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G A Pangalis

Publications and source records attributed to G A Pangalis.

At least 37 records · Page 2Linked to original sources
PubMed1998

Neutrophil 5-nucleotidase reaction in chronic myelogenous leukemia, myelofibrosis with myeloid metaplasia, and polycythemia vera.

A readable and reproducible 5-nucleotidase (5N) cytochemical reaction was developed for blood smear preparation, after modification of the technique of Wachstein and Meisel. The reaction was applied to normal polymorphonuclear neutrophils (NPN) and to neutrophils from patients with chronic myelogenous leukemia (CML), myelofibrosis with myeloid metaplasia (MMM), and polycythemia vera (PV). The following observations were made: (a) 5N was present in NPN, with a mean score of 83.2+/-15.7. (b) In patients with MMM and PV an increased 5N score was observed (mean score 111+/-63.8 and 178.3+/-83.3, respectively). (c) In CML the mean score was 4.9+/-2.2. (c) A statistical comparison of neutrophil 5-nucleotidase (N5N) between CML and MMM and PV patients demonstrated a highly significant difference (p<0.0001). In the present study, we showed that the N5N activity parallels that of NAP in chronic myeloproliferative disorders such as CML, MMM, and PV. It appears that, apart from the already known activity of NAP in myeloproliferative disorders, other enzymes (e.g., N5N) can present a similar behavior with increased or decreased activity.

5'-Nucleotidase↗
PubMed1998

Prognostic relevance of apoptotic cell death in non-Hodgkin's lymphomas: a multivariate survival analysis including Ki67 and p53 oncoprotein expression.

AIMS: To evaluate the independent prognostic value of apoptotic versus proliferative fractions in a series of 92 patients with non-Hodgkin's lymphomas (NHL). METHODS AND RESULTS: Apoptotic fractions were quantified by use of the TdT (terminal deoxynucleotidyl-transferase)-mediated in-situ end-labelling technique (TUNEL), the percentage of positive cells constituting the apoptotic index (AI). Proliferative rate was expressed as percentage of Ki67 positive cells (Ki67 LI). Tissues were also stained for p53 protein with the DO-1 antibody. Patients were followed up until death (n = 33) or for an average of 63 months (n = 56). AI increased with malignancy grade and proliferative activity but was not related to location, cell of origin, clinical stage, bone marrow involvement and p53 expression. In multivariate analysis, overall survival was independently influenced by grade, stage, p53 LI and chemotherapy. The independent predictors of disease-free survival were Ki67 LI location and chemotherapy. AI turned out to be the only independent (negative) predictor of post-relapse survival. On the other hand, a low Ki67 LI increased the risk of relapse (logistic regression analysis) whereas a low p53 LI increased the probability of complete response. CONCLUSIONS: Our results suggest that the combined assessment of apoptotic fraction, proliferative rate and p53 expression may provide important prognostic information independent of other clinicopathological parameters in NHL.

Adolescent↗
PubMed1998

Prognostic implications of proliferating cell nuclear antigen (PCNA), AgNORs and P53 in non-Hodgkin's lymphomas.

We investigated the prognostic value of proliferating cell nuclear antigen (PCNA) and p53 oncoprotein expression and of nucleolar organiser region (NOR) scoring, in relation to classic clinicopathological parameters, in a series of non-Hodgkin's lymphomas (NHL). Paraffin embedded tissue from 91 patients with NHL was stained immunohistochemically with the monoclonal antibodies PC-10 (PCNA) and DO-1 (p53) and histochemically with the AgNOR technique. The median follow-up was 48 (4 to 193) months. The impact of PCNA and p53 expression and of AgNOR number on survival was tested using univariate as well as multivariate analysis, in order to circumvent the heterogeneity in histologic grade, type and therapy. Univariate analysis identified seven variables related to overall survival: histologic type and grade, clinical stage, chemotherapy, p53 labelling index (LI), PCNA LI and AgNOR score, whereas only one parameter i.e. histologic grade influenced disease-free survival. In multivariate analysis stage, PCNA LI and AgNOR score predicted independently overall survival. PCNA was also the only independent predictor of post-relapse survival and histologic grade the most important indicator of disease-free survival. In conclusion, PCNA expression and AgNOR number may be better predictors of overall and post-relapse survival than histologic grade. The latter remains the most valuable prognostic indicator of disease-free survival.

Adolescent↗
PubMed1997

Phase II multicenter study of human CD52 antibody in previously treated chronic lymphocytic leukemia. European Study Group of CAMPATH-1H Treatment in Chronic Lymphocytic Leukemia.

PURPOSE: CAMPATH-1H is a human immunoglobulin G1 (IgG1) anti-CD52 monoclonal antibody (MAb) that binds to nearly all B- and T-cell lymphomas and leukemias. We report the results of a multicenter phase II trial that used CAMPATH-1H in previously chemotherapy-treated patients with chronic lymphocytic leukemia (CLL). MATERIALS AND METHODS: Twenty-nine patients who had relapsed after an initial response (n = 8) or were refractory (n = 21) to chemotherapy were treated with CAMPATH-1H administered as a 30-mg 2-hour intravenous (IV) infusion thrice weekly for a maximum period of 12 weeks. RESULTS: Eleven patients (38%) achieved a partial remission (PR) and one (4%) a complete remission (CR) (response rate, 42%; 95% confidence interval [CI], 23% to 61%). Three of eight patients (38%) with a relapse and nine of 21 refractory patients (43%) responded to CAMPATH-1H therapy. CLL cells were rapidly eliminated from blood in 28 of 29 patients (97%). CR in the bone marrow was obtained in 36% and splenomegaly resolved completely in 32%. Lymphadenopathy was normalized in only two patients (7%). The median response duration was 12 months (range, 6 to 25+). World Health Organization (WHO) grade IV neutropenia and thrombocytopenia developed in three (10%) and two patients (7%), respectively. Neutropenia and thrombocytopenia recovered in most responding patients during continued CAMPATH-1H treatment. Lymphopenia (< 0.5 x 10(9)/L) occurred in all patients. Two patients had opportunistic infections and four had bacterial septicemia. CONCLUSION: CAMPATH-1H had significant activity in patients with advanced and chemotherapy-resistant CLL. The most pronounced effects were noted in blood, bone marrow, and spleen. Preferential clearance of blood may allow harvesting of uncontaminated blood stem cells for use in high-dose chemotherapy protocols.

Adult↗
PubMed1997

Detection of "PNH red cell" populations in hematological disorders using the Sephacryl Gel Test micro typing system.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder characterised by an unusual sensitivity of abnormal red cell population(s) to complement lysis, due to a complete or incomplete defect of various surface molecules, including CD55 and CD59. PNH has been associated with various hematological disorders. Using a newly introduced method, the Sephacryl gel test microtyping system, we investigated the presence of CD55 or CD59 defective red cell populations in several hematological disorders. It was also found that a large proportion of such patients possess CD55 deficient populations, while a smaller but still significant proportion possess CD59 deficient populations. Defective red cell populations were detected in normal subjects as well. These findings need further investigation. Nevertheless the Sephacryl Gel Test microtyping system although non specific, seems to be useful in screening for the PNH and/or "PNH-like" red cell defect in several hematological disorders.

CD55 Antigens↗
PubMed1997

Leukaemia cutis preceding acute myelomonocytic leukaemia.

We report a case of acute myelomonocytic leukaemia (AMML) who presented with a striking leukaemic infiltration in the frontal area of the scalp that was also rapidly followed by infiltrates in other sites of the skin, mainly in the upper thoracic wall. Leukaemic skin infiltration developed independently of his haematological status; nevertheless, he rapidly progressed to acute leukaemia. We emphasise the importance of early recognition and identification of such lesions with a subsequent early application of systematic antileukaemic therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Molecular demonstration of BCR/ABL fusion in two cases with chronic myeloproliferative disorder carrying variant Philadelphia t(14;22)(q32;q11).

We report two cases with chronic myeloproliferative disorder which were found to carry simple variant Philadelphia (Ph) t(14;22)(q32;q11) in unstimulated bone marrow mononuclear cells. Both cases were characterized molecularly by Southern blot, reverse transcription-polymerase chain reaction (RT-PCR), and direct sequencing of the RT-PCR products. In the first case (female, aged 65, in blastic transformation which developed one year after the initial diagnosis of myelofibrosis), a t(14;22) (q32;q11) was found in association with several other chromosomal abnormalities [48,XX,+X,+5,del(5) (q12q32),+8,der(9)t(9;11)(q32;q11),-11]; molecular analysis demonstrated the presence of a BCR-ABL chimeric gene and mRNA transcript of the b2-a2 type. In the second case (female, aged 16, with clinical and hematologic features typical of chronic myelogenous leukemia in chronic phase), a t(14;22) (q32;q11) was identified as the sole karyotypic abnormality; again, molecular analysis demonstrated the presence of a BCR-ABL chimeric gene and mRNA transcript, this time of the b3-a2 type. Our findings further support the notion that, even when undetectable by conventional cytogenetics, band 9q34 participates in all Ph chromosomes and leads to the formation of chimeric BCR-ABL genes.

Adolescent↗
PubMed1996

Comparative study of the formation and repair of O6-methylguanine in humans and rodents treated with dacarbazine.

The mutagenic, carcinogenic and cytotoxic activity of dacarbazine, a drug employed in cancer chemotherapy, may be related to the induction in DNA of O6-methylguanine (O6-meG), a quantitatively minor but biologically important lesion. In the present study the kinetics of O6-meG formation and repair in blood leukocyte DNA were examined in 20 Hodgkins lymphoma patients treated i.v. with 180 +/- 13 (mean +/- SD) mg/m2 dacarbazine and compared with those observed in various tissues of rodents treated with different doses of the drug. In Hodgkin's lymphoma patients adduct levels reached a value of 0.27 +/- 0.14 fmol/microgram DNA 2 h after dacarbazine administration, while the rate of subsequent loss suggested an adduct half-life of < or = 30 h. Measurement of adduct levels in the same individuals after successive courses of treatment spaced 3 weeks apart (up to 10 treatment courses) demonstrated a consistent individual response and statistical analysis of variance confirmed that intra-individual variation in adduct accumulation after a given dose of dacarbazine accounted for only 5% of the total variance observed. In contrast, inter-individual variation accounted for 70% of the observed variance, with adduct levels 2 h after drug treatment varying approximately 7.5-fold among adduct-positive individuals. No significant depletion of lymphocyte O6-alkylguanine-DNA alkyltransferase (AGT) occurred after patient treatment with dacarbazine. No significant relationship between adduct levels and clinical response to treatment was observed. In rats treated with single or multiple doses of dacarbazine causing varying degrees of AGT depletion the highest levels of O6-meG were seen in the liver, followed by the lymph nodes, bone marrow and blood leukocytes, which showed up to approximately 2-fold lower levels. A similar tissue distribution was also observed in mice and in a single rabbit. These observations suggest that O6-meG levels assayed in blood leukocytes of therapeutically treated humans reflect those present in the -lymph nodes (target tissue for chemotherapy) and the bone marrow (target tissue for leukaemogenesis) and may be utilized as a measure of the drug dose reaching these tissues. The quantitative data reported in this study show that under conditions of no depletion of AGT O6-meG accumulates in blood leukocyte DNA of humans at a rate similar to that observed in rats, suggesting that human susceptibility to any O6-meG-mediated genotoxic effects of dacarbazine may be comparable with that of the rat.

Animals↗
PubMed1996

Fludarabine monophosphate in refractory B-chronic lymphocytic leukemia: maintenance may be significant to sustain response.

In the present study we report our results on the efficacy of Fludarabine monophosphate in 20 B-chronic lymphocytic leukemia (CLL) patients, refractory to conventional chemotherapy. Of the 20 patients 14 were males and 6 females with a median age of 58 years (44-70). Eight had Binet stage B and 12 stage C. They were previously treated with chlorambucil, prednisone, mini-CHOP or irradiation. Their disease duration prior to fludarabine administration was 49 months (7-180). Fludarabine was given at a dose of 25 mg/m2 daily, for five consecutive days, monthly for six months and if responding for six additional months. Treatment was administered on an outpatient basis. Complete response (CR) was observed in 7 patients (33%) and partial remission (PR) in 5 (25%). Of the complete responders 5 were males and 2 females with a median age of 60 years (range 55-68); three of them had stage B and 4 stage C disease; the median number of fludarabine courses for achieving CR was 3 (range 2-5). In all CR patients a residual monoclonal CD5/CD19 positive lymphocyte population was found in the peripheral blood. All CRs relapsed shortly after discontinuation of therapy within 12 months. The main toxicity observed was upper respiratory tract and/or pulmonary infections in 8 patients, requiring hospitalization. Among the CRs one patient died during the administration of the third course of therapy, due to a severe hypersensitivity reaction with Stevens-Johnson syndrome. The importance of maintenance therapy is also stressed as PR was sustained in some patients using 3 day cycles every 2-4 months. One patient was maintained in this fashion for 60 + months. This study showed that fludarabine is effective in CLL patients refractory to conventional chemotherapy thus it may be given as the treatment of choice if such patients still require treatment.

Adult↗
PubMed1995

Effective treatment of disease-related anaemia in B-chronic lymphocytic leukaemia patients with recombinant human erythropoietin.

Nine B-chronic lymphocytic leukaemia (B-CLL) patients suffering from anaemia, due to no obvious cause except their disease, were treated with recombinant human erythropoietin (r-HuEPO). The treatment protocol provided a closed label phase of 3 months duration, during which the patients received r-HuEPO or placebo in a ratio of 2:1, followed by an open label phase, also of 3 months duration, during which r-HuEPO was administered to all patients three times a week s.c. r-HuEPO was given a dose of 150 U/kg of body weight with an escalation of 50 U/kg up to a maximum of 300 U/kg three times a week. Complete response was achieved in 5/9 (55%) patients and partial response in 3/9 (33%). The response obtained was independent of the pretreatment serum EPO levels, the duration of anaemia, the concomitant administration of chemotherapy, the presence of splenomegaly, or the degree of bone marrow infiltration by lymphocytes. It appears that r-HuEPO is very effective in reversing the disease-related anaemia of B-CLL patients.

Aged↗
PubMed1995

Recommended procedures for the classification of acute leukaemias.

The classification of acute leukaemias is now widely based on a combined morphological, cytochemical and immunophenotyping approach. Difficulties are frequently encountered however in reaching an acceptable degree of diagnostic concordance between different laboratories because of variations in the techniques used (in terms of methodologies, reagents and equipment) and diagnostic interpretation. The International Council for Standardization in Haematology (ICSH) convened an expert panel to consider currently available diagnostic techniques with the aim of defining a minimum cytochemical and immunological diagnostic panel that could be used as core components for the classification of acute leukaemia. The proposed ICSH scheme, which attempts to balance the basic requirement for providing precise and informative diagnostic information without limiting its use to only those laboratories with sophisticated facilities, is based on three sequential levels of investigation; primary cytochemistry, intracellular phenotyping and membrane immunophenotyping. The minimum ICSH recommended cytochemistries comprise myeloperoxidase (MPO), chloroacetate esterase (ChlorE) and alpha-naphthyl acetate esterase (ANAE), and standardised methods for these cytochemistries are detailed in this communication. For cases of acute leukaemia that remain unclassified by primary cytochemistry, subsequent immunological analyses for cytoplasmic CD3, CD22, MPO and nuclear TdT are recommended. The ICSH panel considers that the use of these minimum primary cytochemical and intracellular phenotyping procedures will lead to the consistent classification of most acute leukaemias, and that the third level of investigation (membrane immunophenotyping) should be used for the purposes of confirmation, diagnostic clarification of atypical leukaemias, and the subtyping of acute lymphoblastic leukaemias (ALL). The ICSH panel also recognised that there are a number of additional technologies which can provide definitive diagnostic information, such as cytogenetics and DNA genotyping, but these were excluded from the minimum panel because of their restricted availability. While many specialised laboratories, particularly in the areas of diagnostic research, will continue to use individual investigatory protocols, it is considered that the inclusion of the ICSH scheme as core components would lead to greater consistency when comparing independent studies of acute leukaemia.

Acute Disease↗
PubMed1994

Increased natural antibody activity in sera of patients with malignant non-Hodgkin's lymphomas containing paraproteins.

In view of the frequent association between malignant lymphoproliferative diseases and autoimmunity, we studied by ELISA the presence, isotype, and specificity of natural antibodies in sera from 60 patients with malignant non-Hodgkin's lymphomas and 70 healthy controls. The antigens selected were actin, tubulin, myosin, troponin, tropomyosin, keratin, thyroglobulin, single stranded DNA, and the hapten trinitrophenyl. The results of this study were compared with the presence of oligoclonal immunoglobulins in the same sera, as previously detected by Isoelectric Focusing and Immunoblotting. Our results showed that 1) there is a high proportion of autoreactive NHL sera: 28 (46.6%) exhibited high IgG natural antibody activity (Nab) against one or more panel antigens, mostly against keratin, myosin, and tropomyosin, 26 (43.3%) had high IgA Nab activity, mainly against myosin, keratin, and ssDNA, whereas 17 (28.3%) displayed a high IgM Nab activity. The great majority (> 80%) of positive sera was polyspecific, i.e., reacted with at least two panel antigens. 2) A strong correlation exists between the high serum Nab activity and the presence of paraproteins: of the 28 sera exhibiting high IgG Nab activity, 16 (57%) contained oligoclonal IgG, and of the 17 sera exhibiting high IgM Nab activity, 13 (76.4%) contained oligoclonal IgM. The Nabs detected had frequently the same heavy and light chain as the paraproteins. No relationship between the presence of paraproteins with Nab activity and the stage of disease or grade of malignancy was found. We conclude that the high incidence of clonal immunoglobulins of different isotypes with various autoantibody specificities suggests an oligoclonal lymphocyte activation involving Nab producing cells. The significance of such autoreactive clones in NHL patients remains to be elucidated.

Adult↗
PubMed1994

Comparative dosimetry of O6-methylguanine in humans and rodents treated with procarbazine.

The accumulation of O6-methylguanine (O6-meG) in the DNA of blood leukocytes of 21 Hodgkin's lymphoma patients (followed for up to 12 cycles of treatment) treated in the context of MOPP combination chemotherapy with 150 mg procarbazine daily for 10 days was examined and compared to that observed in rats treated with different doses of procarbazine as a single agent once per day for 10 days. In humans, the adduct accumulated in a dose-related fashion and appeared to approach a steady-state after 7-8 days of treatment. Adduct levels on day 10 of the treatment cycle averaged 0.25 +/- 0.09 (mean +/- SD) mumol/molG and, for different individuals, covered a 3-fold range. Intra-individual variability between different treatment cycles was much more limited than inter-individual variability, the two parameters accounting for 8.9% and 84.5% respectively of adduct variance at a constant cumulative dose. Comparison of the dose-response relationships for humans and rats indicates that, under conditions of no depletion of O6-alkylguanine-DNA alkyltransferase (AGT), O6-meG accumulates in blood leukocyte DNA of humans at a rate which is only approximately 2-fold lower than in rats, implying that, to the extent to which O6-meG contributes to the genotoxic activity of procarbazine, human susceptibility to it is likely to be comparable to that of the rat. This is likely to be true also of the bone marrow (the tissue of interest as a target tissue for leukaemogenesis), since the tissue distribution of O6-meG induced by low doses of procarbazine in rats, mice and rabbits indicated that blood leukocyte levels of this adduct closely reflect those in the bone marrow. Based on these results, it is estimated that by the end of a MOPP chemotherapy cycle O6-meG reaches levels of the order of 0.2-0.3 fmol/microgram DNA (0.3-0.5 mumol/molG) in human bone marrow (the target tissue of leukaemogenesis observed after such treatment).

Animals↗
PubMed1994

Influenza virus vaccine in B-cell chronic lymphocytic leukaemia patients.

The clinical reaction and the immunological response to influenza virus vaccine were studied in 43 B-cell chronic lymphocytic leukaemia patients. The Vaxigrip vaccine was administered containing the antigens A/Ghizhou/54/89, A/Singapore/6/86, and B/Yamagata/16/88. The side-effects observed were minimal and well tolerated. Antibody production with titres > 1:20 on day 15 was observed at least for one antigen in 35 patients (81%). In 23 of them (63%) this response was retained on days 30 and 60. Patients with IgG levels (< 700 mg/dl) responded less well as compared to those having normal IgG levels (> 700 mg/dl).

Adult↗
PubMed1994

B-cell lymphoma of large multilobated type: an immunohistochemical study of 8 cases and review of the literature.

Large multilobated cell lymphomas represent an heterogenous group comprising both B-cell and T-cell subtypes. The correct lineage identification of each subtype cannot be based on morphologic grounds, as it has already been stressed by other authors, and demands the use of immunophenotyping methods. In this study we review the literature and present eight new cases of large multilobated B-cell lymphoma which have been immunophenotyped in paraffin sections with a panel of monoclonal [L26 (CD20), 4KB5 (CD45R), UCHL1 (CD45RO), MT1 (CD43)] and polyclonal (anti-CD3, anti-kappa, anti-lambda) antibodies. We further investigated the expression of c-myc p62 oncoprotein and of proliferating cell nuclear antigen (PCNA) using the monoclonal antibodies c-myc 1-9E10 and PC-10 respectively. In all cases the neoplastic cells were positive for L26 (CD20) and negative for anti-CD3. Five cases were positive for 4KB5 (CD45R) while six cases stained positively for UCHL1 (CD45RO) or MT1 (CD43). Four cases were monoclonal in respect to light chain restriction. Immunoreactivity with c-myc 1-9E10 and PC-10 was observed in all cases. As far as c-myc 1-9E10 is concerned, positive cells constituted more than 45% of the neoplastic population in six cases, whereas in all cases the percentage of PC-10 positive cells was greater than 45%. The staining pattern was nuclear and/or cytoplasmic for c-myc 1-9E10 but solely nuclear for PC-10. The elevated c-myc and PCNA expression are indices of high proliferation rate in this type of lymphoma and may suggest a high malignancy grade.

Adolescent↗
PubMed1994

Low grade non-Hodgkin's lymphomas: disease control with mitoxanthrone monotherapy in patients refractory to conventional therapy.

Salvage treatment modalities for refractory low grade non-Hodgkin's lymphomas (LGNHL) are limited. In the present analysis we investigate the effectiveness of mitoxanthrone monotherapy in resistant LGNHL. Fourteen patients from our Unit were studied. Eligibility criteria were as follows: histologic type of LGNHL, performance status 0, 1 or 2, clinical stage II, III or IV, A or B and refractoriness to conventional chemotherapy. The treatment protocol provided intravenous infusion of mitoxanthrone 6 mg/m2 daily for 3 days every three to four weeks. The median number of treatment cycles until now was 4 (1-8). A minimum of 3 cycles was necessary for documentation of response. For the staging and response of our patients well known criteria were used. The term minor response (MR) was introduced for those patients who had less than 50% disease regression. Of the 14 patients one could not be evaluated. Among the remaining 13, one achieved complete remission (CR) (7.7%), six partial remissions (PR) (46.2%), three MR (23%), two remained stable (SD) (15.4%) and one had disease progression (DP) (7.7%). Overall response rate (CR + PR) was 53.9%. Response to treatment was better in patients with less pretreatment (one-two prior treatments) than in heavily pretreated ones (more than three) and this relation was found to be statistically significant (p < 0.05). In addition it seems that follicular small cleaved or mixed lymphoma and patients with less bulky disease responded better, although these differences could not be documented as statistically significant. The follow up of our patients is too short for any meaningful conclusions about the duration of response to be drawn.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Accumulation of O6-methylguanine in human DNA after therapeutic exposure to methylating agents and its relationship with biological effects.

O6-Methylguanine has been measured in peripheral blood leukocytes of 14 patients during one or more cycles of treatment with procarbazine (daily treatment for 10 days) and in 12 patients during one or more cycles of treatment with dacarbazine (single dose per cycle). Adduct formation at levels up to about 0.4 fmole/microgram DNA was detected in all procarbazine- and all but one dacarbazine-treated patients at some point after treatment. O6-Methylguanine accumulated during procarbazine treatment in a dose-related manner (mean rate of accumulation 2.8 x 10(-4) fmole/microgram DNA per mg/m2 dose) and appeared to approach a plateau by the end of the cycle (above 600 mg/m2 cumulative dose). The average rate of O6-methylguanine formation 2 hr after dacarbazine treatment was 11 +/- 8 x 10(-4) fmole/microgram DNA per mg/m2 dose. Individuals examined on more than one treatment cycle with either drug showed broadly similar methylation responses. The rate of adduct accumulation showed a nonsignificant, negative correlation with the pretreatment lymphocyte levels of the repair enzyme O6-alkylguanine-DNA alkyltransferase (AGT) in the case of procarbazine and no correlation in the case of dacarbazine. No consistent lymphocyte AGT depletion was noted as a result of treatment with either drug. No correlation between O6-methylguanine formation and hematological toxicity was observed. In eight patients showing full remission after treatment with dacarbazine, the value of O6-methylguanine (averaged over all the cycles) was 0.252 +/- 0.120 fmole/microgram DNA while in four patients showing partial or no response it was 0.087 +/- 0.110 fmole/microgram DNA (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗