 female and 11 male) aged from five to 83 years were investigated. Platelet blood count ranged from 4 to 106 x 10(9)l (mean value was 43 x 10(9)/l). Megakaryocyte abundance was determined in 19/34 ITP patients. Megakaryocytes were numerous in 11/19, present in 7/19 ITP patients and in one patient low megakaryocyte number was registered. In all 34 ITP patients autologous platelet labelling with 111In-oxinate was performed and labelled platelets were reinjected to the ITP patients. This enabled platelet life span, production, sequestration index and sequestration/destruction site determination. Platelet life span ranged from 0,4-5 days (mean value was 1 day). Mean value for platelet production index was 1,1. Platelet sequestration/destruction site in 16 ITP patients was the spleen, and in two it was the liver. Mixed platelet sequestration/destruction site (the liver and the spleen) was registered in 7 ITP patients, while predominantly splenic sequestration/destruction was present in 9 ITP patients. All 34 ITP patients were later submitted to splenectomy, which is a therapeutic option in ITP. Splenectomy result was favorable in 28/34 ITP patients while it was unfavorable in 6/34 (17,6%). Highly significant correlation was noticed between the splenectomy result and platelet sequestration site (p < 0.01). On the other hand, there was no correlation between the splenectomy result on one side, and patient's age, sex, megakaryocyte abundance, platelet production, life span and blood count on the other. Splenectomy result was favorable in all ITP patients with splenic sequestration/detruction of labelled platelets. It was unfavorable in ITP patients with hepatic sequestration of labelled platelets. In ITP patients with mixed platelet sequestration (hepatic and splenic) there were more unfavorable than favorable splenectomy results. Non-invasive method of platelet labelling and platelet sequestration/ /destruction site determination makes easier the clinicians' and ITP patients' decision for the splenectomy in the case when the spleen is the only sequestration site of the labelled platelets, and against the splenectomy, when exclusively hepatic platelet sequestration/destruction is registered.

Myelofibrosis in primary myelodysplastic syndromes: clinical and biological significance.

In a retrospective study of 236 patients with primary myelodysplastic syndromes (MDS), 130 cases (55.1%) revealed myelofibrosis in bone marrow biopsies. It was observed that fibrosis mostly occurs focally or patchy, and collagen deposits were found very rarely (only four patients). The histopathology of bone marrow biopsies revealed several differences between fibrotic and non-fibrotic MDS: cellularity is significantly higher, dysmegakaryopoiesis is more pronounced, plasmocytes and mast cells are more often increased, and disturbance of marrow topography (particularly of the MK- and G-line) can be found more frequently in MDS with myelofibrosis. Reticulin fibrosis occurred in all subtypes of MDS; however, there was a higher incidence in chronic myelomonocytic leukemia. The frequency of abnormal growth of GM-progenitors was significantly higher in the MDS cases with myelofibrosis, compared to the cases without fibrosis. Clinical data showed significantly higher WBC, more frequent presence of immature granulocytes, and higher percentage of myeloblasts in peripheral blood and bone marrow in MDS with myelofibrosis compared to cases without myelofibrosis. Life expectancy was reduced to 13 mo, compared with 35 mo in MDS without fibrosis (p=0.00055). Time to leukemic transformation was 32 mo in MDS with fibrosis, compared with >56 mo in MDS without fibrosis (p=0.015). Myelofibrosis therefore seems to herald a poor prognosis.

Biological and clinical significance of clonogenic assays in patients with myelodysplastic syndromes.

Biological and clinical significance of growth pattern of hematopoietic progenitors were investigated in 117 patients with primary myelodysplastic syndromes (MDSs) at referral. Abnormal (i.e., "leukemic" or absent) growth of GM colonies (CFU-GM) and GM clusters was found in 47% of patients with "advanced" MDS (RAEB, RAEB-t, and CMML) and in 15% of "low-risk" (RA/RARS) patients. In vitro erythropoiesis was decreased in most of the patients, with significantly lower number of BFU-E in "advanced" MDS than in RA/RARS patients. Megakaryocyte progenitors (CFU-MK) were very low or absent in almost all the patients, regardless of the FAB type. Significant correlation was demonstrated between the number of BFU-E and hemoglobin concentration and between number of CFU-MK and platelet count. Growth capacity of GM progenitors appears to be in proportion to "myeloproliferative" capacity of the malignant clone. T-cell depletion had no influence on growth capacity of hematopoietic progenitors, nor did colony growth respond in a dose-dependent manner to different concentrations of LCM. Growth capacity of MDS hematopoietic progenitors was independent of Bournemouth score, of the presence and type of cytogenetic abnormality, and of the expression of CD95 and caspase-3 antigens on bone marrow cells. However, in patients with "abnormal" growth of GM progenitors, CD34 antigen expression was significantly higher than in patients with "normal" growth. "Abnormal" GM growth was found to be independently predictive regarding the survival and the risk for AML development. In contrast, the prognostic value of erythroid and megakaryocyte cultures was found to be limited.

[Results of treatment in patients with hairy cell leukemia with splenectomy, alpha-interferon and deoxycoformycin]. / Rezultati lecenja bolesnika s leukemijom vlasastih celija primenom splenektomije, alfa-interferona i deoksikoformicina.

INTRODUCTION: The ability of interferon alpha and purine analogues to induce long-lasting remissions in the majority of patients with hairy cell leukaemia has revolutionized the treatment [16, 17, 24, 25], but also provoked dilemma and different opinions about the initial treatment or first line therapy. Splenotomy, the first standard treatment, increases peripheral blood counts but half of the patients require a later systemic therapy because of progressive cytopenia. On the other hand, it has been shown that splenotomy performed after achieving complete remission with interferon alpha or purine analogues contributed to spleen infiltration with hairy cells [37, 38]. PATIENTS AND METHODS: In our study we analysed results of treatment of 44 patients with hairy cell leukaemia who were followed-up for 8 years. Patients were treated with three treatment modalities, mostly successively. Splenotomy++ was performed in 34 patients as a first line therapy (Group I); interferon alpha in 24 patients; in 10 patients as a first line therapy without splenotomy (Group II) and in 14 patients as a second line therapy after splenotomy (Group III). Deoxycoformycin was given to 5 patients as a third line therapy. RESULTS: Our results showed that 20 patients (59 percent) treated only with splenotomy were in haematological remission (Group I). The analysis of prognostic variables demonstrated that at diagnosis patients from Group I, treated only with splenotomy, had at diagnosis higher levels of haemoglobin and thrombocyte counts and a lesser degree of bone marrow (b.m.) infiltration with hairy cells (HCs) than they were found in the other two groups of patients (median Hb = 11.3 g/dL, Plt = 133 x 10(9)/L, HCs in b.m. = 77%). Group II had median Hb = 8.6 g/dl, Plt = 72 x 10(9)/L, HCs in b.m. = 88%, and Group III had median Hb = 9.2 10(9)/L, Plt = 61 x 10(9)/L and HCs in b.m = 90%. Survival curves (Kaplan-Meier method) and Log Rank Statistics showed a significant difference in survival-time (Figure 4) among patients groups (p = 0.0427). Group I had median survival of 270 months; Group II 80 months; and Group III 140 months. Our results demonstrated that different prognostic risk groups existed among hairy cell leukaemia patients and could be identified on the basis of Hb level, Plt count and percent of infiltration of hairy cells into bone marrow. At diagnosis the low risk group of patients (Table 1) had levels of haemoglobin more than 11.3 g/dL; platelet counts more than 72 x 10(9)/L; percent of bone marrow infiltration with hairy cells less than 70%, and expression of lambda type of light chains on leukaemic cells. This group of patients was treated only with splenotomy without systemic therapy. In high risk group of patients the levels of haemoglobin were lower than 8.6 g/dL; platelet counts lower than 60 x 10(9)/L; percent of bone marrow infiltration with hairy cells more than 90% and expression of kappa type of light chains on leukaemic cells. The survival of this group of patients, in spite of initial treatment with systemic therapy with interferon alpha, was shorter. Results of treatment with interferon alpha (Group II and Group III) have demonstrated that the duration of remission in patients who were initially splenectomized and later treated with interferon alpha, was longer (median 31 months) than in patients who were treated with interferon alpha without splenotomy (median duration of remission = 13 months) (Table 3). Results of treatment with deoxycoformycin (Table 4) showed that 3/5 of patients achieved complete remission and 2/5 patients achieved partial remission. Four patients were initially splenectomised and att five patients were treated with interferon alpha before deoxycoformycin. CONCLUSION: On the basis of our results, splenotomy can be recommended as the first-line therapy for low risk patients with hairy cell leukaemia; interferon alpha should be the first-line therapy in high risk patients, and the second-line therapy in l

Recurrent venous thrombosis in a patient with chronic lymphocytic leukemia and acquired protein S deficiency.

A patient with chronic lymphocytic leukemia and an undetectable plasma level of protein S (PS), associated with recurrent venous thrombosis, is described. The laboratory investigation revealed the concomitant presence of an inhibitor directed to PS and a monoclonal protein in the patient's plasma. After treatment with prednisone and cyclophosphamide both the inhibitor to PS and the monoclonal component disappeared.

Megakaryocytopoiesis in refractory chronic immune thrombocytopenia.

The extent of megakaryocytopoiesis (Mk-poiesis) and clinical outcome are evaluated in 14 patients with severe refractory chronic immune thrombocytopenia (rchr ITP). Three out of 14 patients died due to hemorrhage. The number of bleeding episodes and the number of treatment modalities proved to be both sensitive prognostic survival parameters (p < 0.05). Thirty two corticosteroid responsive chr ITP patients (chr ITPPR), 15 not treated patients (chr ITP(NT)) and 14 healthy volunteers (C) served as a control. There was a significant difference in the platelet count between the study groups (p < 0.05). The number of megakaryocytes and promegakaryoblasts per mm3 of bone marrow were significantly lower in rchr ITP patients (p < 0.05) than in chr ITP(PR) and in chr ITP(NT) group, thus implying an inadequate Mk-poiesis in rITP chr patients. From the data presented here it may be suggested that the inadequate Mk-poiesis is operating in rchr ITP.

[Laboratory identification of blood hypercoagulability]. / Laboratorijska identifikacija hiperkoagulabilnosti krvi.

For many years, the laboratory investigation of patients with thrombophilia has lagged behind that of patients with bleeding diathesis. The improved understanding of the mechanisms that control and regulate coagulation, and resultant recognition of new defects have greatly stimulated clinical laboratory interest in this area. Assays regarding the developed resistance to activated protein C, deficiencies of antithrombin, protein C and protein S, and the presence of antiphospholipid antibodies are widely available and should be a part of investigations of patients with idiopathic thrombosis. Such a study would likely provide an explanation of thrombosis in 40-60% of patients. Abnormalities of fibrinogen and fibrinolysis may be explained, although such defects are currently considered rare. More sophistic assays are being developed to detect abnormalities de to factor V Leiden and prothrombin 20,210 gene mutation, which will undoubtedly detect more patients with thrombophilia. Laboratory tests to define the hypercoagulable state are continually being developed. They include tests for novel activation markers. However, acceptance of these approaches by clinical laboratories has been slow.

[Hereditary deficiency of antithrombin III, protein C, protein S and factor XII in 121 patients with venous or arterial thrombosis]. / Nasledni nedostatak antitrombina tri, proteina C, proteina S i XII faktora kod 121 bolesnika s venskom ili arterijskom trombozom.

INTRODUCTION: Hereditary thrombophilia is caused by various inherited disorders which lead to familial tendency to recurrent venous thrombosis usually at an early age and with spontaneous onset. In the studies reported so far, the different prevalence of hereditary thrombophilia among patients with venous thrombosis was found, greatly depending on criteria for selection of patients. Arterial thrombosis is most often the consequence of arteriosclerosis but the prevalence of hereditary thrombophilia among young patients with arterial thrombosis and without recognized risk factors for arteriosclerosis is not known . In this study, the frequency of hereditary deficiencies of antithrombin III (AT III), protein C (PC), protein S (PS), plasminogen (PLMG), factor XII (F XII) and dysfibrinogenaemia was investigated over a 2-year period in 121 patients with venous or arterial thrombosis selected according to the recommendations of the British Committee for Standards in Haematology. PATIENTS AND METHODS: The study included total a of 121 patients (58 males and 63 females) with documented venous or arterial thrombosis. Table 1 shows patient's characteristics regarding gender, age and clinical manifestation of thrombosis. Each patient fulfilled at least one of the following criteria: a) venous thrombosis prior to the age of 45; b) arterial thrombosis prior to the age of 30, without risk factors for arteriosclerosis; c) recurrent thrombosis; d) familial tendency to thrombosis; e) thrombosis of unusual localization. A detailed history was taken from each patient on earlier personal or familial occurrence of thrombosis. For the purpose of this study, thrombophilia was characterized as congenital when the deficient protein was constantly below normal value and when the same deficiency was confirmed in a close family member; acquired when the acquired disorder predisposing to thrombosis was present in absence of constant protein deficiency; and idiopathic when the cause of thrombosis was unknown. All tests were performed in plasma obtained after centrifugation of venous blood anticoagulated with 0.129 mol/1 sodium citrate. Concentrations of fibrinogen, PT, PTT and F XII were measured by standard clotting methods. At III, PC and plasminogen activity were determined by chromogenic methods using commercial reagents (Boehring, Marburg, Germany). AT III, PC and total PS antigen were assayed by Laurell immunoelectrophoresis. The presence of lupus anticoagulant was investigated by recommended tests. RESULTS: A total of 15 patients (12.4%) fulfilled criteria for hereditary thrombophilia. Seven of them (5.8%) had AT III deficiency, five (4.1%) PC deficiency, two (1.6%) PS deficiency, and one patient had F XII deficiency. Secondary thrombophilia was found in 21.5% of patients and the cause of thrombosis in 66.1% of patients was not elucidated. A high frequency of hereditary thrombophilia has been found in patients with arterial thrombosis (40%). Among patients with hereditary thrombophilia thrombosis occurred at significantly younger age (29.9 vs. 42.2 and 40.9 yr.) compared to the patients with secondary and idiopathic thrombophilia, respectively. Patients with hereditary thrombophilia had also a higher occurrence of positive family history related to thrombosis (66.7% vs. 7.7% and 27.5%). DISCUSSION: The prevalence of hereditary thrombophilia in nonselected patients with venous thrombosis is relatively low, and for that reason the selection of patients, according recommended criteria, in whom the screening tests for congenital thrombophilia should be performed, is strongly suggested by many authors. In our study we used the generally accepted recommendations for investigation of patients with venous and arterial thrombosis. The presence of congenital thrombophilia was found in 15 (12.4%) of 121 studied patients, what is in accordance with results of other similarly designed studies. (ABSTRACT TRUNCATED)

Comparative morphometric study of immunohistochemical versus conventional staining for the evaluation of megakaryocytopoiesis in normal and pathological bone marrow biopsies.

Identification of megakaryocytes by immunohistochemistry may be superior to hematoxylin-eosin (HE) stain method for assessing megakaryocyte size and number in clinical specimens; however, a side-by-side comparison of the two methods has not been reported. In the present study, comparative morphometry using both methods was performed on marrow biopsies of normal individuals, and of patients with myelodysplastic syndrome, chronic myeloid leukemia and immune thrombocytopenia. Morphometric results in the present study showed that precise megakaryocyte size can be calculated in normal and pathologic bone marrow sections by using HE stain if one employs stereological corrections. In contrast, megakaryocyte numbers can be more precisely detected by immunohistochemistry than by HE stain, particularly in myelodysplastic syndrome and chronic myeloid leukemia. Differentiation disturbances and ineffective megakaryocytopoiesis in myelodysplastic syndrome were demonstrated by immunomorphometric analyses.

[Use of the Karnofsky index in the evaluation of patients with acute leukemia]. / Primena indeksa po Karnofskom u proceni stanja bolesnika sa akutnom leukemijom.

The longitudinal study of prospective character was performed during the treatment with the aim to test if Karnofsky's index is an instrument susceptible to the changes in performance status in the population of adult patients with acute leukemia. Performance status points out the person's independence in every day activities and personal care, and more widely, the independence in social and other activities. The aim was to establish its changes in adult patients and its possible prognostic value for the therapy success. The prognostic value of person's activity level was confirmed for the survival length and the lasting, but not for the complete remission achievement. It was concluded that Karnofsky's index was sensitive only for large changes in functional status of acute leukemia patients.

[Thrombophilia, prethrombotic conditions, hypercoagulability]. / Trombofilija, pretrombotsko stanje, hiperkoagulabilnost.

The editorial deals with the state of art from the terminological point of view a very important problem of thrombosis and thromboembolic states. According to world medical statistics these diseases are one of the most frequent causes of illness and death. The rationale for the writing of this editorial is imposed by many controversies in Serbian medical literature related to diagnosis, treatment and especially prophylaxis of these pathologic states and the state of the art of the above mention problems in foreign medical literature. On the basis of the study of the state of the art in foreign medical literature. It could be concluded that the biochemical basis of thrombophilia, pre-thrombotic states and hypercoagulability is, in fact, the same phenomenon with regard to the disturbed dynamic balance between activating factors of haemostatic system and inhibitory factors. Activating factors of haemostatic system are prevailing in these pathological condition. The difference is express, however, in a different clinical feature of this unbalance which lead, earlier or later, to thrombosis. It is emphasized that markers which predicts occurrence of thrombosis have not yet been recognized and that the significance of the activation of the haemostatic system have to be established by multicentre investigations, i.e. that the role of these markers in the development of thrombotic diseases should be established. At the same time, on the review of the current Serbian medical literature, it is concluded due to lack of technical prerequisites the current doctrinaire definition of the above mentioned states can not be carried out in our medical institutions and laboratories.

Multifocal plasmacytoma of hand and foot bones.

Simultaneous occurrence of localized plasmacytomas of both hands and feet has not been reported so far. Here we report a 40-year old female patient, who had at presentation pain and deformity. Of hands and feet, with numerous cystic lytic lesions of phalangeal, metacarpal and metatarsal bones, detected by X-rays. The biopsy of the affected bone showed moderately differentiated plasmacytoma of lambda light chain type (lambda-LC). Serum and urine biochemical analysis revealed the existence of lambda LC monoclonal component. The patient was treated by local radiotherapy and subsequent systemic chemotherapy, which consisted of 3 cycles of the M-2 protocol and 7 cycles of melphalan-prednisone. Five years after the diagnosis, the absence of plasmacytoma was confirmed by puncture biopsy of the left hand phalanx. Monoclonal protein in serum and urine was not detected.

In vitro drug sensitivity of leukemic progenitors and P-glycoprotein expression in adult acute myeloid leukemia: correlation with induction treatment outcome.

We have investigated the self-renewal capacity (PE2) and in vitro sensitivity to cytosine-arabinoside (ara-C) and daunorubicine (DNR) of leukemic progenitors (CFU-AML) to determine the significance of these tests for predicting induction treatment outcome in 75 adult acute myeloid leukemia (AML) patients. In addition, in a part of this group of patients (n = 46) we determined the expression of P-glycoprotein (P-gp) immunocytochemically and correlated those results with the therapeutic response. We have evaluated 66 patients who showed the following responses: 28/66 complete remissions (CR), 16/66 resistant leukemias (RL) and 22/66 early deaths (ED). The PE2 value was significantly higher in patients with RL than in patients with CR (p < 0.00375). CFU-AML sensitivity to ara-C and DNR alone was not different between response groups, but the difference in CFU-AML sensitivity to the combination of drugs between patients with CR and RL was not significant, although a trend was noted (p < 0.06). P-gp expression was found in only 1/18 patients who achieved CR but in 9/11 patients with RL and 7/11 patients with ED, which is a highly significant difference (p < 0.0006). We concluded that both PE2 and P-gp expression in AML cells are valuable predictors of therapeutic response in adult AML and should be included in creating the best therapeutic approach to AML patients.

The determination of spontaneous megakaryocyte colony formation is an unequivocal test for discrimination between essential thrombocythaemia and reactive thrombocytosis.

Spontaneous colony formation from bone marrow megakaryocyte progenitors (BMsCFU-Mk) was studied in 24 patients with essential thrombocythaemia (ET), 20 patients with reactive thrombocytosis (RT), 20 patients with polycthaemia rubra vera with thrombocytosis (PRVtr), 16 patients with chronic myeloid leukaemia with thrombocytosis (CMLtr) and 18 normal control subjects (C). The culture medium which was used in the methylcellulose assay in vitro contained 30% of plasma from a single patient with hereditary haemochromatosis. Remarkable BMsCFU-Mk growth was recorded in all patients with ET but in none with RT or in C. BMs-CFU-Mk were present in 11/20 patients with PRVtr and 7/16 patients with CMLtr. Spontaneous bone marrow erythroid progenitors (BMsBFU-E) were also determined in these patients. BMsBFU-E were found in 21/24 patients with ET and none in the patients with RT and C. All patients with PRVtr and one patient with CMLtr showed BMsBFU-E. We conclude that our implementation of the in vitro methylcellulose assay allows the BMsCFU-Mk to be used as an unequivocal test for discrimination between ET and RT which has not been shown in previously published studies. In addition, we present evidence that in 10 patients BMsCFU-Mk and/or BMsBFU-E growth in the test persisted after long-lasting haematological remission.

Three monoclonal IgG components, an IgG4(lambda), an IgG2(kappa) and an IgG1/IgG3 (kappa) Gm(f,b) hybrid, in a single myeloma patient.

An unusual triclonal IgG combination in the serum of a 56-year old male with clinical stage IIIB multiple myeloma is reported. The patient initially had an IgG4(lambda) monoclonal protein in his serum and later developed an IgG2(kappa) and an IgG (kappa) which possessed the characteristics of both IgG1 and IgG3 subclasses with an unusual combination of allotypic markers. Three M-proteins did not share idiotypic determinants. A rare class-switch recombination followed by mutation has been considered as a possible mechanism leading to this combination.

[Acute myeloblastic leukemia during pregnancy]. / Akutna mijeloblastna leukemija u trucnoci

We present a pregnant woman, with diagnosis of acute myeloblastic leukemia (AML) established in the third trimester of pregnancy. She was delivered by Caesarean section at the end of 36th gestational week, and a healthy, mature-for-date, male infant was born. Combined chemotherapy (YU-AML protocol) was administered a week after the delivery, but the patient died after 7 months, due to resistant disease. We discuss actual problems that make an approach to pregnant patient with AML specific and individual.

[Chronic lymphocytic leukaemia associated with polycythemia vera]. / Hronicna limfocitna leukemija kod bolesnika s pravom policitemijom.

Simultaneous or sequentional but spontaneous occurzence of polycythaemia vera and chronic lymphocytic leukaemia is very unusual. Moreover, the pathogenesis of these two malignancies has not yet been explained. The authors discribed a 64-year-old man with remarkable mild clinical course of polycytheameia vera associated with chronic lymphocytic leukaemia, lasting more than 5 years. Bone-marrow cell culture revealed spontaneous growth of erythroblast progenitors (BFU-E, CFU-E) and reduced number of haemopoietic progenitorus, mainly due to lymphocyte bone marrow infiltration. The patient plasma selectively inhibited growth of the BFU-E and CFU-E progenitor cells of normal bone-marrow, suggesting that some inhibitor of erythrocytopoiesis influenced supression and/or control of one disease by the other.