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Biomedical subjects

G Papa

Publications and source records attributed to G Papa.

At least 37 records · Page 2Linked to original sources

Minimally differentiated acute myeloid leukemia (AML-M0): a distinct clinico-biologic entity with poor prognosis.

FAB proposals for the diagnosis of AML-M0 represent the formal recognition of a distinct entity which has been described over the past few years by several authors and called minimally differentiated acute myeloid leukemia. By definition, AML-M0 includes acute leukemias which do not fit morphological and cytochemical criteria for the diagnosis of AML, and for which myeloid lineage assignment can be made by immunological assay showing positivity for MPO, CD13, and CD33 and negativity for lymphoid markers. Involvement of an early myeloid progenitor in the leukemic process is a possible theory hypothesized to explain the existence of such a form. Validity of this assumption has been based on the observation that AML-M0 frequently bears "stem cell" markers such as CD34, HLA-DR, Tdt, CD7, and promiscuous IgH/TCR gene rearrangements, which are thought to occur in uncommitted cells. Finally, AML-M0 very frequently carries cytogenetic abnormalities common to MDS or secondary AML, such as -5/5q- or -7/7q- deletions and or complex karyotype. In our experience, AML-M0 is also very often associated with the MDR phenotype, which in turn has been found strictly linked to "stem cell" features, especially in MDS. These biological aspects, altogether, translate into a very unfavorable prognosis, confirming even from a clinical point of view that AML-M0 is a distinct entity. In conclusion, "stem cell" markers, MDR phenotype, complex chromosome lesions, frequent occurrence in elderly patients, and intrinsic chemoresistance characterize AML-M0 and indicate the need for tailored treatments, possibly involving the use of MDR modulators and/or differentiating agents.

Humans↗

In vitro inhibitory activity of citreoviridin against HIV-1 and an HIV-associated opportunist: Candida albicans.

Citreoviridin, a mycotoxin produced by some molds of the genera Penicillium and Aspergillus, inhibits the growth of bacteria of the Bacillus genus. Since significant information was not available on the effects of citreoviridin on eukaryotic cells and viruses, this molecule was tested on CD4+ T-lymphoid cell lines, on HIV-1 and on Candida albicans, which sometimes complicates HIV-infection. Antiviral activity was detected in H9 HTLV IIIB cells, a clone chronically infected by HIV-1. Citreoviridin reduced p24 in the supernatant of H9 HTLV IIIB in a dose-dependent manner with a pharmacological selectivity index of 2.6. In C. albicans, the effects of the mold-derivative were evaluated on some parameters associated with pathogenicity and virulence: cellular proliferation, germ tube production, expression of heat shock mannoproteins, release of proteases and phospholipases. At a 12.5 microM dose, citreoviridin showed a marked inhibitory effect on all parameters analyzed. As regards the mechanism of action, it is possible to hypothesize that the effects of citreoviridin may be due to a reduction of protein synthesis, since it inhibited the replication of HIV-1 at post-integrational stages and reduced the intracellular RNA and protein content in C. albicans.

AIDS-Related Opportunistic Infections↗

High-dose chemotherapy followed by autologous bone marrow transplantation versus dexamethasone, cisplatin, and cytarabine in aggressive non-Hodgkin's lymphoma with partial response to front-line chemotherapy: a prospective randomized italian multicenter study.

PURPOSE: To evaluate, in a prospective multicentric study, the efficacy of a conventional salvage chemotherapy (dexamethasone, cisplatin, and cytarabine [DHAP]) versus high-dose chemotherapy (carmustine, etoposide, cytarabine, and cyclophosphamide [BEAC]) followed by autologous bone marrow transplantation (ABMT) in patients with aggressive non-Hodgkin's lymphoma (NHL) in clinical partial response (PR) after two thirds of a conventional front-line therapy. PATIENTS AND METHODS: From August 1988 to August 1991, 286 patients with aggressive NHL were randomized in seven Italian institutions to receive fluorouracil, methotrexate, cytarabine, cyclophosphamide, doxorubicin, vincristine, and prednisone (F-MACHOP) or methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) as front-line therapy. Of the 286 patients enrolled onto the trial, 77 (27%) were considered in PR after two thirds of the front-line therapy, and 49 of 77 (64%) were randomized: 27 to receive DHAP chemotherapy and 22 to receive BEAC followed by ABMT. RESULTS: The response after second-line treatment was as follows: in the DHAP group, four patients (15%) achieved a complete remission (CR), 12 (44%) remained in stable PR, and 11 (41%) showed progressive disease; in the ABMT group, three patients (14%) obtained a CR, 18 (82%) obtained a stable PR, and one (4%) progressed, with an overall response (CR + stable PR) of 59% and 96% (P < .001) in the DHAP and ABMT groups, respectively. The overall survival was 59% versus 73% and the progression-free survival (PFS) was 52% versus 73% in the DHAP and ABMT groups, respectively (P, not significant). The toxicity was mild, particularly in the ABMT group, and no treatment-related deaths occurred in either group. CONCLUSION: Because of the small number of patients randomized, we were unable to determine whether ABMT or a standard salvage regimen (DHAP) is superior for PR patients. However, we confirmed that myeloablative treatment is a safe and well-tolerated procedure in this category of patients and this may enable us to evaluate its role as part of a front-line treatment in poor-risk NHL patients.

Adolescent↗

Allergic respiratory diseases and environmental pollution: experience in the printing/paper-manufacturing industry.

Several studies have shown a correlation between airborne pollutants and respiratory disorders. To determine whether professional exposure to industrial pollution might represent a risk factor for allergic respiratory diseases, we administered allergologic tests to 275 workers employed in a paper-making/printing factory and to a control population composed of 160 office workers from the same urban area. All subjects were evaluated on the basis of personal and family histories, the results of prick tests with common airborne allergens, specific serum IgE levels, pulmonary function test, and standard chest radiography. The percentage of subjects with allergies in the factory-worker group (67/275; 24.4%) was significantly higher than that observed among the office workers (20/160; 12.5%) (chi-square test: 8.17; P < 0.01). Of the 67 factory workers with allergies, 94% had histories of daily exposure to aliphatic hydrocarbons. The results of this study indicate that exposure to the latter type of industrial pollutants is associated with a significantly higher prevalence of allergic respiratory diseases.

Adult↗

Cytogenetic analysis is non-informative for assessing the remission rate in chronic myeloid leukemia (CML) patients on interferon-alpha (IFN-alpha) therapy.

Cytogenetic analysis is considered pivotal for assessing the remission rate in CML patients on IFN therapy. On the basis of general agreement, at least 25 metaphases should be analyzed in each case. The main limitations to this approach are: 1) the small number of analyzable metaphases generally found in cytogenetic preparations from IFN-alpha-treated patients; and 2) the inability of this technique for scoring interphase cells. We compared the results of cytogenetic analysis and double-color FISH detection of bcr/abl genes fusion in 13 CML patients on IFN-alpha therapy (marrow sampling for cytogenetic and FISH analysis was carried out after 12 months in all patients and repeated after 18 months of IFN therapy in patients 4, 6, and 8). In five specimens, 20 to 25 cells were evaluable for cytogenetic examination, in another five no analyzable metaphases were scored, and in the remaining six samples two to 14 cells could be analyzed. With FISH detection at least 100 cells were easily scored in each specimen (mean number, 175). Comparing the results carried out with the two methods in different samples it emerged that cytogenetic analysis led to improper conclusions as regards the rate of Ph positivity, even in those patients where 20-25 metaphases were analyzed. Although many more cases have to be studied to establish the role of FISH analysis in Ph-positive patients, we are of the opinion that cytogenetic analysis is unfit for easily and accurately assessing the actual quality of remission in IFN-treated subjects.

Chromosome Aberrations↗

Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Leukemia Cooperative Groups.

BACKGROUND: Allogeneic or autologous bone marrow transplantation and intensive consolidation chemotherapy are used to treat acute myelogenous leukemia in a first complete remission. METHODS: After induction treatment with daunorubicin and cytarabine, patients who had a complete remission received a first course of intensive consolidation chemotherapy, combining intermediate-dose cytarabine and amsacrine. Patients with an HLA-identical sibling were assigned to undergo allogeneic bone marrow transplantation; the others were randomly assigned to undergo autologous bone marrow transplantation (with unpurged bone marrow) or a second course of intensive chemotherapy, combining high-dose cytarabine and daunorubicin. Comparisons were made on the basis of the intention to treat. RESULTS: A total of 623 patients had a complete remission; 168 were assigned to undergo allogeneic bone marrow transplantation, and 254 were randomly assigned to one of the other two groups. Of these patients, 343 completed the treatment assignment: 144 in the allogeneic-transplantation group, 95 in the autologous-transplantation group, and 104 in the intensive-chemotherapy group. The relapse rate was highest in the intensive-chemotherapy group and lowest in the allogeneic-transplantation group, whereas the mortality rate was highest after allogeneic transplantation and lowest after intensive chemotherapy. The projected rate of disease-free survival at four years was 55 percent for allogeneic transplantation, 48 percent for autologous transplantation, and 30 percent for intensive chemotherapy. However, the overall survival after complete remission was similar in the three groups, since more patients who relapsed after a second course of intensive chemotherapy had a response to subsequent autologous bone marrow transplantation. Other differences were also observed, especially with regard to hematopoietic recovery (it occurred later after autologous transplantation) and the duration of hospitalization (it was longer with bone marrow transplantation). CONCLUSIONS: Autologous as well as allogeneic bone marrow transplantation results in better disease-free survival than intensive consolidation chemotherapy with high-dose cytarabine and daunorubicin. Transplantation soon after a relapse or during a second complete remission might also be appropriate.

Adolescent↗

First report of t(8;21)(q22;q22) in a case of de novo acute monoblastic leukemia.

Here we describe the case of a 30-year-old man with a diagnosis of de novo acute monoblastic leukemia (FAB M5a), whose karyotype analysis revealed the presence of the translocation (8;21)(q22;q22) as the sole chromosome anomaly. In spite of the rather good prognosis patients suffering from acute leukemia and carrying this translocation are supposed to have, our patient had a very poor outcome, including an early relapse resistant to any treatment and meningeal localization. Death occurred within 5 months from diagnosis. To our knowledge this is the first report of t(8;21)(q22;q22) in de novo acute monoblastic leukemia.

Adult↗

Trisomy 4 as the sole karyotypic anomaly in acute biphenotypic leukemia with B lineage markers and in acute minimally differentiated myeloid leukemia (M0).

Trisomy 4 is a recently defined chromosomal aberration in acute leukemia. The first reports suggested that this cytogenetic anomaly belongs to the M4 leukemia subtype of the FAB classification, but recent reports have described this alteration in a wider spectrum of leukemia subtypes. Here we report two cases of trisomy 4 as the sole chromosome anomaly: one was observed in a patient with acute biphenotypic leukemia with B-lineage markers and the second in a patient diagnosed with acute minimally differentiated myeloid leukemia (M0) with myelodysplastic features. To our knowledge these are, respectively, the first and second reports of trisomy 4 as the sole chromosomal anomaly in these leukemia subtypes.

Acute Disease↗

Chemosensitivity to triazene compounds and O6-alkylguanine-DNA alkyltransferase levels: studies with blasts of leukaemic patients.

BACKGROUND: A clinical pilot study performed by our group showed that dacarbazine can induce a marked reduction of blast cells in patients with acute myelogenous leukaemia (AML). Leukaemic blasts (LB) from responsive patients showed low levels of O6-alkylguanine-DNA alkyltransferase (OGAT). DESIGN: An in vitro study was performed to evaluate OGAT levels and sensitivity to temozolomide (a triazene compound that spontaneously decomposes into the active metabolite of dacarbazine) in a relatively large number of LB samples. RESULTS: OGAT levels varied widely among the LB of different patients, with a mean value higher in acute lymphoblastic leukaemias than in AML. About 25% of LB obtained from patients with AML showed low OGAT activity, in the range corresponding to that observed in leukaemic patients responsive to dacarbazine in vivo. A reasonable inverse correlation was found between OGAT levels and LB sensitivity to temozolomide. CONCLUSIONS: Triazenes could have a therapeutic potential in human leukaemias. Moreover, OGAT determination could provide rapid and reliable information about a patient's susceptibility to these antitumor agents.

Adolescent↗

Diagnostic work-up for food-dependent, exercise-induced anaphylaxis.

Fourteen patients with suspected food-dependent, exercise-induced anaphylaxis (EIAn) were subjected to prick tests with commercial food extracts and common airborne allergens, prick + prick tests with fresh foods, determination of total IgE levels, and specific IgE for 31 foods (CAP System FEIA RAST). All were positive for two or more foods; 10 presented hypersensitivity to 11 or more foods. On the basis of these findings, history data, and responses to food-exercise challenges (treadmill stress tests 90 min after meals containing none of the suspected foods and none associated with skin-test and/or RAST positivity) and suspected food-exercise challenges (SFECs - administered after meals containing the suspected food), three patients were diagnosed as having specific food-dependent EIAn (for wheat in two cases, tomato in one). In nine others, the presence of specific IgE for numerous foods (including those suspected on the basis of histories and utilized in the SFECs) suggests involvement of specific food hypersensitivity, although SFEC confirmation could not be obtained. Avoidance of all foods associated with test positivity 4 h before exercise has prevented all further EIAn episodes in these 12 patients. In two others, the reactions did not appear to be related to IgE directed against specific food allergens, and these subjects have eliminated further reactions by avoiding all meals for the 4 h preceding exercise. These findings emphasize the importance of allergologic testing with a wide panel of food allergens (including foods used for seasoning, such as garlic or parsley) in all patients with suspected food-dependent EIAn. Prick + prick tests with fresh foods and the CAP System RAST disclosed numerous hypersensitivities.

Adolescent↗

Evaluation of adverse cutaneous reactions to aminopenicillins with emphasis on those manifested by maculopapular rashes.

We assessed 195 subjects with histories of adverse reactions to aminopenicillins, using 1) skin tests with penicilloyl polylysine (PPL), minor determinant mixture (MDM), benzylpenicillin (PG), amoxicillin, and ampicillin (read after 20 min and 48 h); 2) patch tests with PG, amoxicillin, and ampicillin; and 3) RAST for penicilloyls G and V. Oral challenges with ampicillin, amoxicillin, and penicillin V were administered to 34/60 patients reporting maculopapular reactions. Immediate hypersensitivity (IH), in most cases for both penicillin and aminopenicillins, was diagnosed (based on skin tests, RAST, or both) in 35 subjects who had suffered anaphylactic shock, or urticaria, angioedema, or both urticaria and angioedema. Thirty-three of the 60 subjects reporting maculopapular reactions presented delayed intradermal and patch-test positivity, indicating delayed hypersensitivity (DH), for ampicillin and amoxicillin, and three were also positive for PG. Diagnoses were confirmed with oral challenges in 18/33. The remaining 27/60 were negative in all allergologic tests, with oral-challenge confirmation in 16. Our findings highlight the importance of the amino group in DH to aminopenicillins. Moreover, the mean time interval between the last reaction and our tests was significantly (P < 0.01) longer in DH subjects (54.96 months) than in those with IH (18.62 months), suggesting that the time of testing is less important in cases of DH.

Adolescent↗

Cisplatin increases sensitivity of human leukemic blasts to triazene compounds.

High levels of O6-alkylguanine-DNA-alkyltransferase (OGAT) can, at least in part, account for tumor cell resistance to O6-alkylguanine alkylating agents, including triazene compounds. A pilot clinical study indicates that dacarbazine can induce a marked decrease of leukemic blasts in patients affected by acute myelogenous leukemia (AML) with low pretreatment levels of OGAT activity. In this study we show a synergistic antitumor effect between cisplatin (CDDP) and temozolomide (an in vitro active analog of dacarbazine), following combined in vitro treatment of leukemic blasts. Synergistic effect appears to be CDDP-dose dependent. In vivo treatment of leukemic patients with CDDP was followed by a reduction of OGAT activity in 2 out 3 cases. These data point out that CDDP could be a good candidate for depleting OGAT protein of leukemic cells, thus reversing tumor cell resistance to dacarbazine.

Adult↗

Recombinant interferon alpha 2a, thymopentin and low doses of cytosine arabinoside for the treatment of myelodysplastic syndromes: a pilot study.

Eighteen patients (pts) with myelodysplastic syndrome (MDS) were treated with thymopentin (TP) (50 mg subcutaneously for 5 days) and recombinant interferon alpha 2a (rIFN alpha 2a) (3 MU/m2 subcutaneously on the sixth day); the courses were delivered every week. Moreover those pts with > or = 10% blasts in the bone marrow were additionally treated with low dose cytosine arabinoside (LDARAc) (20 mg standard dose, subcutaneously, twice a day for seven days every four weeks). Sixteen pts were finally assessable for response. Seven pts (44%) were classified as good responders, 5 (31%) had a PR; the overall response rate (GR+PR) was 75%. Two pts (12.5%) showed stable disease and the 2 remaining (12.5%) had progressive disease. Six pts with an initial moderate anemia never required supportive care before and during the therapy; in contrast to 10 pts who were transfusion-dependent. After six months of therapy 2 pts decreased their transfusional needs by 50% (1 of them did not receive any transfusion over the following six months of therapy); 2 pts needed no packed red cell infusions and 1 pt decreased his transfusional support by 75%. Five pts kept an unchanged supportive care load. The overall median survival was 12.5 months. Therapy was generally well tolerated with acceptable compliance; the most frequently recorded side effects were neutropenia and thrombocytopenia grade 2-3 among the group receiving LDARAc. However no life-threatening infectious episodes or bleeding were observed. TP, rIFN alpha 2a and LDARAc can be safely administered on an outpatient basis to MDS pts and appears to have significant activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

CD7 expression in acute myeloid leukemia.

The clinical significance of the expression of CD7 antigen on the blasts of 207 consecutive patients with de novo acute myeloid leukemia (AML) was evaluated. For this purpose, fifty-three CD7+ patients (23 females and 30 males; mean age 52 years) were analyzed and classified into the following subtypes according to French-American-British (FAB) classification: 7 M0, 13 M1, 9 M2, 1 M3, 9 M4, 14 M5. Immunophenotypic studies were carried out by flow cytometry and blast cells were selected on the basis of forward light scatter gating and pan-myeloid marker, either CD13 or CD33. All the CD7+ patients were negative for surface CD3 and T-cell-receptor (TCR) molecules. We found no correlation between CD7 expression and sex, age, hepatosplenomegaly and/or central nervous system involvement. The immaturity of CD7+ leukemic cells was supported by the high expression of CD34 (P = 0.001). CD7 positivity was significantly associated with a white blood cell count (WBC) greater than 100 x 10(9)/L (P = 0.003). P-Glycoprotein (P-170) expression was also evaluated in 135 patients by a flow-cytometric assay: there was a close relationship between CD7 and P-170 positivity (P < 0.001). For remission induction, all patients received therapeutic regimens routinely used for AML. The complete remission (CR) rate was significantly lower in CD7+ cases (32% vs 74%, P = 0.001). The overall survival and disease free survival rate of CD7+ AML was lower than those of CD7- patients (P < 0.001 and = 0.002, respectively). CD7+ AML with coexpression of CD14 had a particularly unfavourable response and prognosis in comparison with CD7+ patients without CD14.(ABSTRACT TRUNCATED AT 250 WORDS)

ATP Binding Cassette Transporter, Subfamily B, Mem↗

MACOP-B vs F-MACHOP regimen in the treatment of high-grade non-Hodgkin's lymphomas.

A prospective randomized study on aggressive non-Hodgkin's lymphomas was conducted by investigators at several Italian institutions with the intent of comparing two third-generation conceptually different regimens: the regimen containing methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B), a short-term continuous twelve-week therapy, and F-MACHOP (5-fluorouracil, methotrexate with leucovorin rescue, cytarabine, cyclophosphamide, doxorubicin, vincristine, and prednisone), a monthly intensive cyclic treatment combining prednisone with six active non-cross-resistant cytotoxic drugs. The goals of this study were the response rate, relapse-free survival, and incidence of hematologic and nonhematologic toxicities. Two hundred-eighty-six patients included between 15 and 60 years fulfilled the criteria for entry to the study; 140 patients were treated with MACOP-B and 146 with F-MACHOP. The minimum follow-up was 24 months. Clinical characteristics of all patients were similar and known prognostic factors were equally distributed between the two groups. Complete remission (CR) was achieved by 61% and 67% of the patients treated with MACOP-B and F-MACHOP, respectively; 4% and 6% were primarily resistant, 2% and 5%, respectively, died of causes directly related to therapy. At 50 months, 74% of all CR patients were alive without disease and there were no significant differences in relapse-free survival between the two groups: 75% in the F-MACHOP group and 73% in the MACOP-B group at 50 months. There was a higher incidence of mucositis among patients treated with MACHOP-B than among those given F-MACHOP (11% vs 3.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Leukocyte alkaline phosphatase score in plasma cell dyscrasias: correlation with disease severity and circulating levels of granulocyte-colony stimulating factor.

In this study the leukocyte alkaline phosphatase (LAP) score in 106 patients with multiple myeloma (MM) in various phases of the disease (66 at diagnosis, 18 in plateau phase, 22 in relapse) was examined and compared with the score of 68 patients with monoclonal gammopathy of undetermined significance (MGUS) and 53 normal volunteers. In addition, the circulating levels of granulocyte-colony stimulating factor (G-CSF) were measured to explore the possible involvement of this cytokine in the pathogenetic mechanisms that lead to increased LAP activity. The results showed that the mean LAP score in patients with MGUS was comparable to normals and significantly lower than in MM (p < 0.001). Also, it increased with increasing tumor mass, and was lower in myelomas with stable disease than in those with active disease. G-CSF concentrations closely mirrored the behaviour of LAP score (r = 0.850, p < 0.001), significantly differing between each group of individuals. Its mean levels in MGUS were comparable to those of controls, whereas they were significantly increased in MM (p < 0.001), again with escalating values from cases with low tumor mass to advanced stages, and with lower concentrations in patients in plateau phase than in those in relapse. A significant correlation was found between G-CSF and neopterin levels (r = 0.578, p < 0.001), thus indicating an origin of the cytokine from monocytes and macrophages. These findings suggest that LAP scoring may assist in distinguishing benign from malignant paraproteinemias and may be used to follow the progression of plasma cell neoplasias.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Phase III comparative trial using CHOP vs CIOP in the treatment of advanced intermediate-grade non-Hodgkin's lymphoma.

Until now, literature data support the fact that the CHOP regimen represents the standard first line treatment for patients with advanced intermediate-grade non-Hodgkin's lymphoma. Recently, idarubicin has been introduced in clinical trials because of its favourable preclinical profile: it is more active than daunorubicin and doxorubicin against a number of experimental tumour systems and is significantly less cardiotoxic in animal models. From March 1991 to June 1993, 115 previously untreated patients with stage II to IV intermediate-grade non-Hodgkin's lymphoma, according to the Kiel classification, were enrolled in a phase III comparative trial. The objectives of the study were to compare the efficacy and safety of using idarubicin instead of doxorubicin in the polychemotherapeutic regimen CHOP (cyclophosphamide, doxorubicin, vincristine, and dexamethasone). Of the 115 patients registered for the trial, 103 were evaluable: 52 received CH (doxorubicin)OP and 51 received CI(Idarubicin)OP. Known prognostic factors were equally distributed among the two groups. There were no significant differences between the 2 groups in the rates of partial and complete response. The overall response rate was 87%, with complete response in 62%: 63% in the CHOP group, and 59% in the CIOP group. At 30 months (median 20 months), 86% of all CR patients were alive without disease in the CHOP group and 85% in the CIOP group. Patients treated with CHOP experienced severe alopecia more frequently (P = .004). Only three patients in the CIOP group showed cardiac adverse events (1 moderate and 2 mild), while in the CHOP group 4 mild, 2 moderate and 1 severe were recorded. LVEF monitoring was carried out in 31 patients of the CHOP group and in 27 of the CIOP group. A median drop of 8.3% of the LVEF was observed in patients treated with CHOP regimen as compared to 4.8% in patients with CIOP regimen (P = .0001). In this trial, the "idarubicin arm" (CIOP regimen) was found to have an equivalent therapeutic efficacy and, slightly, reduced clinical toxicity in comparison to the standard doxorubicin-containing CHOP regimen in patients with intermediate-grade non-Hodgkin's lymphoma.

Adult↗