Dyserythropoietic changes and sideroblastic anemia in patients with hairy cell leukemia before and after therapy with 2-chlorodeoxyadenosine.

Active hairy cell leukemia is associated with an increase of RDW (Red Cell Distribution Width) which normalizes after successful therapy with 2-chlorodeoxyadenosine (2-CdA). To clarify this phenomenon, bone marrow films performed before therapy with 2-CdA and after its successful completion were subjected to careful evaluation. Dyserythropoietic changes were present in 5 out of 17 patients before the therapy with 2-CdA. In 2 patients the changes were only slight, characterized by irregularities of the shape of nucleus and nuclear contour, in the remaining 3 patients the changes were marked, represented by nuclear lobulation, karyorrhexis and binuclearity, with the presence of ringed sideroblasts in one of them. After therapy with 2-CdA complete hematologic remission was achieved in 4 patients with disappearance of dyserythropoietic changes and normalization of RDW values. In the last patient with ringed sideroblasts despite complete remission with disappearance of tumoral cells in the bone marrow as demonstrated by immunohistochemical analysis of trephine bone marrow biopsy with monoclonal antibody DBA 44 the condition deteriorated, RDW remained unchanged, the sideroblastic anemia progressed.

Long-term results in hairy cell leukemia treated by splenectomy.

Splenectomy as a therapeutic modality has been evaluated in a group of 24 consecutive patients. Before and after splenectomy only supportive therapy was applied with the exception of two patients in whom corticosteroids were administered because of vasculitis. Radiation therapy was applied in one patient because of massive retroperitoneal lymphadenopathy. One patient received Leukeran shortly before the fatal outcome because his response to splenectomy was poor. Out of 24 patients 14 patients died. The median survival for the partial responders and non-responders was 6 months only. Patients with a complete response did not reach median survival yet and 8 of them (33% of the whole group) have been alive for more than 9 years, one patient for more than 20 years. Two distinct groups of patients with respect to the outcome of splenectomy can be distinguished: The first group is characterized by a rapid fatal outcome mostly within two years after splenectomy, the second group has a more favorable course with a plateau and only occasional deaths after the fourth year.

Serum soluble IL-2 receptor as a reliable and noninvasive marker of disease activity in patients with hairy cell leukemia.

Hairy cell leukemia is a chronic lymphoproliferative disorder of B-cell lineage. Malignant cells express the interleukin-2 receptor (IL-2R) which is released in vitro as well as in vivo. The sera of patients with hairy cell leukemia contain elevated levels of this soluble receptor (sIL-2R). Sera of 24 patients with hairy cell leukemia were tested for sIL-2R. In 9 patients treated with 2-chlorodeoxyadenosine an improved clinical status was associated with decreasing serum sIL-2R. The maximal rate of decrease of sIL-2R level was observed within the second and the third week after the therapy initiation. Patients with disease progression had an increase in serum sIL-2R level. Our results suggest that serial measurement of sIL-2R level can be used as a reliable, noninvasive means to assess the disease activity and its response to therapy.

The increase of the rate of hemopoietic recovery and clinical benefit of the erythropoietin (EPO) and granulocyte colony-stimulating factor (G-CSF) with peripheral blood progenitor cells (PBPC) after intensive cyclic chemotherapy in high-risk breast cancer patients.

The role of erythropoietin (EPO) plus granulocyte-colony stimulating factor (G-CSF) combination in hemopoietic recovery was studied in patients with high-risk breast carcinoma and compared to a control group of previously treated identical patients who were not given EPO plus G-CSF. Eleven consecutive patients admitted to this study had Stage III or IV breast cancer. They received 6 cycles of intensive chemotherapy (epirubicin 150 mg/m2 and cyclophosphamide 1300 mg/m2). The 1st cycle served for mobilization of peripheral blood progenitor cells (PBPC). At its end leukaphereses collections of PBPC were performed to be used as hematologic support (PBPCT) in the 5 remaining cycles. The administration of EPO plus G-CSF was started when leukocyte (WBC) count in peripheral blood dropped below 1 x 10(9)/l and hemoglobin (Hb) level fell below 100 g/l. The treatment was stopped when leukocyte count rose to 5 x 10(9)/l and Hb to 130 g/l. EPO plus G-CSF combination after PBPCT produced significant effects in terms of hemopoietic recovery, clinical benefit and supportive care requirements when compared with 12 historic control patients: Periods of leukopenia were shorter which resulted in reduced risk of infectious complications. The grades of leukopenia in the study and control groups were as follows: grade 4 (36 vs. 18%), grade 3 (57 vs. 30%), grade 2 (7 vs. 13%) respectively. Significantly shorter was the time of PLT recovery < 50 x 10(9)/l (p < 0.001). The grades of thrombocytopenia were: grade 4 (29 vs. 11%), grade 3 (21 vs. 12%), grade 2 (25 vs. 36%) respectively. The number of necessary transfusions was significantly reduced as well as the length of hospital stay (p < 0.001). In conclusion, our results obtained in this study confirm that combination of EPO plus G-CSF not only increases the rate of hemopoietic recovery, reduces the number of necessary red blood cell and platelet transfusions but, at the same time, simplifies the clinical management and is more tolerable for the patients.

The value of bone marrow biopsy in the prognosis of hairy cell leukemia (HCL).

Histological findings in the bone marrow and their changes in the course of the disease and therapy were evaluated with respect to the prognosis in a group of 32 patients with hairy cell leukemia (HCL). Two types of bone marrow infiltration by hairy cells (HCs), the diffuse type and the interstitial type, respectively were found. The diffuse type of infiltration and the minimal or absent residual hematopoiesis (RH) at presentation were found with statistical significance to be unfavorable prognostic findings when compared with interstitial infiltration and persisting RH (p < 0.01). Reticulin fibrosis is a characteristic finding in HCL and was found in all but 2 patients.

Red cell distribution width (RDW) as a marker of disease activity in patients with hairy cell leukemia.

UNLABELLED: Red cell distribution width (RDW) was examined in 18 patients with hairy cell leukemia (HCL) treated with 2-chlorodeoxyadenosine (2-CdA), in 5 patients treated with Interferon alpha (IFN-alpha) and in 9 patients subjected to splenectomy. Out of 18 patients treated with 2-CdA one patient was excluded of the study because of association of HCL with acquired sideroblastic anemia. In the remaining 17 patients the mean value of RDW before therapy was 18.8% (range 13.5% to 25.0%) and dropped after successful therapy after 6 to 12 months to the mean value of 13.6% (range 11.2% to 17.9%) and after 18 months to 13.4% (range 12.6% to 14.7%) (p = 0.00015 and p = 0.00049 respectively). The hemoglobin level increased from the mean value of 119 g/l (range 99 g/l to 157 g/l) before therapy to the mean value of 145.9 g/l (range 127 g/l to 172 g/l) after 6 to 12 months and after 18 months to 147.8 g/l (range 132 g/l to 168 g/l) (p = 0.000017 and p = 0.00036 respectively). The same trend was observed in the group of patients treated with IFN-alfa. The RDW decreased from the mean value of 21.3% (range 18.8% to 28.7%) to the mean value of 15.3% (range 12.4% to 16.7%), (p = 0.031). The hemoglobin level increased in this group of patients from the mean value of 115 g/l (range 98 g/l to 127 g/l) to the mean value of 136 g/l (range 127 g/l to 146 g/l) (p = 0.031). In 9 patients in complete hematologic remission 34 to 293 months after splenectomy the mean value of RDW was 13.9% (range 13.0% to 15.5%). CONCLUSION: Increased RDW in HCL is associated with active disease and is reversible after successful therapy. This phenomenon has not been reported in the literature yet. Preliminary results show that the increase of RDW may be due to the dyserythropoiesis.

Long-term results in hairy cell leukemia treated with 2-chlorodeoxyadenosine.

We treated 19 patients with hairy cell leukemia (HCL) with 2-chlorodeoxyadenosine. 15 patients followed up at least 6 months were evaluated. The follow up period varied between 6 months and 37 months (median, 19 months). 8 patients were previously treated. The overall response in 15 evaluable HCL patients was 100%, with 87% complete hematological remissions including three patients with retroperitoneal and mediastinal lymphadenopathy and one patient with leukemic infiltrates of the cornea: 13% of patients achieved partial hematological remission. Soluble interleukin-2 receptor (sIL-2R) considered as a reliable non-invasive marker of HCL tumor burden dropped from the median of 1350 pM/ml (range 188 to 9000 pM/ml) to the median of 84.3 pM/ml (range 37 to 382 pM/ml) RdW which reflects the anisocytosis of red cells decreased after therapy from the median of 20.6% (range 13.1-25.0%) to the median of 13.7% (range 12.4-16.3%).

[Monitoring minimal residual disease in patients with hairy cell leukemia in complete remission after treatment with 2-chlorodioxyadenosine]. / Sledování minimální reziduální nemoci u nemocných s vlasatobunecnou leukémií v kompletní remisi po terapii 2-chlorodeoxyadenosinem.

Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine (2-CdA) induces in 85% patients complete remission. Complete remission is defined as the condition when signs of activity of the disease are absent, splenomegaly and lymphadenopathy are absent, the hemoglobin concentration is > or = 120 g/l, the absolute number of granulocytes is > or = 1.5 x 10(9)/l and the number of thrombocytes is > or = 100 x 10(9)/l. In complete remission in the peripheral blood, bone marrow aspirate and bioptic samples obtained by trephin bone marrow core biopsy, using standard staining (hematoxylin-eosin and May-Grünwald-Giemsa's method), no leukemic cells are present. When more sensitive methods are used (immunophenotyping, immunohistochemistry or molecular genetic methods), a persisting leukemic population can be detected which is described as minimal residual disease (MRD). For detection of MRD the authors used immunohistochemical examination of bone marrow with DBA.44 antibodies. As leukemic cells they described those which produced intense cytoplasmic and membrane positivity with antibody DBA.44 and corresponded morphologically to hairy cells. For evaluation computer analysis of the picture LUCIA-M was used. The infiltration grade was examined on three areas of standard size (3 x 65,265 micron 2) and expressed in percent. A total of 45 trepanobioptic specimens from 21 patients were examined who achieved after treatment with 2-CdA complete remission. In all samples suitable for evaluation the presence of leukemic cells (MRD) was detected with a median of 3% and a range of 1% to 18%. With induction of complete remission correlates also the low serum level of the soluble receptor for IL-2 (sIL-2R). In a female patient after 24 months of treatment with 2-CdA the grade of leukemic infiltration rose from 1% to 12% and during the 36th month to 50% DBA.44+ leukemic cells. The incipient relapse in this patient was not associated, despite marked infiltration of bone marrow, with failure of hematopoiesis and a marked rise of sIL-2R.

[A fatal hemorrhagic condition after rodenticide ingestion]. / Smrtelný krvácivý stav po pozití rodenticid.

The authors describe a fatal haemorrhagic condition in a 53-year-old man which developed after assumed ingestion of so-called "superwarfarins". Symptoms of intoxication with substances of the warfarin type include the sudden development of haemorrhagic diathesis, marked prolongation of INR and APTT with persisting pathological values of these tests after the usual substitution doses of vitamin K1. The fluctuation of INR and APTT values during repeated examinations is also striking. In the event of such a coagulation finding it is important to consider possible superwarfarin intoxication, even if it is difficult to provide direct evidence, as it is not possible to assess the ratio of vitamin K1 and K 1, 2, 3 epoxide.

[Immunocytochemical phenotyping of centroblastic lymphoma cells]. / Imunocytochemická fenotypizace bunek centroblastického lymfomu.

Using immunocytochemical phenotyping, the authors assessed the origin of malignant cells in a patient with malignant centroblastic lymphoma. The lymphoma cells expressed the thymocytic surface molecule CD1, pan T-lymphocytic markers CD2, CD5, CD6, CD7 with concurrent absence of complex CD3 and receptors for antigen on T lymphocytes. The proliferating activity of malignant cells could not be controlled by intensive cytostatic therapy.

[An unusual course in hairy-cell leukemia with marked abdominal lymphadenopathy, leukemic infiltration of the cornea and skin changes]. / Neobvyklý prubeh leukémie s vlasatými bunkami s výraznou abdominální lymfadenopatií, leukemickými infiltráty ocní rohovky a kozními zmenami.

The authors describe a female patient suffering from hairy-cell leukaemia. Already at the onset of the disease, apart from marked splenomegaly, sonography revealed marked retroperitoneal lymphadenopathy. During the subsequent course skin changes developed such as vasculitis and leukaemic infiltrates of the cornea on both eyes. The patient was successfully treated with 2-chlorodeoxyadenosine (2-CdA, Leustatin).

[Lymph node enlargement in hairy cell leukemia and problems with significant abdominal lymphadenopathy]. / Zvetsení uzlin u leukemie s vlasatými bunkami a problematika výrazné abdominální lymfadenopatie.

Enlargement of nodes in leukaemia with hairy cells (LVB) during the initial examination is rarely encountered. In the final stage of the disease it was found in six of our ten patients. A special situation is marked enlargement of retroperitoneal nodes observed in two patients. In one of them the nodes diminished after irradiation, in the second patient irradiation was not possible because of severe pancytopenia. Treatment with alpha-interferon failed previously in this patient. The question remains whether marked enlargement of the abdominal nodes is part of the picture of the disease or whether it is the manifestation of transformation of the disease into a more acute type. The authors recommend examination of the abdominal nodes by means of computed tomography (CT) already during the initial examination and during the subsequent course of the disease, in particular when there are signs of relapse.

[A fully implantable port system for venous access. Personal experience with 91 patients]. / Plne implantabilní portové systémy pro zilní aplikaci. Nase zkusenosti u 91 nemocných.

A fully implantable venous port system with a cannula inserted into the central venous system was implanted to 91 patients. The system was used for the administration of different types of intravenous preparations, incl. transfusions of erythrocyte mass and parenteral nutrition. With in the framework of autologous transplantation via the port system haematopoietic progenitor cells from the peripheral blood stream were administered. Part of the introduced systems was used for monitoring of the central venous overpressure and for collecting blood samples. The system was introduced on an average for 289 days, with a median of 245 days, range 82-872 days. During the implantation seven complications developed, in three instances the port was removed prematurely. During treatment 16 complications were observed, which in six instances led to early explantation of the venous port. The number of complications in total amounted to 0.87 per 1000 treatment days. The system was well tolerated by the patients because of its functional effectiveness and minimal cosmetic changes, and because it is not demanding it was also accepted well by the nursing staff.

Hairy cell leukaemia, its therapy and prognosis (historical review with own experiences).

The best treatment protocol for hairy cell leukaemia (HCL) has not yet been defined. Different chemotherapies failed to demonstrate sustained benefit. Splenectomy certainly has been beneficial for many patients but has no effect on bone marrow infiltration by leukaemic cells. The introduction of Interferon-alpha (IFN-alpha), 2-deoxycoformycin (DCF) and 2-chlorodeoxyadenosine (2-CdA) in the therapy of HCL dramatically improved treatment options during the past decade. IFN-alpha does not have curative potential in HCL. 2-CdA seems to be more promising than DCF. Serum IL-2R level can be used as non invasive means to assess disease response to therapy. The predictive reliability of this test remains to be evaluated. The definition of complete remission remains open being greatly influenced by the sensitivity of the methods applied to detect residual disease. The role of the spleen as the reservoir of malignant cells can not be excluded in respect to the relapses of the disease.

[Leukemic infiltration of the cornea in a patient with hairy-cell leukemia]. / Leukemické infiltráty rohovky u nemocné leukémiís "vlasatými bunkami".

The authors describe the infiltrations of the cornea in both eyes of a patient (women) who suffered from leukaemia with "long-haired cells". The treatment was successful with 2-chlordeoxyadenosine (Leustatin). Knowledge of leucaemic infiltration in the cornea is accentuated for successful treatment in connection with basic disease.