The effect of 2-h infusion of 2-chlorodeoxyadenosine (cladribine) with prednisone in previously untreated B-cell chronic lymphocytic leukaemia.

2-Chlorodeoxyadenosine (2-CdA) is a new antimetabolite chemotherapeutic agent active in indolent lymphoid malignancies. In this retrospective study, 69 previously untreated patients with B-cell chronic lymphocytic leukaemia (B-CLL) were treated with 2-CdA administered at a dose of 0.12 mg/kg daily in 2-h intravenous infusion for 5 consecutive days. 45 patients also received prednisone 30 mg/m2 orally each day for 5 days starting with 2-CdA courses. Patients were given 2-6 courses (mean 4.6) of 2-CdA repeated usually at monthly intervals. If a complete response was achieved, no further 2-CdA courses were administered. Guidelines for response were those developed by the NCI Sponsored Working Group. Complete response (CR) was achieved in 26 (38%) and partial response (PR) in 27 (39%) cases, giving an overall response rate of 77%. 16 patients (23%) did not respond to 2-CdA. In the subgroup of 45 patients receiving 2-CdA with prednisone, CR was obtained in 15 (33%) and PR in 20 (44%) patients giving an overall response rate of 78%. CR was achieved in 11 (46%) out of 24 patients treated only with 2-CdA and in 7 cases (29%) PR was observed, giving an objective response rate of 75%. The differences between both subgroups were not statistically significant. However, we observed a relationship between the response and the number of courses of 2-CdA given in patients receiving and those not receiving prednisone. In the subgroup receiving 2-CdA with prednisone, an earlier response to 2-CdA was observed. In this group a response was achieved in 9 (20%) patients after two courses of 2-CdA and in 18 (40%) after four courses. In the subgroup receiving only 2-CdA, 17 (71%) responses were obtained after six cycles.

Intermittent 2-hour intravenous infusions of 2-chlorodeoxyadenosine in the treatment of 110 patients with refractory or previously untreated B-cell chronic lymphocytic leukemia.

The purpose of our study was to determine the effectiveness of 2-CdA in 2-hour intravenous infusions in the treatment of B-CLL. One hundred and ten patients with B-CLL received 1 to 10 courses of 2-CdA (median 2.5) at a dosage of 0.12 mg/kg daily for 5 consecutive days. Eighteen of them were untreated and 92 relapsed or became refractory to previous therapeutic modalities. Complete remission (CR) was achieved in 8 (7.3%) and partial remission (PR) in 35 patients (31.8%) giving an overall response rate of 39.1%. In 3 patients, cross-resistance to fludarabine was noticed. Toxic effects of 2-CdA were more frequently observed in previously treated patients. Hemorrhagic complications due to drug-induced thrombocytopenia were noticed in 25 (22.7%) and severe infections including sepsis in 14 (12.7%) patients.

Immune profile of patients with reticuloplasmocytoma treated with alkeran and prednisone.

The humoral and cellular immune response was examined in 26 patients with reticuloplasmocytoma. In 14 patients the tests were repeated after 6-8 month treatment with Alkeran and Prednisone. The following parameters were determined: level of immunoglobulin G, A and M, lymphocyte count and differential count (T, B and O), leukocytes migration tests and tuberculine skin test. It appeared from our studies, that patients with reticuloplasmocytoma have defects in humoral and cellular responses, however, the treatment applied, did not influence any of the measured parameters.

Immunological profile in patients with non-Hodgkin's lymphomas.

In 51 cases with non-Hodgkin's lymphoma and in 25 healthy subjects, immunological state was determined by resorting to values of the following parameters of nonspecific immunity: the levels of G, A and M immunoglobulins, antistreptolysins, complement, T and B lymphocytes, monocytes, granulocytes and the skin test with recall antigens. The values were expressed according to the points system of Nagel et al. The results of studies revealed that in all but one case the values were lower than in controls. Also certain differences in immunological profile between respective lymphoma types were observed.

[Results of treating patients with highly malignant non-Hodgkin's lymphomas; comparison of treatment efficacy with CHOP and CBVPM-AVBP]. / Wyniki leczenia chorych na chloniaki nieziarnicze o wysokiej zlosliwosci; porównanie skutecznosci leczenia schematami CHOP i CBVPM-AVBP.

The treatment of highly of 43 patients with highly malignant non-Hodgkin lymphomas were analysed and assessed. These patients were treated at the Department of Hematology, Pomeranian Medical Academy within 1981-1990. The process was advanced in 76% of and localization of the tumour outside lymph nodes was also seen in 79%. The results of treatment with CHOP regimen used during the first 5 years were compared with CBVPM-AVBP used in 1986-1990. CBVPM-AVBP regimen proved more 4 effective (55% of the complete remissions) than CHOP regimen (37.5% of the complete remission). Mean duration of the complete remission (survival free from the relapse) was 27.5 (1-88) months. Complete remissions were easier to achieve in patients with centroblastic lymphoma in higher percentage. These patients survived longer than those with other highly malignant lymphomas. The authors conclude that further intensification of chemotherapy in case of highly malignant non-Hodgkin lymphomas is justified.

[The mechanism of cell proliferation in acute (immature-cell) leukemia]. / Badania nad mechanizmem proliferacji komórkowej w bialaczkach ostrych (niedojrzalokomórkowych).

In 40 patients with acute leukaemias the 3H-thymidine and mitosis indices were determined in the population of blast cells in bone marrow and the cellularity of bone marrow was determined. The studies were carried out in the first episode of the disease before treatment and in some patients (13) they were repeated during relapse after remission or improvement. The results showed that proliferative activity of blast cells was reduced in relation to precursors of normal granulopoiesis in all forms of acute leukaemia. Myeloblastic leukaemias showed a greater scater of values of both proliferation parameters in relation to lymphoblastic leukaemias. It was found, moreover, that in highly cellular bone marrow the proliferative activity of blast cell population was significantly lower than in patients with low bone marrow cellularity. On the ground of this observation the authors put forward the view that in acute leukaemias the intrinsic mechanism controlling the proliferation of cells is disturbed.

[Treatment of inflammatory changes and stomatitis in patients with acute leukemias and malignant lymphomas using low pressure hydrotherapy--preliminary report]. / Leczenie zmian zapalnych i owrzodzeniowych jamy ustnej u chorych na ostre bialaczki i chloniaki zlosliwe przy pomocy hydroterapii niskocisnieniowej--doniesienie wstepne.

The management of stomatitis, commonly complicating intensive chemotherapy in patients with acute leukemias and malignant lymphomas has been presented. The hydrotherapy equipment of our own construction was designed to wash the oral cavity with large amounts of fluid given at low pressure and constant temperature. This washing solution contained the addition of drugs; its pH was adjusted to the pH of the patients saliva. Preliminary results of this treatment modality have been reported.

[Changes in blood lymphocytes and their subpopulation in patients with myeloblastic leukemia treated with cytostatic agents]. / Zmiany limfocytów krwi ich subpopulacji u chorych na bialaczki mieloblastyczne w czasie leczenia cytostatykami.

Quantitative determinations of lymphocytas were done in the active period of the disease, immediately after treatment by the COAP schedule and during remission. In 6 patients the determinations were done several times during 20 weeks of maintenance treatment. It was found that independently of the stage of the disease the absolute lymphocyte count and the counts of B and T populations were low, while that of lymphocyte O population was raised. It was observed that the reduced count concerned all 4 subclasses of lymphocytes B, that is those with surface receptors for IgA, IgM, IgG and IgE immunoglobulins. In remission the values of lymphocytes and their T and B subpopulations increased, failing, however, to reach the normal values. This rise was more pronounced in the case of lymphocytes T. Lymphocyte depression in these patients is explained by the authors as due mainly to intensive cytostatic treatment.

[Survival of patients and DNA-ploidy of cells in non-Hodgkin's lymphoma of low-grade malignancy]. / Przezycie chorych a DNA-ploidia w komórkach chloniaków nieziarniczych o niskiej zlosliwosci.

DNA-ploidy in lymphoma cells obtained from lymph nodes of 107 patients with non-Hodgkin's lymphomas of low grade malignancy was studied prior to the treatment introduction. The survival of patients was within the range of 24-126 months (median 63 months). There were 70 hyperdiploidic and 37 diploidic patients. The statistical tendency to prolonged survival was seen among patients with lymphocytic lymphoma (CLL) as compared to other histological types of the disease. There were no statistical differences in the probability of survival (p-P) between diploidic and hyperdiploidic patients either in the whole studied group or in particular histologic types of lymphoma.

[Bone marrow changes in patients with hairy cell leukemia after 2-chlorodeoxyadenosine treatment]. / Zmiany w szpiku chorych na bialaczke wlochatokomórkowa po leczeniu 2-chlorodeoksyadenozyna.

Bone marrow abnormalities were assessed in 6 patients with hairy cell leukemia after 2-chlorodeoxyadenosine treatment. In spite of clinical and haematological remission in all patients, hairy cells and fibrosis were found within the marrow. However, the hairy cells number, the thickness of argentophilic fibres and the extent of fibrosis. It was stressed that in addition to histological analysis with hematoxylin-eosin also other stainings for fibrosis should be applied in the bone marrow evaluation, followed by immunohistochemical and molecular methods which allow to exclude minimal residual disease after leukemia treatment.

[Verification of hematological studies and immunologic phenotype of lymphoma cells in the blood by histological examination of the lymph nodes in non-Hodgkin's lymphoma of low and medium degree of malignancy]. / Weryfikacja badan hematologicznych i fenotypu immunologicznego komórek chloniakowych z krwi badaniem histologicznym wezla chlonnego w chloniakach nieziarniczych o malej i posredniej zlosliwosci.

In 125 patients with non-Hodgkin lymphomas of low or medium malignancy the type of lymphoma determined on the basis of morphological features and immunological phenotype of lymphoma cells in then circulation was verified by histological examination of lymph node. Dissemination of lymphoma cells into blood was found to have occurred in 80% of patients. The highest agreement of histological and haematoimmunological diagnoses was found in lymphocytic lymphoma and lymphoplasmoid (immunocyte) lymphoma, and the lowest one was in centrocytic and centroblastic-centrocytic lymphoma. It is stressed that in a part of the patients histological examination of the lymph node could be abandoned.

[DNA--ploidy in non hodgkin's lymphomas of low malignancy]. / DNA-ploidia w chloniakach nieziarniczych o niskiej zlosliwosci.

Lymphoma cell DNA cytometry in imprints of dissected lymph nodes was performed in 98 patients with low grade non-Hodgkin lymphomas and in 15 patients with reactive lymphadenopathy. The percentage of resting and proliferating cells was also calculated on the basis of computer analysis of DNA amount and cell image. It has been shown that, in contrast to the control group characterized by diploidic DNA amount, DNA aneuploidy was observed in 63.3% of lymphoma patients (DNA hyperdiploidy in 58.2% and DNA aneuploidio-polyploidy in 5.1% of the studied group). The proliferative activity of lymphoma cells was higher in patients with DNA aneuploidy than in DNA diploidic patients and in the control group.

[Treatment of acute leukemias in adults. IV. Treatment results on 375 patients at 9 hematology centers]. / Leczenie ostrych bialaczek u doroslych. IV. Wyniki leczenia 375 chorych z 9 osrodków hematologicznych.

On the basis of standardized protocols of the therapeutic results of acute non-lymphoblastic leukaemias in adults sent to the Institute of Haematology in Warsaw from 8 haematological centres in Poland it was demonstrated that complete remission occurred in 34.4% of patients (129 out of 375 cases). The mean survival time of the patients treated intensively according to programmes I, II, III and IV 8.6 months, those of patients with complete remission - 13.5 months, patients without complete remission - 3.7 months. The most frequent cause of death (82.5%) were infections and/or haemarrhagic diathesis.