Potential Leukemic Cells Engraftment After Hematopoietic Stem Cell Transplantation From Unrelated Donors With Undiagnosed Chronic Leukemia.

BACKGROUND: Donor-related neoplasms are a potential complication of treatment strategies involving stem cell transplantation. Although mechanisms for detection of short-term complications after these procedures are well developed, complications with delayed onset, notably transmission of chronic diseases such as chronic myeloid leukemia (CML), have been difficult to assess. Consequently, we studied the potential of human CML cells to engraft hematopoietic tissues after intravenous implantation in mice. METHODS: Human peripheral blood cells, collected from CML patients presenting with moderately increased white blood cells count before treatment, were transplanted into sub-lethally irradiated, immunodeficient mice. Five weeks after transplantation the nuclear cells were isolated from the murine bone marrow, spleen, and peripheral blood and were used to quantitatively detect human CD45 antigen by flow cytometry; qRT-PCR was used to detect the BCR-ABL1 fusion gene, and the human or murine beta-glucuronidase housekeeping gene was used to examine human-murine chimerism. RESULTS: We found that all evaluated animals had donor chimerism at the selected interval after transplant and the presence of a specific BCR-ABL1 fusion gene transcript was also detected. CONCLUSIONS: Our results suggest that the risk of neoplasm transmission cannot be eliminated during hematopoietic stem cell transplantation from undiagnosed CML donors with borderline leukocytosis. The obtained data confirms the potential of leukemic cells to viably engraft the hematopoietic organs post-transplantation in an immunosuppressed recipient.

Efficacy and safety of lenalidomide treatment in multiple myeloma (MM) patients--Report of the Polish Myeloma Group.

UNLABELLED: The aim of the multi-centre retrospective study was to evaluate the efficacy and safety of lenalidomide (LEN) therapy in patients with resistant or relapsed multiple myeloma (MM) as well as in patients with stable disease (LEN used due to neurological complications). The primary endpoint of this study was an overall response rate (ORR). The secondary endpoints were as follows: time to progression (TTP), overall survival (OS) and the safety of drug use. Data were collected in 19 centres of the Polish Multiple Myeloma Study Group. The study group consisted of 306 subjects: 153 females and 153 males. In 115 patients (38.8%, group A), a resistant myeloma was diagnosed; in 135 (44.1%, group B) a relapse, and in 56 (18.3%, group C) a stable disease were stated. In 92.8% of patients, LEN+DEX combination was used; in remaining group, LEN monotherapy or a combination therapy LEN+bortezomib or LEN+bendamustine and other were used. In the entire study group, ORR was 75.5% (including 12.4% patients achieving complete remission [CR] or stringent CR [sCR]). Median time to progression (TTP) was 20 months. Median overall survival (OS) was 33.3 months. The regression model for "treatment response" was on the borderline of statistical significance (p=0.07), however the number of LEN treatment cycles ≥ 6 (R(2)=17.2%), baseline LDH level (R(2)=1.1%) and no ASCT use (R(2)=1.7%) where the factors most affecting treatment response achievement. The regression model for dependant variable--"overall survival"--was statistically significant (p=0.0000004). Factors with the most impact on OS were as follows: number of LEN cycles treatment ≥ 6 (R(2)=16.7%), treatment response achievement (R(2)=6.9%), ß-2-microglobulin (ß-2-M) level (R(2)=4.8%), renal function (R(2)=3.0%) and lack of 3/4 grade adverse events (R(2)=1.4%). SUMMARY: LEN is an effective and safe therapeutic option, even in intensively treated resistant and relapsed MM patients, as well as in patients with stable disease and previous treatment-induced neurological complications. In particular, the number of LEN treatment cycles ≥ 6 was the factor which affected treatment response achievement the most, together with an important impact on OS.

Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia. Multicenter, phase III study.

To assess the efficacy of an original DAC-7 regimen: daunorubicine (DNR) 60 mg/m2/day, days 1-3; cytarabine (AraC) 200 mg/m2/day, days 1-7; cladribine (2-CdA) 5 mg/m2/day, days 1-5, 400 untreated adult acute myeloid leukemia patients (including 63 with preceding myelodysplastic syndrome), aged 45 (16-60) years were randomized to either DAC-7 (n=200) or DA-7 (without 2-CdA, n=200). The overall CR rate equaled 72% for DAC-7 and 69% for DA-7 arm (P=NS). After a single course of DAC-7 induction, the CR rate equaled 64% and was significantly higher compared to 47% in the DA-7 arm (P=0.0009). Median hospitalization time during the induction was 7 days shorter for DAC-7 compared to the DA-7 group (33 vs 40 days, P=0.002). Toxicity was comparable in both groups. The probability of 3-year leukemia-free survival (LFS) for DAC-7 and DA-7 group equaled 43 and 34%, respectively (P=NS). There was a trend toward higher LFS rate for patients aged >40 years receiving DAC-7 compared with DA-7 regimen (44 vs 28%, P=0.05). This study proves that addition of 2-CdA increases antileukemic potency of DNR+AraC regimen, thus resulting in a higher CR rate after one induction cycle when compared to DA-7, without additional toxicity. It shortens hospitalization time and may improve long-term survival in patients aged >40 years.

Cladribine with prednisone versus chlorambucil with prednisone as first-line therapy in chronic lymphocytic leukemia: report of a prospective, randomized, multicenter trial.

The efficacy and toxicity of cladribine (2-CdA) + prednisone (P) versus chlorambucil (Chl) + P were compared in previously untreated patients with progressive or symptomatic chronic lymphocytic leukemia (CLL) in a randomized, multicenter prospective trial. Eligible patients were assigned to either 2-CdA 0.12 mg/kg per day in 2-hour infusions and P 30 mg/m(2) per day for 5 consecutive days or Chl 12 mg/m(2) per day and P 30 mg/m(2) per day for 7 consecutive days. Three courses were administered at 28-day intervals or longer if myelosuppression developed. The therapy was finished if complete response (CR) was achieved. Of 229 available patients 126 received 2-CdA+P and 103 received Chl+P as a first-line treatment. CR and overall response rates were significantly higher in the patients treated with 2-CdA+P (47% and 87%, respectively) than in the patients treated with Chl+P (12% and 57%, respectively) (P = .001). Progression-free survival was significantly longer in the 2-CdA-treated group (P = .01), but event-free survival was not statistically different. Thirteen percent of patients were refractory to 2-CdA+P and 43% to Chl+P (P = .001). Drug-induced neutropenia was more frequently observed during 2-CdA+P (23%) than Chl+P therapy (11%) (P = .02), but thrombocytopenia occurred with similar frequency in both groups (36% and 27%, respectively). Infections were seen more frequently in the 2-CdA+P-treated group (56%) than in the Chl+P-treated group (40%; P = .02). Death rates have so far been similar in patients treated with 2-CdA (20%) and with Chl (17%). The probability of overall survival calculated from Kaplan-Meier curves at 24 months was also similar for both groups (78% and 82%, respectively). (Blood. 2000;96:2723-2729)

Cladribine with or without prednisone in the treatment of previously treated and untreated B-cell chronic lymphocytic leukaemia - updated results of the multicentre study of 378 patients.

Between January 1992 and January 1999, we treated 378 B-chronic lymphocytic leukaemia (CLL) patients with cladribine (2-CdA), and 255 of the patients were also treated with prednisone. A total of 194 patients were previously untreated, and 184 had relapsed or refractory disease after previous other therapy. Complete response (CR) was obtained in 111 (29.4%) and partial response (PR) in 138 (36.5%) patients, giving an overall response (OR) rate of 65.9%. CR and OR were achieved more frequently in patients in whom 2-CdA was a first-line treatment (45.4% and 82.5% respectively) than in the pretreated group (12.5% and 48.4% respectively) (P < 0.0001). The median duration of OR for previously untreated patients was 14.7 months and for pretreated patients 13.5 months (P = 0.09). The median survival evaluated from the beginning of 2-CdA treatment was shorter in the pretreated group (16.3 months) than in the untreated group (19.4 months) (P < 0.0001). A total of 117 (63.9%) patients died in the pretreated group and 63 (32.6%) in the untreated group. In pretreated patients, 2-CdA + prednisone (P) and 2-CdA alone resulted in similar OR (51.0% and 45.0% respectively; P = 0.4). In contrast, in untreated patients, 2-CdA + P produced a higher OR (85.4%) than 2-CdA alone (72.1%) (P = 0.04). Infections and fever of unknown origin, observed in 91 (49.4%) pretreated and 74 (38.1%) untreated patients (P = 0.03), were the most frequent toxic effects. Our results indicate that 2-CdA is an effective, relatively well-tolerated drug, especially in previously untreated CLL.

Computerized morphometric analysis of human leukemic and lymphomatous cells in various histological environments of central nervous system.

The leukemic and lymphomatous cells appear within the central nervous system (CNS) in 5 different environments: in CNS vessels, perivascular spaces, meninges, nervous tissue and in CNS hemorrhages. A computerized analysis of geometric and densitometric parameters of neoplastic cells in these compartments were done for better recognition of penetration and spreading of leukemia and lymphoma within the CNS. A post-mortem neuropathological investigations were carried out on 16 patients deceased due to acute myeloblastic leukemias (M1, M2), blastic phase of chronic myelogenous leukemia, lymphoblastic lymphoma and acute lymphoblastic leukemia. Following nuclear parameters of neoplastic cells were analyzed: area, "form factor", mean, minimal and maximal density. An evident differentiation of nuclear parameters within the CNS environments was found. The nuclei within the perivascular spaces and especially in CNS hemorrhages were significantly shrunken and dense (p < 0.01), but not evidently deformed. The intracerebral infiltrates appeared to be most differentiated group (p < 0.01). Morphometric values of leukemic and lymphomatous cells show regressive changes of neoplastic cells within the CNS perivascular spaces, nervous tissue and in CNS hemorrhages. These changes depend on unfavorable factors in the mentioned CNS environments, and also on time of cell persistence in these regions. Meninges were found to be the only CNS structure facilitating the survival and proliferation of leukemic and lymphomatous cells.

Computerized morphometric analysis of the cerebellum in patients with lymphoblastic lymphomas of various survival time.

Post-mortem neuropathological investigations of the cerebellum were carried out in 15 patients deceased due to lymphoblastic lymphoma (LBL). In patients with survival time of LBL longer than 20 months, neuronal structures of the cerebellum appeared to be significantly rarefied. It was especially observed within granular layer, less frequently in Purkinje and dentate nuclei cells. In cases with longer survival time shrinkage and deformation of neurons, especially Purkinje and dentate nuclei cells were observed. The morphometric analysis suggests that the cerebellar neuronal changes might be a consequence of remote effects of LBL on nervous tissue. The longer survival time contribute to the nervous system exposure on remote effects of neoplasm. The dentate nuclei cells are damaged due to remote effect of lymphoma, irrespective of Purkinje cells destruction.

2-chlorodeoxyadenosine (cladribine) in the treatment of hairy cell leukemia and hairy cell leukemia variant: 7-year experience in Poland.

Between January 1991 and December 1997, 103 patients, 97 with typical hairy cell leukemia (HCL) and 6 with HCL-variant (HCL-V) were treated with 2-chlorodeoxyadenosine (2-CdA) given as 2-h infusion for 5 consecutive d at a daily dose 0.12 mg/kg. To our knowledge this is the largest cohort of HCL patients treated with this type of regimen. Median follow-up amounted to 36 months. Fifty-six of 97 patients with typical HCL were newly diagnosed and 41 were relapsed after previous treatment. Splenectomy as a first-line therapy was performed in 23 patients and 18 remaining patients received prednisone, chlorambucil or interferon-alpha (IFN-alpha) alone or in combinations. Seventy-five (77.3%) patients entered CR and 18 (18.6%) achieved PR, giving an overall response rate of 95.9%. The mean time of first CR duration amounting to 32 months (range 3-72) did not correlate to the number of 2-CdA cycles. 2-CdA was equally effective in treatment of newly diagnosed patients and patients who relapsed after previous therapeutic procedures. Relapse of the disease occurred in 20 of 75 patients who achieved CR after 2-CdA and was usually manifested by very discrete changes in peripheral blood counts (neutropenia and/or relative lymphocytosis). The mean progression-free survival (PFS) time in this group was 37.4 (range 10-66) months. Ten of 20 relapsed patients were retreated with 2-CdA given an identical course to the first one. Seven patients entered second CR lasting 19+ (range 8-47) months and 3 experienced PR. This confirms the previous observations that 2-CdA gives no resistance to leukemic clone. Ten remaining patients have not required retreatment so far and remain in a good clinical and hematological state. The results of HCL-V treatment with 2-CdA were poor. Only 2 patients achieved PR and 4 patients did not respond to this drug. Seven patients (5 with typical HCL and 2 with HCL-V) died, 3 of causes unrelated to the disease. Second neoplasms were noted in 5 patients. 2-CdA-related side effects resulted mainly from myelosuppression and infectious complications. In conclusion we confirm the effectiveness of 2-CdA in inducing CR in patients with typical HCL, but this drug is unable to completely eradicate the leukemic clone which results in the relapse of the disease. The real incidence of the relapse rate may be underestimated unless bone marrow biopsy is performed. The results of our study indicate that a 2-h infusion of 2-CdA in HCL patients is at least as effective as a 24-h infusion but more convenient to the patients, and may be given on an outpatient basis.

[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.

[A case of centroblastic lymphoma of the thyroid gland]. / Przypadek chloniaka centroblastycznego tarczycy.

A case of a 49-year male patient with centroblastic lymphoma of the thyroid gland is presented. Centroblastic lymphoma was diagnosed with cytological and immunocytochemical examination of the biopsy specimen, and verified with histological examination of tumor section collector intraoperationally. Diagnosed tumor was classified as II AE degree. No signs of lymphocytic thyroiditis co-existing with centroblastic lymphoma were noted. The patient was treated chemically with CBVPM/AVBP regimens for 8 months. Complete remission still lasting, i.e. 96 months after completion of chemotherapy, was achieved.

2-Chlorodeoxyadenosine (cladribine)-related eosinophilia in patients with lymphoproliferative diseases.

Eosinophilia and allergic skin reactions are uncommon events after 2-chlorodoxyadenosine (2-CdA, cladribine) administration. A multicentre retrospective analysis of eosinophilia in 360 patients treated with 2-CdA for lymphoid malignancies has been made. B-cell chronic lymphocytic leukaemia (B-CLL) was diagnosed in 153, hairy cell leukaemia (HCL) in 68, low-grade non-Hodgkin's lymphoma (LGNHL) in 119, high-grade NHL in 2 and Waldenstrom's macroglobulinaemia (WM) in 18 patients. 2-CdA was administered at a dose 0.12 mg/kg/d in 2-h intravenous infusion for 5 consecutive d. The courses were repeated monthly. Patients with HCL received 1 cycle of 2-CdA, with NHL 2-6 (mean 3.5) cycles and with B-CLL 3-6 (mean 5) cycles. Twenty patients (5.5%), including 5 with HCL, 6 with LGNHL, 7 with B-CLL and 2 with WM, developed peripheral blood eosinophilia. The mean values of absolute eosinophil count were 0.78x10(9)/l (0.58-1.06x10(9)/l), 0.71x10(9)/l (0.52-1.3x10(9)/l), 85 (0.56-1.82x10(9)/l) and 0.75 (0.74-0.76x10(9)/l), respectively. Eosinophilia occurred in 13 patients after 1 course, in 4 after 2 courses, and in 5 after > or =3 courses of the therapy. In 17 cases it resolved spontaneously. Allergic skin lesions with pruritus were noticed in 3 patients simultaneously with an increase in eosinophil count. All of them required antihistaminic drugs and/or corticosteroids. One patient with B-CLL experienced repeated episodes of eosinophilia. The highest incidence of 2-CdA-induced eosinophilia was noticed in patients with MW (11.1%) and HCL (7.4%) who received only 1 cycle of this drug and entered a complete remission. This side effect was less frequently observed in LGNHL and B-CLL, i.e. in 5.0% and 4.6% of cases, respectively. The mechanism of 2-CdA-induced eosinophilia is not clear. It has been postulated that massive tumour cell lysis may trigger a release of IL-5 and probably other cytokines. The allergic mechanism of 2-CdA-induced eosinophilia is also possible, especially in patients with simultaneous skin reactions.

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.

F wave studies after intrathecal methotrexate administration.

Electrophysiological examinations were done on 20 patients aged 40-71 years with recently diagnosed high grade non-Hodgkin's lymphomas. General chemotherapy and intrathecal chemotherapy in order to prevent central nervous system (CNS) involvement were begun. On the first day of chemotherapeutic cycle patients received intrathecally methotrexate (ITMTX) and prednisolone. Electrophysiological study was carried out twice in each subject: before ITMTX injection and a day after injection. The study procedure included: a conventional nerve conduction examination (peripheral conduction velocity and compound muscle action potential amplitude), the F wave latency and amplitude measurement and F ratio (F-M-1/2M) calculation for peroneal and tibial nerve bilaterally. Results of the first and the second examinations were statistically compared by t-Student's test. No significant differences between values of estimated parameters were found. The study revealed no recent alterations in proximal, paraspinal motor conduction and motor neuron excitability due to antidromical activation after single ITMTX administration.

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.

2-chlorodeoxyadenosine (2-CdA) in 2-hour versus 24-hour intravenous infusion in the treatment of patients with hairy cell leukemia.

Forty one patients with hairy cell leukemia (HCL) were treated with 2-chloro-deoxyadenosine (2-CdA) administered in various schedules. Complete remission (CR) was achieved in 31 (76%) patients and partial remission (PR) in 9 (22%). The mean duration of remission (CR + PR) was 25.2 months (range 9-45 months). One patient did not respond to therapy. Twelve out of 16 patients (75%) achieved CR after 5-day intravenous infusions of 2-CdA and 19 out of 25 patients (76%) after 7-day courses. In 19 out of 23 patients (82.6%) CR was achieved after intermittent 2-hour infusions and in 12 out of 18 (66.7%) after continuous 24-hour infusion. The differences were not statistically significant. Side effects of 2-CdA were similar in both groups except for infections, which were less frequently observed in the group treated for 5 days. The results of our study suggest that 2-CdA can be effectively administered to patients with HCL using 5-day courses and a 2-hour daily infusion.

Leukemic cells growth fraction in the central nervous system in blastic phase of chronic myelogenous leukemia.

Clinical and neuropathological investigations were carried out in 6 patients, deceased due to blastic phase of chronic myelogenous leukemia (BPCML). Growth fraction of leukemic cells in peripheral blood, cerebrospinal fluid and in the central nervous system (CNS) was studied, using mitotic index and immunohistochemical staining technique with the monoclonal antibody antiproliferating cell nuclear antigen (anti-PCNA). The results suggest that in BPCML the proliferative activity of leukemic cells is low both in peripheral blood, cerebrospinal fluid, cerebral leukostasis and within the leptomeningeal and intracerebral infiltrates, even in cases with a very high white blood cells count. It can confirm the opinion that in BPCML, accumulation rather than proliferation of leukemic cells plays an important role in the development of the CNS leukemia.

[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.

[Transthyretin and albumin in cerebrospinal fluid in patients with acute leukemias or lymphomas of high grade malignancy]. / Transtyretyna i albumina w plynie mózgowo-rdzeniowym u chorych na ostre bialaczki lub chloniaki o wysokim stopniu zlosliwosci.

Transthyretin and albumin in lumbar cerebrospinal fluid (CSF) and in serum were repeatedly assessed in 40 patients with acute leukemias or high grade non-Hodgkin's lymphomas. The patients were divided into 3 groups. Group I-5 individuals with clinical manifestations of leukemic or lymphomatous meningosis; Group II-33 cases with no clinical data of central nervous system involvement by neoplasm (leukemia/lymphoma); Group III-2 patients in whom extramedullary solid leukemic or lymphomatous infiltrations were diagnosed. It was revealed that blood-brain-barrier dysfunction due to neoplastic infiltration of leptomeninges went with an increase of albumin blood-CSF barrier dependent- and with decrease of blood-CSF barrier-independent transthyretin concentrations. In patients with extramedullary tumors an evident increase of albumin and total-CSF transthyretin and no blood-CSF barrier-independent transthyretin concentrations below the tumor location were observed. It can betray a complete block of the vertebral canal subarachnoid space below the neoplastic compression of the spinal cord. Cytostatics application, either general or intrathecal, did not influence the CSF albumin and transthyretin levels.

[Dysfunction of the blood-brain barrier in patients with acute leukemias or lymphomas of high grade malignancy]. / Zaburzenia funkcji bariery krew-mózg u chorych z ostrymi bialaczkami lub chloniakami o wysokim stopniu zlosliwosci.

In 38 patients with acute leukemias or non-Hodgkin's lymphomas of high malignancy the blood-brain barrier (BBB) was prospectively analysed by means of QAlb value (QAlb = cerebrospinal fluid albumin/serum albumin). Cerebro-spinal fluid and serum were taken before each intrathecal methotrexate administration according to central nervous system (CNS) prophylaxis or treatment of CNS involvement by neoplasm. Patients were divided into two groups. Group I consisted of 5 individuals with clinical manifestations of CNS involvement by leukemia or lymphoma. Group II contained 33 patients without neurological symptoms. Besides, group II was subdivided into other two groups: group IIa-patients with BBB analysis before cytostatics application, and group IIb-patients in which BBB was analysed after the administration of at least one cycle of protocols, used in general chemotherapy, including intrathecal methotrexate injection. In group I BBB changes were observed in 10 out of 12 assessments (sensitivity 83.3%). In group II BBB impairment was revealed in 11 out of 52 assessments (specificity 78.8%). The differences in QAlb values between groups I and II were statistically significant (p = 0.0008), whereas there were no significant differences between QAlb values in groups IIa and IIb. Basing on their investigations, the authors conclude that neoplasm invading CNS should be considered as essential risk of BBB impairment, whereas intrathecal and general chemotherapy appear to be less important in BBB injury.

Central nervous system leukostasis in patients with leukemias and lymphomas.

The clinical and neuropathological investigations have been done on 133 autopsied patients died of leukemia or non-Hodgkin's lymphoma of high malignancy. A study was performed to analyse the role of various factors particularly with respect to adhesion and aggregation in the CNS leukostasis development. The findings were also designated to evaluate the distribution of leukostasis in different CNS regions and to recognize its intensity in various CNS vessels. Basing on the studies the authors conclude that the risk of CNS leukostasis increases evidently when the leukocyte counts are elevated above 50 G/l. The adhesion and aggregation of leukemic and lymphomatous cells as well as local anatomical factors in the CNS vessels play and important role in the CNS leukostasis development, which is more intensive in the white matter and leptomeninges. The medium-sized vessels are much involved, whereas cortical capillaries are relatively less affected by leukostasis. The CNS leukostasis appears to be dynamic and reversible phenomenon, which undergoes fluctuations according to the leukocyte counts increase or decrease.