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Biomedical subjects

G Juliusson

Publications and source records attributed to G Juliusson.

At least 55 records · Page 3Linked to original sources
PubMed1995

Expression of deoxycytidine kinase and phosphorylation of 2-chlorodeoxyadenosine in human normal and tumour cells and tissues.

Deoxycytidine kinase (dCK) activates several clinically important drugs, including the recently developed antileukaemic compound 2-chlorodeoxyadenosine (CdA). The distribution of dCK in cells and tissues has previously been determined by activity measurements, which may be unreliable because of the presence of other enzymes with overlapping substrate specificities. Therefore we have measured dCK polypeptide levels in extracts of normal and malignant human peripheral blood mononuclear cells, gastrointestinal tissues and sarcomas, using a specific immunoblotting technique, as well as the phosphorylation of CdA in the same extracts. High levels of dCK were found in all major subpopulations of normal mononuclear leucocytes (120 +/- 19 ng dCK/mg protein) and in B-cell chronic lymphocytic leukaemia (81 +/- 30 ng/mg, n = 23). Hairy-cell leukaemia contained lower levels (28 +/- 23 ng/mg, n = 7), as did three samples of T-cell chronic lymphocytic leukaemia (18 +/- 14 ng/mg). Phytohaemagglutinin stimulation of normal lymphocytes did not lead to any substantial increase in either dCK activity or protein expression (less than 2.5-fold). The human CEM wt T-lymphoblastoid cell line contained 56 +/- 1 ng/dCK/mg protein, while in the CEM ddC50 and AraC8D mutants that lack dCK activity, no dCK polypeptide could be detected. In colon adenocarcinomas, the dCK content was significantly higher (20 +/- 9 ng/mg, n = 20) than in normal colon mucosa (8 +/- 3.5 ng/mg, n = 19, P < 0.05). A similar pattern of dCK expression was found in gastric adenocarcinomas (21 +/- 13 ng/mg, n = 5) and normal stomach mucosa (6 +/- 5 ng/mg, n = 5, P < 0.15). One leiomyosarcoma and one extra-skeletal osteosarcoma showed dCK levels comparable with those found in normal lymphocytes (84 +/- 6 and 109 +/- 4 ng/mg, respectively), while other sarcoma samples contained lower levels, comparable to the gastrointestinal adenocarcinomas (20 +/- 7 ng/mg, n = 12). Thus, dCK is expressed constitutively and predominantly in lymphoid cells, but it is also found in solid non-lymphoid tissues, with increased levels in malignant cells. The phosphorylation of CdA in crude extracts showed a close correlation to the dCK polypeptide level.

Blotting, Western↗
PubMed1995

Neutropenic fever following cladribine therapy for symptomatic hairy-cell leukemia: predictive factors and effects of granulocyte-macrophage colony-stimulating factor.

BACKGROUND: Neutropenic fever is the commonest complication of cladribine therapy for hairy-cell leukemia (HCL), leading to a 3% mortality rate. Our aim was to identify predictive factors and evaluate the effects of concomitant granulocyte-macrophage colony-stimulating factor (GM-CSF). PATIENTS AND METHODS: We studied 102 patients with active HCL given cladribine for 7 days. Pretreatment parameters predicting neutropenic fever were analysed. Twelve patients at high risk for febrile complications also received 400 micrograms GM-CSF per day on days 1 through 21. RESULTS: Pretreatment anemia, hypocholesterolemia, bone marrow differential with a high percentage of hairy cells and a low percentage of myelopoietic cells, low albumin, and high C-reactive protein predicted neutropenic fever. The addition of GM-CSF did not improve the kinetics of recovery for neutrophils, hemoglobin or platelets, as compared to matched control patients. However, GM-CSF significantly reduced cladribine-induced lymphopenia, but not the incidence of neutropenic fever. CONCLUSION: Factors predicting febrile neutropenia were identified. GM-CSF protected from cladribine lymphotoxicity but did not improve neutropenia or febrile episodes.

Cladribine↗
PubMed1995

Low-dose cladribine for symptomatic hairy cell leukaemia.

Cladribine is an effective therapy for hairy cell leukaemia (HCL), but the standard regime is frequently complicated by neutropenic fever and prolonged T-cell depression. We studied 102 patients with active HCL following treatment with various doses of cladribine given for 7 d. Two patients received 1 mg cladribine/m2/d without toxicity or effect. Eight subsequent patients received 2 mg cladribine/m2/d, and normalized cytopenia as quickly as 94 control patients receiving a standard dose (3.4 mg/m2 or 0.085 mg/kg), with significantly less lymphopenia and a similar complete remission rate.

Adult↗
PubMed1995

Mitoxantrone, etoposide and ara-C vs doxorubicin-DNA, ara-C, thioguanine, vincristine and prednisolone in the treatment of patients with acute myelocytic leukaemia. A randomized comparison.

Complex-binding of anthracyclines to DNA may increase their therapeutic efficacy. In a previous randomized trial patients with acute myelocytic leukaemia (AML) receiving combination chemotherapy including a DNA-bound doxorubicin preparation had a longer duration of first complete remission (CR) and survival than patients receiving free doxorubicin. In a parallel phase I/II study a combination of mitoxantrone, activity. In this randomized study of AML patients (15-60 years) induction treatment with MEA was compared to a combination of doxorubicin/DNA conjugate ara-C, thioguanine, vincristine and prednisolone (POCAL-DNA). The study was closed after an interim analysis of 86 patients. Thirty-five/42 (83%) and 20/44 (45%) patients entered CR in the MEA and POCAL-DNA groups, respectively (p < 0.001). With rescue therapy the corresponding figures were 88 and 64% (p < 0.02). Median survival was 27.8 and 13.1 months for MEA and POCAL-DNA patients, respectively (p < 0.03). In conclusion, the MEA regimen has a very high antileukaemic activity in good accordance with our previous experience. Since we could not reproduce our earlier clinical results using DNA-bound anthracyclines, the source and preparation of DNA seem to be of major importance.

Adolescent↗
PubMed1995

Subcutaneous injections of 2-chlorodeoxyadenosine for symptomatic hairy cell leukemia.

PURPOSE: To evaluate the clinical efficacy and safety of 2-chlorodeoxyadenosine (CdA) when administered by subcutaneous injection to patients with symptomatic hairy cell leukemia (HCL), and to evaluate predictive factors for response. PATIENTS AND METHODS: Seventy-three patients were given CdA as a subcutaneous injection once daily for 7 days. Complete remission (CR) required normalized blood counts and the absence of B-ly 7-positive bone marrow cells by flow cytometry. CdA concentrations in plasma following the first injection were analyzed by high-pressure liquid chromatography. RESULTS: Fifty-nine patients (81%) achieved a durable CR after one (n = 55) or two courses, and 10 had a partial remission (PR). With a median follow-up duration of 20 months, no patient had a clinical relapse. Neutropenic fever that required intravenous antibiotics occurred in 28 patients (38%). No toxicity at injection sites was observed. Incomplete response was predicted by an elevated lymphocyte count and serum beta 2-microglobulin level, and by a high percentage of hairy cells in the bone marrow. Plasma CdA levels were similar to those achieved from intravenous administration. CONCLUSION: Subcutaneous injection of CdA is safe and as effective as continuous infusion without problems associated with the mode of administration. Our schedule simplifies CdA treatment and can be generally recommended.

Adult↗
PubMed1995

Cellular pharmacokinetics of 2-chloro-2'-deoxyadenosine nucleotides: comparison of intermittent and continuous intravenous infusion and subcutaneous and oral administration in leukemia patients

2-Chloro-2'-deoxyadenosine (CdA) is a new purine nucleoside analogue with major activity in lymphoproliferative diseases. Its intracellular nucleotides, in particular the 5'-triphosphate, are thought to be the pharmacologically active metabolites. The present study was undertaken to elucidate the cellular pharmacokinetics of these active metabolites in leukemia patients during CdA treatment. The concentrations of CdA in plasma and of CdA nucleotides (CdAN) in leukemic cells were measured by liquid chromatography in 69 patients with chronic lymphocytic, acute myeloid, and hairy cell leukemia after intermittent and continuous i.v. infusion, s.c. injection, and p.o. administration. The t1/2 of CdAN during the first dose interval was 13.8 h (n = 67), while after the last dose the t1/2 was 32.7 h (n =8). The area under the concentration versus time curve was similar after intermittent and continuous infusion, 268.3 and 237.8 &mgr;m/h, respectively (n = 7). The area under the concentration versus time curve after p.o. administration (0.24 mg/kg) was slightly lower than that after intermittent infusion (0.12 mg/kg), 120.6 versus 188.8 &mgr;m/h (P < 0.05, n = 7). However, when all p.o. administrations (n = 16) were compared with all 2-h infusions in other patients with chronic lymphocytic leukemia (n = 32), there was no significant difference (149.6 versus 168.6 &mgr;m/h). The cellular concentration of CdAN was 320 times higher than the plasma concentration of CdA, but there was no correlation in individual patients (r2 = 0.02, n =69). The t1/2 of CdAN was significantly shorter in patients with acute leukemias (9 h) compared to those with chronic lymphocytic (12.9 h) and hairy cell leukemias (15.1 h). The area under the concentration versus time curve of CdAN in leukemic cells from the 11 patients with hairy cell leukemia given CdA s.c. was in the same range (179.8 &mgr;m/h) as in patients with chronic lymphocytic leukemia. The retention of CdAN in leukemic cells supports intermittent administration. The lack of correlation between cellular and plasma drug concentrations indicates that plasma drug concentrations are not useful for individualization of dose.

Journal Article↗
PubMed1994

Multilevel regulation of low-density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase gene expression in normal and leukemic cells.

Altered cholesterol homeostasis has been noted in malignant cells, which led us to explore the regulation of cholesterol metabolism in normal and leukemic cells. The mean low-density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activities were fivefold and threefold higher in mononuclear blood cells from 33 patients with leukemia, compared with cells from 23 healthy subjects, whereas elevations in RNA levels were twofold and 40% only. The activities of the two proteins correlated in normal cells (r = .46), whereas an inverse correlation was found in leukemic cells (r = -.40). Relatively weak correlations were found between LDL receptor RNA levels and receptor activity in normal (r = .48) and leukemic cells (r = .49), and HMG-CoA reductase RNA levels correlated (r = .53) with reductase activity in leukemic cells only. The ratios of protein activities to RNA levels in cells were constant during consecutive blood samplings and similar in leukemic blood and bone marrow cells from the same individual. During cholesterol deprivation, protein activities increased more than RNA levels, and leukemic cells with high LDL receptor activity showed a partial resistance to the suppressing effect of sterols on LDL receptor gene expression. The results demonstrate that LDL receptor RNA levels alone can not explain variation in receptor activity, suggesting post-RNA regulation of LDL receptor expression, similar to what has been described for HMG-CoA reductase. Taken together, the present results suggest multilevel regulation of both proteins and demonstrate that each cell clone, normal or malignant, has a unique ratio of protein activity to RNA level. Leukemic cells, in contrast to normal cells, can meet increased cholesterol requirements by either elevated LDL receptor activity or increased cholesterol synthesis, which is of potential interest for diagnosis and specific treatment of leukemia.

Adult↗
PubMed1994

Flow cytometry of blood and bone marrow cells from patients with hairy cell leukemia: phenotype of hairy cells and lymphocyte subsets after treatment with 2-chlorodeoxyadenosine.

By flow cytometry and an extensive set of markers, we characterized leukemic cells from the blood and bone marrow of 68 symptomatic patients with hairy cell leukemia (HCL). Hairy cells identified in the large cell gate always expressed CD19, CD20, HLA-DR, CD45RA, and B-ly 7. Other markers were occasionally expressed, such as CD38, CD45RO, CD23, CD15, CD4, CD5, and CD10 (expressed on more than 20% of the hairy cells in 44%, 25%, 21%, 18%, 12%, 10%, and 5% of evaluated cases, respectively). During treatment with 2-chlorodeoxyadenosine (CdA), the median lymphocyte counts decreased from 2,000/microL to 300/microL. Flow cytometry was repeated at the nadir (n = 24) of lymphocyte counts, at 3 months (n = 46), at 6 months (n = 50), at 1 year (n = 39), and at 2 years (n = 12) after treatment. The initial decrease of CD8+ and CD20+ cells was greater than that of CD4+ and natural killer (NK) cells, leading to an increasing CD4/CD8 ratio. Median nadir values of CD4+, CD8+, CD20+, and NK cells were 128/microL, 78/microL, 10/microL, and 13/microL, respectively. The subsequent recovery was quicker for CD8+ and NK cells, leading to a normalization within 3 months, whereas CD20+ and CD4+ cells required 1 or 2 years to enter the normal range. The CD4/CD8 ratio thus decreased after the nadir and remained less than 1. CD45RA+ CD4 cells and CD45RA+/CD45RO+ double-positive cells were less affected by CdA. Activated T cells, ie, HLA-DR+ cells, rarely decreased below the normal range and often recovered with an overshoot. CD10+ cells increased in the bone marrow posttreatment as an indication of normal B-cell regeneration in 16 of 36 (44%) patients. The quick regeneration of certain lymphoid subsets might explain the lack of late infections in CdA-treated HCL patients.

Adult↗
PubMed1994

Hairy cell leukemia is characterized by clonal chromosome abnormalities clustered to specific regions.

Cytogenetic analysis was performed on B-cell mitogen-stimulated cells from 36 patients with symptomatic hairy cell leukemia. Evaluable metaphases were achieved from 30 patients, and (67%) showed clonal abnormalities. Recurrent chromosomal aberrations involving chromosomes 1, 2, 5, 6, 11, 19, and 20 were found. The abnormalities were mostly deletions and inversions, whereas translocations and numerical abnormalities, except trisomy 5, were rare. Fourteen patients showed multiple clones, which mostly were unrelated and found in different combinations in individual cells. Cells with non-clonal abnormalities identical to those found in clonal changes in other patients were common. Chromosome 5 was involved in clonal aberrations in 12 of 30 (40%) patients, most commonly as trisomy 5 (n = 4), or pericentric inversions (n = 6) and interstitial deletions (n = 4) involving band 5q13. Three patients showed two and 1 patient three different clones that involved chromosome 5. In addition, 1 patient had a rare constitutional inversion of chromosome 5 with breakpoints at p13.1 and q13.3. Pericentric inversions and interstitial deletions of chromosome 2 occurred clonally in 4 patients (13%) and in single cells of another 6 patients. Deletions of chromosome 1 at band q42 was found in 5 patients, and 1 patient had a translocation between 1q42 and a supernumerary chromosome 5. Deletions of 6q and 11q were similar to those commonly found in other lymphoproliferative disorders. Trisomy 5, structural abnormalities involving the pericentromeric regions of chromosomes 5 and 2, and 1q42 abnormalities were findings distinguishing the karyotypes in hairy cell leukemia from those of other hematologic malignancies.

Adult↗
PubMed1994

[Subcutaneous therapy of hairy cell leukemia with 2-chlorodeoxyadenosine].

The efficacy of subcutaneous 2-chlorodeoxyadenosine (2-CdA) was explored in eight patients with symptomatic hairy cell leukemia. This study is an interim report of a larger ongoing internordic multicentre clinical trial of subcutaneous 2-CdA in patients with hairy cell leukemia. The present results strongly indicate that subcutaneous therapy with 2-CdA induces an impressive therapeutic response which is fully comparable to the traditional continuous intravenous treatment with 2-CdA. The morbidity was acceptable, and the patient compliance to subcutaneous 2-CdA was excellent. In terms of the rate of complete remission (70-90%), therapy with 2-CdA in hairy cell leukemia is superior to any other drug. Consequently, 2-CdA is expected soon to displace both interferon alpha and deoxycoformycin as first line therapy in hairy cell leukemia. A long follow-up time is required, though, to decide whether 2-CdA is capable of curing patients with hairy cell leukemia.

Adult↗
PubMed1994

[Progress in the treatment of hairy cell leukemia. Subcutaneous administration of 2-chloro-deoxy-adenosine for 7 days].

Hairy cell leukemia is a rare chronic B-lymphocyte malignancy characterized by pancytopenia, splenomegaly, immunological abnormalities and morphologically typical neoplastic mononuclear cells in blood and bone marrow. Until recently the disorder was treated with splenectomia and/or alpha-interferon. Intravenous infusion of 2-chloro-deoxy-adenosine (2-CdA) is a new and efficacious treatment principle making hairy cell leukemia a potentially curable disease. A Nordic cooperative study is currently examining the effects of 2-CdA given subcutaneously for seven days. 19 Norwegian patients are included so far, with encouraging results. The long-term effect of 2-CdA is not yet known. The high remission frequency, the short duration of the treatment and the few side effects make this drug a natural first choice in treating hairy cell leukemia.

Adult↗
PubMed1994

Protein binding of 2-chloro 2'-deoxyadenosine (cladribine) in healthy subjects and in patients with leukaemia.

The plasma protein binding of 2-chloro-2'-deoxyadenosine (CdA) at 37 degrees C was studied by ultrafiltration in 5 healthy volunteers, in 11 patients with haematological malignancies and in purified protein preparations. In the patients, the binding of CdA to plasma proteins was 25.0% and in healthy subjects it was 21.1%. In a solution of human serum albumin (40 g.l-1), 24.3% CdA was bound, but less than 5% was bound in a solution of alpha 1-acid-glycoprotein (0.7 g.l-1). No dependence of binding on the concentration of CdA was found within a range 25-1000 nmol.l-1. In conclusion, due to its limited binding to plasma proteins, any change in the binding of CdA is unlikely to have a major influence on its pharmacological effect.

Adult↗
PubMed1994

Analysis of 2-chloro-2'-deoxyadenosine in human blood plasma and urine by high-performance liquid chromatography using solid-phase extraction.

A reversed-phase high-performance liquid chromatographic (HPLC) method for the simultaneous determination of a new and promising anticancer drug, 2-chloro-2'-deoxyadenosine (CdA), and its metabolite, 2-chloroadenine (CAde), in plasma and urine was developed. A solid-phase extraction procedure with guaneran as internal standard (IS) was used. Plasma (1 ml) or diluted urine (1/100) mixed with 1 ml of phosphate buffer (10 mM, pH 6.5) was applied on a C8 isolute cartridge, which was prewashed with acetonitrile and phosphate buffer. The cartridge was further washed with 2.5 ml of 1% acetonitrile/phosphate buffer and 2.5 ml of hexane/dichloromethane (50/50). The compounds were eluted from the cartridge with 2.5 ml 5% MeOH in ethyl acetate. Chromatographic separation was achieved on C18 column eluted isocratically with phosphate buffer (10 mM, pH 3.0) containing 11% MeOH and 7% acetonitrile, and ultraviolet (UV) detection at 265 nm. Recoveries of CdA and CAde at 100 nmol/L were 90.6 +/- 4.9 and 98.7 +/- 7.8%, respectively. Recovery of IS was 96.1 +/- 6.1% at 250 nmol/l. The inter- and intraday coefficients of variation (CV) were < 10% at different concentrations within the range 1-500 nmol/L for both substances. In plasma, limits of detection of CdA and CAde were 1 and 2 nmol/L, respectively. In urine, the limit of detection was 100 nmol/L for both compounds. Standard curves were linear up to 50 and 500 nmol/L for urine and plasma, respectively. The present method will be a useful tool for further investigations of the pharmacokinetics of CdA in patients treated with different routes of administration.

Chromatography, High Pressure Liquid↗
PubMed1994

T-cell receptor beta gene rearrangements in leukaemic B-cells from patients with chronic lymphocytic leukaemia: association with chromosome 6 deletions.

Rearrangement of immunoglobulin genes is a characteristic finding in normal B-cells and in leukaemic cells of B-cell origin. In some leukaemic cells simultaneous cross-lineage rearrangement of immunoglobulin- and T-cell receptor (TcR) genes occur. We have analysed TcR beta gene rearrangement in 100 patients with B-cell chronic lymphocytic leukaemia. All samples expressed CD5, CD19 and CD20 and six patients had rearrangements of both immunoglobulin and TcR beta genes. Analysis of gene expression in cells with TcR beta gene rearrangement indicated production of truncated TcR beta transcripts but no expression of the T-cell markers CD3, CD4, CD8, TcR alpha beta or delta on the cell surface. Three of the patients with both Ig and TcR beta rearrangement (50%) were 44 years or younger at diagnosis and cells from three such patients expressed IgG. Three of the six patients had a terminal deletion of the long arm of chromosome 6 with different breakpoints, with or without other chromosomal abnormalities, whereas 6q deletions were found in 4/94 patients without TcR beta gene rearrangement (4.3%) (P = 0.001). This study indicates a correlation between TcR beta gene rearrangement and deletion of chromosome 6q.

Antigens, CD↗
PubMed1994

Phosphorylation of 2-chlorodeoxyadenosine (CdA) in extracts of peripheral blood mononuclear cells of leukaemic patients.

2-Chlorodeoxyadenosine (CdA) is an antileukaemic agent used in treatment of hairy cell leukaemia (HCL) and chronic lymphocytic leukaemia of B- and T-cell type (B-CLL and T-CLL). The aim of this study was to elucidate the interpatient variability of CdA phosphorylation and its relation to response to CdA treatment. In extracts of peripheral blood mononuclear cells of patients with B-CLL (n = 39), CdA phosphorylation was significantly higher than in HCL (n = 19) when calculated per protein (391 +/- 155 pmol CdA phosphorylated/mg protein/min versus 288 +/- 166 pmol/mg/min, P < 0.001), but was the same when calculated per cell (12 +/- 5.9 pmol/10(6) cells/min versus 14 +/- 5.9 pmol/10(6) cells/min) due to a larger cell volume in HCL. In T-CLL (n = 6), CdA phosphorylation was significantly lower than in B-CLL, both when calculated per protein (128 +/- 68 pmol/mg/min, P < 0.001) or per cell (5.7 +/- 2.7 pmol/10(6) cells/min, P < 0.05). This low CdA phosphorylation in T-CLL was unexpected because normal B- and T-lymphocytes contain equal amounts of CdA phosphorylation. With B-CLL, 21 patients who responded (complete and partial response) to CdA treatment showed a significantly higher CdA phosphorylation than 13 patients not responding to CdA treatment (456 +/- 170 pmol/mg/min versus 309 +/- 97 pmol/mg/min, P < 0.01). We conclude that the level of CdA phosphorylation is correlated with the response of leukaemias to CdA treatment.

Cladribine↗
PubMed1994

Increased intracellular concentrations of doxorubicin in resistant lymphoma cells in vivo by concomitant therapy with verapamil and cyclosporin A.

The tumor cell uptake of doxorubicin was studied in vivo in cells from 2 patients with clinically resistant leukemic lymphomas treated with continuous infusions of doxorubicin 9 mg/m2 and vincristine with oral dexamethasone. After 24 hours, intravenous or oral verapamil was added and in one treatment course intravenous cyclosporin A was given. Plasma and intracellular doxorubicin concentrations and plasma concentrations of verapamil and norverapamil were determined with HPLC. In the 1st patient the intracellular uptake rate of doxorubicin was increased from 0.007 to 0.013 nmol/mg protein/h after the start of verapamil infusion. In the first treatment course of patient number 2, the intracellular concentration of doxorubicin was increased by 280% during a 6-h infusion of verapamil. When this patient in the next treatment course was given oral verapamil, no significant effect on doxorubicin uptake was seen. However, when 100 mg of cyclosporin A was added in three intravenous injections at 8-h intervals, the doxorubicin concentration in the tumor cells increased from 0.027 to 0.086 nmol/mg protein. In conclusion, this study shows that the intracellular concentrations of doxorubicin can be increased also in vivo during patient therapy by the addition of verapamil or cyclosporin A.

Adult↗
PubMed1994

Immunological and genetic abnormalities in chronic lymphocytic leukaemia. Impact of the purine analogues.

Chronic lymphocytic leukaemia (CLL) is a disease characterised by several immune defects such as frequent autoimmune complications and functional T-cell defects, which lead to an increased risk of infections (mostly bacterial) and other tumours. Clonal chromosome abnormalities are identified in half of the patients, and trisomy 12, the most common aberration, is present in about one-third of patients with clonal changes. The commonest structural abnormalities involve chromosome 13 at band q14, the site of the retinoblastoma tumour suppressor gene. A gene located telomeric to the Rb1 gene, identified by the D13S25 probe, might be a better candidate for a pathophysiologically relevant gene in CLL, since repeated reports have identified homozygous deletions of this site. The purine analogues fludarabine and cladribine (2-chloro-2'-deoxyadenosine) and the adenosine deaminase inhibitor deoxycoformycin all have therapeutic effects in a range of lymphoproliferative disorders. Prolonged immunosuppression with low CD4 cell counts frequently occurs and, subsequently, opportunistic infections may be seen. This has to be taken into consideration when treating patients with any of these potent drugs.

Antineoplastic Agents↗